2020(S08) Lecture:week 5

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Week 5 Tuesday

Today will be a project work day with your advanced student mentors. You might consider reviewing the project organizer or the requirements for the 3 ideas presentation or the student resources list. There is no lecture log required for today but you should update your project development notebook, electronically if you're keeping it that way, or on paper if that's your preferred style. Your 3 ideas presentation will be one week from tomorrow.

Homework for Thursday

Read the chapter you were given written by Charles Weiner that was photocopied from the "Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology." The chapter serves three important purposes for our class. First, it provides some context for the upcoming video presentation of the 1974 Cambridge City Council Hearings. These hearings enabled the citizens of Cambridge to directly address the scientists themselves and question the intent and efficacy of national safety guidelines for recombinant DNA work. The video was made and made available to us by Charles Weiner and it will be shown on Thursday in class. Second, this chapter will give some timeline for the development of the technology itself as well as for the meetings and hearings that addressed its hazards. Finally, this chapter gives some insight into the polarizing viewpoints and biases inherent in many of the discussions associated with these issues.
There are three short parts to this assignment and you should spend no more than 1 hour reading the chapter and answering these questions.

  • Part 1: What is recombinant DNA?
To illustrate your understanding of genetic engineering techniques, describe how you might make the DNA that programs the GloFish shown here
image of GloFish from Wikipedia entry about Recombinant DNA
. Call the gene for glowing "GFG" and the fish plasmid "pFP."
  • Part 2: Key events for regulation of experiments involving recombinant DNA

Concisely describe the relevance/importance of

    • 1973 Gordon Conference
    • 1974 Berg letters in Nature and Science
    • 1975 Conference in Asilomar
    • Recombinant DNA Advisory Committee

All of these are described in Charles Weiner's chapter that you were given.

  • Part 3: Public scrutiny of and say in research decisions

Consider these three quotes and then

    • give your idea(s) about how to best engage the public in the scientific enterprise
    • comment on one author's viewpoint or agenda, as best you can glean from the short quote
    • and finally say if you think the publication was an appropriate places to express that author's viewpoint

Quote 1: from pg 910 of Encyclopedia chapter (above) "The motive from the start was to avoid public interference and to demonstrate that the scientists on their own could protect laboratory workers, the public and the environment."
Quote 2: from Open Letter to the Asilomar Conference written by Science for the People "There is little evidence that the technologies being discussed at this meeting arise from social or medical needs of large segments of the population. Rather, they represent specialized interests including those of the scientific community itself."
Quote 3: from Summary Statement of the Asilomar Conference written by Paul Berg et al and published in Proceedings of the National Academy of Science "In the longer term, serious problems may arise in the large scale application of this methodology in industry, medicine and agriculture. But it was also recognized that further research and experience may show that many of the potential biohazards are less serious and/or less probable than we now suspect."

Upload your answers to the following questions into your personal design portfolios that are here

Week 5 Studio

Today will be a second project work day with your advanced student mentors. You should organize your progress and task list and thinking in your project development notebook, be it electronic or on paper, depending on your preferred style. Your 3 ideas presentation will be one week from today.
For one hour, the advanced students will discuss a journal article. You are welcome to listen to that presentation/discussion or continue to work independently.

Week 5 Thursday

Challenge: "Refrain from using the alphabet"

Turning back the clock: 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. Charlie Weiner made this videotape for the the MIT Oral History Program Recombinant DNA History Project, and he has generously shared it with us. The title of the video is, *“Hypothetical Risks, The Cambridge City Council hearings on DNA experimentation in Cambridge.”
It was recorded at the City Hall Cambridge MA 1976 and though 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 academic debates or over-emotional public reaction.
The cast, listed in the order of speaking:

  • Mr. Alfred Vellucci, Mayor of Cambridge,
  • 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

Their exchanges 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
  2. Self-regulation vs government legislation
  3. Scientific process
  4. Rhetoric
  5. Past performance as indicator of future returns?
  6. Preparedness
  7. Scenario building
  8. Detection and 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. This can be done by watching the BSL video that is here.

