case study on biology

Using Case Studies with Large Classes

Why Use Case Studies?

Case studies are powerful tools for teaching. They explore the story behind scientific research to understand the phenomenon being studied, the question the scientist asked, the thinking they used to investigate it, and the data they collected to help students better understand the process and content of science.

A strength of this approach is that it gives students the chance to consider how they would investigate a topic. Their answers are often similar to what the researchers being studied did. But students also come up with novel perspectives and unique approaches to the problems.

Many BioInteractive resources lend themselves to a case study approach. In most instances, what I ultimately decide is to convert the resource into a case study. For example, the video Animated Life: Mary Leakey is an excellent tool to get students thinking about the logic scientists use to study fossils and extinct species. Data Point resources are also a rich source of figures and questions that can be copied and pasted into a presentation to provide a brief case study that introduces a topic.

The Challenge for Large Classes

Many BioInteractive activities are structured in a way that they are particularly useful for smaller groups and classes. And by smaller, I am thinking of fewer than 50 students. To some colleagues, that may seem to be a large class size. Indeed, in many instances, it probably is more than is optimal.

However, when I refer to large classes, what I am thinking of are the large introductory classes encountered in many colleges and universities in which enrollment can range from 100 to 500 or more depending on the institution. Classes of this size present instructors with the dual challenges of not just numbers but also anonymity. It’s logistically unmanageable to share and distribute printed copies of handouts or worksheets.

How to Scale Up

So how can an instructor promote the interaction that is essential to the success of these types of case study activities in such a large group? These are issues I grappled with when I went from teaching at a small liberal arts college where my classes were smaller than 30 to teaching at a large university with classes of several hundreds. I have found what I think are four parts to an effective solution.

1. Define a learning objective.

First and foremost, whether I have 30 or 300 students, I try to think about why I want to use a particular BioInteractive resource. I consider what it is that I want the students to do or think about while using the resource. How do I want them to be different after completing the assignment? In essence, I define the learning objective so I can determine the most effective platform and approach to deliver the lesson utilized in the resource.

2. Create presentations with strategic pause points.

PowerPoint is a common tool for delivering material in large classrooms. It is quite easy to take images and questions from BioInteractive resource PDFs and insert them into slides. After reading the teaching notes and text in the student handouts, it’s relatively simple to develop the story that weaves the slides together in an interrupted case study. This is a style of case study that progressively leads students through the information with carefully planned “reveals” of information and strategically placed questions as stopping points to ponder the material along the way.

Videos are also fabulous resources to use during interrupted case studies in class. For example, I regularly use the video Niche Partitioning and Species Coexistence , which describes Dr. Rob Pringle’s work on niche partitioning in the savanna, as the core of a video case study in class. After the class watches the video for a few minutes, I stop and ask students about the phenomenon being studied and approaches that could be used to answer different questions.

I often use the following questions/prompts:

• Why would anyone care about factors shaping species presence or absence?
• Think about what factors could be important influences on shaping species richness in a community.

How can we use modern techniques to study what an animal is eating when we can’t watch the animal eat? The video does an excellent job of addressing these topics and showing how researchers developed a creative approach to applying molecular techniques to answer ecological questions. How awesome is it that one video can help students tie together the central dogma, ecological theory, and community concepts! Depending on how much an instructor wants to structure the video case study in advance, it is even possible to embed small video clips and questions directly into a PowerPoint presentation.

3. Have students use clickers.

How should we tell the scientific story to large numbers of students and engage them in it? Clickers are a particularly helpful tool for asking questions about experiments, concepts, or results, because they present students with a specific moment when they need to choose among different options for a survey of their opinion or decide among right and wrong answers in a multiple-choice question.

For example, I typically start a case study with survey questions asking students to identify what they think is the most important item on a list of potential phenomena or to give their feedback about an issue in a Likert-scale response. Later, as the case study develops, I ask more specific questions about the experiment that require students to predict experimental outcomes or interpret a figure. For example, when I use the video The Effects of Fungicides on Bumble Bee Colonies , I show students several bar graphs with possible outcomes for the experiment and have them pick which they think the researchers will observe. After revealing the actual results, I ask them questions about interpreting the results and whether the results support the experimental hypothesis. I always allow students to talk and help one another during clicker questions to enhance their interaction and give them a choice to go along with a group opinion or answer based on their individual thinking.

4. Flip the classroom.

Another effective way to use BioInteractive resources in large classes is to use videos to flip a class session. BioInteractive animations and short films are rich with information that can pique interest, start discussions, or provide fundamental information. For example, I recently had my students watch the Genes as Medicine short film outside of class time. I asked them to then imagine they were an alien that found this video clip and to consider what information it would give them about life on Earth. This sparked a lively discussion about what life is to start the next class meeting that was more interesting than me going through a checklist of terms and definitions. Students had to uncover the characteristics of life from the video for themselves.

Benefits and Takeaways

What I hope these hints and suggestions from my own experiences show is how relatively simple it can be to scale up these resources to engage a class of any size. When they first encounter case studies, students can be a little unsure about this approach that requires them to talk to one another in a setting where they are expecting to be a face in the crowd. However, after they experience one or two case studies, I can see groups of students talking and exchanging ideas about the case. They are no longer passive listeners sitting in a room but instead have become active problem solvers seeking answers together. I can leave the stage and mingle through the room to listen to their discussions and encourage them as they develop their answers. This also gives me an opportunity to interact with students besides those sitting in the front row and to further develop a sense of community and connection, solving one of the challenges with big classes: anonymity.

It has been my experience that students quickly adapt to and begin to enjoy this approach. Rather than sitting in class watching yet another series of PowerPoint slides flash by, they are thinking and talking about science with one another. After my students talk things through with their neighbors and “shoulder buddies” during a case study, I find that they are more likely to speak up in class during the case study and at other points during the course.

At the beginning of the semester, I can barely get anyone to answer a question. After a few case studies, students begin asking and answering questions (even when we aren’t doing case studies), and the level of participation by different students in the room is noticeably higher. So in addition to case studies being a more interesting way for me as the teacher to present material to students and explore different biological topics, this approach also has the added benefits of helping build confidence within individual students and community among students, which makes a more rewarding and exciting learning environment for everyone.

Educational case studies based on examples of simulated or real research data can engage students in the process of thinking like a scientist, even when it is not possible to get into the field or laboratory to actually run an experiment. They can help overcome the challenges of data analysis and interpretation that are at the core of science education experiences. The collections of different resources available through HHMI BioInteractive provide a menu of modules for instructors to choose from that do just that. They get students to explore important biological topics from a variety of different approaches and look at the world through the lenses of different scientists. Regardless of what the actual format of a resource is when I encounter it, I know that it is possible to scale it up in some way to meet the needs of my classes.

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Phil Gibson is a professor at the University of Oklahoma, where he enjoys teaching his students that learning a little botany never hurt anyone and is probably good for them in the long run. When he’s not thinking about new resources to use in class, he enjoys hiking with his family, listening to music, and cooking outrageously large breakfasts on the weekends.

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Kim Parfitt describes two activities (now merged into the activity “Scientific Inquiry and Data Analysis Using WildCam Gorongosa”) associated with the WildCam Gorongosa project. She also discusses a short film on lion populations in Gorongosa that she uses to introduce the topic.

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The Biology Corner

Biology Teaching Resources

Case Study – Mitosis, Cancer, and the HPV Vaccine

Students in my anatomy class get a quick review of the cell and mitosis. This activity on HPV shows how the cell cycle relates to overall health. In fact, many of the chapters in anatomy have anchoring phenomena on diseases and health. For example, cystic fibrosis is a cellular transport problem, but has serious effects on the lungs and respiratory system

When learning about the cell, we discuss how Tay-sachs is a disease associated with the lysosomes, and cystic fibrosis is a membrane transport problem. The older anatomy students can no see how those organelles are related to the overall health and functioning of the body.

This activity discusses how cancer is a problem with the cell cycle. Viruses, like HPV, or human papillomavirus, can disrupt the cell cycle and cause cervical cancer. The project reads like a case study, where students read text and answer questions.

They also analyze data from the CDC and even interpret infographics to help them understand the association between mitosis (cell cycle) and cancer.

The activity also asks them to evaluate the need for the HPV vaccine in both girls and boys by comparing data regarding cases of other types of cancer that can be associated with the virus.

Students can write the answers directly on the slides which can be assigned and submitted through Google Classroom. The final slide asks for a synthesis of the information and to take a position on whether young people should get a vaccine to protect against certain types of cancer.

There is no right or wrong answer, I only ask that my students justify their position with scientific details that show their understanding of the cell cycle and viruses.

The TpT link has answers or suggested responses as well as a download of the PowerPoint version of Google Slides.

Shannan Muskopf

American Society for Microbiology

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By PETER OMMUNDSEN Problem-based learning (PBL) is an exciting way to learn biology and is readily incorporated into large classes in a lecture hall environment. PBL engages students in solving authentic biological case problems, stimulating discussion among students and reinforcing learning. A problem-based learning environment emulates the workplace and develops self-directed learners. This is preferable to a mimetic learning environment in which students only watch, memorize, and repeat what they have been told. The examples given here are suitable for use in a first year college biology lecture theater, but the method is applicable to any class size and educational level. [A more detailed explanation of PBL in Biology may be found in Chapter Four of INSPIRING STUDENTS, published in 1999 by Kogan Page.] METHOD FOR INSTRUCTORS (1) Form Small Groups You may decide to devote all or part of a class session to PBL, but students must form small work groups during that time. Ask the students to form groups of 3-5 people, or assign the groups yourself or by lottery.

Present the students with a brief problem statement (preferably on a printed work sheet, an example of which is shown below), e.g., "A 28-year-old man appears to have osteoporosis." In some cases a video clip or specimen might be used as a trigger. Emphasize to the students that they are dealing with an authentic case history. Bizarre problems work best [more examples follow]. Prior to class you should review the case history and arm yourself with data that can be released incrementally (progressive disclosure) as the case proceeds. There is a comprehensive data set for the osteoporosis problem in the New England Journal of Medicine, 1994, 331:1056-61; 1088-9. Needless to say, the students should not be given the reference, as the objective is to solve a problem, not read a solution.

Ask the groups to brainstorm possible causes of the osteoporosis. Each group will have to discuss, review, or investigate the biology of bone, including the role of osteoblasts, diet, vitamin D, parathyroid hormone, growth hormone, calcitonin, kidney function, etc. This is when much learning occurs, as the students help each other understand the basic biology. PBL students must reflect upon biological mechanisms rather than just memorize facts (as might occur in some traditional lecture-only courses). The instructor circulates among the groups, providing assistance but not solutions. The groups may well explore avenues unanticipated by the instructor. This is highly desirable and should not be discouraged. The instructor should avoid controlling the agenda of the groups. Each group ranks its hypotheses in order of priority and prepares requests for more data. (E.g., for calcium deficiency hypothesis -- "What did he usually eat?")

Ask that a rep from each group place their top priority hypothesis or data request on the chalkboard (if already entered by another group, place their second choice, etc.). If this is not practical, ask for oral suggestions from the groups when the small group work is halted and the class is reconvened. Student suggestions may include -- Low calcium diet Immobility Low density of vitamin D receptors Calcitonin deficiency Excessive PTH Chronic acidosis buffered by salts mobilized from bone The small group work can be stopped and the instructor can briefly discuss the ideas with the entire class. It is important to value every contribution, to assist the students in analysis of the biology involved, and to provide further information [he was not immobile, he had a normal diet, etc.]. The students can be prompted for data requests: "If you could ask for just three test results from examination of this man, what would they be?" It is not likely that the students will solve a problem on the first pass, and the feedback from the instructor motivates the next round of small group work. The students could now be told that the man's lumbar spine density is 3.1 standard deviations below the average age-matched healthy female (osteoporosis = 2.5+ SD), his height is 204 cm, his left middle finger is 10 cm, and knee films show open epiphyses. (The students should now be able to figure out that the man may still be growing at age 28). The cycle of small group work and instructor feedback can be continued during the current class session or on future occasions. The key to managing a PBL session is providing continual feedback to maintain student enthusiasm while simultaneously prolonging the resolution of the problem to ensure that adequate learning occurs.

At this point in our example the groups will likely focus on the hormones required for epiphyseal closure and bone mineralization. They may ask you for serum estrogen levels (high) which will suggest estrogen-resistance. Were estrogen receptors defective? (Yes.) When a reasonable number of groups have solved the problem, you might request a brief written analysis from each group describing the biology involved in the case. Students may be asked to include certain key words in their reports. If you wish to further pursue this case at a later date you could tackle the genetics of the defect. (C to T transition in the estrogen receptor gene in both alleles causing a premature stop codon; both parents heterozygous with consanguinity in the pedigree.)

Effective problem-solving requires an orderly approach. Problem-solving skills do not magically appear in students as a result of instructors simply throwing problems at them. Our students use the following heuristic: "How to make a DENT in a problem: D efine, E xplore, N arrow, T est."

What exactly are you trying to determine? Does the problem have several components? If several, state them separately. Does everyone in the group agree with the way the problem has been framed? Ask group members to "think out loud," as that slows down their reasoning and enables people to check for errors of understanding.

Brainstorm ideas that may contribute to a solution. Justify your ideas to group members. Clarify for them the biology involved. Have them paraphrase your ideas. Listen carefully to the ideas of other group members and give positive feedback. Make a list of learning issues. What do we know? What don't we know? Is this problem analagous to any past problem? What core biological concepts may apply to this problem? Assign research tasks within the group.

After developing a list of hypotheses, sort them, weed them, and rank them. List the type of data required to test each hypothesis. Give priority to the simplest, least costly tests. It is easier to get information on the diet of a subject than it is to do sophisticated biochemical tests.

Seek from your instructor the data that you need to test your ideas. If all your possible solutions are eliminated, begin the cycle again: define, explore, narrow, test. When you encounter data that confirm one of your hypotheses you may be asked to write a biological explanation of your solution and justify it using the available evidence.

Following are examples of typical case problems that have been culled from biological journals and that have been successfully class-tested at the first-year college level. A sample student work sheet may be seen by clicking here .

A 58-year-old woman experienced attacks of confusion: she would repeat the same question 30 times even though it was answered for her each time. [New England Journal of Medicine 315:1209-19.] This is a good introductory case, as the students are able to generate a wide range of ideas: Alzheimer's Disease, trauma, alcohol abuse, atherosclerosis, arrhythmia, hypotension, cancer, epilepsy, diabetes, hypocalcemia, emphysema, dehydration, hypoglcemia, stroke, etc. The students perceive that the class as a whole is a credible learning resource, and the instructor can help the class reflect upon the biological implications of each suggestion. Eventually the students will ask the circumstances of the woman's attacks (e.g., "Following alcohol consumption?") When the students learn that the attacks occurred in the late afternoon, they will likely focus on diet and blood sugar. The instructor might at this point present a short talk on carbohydrate function and blood sugar regulation. This can be done using a transparency, with copies available to the students. It is important in a PBL environment to minimize the time required for note-taking. The students will ask for information on the woman's blood glucose level (1.6 mmol/L) and urine glucose level (zero). The student groups can now brainstorm and investigate possible causes of the low blood glucose: glucagon deficiency, insulin poisoning, anorexia nervosa, extreme exercise, etc. They may ask for an x-ray image of her abdomen, which the instructor can display as a transparency copied from the article. The students can be assisted in identifying the anatomy, including an abnormal mass in the pancreas (an insulin-secreting tumour). Additional discussion and learning opportunities can be generated by displaying copies of the ultrasonogram, angiogram, histopathology, etc. The students in each group may then collaborate in writing a brief report that explains the biology of the case.

Sabrina the cat fell 32 stories from a New York skyscraper and easily survived, as do most cats that fall from skyscrapers, especially those that fall more than several stories. Not so for humans. Why? [Natural History Magazine, August 1989: 20-26.] This intriguing case requires students to confront (or review) fundamental concepts that have wide application in biology, including allometry, momentum, stress, compliance, friction, surface area, acceleration, equilibrium, adaptation, and natural selection.

A woman with type AB blood gave birth to a child with blood type O. A second type-O child was born six years later. [Nature 277:210-211.] This case appears to contradict Mendelian inhertiance, which the students will be obliged to thorougly review, but it also demands that they make a rigorous examination of meiosis, gametogenesis, fertilization, and early development in order to propose some credible explanatory mechanisms.

A farmer was alarmed to notice tomato plants that were stunted and withered. This case initially requires the students to carefully reflect upon many basic concepts of plant anatomy, histology, physiology, ecology, and pathophysiology. Students might discuss and explore possible effects of soil quality, water relations, humidity, transpiration, hormones, and nutrition. Students should be encouraged to explore examples of pathogenic mechanisms, perhaps involving TMS, wilt fungi, wilt viruses, stunt viruses, and wilt bacteria. Ultimately the cause may be attributed to ABA deficiency, and the instructor might suggest this by introducing evidence of viviparity. Students can then focus on the roles of ABA and ethylene, and further work might address the genetics of the defect. . There is a comprehensive literature on ABA-deficient mutants, and many easily accessible web resources, e.g., Plant Biology 2000 Abs 706, XVI International Botanical Congress Abs 6158, etc.

A 94-year-old woman admitted to hospital for pneumonia had a swollen abdomen. A CT scan revealed a fetus. The woman had dementia so was unable to explain what had happened. [New England Journal of Medicine 321:1613-14.] This case prompts exhaustive brainstorming of all aspects of reproductive physiology and will produce many imaginative hypotheses.

In a coyote-control experiment coyote population density was greatly reduced. The number of rodent species then declined from ten to only two! Rodent species richness did not change on comparison areas where coyote density remained high. [Journal of Wildlife Management 63:1066-81.] This case opens many avenues of biology for exploration, including trophic levels, population regulation, population limitation, competitive exclusion, niche breadth, keystone species, umbrella species, predator control policy, biodiversity, and species richness.

A 24-year-old man experienced abdominal pain, diarrhea, and distention whenever he consumed sugar. This was a life-long problem. [New England Journal of Medicine 316:438-442.] This case ensures that students master the taxonomy of carbohydrates, and the physiology of carbohydrate digestion and absorption.

A woman encountered her 30-year-old daughter squeezing the toothpaste and unable to let go. Later that day the daughter was found holding the doorjamb and unable to move forward. [New England Journal of Medicine 317:493-501.]

Obtain a selection of DNA-typing profiles (RFLP autorads or STR electropherograms) from local police, and construct a brief but equivocal fictional case history. Divide the class into to groups of five � each group with one judge, two prosecutors and two defense attorneys. Each student should have a copy of the case and copies of raw DNA profiles. (The old autorads force the students to measure by hand.) Each side must argue the evidence before the judge and submit to the instructor a brief written report along with a written decision from the judge. This exercise demands that students help each other to thoroughly understand the genetics, and the proceedings result in much hilarity. It is desirable to introduce some complexity, for example we included an autorad from blood on a knife that contained specimens from several people. Another good source of DNA typing problems is wildlife census data from hair traps (e.g., grizzly bears).

