Week 1 Readings
Why are you here? Why engineer biology? What’s unique about living matter?
Please read and consider the below. Monday’s materials can be skimmed following Monday’s class. Wednesday’s and Friday’s materials should be studied before class. The questions given are only study questions not homework to be graded. Talk about anything you find interesting with your classmates, friends, or TAs, as you like, using Piazza or email the instructors!
Post-class readings from Monday
What has been the impact of engineering interacting with biology?
Here you will review the role that bioengineering, with a core emphasis on living matter, has already had in the world. Stated differently, we ask: Why has bioengineering mattered?
Goal 1: After considering the following examples you should be able to describe example impacts of bioengineering on humanity and civilization to this day.
Goal 2: Prepare yourself for a constructive class discussion about the future impact and ramifications of engineering living matter for realizing a future to benefit, and not to harm, all people and the planet.
First let’s examine in more detail an interesting topic, some of the ancient origins of bioengineering:
Is bioengineering a new field? What events mark the “start point” of bioengineering? For example, as far as we know fermentation of beer or use of lactic acid bacteria to make cheese or yogurt dates back to 7000 - 6000 BC. Is that the start of bioengineering? Or is the starting point the work of Leonardo da Vinci in 1450 in analyzing muscles and joint functions? Perhaps it is the work of Anton van Leeuwenhock and his amazing microscopes in the 1600s that enabled him to see bacteria everywhere. Or is the origin more recent, beginning with the discovery of penicillin? Is it the discovery of the double helical structure of DNA? And what of the various strategies and types of application that humanity has developed in partnering with living matter and nature in order to solve problems? Perhaps partnership between humanity and biology is as old as humanity, by definition.
Here, we organize these partnerships into three general categories:
First, is the application of the new tools and technologies to engineer for living matter. I.e., using other modes of engineering to do something for biology as a science or biology as a type of stuff. Examples of this category include prosthetic limbs, surgical tools, microscopes, technologies for controlled drug delivery, and machines to read and write DNA.
Second, is the use or adaptation of living matter as a type of material (cells, enzymes, plants, animals) towards various goals. We call this engineering with living matter. This approach has brought us, for example, vaccines such as for polio, leather made with mushrooms in place of vertebrates, and initial progress in growing human some types of human tissues.
The third and final category is the engineering of living matter. This involves the manipulation of biological organisms directly, typically starting from their DNA. This approach has brought us innovations like large scale manufacturing of human therapeutics via microbes (e.g., insulin), genetically modified plants (e.g., virus-resistant papaya), therapeutic immune cells for fighting some types of cancer, (e.g,. CAR-T cells), animal-free meat, and so on.
Let’s examine one example from each category. Please note, there are a few questions after each example (10 total). Please think of these as study questions, not questions on an assignment. I.e., you do not have to turn in anything from the reading and study questions in the pre-class material. We estimate you will spend about 10 minutes on each example, or more but only if you wish to follow-up re: details via the curated links provided.
Example 1 - Microscopes
The history of the microscope is an amazing example of how partnership between engineering (i.e., building a new technology) and biology can enable an entirely new paradigm (i.e., world) of discoveries.
In mid 17th century Anton van Leeuwenhoek was an amature lens maker (he ran a haberdashery business). Van Leeuwenhoek was not a trained scholar; he didn’t speak Latin, the scientific language of his time. But he was an excellent lens maker, incredibly curious, and a meticulous experimentalist. His unique lenses (small spheres of glass) enabled him to magnify objects up to 270 times. Leeuwenhoek’s simple microscope was the best microscope of his time. Prior to his work the typical compound microscopes were only able to magnify objects only up to 20-50 times. He was perhaps the first person to see many forms of living matter. [1,2]
Observations enabled by microscopes were one of the most visceral discoveries that astounded the public, including all of the many microorganisms that can be found in a drop of water, a historical depiction of which is shown below.
Q.1. What do you think was the impact of the invention of the microscope? How do you think it changed the attitudes of both the practitioners (scientists) and the citizens of 17th century?
Q.2. Do you think the developer of the early microscopes could predict all the many applications of their technology to this day?
