20.020 | Spring 2009 | Undergraduate

Introduction to Biological Engineering Design

Lecture and Studio Notes

Session Key

L = Lecture
S = Studio

The lecture and studio notes for each week are linked in the following table.

WEEK # SES # TOPICS ACTIVITIES NOTES PAGES
1 L1 Design, build, test Paper airplane Week 1 Notes
S1 Sampling of past projects iGEM project review
L2 Science as a take-apart Take apart a tape recorder
2 L3 Engineering as a rebuild Reassemble the tape recorder Week 2 Notes
S2 Broader project landscapes Scripts and storyboards
L4 Decide what’s worth doing Play “Decide” (an exercise in policy and team dynamics)
3 S3 Sorting hat into project camps Temporary teams brainstorm project ideas Week 3 Notes
L5 Knowns vs. unknowns The Clock of the Long Now
4 L6 Backyard biology Kitchen DNA, Lego™Phoresis Week 4 Notes
S4 Project teams assigned Work on team contract and Facebook page
L7 FooCampers guide to bioengineering More Lego™Phoresis
5 L8 Scientist as activist Video of DNA experimentation hearings, 1976 Week 5 Notes
S5 Design day 1

MIT Libraries research guide webpage

Work on projects
L9 Interface between scientific/engineering community and the broader public Guest lecture by Prof. Jonathan King, MIT
6 L10 Project work day   Week 6 Notes
S6 3 ideas presentations  
L11 3 ideas feedback Final project selection
7 L12 System overviews Flip books, iGEM “bacterial buoy” project Week 7 Notes
S7

Design day 2

Abstraction in action part 1: systems to devices

 Work on projects
L13 Abstraction in action part 2: devices to parts  
8 L14 Parts and registry   Week 8 Notes
S8 Design day 3 Test and debug; data-driven decision making
L15 Hypothesis-driven engineering Validate system operation, learn from modes of failure
9 L16 Project work day   Week 9 Notes
S9 Tech spec review presentations  
L17 Tech spec feedback Plan project re-design
10 L18 Reliability Failures of materials, system performance and human sources Week 10 Notes
S10 Re-design day 1 Join Registry of Standard Biological Parts
L19 Ownership and sharing Inventor vs. investor role playing
11 S11 Re-design day 2 Drew Endy teaching Week 11 Notes
L20 Project work day Drew Endy teaching
12 L21 Project work day (cont.)   Week 12 Notes
S12 Consulations on projects  
L22 Tips on oral presentations  
13 L23 Project work day   No notes – see projects page for presentations
S13 Final presentations day 1 Three teams present
L24 Q&A and project work Class evaluation
14 L25 Q&A and project work (cont.)   No notes – see projects page for presentations
S14 Final presentations day 2 Three teams present
L26 Wrap-up and celebration  

Lecture and Studio Notes index | Next week »

Lecture 1: Design, Build, Test

Studio 1: Sampling of Past Projects

Lecture 2: Science as a Take-apart

Lecture 1: Design, Build, Test

Course orientation slides (PDF - 1.2MB)

Challenge: Project Runway

Instructions: Today you will design, build (i.e. fold) and launch a paper airplane. Your goal is to make a plane that flies further than anyones. Working in teams of 3, choose one person to be the designer, one to be the builder, and one to be the launcher. You can talk to each other at all stages but be sure each person does the assigned job and that someone takes notes of your work together (decisions, uncertainties, disagreements, expertise etc). Your team may use the internet if you want. The designer has one dollar to spend and your team must keep track of costs. No refunds will be issued for parts you do not use. In the event of a tie, cost and aesthetics will serve as the tie breaker. Relevant materials cost:

  • paper is 30 cents a sheet
  • paper clips are 10 cents each
  • scotch tape is 5 cents per 1 inch strip
  • pennies cost 20 cents each
  • a pencil costs 10 cents
  • scissors are unavailable
  • a test flight before the competition costs 30 cents.

Your team has 20 minutes to design and build a plane for the competition. If you are not ready to launch at this time, you will forfeit.

Why are we doing this??

  • “to give us a way to visualize a design that may seem unlikely and that may not seem like it would work”
  • “to give us a problem we might feel is more approachable”
  • “the most complicated design isn’t always the best. Simple works”
  • “how different all the plane designs are, even starting with the same materials.”
  • “I think it was difficult to decide on rolls”

Comments courtesy of the students. Used with permission.

Homework

PDP1: Letter on a Real World Problem that You Would Like to Solve

Due at next class.

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Studio 1: Sampling of Past Projects

Part 1: Wednesday Matinee

Instructions: Today you will have the opportunity to watch two videos showcasing completed iGEM projects. “iGEM” stands for the “international Genetically Engineered Machines” competition. It is a summer-long opportunity for teams of students working at colleges and universities around the world to design and build genetically engineered machines, many of which use standard biological parts from the Registry of Standard Biological Parts. The videos will orient you to the kinds of accomplishments realized in a summer by teams of undergraduates and their advisers.

Our First Feature Presentation

Our first featured presentation will emphasize some of the “biology” that’s often present in “synthetic biology.” As a class we’ll watch:

In watching their project we can focus on

  • cell-cell communication, sensing and chemotaxis
    • our ppt review of these processes (PDF)
  • phage life cycles, DNA transfer mechanisms and “parts”
    • our ppt review of these processes (PDF)

Left: sensing phage; Right: lytic phage. (Courtesy of DKFZ/Univ. Heidelberg/iGEM Team Heidelberg. Used with permission.)

Note that this team developed a tremendously useful Web site that describes both their project, their human practice work and the basic background a person might need to understand the work. If your molecular biology is rusty, you can refresh your memory here.

Our Second Feature Presentation

Eau D’coli. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Our second featured presentation will emphasize some of the “engineering” that can be accomplished in a summer by a talented group of undergrads much like yourselves. As a class we’ll watch:

  • The 2006 iGEM team from MIT describing a neat project for fine chemical synthesis. (These files are presented courtesy of the 2006 MIT iGEM Team: Stephen T. Payne, Reshma P. Shetty, Veena Venkatachalam, Kate Broadbent, Delbert Green II, Boyuan Zhu, Barry Canton, Austin J. Che, Jason R. Kelly, Samantha C. Sutton, Thomas F. Knight, Jr and Drew Endy.)

Their project will allow us to focus on

  • programming genetic logic, growth phases of bacterial cultures, ethical questions of human experimentation
    • our ppt review of these processes (PDF)

After Each Presentation

You will have 10 minutes to gather with your fellow moviegoers and discuss what you saw, using these “iGEM review questions” as a guide for your conversations:

  1. what was the problem this team chose to address and why?
  2. is this an important problem and why or why not?
  3. did they succeed in part or in total?
  4. are there aspects of the work that are unclear to you?
  5. if you could ask this team one question what would it be?

Why are we doing this??

Most of our studio session today was spent considering two projects carried out by undergraduates not unlike yourself. The iGEMers worked in teams (as you will) to figure out what they wanted to build (as you will) and then spent some time in the lab realizing their project (not possible in this class but you could join the iGEM program this summer, as three of the 20.020 students from Spring 2008 did!). Remember that these are just two projects of many and you should feel motivated by them to work this term on a project that’s important to you. The projects also highlight a few of the many widgets in the toolbox for biological engineers. You might want to revisit these projects as the details of your project becomes clearer.

Part 2: Dear John

As homework you were asked to draft a letter describing a real world problem or opportunity you have inherited that could be addressed in the near term. You should discuss these letters at your team tables and make some notes about them on the white boards. For example,

  • who were they addressed to?
  • how many problems/opportunities did each letter address?
  • what areas were tackled?
  • how many also proposed solutions to these problems?

After about an hour of discussion at your tables, you’ll have a chance to hear from the other groups. Be sure to take notes on your letter about any new ideas, clarifications, or thoughts you have from the discussion. You will turn in a revised letter before tomorrow. (and note that if you’ve finished your discussion about the letters early you can get to work on the homework below).

Homework for Tomorrow’s Challenge Session

PDP2: iGEM project review questions

Due at next class

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Lecture 2: Science as a Take-apart

Challenge: Sexy on the Inside

  1. Watch this video in which Gever Tulley talks about learning by doing. “Gever Tulley on 5 Dangerous Things You Should Let Your Kids Do.” TED.com. March 2007. Accessed October 16, 2009.
  2. Watch this video of a person taking apart a MacBook Air. Mascari, Christopher. “MacBook Air Tear Down: Sexy On the Inside Too.” Gizmodo, January 24, 2008. Accessed October 16, 2009.
  3. Working in groups of 3, you will take apart a tape recorder. One person should work the tools, another should record the process (e.g. “began by taking off back panel), another should keep a parts list (e.g. “4 Phillips-screws 3 mm long from back panel”) and should record the purpose of each component (e.g. “Phillips screws held back panel in place). Your team’s goal is to disassemble the tape recorder into the greatest number of re-usable parts… note of the word “reusable” since next time we meet, the goal will be to reassemble your tape recorder into a working machine. As you work, you may find it helpful to describe what you think each component does and if it’s made of sub-components that can be separated further without forever destroying the component’s function.
    • “One of the problems of taking things apart and seeing how they work—supposing you’re trying to find out how a cat works–you take that cat apart to see how it works, what you’ve got in your hands is a non-working cat,” Douglas Adams
  4. If there’s time, watch this video showing the inner life of the cell, an understanding largely achieved by scientific “take apart” techniques. Marchant, Beth. “Cellular Visions: The Inner Life of a Cell.” StudioDaily, July 20. 2006. Accessed October 16, 2009.