121 cases of illness were characterized by sleeplessness, headache, tachycardia, shortness of breath, sweating, tremor, heat intolerance, and weight loss. [New England Journal of Medicine 316:993-998.]

A fitness test of applicants to a fire department resulted in 32 hospitalizations with back pain, muscle pain, and reduced urine output. One person died. [MMWR 39:751-6.] The students will at some point address muscle physiology. What happens when muscle cells break during exertion? What are the consequences of hyperkalemia on the heart? Where does all the potassium originate? What are the effects of myoglobin on the kidneys? What is the impact of oxygen free radicals produced by damaged muscles?

An 80-year-old woman suffered from confusion, falls, and fractures. Her lungs were gritty like hard sponges. [New England Journal of Medicine 315:1209-19.]

A one-year-old boy began to have recurrent bacterial infections including pneumonia, sinusitis, and middle ear infections. This pattern continued, and at age 9 he developed Hodgkin's disease. He is HIV-negative. [New England Journal of Medicine 320:696-702.]

In one mite species of the genus Adactylidium the male is born, does nothing, and dies within a few hours. What evolutionary selection pressures might have shaped this life-style? [Stephen J. Gould, The Panda's Thumb (book) pp 73-75.]

An 88-year-old man had eaten 25 eggs per day for many years, yet his serum cholesterol was only in the range of 150-200 mg/dL. [New England Journal of Medicine 324:896-900.]

An 18-year-old man fatigued quickly during exercise. [New England Journal of Medicine 324:364-9.] This is an excellent case for application of principles of cellular energy metabolism.

Four hundred people at a rock concert collapsed or experienced faintness, with possibly as many as six different proximal causes. [New England Journal of Medicine 332:1721.] Students must reflect on the biology of a number of organ systems: fasting hypoglycemia, fasting acidosis, orthostasis, hyperventilation-induced cerebral vasoconstriction, Valsalva pressure from screaming and crowding, etc.

A forest patch was logged, then replanted, but within seven years the newly planted trees began to die. [Local example -- acid precipitation, leaching of soil nutrients, inadequate woody debris left on ground as a soil nutrient bank after logging.]

A rattlesnake can flick its tail 90 times per second. (Compare that to the speed at which you can flick a finger and address the possible differences in muscle biology.) [Science News 150:53 July 27 1996.]

A 26-year-old woman complained of weakness and lassitude. Her blood pH was 7.56 and her arterial pCO2 was 45.2 mMol. Blood pressure was 90/60. This is a terrific case, well presented, with a wealth of data on blood gas and electrolyte values. The case requires students to consider the functional interaction of several organ systems. [Nephrology Dialysis Transplantation 16:1066-1068.] A printable pdf copy is available at Teaching Point .

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• Published: 26 June 2024

Deconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists

• Ashty S. Karim   ORCID: orcid.org/0000-0002-5789-7715 1 , 2 ,
• Dylan M. Brown   ORCID: orcid.org/0000-0001-8153-7683 1 , 2 ,
• Chloé M. Archuleta 1 , 2 ,
• Sharisse Grannan 1 , 3 ,
• Ludmilla Aristilde   ORCID: orcid.org/0000-0002-8566-1486 1 , 4 ,
• Yogesh Goyal   ORCID: orcid.org/0000-0003-3502-6465 1 , 5 , 6 ,
• Josh N. Leonard   ORCID: orcid.org/0000-0003-4359-6126 1 , 2 ,
• Niall M. Mangan   ORCID: orcid.org/0000-0002-3491-8341 1 , 7 ,
• Arthur Prindle 1 , 2 , 8 ,
• Gabriel J. Rocklin 1 , 9 ,
• Keith J. Tyo   ORCID: orcid.org/0000-0002-2342-0687 1 , 2 ,
• Laurie Zoloth 1 , 10 ,
• Michael C. Jewett 1 , 2   nAff13 ,
• Susanna Calkins   ORCID: orcid.org/0009-0001-3653-0236 1 , 11   nAff14 ,
• Neha P. Kamat   ORCID: orcid.org/0000-0001-9362-6106 1 , 2 , 12 ,
• Danielle Tullman-Ercek   ORCID: orcid.org/0000-0001-6734-480X 1 , 2 &
• Julius B. Lucks   ORCID: orcid.org/0000-0002-0619-6505 1 , 2  

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• Synthetic biology

Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists.

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Introduction.

Synthetic biology is the fundamental science and engineering research that allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Synthetic biologists leverage tools and concepts from biology, chemistry, physics, mathematics, engineering, computer science, and the social sciences to harness the enormous diversity of biological function, creating new biological systems that are advancing agriculture 1 , 2 , sustainable biomanufacturing 3 , 4 , 5 , and medicine 6 , 7 , 8 , 9 . Recognition of this potential has led to synthetic biology becoming a major driver of the growing bioeconomy 10 , 11 , 12 . This in turn has created a surge of interest in synthetic biology, attracting an increasing number of researchers and students from around the world who bring diverse backgrounds and perspectives to the field.

While the potential of synthetic biology is clear, developing an approach to train students that meets the diverse needs of this field faces two related challenges. The first challenge is that the field has developed from threads rooted in multiple individual disciplines, resulting in a broad diversity of concepts that must be taught and integrated. At the core are the biological concepts that explain how a function is encoded within a DNA sequence, how control of gene expression activates this function, and how this function can be changed by manipulating the DNA sequence. Building upon this, early synthetic biology incorporated concepts from physics and computer science abstractions that viewed biological components as being ‘wired’ in genetic networks that controlled information flow, much like electronic circuits 13 , 14 , 15 . At the same time, systems biologists were using some of these concepts to study and manipulate cellular networks and signaling pathways 16 , 17 , and chemical engineers were using principles of dynamics and control to engineer metabolic processes for bioproduction 18 , 19 . From these roots, mathematical approaches developed in systems biology were added 20 as well as concepts from chemistry to create new components not yet found in nature 21 . As the field has advanced concepts out of the lab and into the world, approaches from ethics, social sciences, business, and law have become important to incorporate so that researchers innovate responsibly with positive societal impacts 22 , 23 , 24 .

The conceptual breadth of synthetic biology is difficult to cover in any single training program which gives rise to the second challenge for training in synthetic biology—undergraduate and graduate students are often siloed within single disciplines and degree programs, creating barriers to learning outside of these traditional boundaries. Thus, students receive most of their exposure to synthetic biology through elective courses or research in labs rather than through a structured curriculum as might be associated with other mature disciplines. This can lead to synthetic biology training that emphasizes a narrow set of concepts over others or focuses on content rather than “science practices” 25 that are known to support deep learning 26 , 27 . For example, there might be an intense focus on training students how to manipulate CRISPR genome editing systems on the molecular scale, but very little integration of how deficiencies of the molecular-level genome targeting affect the function of the larger cellular system, tissue, or organism in which the CRISPR system is utilized.

The field must overcome these training challenges, as integration of these multi-disciplinary concepts is critical for developing successful synthetic biology technologies. For example, cellular synthesis of products from sustainable feedstocks requires understanding the underlying reaction chemical kinetics (chemistry), enzyme biophysics and substrate transport (physics), genetic regulation of enzymes and cellular physiology (biology), reactor vessel scale-up (engineering), and socio-techno-economic analyzes (business). Similar combinations of expertise are also required to create synthetic biology technologies that address other important societal goals in sustainability, environmental health, and human health.

Fortunately, important first steps to developing new training approaches are beginning to happen with the emergence of new undergraduate opportunities and PhD programs in synthetic biology. For high school students and undergraduates, experiential learning opportunities have emerged to facilitate hands-on learning, such as BioBits Kits 28 , 29 , 30 , 31 , the ODIN marketplace for genetic engineering supplies 32 , BioBuilder 33 , and others 34 , 35 . In addition, opportunities such as the international Genetically Engineered Machines (iGEM) competition, the Build-a-Genome Course 36 , and the Cold Spring Harbor Summer Course in Synthetic Biology have paved the way to explore synthetic biology and this integration of disciplines. Though, there is an opportunity to refine and expand these efforts with an overarching framework that more systematically incorporates concepts from the many fields contributing to synthetic biology. At the PhD level, two notable programs in the US (Rice University) and the UK (Imperial College) have begun to explore systematic approaches to training in synthetic biology. Rice’s PhD program covers physical biology, systems biology, and synthetic biology, requiring one dedicated course in synthetic biology. Imperial College’s program starts with a Master of Research degree followed by a PhD with courses in systems biology and synthetic biology. Both programs are structured to provide training to students to integrate concepts across disciplines but require significant prerequisites in STEM. But how do students who may not have access to one of these programs receive this type of synthetic biology training? The Engineering Biology Research Consortium (EBRC) has worked to address this by creating an “Introduction to Engineering Biology” curriculum module to give students a basic understanding of the tools, technologies, and opportunities in synthetic biology 37 . While each of these programs are important first steps, a critical opportunity remains for creating a new approach to synthetic biology training that can: (1) teach synthetic biologists of the future how to traverse and integrate multiple disciplines into their understanding of the field, no matter what their specific background; (2) be accessible to students from a range of backgrounds in order to democratize opportunity and access to synthetic biology concepts; and (3) be adaptable to incorporate advances in a rapidly changing field.

To address this opportunity, we created a conceptual framework for synthetic biology training that can be used in any course or program, developed over the past several years as part of the National Science Foundation-sponsored “Synthesizing Biology Across Scales“ graduate training program at Northwestern University. The framework is based on the observation that every synthetic biology technology is made up of components that function across multiple scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—and that the success of these technologies is deeply dependent on their interfaces (Fig.  1 ). This scales framework can be found in other engineering disciplines as well, such as in electrical and computer engineering where technologies naturally break down along scales, from transistors, to circuits, to chips, to devices, and integrate across scales to enable powerful applications.

A schematic representation of the deconstruction framework: biotechnologies can be deconstructed along scales to identify biological phenomena that are important to the technology at each scale, understand the principles by which these phenomena work at that scale, and identify the important interfaces between scales where engineering challenges often arise. Deconstructing technologies along scales allows multidisciplinary concepts to be mapped and applied at individual scales (annotated) and allows new technologies to be reconstructed by combining elements and applying concepts at each scale.

Here, we describe a course-based implementation of the scales framework that teaches undergraduates, masters, and PhD students how to deconstruct synthetic biology across scales, analyze how components interact at interfaces between scales to yield emergent phenomena, conceptualize how to combine components across scales to create new synthetic biology solutions to global challenges, and incorporate the consideration of ethics when developing synthetic biology technologies. Our vision is that training students to deconstruct synthetic biology technologies across scales will help them (1) recognize where their domain expertise fits within a particular synthetic biology technology, (2) identify their own knowledge gaps that can be filled through additional topical learning or research collaborations, and (3) gain a holistic picture of the landscape of pieces that must work together to create a successful technology. Each of these “science practices,” which allow students to actively engage in scientific inquiry, promotes disciplinary learning and development as a scientist 25 . Emphasizing the societal scale, we hope to drive responsible innovation by training students to think of concepts in ethics, access, equity, and societal-level impact early and often throughout the development of synthetic biology technologies. We envision that the scales framework and the corresponding deconstruction approach is a launching point for the field of synthetic biology to provide a foundational way of training the next generation of synthetic biologists.

The scales framework for synthetic biology

The scales framework is a conceptual way to understand how to build synthetic biology solutions to address societal challenges how biological phenomena work across multiple scales (Fig.  1 ). The deconstruction approach to teaching this framework posits that for a given synthetic biology technology, the components and functions that work together to form that technology can be thought of as working along distinct scales: molecular, circuit/network, cellular, biological communities, and societal. Each of these scales represent a distinct set of components and functions and the physical, chemical, biological, and social science concepts that naturally drive function or impact at that scale. In addition, interactions between components at the interfaces between these scales often give rise to emergent behavior and engineering challenges that are important for real-world applications. Below we briefly describe the components, functions, and concepts that arise at each scale.

The molecular scale includes the individual molecular components of biological systems (e.g., nucleic acids, proteins, lipids, metabolites) and the physical, chemical, and mathematical principles required for understanding and engineering the function of these components. Driving concepts at the molecular scale include the biophysics of protein and RNA folding (including concepts such as free energy folding landscapes and folding kinetics), molecular interactions, enzymology, and others 38 , 39 . The functions that occur on this scale are molecular structure, complex assembly 40 , catalysis (enzymes) 41 , motion (molecular motors) 42 , charge transport 43 , and others that are carried out by individual molecules.

The components of the network/circuit scale consist of collections of molecules that interact to give rise to higher-order functions, often depending on which subset of interactions are present. Network/circuit scale functions are those that biological systems utilize to propagate information, coordinate physiological states, and implement control over those states 44 , 45 . Common biological functions at this scale include coordination and regulation of gene expression (transcription/translation), propagation of information in biological systems in signaling networks, and control of molecular transformations in metabolic reaction networks 44 , 45 , 46 , 47 , 48 .

Phenomena at the cell/cell-free systems scale encapsulate the components of the molecular and network/circuit scale, creating a biochemical environment that supports systems-level functions. Biological functions at this scale include coupled transcription, translation, and post-translational modification 49 , mechanobiology 50 , cell division 51 , exo- and endocytosis 52 , cell sensing 53 , somatic hypermutation (i.e., antibody production) 54 , homeostasis 55 , and transport 55 , 56 . Sometimes these functions can be spatially organized within a range of cellular components such as lipid vesicles, bacterial microcompartments, and macromolecular condensates that organize molecules in membrane-less organelles 57 , 58 . At this scale, concepts that govern the behavior include molecular transport, reaction diffusion, energy and redox balance, and others. Cell-free systems are included here because they can perform many of the same functions as cells with similar levels of biological complexity 7 , 59 , 60 .

The components of the biological communities scale include multi-cellular interactions and communities of organisms that work together to give rise to higher-order functions and emergent behaviors 61 . There is a rich diversity of systems at this scale, ranging from microbiomes and biofilms to tissues, organs, and even whole bodies 62 , 63 , 64 , 65 , 66 . Biological functions that occur on this scale include emergent microbial community dynamics 65 , cell-cell signaling 67 , 68 , biofilm formation 69 , tissue-scale phenomena such as tissue growth 70 , regeneration and function, cell-material interactions, inter- and intraspecies metabolic interaction 71 , and others 72 , 73 , 74 . Population dynamics, microbial ecology, metagenomics, and micro- and macroevolution play a significant role at this scale.

Finally, the societal scale encompasses concepts that will determine how synthetic biology technologies impact, influence, and change the world around us. Functions at this scale include technology distribution; equity and affordability in technology access; social, biological, and economic sustainability; public perception; legal and regulatory aspects of technology (intellectual property and policy); and more 24 , 75 , 76 , 77 . The concepts associated with this scale include the philosophical ethics of synthetic biology research, stakeholder interaction and analysis, frameworks for user studies and field trials, lifecycle analysis, and quantitative estimates of the needs and viability of synthetic biology technologies 78 , 79 . Traditionally this scale has been separated from science and engineering at the other scales, yet it contains components and functions driven by scientific principles similar to the other scales. Recognizing the need to train ethically minded practitioners, we emphasize the integration of the societal scale as one of the five key scales so that we consider it as an important part throughout training and technology development.

The interfaces between these scales give rise to emergent behavior important for applications, though this can also present challenges for engineering. By understanding these interfaces, we can learn general “rules” to emergence of complexity and, in turn, engineer-improved technologies. We can understand these interfaces through common methods for bridging across scales. For instance, mathematical techniques such as mean-field averaging, which assumes that many identical components interact in similar ways 80 , and asymptotic analysis, which characterizes the strongest interactions between heterogeneous components 81 , enable us to analyze the transition between scales. The fundamental properties, process, and results of mapping interactions to macro-level behavior inform our understanding of the emergence of complexity across scales 82 , 83 , 84 , 85 , 86 .

For some technologies that we deconstruct, the scales are clear. Practitioners can identify a global challenge (e.g., chemical production, environmental health, human health) and deconstruct synthetic biology technologies that address them (e.g., semi-synthetic artemisinin, bacterial nitrogen fixation, CAR-T therapeutics) (Box  1 ). However, for some technologies, scales with strong interfaces may naturally blur together; for instance, it is hard to define exactly when a molecular scale complex that regulates protein phosphorylation begins to process and propagate information through a phosphorylation cascade at the network scale 87 . Learning to deconstruct synthetic biology solutions allows practitioners to understand when the boundaries between scales become ‘fuzzy’, so that they can take advantage of the gradation of phenomena that occur across different spatial and temporal scales and engineer them accordingly. By using case studies on real-world synthetic biology technologies, we can teach core concepts of the field to students from diverse backgrounds in an interactive and engaging way.

Box 1. Deconstruction case studies

The deconstruction approach provides a framework to analyze synthetic biology technologies through case studies . Synthetic biological systems that address challenges in (A) the environment (nitrogen fixation), (B) sustainable bioproduction (semi-synthetic artemisinin production), and (C) human health (CAR-T therapies) are deconstructed along scales.

Box   1 Text . Many synthetic biology technologies can be broken down into components that must work together across the molecular, circuit/network, cellular, and biological communities scales. For each technology, societal scale concepts concerning ethics, equity, access, intellectual property, and business considerations are critical to its success. Here are several examples of flagship synthetic biology technologies deconstructed across these scales.

Environmental Health—nitrogen-fixing bacteria for sustainable fertilizers. Nitrogen-fixing bacteria that can produce fertilizer compounds offer a potential solution for sustainable farming, currently challenged by an over-reliance on energy-intensive chemical fertilizers that cause environmental contamination when overapplied 91 . Engineering a bacteria to produce enough fixed nitrogen for farming needs requires understanding and engineering across scales. At the molecular scale, the core nitrogen-fixing reaction is carried out by the nitrogenase enzyme complex 92 , 93 . Nitrogenase requires coordinated interaction with electron-transporting proteins that work together at the network/circuit scale 92 , 108 . Also important at the network/circuit scale are the layers of genetic circuitry that coordinate the synthesis of the many nitrogenase components and its cofactor synthesis enzymes—this regulation must be understood as it presents potential barriers to controlling nitrogenase expression 108 . Both of these scales are embedded in a cellular chassis that must support their function 94 , 95 . Finally, the eventual application of a nitrogen-fixing bacteria in the soil requires considerations at the biological communities scale to understand how this bacteria would interact with the native soil microbiome and the target plants 109 , 110 . At the societal scale, questions arise as to the safety and biocontainment strategies needed when releasing engineered organisms, technology access, which intellectual property strategies that can benefit the most people including farmers, and stakeholder analysis to understand if the technology will be adopted.