After watching the videotape

As a class we will consider the following exchanges and what they tell us about the 8 considerations listed above. The quotes (as accurate as I can render them!) are presented in the order in which they appear in the videotape itself.

Videoclip 1

Mayor of Cambridge, Alfred Vellucci: “Refrain from using the alphabet. Most of us in this room including myself are laypeople. We don’t understand your alphabet. So you will spell it out for us so that we know exactly what you’re talking about because we are here to listen”

Videoclip 2

Dr. Mark Ptashne: “Let me begin by giving you a blanket statement of fact. No known dangerous organism has ever been produced by recombinant DNA experiments. …You must realize that unlike other real risks involved in experimentation, the risks in this case are purely hypothetical…I believe it to be the opinion of the overwhelming majority of microbiologists that there is in fact no significant risk involving experiments authorized to be done by the federal guidelines in P1, P2 or P3 laboratory.”

Videoclip 3

Dr. Daniel Branton: “Our awareness of these tremendous potentials clearly does not relieve us of the responsibility to exercise the utmost caution in regulating work with recombinant DNA...What we have been asked to do and what we are doing…is to regulate research that does not pose a known threat to public health and that is extremely unlikely to impose such a threat.”

Videoclip 4

Dr. Maxine Singer: “I must say that I’ve been surprised recently to find myself put among those who are considered to be unconcerned. I have been concerned and I continue to be concerned. I feel that these guidelines are a very responsible response to that concern....The whole deliberation within the NIH has been a very open process”

Videoclip 5

Mayor Vellucci:

  • “Can you make an absolute 100% certain guarantee that there is no possible risk which might arise from this experimentation?
  • Is there zero risk of danger? Answer that question too please.
  • Would the experiments be safer if they were done in an isolated P4 lab, not a lab in a populated area of the country?...
  • Is it true that in the history of science mistakes have been known to happen?
  • Do scientists ever exercise poor judgment?
  • Do they ever have accidents?
  • Do you possess enough foresight and wisdom to decide which direction the future of mankind should take?
    The great war poet Joyce Kilmer once wrote: Poems are made by fools like me but only God can make a tree. I have made references to Frankenstein over the past week and some people think this is all a big joke but it was my way of describing what happens when beings are put together in a new way. This is a deadly serious matter, sir/madam/sir. It is not a laughing matter please believe me. If worse comes to worse we could have a major disaster on our hands. I guarantee everyone in this room that if that happens, no one will be laughing then.”

Videoclip 6

Saundra Graham: “I’m still wondering why this has been dropped in our laps. There must be a great division that the political world… now has to settle an issue in the scientific world, there must be something terribly wrong going on. That nobody knows what kind of guidelines should be adhered to and that we are going to have to make that judgment on the basis of—excuse my language—national security. We are not scientists and my God in n years on the council I never thought I’d have to make a scientific political decision...I don’t understand why it has to be in place in our laps if the risk is so low or if there is almost zero chance of anything happening to the public, that we have to make that decision. And that makes me leery of what kind of experiment this is really all about because even in the nuclear experiments they never came to the city council for us to make those decisions.”

Videoclip 7

David Clem and Maxine Singer:

  • DC: Does the NIH fund recombinant DNA research?
  • MS: Yes
  • DC: And is it also the NIH that regulates that research?
  • MS: Yes
  • DC: Dr. Singer, do you believe, personally, that there should be civilian control of the military?
  • MS: Uh that’s a very difficult question for me to answer personally since I’ve come as an employee of the National Institutes of Health and it’s a question that obviously is surprising for me because it’s something unexpected and not right on the topic
  • DC: Well you see I think it is right on the topic because I think that is in fact the fundamental issue here. I really don’t give a damn about a P3 laboratory at Harvard University because I can’t visit that lab and discover if it’s P1, P2 or P4 or whatever. I don’t have the expertise to analyze or investigate any kind of laboratory facility at Harvard University but it strikes me as very to the point that there is an important principle in this country that the people who have an invested self-interest in certain types of activity shouldn’t be the ones who are charged with not only promulgating it but regulating it. This country missed the boat with nuclear research and the atomic energy commission and we don’t want to find ourselves in one hell of a bind because we are allowing ourselves to allow one agency with a vested interest to initiate, fund and encourage research and yet we are assuming they are non-biased and have the ability to regulate that and more importantly to enforce their regulation
  • MS: Now that I understand your question better, I’ll say that I share your concerns over that. Nevertheless it is true that the National Institutes of Health thus far has undertaken the most serious analysis of this question.
  • DC: The problem I have with that statement is that I can’t accept at face value that the NIH has gone further than anyone else in terms of trying to establish appropriate guidelines and procedures but I submit to you that that’s not far enough and that it is not worth the so called hypothetical risk to toy around with idea without until we have a better set of guidelines.

Videoclip 8

David Clem “I find it strange that Dr. (p)Tashne asserts that the reason he and his colleagues want to do this research is that they don’t have enough knowledge about the way the organisms are organized and yet they have enough understanding to establish that the risk is minimal. That, to me, seems like a contradiction in terms."

Videoclip 9

David Clem and Mark Ptashne

  • MP:No no what I mean by saying hypothetical is quite precise. That unlike dealing with known pathogens, there has never been shown that recombinant DNA experiments can results in production of a pathogen. Do I make that quite clear? Hypothetical in the sense that nothing has ever been demonstrated.
  • DS: Alright you made the statement that no known pathogen has ever been made by a recombinant DNA experiment. Just what exactly are you going to do if you do produce one?”
  • MP:Um well I I As near as I can tell the probability of that is extraordinarily low. Now I know you don’t like science that tells us that there are risks involved but they are extraordinarily low. I can only tell you, indicate to you, that what is meant by that is the risks are less than the typical kinds of risks you engage in everyday, walking across the street, you can disagree with the statement but this is the point I’m making.

Videoclip 10

David Clem and Mark Ptashne

  • DC: Well what are you going to do if you produce an organism that you know to be dangerous.
  • MP: Well the answer to that is we’d immediately destroy it and anything.
  • DC: You believe that research in a P3 facility gives you that kind of control. That if you produce an organism you can control it and stop it.
  • MP: The occasional organism will escape, on an ant or on your clothes. Does that answer your question?
  • DC: It answers my question but it seems to me that if you’re so able to use some real common sense knowledge that dosage might have something to do with it. That you know a smaller dose is less likely to be as lethal as a larger dose, then why don’t you use some other common sense that says we oughtn’t do this research where there’s fewer people around.

Videoclip 11

Ruth Hubbard:
“proposed that these experiments be done in containment facilities (so called), but everyone agrees that these facilities cannot in fact contain E. coli because it will inevitably be carried out by the people who work in the facility, on their clothes, in their hair, on their skin in their throat. And will be communicated by them to other people. It is quite possible that these people themselves will not get sick from these E. coli they carry but then when they come in contact with people who are more susceptible, like for ex people who have just taken a course of penicillin that kills all the bacteria in their gut and who are therefore in the process of developing a new culture of bacteria that they may take up large cultures of these strains and may get sick. Another example, newborn infants have no bacteria in their gut and gradually aquire them. Should people doing this kind of work be allowed to come in contact with newborns, should they be isolated from them there are a whole host of question that could be answered by working on animals and that we do not know the answers to at this time. The point is that we don’t know and the people who want to go ahead with the work don’t know because this kind of work has not been done before. The best course, therefore is to be extremely cautious until we know more, in particular with coli because if a dangerous strain of coli gets going, since it can move in us and in so many other places, it can multiply rapidly and can get all over the place before we even know that it is out and after that we cannot call it back.”