Why are we doing this??

Taking something apart is one way to understand how it works. Having disassembled a simple machine, you should consider what you’ve gained from the process. What did you learn? What about this challenge resembled science and what did or didn’t feel like engineering? Was the tape player build to enable this sort of work? What (else) has the tape player been built for/ optimized for? What are the chances you’ll be able to re-assemble this machine next week?

Feedback from students:

  • advice: “draw pictures, taking pictures would be even better”
  • what would have helped? “more time, not having to reassemble, knowing which parts can be broken, if the tape player was build for human understanding and use”
  • thoughts for next time: “I hope not every part is needed"“it would have been easier if we could re-assemble it right away rather than wait until Tuesday”
  • what were these built for: “these are battery eaters, optimized for disposable, cheap economy”
  • woulda-shoulda-coulda: “we should have tested it before we took it apart”
  • If the tape player had been built to take apart, thered probably be…“fewer parts esp if not all parts are needed” “easier open/close, no hidden clips” “documentation” “higher quality parts”

Comments courtesy of the students. Used with permission.

Homework

PDP3: Script and Storyboard

Due at next week’s studio.

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Lecture 18: Reliability: Accidents Waiting to Happen

Studio 10 Re-Design Day 1

Lecture 19: Ownership and Sharing

Lecture 18: Reliability: Accidents Waiting to Happen

Not all engineers are pessimists but since good designs anticipate failure modes, many engineers must at least consider Murphy’s Law (what can go wrong will go wrong) as they flesh out the details of their designs. Like Daedalus’ wax wings flown too close to the sun, even designs that work well have limits and breaking points. If an engineered object is to work reliably, then the designers will have to carefully examine its multiple points of failure, including the three that today’s challenges address: extreme forces, performance variations, and h.uman fallibility.

Challenge 1: Reliable Materials/use

Modified from a lesson described in: Petroski, Henry. To Engineer Is Human: The Role of Failure in Successful Design. New York, NY: Vintage, 1992. ISBN: 9780679734161.

Boxes of paper clips don’t usually come with “a money back guarantee” since nearly everyone in the world who uses paperclips finds them a reliable way to hold a few pieces of paper together. But bend the paperclip wide a few times and it’s likely to break. How many times will that be? We’ll do a quick experiment to find out. Each of you will bend a paperclip back and forth until it breaks and we’ll plot the data on a histogram.

Distribution of bends needed to break paperclip.

Did all the paperclips break after the same number of bends? If so, why? If not, why not?

Reason 1:

Reason 2:

Mapping These Ideas to Your Project

This paperclip challenge spotlights two modes of system failure, namely

  1. fatigue of the materials that comprise the device and
  2. application of uncharacteristic forces.

As you’ve seen these affect each paperclip to differing degrees. When thinking about biotechnologies, what is akin to “material fatigue”? What situations might be considered uncharacteristic? How cell to cell differences can be taken into account is touched on in the next challenge but here let’s apply material and use variations to the Eau dcoli project from the MIT 2006 iGEM team. Recall, these bacterial cells were designed to smell like bananas when they reach stationary phase.

Expression of Eau d’coli behavior. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Schematic of the Eau d’coli banana odor generator. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

  1. In your groups imagine at least two ways that the genetic material in this system might “fatigue” and how you’d know.
  2. Next define at least two environmental conditions that would derail the system and decide how likely these conditions are.

Challenge 2: Reliable Performance

The first challenge today addressed catastrophic failure–if breaking a paperclip can be called “catastrophic.” The activity makes clear how engineers can enhance reliability by anticipating then obviating failure modes. Certainly, weaknesses can be tested and quantified, leading to reliability terms such as the “MTTF” (Mean Time To Failure). And certainly there are simple things to try that lengthen “MTTF” such as specifying operating conditions (“don’t repeatedly bend the open clip back and forth") or including redundant functions (“use two paper clips when in doubt”). But catastrophic failure is only one way to fail. Today’s second challenge will consider another mode of failure, namely unreliable performance.

The framework presented here is attributed to Reshma Shetty and the thesis work she did in the labs of Tom Knight and Drew Endy. She has developed a framework for characterizing transcription-based logic devices that we will modify to talk about system-level behavior.

To introduce digital devices and means for guiding reliable behavior, we’ll watch the BioBuilder animation “Genetic Digital Devices.”

Digital vs Analog Logic

As our starting point we’ll consider the simplest Boolean logic gate, the inverter or NOT gate. This gate has just one input. When that input has a logical value = 1 the output of the inverter is logical value = 0. And when the input value is = 0, the output is =1. The truth table and transfer curve for such a digital logic device is shown:

Inverter logic, digital signal. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Inverter transfer curve for digital signal. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Expression profile for Eau d’coli. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

The inverter’s transfer curve should remind you, just a little, of the shape of the curves we’ve already seen for the wintergreen and banana smell generators in the Eau d’coli project. Recall that the devices in this cell are controlled so that the wintergreen scent is generated only in log phase growth of the cell and the banana scent is generated only in stationary phase. The wintergreen scent, for instance, is programmed by a combination of a sensor (stationary phase promoter), a logic device (inverter), and an actuator (odor production). In fact if you examine the system level diagram that the team specified you’ll see an inverter device regulating the conversion of salicylic acid to methyl salycilate.

Eau d’coli device-level system diagram. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Left: analog vs digital transfer curves; right: thresholds for system operation. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Mapping the log-to-stationary phase concentration of methylsalycilate (in green) to the digital transfer curve (in red), you can see that activity of the green boxed wintergreen-generating device is swinging from a high value to a low value but the trip point (the input value at which the device inverts the output signal) is not precise. To impose digital logic on the analog signal, we’ll have to impose thresholds. Thresholds designate a value above which the input for the device will be given a logic value = 1 and below which the logic value will = 0. You’ll note that the thresholds still leave some values that have unspecified consequences for the operation of the device. You’ll also note that the steeper the slope of the curve, the more accurately the gated signals will perform.

Please note that we have modified a framework that’s useful for characterizing individual devices (e.g. sensors, logic devices, actuators) in order to describe the behavior of a system built with those devices. We’ve done this to help think about reliability in performance. Once your understanding of this description is solid for the system overall, it’s worth thinking about the performance of each device that comprises the system and what the error rates might be for each.

Performance Implications

In your group you should consider the following 3 questions:

  1. When thinking about biological analog to digital converters, what aspects of biology should be taken into account? (Note: you can restrict your thinking to systems that are controlled by transcriptional logic)
  2. What would be the consequence of a 10% error in the logic output for the wintergreen generating device? Would this be a tolerable error rate for this system?
  3. Would a 10% error rate be acceptable for a device in your own project? Why or why not?

Challenge 3: Reliable Sources

Here’s a story that’s been passed from teacher to teacher: two students spend the night before their big final exam at a party and they end up sleeping through the test. They tell the teacher that a flat tire is what kept them from the exam and the teacher, seemingly gullible, lets them retake the exam in separate rooms. The exam has only one question: which tire?

Very cute. Very clever. But is it true or urban myth? How do you know? Today you’ll have a chance to sniff out fact from fiction with a scientific game of “I doubt it.” You’ll hear three short stories from the scientific literature and you need to pick the fake one from the mix. This sniffing out of the truth will be harder than you might think. For one thing, these stories will be drawn from recent scientific developments and nature is incredibly imaginative. Consequently things that sound impossible turn out to be very real. In addition, there is often a personal set of beliefs that everyone works within, making stories that validate or reinforce those beliefs seem more plausible. One instance of such bias is the hoax article about climate change that many bloggers righteously touted as the truth revealed (Wikipedia page | PDF of hoax paper).

PS. The tire story turns out to be largely true as reported by the Chronicle of Higher Education. Many thanks to Duke Chemistry Prof. James Bonk for a great, mostly true story to tell.

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Studio 10: Re-Design Day 1

Join the Registry!

Please designate one person from your team as the person to obtain an account at the Registry of Standard Biological Parts. You and your project team should identify a part that you’d like to spotlight from your project and then enter it into the Registry. See the details of this requirement in the Final Presentation guidelines.

Project Redesign Day

Today’s session is devoted to working on your projects.

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Lecture 19: Ownership and Sharing

This challenge was originally developed and written by Drew Endy.

Challenge: Inventor and Investor Role Playing

Many useful genetic parts are currently protected by patents. For example, “uses of green fluorescent protein” are protected by United States Patent #5,491,084 (PDF). At least 200 more recent patents protect additional uses of various fluorescent proteins. Patents are a legislated form of “intellectual property” by which inventors are granted a limited-time monopoly (~17 years) during which they can control access to the patented technology (e.g., by selling exclusive or non-exclusive licenses). In establishing the U.S. patent system, the founders of our country wanted to balance the sharing of inventions (e.g., via the publishing of patent applications) while also encouraging the investment and profit needed to drive innovation.

For today’s challenge, you will act as either the inventors and patent holders of various genetic parts or the investors hoping to assemble and earn $ off a completed system.