Biochemical Production—semi-synthetic artemisinin production. Artemisinin is a frontline anti-malarial drug produced in the plant Artemisia annua , and its availability can be challenged by seasonal production variation 111 . Microbial bioproduction of more artemisinin requires understanding and engineering across scales. Often bioproduction strategies genetically integrate metabolic pathways into a heterologous host that is then further engineered to make the molecule of interest 18 . At the molecular scale, artemisinin production requires tailored cytochrome P450s and dehydrogenases 96 . At the network scale, these enzymes, along with others, must work together in metabolic pathways with carbon flux carefully controlled to minimize toxic intermediates and side reactions 112 , 113 . This control requires selection of an appropriate cellular scale host organism that can support the necessary central carbon metabolism and tolerate the acid toxicity of the product 114 , 115 . As production is scaled, the communities scale becomes important, as scale up requires populations of cells to interact with one another in a complex bioreactor environment where availability and transport of nutrients (e.g., oxygen levels, pH) can become important 116 , 117 , 118 . At the societal scale, questions of cost and profitability, sustainability of production, infrastructure requirements, accessibility to the biochemicals, public perception, and acceptance of the technologies naturally arise.

Human Health—CAR-T cell therapy. Chimeric antigen receptor (CAR) T-cell therapy is a promising approach to provide treatments for an expanding range of cancers 97 , 98 , 119 . CAR-T therapies are designed to reprogram the natural abilities of the human immune system to recognize cancer cells and trigger their destruction, and as such they require engineering and consideration across multiple scales. At the molecular scale, a key challenge is designing the CAR protein to recognize features that are unique to the surface of cancer cells while not recognizing healthy cells 120 . Once a cancer cell is recognized, the CAR must activate processes at the network scale within the T cell, triggering cell-mediated killing and gene expression programs 121 . At the cellular scale, the importance of cell identity becomes critical, since CARs can be implemented in a range of immune cell types, with each choice impacting CAR performance 121 . At the biological communities scale, concepts related to side effects (including off-target and on-target activity) become important, creating a natural interface to the molecular scale at which CAR variants can be engineered to have improved specificity 122 . In this scale, concepts such as transport also become important, such as distinct challenges associated with using CAR-T cell therapies to treat solid tumors because of limited penetration, as compared to blood cancers in which T cells can more readily access cancerous cells. At the societal scale, challenges and concepts related to safety, ethics, clinical trials and cost and access of the treatment become important when analyzing the success of the technology 123

A case studies-based course in the deconstruction approach

Our course teaches senior undergraduate students and first-year graduate students from a range of degree programs how to analyze problems and solutions related to synthetic biology through the deconstruction approach. The learning objectives of this course are for students to be able to: (1) deconstruct biological phenomena along the scales that they occur; (2) analyze how engineering choices made at one scale affect biological function at another scale; (3) assemble potential synthetic biology solutions to global challenges across scales; and (4) identify the scientific value and impacts of synthetic biology research on broader societal goals, as well as ethical considerations that arise. The course has no prerequisites and was designed to achieve these learning objectives through a case studies pedagogical approach, which is proven to enhance learning and student engagement 88 , allowing integration of multi-disciplinary concepts across scales.

For the course, we identified three of the most pressing global challenge areas currently being addressed by synthetic biology to develop case studies—environmental health, biochemical production, and human health (Box  1 ) 2 . Each challenge area is taught over the course of a three-week module and includes a historical basis for the global challenge (e.g., defining the problem), current synthetic biology research and commercial endeavors in this area, a deconstruction of at least one poignant example, homework assignments (e.g., investigating and designing solutions), student presentations (e.g., explanation), and a guest lecture by an expert in that area. We introduce each challenge area loosely based on the Heilmeier Catechism 89 , defining the problem, how it is addressed today, how synthetic biology might play a role in addressing it, and a discussion on the societal risks, success, and future of synthetic biology in the challenge area. Each module builds on the previous module, adding a deeper layer of understanding of the deconstruction approach (Fig.  2 ). For example, in the first module we define the scales in the context of a guided case study, in the second module we ask students to weight the importance of each scale to a chosen technology, and in the third module students tackle the challenges at the interfaces between scales. While our course used environmental health for module 1, biochemical production for module 2, and human health for module 3 (Fig.  2 ), the progression of modules can be taught using any topic sequence, allowing the course to be adapted to the needs or interest of different teaching environments and to new topics that emerge as the field progresses. In addition, the division of the course into modules is naturally amenable to team teaching approaches.

The course is split across three modules with each subsequent module exploring deeper concepts of the deconstruction approach. Different case studies can be used to implement each module, depending on instructor and student interests. Here we show the progression from environmental health to biochemical production to human health topics in the Northwestern course.

We begin the course by introducing environmental health challenges in the context of United Nations Sustainable Development Goal 3 90 —good health and well-being—and survey the many ways synthetic biology could contribute to solutions in soil, water and air quality, carbon sequestration, waste valorization, remediation, sustainable resource recovery, sustainable biomaterials, recycling, and sustainable fertilizers. We then focus on our first major deconstruction case study on bacterial nitrogen fixation for sustainable fertilizers (Box  1 ). The nitrogen fixation example also serves as the first introduction to the five scales, as it is deconstructed in the narrative of imagining a synthetic biologist wanting to address the environmental challenge of chemical fertilizers. After a historical introduction to Crooke’s challenge of the need for fertilizers, the geopolitics of fertilizer distribution, and the development of the Haber-Bosch process 91 , we then imagine how a synthetic biologist may partner with nature to create a more sustainable way to produce fertilizer. This naturally starts at the cellular scale by identifying nitrogen fixing bacteria, and quickly dives into the molecular and network/circuit scales on the quest to understand how to engineer the microbe to fix more nitrogen through understanding the nitrogenase enzyme complex and its regulation 92 , 93 . Reviewing the literature gets us back to the cellular scale to understand which microbes are optimal 94 , 95 . The biological communities and societal scales naturally emerge when we consider applying engineered microbes to the field. Two guest lectures in this area, one focusing on academic synthetic biology research in this area and another representing synthetic biology startup companies, give students multiple perspectives to understand how this area is actively being pursued.

The focus on fertilizer and agriculture naturally transitions the course to the biochemical production challenge area, where we begin by understanding how commodities such as food, energy, water, materials, and chemicals are intricately linked, and how holistic understanding of a challenge area can give rise to useful solutions. We deconstruct early advances of molecular biology and early synthetic biology technologies such as golden rice, Roundup Ready® crops, and first, second, and third generation biofuels. Our major deconstruction case study in this section is the semi-synthetic artemisinin project 96 (Box  1 ), where we use class time to deconstruct the technology along each scale and identify the scales in which key hurdles were overcome during the project. Importantly, we discuss the number of resources that were dedicated to the project, the amount of fundamental knowledge that was gained, the technologies developed during the project that are being used in other areas of synthetic biology, and the current commercial use of the technology as way to evaluate the success of the project. An industry speaker is included in this section to give students perspective on sustainable bioproduction products that are actively being marketed and sold.

The course finishes with the human health challenge area, where we begin by introducing the unique layers of complexity that occur at the biological communities and societal scales. We frame the need for synthetic biology solutions in human health by discussing the historical development of pharmaceuticals and the promise of synthetic biology for developing new therapeutic approaches 6 . We then dive into cell-based therapies and recent synthetic biology tools that allow for molecular, network, and cellular scale engineering of mammalian cells, and control of variability across a population of cells. Our deconstruction case studies in this section are CAR-T-cell therapies 97 , 98 (Box  1 ) and gene drives 99 . Following a student-led deconstruction of these activities, we use discussion-based learning techniques to emphasize the ethics of human subject research through case studies on the use of HeLa cells and personal genomics. Our guest lecturer in this area is a societal scale expert (e.g., bioethicist, artist) that emphasizes the application of societal scale concepts in the course. In addition, we include a guest lecture from one of our faculty to introduce research actively being pursued in our institution.

An important component of our pedagogy is activities for students to actively deconstruct technologies across scales, including individual assignments, small-group evaluation of technologies, and cooperative learning activities based on inclusive teaching practices 100 , 101 , 102 (Fig.  3 ). This begins in the environmental health section where students are assigned to pick a technology and deconstruct it without the scales framework introduced ( assignment 1 ). Once the nitrogen fixation technology is deconstructed in lectures, they are then asked to revisit the deconstruction of this same technology with the scales framework ( assignment 2 ), and present to class. In the biochemical production section, the course begins to flip from instructor-centric to student-centric deconstructions through additional group work. We randomly paired students together and asked them to pick a technology to deconstruct and go beyond just identifying the scales by weighting the importance of each scale within their chosen technology (Fig.  3A ). We found that students interpret the importance of scales differently. For example, two students focusing on food alternatives found different scales are important for different technologies, while in some metabolic engineering examples, students found the network/circuit scale to be of importance regardless of the selected technology. This type of cross-case comparison helped promote the abstraction of deconstruction concepts.

A Students deconstructed technologies in groups of two and assessed the importance of each scale for their given technology. Each group was asked to rank how important each scale was for their selected synthetic biology technology from 0 (no importance) to 10 (high importance). Radar plots are displayed for different student groups’ responses where each geometric shape or area represents one response. Differences in student responses on ‘the importance of scales’ are depicted in three ways: deconstructing the same technology, deconstructing different technologies that aim to tackle a similar problem, and deconstructing similar technologies within a research area. B Students deconstructed technologies across scales using an inclusive teaching technique called a jigsaw group activity. Each circle represents one student in the course, each letter is a specific scale, and each number corresponds to a specific grouping of students that are assigned a different technology. Home groups allow students to frame their deconstruction across different scales, while scale expert groups allow students to gain expertise in a scale by comparing across different technologies. Reassembling back into home groups allows students to share their expertise and learn from each other. Discussing the societal scale across technologies as a class allows comparisons between different technologies.

In the human health section, CAR-T and gene drives are deconstructed through a unique jigsaw method, a cooperative and inclusive learning approach that requires students to address a complex problem from various theoretical and/or methodological approaches (Fig.  3B ) 100 , 101 , 102 . Students are first split into several “home (jigsaw) groups” consisting of one “scale expert” at the molecular, network, cell/cell-free, and biological communities scales to discuss a game plan to deconstruct their assigned technology. While students do not necessarily have expertise in their assigned scale, using the term ‘expert’ is meant to inspire confidence in students to learn scale concepts and then empower them to teach their peers. Students then divide small “scale expert groups” and use peer instruction to develop deep knowledge in a specific scale (a ‘piece of the puzzle’). The students then return to their home groups, synthesize their expert information into a compelling deconstruction of their technology and together discuss the societal scale. At the end of this activity, we come back to a large group discussion of technology challenges across scale interfaces and the societal implications of the technology.

Throughout the course, each student is assigned to conduct a newsreel presentation by presenting one synthetic biology research article and one news item of their choice to the class using the scales framework, creating a consistent source for ethics discussions and other societal scale topics. Finally, students perform and present a deep dive deconstruction of a technology of their choice as their final project. In this way the course incorporates a wide range of technology case studies that are both instructor and student chosen. The ability for students to drive most of the topic selection (e.g., engaging in the practice of science) in this course builds off the known positive impact of choice on student engagement 103 and allows course content to adapt as the field of synthetic biology evolves.

By framing the course around biotechnologies and the scales of synthetic biology, we can teach synthetic biology in a way that is agnostic to student backgrounds and expertise. In this way, we can introduce multi-disciplinary concepts from biology, chemistry, physics, mathematics, computer science, engineering, and the social sciences in the context that they are needed within a given scale. This helps students identify where their background and expertise can be incorporated within a synthetic biology technology. The scales framing also allows students to identify their own knowledge gaps so that they can fill them with further study and collaboration.

Evaluating success of the deconstruction approach

Teaching a course rooted in quantitative fundamentals of synthetic biology technologies, but largely taught through learning how to define problems, develop models, construct explanations, and build arguments (e.g., scientific practices) has proven to be a rewarding experience for students. In total, 103 students from chemistry, biology, biomedical engineering, civil and environmental engineering, and chemical engineering programs took the course across three separate years that the course was offered at Northwestern University. Students across implementations of the course resonated with the deconstruction approach as can be seen from an analysis of end-of-course written reflections as part of their final projects (Table  1 ). Responses, subjected to thematic analysis 104 , revealed that students not only enjoyed the course but also developed holistic ways of thinking, critical thinking skills, an ability to recognize challenges at the interface between scales, and an understanding of how they would use the deconstruction approach outside the course (e.g., reading literature, career aspirations). Years after taking the course, one student reflected in an interview that, “[the scales framework] has been super helpful for the conception of my own research because I’m often on the lower scales, more of the mechanisms and specific interactions of molecules and proteins. Anytime we’re making single changes to add more of this one component to our mixture, it really changes everything else … and it goes beyond these lower-level interactions. It’s not that I’m consciously trying to think in that way, but I think it’s been baked into me. These scales all do interact and are relevant. Even when it feels like I’m making small changes, I feel I need to stop and consider the potential for repercussions and effects that would climb up the ladder.” Students have applied and seen value in the skills developed in the course years after taking the course.

Integrating the societal scale into a STEM course

An important goal of the deconstruction approach is to train students to think about the societal scale impacts of their work as it is being conceptualized, rather than after it has been done. Traditional science and engineering training often leaves out societal scale components or relegates them to special courses in the humanities (e.g., bioethics) or business (e.g., intellectual property) that do not fully integrate these topics within science and engineering. We integrated the societal scale into our course in three specific ways: (1) training students to identify challenges at the societal scale, and biological functions needed to address these challenges, through course assignments; (2) creating space for students to explore the connectedness of how science and engineering choices made at one scale could drive outcomes at the societal scale through in-class discussion grounded in bioethics best practices 105 ; and (3) inviting a guest lecturer with expertise in bioethics and the societal scale to guide an informed and meaningful discussion around this scale using examples from their own work. Our intent was to introduce students to the many topics this scale encompasses (e.g., bioethics, technology access and equity, intellectual property, business models, investment strategies, and policy), teach them to identify connections between the societal scale and the four other scales and teach them how to discuss and grapple with societal scale challenges for any technology.

Our specific societal scale and bioethics discussion activities were based on bioethics best practices 105 . We conducted think-pair-share class discussions with prompts along several themes: (1) themes related to societal perceptions of biotechnology; (2) themes related to unintended consequences of developing biotechnologies; and (3) themes related to additional safeguards and regulatory processes that could be developed in response to unintended consequences. For example, during the human health part of the course when we discussed gene drives as a method to combat malaria. Our discussions touched on intellectual property, genetically modified organisms, and regulations; molecular and cellular approaches to biocontainment to mitigate risk; and public perception of technology and what is natural. We wove these types of concepts into each case study, student deconstruction assignments and discussions, and a standalone discussion of the ethics of human subject research. The most recent iteration of the course also had an artist lead discussion of how science and art can interface to impact the world. As a result, students often expressed excitement and eagerness to think about the societal scale and how they might advance or disrupt the world in which we live. In our discussions we did not try to seek an answer to questions at this scale but rather focused on presenting and discussing different viewpoints, emphasizing the importance of considering societal scale challenges. Many students came away with their viewpoints expanded, with 34% commenting on the importance of societal scale thinking (Table  1 ).

Adapting the approach to other learning environments

In developing the course, we created a syllabus, a schedule, and content that is designed to be adapted to other learning environments. Our goal is for the scales framework and the deconstruction approach to be adaptable to support a range of learning objectives within different institutions and programs and to be adapted to changes with the field. Towards this goal, we have created and included here a modular version of our course structure, a syllabus, and the three evaluated deconstruction assignments with corresponding rubrics for any instructor who would like to use them or adapt them for a course in synthetic biology (see Supporting Information). The content can be used in several ways. If instructors are comfortable with the progression of topics from environmental health to biochemical production to human health, then the course plan could be used verbatim to implement a full course that could serve as an introduction to synthetic biology, or as a second course in synthetic biology. If instructors would rather begin with a different topic area, then they could use our course plan and structure as an example and choose a different framing example in a different topic area (Box  1 ) to do a full deconstruction of a technology at the beginning of the course, followed by similar activities to explore other topic areas. This method could also be used to implement a standalone module on the deconstruction approach within a different synthetic biology course. In this model, case studies can be used to get students excited by the field before deep diving into synthetic biology tools and principles that are typically discussed in introductory synthetic biology courses. It was important to select case studies that we as instructors had expertise in to give the most enriching experience for our students and to help facilitate their learning. Including more formal cross-case study comparisons would help enhance student understanding of the deconstruction approach and mobilize knowledge. Portions of the course could even be used as modules to add an ethics component to an existing synthetic biology course. In addition, the three framing deconstruction assignments can be added into existing courses to teach and evaluate student learning of the deconstruction approach. While our implementation of the course was tailored to a mixed class of advanced undergraduates, masters, and beginning PhD students, we envision the approach being easily tailored to other groups.

Over three years of implementing this course, several best practices for implementation appeared. Initially the course was developed for synchronous, remote learning and was adapted to in-person sessions which means that the course is fully compatible with remote, in-person, or hybrid teaching. At the heart of the course are student presentations and discussions. This made the course challenging to implement when class sizes reached more than 30 students. The number and type of presentations can be changed to address this. We also struggled to identify the proper number of assignments and in-class activities given that most assignments were free-form writing. Giving comprehensive rubrics and instructions helped manage expectations and improved student enjoyment of the course. While we had no prerequisites for the course, many students who took previous biology and/or synthetic biology courses had an advantage. Implementations of the course where this is the only available course in synthetic biology may benefit from an “introduction to synthetic biology” module to familiarize students with tools and techniques in the field. Despite differences in prior knowledge, we had students come to this course from chemistry, biology, engineering, and biotechnology and left inspired to work in synthetic biology.

Looking to the future

As the field of synthetic biology matures, there is a compelling opportunity to explore common training approaches across institutions that can be used to accelerate progress in the field even further. As a highly multi-disciplinary field, it can be challenging to find a convergent training approach that incorporates cross-field concepts while giving students and practitioners a common language to integrate these concepts towards a common engineering goal. We believe that by emphasizing the scales of engineered biological systems and their application use cases, the scales framework and the deconstruction approach helps to achieve this goal and can incorporate discipline-specific concepts simultaneously. In this way, the scales framework facilitates the teaching of “science practices” (e.g., modeling, explanation, argumentation) 25 and core ideas of 21st-century science which will facilitate developing disciplinary expertise and versatility 26 , 27 .

Here, the scales approach has allowed us to train students from a range of disciplinary backgrounds in common, multi-disciplinary concepts. Teaching students first how to deconstruct technologies along scales and then identify concepts that apply at each scale, allows them to integrate diverse concepts together in the context of how they are used for engineering. While biological emergent behavior lends itself to the scales-based framework, synthetic biology has traditionally been skewed towards the molecular and circuits/network scales. In contrast, bioengineering and biomedical engineering are traditionally skewed towards the cell and biological communities scales. Yet often the goals of synthetic biologists and bio/biomedical engineers are the same: to tackle a global challenge with biological solutions. The scales framework allows for appreciation of all the scales, which we hope encourages researchers to seek out knowledge of traditionally overlooked scales and work across scales to develop impactful biotechnologies.