Videoclip 12

Jonathan King:
in the first place I’d like to absolutely dissociate from myself from most of the biologists to who Dr. Ptashne in particular referred to: 'most of the biologists don’t think it’s dangerous. Most of the biologists don’t think it’s of concern.' Most of the biologists I know are turning over in their sleep over this issue. You were told by Dr. Ptashne that small pieces of DNA introduced into E. coli are not likely to render it dangerous or pathogenic. This is absolutely false. It’s well known in the scientific community that antibiotic resistance is associated with small pieces of DNA introduced into bacteria. These are called plasmids, the same ones that were defined by Dr. Ptashne at the Mile symposium that took place at MIT last week. It’s a symposium to kind of push the benefits of this research. A number of scientists presented evidence showing that the pathogenicity of E. coli—the ability of E. coli to make you sick--- is exclusively associated with small elements of DNA which allow it to stick to your small intestine so it can’t be washed out. The other allowed it to make a toxic agent to make you sick. They presented there was no danger of escape. I’d like to go down on record as saying this is a patently false statement. In fact it’s absolutely certain that they will escape since in the highest containment facility that ever existed in the United States, where every person associated with it was highly trained there were 423 cases of laboratory-acquired infections at the time and this is situation where everybody who got sick, got a cold, didn’t feel well had to report to a physician who was specially trained and who assumed they were sick. Now I don’t know how all of the scientists can know that none of these organisms are dangerous because neither Harvard nor MIT has a program in which every person who works in a laboratory is regularly screened to make sure they haven’t picked up a lab acquired infection. How do you know when some comes in and says 'I was out for the last few days. I had a bug. I didn’t feel good. That it wasn’t something picked up in a lab.'

Before you leave class today

You should also record your ideas in your lecture response log here where you'll note

  • what the activity was
  • why you think it might have been included in this class
  • if the activity helped you think about:
    • ways to make biology easier to engineer
    • clever ways nature solves physical challenges
    • ways nature innovates
  • if the activity has given you any new tools/considerations that could be useful for your project.

If there is any time left in lecture, you and your team can continue to work on your 3 ideas presentation for next week.

Homework for Tuesday

Read the photocopied handout from Jon Beckwith's book, "Making Genes Making Waves."
This chapter was chosen for you to read because it includes several important lessons drawn from the author's personal history and his career development. The chapter also includes some important scientific content about bacteriophage and E. coli's lac operon. Near the conclusion, it presents a rare, first-hand account of an emerging technology, namely direct gene manipulation, that was immediately recognized for its pioneering and frightening possibilities. As described in this chapter, Jon Beckwith's scientific work enabled the lacZ gene from E. coli to be purified, making the ability to purify any gene from E. coli seem close at hand. A future in which genes from any kind of cell (prokaryote or eukaryote, e.g. human) might be moved at will from one cell to another was suddenly more realistic than it had ever been.
Spend ~ 1 hour reading the chapter and answering the following questions:

  1. From pages 16-28: Find 1 sentence related to Professor Beckwith's development as a scientist that struck you for its relevance, its surprising nature, its humor, etc. Give the quote and explain its relevance to you.
  2. From page 28-end: In plain language describe what is being shown in
    • figure 1 panel A
    • figure 1 panel C
    • figure 1 panel E.
    • figure 2, top and bottom of image where there are squiggles
    • figure 2, middle where there is one thicker line. Be sure to say why the line is thicker.
    • figure 2 vs figure 3. What has been done to the material in figure 2 to make it appear as it does in figure 3.
  3. From page 36: Comment on the quote, "We have no right to pat ourselves on the back." For example think about:
    • Why was it said?
    • Do you agree with the thought?
    • Would you have said it?
    • Is there some emerging technology you are imagining this century might similarly "hold dangers for humanity."
    • Finally, is your thinking affected by the public reaction to the comment ("newspaper headlines warned of the imminent creation of new Frankenstein's monsters.")?

Upload your answers to the following questions into your personal design portfolios that are here
Very last thing (promise) is to come to class on Tuesday with a question to ask Prof. Beckwith. Write this question on a 3x5 card or piece of paper so we can collect them and give him some choice of topics to address. Thanks!!