If you are an Inventor

  • Each inventor holds a patent or two that cost either $1, $2 or $5 to secure. You will have to “pay” this money up front and will be reimbursed at the end of the day, either by the investor who will want to license your technology or by the clients/teachers.
  • Patent holders may license the use of their patents for profit (exclusively or non-exclusively), or give away the rights for free
  • Patent holders will not know how much the final client/teachers are willing to pay for the complete Eau d’coli system
  • Be aware that there are 12 components needed to produce a full Eau d’coli system, namely:
  1. A genetically encoded “inverter”
  2. A “constitutive promoter”
  3. A “stationary phase promoter”
  4. A “transcription terminator”
  5. A “weak ribosome binding site”
  6. A “strong ribosome binding site”
  7. The gene encoding the “ATF1” enzyme
  8. The gene encoding the “BSMT” enzyme
  9. The gene encoding the “PCHA” enzyme
  10. The gene encoding the “PCHB” enzyme
  11. The gene encoding the “BAT2” enzyme
  12. The gene encoding the “THI3” enzyme

If you are an Investor

  • Each investor is seeking to license the complete set of genetic parts needed to encode the Eau d’coli system.
  • The first investor who is able to acquire licenses for all the genetic parts needed to encode the full Eau d’coli system will earn real cash money!! The pay out will be told to the investor group but should not be shared with the inventors and patent holders.
  • The winning investor (if any) will be required to pay all inventors whatever fees might have been negotiated in obtaining the rights to use various genetic parts.
  • If the promised fees are less than the pay out then the investor can keep any additional cash (really).
  • If the promised fees are greater than the pay out then the investor must pay all additional licensing fees out of their own cash reserves. (really, but it would be better to re-negotiate your licensing deals than to have this challenge cost you $$).

Good luck and, perhaps, great profits!

Why are we doing this??

After the challenge, we’ll consider the following questions:

  1. Was it easy or difficult to license parts?
    • hard to license parts, wanted more $, limited # of patents to be had, competition for same parts,
  2. What determined the value of a part? Did inventors tend to overvalue parts? Did investors tend to undervalue parts?
    • cost of production
    • how much the investor wanted
    • knowing how much the completed system is worth would have helped value the parts,
    • if there’s no other competition
  3. Were any parts licensed for free? Why?
    • no…but for the good of the many
  4. The challenge system in today’s class contained 12 parts. Would it be easier or more difficult to license the parts for a system that contained fewer parts (e.g., 3 parts)? What about more parts (e.g., 100 parts)?
    • fewer parts easier…because it would drive down costs
    • or harder if more competitive
    • how many own enzymes or parts
    • net benefit
  5. In the “real world” deals are often brokered between the same parties more than once…this year you have a deal for Eau d’coli, next year for something else. How would the fact that you may have to deal with the investor/inventor again change the dynamic of today’s challenge?
    • I told other investors about existing deals…
    • inventor set minimum price

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Lecture 21: Project Work Day

Studio 12: Consulations

Lecture 22: Tips on Giving Talks

Lecture 21: Project Work Day

Use class time to work on the projects.

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Studio 12: Consulations

This week, we have arranged for each project team to consult with at least a couple of advisors having relevant experience.

Boost the Body (Hepatitis C treatment)

ENERGYneering (algae biofuel)

Meat! (in vitro food)

oncoCURES (early metastasis detection)

Sleep-away (alertness aid)

Trash to Treasure (accelerated composting)

  • Randi Mail, Cambridge MA recycling director
  • Chia Wu, MIT (Gerald Fink lab)

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Lecture 22: Tips on Giving Talks

Today we consider tips and tricks that you might use to construct and deliver even better presentations.

  • Slides with some notes: (PDF)
  • Video that illustrates a lot of powerpoint “do’s” and “don’ts.” ADMCVideos. “Part 3 - PowerPoint Do’s and Don’ts.” YouTube. January 26, 2009. Accessed October 20, 2009. http://www.youtube.com/watch?v=cyPckg8eNVM.

Happy Presenting!

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Lecture 3: Engineering as a Rebuild

Studio 2: Broader Project Landscapes

Lecture 4: Decide What’s Worth Doing

Lecture 3: Engineering as a Rebuild

Challenge: Extra Credit for Extra Parts?

Instructions: Last week you tried to understand a tape recorder by considering the components and subcomponents that operate inside it. Today you will demonstrate your understanding of the machine by re-assembling it from those components…"what I cannot create, I do not understand*.*" and all that…Take a careful look at your parts list and your notes from last time. The team that can reassemble their tape recorder from the greatest number of parts will win this challenge. You have 1/2 an hour to work on this task.

Data from last week’s take-apart

TEAM PARTS SUCCESS?
1 22 Not really spinning or working
2 42 Duct-tape masterpiece (see photo below), singing from tape, radio working
3 24 Fully reassembled, radio working
4 31 Next step full-disassembly
5 34 Play and stop, no sound
6 27 Spinning but uncertain of tape playing
7 34 Singing in Martian, but reversing spring to bring to earth
8 30 Motor was a one-time spinner

At the end of the 1/2 hour we will spend some time tallying the successes of the groups.

Duct-tape masterpiece from Team 2 (Photo courtesy of Ryan Alexander and anonymous students CN and DZ. Used with permission.)

Why are we doing this??

Even if you were only partially successful in reassembling your tape player, there are probably a lot of things you’ve learned…things that would help you or the next person to successfully reassemble a tape player, things that reflect back on the take-apart exercise, aspects of the exercise that are common to any scientific or engineering effort (and remember your work this term will have elements of both!). We’ll work as a class to add more ideas, questions and thoughts to this list.

Comments from 2009 students (courtesy of the students, and used with permission.)

  • advice: “draw pictures, taking pictures would be even better”
  • what would have helped? “more time, not having to reassemble, knowing which parts can be broken, if the tape player was build for human understanding and use”
  • biggest obstacle: “not having the right experience to solder or build circuit”
  • secrets to success: “good notes, Duct tape, didn’t try rebuild as it was”
  • advice to next year’s students: “bring a camera, don’t lose things, know which direction the springs go in, not all parts are needed”

Homework for Tomorrow’s Studio Session

Complete PDP3: Script and Storyboard

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Studio 2: Broader Project Landscapes

WHAP! BAM! Gadzooks!

Warm-Up

Begin today by reading the following script (PDF)

Next, we’ll look at the storyboards associated with this script.

Finally, we’ll watch the animation that was generated from this script and posted to BioBuilder.

Work Out

Next, think about how to storyboard your script. You do not need any fancy animation tools and there’s no extra credit for finishing first or for fancy images. Ideally you’ll use no more than 4 sheets of paper to fully sketch your script. Please be sure your name is on all the pieces of paper. You have up to an hour to complete your sketches.

When you have completed your sketches, find a place on the wall to hang your work (script and drawings), and then spend 1/2 an hour walking around the room checking out what others have done.

Why are we doing this??

This poster session is a quick way to scope out the landscape of interests in the class. In addition, drawing is a time honored (but under-utilized) way to learn science. See:

> Lerner, Neal. “Drawing to Learn Science: Legacies of Agassiz.” J Technical Writing and Communication 37, no. 4 (2007): 379-394.

Next week you will be divided into temporary “camps” around particular topics and you’ll generate a camp catalog of ideas. Then you’ll get to choose your top three items from all the camp catalogs and be sorted into final teams with common interests. Tomorrow’s challenge session will help you further decide what kinds of things are important to you and also what kinds of team dynamics matter most to you.

Homework for Tomorrow

To set the stage for tomorrow’s group challenge, please read the following article:

Jack, Andrew. “UK Baby Tested for Cancer Gene Due Soon.” FT.com (Financial Times), December 20, 2008. [May be viewed at FT.com with free registration.]

Tomorrow we will spend time thinking about the impact and perception of technological advances, especially bio-medical ones like Pre-implantation Genetic Diagnosis (PGD).

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Lecture 4: Decide What’s Worth Doing

Challenge: You Decide

The topic on today’s table is Pre-implantation Genetic Diagnosis (PGD). With a minimum of 4 people at a table (or a maximum of 8 people) you can start to play “Decide.” Before our challenge hour is through, your team will have to develop a “Policy Position” on this topic. Everyone at the table will start with

  • one place-mat/work-board describing the issue
  • White story cards
  • Green information cards
  • Blue issue cards
  • Red challenge cards
  • Yellow cards to facilitate discussion

Phase 1: Set-up

  1. Begin by choosing a reader to read (out loud!) the topic’s description that’s written in the upper left-hand corner of each place-mat.
  2. Choose a different reader for the 4 policy positions that your group will ultimately decide between.
  3. Finally choose a different reader to read out loud the discussion guidelines that are written in the bottom left-hand corner of each place-mat.

Phase 2: Learning

This phase will require ~30 minutes

  1. Each player should read the white story cards and choose 1 they find most compelling to keep on their place mat.
  2. Each player should read the green information cards and choose 2 they believe are the most significant to the story they’ve chosen. These cards can also be placed on their place-mat.
  3. Each player should read the blue issue cards and choose 2 they believe are the most significant to the story they’ve chosen. These cards should be placed on their place-mat.

Phase 3: Discussion

This phase will require ~30 minutes. There are many ways to structure the discussion but you can, as a group, decide

  • if you would like a “free form” discussion in which players may participate in any order and yellow cards can be used to signal frustration with the speaker, 

    or

  • if you would like a “round table” discussion in which conversation proceeds from player to player around the table and “talk money” can be used to talk out of turn (everyone has two “talk money” chits on their place mats).

Once the ground rules for discussion are set, someone should distribute the red cards, one to each player, face down. Next someone should begin by summarizing their story and the relevant information and issues. Depending on the discussion style you’ve chosen, you may want to follow up on this starting story or proceed around the table. If conversation slows down or needs some motivating, the challenge cards can be used. By the end of the 30 minute discussion your group should be able to cluster the stories, issues, and information in some way that makes sense to everyone. This means physically moving the cards for related ideas and positions into piles.