While we have started to lay the framework for a deconstruction approach to teaching synthetic biology, it is far from complete. As the field evolves, it is our hope that the deconstruction approach evolves with it. We can already see evidence of this through the definition of the scales. For example, in our recent implementation of the course during a deep dive into CRISPR gene drives, students challenged our definition of the biological communities scale and actively discussed whether a new scale should be added to encapsulate concepts relevant to organismal populations such as population genetics. In addition, drawing connections to how different other fields use the scales framework—like computer engineering where technologies are built from transistors, to circuits, to chips, to devices—can further refine its application to synthetic biology and drive additional innovation. For example, the existence of computer-aided design tools that can be used within and across scales to design computer systems is a powerful encapsulation of the scales framework and is a particularly exciting prospect for synthetic biology 106 , 107 . Using this central framework, iterations of this course could be developed that bring in additional discipline-specific concepts, pointing out when in each synthetic biology technology those concepts can be applied. In this way, a student trained in that discipline can learn when and how to collaborate with researchers in other disciplines, addressing the need to learn to integrate and traverse disciplines. We anticipate that continued adoption, discussion, and development of the deconstruction approach will allow the concepts to be refined to match the needs of the field.

We envision the deconstruction approach to be more than just a pedagogical approach to teaching synthetic biology. Rather, we hope that it is viewed as a way of thinking for synthetic biologists of the future. By teaching students to think across scales, we hope that their holistic view of what it takes to make a successful synthetic biology technology will allow them to identify knowledge gaps that can be filled by new learning, new collaborations, or even drive new research to fill those gaps. By placing the societal scale on equal footing with the other scales, we hope to create an ethically minded workforce that will drive responsible innovation. And by emphasizing how many disciplines are needed across scales to achieve success, we hope to welcome diverse perspectives to the field of synthetic biology so we can all work towards solving society’s grand challenges together.

Supporting Information

The following supplemental materials are provided on the Northwestern Arch database ( https://doi.org/10.21985/n2-x989-tb47 ) to aid the adoption and adaption of the scales framework and deconstruction approach to other learning environments:

Northwestern_CSB_Deconstructing_SynBio_Content_Map.pdf – a table outlining how the course content can be delivered across a ten-week course. Modules on environmental health, biochemical production and human health are outlined. A schedule for the provided assignments is given, along with how to integrate guest lectures.

Northwestern_CSB_Deconstructing_SynBio_Syllabus.pdf – example syllabus for the deconstructing synthetic biology course.

Northwestern_CSB_Deconstructing_SynBio_Assignment_1-First_Deconstruction.pdf – the first deconstruction assignment given to students before they have been taught about the scales framework.

Northwestern_CSB_Deconstructing_SynBio_Assignment_2-Second_Deconstruction.pdf – the second deconstruction assignment given to students immediately after they have been taught about the scales framework.

Northwestern_CSB_Deconstructing_SynBio_Assignment_3-Final_Project.pdf – the course final project entailing a deep dive deconstruction using all the principles learned in the course.

Data availability

The full set of deidentified responses used for thematic analysis in Table  1 can be made available upon reasonable request pending ethical consideration of intended use.

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Acknowledgements

We thank all 103 students that participated in this course and our evaluations since 2021 as without them this would not be possible. We would also like to provide many thanks to several colleagues that have provided various forms of feedback on the conceptual framework and this manuscript: Mark Blenner (University of Delaware) for trying out an early version of the course content; Mary Dunlop (BU), Richard Murray (Caltech), Joff Silberg (Rice), Kristala Prather (MIT), Ron Weiss (MIT), and Natalie Kuldell (MIT) who serve on the Synthetic Biology Across Scales (SynBAS) NSF National Research Traineeship (NRT) advisory board who provided critical feedback on the development of the deconstruction approach; and Ron Vale (HHMI) and Tim Mitchison (Harvard) for advice on publishing this work. We would also like to thank Karsten Temme (Pivot Bio), Michael Köpke (LanzaTech), Sam Weiss Evans (Harvard), Weston Kightlinger (Resilience), Jennifer Brophy (Stanford), Khalid Alam (Stemloop), Marilene Pavan (LanzaTech), and Dario Robleto for invaluable contributions made to developing the deconstruction approach through their guest lectures. The development of the deconstruction approach was supported by the National Science Foundation through the SynBAS NRT program (2021900) and by the Bachrach Family Foundation. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

Author information

Michael C. Jewett

Present address: Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA

Susanna Calkins

Present address: Nexus for Faculty Success, Rosalind Franklin University of Medicine and Science, Chicago, IL, USA

Authors and Affiliations

Center for Synthetic Biology, Northwestern University, Evanston, IL, 60208, USA

Ashty S. Karim, Dylan M. Brown, Chloé M. Archuleta, Sharisse Grannan, Ludmilla Aristilde, Yogesh Goyal, Josh N. Leonard, Niall M. Mangan, Arthur Prindle, Gabriel J. Rocklin, Keith J. Tyo, Laurie Zoloth, Michael C. Jewett, Susanna Calkins, Neha P. Kamat, Danielle Tullman-Ercek & Julius B. Lucks

Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, 60208, USA

Ashty S. Karim, Dylan M. Brown, Chloé M. Archuleta, Josh N. Leonard, Arthur Prindle, Keith J. Tyo, Michael C. Jewett, Neha P. Kamat, Danielle Tullman-Ercek & Julius B. Lucks

Independent Evaluator, Lake Geneva, WI, 53147, USA

Sharisse Grannan

Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, 60208, USA

Ludmilla Aristilde

Department of Cell and Developmental Biology, Northwestern University, Chicago, IL, 60611, USA

Yogesh Goyal

Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL, 60201, USA

Niall M. Mangan

Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL, 60611, USA

Arthur Prindle

Department of Pharmacology, Northwestern University, Chicago, IL, 60611, USA

Gabriel J. Rocklin

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A.S.K.—Devised and developed the deconstruction concept, developed and taught the course, wrote the manuscript, made figures, and edited the manuscript. D.M.B.—Developed the course, wrote the manuscript, made figures, and edited the manuscript. C.M.A.—Developed the course and edited the manuscript. S.G.—Developed the course evaluation approach, performed course evaluation, collected, and analyzed evaluation data, and edited the manuscript. L.A.—Developed the deconstruction concept and edited the manuscript. Y.G.—Developed the deconstruction concept and edited the manuscript. J. N. L.—Devised and developed the deconstruction concept and edited the manuscript. N.M.M.—Developed the deconstruction concept and edited the manuscript. A.P.—Developed the deconstruction concept and edited the manuscript. G.J.R.—Developed the deconstruction concept and edited the manuscript. K.J.T.—Devised and developed the deconstruction concept and edited the manuscript. L.Z.—Developed the deconstruction concept, developed the approach to integrating ethics into the course, and edited the manuscript. M.C.J.—Devised and developed the deconstruction concept and edited the manuscript. S.C.—Developed the deconstruction concept, developed the course evaluation approach, performed course evaluation, collected and analyzed evaluation data, and edited the manuscript. N.P.K. – Devised and developed the deconstruction concept and edited the manuscript. D.T.E.—Devised and developed the deconstruction concept and edited the manuscript. J.B.L.—Devised and developed the deconstruction concept, developed and taught the course, wrote the manuscript, and edited the manuscript.

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Karim, A.S., Brown, D.M., Archuleta, C.M. et al. Deconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists. Nat Commun 15 , 5425 (2024). https://doi.org/10.1038/s41467-024-49626-x

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Case Study Questions Class 10 Science Life Processes

Case study questions class 10 science chapter 6 life processes, cbse case based questions class 10 science chemistry chapter 6.

Carbon and energy requirements of the autotrophic organism are fulfilled by photosynthesis. It is the process by which autotrophs take in substances from the outside and convert them into stored forms of energy. This material is taken in the form of carbon dioxide and water which is converted into carbohydrates in the presence of sunlight and chlorophyll. Carbohydrates are utilised for providing energy to the plant.

Ans: 6CO2 +12H2O + Chlorophyll & sunlight👉 C6H12O6 + 6O2 + 6H2O

Ans: The process present in the surface of a leaf or the stem of a plant to allow the exchange of gases.

CASE STUDY : 2

The alimentary canal is basically a long tube extending from the mouth to the anus. In Fig. 6.6, we can see that the tube has different parts. Various regions are specialised to perform different functions.

Ans: Small intestine

iv) What are villi?

lipase – breakdown of emulsified fats

CASE  STUDY : 3

Ans: The conversion of pyruvate into ethanol, CO2 & energy take place in the absence of air(oxygen),  it is called anaerobic respiration.

Ans- i) fish- gills

ii) frog- skin, lungs

CASE STUDY : 4

Case study : 5.

The heart is a muscular organ which is as big as our fist. Because both oxygen and carbon dioxide have to be transported by the blood, the heart has different chambers to prevent the oxygen-rich blood from mixing with the blood containing carbon dioxide. The carbon dioxide-rich blood has to reach the lungs for the carbon dioxide to be removed, and the oxygenated blood from the lungs has to be brought back to the heart. This oxygen-rich blood is then pumped to the rest of the body.

Ans: Vena cava carries deoxygenated blood from body to heart.

Ans: The force that blood experts against the wall of a vessels is called hypertension or high blood pressure.

CASE STUDY : 6

Ans: The loss of water in the form of vapour from the aerial parts of the plant.

v) How does plant remove their waste product?

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National Research Council (US). Intellectual Property Rights and the Dissemination of Research Tools in Molecular Biology: Summary of a Workshop Held at the National Academy of Sciences, February 15–16, 1996. Washington (DC): National Academies Press (US); 1997.

Intellectual Property Rights and the Dissemination of Research Tools in Molecular Biology: Summary of a Workshop Held at the National Academy of Sciences, February 15–16, 1996.

• Hardcopy Version at National Academies Press

5 Case Studies

• Introduction

Each of the following cases involves an important research tool in molecular biology, and each was chosen to illustrate a form of protection of intellectual property and a pattern of development involving both the public and the private sector. For each case, we present background material and a summary of the discussion that raised issues peculiar to the case.

The ideal strategies for the handling of intellectual property in molecular biology are not always immediately obvious, as these case studies illustrate. For most, final decisions have not been made about how access to these research tools will be controlled. Such decisions might be modified in response to both scientific and legal developments.

• Recombinant DNA: A Patented Research Tool, Nonexclusively Licensed With Low Fees

The Cohen-Boyer technology for recombinant DNA, often cited as the most-successful patent in university licensing, is actually three patents. One is a process patent for making molecular chimeras and two are product patents—one for proteins produced using recombinant prokaryote DNA and another for proteins from recombinant eukaryote DNA. Recombinant DNA, arguably the defining technique of modern molecular biology, is the founding technology of the biotechnology industry (Beardsley 1994). In 1976, Genentech became the first company to be based on this new technology and the first of the wave of biotechnology companies, which in fifteen years has grown from one to over 2000.

The first patent application was filed by Stanford University in November 1974 in the midst of much soul-searching on the part of the scientific community. Stanley Cohen and Herbert Boyer, who developed the technique together at Stanford and the University of California, San Francisco (UCSF), respectively, were initially hesitant to file the patent (Beardsley 1994). Several years of discussion involving the National Institutes of Health (NIH) and Congress followed. By 1978, NIH decided to support the patenting of recombinant DNA inventions by universities; in December 1980, the process patent for making molecular chimeras was issued. The product patent for prokaryotic DNA was issued in 1984. The patents were jointly awarded to Stanford and UCSF and shared with Herbert Boyer and Stanley Cohen. The first licensee signed agreements with Stanford on December 15, 1981. As of February 13, 1995, licensing agreements had generated $139 million in royalties, which have shown an exponential increase in value since their beginning. In 1990–1995 alone, the licensing fees earned $102 million.

This case has three key elements. First, the technology was inexpensive and easy to use; from a purely technical standpoint, there were only minimal impediments to widespread dissemination. Second, there were no alternative technologies. Third, the technology was critical and of broad importance to research in molecular biology.

The technology was developed in universities through publicly funded research. The strategy used to protect the value of the intellectual property was to make licenses inexpensive and attach minimal riders. The tremendous volume of sales made the patent very lucrative. Every molecular biologist uses this technology. However, not all inventions are as universally critical. Only a few university patents in the life sciences, such as warfarin and Vitamin D, have been even nearly as profitable as the Cohen-Boyer patent. Clearly, had this technology not been so pivotal for molecular biology or had an equally useful technology been available, the licenses would not have been sold so widely and the decision to license the technology might have met with more resistance.

The Cohen-Boyer patent is considered by many to be the classic model of technology transfer envisaged by supporters of the Bayh-Dole Act, which was intended to stimulate transfer of university-developed technology into the commercial sector. Ironically, it presents a different model of technology than that presumed by advocates of the Bayh-Dole act (for discussion, see chapter 3 ). Lita Nelsen, director of the Technology Licensing Office at the Massachusetts Institute of Technology (MIT), noted that the premise of the Bayh-Dole Act is that exclusivity is used to induce development and that universities should protect their intellectual property because without that protection, if everybody owns it, nobody invests in it. ''The most-successful patent in university licensing, in the entire history of university licensing, is the Cohen-Boyer pattern which is just the reverse. It is a nonexclusive license. It provides no incentive, just a small tax in the form of royalties on the exploitation of the technology.''

The biotechnology boom that followed the widespread dissemination of recombinant DNA techniques transformed the way universities manage intellectual property. It also fundamentally changed the financial environment and culture of biological research.

Nelsen described two ways in which this patent was so successful in fostering the aims of the Bayh-Dole Act. First, it got the attention of biologists by showing the advantages of protecting intellectual property. Stanford earned respectability for the venture by involving NIH and discussing in a public forum how this technology could be disseminated in a way that would not impede research. Second, it got the attention of university chancellors. They began to see that licensing, patenting, and technology transfer might have some financial benefits for the university. Nelsen commented that "that went a little too far. Everybody was waiting for $100 million per year out of their technology transfer offices. Most of them did not get it, and most of them are never going to get it." In the meantime, technology transfer managers developed more experience and became professionalized. They began to learn how to decide what to patent, how to market technology, and how to close deals at reasonable prices and with reasonable expectations. And industry learned how to negotiate licenses with universities.

Nelsen concluded that the whole biotechnology industry came out of the Cohen-Boyer patent, not only because Cohen-Boyer developed gene splicing, but because universities learned how to do biotechnology and early technology licensing—even if the first example was paradoxical.

The decision to negotiate nonexclusive, rather than exclusive, licenses was critical to the industry. If the technology had been licensed exclusively to one company and the entire recombinant DNA industry had been controlled by one company, the industry might never have developed. Alternatively, major pharmaceutical firms might have been motivated to commit their resources to challenging the validity of the patent.

Nelsen noted that at most major universities, it has become standard in industry-sponsored research agreements that the university will retain ownership of any resulting patents but almost without exception will grant the sponsor a first option to an exclusive license. With the increase in university-industry partnerships this applies to more research than in past years. Moreover, the Bayh-Dole Act encourages universities to grant exclusive licenses to companies even if the research was publically sponsored. But as the next case study shows, even when a company holds exclusive rights to a fundamental technology, it might choose to disseminate the technology broadly.

• PCR and TAQ Polymerase: A Patented Research Tool for Which Licensing Arrangements Were Controversial

Polymerase chain reaction (PCR) technology presents an interesting counterpoint to the Cohen-Boyer technology. Both are widely used innovations seen by many as critical for research in molecular biology. However, the licensing strategies for the two technologies have been quite different, and they were developed in different contexts.

PCR allows the specific and rapid amplification of targeted DNA or RNA sequences. Taq polymerase is the heat-stable DNA polymerase enzyme used in the amplification. PCR technology has had a profound impact on basic research not only because it makes many research tasks more efficient, in time and direct cost, but also because it has made feasible some experimental approaches that were not possible before the development of PCR. PCR allows the previously impossible analysis of genes in biological samples, such as assays of gene expression in individual cells, in specimens from ancient organisms, or in minute quantities of blood in forensic analysis.

In less than a decade, PCR has become a standard technique in almost every molecular biology laboratory, and its versatility as a research tool continues to expand. In 1989, Science chose Taq polymerase for its first "Molecule of The Year" award. Kary Mullis was the primary inventor of PCR, which he did when he worked at the Cetus Corporation. He won a Nobel Prize for his contributions merely 8 years after the first paper was published in 1985, which attests to its immediate and widely recognized impact. Tom Caskey, senior vice-president for research at Merck Research Laboratories and past-president of the Human Genome Organization, attributes much of the success of the Human Genome Project to PCR: "The fact is that, if we did not have free access to PCR as a research tool, the genome project really would be undoable. . . Rather than bragging about being ahead, we would be apologizing about being behind."

Whereas recombinant DNA technology resulted from a collaboration between university researchers whose immediate goal was to insert foreign genes into bacteria to study basic processes of gene replication, PCR was invented in a corporate environment with a specific application in mind—to improve diagnostics for human genetics. No one anticipated that it would so quickly become such a critical tool with such broad utility for basic research.

Molecular biology underwent considerable change during the decade between the development of recombinant DNA and PCR technologies (Blumenthal and others, 1986). The biotechnology industry emerged, laws governing intellectual property changed, there was a substantial increase in university-industry-government alliances, and university patenting in the life sciences increased tenfold (Blumenthal and others 1986, Henderson and others). There was virtually no controversy over whether such an important research tool should be patented and no quarrel with the principle of charging licensing fees to researchers. The controversy has been primarily over the amount of the royalty fees.

Cetus Corporation sold the PCR patent to Hoffman-LaRoche for $300 million in 1991. In setting the licensing terms for research use of PCR, Roche found itself in a very different position from Stanford with respect to the Cohen-Boyer patent. First, it was a business, selling products for use in the technology. That made it possible to provide rights to use the technology with the purchase of the products, rather than under direct license agreements, such as Stanford's. This product-license policy was instituted by Cetus, the original owner of the PCR patents. An initial proposal to the scientific community by the president of Cetus for reach-through royalties—royalties on second-generation products derived through use of PCR—was met with strong criticism. Ellen Daniell, director of licensing at Roche Molecular Systems, noted that the dismay caused by the proposal has continued to influence the scientific community's impression of Roche's policy.

Roche's licensing fees have met with cries of foul play from some scientists who claim that public welfare is jeopardized by Roche's goals. Nevertheless, most scientists recognize that Roche has the right to make business decisions about licensing its patents. The fact that Roche had paid Cetus $300 million for the portfolio of PCR patents led some observers to think that Roche intended to recoup its investment through licensing revenues, a point that Daniell disputed. She pointed out that Roche's business is the sale of products and that licensing revenues are far less than what would be needed to recoup the $300 million over a time period that would be relevant from a business viewpoint. Daniell listed Roche's three primary objectives in licensing technology:

• Expand and encourage the use of the technology.
• Derive financial return from use of the technology by others.
• Preserve the value of the intellectual property and the patents that were issued on it.