Q.3. Identify one example of a modern day necessity that would have been impossible without the invention of the microscope (yes, there are many examples but just identify your favorite!).
Q.4. Now, let’s think about a contemporary technology that enables us to read DNA. DNA sequencing technology allows you to take a physical sample of DNA (e.g., the genome of an organism, which is the physical object comprising all the DNA of an organism) and identify the specific sequence of DNA bases (typically represented by the letters A, T, C, and G) that comprise the DNA. (Don’t worry if you do not know much about the details DNA sequencing, we will cover this later in the course. optional link) What do you think has been the impact of DNA sequencing technology? Stated differently, what do you think has been the impact of being able to read out the “letters” in DNA encoding organisms. Do you know of any current applications of DNA sequencing? Can you imagine what would be the impact of DNA sequencing in 10, 50, or 100 years given developments occurring right now?
If you are excited about learning more about microscopy please follow this fantastic optional link. If you want to know more about the discovery of bacteria by Van Leeuwenhoek please follow this optional link 2.
Example 2 - Polio Vaccine
Polio is a crippling and potentially deadly disease and is caused by the very contagious poliovirus that spreads rapidly from person to person. Polio can lead to paralysis if the virus invades the person’s brain and spinal cord. About 1 out of 200 people infected with poliovirus will suffer from this outcome.
In the early 20th century, fewer diseases frightened parents more than polio. Children could come down with polio suddenly, and rapidly suffer from permanent paralysis in one or both legs. A tank respirator, better known as “Iron Lung,” was developed to help patients breathe. These giant tanks engulfing a whole person from their neck down were often required as a long-term solution and patients’ survival depended (and depends) on them. Here is an additional interview with people that depend on iron lungs for their survival to this day. [3,4]
In 1955, Jonas Salk and his team successfully developed a vaccine for polio. Salk’s team manipulated the virulent poliovirus to inactivate it. This inactivation engineered the native virus into a form that was safe to the host (i.e., person) but still had the immune stimulating components that would lead to successful immunization via the vaccine.
Watch this video which will bring you back to 1955 when the clinical trials for the vaccine were released.
Q.5. What do you think was the social impact of the successful development of the polio vaccine?
Q.6. What cultures and attitudes had to be coupled with Salk’s discovery to ensure the transfer and success of the vaccination campaign?
Q.7. The video of the released clinical trial results shows the public’s excitement and faith in research at that time. What discoveries today would lead to that type of response? Could bioengineers take for granted a similar response today? Why or why not?
Example 3 - Ringspot Resistant Papaya
In the early 90s, hundreds of Hawaiian papaya farmers were in the state of panic. Papaya Ring Spot Virus (PRSV), named since it leaves discolored spots resembling tiny rings, were spreading across their fields. For the next several years, the farmers would lose most of their fields after and crop to PRSV.
In 1992, a plant pathologist at Cornell University, Dennis Gonsalves, who grew up in the region most affected by the virus, suggested a vaccination approach to stop the spread of this devastating virus. After a decade of work Gonsalves and his team carefully genetically modified the papaya plant by inserting a gene from the PRSV. They were able to create (i.e., cultivate) a papaya plant – which they named the Rainbow papaya - that was genetically resistant to the ringspot virus, effectively saving the papaya industry in Hawaii. Their work is an example of engineering of living matter. Here is a fascinating interview with Dennis Gonslaves about the Rainbow Papaya and the social impact titled Why public sector biotechnology research matters?. However, this story did not end there… (read on)
In 2013 anti-Genetically Modified Organism (GMO) groups strongly and successfully advocated, and passed a ban in Hawaii restricting cultivation of GMOs. Naturally this was faced with strong opposition from the local papaya farmers. The bill was amended to make exception of genetically modified papaya (and corn). The ban was turned into law in 2014, which was stuck in a legal limbo. Eventually, a U.S. Court of Appeals overturned the bill ruling that counties in Hawaii could not enact their own GMO bans. However, this was not the end of the story either. The debate over the Hawaii bill sparked numerous bills around the country seeking to limit or to ban GMO food, crops, or ingredients. Finally in 2016 President Obama signed the first national GMO labeling law, which required food makers to list any GMO ingredients. Currently there are numerous active anti-GMO organizations all around the country, as well an many for-profit companies working to make and deliver products (and realize profits) via genetically modified organisms.