Phase 4: Policy Position

Everyone will be given a Policy Position ballot in which they can indicate their level of support for each of the four possible positions. The ballots will be collected and tabulated by one member of the group. Look for common ground in your policy positions or develop a response that better represents any consensus reached by discussion. Designate a spokesperson to report your team’s policy position to the class. Feel free to upload your group’s response to the Play Decide Web site if you’re so inclined.

Why are we doing this??

This game is intended to raise several ideas. First, successful new technologies have consequences. You should always anticipate success and the consequences of success in your work. Second, the game forces you to generate a single policy decision, one that may be difficult to reach as well as unsatisfying to some members of your group. Dealing with “fractured” teams is something none of us can avoid and if today’s challenge gives you even one new tool for dealing with discordance, then that’s a big win. Following are some comments about reaching a single policy decision on PGD.

Comments from 2009 students (courtesy of the students, used with permission):

  • “topic draws on lots of biases. Like stem cells, abortion, genetically engineered humans.”
  • “policy is hard to make fair for everyone”
  • “discussion furthered if there’s a person who offers dissent”

Homework

PDP4 Teamwork and learning styles

Due at Week 3 Studio

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Studio 3: Sorting Hat into Project Camps

Lecture 5: Knowns vs. Unknowns

Studio 3: Sorting Hat into Project Camps

Part 1: The Sorting Hat

Based on the ideas from your letters, comic strips and storyboards the class will be organized into temporary camps. These camps are intended to cluster related projects and will include all the interesting corners and regions of the project areas you’ve defined so far. Each camp will also be assigned one or more senior biological engineering student(s) from 20.902 as the camp counselor(s). Once sorted, you, your camp-mates and your counselor(s) should review and catalog the ideas that got you there. In cataloging your ideas, you should include

  • a name for each project
  • a one sentence description of the problem or opportunity it will address
  • and any idea you’re working on as a solution.

Prepare this catalog as a powerpoint presentation that you will show to the class. The last slide in your presentation should be a recap slide to review all the ideas presented. The last hour of the studio time will be dedicated to the presentation of these camp catalogs.

Part 2: Mapping the World of Projects

Pull up a chair and listen as your classmates present their catalogs of ideas. As you listen , you should make note of those projects from each camp that are most interesting to you and why. For tomorrow you will be asked list your top choice and your second choice for camps and your top three project ideas.

The following presentation files are courtesy of the student authors and used with permission.

  • Infectious diseases: “Catch me if U can” (PDF - 4.1MB)
  • Growing organs, meat, crops: “Growing, growing, grown” (PDF)
  • Biofuels: “Powering up” (PDF)
  • Neurology: “Bettering the human condition” (PDF - 4.8MB)
  • Chronic disease: “Come out swinging” (PDF)
  • Waste problems: “Trash talkin’” (PDF)

Homework

PDP5: Camp Catalog Favorites

Due at next class.

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Lecture 5: Knowns vs. Unknowns

Some framing information about counting and clocks in biology (PDF)

Challenge: The Clock of the Long Now

Humans have had a stable climate for about 10,000 years, let’s hope for another 10,000 at least. Assuming no catastrophic events, what would you like to build now that could still be working 10,000 years from now? How could you build such a long-lasting artifact? Wisely anticipating future needs is part of it. For example carpenters in the 14th century built marvelous wooden cathedrals. At the same time, the builders knew that the beams of the structures would eventually need replacing. So, they planted trees, preparing hundreds of years ahead by providing for the future raw materials needs. What else might need to be pre-positioned to perpetuate an artifact through time?

Ruins of the Roman Forum. (Photo by Drew Endy.)

Instructions: Find your “camp-mates” from yesterday and work together to design a clock inspired by Danny Hill’s specifications for the Clock of the Long Now. Danny called for “a clock that ticks once a year, the century hand advances once every one hundred years, and the cuckoo comes out on the millennium. I want the cuckoo to come out every millennium for the next 10,000 years.” Several design considerations will be important to discuss as you think about how to build a clock that will behave as expected until the year 12,000. Your clock must only keep track of time and years. No cuckoo is needed unless you want one. You will have 45 minutes to address these aspects of your clock’s design and documentation:

  1. longevity: how will you keep the clock working, presuming you’ll have all and only the technology and materials that are available today?
  2. maintenance: how will your children’s children’s children keep this clock working? You can assume they’ll be as smart but no smarter than you.
  3. user’s guide: how will future generations understand this clock without stopping or disassembling it?
  4. improvements: how will you improve your clock over time? It should be possible to improve the clock over time?
  5. prototyping: how will you build and test your clock?

Begin by reviewing the rules for brainstorming (see Part 3 on the Team Building page <**link to section>) then either build consensus around one idea or take a vote for the top 3 and then the top choice. Once the general idea for your clock is set, get to work on each of the design elements listed above. After 45 minutes, each table will report back to the group. You may want to organize your ideas or sketch your plan on the whiteboards.

Why are we doing this??

Designing in the absence of complete knowledge is the norm, not the exception. Once our “clocks for the long now” have been described, we’ll work as a class to add more ideas, questions and thoughts about good designs despite incomplete understanding. We can also collect the problem solving techniques that worked well and those that didn’t.

Comments from 2009 students (courtesy of the students and used with permission):

  • “We started off with a lot of ideas but eventually went for the simplest of all…”
  • “We decided that redundancy was the only thing that might work”

Homework

PDP6: Elements of Good Design

Due at next week’s studio.

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Lecture 6: Backyard Biology

Studio 4: Nip and Tuck

Lecture 7: FooCamper’s Guide to BioEngineering

Lecture 6: Backyard Biology

“The new techniques, which permit combination of genetic information from very different organisms, place us in an area of biology with many unknowns.”

Starting today and continuing into the next two weeks, we’ll consider intentional manipulation of DNA. During this time we’ll consider some of the scientific advances that have enabled genetic engineering. For instance, almost any string of genetic material can now be reliably re-ordered. Additionally, the cross-species barriers to DNA transfer have been reduced to a point that its now commonplace to get a gene of interest expressed in an organism even when that gene came from a wholly different critter. These feats would have seemed like science fiction just 50 years ago when Watson and Crick published the double helical structure for DNA. And just as a replication mechanism did not escape Watson and Crick’s attention when they described DNA’s structure, the potential for positive and negative outcomes from recombinant DNA techniques did not escape anyone’s notice when these techniques were developing. Everyone took notice: the scientists involved, the government oversight groups, the media and the public. As a class, we will consider some of the ethical, legal and policy issues that arose with the advent of recombinant DNA technology. But today we’ll step back and consider the DNA material itself.

  • Is DNA (the physical material) inherently dangerous?
  • What makes it (or could make it) dangerous?
  • How can you tell if it’s dangerous?
  • Are there special places that DNA (the physical material) should be kept?
  • Are there rules that can be enforced about its manipulation?

Why are we doing this??

If you’ve spent time in a research lab, there’s a good chance you’ve worked with DNA there. But is that the only place DNA can be manipulated? What if the techniques and facilities for manipulating DNA were available to everyone? What if they already are? If you’ve never spent time working with DNA, then you’re in for a treat. Today you’ll isolate and purify some DNA using materials found in most any kitchen or garage. And from this challenge, you’ll be better able to judge the capabilities and possibilities of “amateur bioengineering.”

Challenge: Backyard Biology

Part 1: Cookin’ up some DNA in your Kitchen

This protocol is from Karen Kalumuck at San Franscisco’s Exploratorium. Another variation can be found on the University of Utah’s Learn.Genetics site.

Materials

  • Frozen Strawberries
  • Seal-able plastic “baggies” (sandwich and gallon)
  • No 2 Coffee Filters
  • 6% solution of NaCl (dissolve 1/2 tablespoon salt in 1/2 cup water)
  • 25% strength liquid dish soap (1 part liquid soap into 3 parts water)
  • Eye droppers
  • 70% Isopropanol
  • Toothpicks or coffee stirrer

Steps

  1. Obtain 2 small to medium sized strawberries
  2. Place them in a sandwich-sized seal-able plastic baggie.
  3. Add about 1/2 a cup of the 6% NaCl solution, and seal the bag.
  4. Squash the strawberry in the salt solution thoroughly, while it’s in the baggie. Try to break up large pieces of berry into mush.
  5. Add about 2 tablespoons of the detergent solution. Seal the baggie and gently mix the berry mush with the detergent. Avoid producing bubbles/foam.
  6. Optional clean up step: Put the entire extraction (strawberry goo, salt, detergent) through a filter – coffee filter over a cup is just fine. This gets rid of a lot of the stringy strawberry goo, and the extraction is cleaner. Place the cleaned up material that passes through the filter into a new baggie.
  7. Hold the baggie by one of the upper corners so that the mush accumulates in a corner of the baggie. Use a pipette or dropper to gently trickle down about 10 - 20 ml of alcohol down a side crease of the baggie. The alcohol should layer onto the surface of the mush. Hold the bag still (or VERY gently rock back and forth) for 1 minute.
  8. Observe what’s happening at the interface. You should use a coffee stirrer to “spool” up the material at the interface, to save for next time.

Part 2: Lego™phoresis

Cast Your Gel

This design is a variation of one published in Make Magazine Volume 7 “Backyard Biology.”