Roche has established different categories of licenses related to PCR, depending on the application and the users. They include research applications, such as the Human Genome Project, the discovery of new genes, and studies of gene expression; diagnostic applications, such as human in vitro diagnostics and the detection of disease-linked mutations; the production of large quantities of DNA; and the most extensive PCR licensing program, human diagnostic testing services. Licenses in the last-named category are very broad; there are no upfront fees or annual minimum royalties, and the licensees have options to obtain reagents outside Roche.

Discussion about access to PCR technology centered on the costs of Taq polymerase, rather than on the distribution of intellectual property rights. Tom Caskey's view was that "the company has behaved fantastically" with regard to allowing access to PCR technology for research purposes. Bernard Poiesz, professor of medicine at the State University of New York in Syracuse and director of the Central New York Regional Oncology Center, agreed that he knew of no other company that had done as well as Roche in making material available for research purposes. But he also argued that the price of Taq polymerase is too high and has slowed the progress of PCR products from the research laboratory to the marketplace. Poiesz stated that the diagnostic service licenses "are some of the highest royalty rates I have personally experienced." He cited the example of highly sensitive diagnostic tests for HIV RNA, which he said are too expensive for widespread use, largely because of the licensing fees charged by Roche. 1 Caskey felt that Roche should have expanded the market by licensing more companies to sell PCR-based diagnostic products and profited from the expansion of the market, rather than from the semiexclusivity that it has maintained.

Nor are all university researchers satisfied with their access to Taq polymerase. Ron Sederoff commented that—in contrast to the human genomics field, in which funding levels are much higher than for other fields of molecular biology—many academic researchers do not find easy access to the technology. Several workshop participants noted that the high cost Taq polymerase made many experiments impossible for them.

What is the effect of the Cetus-Roche licensing policy on small companies? Tom Gallegos, intellectual property counsel for Oncorpharm, a small biotechnology company, stated that most small companies cannot afford the fees charged by Roche. He noted that the entry fee for a company that wants to sell PCR-based products for certain fields other than diagnostics ranges from $100,000 to $500,000, with a royalty rate of 15%. By comparison, a company pays about $10,000 per year and a royalty fee of 0.5–10% for the Cohen-Boyer license. The effect is an inhibition of the development of PCR-related research tools, with consequent reductions or delays in the total royalty stream and possibly litigation.

Sidney Winter, professor of economics at the Wharton School of Business, suggested that in asking whether the price of some technology is too expensive, one should consider "compared with what?" Compared with licensing and royalty fees for Cohen-Boyer, PCR might seem excessive. If one imagines that the cost of the PCR patent were financed by a tax on the annual US health-care expenditure which was about $1 trillion in 1995 (Source: Congressional Budget Office), that tax would be roughly equal to 0.03% and might be a price worth paying for the advances made possible by PCR technology.

During the workshop, several people distinguished between research tools that are commercial products and tools that have little market value but are important tools for discovery. In the case of PCR, the research tool is both a commercial product and a discovery tool. As such, it raises questions. Are the PCR patents an example of valuable property that would have been widely disseminated in the absence of patent rights? Is PCR an example of a technology that has been more fully developed because of the existence of patent rights? Daniell stated that Roche has added considerable value to the technology, in part through the mechanism of patent rights. There was vigorous discussion and disagreement as to whether the licensing fees justify the value added by Roche.

• Protein and DNA Sequencing Instruments: Research Tools to Which Strong Patent Protection Promoted Broad Access

This case study was selected because it provides a clear example of how patent protection promoted the development and dissemination of research tools. By most standards, this would be considered a successful transfer of technology. The possibility of automated, highly sensitive DNA and protein sequencers was developed in the public sector by Leroy Hood's group at California Institute of Technology (Cal Tech). However, it was only with the help of substantial private investment that these research tools were widely disseminated.

The ability to synthesize and sequence proteins and DNA revolutionized molecular biology; automating these tasks promised to consolidate the revolution. Indeed much of the achievement of the Human Genome Project is attributable to the development of automated sequencing instruments, which greatly reduced the time and cost needed to sequence DNA. Because the effects of genes depend on the proteins that they encode, protein sequencing has been a key step in deciphering gene function. Until automated sequencing instruments were widely available, only a few laboratories had access to this technology.

The prototypes for these instruments were developed in Hood's laboratory during the years 1970–1986. Over a period of six or seven years, the team of scientists assembled by Hood increased the sensitivity of protein sequencing instruments by a factor of about 100. That transformed a difficult and uncertain task into one that could be reliably accomplished with the minute quantities of purified proteins that so often limited the scope of the analysis. Hood's laboratory was the first to sequence lymphokines, platelet-derived growth factor, and interferons. After those successes, he was approached by many scientists who asked why the technology could not be made available to the whole research community. Since the middle 1990s, the technology has become widely available.

The broad availability of sequencing technology is due, in no small part, to Hood's perseverance in the face of widespread skepticism. His 1980 manuscript that described, for the first time, automated DNA sequencing was delayed by the journal Nature on the grounds that this technology sounded like "idle speculation." Hood wrote three or four proposals to NIH and the National Science Foundation but was unable to obtain funding for his instrumentation work. The bulk of the support for this technology came from the private sector, and even then companies were reluctant to invest in developing the sequencing instrumentation. He approached nineteen companies, all of which declined to support the development of the sequencers. Eventually, he obtained funding from Applied Biosystems (ABI), but even this support required difficult negotiations between Cal Tech and ABI. ABI insisted on, and received, an exclusive license. As Hood told it, the argument that convinced Cal Tech to support the arrangement was that "if the scientific community wants these instruments, it is our moral obligation to make them commercially available."

At the time of this workshop, ABI had sold more than 3,000 DNA sequencers and more than 1,000 protein sequencers worldwide (although some elements of the technology, such as peptide synthesis, were not protected by patents, most of the instrumentation was patented by ABI). Sequencing facilities that serve multiple investigators are now standard features at research universities. That is not to say that licensing of this technology has been without controversy. Cal Tech licensed the technology to ABI with the stipulation that ABI would sublicense it under what Cal Tech considered reasonable terms. A number of companies have argued that ABI's terms are not reasonable. As with PCR, the situation is complicated in that the primary licensee claims that its license fees reflect what it needs to charge to earn a reasonable return on its investment in developing the technology.

ABI is clearly the leader in the world market for DNA sequencers. But other companies, such as Pharmacia and LI-COR, have important market shares. LI-COR has established a niche in the market with its infrared fluorescence DNA sequencer; infrared light has low background fluorescence, which allows for the development of more robust, solid-state instrumentation than is possible with other DNA sequencing technology. LI-COR is typical of many small biotechnology companies in its reliance on its patent portfolio. Harry Osterman, director of molecular biology at LI-COR, noted that "DNA sequencing is more than just an instrument, it is a system. To make a viable product, all the disparate pieces need to be integrated. That makes for a challenging intellectual property and licensing exercise, unless you have the internal funds to do everything. You require instrumentation, software, chemistry, and microbiology." Patent protection allows a small company to negotiate cross-licenses, which are critical in systems technologies, such as sequencing instrumentation. It can provide an opportunity that a small company would not otherwise have to compete in a market.

One might argue that patent protection served both the large company (ABI) and the small company (LI-COR) in bringing their sequencing technology to the market. In the case of ABI, patent protection afforded them the opportunity to develop a complex system of technology in an orderly and efficient manner, as proposed by the prospect development theory presented by Richard Nelson in chapter 3 . In the case of LI-COR, patent protection of sequencing systems enabled it to negotiate the cross-licenses needed to develop its product fully. In both cases, private support has driven the development and dissemination of a research tool. The public and private sectors seem to have gained equally.

• Research Tools in Drug Discovery: Intellectual Property Protection for Complex Biological Systems

Research tools in drug discovery present an example of the difficulties in protecting intellectual property when technologies involve complex biological systems that lack discrete borders. The information is often broad and refers to general categories of matter, such as a class of neural receptors, rather than finite entities, such as the human genome, or specific techniques, such as PCR or recombinant DNA techniques. Controversies have emerged over broad patents, which some see as stifling research on and development of useful drugs and others see as critical to the translation of research knowledge into useful products. The focus of the discussion in the workshop was the tension between the dependence of small biotechnology companies on patents and the difficulties created when research on complex biological systems is restricted by a thicket of patents on individual components of the systems.

When research on a complex system—for example, receptor biology or immunology—requires obtaining multiple licenses on individual components of the system, the potential for paying substantial royalty fees on any useful application derived from that product can be daunting. "Royalty stacking" can swamp the development costs of some therapies to the point where development is not economically feasible. That is a problem particularly in gene therapy, where the most promising advances now are related to rare genetic diseases that present small markets.

Bennett Shapiro, vice-president for worldwide basic research at Merck Research Laboratories, argued that the central issue is not about patenting, but about access, about encouraging the progress of biomedical research. Problems can arise when access to related components of biological systems is blocked. For example, schizophrenia is often treated with compounds that suppress dopaminergic neurotransmission. Many such compounds, for example haloperidol, act nonspecificially and suppress the entire family of dopamine receptors. People who take those compounds for schizophrenia often develop other disorders some of which resemble Parkinson's disease, another disease involving the dopamine system. A rational approach to discovery of improved schizophrenia drugs would be to target specific dopamine receptors. But if different companies hold patents on different receptors, the first step on the path to an important and much needed therapeutic advance can be blocked.

Shapiro commented that when only one company starts along the path of discovering a particular type of drug, its chance of discovering it is very low. Merck supports only a tiny fraction of total biomedical research, and it benefits enormously from research going on elsewhere in the world. It is in Merck's interest to share the results of its research with the understanding that they can be even more useful if placed in the pool of worldwide research resources.

It is interesting to compare that perspective on drug discovery with the early history of radio and television, other examples of complex systems of which many components were patented individually. In chapter 3 , Richard Nelson noted that it was not until cross-licensing practices became widespread in the early development of radio and television that important advances that enabled broad access to the technology took place. When the intellectual property was sequestered in the hands of a few companies, the entire electronics industry remained sluggish. Of course, the progress of the industry overall must be balanced by the financial needs of individual companies. Shapiro noted that Merck has felt the need to become more energetic about patenting than it was years ago. For example, carrageenan footpad assays were used to develop non-steroidal anti-inflammatory drugs. The assays were in the public domain, and many companies used them to develop new drugs. Today, Merck would patent such an assay and use its patent position to trade with other companies for access to other research tools.

James Wilson, director of the Institute for Human Gene Therapy at the University of Pennsylvania, described his experience with the different ways in which patents on research tools are used. One is to block others from using the tools—to protect one's proprietary use—which he did not see as economical. Genetic therapy patents might not generate enough financial return to offset the investment costs. Wilson also suggested that genetic therapy patent files are only going to waste money in lawsuits brought against those patents. Second is to generate revenues for universities to support their infrastructures, although, as Lita Nelsen noted, most universities are not likely to earn much from patent revenues. The third is to barter so as to continue development without creating an economic disadvantage.

Like previous panelists, Larry Respess of Ligand Pharmaceuticals, argued that the chances of survival of a small biotechnology company would be slight without patents. He noted that the biotechnology industry is composed of small companies that have grown through venture capital and public offerings and that finance research through equity, not product revenues. The goal is to develop products and then evolve into an independent company.

Wilson also pointed to a dramatic increase over the last two to three years in the difficulty in transferring material between universities. Nelsen emphasized that university technology transfer managers are still learning. And many decisions of the US Patent and Trademark Office (PTO) are controversial and under close scrutiny by those charged with managing intellectual property.

In commenting that "it is hard to know what the proprietary landscape is going to be, but it will be complex, whatever it is," Wilson summarized many of the workshop participants' comments.

Changes in Biotechnology Strategies

Respess discussed how R & D strategies for biotechnology have changed over the last twenty years. The biotechnology industry was born in about 1975 by Genentech, and most of the companies that followed Genentech pursued a similar strategy. Their objective was to produce and sell therapeutically-active large protein molecules, which was made possible by the availability of the Cohen-Boyer technology. The strategy was to discover and try to patent a gene for such a protein; it was hoped that the gene could be used to express abundant quantities of the protein. Some of the early examples are insulin, growth hormone, erythropoietin, and the interferons.

The advantages of that approach were that everyone knew that the products would be useful and that recombinant techniques were efficient for production, compared with earlier techniques of extraction from cadavers and tissue. Another advantage—albeit not from a scientific viewpoint—is that it is easy to sell to the investment community; it was a simple, easily understood model. Respess described the raising of capital in the early days of biotechnology as "unbelievable. You could found a company and, within a relatively short time, go public and raise many millions of dollars." However, those days are now past, in part because of the intrinsic limitation of large protein molecules: they are expensive to produce and to deliver to patients (they must be delivered by injection). The drug targets that are easy to identify have already been exploited.

A newer biopharmaceutical strategy emerged—not to discover large proteins or other large-molecule drugs, but to find other therapeutically active small molecules. These are the traditional targets of pharmaceutical research, but a biopharmaceutical company uses modern biotechnology and insights from molecular biology to get to the ultimate target product more quickly and efficiently. This approach has several advantages. The drugs are conventional and can typically be given orally, as well as by injection; they are relatively easy to manufacture; and the Food and Drug Administration is very familiar with such drugs, which makes it easier to get a new drug approved. The problem from a small company's perspective, however, is that it takes a very expensive infrastructure. Ultimately, synthesizing small molecules means making many molecules, and medicinal chemistry is very expensive. You have a tool, but you do not have any products in hand.

• Expressed-Sequence Tags (ESTs): Three Models for Disseminating Unpatented Research Tools

An expressed-sequence tag (EST) is part of a sequence from a cDNA clone that corresponds to an mRNA (Adams and others 1991). It can be used to identify an expressed gene and as a sequence-tagged site marker to locate that gene on a physical map of the genome. In 1991 and 1992, NIH filed patent applications for 6,800 ESTs and for the rapid sequencing method developed by Craig Venter, who was a scientist at NIH. The PTO rejected NIH's application and when Harold Varmus became director of NIH, he decided not to appeal. But controversy caused by the initial patent application continued. In 1992, Venter left NIH to form The Institute for Genome Research (TIGR), a nonprofit company, and William Haseltine joined the newly established private company, Human Genome Sciences (HGS), a for-profit company that initially provided almost all of TIGR's funding. The focus of the controversy then moved from the public to the private sector, and it changed from an issue about patenting research tools to an issue of access to unpatented research tools. Like many other research tools, ESTs fill different roles and some of the controversy has involved disputes of the relative importance of ESTs for uses other than research.

Two factors have contributed to the controversy over intellectual property issues in this particular setting. First is the perception that some of the participants have been staking out intellectual property claims that extend beyond their actual achievements to include discoveries yet to be made by others. There is no question that ESTs constitute a powerful research tool. Questions about the patenting of ESTs have focused on the criteria of utility. ESTs are of limited value without substantial and nonobvious development. Initially a public institution, NIH, proposed to patent discoveries that both scientists and some representatives of industry felt belonged in the public domain. More recently a private institution, Merck, has assumed the quasigovernment task of sponsoring a university-based effort to place information into the public domain. While other private companies have provided funds for public sector research, such as in the Sandoz-Scripps agreement, these efforts have not been with the expressed purpose of putting information into the public domain.

This is a particularly interesting case study, in part because it began as a controversy over patents—over what could be patented, what should be patented and what would be the effect of patenting. It has evolved into a controversy over the dissemination of unpatented information and the terms on which that information will be made available.

Different firms have taken different approaches to the dissemination of these unpatented research tools, thus providing a natural experiment with which to study three models for disseminating the same sort of information. The models all arose in the private sector, and we can assume that although each firm adopted a different strategy, they had the same ultimate goal of maximizing the value that they could obtain from the information. Merck has put the information in the public domain, Human Genome Sciences (HGS) initially adopted an exclusive-licensing model, and Incyte adopted a broad licensing approach of offering nonexclusive licenses to its database to as many firms as would sign up. Putting information in the public domain limits opportunities to exploit it as a trade secret by controlling access to it. Patents, or the patent applications of private database owners, potentially limit the ability to use the information that is in the public domain if any patent rights are ultimately obtained.

• HGS. The strategy of HGS has been to form a major partnership with the pharmaceutical firm SmithKline Beecham (SKB) 2 , with which it agreed to provide a three year exclusive license to its EST database. SKB has sublicensed its rights to a major Japanese pharmaceutical company, Takeda Chemical, Ltd., and HGS also has 200 restricted-licensing arrangements with university researchers. The TIGR database contains a limited portion of the data created by HGS and all of the data created by TIGR before April 1, 1994 which is when TIGR stopped work on human cDNAs. TIGR provides two levels of access to its EST databases. At the first level, an investigator is allowed access to sequences that are owned by HGS that overlap or are identical with sequences already in the public domain and for which public databases are available. At the second level, investigators are allowed access to about 70,000 sequences that are not listed in the publicly available databases (Genbank or the European databases). To obtain the second level, an investigator must agree to disclose any invention that is made at any time after access is gained. Furthermore, HGS or the Institute for Genome Research (TIGR) must be allowed at least six months to negotiate a licensing agreement. 3 The public does not have access to the much larger HGS cDNA database.
• Merck. Merck is interested in using the information from ESTs for furthering its research efforts. The Merck Gene Index was established to fill a public-access gap and was developed in partnership with established genome centers. Sequencing is carried out at Washington University, and the data are handled at the Los Alamos Laboratories. The international databases are a direct source of the information. A biotechnology company has taken all the clones into its distribution system and will freely distribute its materials. Other institutions, such as TIGR and Genethon, have entered sequences into this public database.
• Incyte. Incyte's strategy has been to offer nonexclusive licenses to its database. As of the time of the workshop, six companies (Pfizer, Upjohn, Novo Nordisk, Hoechst, Abbott Laboratories, and Johnson & Johnson) have contributed in the aggregate, around $100 million, exclusive of contingency payments and royalty payments for access to this database. Even as the Merck data continue to be placed in the public domain, Incyte continues to sign up new subscribers; there seems to be continuing value for the subscribing firms to obtain access to one of the private databases. This strategy is interesting not only for what it says about the nonexclusive-licensing strategy but because this is the most current information as to the relative values of the private databases versus the public-domain database.

The Informational Value of ESTs Is Rudimentary

None of the participants disputed the value of ESTs as research information, but several commented on the rudimentary nature of the information. Having an EST in hand does not guarantee a practical strategy for obtaining the identity of the gene of which the EST is but a fragment. Furthermore, if the gene identified is unknown, there remains substantial investment in understanding its function. It has been successfully accomplished in many cases, and many specific strategies have been developed over the years for approaching this task. Nonetheless, it remains fraught with uncertainty. In 1995 the Human Genome Organization (HUGO) issued a statement on ''Patenting of DNA sequences'' arguing that the nature of sequence information is so rudimentary that to limit access to it is to impede development of medical advances.