Q.8. What do you think was the social impact of the successful development of the Rainbow Papaya?
Q.9. What cultures and attitudes were coupled with the development and cultivation of the Rainbow Papaya?
Q.10. Who are the stakeholders in the debate between the pro Rainbow Papaya and the anti-GMO campaign? Who (or what process) should decide the outcome of this debate?
If you are excited about the ringspot resistant papaya and want to learn more, follow these optional links: link 1, link 2, and link 3.
Summary
In Day 1’s post-class material you reviewed representative cases highlighting the impact and role of bioengineering, broadly defined, in society. First, you examined the role and development of a transformative technology, the microscope, that opened opportunities and vistas previously inconceivable. From this you examined, what tools and technologies do we want coupled with biology? Next, you examined development of a life saving vaccine for polio (an example for engineering with biology). Here you examined what cultures do we want coupled with bioengineering? Finally, you learned more about the Rainbow Papaya as a case for engineering of biology. Here you began to examine what futures we wish to realize via bioengineering? And who gets to decide?
Additional References:
[1] History of the microscope [2] Ed Young, I Contain Multitude [3] CDC Poliovirus [4] History of Polio vaccines [5] Erin Brodwin “This Cornell scientist saved an $11-million industry [6] Ban in Hawaii on GMO Crops Is Ruled Invalid [7] U.S. GMO food labeling bill passes Senate ________________
Preclass for Wednesday
What’s Unique About Living Matter?
Here you will learn and think about what makes living matter such a unique material when compared to inert matter by considering the specific and distinctive properties and capabilities of biological stuff from an engineers perspective.
Goal: After watching the following video you should be able to explain the properties of living matter that make it more effective at solving many engineering challenges compared to inert matter.
You can watch this video from Stanford Bioengineering Prof. Jan Liphardt detailing the unique properties of living matter. Write down any questions you have so you can ask your peers, TA’s, and professors in class or office hours.
Q.1. Think of at least two more applications which could benefit from the use of living matter that weren’t mentioned in the video.
Q.2. According to the video, what is the universal code that makes engineering and tinkering with living matter feasible?
Q.3. Describe what it means that living matter functions and is organized on many orders of magnitude (multiple scales). Think about an additional example (video discusses the brain) to explain organization from nanometers to meters to scale.
Q.4. What did you find most surprising?
Preclass for Friday
A specific skill we wish you to learn or improve is how to quickly and effectively benefit from research reports that appear routinely on the “front lines” of bioengineering. To gain or improve your research manuscript analysis skills please study the two papers listed below. NOTE — we are not asking you to read these papers. Rather, simply apply the first five points as noted below. Your two objectives are to see if you can identify the main claim in the paper (only by skimming and thinking about the title and the abstract) and then to see if you can determine where in the paper the evidence is presented that supports the main claim (only by skimming and thinking about what is presented in the figures or illustrations). Please practice the method outlined below before class on Friday on the two papers given here.
How to read a research paper:
(0) DO NOT SIT DOWN AND READ THE ENTIRE PAPER. STOP. DO WHAT FOLLOWS INSTEAD.
(1) Read the title. Does it make any sense? Note words you don’t understand.
(2) Read the abstract. Find the single most apparent or remarkable claim.
(3) If you fail to find any main claim from the abstract don’t bother reading the paper.
(4) Skim the figures, looking for evidence in support of the main claim.
(5) If you can’t find clear and apparent evidence in support of the main claim stop spending time on the paper.
STOP HERE REGARDLESS AND DECIDE IF YOU HAVE MORE TIME TO SPEND ON THE PAPER
(6-10) If you are spending more time on the paper the next thing to do is to find the main weakness or limitation of the work. Finding the main weakness requires much more effort, beyond scope of Intro to BIOE.
Papers
github source code for teaching staff