Materials

  • small plastic container
  • scissors
  • masking tape
  • Lego blocks
  • agar-agar
  • running buffer
    • 500 ml bottled water
    • pinch of table salt
    • 1/4 tsp baking soda
    • Aquarium pH kit to check pH ~7.5
    • adjust with more water or baking soda as needed
  • microwave

Note: you’ll cast your gel this time and run the DNA through it next time.

Design

1. Cut ends off small container and tape closed. (Courtesy of Make Magazine. Used with permission.)

2. Arrange Legos for casting wells. (Courtesy of Make Magazine. Used with permission.)

3. Melt 1/2 tablespoon agar-agar with 1/2 cup running buffer in a paper cup and pour gel ~1cm thick. Lego casting wells should be embedded in agar-agar while liquid but not touch bottom of container. You might consider resting the casting tray in a larger container in case the tape leaks. (Courtesy of Make Magazine. Used with permission.)

4. Once gel has solidified, remove Legos, tape and add DNA with glycerin/red food coloring. (Courtesy of Make Magazine. Used with permission.)

Homework

PDP7: DIYbio reflections

Due at this week’s Studio session.

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Studio 4: Nip and Tuck

In today’s studio, project teams will be assigned. These teams are loosely grouped around common interests, be they project areas or project approaches. Once you have assembled into your groups, be sure to introduce yourselves, exchange contact information and figure out which interests landed you on the same team. Then you can use the rest of the studio time to work on your team’s “facebook” page and your “team contract.” The required content for each is:

Team Facebook Page

  • a name for your team
  • the names of your team members
  • the names of your team mentors (20.902 students who will be the go-to folks for questions and guidance on your project)
  • what challenge your team will address
  • what ideas you have agreed to work on (at least 3, no more than 5)

As you develop your ideas, you might also want to keep in mind the requirements for your “3 ideas presentations” that will take place in two weeks. Think about what you will have to present, and how you would like to present it. Maybe the work could/should be divided up or maybe you need to hash out ideas on the spot together. You will use the time today and all of next week studio time to make real progress on these high level questions about your project.

Team Contract

These team building tools have been developed by MIT’s Gordon Engineering Leadership Program, appreciating that teamwork and leadership underlie nearly all successful engineering projects.

Start by reading (independently) this short article that describes the different kinds of teams that exist and some common stages that teams go through.

Philips, Patricia. “So, You’re Going to be a Member of a Team.” Chemical Engineering Progress 93, no. 1 (January 1997): 141-144

Once everyone has finished reading, discuss the article as a group, paying particular attention to team and individual roles and responsibilities as they may relate to your particular project and team.

Then as a team, work through the following questions in order to form your team contract. You can work through the questions fast or slow, all of them or just a few. After considering these questions, write a team contract that you can all agree to work with for the rest of this term.

Questions To Consider To Create a Team Contract

These questions have been adapted from Lori Breslow’s work at MIT for the subject, 15.279 Management Communication for Undergraduates (source: “Teamwork Questionnaire” the Study Materials section of this class in MIT OpenCourseWare).

Part 1: Goals

  • What are the goals of the team?
  • What are your personal goals for this assignment?
  • What kind of obstacles might you encounter in reaching your goals?
  • What happens if all of you decide you want to get an “A,” but because of time constraints, one person decides that a “B” will be acceptable?
  • Is it acceptable for two or three team members to do more work in order to get an “A”?

Part 2: Meeting Norms

  • Do you have a preference for when meetings will be held? Did you have a preference for where they should be held?
  • How often do you think the team will need to meet outside of class? How long do you anticipate meetings will be?
  • Will it be ok for team members to eat during meetings?

Part 3: Work Norms

  • How much time per week do you anticipate it will take to make the project successful?
  • How will work be distributed?
  • How will deadlines be set?
  • How will you decide who should do which tasks?
  • What will happen if someone does not follow through on a commitment (e.g., missing a deadline, not showing up to meetings)?
  • How will the work be reviewed?
  • What happens if people have different opinions on the quality of the work?
  • What will you do if one or more team members are not doing their share of the work?
  • How will you deal with different work habits of individual team members (e.g., some people like to get assignments done as early as possible; others like to work under the pressure of a deadline)?

Part 4: Decision Making

  • Do you need 100% approval of each team member before making a decision?
  • What will you do if one of you fixates on a particular idea?

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Lecture 7: FooCamper’s Guide to BioEngineering

Challenge: Lego™phoresis (con’t)

Materials

  • steel wire
  • large plastic container
  • loading buffer
    • 1/4 tsp glycerine/glycerol
    • a few drops red food coloring
    • DNA you isolated from strawberries
  • remaining running buffer from part 1
  • 9V batteries
  • Aquarium antimicrobial (ideally 2.3% methylene blue diluted 1:100 in bottled water) to stain DNA in gel after run

9V batteries in series to power DNA through the gel. (Courtesy of Make Magazine. Used with permission.)

Homework

PDP8: Recombinent DNA and Asilomar

Due at next class session.

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Lecture 8: Scientist as Activist

Studio 5: Design Day 1

Lecture 9: Interface Between Scientific/Engineering Community and the Broader Public

Lecture 8: Scientist as Activist

Challenge: “Refrain From Using the Alphabet”

Turn back the clock to 1976. It’s three years after the scientific community raised concern about the safety of recombinant DNA experiments. It’s one month after the NIH issued guidelines to regulate recombinant DNA work. The Cambridge City Council is meeting with scientists from nearby institutions to discuss the consequence of these guidelines for the community surrounding the laboratories and to consider additional resolutions and actions that the city might take to ensure the safety of its citizens.

In this class, we’ll watch a video produced by Charlie Weiner, Professor Emeritus in MIT’s Program in Science, Technology, and Society, for the MIT Oral History Program Recombinant DNA History Project. [Unfortunately this video is not publicly available].

  • “Hypothetical Risks, The Cambridge City Council hearings on DNA experimentation in Cambridge.” Recorded at City Hall, Cambridge MA, 1976.

Although the audio and the video quality have degraded, it provides an invaluable window into the dynamics of these debates, showing the human side of what can sometimes, in retrospect, look like merely academic debates or simplified as over-emotional public reaction.

The cast, listed in the order of speaking:

  • Mr. Alfred Vellucci, Mayor of Cambridge (1970-71, 1976-77, 1982-83, 1988-89)
  • Dr. Mark Ptashne, Prof. of Biochemistry and Molecular Biology, Harvard University
  • Dr. Daniel Branton, Chairman Safety Committee, Harvard University
  • Dr. Maxine Singer, Biochemist, National Institutes of Heath (NIH)
  • Ms. Saundra Graham, Cambridge City Council
  • Mr. David Clem, Cambridge City Council
  • Dr. Ruth Hubbard, Prof. of Biology, Harvard University
  • Dr. Jonathan King, Prof. of Biology, MIT

Why are we doing this??

The exchanges we’ll hear in this video highlight many relevant aspects of emerging technologies, not only recombinant DNA. After we watch the videotape we will consider, as a class, some of the dialog and the lessons we might apply from this history to biotechnologies coming on line today (and tomorrow). These considerations include:

  1. Risk assessment (including: is past performance an indicator of future success?)
  2. Self-regulation vs government legislation (including: trust/us vs them/honesty/openness as well as accountability)
  3. Scientific process
  4. Rhetoric
  5. Preparedness
  6. Scenario building
  7. Detection
  8. Surveillance

Beyond keeping these topics in mind as you watch the video, you should also be familiar with the kinds of biosafety (then called biohazard) levels that will be discussed and what each level (then called P1, P2, P3, and P4 now called BSL1, 2, 3, 4) means. Please refer to the BioBuilder biosafety levels animation.

Just Before Watching the City Council Videotape

We’ll review some details about recombinant DNA that are relevant to the videotape:

  • What is a recombinant DNA experiment?
  • What technical advances and techniques are involved in making/propagating recombinant DNA?
  • What has been done with recombinant DNA in the last 30+ years? What hasn’t been done?
  • More specifically: what hasn’t been done that was of concern at the time these techniques came on line?

After Watching the City Council Videotape

As a class we will consider various exchanges among the hearing participants, and what they tell us about the considerations numerated above.

Homework for Tomorrow’s Studio Session

Please review the requirements for the project 3 ideas presentation. Your presentation will be one week from tomorrow. You’ll have all of tomorrow’s studio session to work on your 3 ideas and that time will be best spent if you come to the studio with an agenda.

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Studio 5: Design Day 1

Today will be a project work day with your advanced student mentors. You should organize your progress and task list and thinking in your project notebook log, be it electronic or on paper, depending on your preferred style. Your 3 ideas presentation will be one week from today.

We will start the day with a short presentation from Howard Silver, Co-Head & Biological Engineering Librarian Engineering & Science Libraries. He will come to the studio time with some helpful hints for finding and organizing references, but he’s also happy to answer your particular questions.

MIT Libraries. Research Guide for 20.020.

Homework for Tomorrow’s Guest Lecture by Prof. Jonathan King, MIT

  1. Think a little more about the Cambridge city council hearing video we watched earlier this week and any questions or concerns you still have circling in your mind. Write down one question you’d like to ask Prof. King.
  2. Please read this ScienceNow overview article about the proposed BSL-4 facility that is being considered for South Boston.