Several uses have been suggested for genes and gene fragments to claim utility requirement for patent protections. They include the use of genes or gene fragments for categorizing, mapping, tissue typing, forensic identification, antibody production, or locating gene regions associated with genetic disease. However, each of those suggested uses may not be carried out without considerable further effort and additional biological information that is not inherent in the sequence alone. Many of the workshop participants concurred with the HUGO statement that without databases to provide further information, the informational value of ESTs themselves is very limited.

William Haseltine, CEO of HGS, noted that patent applications filed by HGS for ESTs involve considerably more than simply identification of the gene fragments and involve information about the stage of development and tissue type in which those genes are expressed. He further commented that the importance of the EST database is not simply that the fragments are identified, but that the database itself provides a high level of information.

The Value of ESTs Could Be Reduced by Limiting Access

Many of the workshop participants echoed the HUGO statement of concern that "the patenting of partial and uncharacterized cDNA sequences will reward those who make routine discoveries but penalize those who determine biological function or application. Such an outcome would impede the development of diagnostics and therapeutics." Both Harold Varmus and Gerald Rubin suggested that some researchers are likely to be discouraged from working on patented ESTs for fear that the patent holders would lay claim to their future discoveries, particularly discoveries about gene function, which are clearly of far greater biological utility than the identification of anonymous fragments and are more likely to have useful applications for human health.

Several previous reports have stated that research-tool claims should not be so broad as to block the discoveries outside of the patent (House of Commons Science and Technology Committee 1995, National Academies Policy Advisory Group 1995). No one at the workshop argued otherwise.

Fragile X syndrome, which is the most-common form of mental retardation, provides an example of how ESTs can contribute to human disease. The name refers to the fact that the X chromosome is easily broken. Caskey described how he, Steve Warren, and Ed Benustra used an EST to discover that the genetic defect involves multiple repeats of the nucleotide triple CGG. They went on to characterize the gene, and that provided the information necessary to develop what is now the most widely used diagnostic test for fragile X syndrome. When they made their discovery, the sequence information on the gene involved gave no information on function. It was investigators like Bob Nussbaum, and Dreyfus, at Philadelphia, who went on to identify the gene's function.

Caskey suggested that if speculative claims were permitted among a certain set of ESTs the rights of investigation to discover that gene would be denied.

James Sikella cited the example of the HIV patent, which is jointly held by the US and French governments. The patent has not been tightly restricted for investigational use. At the time of its filing, its sequence and functions were not described. Many discoveries about HIV have evolved from that sequence information, and Sikella noted that it would have been a disservice to the public if the sequence information had not been available as a general research tool.

The Human Genome Is Finite

As of this workshop, some 27,000–5,000 human genes were represented in the database. Humans are estimated to have about 80,000–100,000 genes, so that represents about one-fourth to almost half of the total. Tom Caskey predicted that as the database begins to be flooded with sequence information, there will be a higher stringency on patents and patent claims will be directed more toward functional aspects of the genes, rather than being primarily descriptive.

Caskey also described how the usefulness of the gene index has improved with the addition of more sequences. When the general location of a disease gene is known from genetic mapping, limited sequencing is an important strategy for finding the gene. By sampling the critical region, the small bits of sequences can be used to search for homologies in the gene sequence database. In this way, a previously sequenced gene or gene fragment can be identified as being located in a critical region. Such a gene is then a prime suspect for more detailed studies in those individuals carrying the disease. Initially, the success rate for this technique of finding disease genes in positionally cloned regions was only about 40%. As the size of the gene database increases, so does the success rate. This is, therefore, becoming a fast and facile method for identifying a disease gene in a critical region identified by genetic mapping.

Sikella suggested that the success of the Human Genome Project may be measured, in part, by how the knowledge that it generates benefits society. He emphasized the importance of making these benefits available in a cost-effective way.

The Advent of DNA Sequencing Presents Important Questions about Patentability

Leon Rosenberg commented that "although the debate seems to have cooled a bit, the issues surely have not been resolved." Tom Caskey of Merck and William Haseltine of HGS both commented that they have no quarrel with the current criteria for patents, but they express different views as how those criteria should be interpreted. Since the workshop, HGS has received patents on a number of ESTs with broader claims of utility than the initial EST patent applications filed by NIH in 1974. Whether this will influence the debate over ESTs is an open question. Caskey noted that after one has an EST, identifying the full length sequence cDNA is the obvious next step. And yet this rarely leads to precise knowledge of that gene's function. He predicted that the complete cDNA sequences might become the 1997 version of ESTs—that is, research tools which many people do not believe meets the full potential criteria of novelty, nonobviousness, and utility. Rosenberg suggested that "the biomedical research community has not yet truly grappled with the possibility that a large number of genes could be controlled by the rights of a relatively small number of parties who could not possibly hope to fully exploit their potential value." He suggested that if research tools are not made available to the scientific community and others, we will have to confront this issue directly, whether that requires changes in patent law or other equally drastic directions.

• Adams MD, Kelley JM, Gocayne JD, Dubnick M, Polymeropoulos MH, Xiao H, Merril CR, Wu A, Olde B, Moreno RF, Kerlavage AR, McCombie WR, Venter JC. 1991. Complementary DNA sequencing: expressed sequence tags and human genome project . Science 252(5013): 1651–1656. [ PubMed : 2047873 ]
• Beardsley T. 1994. Big time biology . Sci Amer. November: 90–97. [ PubMed : 7997867 ]
• House of Commons Science and Technology Committee. 1995. Human genetics: the science and its consequences , Vol.1. London, UK: House of Commons;
• National Academies Policy Advisory Group. 1995. Intellectual property and the academic community . London: The Royal Society. 65p.

Royalty rates refer to a charge based on the revenues earned by the licensee and are different from the up-front fees and annual minimum royalties referred to earlier. As a member of a not-for-profit institution, Poiesz was offered the choice between a 9% or 12% royalty rate, with the lower rate available to those who agreed to use Roche-manufactured DNA polymerase for their testing.

Takeda Chemical, Ltd., the largest Japanese pharmaceutical firm, is another partner. Since the workshop, HGS has directly licensed three other companies: Schering-Plough, Merck KGAA (a German company, not affiliated with US Merck), and Synthelabo (a French company).

After April 1, 1997, all of the original EST sequences in the HGS-TIGR databases completed by April 1994 will be publicly available with no restrictions.

• Cite this Page National Research Council (US). Intellectual Property Rights and the Dissemination of Research Tools in Molecular Biology: Summary of a Workshop Held at the National Academy of Sciences, February 15–16, 1996. Washington (DC): National Academies Press (US); 1997. 5, Case Studies.
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Cancer in the Classroom: A Case Study Analysis

Author: Lisa Franchetti

G.W. Carver High School of Engineering and Science

Seminar: Cancer Biology and Technology

Grade Level: 9-12

Keywords: Biology , cancer , cell cycle , life science , mutations

Cancer Biology is a topic that is not often covered in high school science classes. This unit serves to help students develop critical thinking and research skills to gain a better understanding of the biology of cancer formation. In this unit students will learn about the molecular development of cancer and potential risk factors. The unit is based on a case study which focuses on colon cancer. Using this case study students will research the sequential mutations associated with colon cancer, common diagnostic techniques, and treatments. Students will also analyze cancer risk factors to develop a personal cancer risk reduction plan. In the last portion of the unit students will have the opportunity to explore careers involved in the treatment, diagnosis, and support of cancer patients.

Download Unit: Franchetti-lisa.pdf

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Full Unit Text

Content objectives.

Cancer Biology is a topic not often covered in high school science classes in the School District of Philadelphia. Based on the curriculum sequence, cancer is either discussed briefly while learning about the cell cycle or not at all. The lack of integration of cancer curriculum in the pacing guidelines may be the result of the yearly progression of topics required for standardized testing; however, cancer biology is a topic that we could integrate into multiple units in the curriculum. Students are aware of cancer and may even have personal experience with cancer in their families but they are not formally taught about cancer and may have many misconceptions on the topic. This directly relates to the fact that ninth-grade biology students in the SDP are not exposed to relevant disease topics when learning fundamental biological principles. These common misconceptions provide an opportunity for educators to bridge the gap of knowledge while still covering required course content. Cancer as an overarching theme provides students with a mechanism to explore a wide array of biology topics ranging from the deregulation of the cell cycle to mutations and environmental influences on gene expression.  A more rigorous approach to exploring cancer could allow students to gain a thorough understanding of the biological processes of disease formation and the relationship between cellular systems and disease progression. This unit serves to integrate cancer biology topics into a 9 th -grade general biology course to help students understand the relationship between cells, cell cycle, cell regulation, mutations, the environment, and cancer.  

According to a report released in September 2020 by the Drexel University Urban Health Collaborative, “7,972 people in Philadelphia were newly diagnosed with cancer in 2016. This amounts to 478 new cases of cancer for every 100,000 Philadelphians.” Cancer incidence was also examined according to income demographic. The analysis shows a significant increase in both new cancer diagnoses as well as cancer deaths among people in lower income neighborhoods as compared to higher income neighborhoods (“Cancer and Health Disparities in Philadelphia”).  In this report on cancer in Philadelphia, the researchers identified the most frequently diagnosed cancers in men to be prostate, lung and colon and in women the three most common types were breast, lung, and colon cancer (“Cancer and Health Disparities in Philadelphia”). Of these top three cancer types for males and females, African Americans have a 20% higher incidence of colon cancer as compared to Caucasians, are more likely to develop colon cancer at a younger age, and more likely to die of their disease.  African Americans have the lowest five-year survival rate of any racial group in the US in this context. There are significant disparities in access to screening in lower socioeconomic neighborhoods. The report also indicates early screening by colonoscopy is on average only being conducted by 70% of the male and 75% of female participants screened (“Cancer and Health Disparities in Philadelphia”) https://www.health.harvard.edu/blog/racial-disparities-and-early-onset-colorectal-cancer-a-call-to-action-2021031722136 .  Additionally, in an article from the Philadelphia Tribune the average age recommended for screening by the American Cancer Society is 45 and other health organizations have recommendations starting at 50; however, there has been an increase in incidence of diagnosis with colon cancer under the age of 50 since the 1990s (Howard and Karmini). Figures from the colorectal cancer alliance indicate that the rates for people under 55 increased by 2% per year. According to the American Cancer Society, “In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined. It’s expected to cause about 52,980 deaths during 2021” (American Cancer Society). These figures indicate there is a need to raise awareness around colon cancer screening, diagnosis, and treatment in the US and specifically for our students and their families within Philadelphia. For this reason, I opted to use colon cancer as the type of cancer that will drive the units of study for my curriculum.

Students will begin exploring cancer biology using a colon cancer case study analysis. In these case studies, the students will follow a patient from when they are symptomatic to their diagnosis through treatment. The students will first review a patient’s symptoms and medical history/family history, then explore common misconceptions about colorectal cancers. By exploring cancer misconceptions they will gain a greater understanding about the truths and myths about cancer and they will learn about the incidence of colorectal cancer in their communities. During these initial lessons students will also begin to explore cancer initiation at the cellular level, integrating fundamental biological concepts and key themes in biology including the cell cycle, deregulation of the cell cycle, mutations in genes that cause deregulation of the cell cycle regulators and how this relates to disease progression. Some biology concepts that will be critical for these case studies are implementing sections where the students learn about the properties that distinguish a normal cell from a tumor cell. We will also discuss symptoms of colon cancer and learn about screening techniques that are used to diagnose cancer, the biological concepts that allow colonoscopies to detect pre-cancer in the colon, and how blood in the stool may be an early sign of colon cancer.

In the unit’s second part students will investigate genetic mutations that arise during replication, transcription, and translation. They will explore the central dogma of molecular biology and examine how errors in these processes lead to mutations which are associated with cancer development. During the lessons, students will apply these concepts to understand the stepwise mutations that lead to colorectal cancer. Although there are both acquired mutations and inherited mutations, students will primarily focus on the inherited gene mutations that cause syndromes associated with colorectal cancer formation. According to the American Cancer Society there are four primary types of inherited mutations: Familial adenomatous polyposis (FAP which is also associated with attenuated FAP and Gardner syndrome), Lynch Syndrome (hereditary non-polyposis colon cancer, or HNPCC), Peutz-Jeghers Syndrome, and MUTYH-associated polyposis (MAP) (American Cancer Society). FAP and the related syndromes as well as Peutz-Jeghers Syndrome are associated with mutations in the tumor suppressor genes APC and STK11 respectively. HNPCC is caused by a mutation in one of several DNA repair genes. Lastly, MAP is caused by mutations in the MUTYH gene that is involved in DNA proofreading during cell division (American Cancer Society). Since each of these types of cancer is caused by a different type of mutation, at the end of this unit I would like to provide case study evidence and have students compose a CER (claim, evidence, reasoning) prompt. In this prompt they would examine the evidence and provide rationale for diagnosing the individual with the specific mutation responsible for the colorectal cancer in the case study.

In the third part of the curriculum students will research cancer treatment, risk reduction strategies, and cancer careers. In this portion of the curriculum students will analyze current cancer treatment protocols and generate a treatment plan for the case study patient. During this component students will work in small groups to formulate a presentation on the treatment method they selected for the case study patient and provide evidence from a literature search which examines why their methodology would be effective in treating the patient. Students will also evaluate their own risk factors for developing cancer and will be crafting a risk reduction plan. The last component for the third part of the curriculum is exploring careers in cancer. Many students are familiar with oncologists but are far less aware of the role of pathologists, genetic counselors, researchers, chemists, molecular biologists, etc. Exposing students to different career paths in science is critical as they begin planning for their college or technical careers and beyond. As an end point of this research I would like students to generate a potential career in cancer profile in which they select a career and research job components. In this project the students would identify the job description, education/training requirements, salary/earnings/benefits, and a description of “a typical day in the life” of a person in that career.

According to the National Cancer Institute (NCI one of the institutes that makes up the National Institutes of Health – NIH) cancer is the name given to a collection of related diseases. Cancer occurs when the body’s cells begin to divide uncontrollably. Cancer can start in any somatic (body) cell or gamete (sex or germ cell). If the cancer forms due to a mutation in the gene of a germ cell it can be passed down to offspring thereby making it an inherited form of cancer. During development, cells grow and divide to form new cells and generate organs in the body and if these cells become damaged they enter apoptosis (a cellular death program). When this process is disrupted and damaged cells continue to divide and no longer die thus they grow out of control and form tumors. Cancers that occur in organs in the body will form masses or solid tumors, while blood cancers can form masses in many parts of the body. Tumors can be either benign (noncancerous and will not spread throughout body) or malignant (cancerous). Malignant tumors will invade nearby tissues and often travel to distant organs causing metastatic disease.

Colon Cancer

Colon cancer is cancer that is located in the large intestine and specifically in the colon- the end of the digestive tract. Colon cancer is typically found in older adults but does not discriminate based on age. In colon cancer the first stage of the disease typically begins as a benign (noncancerous) polyp on the inside of the colon. If the polyps are unchecked or not removed, the benign polyps could progress to malignant cancer by acquiring further mutations.

According to the National Cancer Institute (NCI) cancer is a genetic disease that is caused by changes at the genetic level which influence cellular growth. For this reason, cancer is considered to be caused by a deregulation of the cell cycle. The genetic changes can be spontaneous or inherited but will all result in abnormal cell division. During the normal cell cycle cells proceed through a series of regulated steps in which the cell grows, replicates DNA, grows again, and eventually undergoes nuclear division. This process is divided into G0, G1, S, G2, and M. The cell cycle is regulated by tumor suppressors, proto-oncogenes, and DNA repair genes which help to regulate cell division according to cellular growth signals. Tumor suppressors function to stop the cell cycle when conditions de-regulate cell growth while proto-oncogenes function to progress cells through the cycle when conditions support growth. DNA repair genes are involved in repairing damaged DNA in cells. Often times the cell is signaled to enter the G0 (resting or quiescent phase) which can be a temporary or permanent when the cell should not be in a growth phase. Cancer cells have abnormal signaling where tumor suppressor genes are inactivated and/or proto-oncogenes are overexpressed. The changes allow the cells to bypass the normal checkpoints in the cell cycle thereby promoting cell division and tumor formation. When cells acquire mutations in DNA repair genes this often leads to even more gene mutations which will either cause the cells to die or cause them to become cancer cells.

Normal vs Cancer Cells

Cancer and normal cells are microscopically different. According to the American Cancer Society some features that pathologists look for when screening cancer cells include cell shape, cell size, nuclear size and shape, and cellular arrangement. In terms of size and shape, cancer cells are abnormal. Cancer cells can be larger or smaller than normal cells and often appear distorted. Although size and shape may vary depending on the individual type of cancer, they can be distinguished from normal cells by the size of their nucleus and the ratio between the size of the nucleus compared to the amount of cytoplasm in a cell among other features. The nucleus is the control center of the cell and is responsible for storing genetic information in the form of deoxyribonucleic acid (DNA). In cancer cells the nucleus is typically abnormal in terms of size and shape. The nucleus also tends to look larger and darker microscopically because cancer cells contain more DNA.  Since the nucleus is larger and takes up more space in the cell the cytoplasm in cancer cells tends to be smaller compared to normal cells. Cancer cells may also have multiple nuclei and nucleoli as compared to a single nucleus and nucleoli in a normal cell.

From DNA to Protein

The central dogma of molecular biology revolves around the process of transcription and translation. Both normal cells and cancer cells use these processes during cellular division to produce the necessary proteins from the DNA template. This entire process begins with DNA replication during S phase in the cell cycle. DNA replication is a series of enzymatic steps which are used to make a new copy of the DNA helix. The entire process is semi conservative where one strand of the DNA is used to make a new copy of the genetic information for the cell. This DNA is then passed into the cells during division.  One of the enzymes involved in this process is DNA polymerase. DNA polymerase is used as a proofreader and is responsible for identifying and replacing errors during DNA replication. Errors during this process could lead to breaks or the integration of incorrect bases in the DNA ultimately resulting in cancer. During the process of transcription DNA is used as a template to convert the genetic information from DNA into RNA. While the process of translation uses RNA to produce proteins. Errors in the processes of transcription and translation can also be associated with cancer formation.  Genes control how proteins are made and proteins have specific cellular functions. The production of abnormal proteins during translation could result in alterations of cellular functions which could be associated with defects in cell cycle and division causing normal cells to transform into cancer cells.