Kaiser, Jocelyn. “NIH Criticized for Flawed Review of Biosafety Lab.” ScienceNOW Daily News, November 29, 2007. [Article discusses this report by the National Research Council. “Technical Input on the National Institutes of Health’s Draft Supplementary Risk Assessments and Site Suitability Analyses for the National Emerging Infectious Diseases Laboratory, Boston University: A Letter Report.” National Academies Press, 2007.]

In light of what you heard today about the reactions that neighbors have to nearby research programs, think about the comments that concerned citizens and scientists might raise to those planning the facility and constructive conversations that supporters of the facility could initiate.

Professor King’s talk tomorrow will use these ideas as points of departure. Please come with these assignments prepared so you can take full advantage of this opportunity to talk with him.

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Lecture 9: Interface Between Scientific/Engineering Community and the Broader Public

Guest Lecture by Professor Jonathan King, MIT

Jonathan King is a Professor of Molecular Biology at MIT. His laboratory studies protein folding, including thermal stress responses in marine cyanobacteria and their phages. In addition, Professor King has long been concerned with the social, economic and public health consequences of biomedical research. He was a founder of the Council for Responsible Genetics and served as Co-Chair of its Committee on the Military Use of Biological Research. We are very fortunate to have him address our class. His talk will reflect on the emergence of past/present/future technologies as well as the interface of the scientific and engineering community with the broader public to address public concerns.

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Lecture 10: Project Work Day

Studio 6: 3 Ideas Presentation

Lecture 11: Project Selection Day

Lecture 10: Project Work Day

Today will be a project work day with your advanced student mentors. Please be sure to reviewing the project organizer and the requirements for the 3 ideas presentation. You could also consider the team building resources and review your team contract if that seems right. Finally, you should update your project development log to keep the record of your work up to date.

Homework

When it is ready, please submit your 3 ideas presentation.

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Studio 6: 3 Ideas Presentation

Today we will hear from each topic area. After each presentation you will be asked to offer feedback to the presenters on the relative merits according to these 4 criteria.

  • Which of the 3 ideas addresses the most important challenge or opportunity?
  • Which of the 3 ideas would have the greatest impact if fully successful?
  • Which of the 3 ideas is most competitive with alternative technologies?
  • Which of the 3 ideas has greatest certainty and fewest unknowables?

See the projects page for these student presentations.

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Lecture 11: Project Selection Day

Today is a delicate and important day for your team since now you must decide (or set a concrete plan for deciding) which of the 3 ideas you presented yesterday is the one you’ll take forward. In making this decision you have many considerations to weigh:

  1. what you’ve learned from the research and preparation that went into the 3 ideas presentation
  2. what your teammates have worked on and discussed
  3. what your team advisers have contributed
  4. the questions you were asked by the audience after your presentation
  5. what you heard in the other presentations (any great ideas or sobering thoughts from the work other groups have done?)
  6. the feedback on the 4 criteria for project selection (importance, impact, competing technologies, knowns/unknowns)
  7. the upcoming goals and needs that will enable your team to specify the design you choose, namely the contents of the tech spec review

Every group should begin by sharing their impressions of yesterday’s 3 ideas presentations, and offering an opinion on where your team stands.

Path 1

If, after this discussion, your team is still undecided as to which project would be most appropriate to take forward, then try reading this 4 page excerpt from Peter Scholtes’s Team Handbook, focusing on the steps for consensus building.

Scholtes, Peter, et al. The Team Handbook, 3rd ed. Madison, WI: Oriel Incorporated, 2003, pp. 3-26 through 3-29. ISBN: 9781884731266. [Preview in Google Books.]

  • Have someone read when to use consensus building approaches to make sure this is the appropriate approach for your group
  • Follow the tips sheet to reach consensus (or discuss then vote if that is the method your team chooses)

Once you have chosen one of the three project ideas to take forward, continue to “Path 2” if you have time or decide what you will work on between now and when we meet again next week.

Path 2

If, after the discussion about yesterday’s 3 ideas presentations, your team is in agreement as to which one of the three ideas you’ll take forward, then you’re ready to dig into the nitty-gritty of design details and specification.

  • Begin by reviewing, as a team the deliverables for the next stage of your project, namely the tech spec review
  • Next, look carefully at one example of a technical specification, that of the “Polkadorks” team from the 2004 IAP class. At a minimum, you should make sure everyone on your team understands the kinds of descriptions (timing diagram vs parts list etc) that they are showing on their project page and if there’s time, you might consider what needs to be done with your project idea to collect these details. There will be time next week to continue that work together.

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Lecture 12: System Overviews

Studio 7: Design Day 2; Abstraction in Action Part 1

Lecture 13: Abstraction in Action Part 2

Lecture 12: System Overviews

Over the next few weeks we will spend nearly all of our lecture and studio time specifying these aspects of your project:

  • a system overview
  • a device list
  • a timing diagram
  • a parts list

Be ready to revise what seemed like completed aspects of your project as you learn more about what’s available and how things work.

Design/revise/design/revise/design/revise….that’s what the next few weeks will be all about.

Project Selection Status

Today we’ll begin with a brief report of each team’s project selection status.

Challenge: System Overview

Part 1: Flip Books

Here’s a warm up challenge to show what is meant by a system overview

  • Working independently, you should take 10 minutes to sketch a process into a flip book (materials to be provided). The process you choose to illustrate is up to you. It can be a plant growing, a house of cards being built, or a happy message appearing letter by letter on a computer screen. What you choose is limited only by the number of pages in your book, your ability to draw, and the limited amount of time you’re given to complete this challenge. 10 minutes only!
  • Before we move on to the next part of today’s class we’ll hear from some of the flip-book drawers to learn what worked well and what didn’t about this way to overview and illustrate a system.

Part 2: Bacterial Buoy

Next you and your project team will generate a system overview for the Melbourne 2007 iGEM “coliform” project.

  • The Melbourne team wanted to build a 3D floating mass of bacteria that adhered to one another when the cells detected both blue and red light. In other words: at the intersection of an incoming red light beam and blue light beam, a solution of bacteria would clump and remain suspended in its growth media.

Coliformers from Melbourne’s iGEM 2007 team. (Courtesy of Phillip Dodson. Used with permission.)

  • As a class we’ll watch the first 5 minutes of the Melbourne team’s iGEM presentation. (MPEG - 31.2MB)
  • Next your project team should work out a system overview for the coliform project. You can get an unused flip book (or use the back of one from the warmup exercise), or come up with some other mechanism of illustrating how the Melbourne team’s system would work. You should not spend more than 10 minutes on this activity. When you are done, delegate someone to explain what you’ve done as a team and what questions arose as you worked. Then you and your team can get right to work on the last thing planned for today’s lecture.

Why are we doing this??

As a class we’ll consider the value of having a clear system overview.

Comments from 2009 students (courtesy of the students, used with permission):

  • “easier to do if there are simple steps.”
  • “tried to illustrate cracking an egg, which has lots of steps and I’m not done”
  • “drew people gathering and building a building. Hard part was redrawing the same building each time.”
  • “is the buoyancy inherent?” “would cells concentrate unless light present?”" would the system work with red light then blue light or do both need to be present at the same time?"

Part 3: Your Idea Here

Finally, take the rest of today’s lecture time to illustrate or specify the system overview of your team’s project. You do not need to make a flip book unless you find this a useful way to brainstorm and define the outstanding issues. Ideally some version of the system overview you generate today will be shown in your Tech Spec Review.

Before Tomorrow’s Studio Time

If there are outstanding issues related to the system overview for your project be sure everyone on your team knows how you’ll solve the issue(s) and make a plan to come to studio tomorrow with materials for finishing the system overview and getting good work done on the device list and, perhaps the timing diagram.

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Studio 7: Design Day 2; Abstraction in Action Part 1

Are there tools or methods for breaking down a complicated problem into simpler parts?

  • Watch the BioBuilder abstraction animation.
  • Walk through one sample abstraction hierarchy that may guide synthetic biology

This abstraction hierarchy is modified from one of Drew Endy’s slides. It gives us a framework for how to intentionally engineer various aspects of biological systems.

LAYER DEFINITION
System Multiple devices hooked together to realize a goal
Device Multiple parts with a higher level function
Part A finite sequence of nucleotides with a specific function
DNA Sequence of nucleotides

Abstraction hierarchy for a biological system.

Part 1: Abstraction in Action: Systems to Devices

Here are three quick examples to put the abstraction hierarchy in action.

First up: Arsenic detector

Abstraction hierarchy example: arsenic detector.

Recall the University of Edinburgh 2006 iGEM project that was described as an Arsenic Detector in the “abstraction” BioBuilder video. The system was designed to sense arsenic and result in a color. Two devices were used to build this system. The first device sensed arsenic and gave rise to a signal when arsenic was detected. And if the second device sensed the signal from the first device, then it gave rise to a color. The device-level system diagram is pretty straightforward, but makes clear that you could swap out the first device for a different sensor, as long as the output could still be interpreted by the second device. Similarly you could change the output from color to anything, as long as the input to that color-generating device was paired to the output of the arsenic sensor.

Next: Bacterial buoy

Consider again the coliform project from the Melbourne 2007 iGEM team. The team listed six devices they needed to realize their idea:

  1. a red light sensor
  2. a blue light sensor
  3. an and gate to trigger a cellular behavior when both lights are present
  4. a GFP reporter to monitor easily/quantifiably the and gate’s function
  5. expression of adhesive proteins under the control of the and gate
  6. a gas vesicle expression cassette to produce naturally buoyant bacteria

Working with your project team at the white boards, draw a device-level system diagram for the six devices listed here. These devices should be “wired” together in a meaningful way so the inputs and outputs can be understood as entry and exit wires. As inspiration look at this automotive wiring diagram from lotuselan.net and note how the ordered connection of devices can help you understand how this system works

Diagram mapping the arsenic detector to the system and device layers. (Figure by MIT OpenCourseWare.)

After just 5 minutes we’ll see the device level system diagrams that you’ve drawn for this system and discuss any outstanding questions or concerns.

And finally: Polkadorks

Let’s try a more dynamic system. The Polkadorks 2004 IAP iGEM team wanted their engineered cells to “form, diffuse, and form again in random areas on the plate. Our system should thus form time-varying patterns based on local random time-varying symmetry breaking.” Check out the Polkadorks animation.

Animation of the Polkadorks system. (Courtesy of Ziyan Chu, Roshan Kumar, Stephen Lee, and Joe Levine. Used with permission.)

  • As a class we’ll
    • describe the system in plain language, then
    • list the devices needed to implement the system
  • Then as a team you’ll have 10 minutes to draw a device-level system diagram.
  • Finally, as a class, we’ll look at the timing diagram that the 2004 IAP team wrote.

Timing diagram from Polkadorks. (Courtesy of Ziyan Chu, Roshan Kumar, Stephen Lee, and Joe Levine. Used with permission.)

You’ll see that the devices (or the named connections between these devices) are listed on a y-axis and time is shown on an x-axis. The timing diagram indicates the timing for operation of each device or wire, including the persistence of each device’s signal through time—shown as PS (protein synthesis) and PD (protein degradation). You and your team should take 10 minutes to make a timing diagram for the Polkadork’s devices that you have wired together. You can keep a running list of any uncertainties. After 10 minutes of work, we’ll have each team report back to the group to see how we did and what questions still remain.

Part 2: Get Busy!

Start applying these ideas to your team’s project. You can work on a device list, a device-level system diagram and a timing diagram if you’re ready. Be sure to keep your project notebook up to date and help keep each other great.

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Lecture 13: Abstraction in Action Part 2

We’ve been working hard this week to move between the System and Device levels of an abstraction hierarchy and today we’ll drop down one more level to think about the parts that make up a device. The device we’ll consider is switch made from RNA, but first we’ll look at a “classic” device, namely an inverter, and the parts that make it up.

Challenge: Abstraction in Action: Devices to Parts

Part 1: Four-part Inverter

Recall the Eau d’coli project from the 2006 MIT iGEM team. Their goal was to replace the nasty smell of bacteria with wintergreen smell during log phase growth and banana smell during stationary phase growth. In fact some of you added the banana smell generator (BSG) to bacterial cells yourself thanks to the Foo Camper’s Guide to BioEngineering that we tried way back in Week 4 of this term. We also talked about the engineering ideas behind the Eau d’coli project way WAY back in Week 1. Today we’ll focus in on one device within the system, namely the inverter that was used upstream of the wintergreen generating device (WGD), turning it off during stationary phase.

Abstraction hierarchy example: Eau d’coli.

The abstraction hierarchy shown above zooms in on the inverter part that reverses the signal from the stationary phase promoter. This turns the wintergreen generating device off in stationary phase and on in log phase. The inverter part that’s shown is a permutation of a natural gene that encodes the tetracycline repressor protein.

Eau d’coli inverter part.

Within this gene, we can define 4 “parts:” a promoter, a ribosome binding site (RBS), an open reading frame (ORF) that encodes the tet repressor protein, and a transcriptional terminator so the RNA polymerase transcribing the gene doesn’t continue down to the next sequences downstream. The promoter is repressed by the tetR protein itself, allowing for a simple rearrangement that makes a useful inverter device. You can imagine a family of 4-part inverters that might be made for every repressor protein we know (lac repressor, lambda repressor, etc). The number of these proteins is finite, however, and there will almost certainly be a time when a transcription-based device will not be optimal, so for the next part of today’s challenge you are asked to make an RNA-based switch. This challenge will draw upon your understanding of basic biology, your ability to find resources, and your ability to work as a team. Good luck!

Part 2: Let’s Make a Switch

Working in your project teams, develop a design for a genetically encoded switch that works through the expression of a regulatory RNA. Your team’s design should include (a) a high level system diagram, (b) a full list of devices and parts, (c) a source for all the necessary DNA parts (be it research lab or synthesis company), (d) a plan for testing the most important components of your switch, and (e) the final cost associated with building and testing your device. You have 45 minutes. Your team’s budget for this project is $1000. The winning team will have the most versatile RNA-switch that costs the least to construct and test.

  • Note: This activity features an “All questions answered” work environment. Ask lots of questions.
  • Hint: Your DNA synthesis budget may not be large enough to pay for synthesis of all the parts needed to make the switch.
  • Hint: Your team may not have enough time to design everything needed to make the RNA-based switch.
  • Hint: Spend 2 minutes right now thinking about all the things that need to come together over the next 45’ for your team to be successful.
  • Question: How will you check that everybody on your team understands what is going on?

Why are we doing this??

After we hear from all the teams about their RNA-switch details, we’ll consider what was challenging about this endeavor, what it revealed about building genetic programs, and how to optimize teamwork and productivity:

Comments from 2009 students (courtesy of the students, used with permission):

  • “it was hard…there wasn’t enough time…we didn’t know where to start…teamwork had to be figured out…being creative is hard…white boards helped…knowing a lot helps…to know things: ask others, research, copy existing ideas…”

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Lecture 14: Parts and Registry

Studio 8: Design Day #3

Lecture 15: Hypothesis-Driven Engineering

Lecture 14: Parts and Registry

Welcome Back Project Status Report

We’ll start this session with a brief status report from each project team.

Challenge: Parts

Part 1: Poetic Parts

This challenge was inspired by the This American Life episode “Mistakes Were Made.” Chicago Public Radio, April 10, 2009.

Consider the content of “This is Just to Say,” a poem by William Carlos Williams.

The poem is often taught in poetry classes and often spoofed. Consider, for instance, the spoofs by Kenneth Koch in “Variations On A Theme By William Carlos Williams.”

And one more spoof from the blog Somewhere in the Suburbs.

If you wanted to write your own spoof of the William Carlos Williams poem, you might begin by comparing the structure of these four poems. As a starting point they can be broken into 5 elements, namely

  • 2 part situation
  • “forgive me,” and
  • 2 part explanation.

or mapped into a table like so:

SITUATION (PART 1) SITUATION (PART 2) FORGIVE ME EXPLANATION (PART 1) EXPLANATION (PART 2)
         
Text of the afore-mentioned poems, as mapped into these elements,  
removed due to copyright restrictions
         

Mix and Match Poetry

Now we can try to swap these poetic elements to see what interesting and clever spoofs we write. How about:

SITUATION (PART 1) SITUATION (PART 2) FORGIVE ME EXPLANATION (PART 1) EXPLANATION (PART 2)
I have eaten the plums that were in the icebox and I broke your leg Forgive me but it was morning, and I had nothing to do and I wanted you here in the wards where I am the doctor

That seems to work but is it better? Let’s try again:

SITUATION (PART 1) SITUATION (PART 2) FORGIVE ME EXPLANATION (PART 1) EXPLANATION (PART 2)
I chopped down the house and which you were probably planning to air dry Forgive me they were delicious it would not be so short and so small

Well shoot, that’s horrible. For one thing: It doesn’t say anything understandable—this can be broadly described as a problem of functional compostion. For another thing: the connection between the different elements is, well, “awkward” at best—this can be broadly described as a problem of physical composition. If physical and functional composition of poems were working perfectly then every part would grammatically connect to the ones that flank it, and the meaning of the connected pieces would be interpretable at worst and clear at best.

Part 2: Genetic Parts

The physical and functional assembly of the poetic parts can be mapped to biological engineering once we define what a genetic “part” is. Let’s start by extending what we did with the William Carlos Williams poem, namely let’s consider a few natural genetic compositions, see what common elements compose them, and then try to bin these so we might compose new genetic elements by mixing and matching parts.

The bacterial lac operon is one we’re already familiar with from our conversation earlier in the term.

Diagram of bacterial lac operon.

There are several genes encoded by this composition. LacI is made and we can see it’s flanked by a promoter and a terminator. Lac Z, Y, and A are also made and they are flanked by a promoter + an operator on one end and a terminator on the other. So some genetic parts we might consider naming are:

  • promoter
  • operator
  • protein-coding gene
  • transcriptional terminator

Recombinant DNA technology gives us great power to move pieces of DNA around but it doesn’t answer all the questions we might have about the resulting composition. For instance, are promoters/operators/genes and terminators all the parts we need to write a genetic program. Would the promoter that’s in front of LacI make sense in front of LacZ, Y, and A? Is there something important about the junction of the parts?

For an introduction to systematic examination and nomenclature of genetic parts, watch Device Dude and Systems Sally’s introduction in the BioBuilder animation “Genetic Programs: Why Parts Don’t Simply Snap Together.”

Part 3: The Registry of Standard Biological Parts

The animation ends with a screen shot from the BioBricks™ Foundation, a not-for-profit organization that “encourages the development and responsible use of technologies based on BioBrick standard DNA parts that encode basic biological functions.” BioBricks represent one kind of standard biological parts, standardized to enable reliable physical composition.

Just as we mixed and matched poetic elements, here are some mixed and matched genetic elements made from BioBrick parts.

Some mixed and matched genetic elements made from BioBrick parts. (Courtesy of the BioBricks Foundation.)