A mutation is simply a change in the DNA sequence. Not all mutations have negative impacts on the cell. However, some mutations are directly associated with the formation of cancers. According to Cancer.net there are two types of mutation- acquired and germline. Acquired mutations are the most common causes of cancer and these occur from damage that occurs (is acquired) over a person’s lifetime. Acquired mutations are not found in all cells and cannot be passed down to offspring during reproduction. Some factors that can contribute to acquired mutations include tobacco use, exposure to ultraviolet radiation, viruses, and advanced age. Germline mutations are hereditary mutations that can be passed from parent to offspring in the sperm or the egg. Since these cells are used to produce the entire organism germline mutations will be present in every cell in the body. The statistics from Cancer.net indicate that inherited cancers account for approximately 5- 20% of all cancers. Although mutations occur regularly, a single mutation is not likely enough to cause cancer. Typically, a series of mutations in specific genes are required for cancers to develop which is why cancer is considered a disease of aging since older individuals had more time to accumulate mutations.

Colorectal Cancer Mutations

There are a series of mutations which have been mapped to occur in a stepwise fashion which are thought to be responsible for the development of colorectal cancer (CRC). The process to becoming a cancer can follow three pathways: Chromosomal instability (CIN), microsatellite instability (MSI), or the CpG island methylator phenotype (CIMP) (Nguyen and Duong). The lessons in this sequence will focus on the CIN pathway because it is the most common pathway for mutations that lead to CRC and is observed in 85% of adenoma-carcinoma transitions (Nguyen and Duong). CRC begins when the normal colorectal epithelium transforms into a benign adenoma. The CIN pathway is typically activated with a mutation in the tumor suppressor gene APC (adenomatous polyposis) which can take many decades to progress. This mutation inhibits a key signaling pathway (Wnt/ ß-catenin) which results in the proliferation, invasion, and metastasis of cancerous cells. In the CIN pathway the early adenoma is transformed to the intermediate adenoma after a mutation in oncogene KRAS (KRAS proto-oncogene GTPase). KRAS is part of a larger signaling pathway that is responsible for cell proliferation, differentiation or survival. Mutations of KRAS in this signaling pathway results in constitutive activation of the downstream targets responsible for cellular proliferation. In other words, the cell receives constant signals to continue dividing. This stage generally persists on average for 2-5 years. The last set of cellular changes in the development of CRC are the deletion of chromosome 18q and the inactivation of TP53 (tumor protein 53). TP53 is a tumor suppressor and a cell cycle regulator that is supposed to trigger cells to stop at G1 or G2 or trigger apoptosis in response to cellular damage. The loss of this function allows damaged cells to progress through the cell cycle. This final step causes the progression to a malignant carcinoma (Nguyen and Duong).  TP53 is the most commonly mutated gene in all cancers.

Colon Cancer Symptoms

Colon cancer typically begins with the formation of polyps but the polyps may be too small to produce symptoms. The most common symptoms as listed on the Mayo clinic website include:

• Change in bowel habits (constipation or diarrhea) or stool consistency
• Blood in stool
• Abdominal discomfort (cramps, bloating, gas, or pain)
• Feeling that bowels do not empty
• Weakness and fatigue
• Weight loss that is unexplained

Colon Cancer Treatments

There are various colon cancer treatment options depending on the stage of the cancer. The treatments outlined in this portion are recommendations provided by the Mayo Clinic based on the tumor stage. For early-stage colon cancer the treatment recommendations are minimally invasive. Some techniques recommended on the Mayo Clinic website include polypectomy, endoscopic mucosal resection, and laparoscopic surgery. The polypectomy is a procedure used to remove polyps that are small and localized. This procedure can often be completed during a colonoscopy. Endoscopic mucosal resection is used to remove larger polyps and some of the lining of the colon. While polyps that cannot be removed during a colonoscopy are removed using laparoscopic surgical procedures. For more advanced stages of colon cancer, the recommendations are more invasive and may include a partial colectomy or ostomy. For the partial colectomy the cancerous portions of the colon are removed and the healthy parts of the colon and rectum are reconnected. The ostomy is performed when the ability to connect the colon and rectum are lost. In this procedure an opening is made in the abdomen and is connected to the bowel as a way to eliminate solid waste from the body. Sometimes this can be temporary while recovering from the surgical procedure and other times this may be permanent. In some cases, the surgical procedures are the first step in treating the cancer. In these case chemotherapy, radiation, immunotherapy, or targeted drug therapies may be required.

Colon Cancer Risks

According to the Mayo Clinic there is an increased risk of colon cancer based on any of the risk factors listed below.

• Older age = >50
• Race= African American
• Personal history of polyps or colorectal cancer
• Other Intestinal conditions = ulcerative colitis and Crohn’s disease
• Inherited syndromes = FAP, HNPCC
• Family history of colon cancer
• Low fiber, high fat diets, diets high in red meat and processed meats
• Sedentary lifestyle
• Diabetes or insulin resistance
• Heavy alcohol use
• Abdominal radiation therapy (used for treatment of previous cancers).

Colon Cancer Risk Reducers

According to the Mayo Clinic there are several ways to reduce the risk factors for colon cancer. The first is to eat a healthy and well-balanced diet. This diet should include fruits, vegetables, and whole grains. If a person drinks alcohol, it should be consumed in moderation. The recommendations are one drink a day for women and two for men. Another way to reduce the risk for colon cancer are to stop smoking and maintain a healthy weight by exercising for 30 minutes per day most days of the week.

Teaching Strategies

The teaching strategies that this curriculum unit seeks to utilize are the following teaching tools:

• Case Studies
• Claim Evidence Reasoning
• Graphic Organizers
• Google Sites
• Think-Pair-Share

Case Studies: One key teaching strategy is the implementation of case studies. Using these methods students will explore cancer through a real-world scenario. During the case study students will have the opportunity to observe, analyze, implement, conclude, and summarize their findings in relationship to cancer. The case studies provide a good opportunity for students to engage in discussions and work through problem solving models. Since the cases are based on actual patient data, there is opportunity for the students to role play different aspects of the cancer care professionals from pathologist to oncologists. The case study method puts the student in the role of a problem solver and allows them to explore research from various perspective and have access to phenomenon that is not typically accessible to high school students.

Claim-Evidence-Reasoning (CER): The CER method provides students a way to organize and scaffold their responses. In the claim portion of the CER students make a statement about something that has occurred which is the premise for the rest of the writing prompt. The evidence section is used to gather and present information that is relevant to the claim. This portion of the writing prompt should provide sufficient evidence to prove or disprove the claim. The reasoning portion of the CER is used to connect the claim and evidence sections through justifying their reasoning and applying scientific principles. In this case the students will be using CER to justify their selection of a patient’s mutational analysis and subsequent diagnosis.

Graphic Organizers: Graphic organizer can take many formats but are used to help students organize, simply, or clarify information. In these lessons teacher-generated graphic organizers will be used to help scaffold the lesson content to support student learning. When used correctly graphic organizers can help guide students to categorize concepts, link interconnected ideas, and help students construct knowledge.  In this unit KWL charts, T-charts, and guided skeleton notes will all be used to help students make connections among multiple topics related to cancer.

Think-pair-share: This technique provides students the opportunity to think individually about topics and answer questions. After individual processing time students share ideas in small groups with their classmates. This section of the activity focuses on building oral communication skills and active listening. These activities also help with student focus because they are responsible for engaging in the conversation- which can be avoided in large group discussions- and increase comprehension of the material. In this unit think-pair-share can be used in most lessons and should help students form hypothesis or engage in discussion about their interpretations of the cancer case study information.

Google Sites: Google sites is an online platform that is similar to Wiki. Using this platform each student will create digital portfolios and collaborate on group projects. In this set of lesson plans students will use Google sites to present their findings on their research about diagnostic methodologies used for cancer. Students are able to include docs, videos, links, and many other formats to share their research. Since this will be used as a whole class group assignment, the site will allow students to contribute in knowledge building in the classroom and help other students to understand complex course content.

Classroom Activities

Cancer in the classroom: A case study curriculum is designed to improve student understanding of biological disease processes and increase their awareness of colon cancer. During this unit students will use a case study approach to develop critical thinking skills, apply foundational biology knowledge, and increase their understanding of genetics in relation to disease progression. Using colon cancer as the anchor for the unit students will explore how cancer develops, risk factors for cancer formation, and potential ways to reduce the risk of colon cancer. The curriculum is based on case studies which focus on the diagnosis of a family member with colon cancer. Students will use information based on real-life case studies to understand the biological components, diagnosis, and treatment of colon cancer.

Part I- Cell Cycle Unit

Essential Question : What is cancer?

Objective : Students will be able to identify common misconceptions about cancer and describe how a normal cell becomes a cancer cell.

NGSS Standard : RST.11-12.7 – Integrate and evaluate multiple sources of information presented in diverse formats and media (e.g., quantitative data, video, multimedia) in order to address a question or solve a problem.

• Warm-up: What do you know about cancer? A think-pair-share activity.

Students will work at their table groups to discuss what they know about cancer. As a table group students will share the information they know with one another. When they regroup, the class as a whole will generate a document on the interactive whiteboard which details all prior knowledge on the topic. This will also be a time for you as the instructor to identify any misconceptions the students may have about cancer in general.

• Activity: Colon Cancer True or False. In this activity students will work as teams to decide which cancer facts are true and which are false. This activity can be completed in a game format or as a whiteboard activity. The activity has a range of questions about cancer in general and questions specific to colon cancer. As you go through the activity a slideshow with the correct answer explanations can be displayed on the whiteboard to ensure all students have access to the correct answers. Instructions: The class will work in groups to determine if the following statements are true or false. To complete the activity students will arrange their chairs into lines. Each team will be provided two index cards with the labels true or false.  After the teacher reads the statement students will decide if the statement is true or false. The last person passes the index card up the line. As the card is passed each student must agree with the answer. If they do not agree they have the opportunity to pass the card backwards to retrieve the other answer card. The first group to get the card to the front with the correct answer earns one point. Teams will earn points based on the number of correct answers. Questions adapted from Statistics at a Glance: The Burden of Cancer in the United States
• Introduce students to the Real-World Scenario Case Study- Meet Lea.

This scenario will be used in all lessons so you can tell the story of Lea’s colon cancer case study while teaching students about the background on cancer formation, diagnosis, and treatment.

• Exit Ticket: What do you believe would be the most useful facts to learn about cancer during the lesson today? Include at least two facts in your response.

Students will analyze the case study and respond to the questions: If someone asked you what is cancer how would you respond? What do you think causes cancer?

Essential Question : What changes in the cell cycle are associated with cancer formation?

Objectives : Students will be able to identify examine how deregulation of the cell cycle leads to cancer. Students will be able to explain the role of tumor suppressors and proto-oncogenes in the regulation of the cell cycle. Students will be able to distinguish between images of healthy cells and images of cancerous cells.

PA Common Core Standards : 3.1.B.A Examine how interactions among the different molecules in the cell cause the distinct stages of the cell cycle which can also be influenced by other signaling molecules. BIO.B.1.1.1 Describe the events that occur during the cell cycle: interphase, nuclear division (i.e., mitosis or meiosis), cytokinesis.

NGSS Standards: HS-LS1-4. Use a model to illustrate the role of cellular division (mitosis) and differentiation in producing and maintaining complex organisms.

• Warm-up: Students generate a KWL chart on what they know, want to know, and have learned about cancer. Students should work to complete the first two columns on the KWL chart leaving the last column blank for the end of the unit. Allow students 5-7 minutes to complete chart and share the results with the class.
• Background on Cancer Presentation- cell cycle and the role of tumor suppressors and proto-oncogenes in cell cycle regulation. This presentation should be used to explain the normal process of the eukaryotic cell cycle and explain the function of tumor suppressors (as brakes) and proto-oncogenes (as the gas petal) in the process.
• Analogy Activity- During the presentation teachers will introduce the analogy of the brakes and gas petals in the car for tumor suppressors and proto-oncogenes. Students will work in small groups to form their own analogies for the process.
• Students will view animations/ images of healthy and cancerous cells. Students will analyze the microscopic appearance of the cells and discuss the differences in the cell morphology focusing on the irregularities in the cytoplasm, chromatin, and nucleus of cancer cells.
• Exit Ticket: Explain two ways you can differentiate between healthy and cancerous cells microscopically.
• Homework: Write a response to the following question: How does the cell cycle relate to cancer formation? In this response include the role of tumor suppressors and proto-oncogenes.

Lesson 3/4:

Essential Question : What screening techniques are used to detect cancer?

Objective: Students will investigate early detection plans and explore diagnostic tools used in colon cancer detection.

NGSS Standards: HS-PS4-5 Communicate technical information or ideas (e.g. about phenomena and/or the process of development and the design and performance of a proposed process or system) in multiple formats (including orally, graphically, textually, and mathematically). RST.11-12.7 – Integrate and evaluate multiple sources of information presented in diverse formats and media (e.g., quantitative data, video, multimedia) in order to address a question or solve a problem.

• Warm-up: What are some common diagnostic tools you have heard about that are used to diagnose cancers?
• Small Group Activity: Assign students to a diagnostic tool research topic. Students will work in small groups to generate a google site which explains each type of diagnostic tool used for the detection of colon cancer. The groups can focus on biopsy, colonoscopy, molecular testing of the tumor, blood tests, computed tomography (CT or CAT) scan, magnetic resonance imaging (MRI), ultrasound, or positron emission tomography (PET) scan. For each of the components the students should identify the type of material/equipment used, the purpose of the testing in relation to colon cancer screening, and how the type of diagnostic testing can be used to inform the doctors about the patient’s condition.
• Student presentations: Students will spend 3-5 minutes presenting their findings about their assigned diagnostic technique. Students will also have the information on the Google site to refer to at a later time to answer questions for the next component of the lesson.
• Diagnostic Tools Analysis Questions: Students will answer a series of questions which are designed to help students determine the most effective preventative and diagnostic screening tools for colon cancer. 1. How could a stool sample be used to help identify colon cancer in a patient? 2. What is the most effective way to detect colon cancer early? 3. What is the most definitive way to diagnose colon cancer? 4. Select 2 diagnostic tools and compare then. Explain the advantages and disadvantages of each tool.
• Case Study Analysis: Given the patients symptoms students will design a diagnostic plan for Lea. Students will suggest the sequence of diagnostic tools they would use to diagnose Lea as healthy or having colon cancer.

Part II- Genetics Unit

Essential Questions : What are mutations? How are mutations formed during the process of replication, transcription, and translation?

Objective: Students will analyze the role of errors during replication, transcription, and translation in the formation of cancer.

NGSS Standards: HS-LS3-2 Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

PA Common Core Standards: 3.1.C.C2 Use molecular models to demonstrate gene mutation and recombination at the molecular level. BIO.B.1.1.1 Describe the events that occur during the cell cycle: interphase, nuclear division (i.e., mitosis or meiosis), cytokinesis. BIO.B.1.2.1 Describe how the process of DNA replication results in the transmission and/or conservation of genetic information. BIO.B.1.2.2 Explain the functional relationships among DNA, genes, alleles, and chromosomes and their roles in inheritance.

• Warm-up: How do genes related to cancer? What type of cell would need to carry the mutation for it to be passed down from parent to offspring (somatic of gamete)? Do you think cancer can be familial (passed down in a family)?
• Central Dogma of Molecular Biology slideshow: During the slideshow teachers will explain the central dogma of molecular biology. These processes will include replication, transcription, and translation. In these lessons’ teachers will discuss how errors in each step could lead to the formation of mutations. Teachers will explain the difference between somatic and germline mutations and how germline mutations could lead to the formation of cancer in offspring.
• Identifying mutations Practice: Students are provided copies of normal DNA sequences and Lea’s DNA sequences to compare. The students will work in small groups to identify if any nucleotide changes exist between the provided sequences. Students will use codon charts to determine if the proteins produced would be affected. Following the analysis, the class will have a discussion on their findings.
• Warm-up: What is your definition of a mutation? What are some impacts of mutations on organisms?
• Introduction to colon cancer genetics slideshow: During the slideshow teachers will explain how mutations arise in genes. The focus of this presentation will be stepwise mutations that occur in colon cancer. Students will learn about the stepwise mutations (APC, KRAS, SMAD4, and p53) that drive the formation of colon cancer.
• Mutation Analysis Activity Part II: Students will examine the mutations from the previous class. Based on information provided in Lea’s case study students will identify which gene is mutated and which stage of cancer Lea likely has based on her mutation profile.
• Exit Ticket: Do you think it is useful to have a genetic profile on cancer patients? Why or why not? Explain.
• Homework: Using the information provided write a letter to Lea describing your findings. Explain the mutation(s) she has in her genetic profile and the correlation (if any) of the stage of disease she has.
• Warm-up: What does it mean for a disease to be inherited? Do you think Lea has an inherited form of colon cancer? Explain your answer.
• Inherited colon cancer slideshow: Teachers will explain the four primary types of inherited mutations: Familial adenomatous polyposis Lynch Syndrome, Peutz-Jeghers Syndrome, and MUTYH-associated polyposis. The slideshow will explain how each type of mutation is inherited and which part of the cell is impacted.
• Case Study CER- Using the evidence from the previous class and Lea’s case study students will compose a CER (claim, evidence, reasoning) prompt. In this prompt they would examine the evidence and provide rationale for diagnosing the individual with the specific mutation responsible for the colorectal cancer in the case study. In this prompt students will use multiple lines of evidence to describe why they selected the particular type of hereditary cancer for Lea.

Part III- Risk Reducers

Essential Questions : What are the most common cancer treatment methods? How can I reduce my risk of cancer? What are potential cancer careers?

Objectives: Students will evaluate cancer therapies. Students will evaluate cancer risks and cancer risk reduction strategies. Students will investigate cancer careers.

NGSS Standards: HS-LS1-6 Construct and revise an explanation based on valid and reliable evidence obtained from a variety of sources (including students’ own investigations, models, theories, simulations, peer review) and the assumption that theories and laws that describe the natural world operate today as they did in the past and will continue to do so in the future

HS-PS4-5 Communicate technical information or ideas (e.g. about phenomena and/or the process of development and the design and performance of a proposed process or system) in multiple formats (including orally, graphically, textually, and mathematically).

RST.11-12.7 – Integrate and evaluate multiple sources of information presented in diverse formats and media (e.g., quantitative data, video, multimedia) in order to address a question or solve a problem.

• Warm-up: What are some cancer treatment therapies you have heard of? What are some benefits and risks of cancer treatment?
• Cancer Treatment Slideshow: Teachers will explain the four treatment types used for cancer. The slideshow will explain how when/how each treatment is used.
• Cancer Case Study Treatment Small Group Research Assignment: During this component student will work in small groups to formulate a presentation on the treatment method they selected for the case study patient and provide evidence from the class presentation and a literature search which examines why their methodology would be effective in treating the patient.
• Warm-up: What do you believe are risk factors for developing cancer? Do you believe you can lower your chances of getting cancer? Why or why not? Explain.
• Cancer Risk Slideshow: Teachers will explain the major cancer risk factors and discuss ways to prevent cancer formation.
• Cancer Risk Reduction Activity: Students will evaluate their own risk factors for developing cancer and will be crafting a risk reduction plan.
• Warm-up: What types of jobs have you heard of that relate to cancer? Do you think all jobs relating to cancer need to be in the medical field? Why or why not? Explain.
• Cancer careers slideshow: Teachers will introduce students to various careers that are involved with cancer patient care (pathologists, genetic counselors, researchers, chemists, molecular biologists, etc.).
• Cancer Careers Profile Activity: Students to generate a potential career in cancer profile in which they select a career and research job components. In this project the students would identify the job description, education/training requirements, salary/earnings/benefits, and a description of “a typical day in the life” of a person in that career. The end product should be a poster that can be displayed in the classroom or a digital product for the website.

Component 1 Readings

• Misconceptions

Unknown. “Know the Facts.” Colorectal Cancer Alliance , 2021, https://www.ccalliance.org/colorectal-cancer-information/facts-and-statistics. Accessed 14 March 2021.

“What is colorectal Cancer.” American Cancer Society , 2021, https://www.cancer.org/cancer/colon-rectal-cancer/about/what-is-colorectal-cancer.html. Accessed 14 March 2021.

“Statistics at a Glance: The Burden of Cancer in the United States.” American Cancer Society, 2021, https://www.cancer.gov/about-cancer/understanding/statistics#:~:text=The%20cancer%20death%20rate%20(cancer,and%20135.7%20per%20100%2C000%20women). Accessed 18 April 2021.

• History of cancer research

“Milestones in Cancer Research and Discovery.” National Cancer Institute (NIH) , 31 August 2020, https://www.cancer.gov/research/progress/250-years-milestones. Accessed 14 March 2021.

Blackadar, Clarke B. “Historical review of the causes of cancer.” World Journal of Clinical Oncology , vol. 7, no. 1, 2016, pp. 54-86. NCBI , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734938/. Accessed 14 March 2021.

• Cancer development (tumor suppressor genes/ oncogenes)

Weinberg, Robert. “How Cancer Arises.” Scientific American , 1996, pp. 62-70.

Lee, Eva Y.H.P, and William J. Muller. “Oncogenes and Tumor Suppressor Genes.” Cold Spring Harbor Perspectives in Biology , vol. 2, no. 10, 2010, p. a003236. NCBI , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944361/. Accessed 14 March 2021.

• Healthy vs Cancerous Cells (morphology)

Mason, Laura. “Cancer Cells Vs Normal Cells.” Cancer Research from Technology Networks , 4 December 2020, https://www.technologynetworks.com/cancer-research/articles/cancer-cells-vs-normal-cells-307366. Accessed 14 March 2021.

O’Connor, C.M, and J.U Adams. Essentials of Cell Biology . Cambridge, NPG Education, 2010. Scitable by Nature Education , https://www.nature.com/scitable/ebooks/essentials-of-cell-biology-14749010/122997842/

“What is Cancer.” National Cancer Institute (NIH) , 9 February 2015, https://www.cancer.gov/about-cancer/understanding/what-is-cancer. Accessed 19 April 2021.

“What do doctors look for in biopsy and cytology specimens.” American Cancer Society , 2014, https://www.cancer.org/treatment/understanding-your-diagnosis/tests/testing-biopsy-and-cytology-specimens-for-cancer/what-doctors-look-for.html . Accessed 19 April 2021.

• Detecting Cancer

Chen, Xingdong, and Jeffrey Gole. “Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.” Nature Communications , vol. 11, no. 3475, 2020. nature.com , https://doi.org/10.1038/s41467-020-17316-z .

Nguyen, Ha This, and Hong-Quan Duong. “The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review). Oncology letters, vol. 16 no. 1, 2018. Spandidos publications, https://www.spandidos-publications.com/10.3892/ol.2018.8679 .

“How Cancer Is Diagnosed.” National Cancer Institute NIH , 2019, https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis. Accessed 14 March 2021.

Tze, Christina, et al. “Understanding colorectal cancer in Malaysia: A mini-review and pioneering colorectal cancer awareness, screening and treatment project.” Journal of Cancer Treatment and Diagnosis , 2017. Journal of Cancer Treatment and Diagnosis , https://www.cancertreatmentjournal.com/articles/understanding-colorectal-cancer-in-malaysia-a-minireview-and-pioneering-colorectal-cancer-awareness-screening-and-treatment-projec.html. Accessed 14 March 2021.

Component 2 Readings

• Genetic mutations and cancer

Cavagnari, Mariana Cavagnari, et al. “Impact of genetic mutations and nutritional status on the survival of patients with colorectal cancer.” BMC Cancer , vol. 19, no. 644, 2019. BMC Cancer , https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-5837-4. Accessed 14 March 2021.

“What is a gene mutation and how do mutations occur?” US National Library of Medicine , 2020, https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/. Accessed 14 March 2021.

• Inherited versus spontaneous mutations (transcription/translation)

Brown, Anna-Leigh, et al. “Finding driver mutations in cancer: Elucidating the role of background mutational processes.” PLOS Computational Biology , vol. 15, no. 4, 2019, p. e1006981. PLOS , https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1006981. Accessed 14 March 2021.

“The genetics of Cancer” Cancer.Net March 2018. https://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics-cancer . Accessed 20 April 2021.

• Colon cancer gene mutations

Lee, Sei-Jung, and C. Chris Yun. “Colorectal cancer cells – proliferation, survival and invasion by lysophosphatidic acid.” Int J Biochem Cell Biol , vol. 42, no. 12, 2010, pp. 1907–1910. National Institutes of Health , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975809/pdf/nihms244944.pdf .

“What causes colorectal cancer?” American Cancer Society , 2021, https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html. Accessed 14 March 2021.

Teaching, Model. “Claim-Evidence-Reasoning (CER).” Model Teaching Education for Better Educators , 29 January 2019, https://www.modelteaching.com/education-articles/writing-instruction/claim-evidence-reasoning-cer. Accessed 14 March 2021.

Component 3 Readings

• Cancer treatments

Pucci, Carlotta, et al. “Innovative approaches for cancer treatment: current perspectives and new challenges.” Ecancermedicalscience , vol. 13, no. 961, 2019. NCBI , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753017/. Accessed 14 March 2021.

Miller, Kimberly, et al. “Cancer treatment and survivorship statistics, 2019.” CA: A Cancer Journal for Clinicians , vol. 69, no. 5, 2019, pp. 363-385. ACS Journals , https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21565. Accessed 14 March 2021.

• Careers in cancer

“Health Professionals Associated with Cancer Care.” American Cancer Society , 2021, https://www.cancer.org/treatment/finding-and-paying-for-treatment/choosing-your-treatment-team/health-professionals-associated-with-cancer-care.html. Accessed 14 March 2021.

• How to reduce your risks?

McDowell, Erin. “10 jobs that are linked to a higher risk of cancer.” Insider , 27 July 2020, https://www.businessinsider.com/jobs-linked-to-higher-risk-of-cancer-2019-7. Accessed 14 March 2021.

Chan, Andrew, and Edward Giovannucci. “Primary Prevention of Colorectal Cancer.” Gastroenterology , vol. 138, no. 6, 2010, 2029–2043.e10. NCBI , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947820/. Accessed 14 March 2021.

“Colon Cancer.” Mayo Clinic, 2021, https://www.mayoclinic.org/diseases-conditions/colon-cancer/symptoms-causes/syc-20353669 . Accessed 21 April 2021.

When thinking about how the unit plan implements the Pennsylvania science standards and Next Generation Science Standards, each of the following unit sections use the corresponding standard(s):

NGSS Learning Standards:

HS-LS1-4. Use a model to illustrate the role of cellular division (mitosis) and differentiation in producing and maintaining complex organisms.

HS-LS3-2 Make and defend a claim based on evidence that inheritable genetic variations may result from: (1) new genetic combinations through meiosis, (2) viable errors occurring during replication, and/or (3) mutations caused by environmental factors.

HS-LS1-6 Construct and revise an explanation based on valid and reliable evidence obtained from a variety of sources (including students’ own investigations, models, theories, simulations, peer review) and the assumption that theories and laws that describe the natural world operate today as they did in the past and will continue to do so in the future

PA Common Core Standards:

Standard – 3.1.B.A Examine how interactions among the different molecules in the cell cause the distinct stages of the cell cycle which can also be influenced by other signaling molecules.

Standard – 3.1.C.C2

Use molecular models to demonstrate gene mutation and recombination at the molecular level.

BIO.B.1.1.1 Describe the events that occur during the cell cycle: interphase, nuclear division (i.e., mitosis or meiosis), cytokinesis.

BIO.B.1.2.1 Describe how the process of DNA replication results in the transmission and/or conservation of genetic information.

BIO.B.1.2.2 Explain the functional relationships among DNA, genes, alleles, and chromosomes and their roles in inheritance.

CBSE Expert

Case Study Questions for Class 11 Biology PDF Download

We have provided here Case Study questions for Class 11 Biology for final board exams. You can read these chapter-wise Case Study questions. These questions are prepared by subject experts and experienced teachers. The answer key is also provided so that you can check the correct answer for each question. Practice these questions to score well in your exams.

CBSE 11th Standard CBSE Biology question papers, important notes, study materials, Previous Year Questions, Syllabus, and exam patterns. Free 11th Standard CBSE Biology books and syllabus online. Important keywords, Case Study Questions, and Solutions.

Class 11 Biology Case Study Questions

CBSE Class 11 Biology question paper will have case study questions too. These case-based questions will be objective type in nature. So, Class 11 Biology students must prepare themselves for such questions. First of all, you should study NCERT Textbooks line by line, and then you should practice as many questions as possible.

Chapter-wise Solved Case Study Questions for Class 11 Biology

• Chapter 1 : The Living World
• Chapter 2 : Biological Classification
• Chapter 3 : Plant Kingdom
• Chapter 4 : Animal Kingdom
• Chapter 5 : Morphology of Flowering Plants
• Chapter 6 : Anatomy of Flowering Plants
• Chapter 7 : Structural Organisation in Animals
• Chapter 8 : Cell : The Unit of Life
• Chapter 9 : Biomolecules
• Chapter 10 : Cell Cycle and Cell Division
• Chapter 11 : Transport in Plants
• Chapter 12 : Mineral Nutrition
• Chapter 13 : Photosynthesis in Higher Plants
• Chapter 14 : Respiration in Plants
• Chapter 15 : Plant Growth and Development
• Chapter 16 : Digestion and Absorption
• Chapter 17 : Breathing and Exchange of Gases
• Chapter 18 : Body Fluids and Circulation
• Chapter 19 : Excretory Products and their Elimination
• Chapter 20 : Locomotion and Movement
• Chapter 21 : Neural Control and Coordination
• Chapter 22 : Chemical Coordination and Integration

Class 11 MCQ Questions

Class 11 students should go through important Case Study problems for Biology before the exams. This will help them to understand the type of Case Study questions that can be asked in Grade 11 Biology examinations. Our expert faculty for standard 11 Biology have designed these questions based on the trend of questions that have been asked in last year’s exams. The solutions have been designed in a manner to help the grade 11 students understand the concepts and also easy to learn solutions.

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On the boundary of exploratory genomics and translation in sequential glioblastoma.

1. Introduction

2.1. wes coverage and mapping quality in the gbm-p and gbm-r cohorts, 2.2. genomic variants in the gbm sample pairs, 2.3. oncogenic and likely oncogenic variants in the 10 gbm sample pairs, 2.4. variants that also frequently occur in tumors other than gbm, 2.5. potential therapeutic targets detected in the 10 gbm sample pairs, 2.6. clonality and tumor mutation rate (tmr) in the 10 gbm sample pairs, 3. discussion, 4. materials and methods, 4.1. subjects of the study, 4.2. sample characteristics, 4.3. sample preparation and quality check, 4.4. tert promoter sequencing, 4.5. library preparation for wes, 4.6. bioinformatics, 4.7. filtering pipeline for variant selection, 4.8. identification of oncogenic and likely oncogenic variants in gbm-p, gbm-r and gbm-s, 4.9. tumor mutation rate (tmr), 4.10. tumor heterogeneity, 5. conclusions, supplementary materials, author contributions, institutional review board statement, data availability statement, acknowledgments, conflicts of interest.

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Tompa, M.; Galik, B.; Urban, P.; Kajtar, B.I.; Kraboth, Z.; Gyenesei, A.; Miseta, A.; Kalman, B. On the Boundary of Exploratory Genomics and Translation in Sequential Glioblastoma. Int. J. Mol. Sci. 2024 , 25 , 7564. https://doi.org/10.3390/ijms25147564

Tompa M, Galik B, Urban P, Kajtar BI, Kraboth Z, Gyenesei A, Miseta A, Kalman B. On the Boundary of Exploratory Genomics and Translation in Sequential Glioblastoma. International Journal of Molecular Sciences . 2024; 25(14):7564. https://doi.org/10.3390/ijms25147564

Tompa, Marton, Bence Galik, Peter Urban, Bela Istvan Kajtar, Zoltan Kraboth, Attila Gyenesei, Attila Miseta, and Bernadette Kalman. 2024. "On the Boundary of Exploratory Genomics and Translation in Sequential Glioblastoma" International Journal of Molecular Sciences 25, no. 14: 7564. https://doi.org/10.3390/ijms25147564

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Skeletal Research Center researcher and Biology adjunct assistant professor Mike Sorrell passes away

For 34 years, J. Michael “Mike” Sorrell worked side-by-side with Skeletal Research Center (SRC) founder Arnold Caplan and countless other researchers from across the College of Arts and Sciences and the School of Medicine. As senior research associate and the director of the Monoclonal Antibody Facility within the SRC, Sorrell’s work played a major role in the advancement of regenerative medicine.

The university community is mourning the passing of Sorrell following a brief illness on June 11.  

“I cherished the time that I spent with Mike as we explored a shared interest in history and current events,” said research associate Jonathan Kenyon. “I am reminded of his sense of humor and recall numerous occasions when he would deliver a witty comment with an anticipatory grin, inviting us to share in his humorous perspective.”

Sorrell, who received his bachelor’s degree and PhD from Temple University, focused much of his research around connective tissues, extracellular matrix, cells that produce those matrices and dermal fibroblasts to study their interactions with vascular cells. He endeavored to design a new generation of tissue engineered organs and to understand the role of fibroblast in wound repair.  

“Mike’s passion for science was evident, despite his reserved demeanor,” said colleague and Senior Research Associate Rodrigo Palacios. “He could engage in extensive discussions about his research and scientific topics in general.” 

While Sorrell joined the biology department as an adjunct assistant professor in 2011, he continued to maintain his SRC office and contributed as a researcher up until his recent passing. 

He was proud of his work with L’Oreal Life Sciences to study human dermal fibroblasts and function in human skin, and with the Armed Forces Institute for Regenerative Medicine on Hyaluronan as a topical delivery vehicle for wound repair, and for burn and wound healing.

Born in Covington, Kentucky, Sorrell was a veteran of the Army National Guard of Pennsylvania where he attained the rank of sergeant. He enjoyed traveling, country music and watching movies. Sorrell also had a passion for history.

Although his parents and brother preceded him in death, Sorrell developed close friendships with coworkers he considered family. He will be missed by many and leaves behind a wealth of memories in the hearts of all who knew him.

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Why Is He Different from Both Parents?

The Genetics of ABO Blood Types

By Jun Liang, William J. Rice

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This case study was developed to teach the topic of human ABO blood type and genetic inheritance in biology courses at the lower undergraduate level or upper high school level. It is suitable for entry level biology, genetics, and physiology courses. The case narrative tells the story of Kevin, a teenager who is puzzled by the fact that neither of his parents can donate blood to him. He and his best friend ask their biology teacher for help, and she explains human ABO blood types at the molecular and genetic level to solve the mystery. The case consists of three sections, which can be used sequentially or separately. After completing the case study, students will understand the molecular basis of ABO blood types and how genes control the phenotype and genotype of an individual. They will also have a better understanding of how human ABO blood type is inherited from generation to generation.

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• Understand the significance of human ABO blood types.
• Explain surface markers, genes, and alleles that determine human blood types.
• Determine the possible genetic makeup of an individual with a given blood type.
• Use genetic principles to determine possible inheritance of ABO blood type.
• Understand antigens and antibodies created in each blood group.
• Explain blood transfusion reactions.

carbohydrate; genetic inheritance; ABO blood type; positive; negative; antibody; blood transfusion; blood serum; Punnett square; Mendelian genetics

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High school, Undergraduate lower division

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Two Crick group leaders elected as EMBO members

• Date created: 9 July 2024
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Crick group leaders Alessandro Costa and Snezhka Oliferenko have been elected members of the European Molecular Biology Organisation (EMBO) .

Former group leaders Paola Scaffidi , now at the European Institute of Oncology, and Kathy Niakan , now at the Cambridge Stem Cell Unit, have also been elected. 

Alessandro Costa studies how molecular machines unravel and copy DNA in our cells . 

EMBO is an international organisation of life scientists with over 8,000 members. It aims to support talented researchers at all stages of their careers, stimulate the exchange of scientific information and help build a cohesive European research environment. Alessandro and Snezhka join 120 new additions to the community in EMBO’s 60 th anniversary year.  

Alessandro Costa, Group Leader of the Macromolecular Machines Laboratory at the Crick, studies how molecular machines unravel and copy DNA in our cells, and how cancer can develop if these machines are faulty.

His team are interested in finding out how the machines that open and copy DNA work together to make sure genetic information is transmitted correctly, and what happens if these processes go wrong.

He is currently using imaging techniques to explore how reactions take place during DNA replication in test tubes, and would now like to visualise these replication machineries actually inside a cell.

Alessandro said: “Being elected a member of EMBO is a great honour. I thank the members of my group past and present, my colleagues and mentors at the Crick and around the world.”

Snezhka Oliferenko investigates how yeast cells grow and divide . 

Snezhka Oliferenko, Group Leader of the Comparative Biology of Mitotic Division Laboratory , investigates how yeast cells grow and divide in a process called mitosis. Her team compare related yeast species to understand mitosis and the different approaches organisms use to complete it.  

Her team investigate how some cells break open the protective envelope surrounding the nucleus during mitosis, compared to others that complete cell division without this step.

Currently, Snezhka is interested in understanding if evolutionary changes in cellular metabolism – the underlying biochemistry of the cell – can help to explain the evolution of complex cellular features, such as organelle properties, cell size and growth rate.

Snezhka said: “I am very honoured to be elected as an EMBO member. Many thanks are owed to my lab members who have driven the science forward contributing greatly to this success. I have always been very lucky to be surrounded by amazing colleagues, who have shaped my research in innumerable ways. Thanks to all these people, I have great fun doing interesting science. I am looking forward to contributing to the European scientific community”.

EMBO Director Fiona Watt said: “The new EMBO Members and Associate Members have made immense contributions to fundamental life science research, and, in many cases, their work has paved the way for innovations that have improved lives and livelihoods around the world. As EMBO marks its 60th anniversary, we celebrate the pivotal roles played by the EMBO Membership in strengthening international life science research and contributing to the EMBO Programmes and activities. I send my warmest congratulations to all those elected.”

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