Just as we could identify “forgive me”-ish elements in the “this is just to say poems” we can see common elements in these genetic compositions: the green arrow element which is = a promoter, but which comes in different flavors (I13452, R0040 or R0011), the red stop signs = transcriptional terminators (B0010, B0012).

The part numbers as well as the DNA itself are collected at the Registry of Standard Biological Parts.

For your final project in this class, you will enter a part into the registry. We’ll look at some good parts and some good documentation in class so you can model your work on those examples.

Before Tomorrow’s Studio Time

If there are outstanding issues related to the system you’re working on for your project be sure everyone on your team knows how you’ll solve the issue(s) and make a plan to come to studio tomorrow with materials for finishing the system overview and getting good work done on the device list and the timing diagram.

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Studio 8: Design Day #3

Part 1: Eau d’coli test/debug

Eau d’coli device-level system diagram. (Courtesy of the 2006 MIT iGEM Team. Used with permission.)

Aye yay yay! Won’t we ever get away from this Eau d’E coli project? Not yet! Take a close look at the device-level system diagram. You can’t see all the underlying BioBrick parts (there are ~24 parts in total). If you were the designer of this system, do you think that the system would work if you just synthesized all the DNA as a single contiguous strand, transformed this new DNA into a cell, and let your genetic program rip!? Or, stated differently, what would be your next step if you tried to get everything working at once, and nothing happened, or, even worse, your engineered DNA killed the cell?

Having a plan for testing and debugging your projects is critical. To help you think about how to develop the best testing and debug plan for your 20.020 projects, spend the next 10 minutes working with your team to outline a testing and debug plan for the Eau d’coli system. Before you get started, designate one person on your team to act as spokesperson. Once the 10 minutes are up, we’ll ask each spokesperson for an accurate description of your testing and debug plan. If you’re having trouble knowing where to start, you might consider:

  1. Use the device level system diagram to sketch out a timing diagram (use a white board).
  2. Think about what this iGEM team could have done if they just added all this DNA to the cell, and then nothing happened (no smell, or worse, all the cells died). How would they go about figuring out what aspects of the project might be working, and what other components need to be revised or fixed?
  3. Finally, look again at the device-level system diagram. Is there anything about the system’s design that makes testing and debugging easier or harder than it might be otherwise? Would you like to change any aspects of the system design to make testing and debug easier?

Part 2: Data-driven Decision-making

Consider once more the Melbourne 2007 iGEM project introduced during Week 1. In a series of questions at the end of their presentation video, the team gets asked about any changes to the gas vesicles device that might allow gas-filled cells to become even more buoyant. Their answer speaks to some scientific work others have done to understand the vesicle-encoding operon, research that has shown at least one gene in the operon is a negative regulator. By deleting that gene, the Melbourne team thinks they might make their cells even more buoyant. If you and your team were the Melbourne team, what would you do with this information?

First let’s review one technical advance that opens a number of options for you, namely DNA synthesis. Then as a class we’ll consider some options–weighing these (or others) in terms of their associated cost (both time and money).

  • Use the entire gas vesicle operon to get the basic Coliform system working then tweak the system later to improve it.
  • Wait to assemble your system until you can perform experiments to know more about each gene in the operon.
  • Divide the team in half, with some launching into the project with the DNA as is, and others studying it and refining it.
  • Spend one week in the library to read all you can about these vesicles and then decide.
  • Place a DNA synthesis order for the full operon (6 kilobases) as well as every single gene knockout and double gene knockout.

Mapping These Ideas to your Project

Now it’s time to look at the list of devices you have identified as part of your project (some of you may have a full list of needed devices and some of you will have only a partial list, in which case you’ll have to consider these ideas now and then revisit them when your device list is complete). What might factor into the cost and time of assembling the devices into your working system? Do you know all you need to know about how they work? Are there easy ways to find out more? Do the devices already exist or will you have to make them yourself? You might want to make a chart that lists your degree of confidence in each device, where confidence is tempered by its cost/time/source/description and perhaps safety/security concerns…something we will return to next week.

Generate a list or table that might be useful as part of your Tech Spec Review next week.

Part 3: Project Work Time

Let’s get busy working on the details of these projects!

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Lecture 15: Hypothesis-Driven Engineering

“Faith is a poor substitute for reason”

Thomas Jefferson

As you hone in on the details of your projects, your team should plan ways to validate the system’s operation and ways to learn from its glitches. We have two quick challenges for you today. The first illustrates that even the “best” answers you can offer that are consistent with all available data remain tentative, that the answer is either strengthened or revised by additional data and that all interpretations are subject to personal biases, human values and the various ways we all think about the world. The second challenge puts you midstream in a flawed design and requires that you consider the modes of failure to debug/troubleshoot the problem.

We will spend only 20 minutes on these challenges and then you and your team can use the rest of today’s lecture time to prepare for next week’s Tech Spec Review

Challenge 1: The Check’s in the Mail

This challenge is adapted from Judy Loundagin’s lesson for the Evolution and Nature of Science Institutes.

  1. One member of your team should serve as scribe (with notebook sheet to be provided). Another should be spokesperson (see item 7, below).
  2. Each team should get one envelope that is filled with fictional checks. Do not look at the checks yet. All envelopes have the same checks.
  3. Remove and examine 4 checks only.
  4. Discuss a plausible scenario which involves those checks.
  5. Once your group has agreed on a reasonable scenario that accounts for the checks, and the scribe has written it down, then you can draw 4 more checks from the envelope. As tempting as they are, the unchosen checks must stay in the envelope, unexamined.
  6. Reconsider your initial scenario to include the information you can glean from all 8 of the checks.
  7. We will take 1 minute to hear from each team. The spokesperson should detail
    • the content of the first 4 checks,
    • the way your team considered their content and
    • the initial conclusion you drew
    • the details of the next 4 checks and
    • the revisions you made to the scenario to accommodate the information.

Finally, the spokesperson should say what kind of check they would expect to see in the envelope if their scenario is correct or what kind of check would blow their ideas out of the water and demand a full re-write of their explanation.

Challenge 2: Soap Stress

Stresses on a cube: compressional stress (left), tensional stress (center), shear stress (right). (Images courtesy of NASA JPL.)

This challenge is adapted from one described at teachengineering.org. We will skip the preliminary descriptions of plate tectonics and just remind you of three stresses that give rise to deformation: compression, tension and shearing forces.

Soap stress in action.

  1. Begin by looking at how the packaged soap is breaking during shipment from the factory to the distributor (a sample of the broken soap will be available for you to look at). Decide as a team which kind of stress could be leading to this kind of damage. Pick only one kind (i.e. not a combination of tension and shear) and rate your confidence in that choice on a scale of 1-10 (1 = we had to pick something so we picked this, 10 = I’d bet my house on it)
  2. Now start counting costs to analyze and fix what you believe to be the failure mode.
    • if you’d like to stress an unbroken soap bar, each bar costs $1
    • if you’d like to use paper to wrap each bar of soap, each sheet of paper costs $0.01
    • if you’d like to use a small piece of cardboard to line each bar of soap, each piece of cardboard costs $0.05
    • if you’d like to use larger sheets of cardboard to line each 12 pack of soap, each large sheet costs $0.50

In 5 minutes, your team will be asked

  • which of the three stresses you believe could be breaking the bars of soap
  • how confident you are with that choice
  • what you’d propose as the best way to fix the problem
  • how much you spent to arrive at that recommendation and what your proposed solution will cost
  • and finally if you are more or less confident in the source of stress that’s breaking the soapbars after this quick round of failure analysis, and debugging.

Be sure to wash your hands before you touch your eyes if you’ve been breaking soap to test it.

Mapping These Challenges to your Project

There is no such thing as either complete knowledge or flawless design. And if you believe, as Henry Petroski does, that “…the central goal of engineering is still to obviate failure, and thus it is critical to identify exactly how a structure may fail,“1 then you and your team will dedicate effort

  • to collecting relevant data that validates or disproves the ideas in your own project; and
  • to anticipating failure modes so debugging your design is trivial rather than backbreaking.

These ideas of validation and debugging should be included in your Tech Spec Review, at least a first go at them.

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1Petroski, Henry. To Engineer Is Human: The Role of Failure in Successful Design. New York, NY: Vintage, 1992, p. 195. ISBN: 9780679734161.

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Lecture 16: Project Work Day

Studio 9: Technical Specification Review Presentations

Lecture 17: Tech Spec Feedback

Lecture 16: Project Work Day

Eek!

Work day in advance of tomorrow’s Tech Spec Review.

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Studio 9: Technical Specification Review Presentations

See the projects page for these presentations.

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Lecture 17: Tech Spec Feedback

Project Re-design

Based on the work you’ve done so far, the questions you heard yesterday after your presentation and the short amount of feedback you’ll get today, it’s time to prioritize what work still needs to get done on your project. Over the next few weeks, we will continue to offer tools for implementing different natural and engineered solutions, and we will try to provide consultants working in these fields to help you see your project through their more experienced eyes. You should leave today’s class with a clear sense of what the work flow for the next few weeks will be.

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Design Features: An Animation Project to Teach Synthetic Biology

Here are some storyboards from our first animation about iGEM. The script was written by Rebecca Adams, Isadora Deese, Drew Endy and Natalie Kuldell. Storyboarding by the talented folks at Animated Storyboards.

Ultimately this and other animations will appear at BioBuilder.  The animations are also collected in this course’s BioBuilder Animations page.

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