Recombinant DNA and Science Policy • iBiology

00:00:15.15 LG: I am Larry Goldstein. I am a professor of cellular and molecular medicine
00:00:20.09 at UC San Diego, and I have the great pleasure today to interview
00:00:24.16 my friend and colleague, comrade in arms, Paul Berg, the Nobel Prize winner
00:00:30.24 and also a recipient of the public policy award from the
00:00:34.16 American Society for Cell Biology. I am going to ask Paul some questions
00:00:37.25 about his life as a science policy advocate
00:00:40.28 and public figure. So, Paul, thank you for taking the time to join me today.
00:00:46.02 PB: Thank you.
00:00:47.22 LG: Good. So, let's start at the beginning.
00:00:50.16 You had a very illustrious career in science,
00:00:55.21 but something made you decide to leave the lab at least part of the time
00:01:00.18 and engage in policy debates. What was it that brought you out for the first time?
00:01:06.11 PB: Well, it certainly wasn't voluntary. It turned out
00:01:11.01 that an experiment which we had planned and were in the midst of
00:01:15.14 elicited a lot of concern among other scientists.
00:01:18.28 The experiment we had in progress was to fuse a small
00:01:23.10 minichromosome containing lambda genes and three genes of E. coli, the GAL operon,
00:01:29.28 and we fused that with SV40 to make a recombinant that it contained.
00:01:34.11 Now this recombinant could propagate in E. coli because it contained the parts on the mini plasmid
00:01:40.16 which allowed it to propagate in E. coli.
00:01:42.23 and it could also be propagated and transfect mammalian cells.
00:01:47.05 So it was kind of a dual-headed thing,
00:01:48.20 and what we wanted to was to be able to make mutations in
00:01:51.23 the SV40 genome in E. coli and then test them in mammalian cells.
00:01:55.28 And the other thing is that we would want to test whether the GAL genes could be expressed
00:02:00.20 in mammalian cells. So that was the idea of the experiment.
00:02:03.05 The point was that we were going to be propagating SV40 genes in E. coli.
00:02:09.09 So the concern was that E. coli is a natural inhabitant in humans
00:02:15.14 and the concern was inadvertently, could you infect humans
00:02:20.29 with the E. coli you were propagating and could that possibly lead to cancer.
00:02:25.13 That was the concern. And depending upon where you came down on the topic
00:02:32.05 you were either vociferous about it or you were just saying, "Forget about it. It's not serious."
00:02:38.02 Ok, but soon after a lot of conversations I became convinced that
00:02:44.01 I could not dismiss the risk, make it zero likelihood.
00:02:48.01 So I thought, well we'll just put it on the shelf and the whole thing died down.
00:02:52.25 A year later, well, not quite a year later, Janet Mertz, a graduate student in my lab,
00:02:59.25 discovered that EcoRI made cohesive ends
00:03:02.14 and she discovered that she could take any two DNAs and join them together.
00:03:06.09 And so Stan Cohen and Herb Boyer then began to actually
00:03:10.28 make a lot of recombinants using E. coli plasmids
00:03:13.26 and checking drug resistance and showing that they could make chimeric DNA molecules.
00:03:19.27 And they talked about it at a Gordon conference,
00:03:24.08 and that elicited the same kind of response amongst a small minority of the audience
00:03:29.03 who said, "Oh my god, you guys can really make some dangerous things."
00:03:33.13 So what happened is that at that Gordon conference they got Maxine Singer
00:03:37.21 and Dieter Soll, who were the co-chairs,
00:03:40.15 to draft a letter to the academy and to publish that letter in Science,
00:03:45.28 calling attention to the great promise that being able to make new
00:03:50.05 kinds of DNA molecules, but also calling attention to the possible dangers and risks.
00:03:56.13 And when the president of the academy got this letter
00:04:01.12 he said, "What do I do with it?"
00:04:03.04 and Maxine said to him, "Call Paul Berg, because he's thought about this problem,"
00:04:08.16 and so he asked me would I put together a group of people who could advise the academy
00:04:14.23 on how to respond to the concerns that had been raised.
00:04:17.23 And so I did. I put together a small group, and we met at MIT.
00:04:25.28 Dave Baltimore, Dan Nathans, myself, Jim Watson, a few other people, Norton Zinder,
00:04:33.00 people who would understand the nature of the problem.
00:04:36.23 We met for a whole day this group, and in the end there was no advice that we could provide.
00:04:42.17 We didn't know what to do. So we said, you know, literally you could pick up the phone
00:04:47.05 and call everybody of your scientific community who is likely to use the technology
00:04:51.09 and say, "Hey, be careful." But we couldn't do that.
00:04:55.23 So we said the next best thing was why don't we just publish a letter in Science,
00:05:00.23 calling attention to the promise, to some of the potential risks that have been raised and
00:05:08.23 essentially asking the scientific community to put a short hold on three kinds of experiments.
00:05:19.24 We didn't call for a moratorium on all this kind of work.
00:05:22.29 There were three kinds of experiments that we specifically called attention to.
00:05:26.00 And in the letter we proposed having an international conference to
00:05:29.26 six or eight months later
00:05:32.01 to examine the risks in more detail and come forward with some recommendations.
00:05:36.11 I think the scientific community got a lot of good kudos from the public for saying
00:05:42.04 here is the problem, scientists called attention to it.
00:05:45.06 LG: You actually got out in front of it.
00:05:45.29 PB: as proposing how to deal with this thing.
00:05:48.24 So if you look back now, you say I got into public policy
00:05:53.25 through my own experiments and just being called on
00:05:58.16 to say what do we do when somebody raised the risks.
00:06:03.00 So the initial so called moratorium letter that came out of the group
00:06:07.13 called for a meeting to deal with it, and so we convened
00:06:14.01 I was the chair of convening the Asilomar meeting
00:06:16.27 and the organizing committee was Maxine, Dave Baltimore,
00:06:19.18 myself, Zinder, Sydney Brenner, we had another person from Europe,
00:06:24.26 and we were going to organize a meeting of experts
00:06:28.06 to try to assess what was the magnitude of the risk,
00:06:31.04 what was the likelihood of them coming true,
00:06:33.17 and how could we proceed in any case.
00:06:37.00 Ok, so the Asilomar meeting was a major event. A hundred and fifty people,
00:06:43.14 a huge representation from the media, which was probably one of the best things we decided.
00:06:48.29 There were fifteen people from the press and newspapers, magazines, and so on.
00:06:53.12 And in those three days we debated.
00:06:58.15 What are the kinds of experiments we want to do?
00:07:00.28 What are the possible risks?
00:07:02.26 And we organized it very well so that the meeting was not all talking about
00:07:05.23 risks, it was talking about science.
00:07:08.12 and that was probably the saving grace of why the meeting succeeded
00:07:12.12 because people came prepared to talk about scientific experiments
00:07:16.12 and they were balanced by discussion.
00:07:19.00 There was a lot of interesting science that came out of the Asilomar meeting.
00:07:22.15 One was the safe bug-the engineered microbe which could not escape from the lab.
00:07:27.26 LG: Right, so the crippled hosts.
00:07:29.24 PB: The crippled hosts. And the second one, so that was Sydney Brenner's idea.
00:07:34.21 LG: It's a good idea.
00:07:35.24 PB: He brought that to the meeting and I think that
00:07:39.27 was what turned people around a lot
00:07:42.10 because suddenly we could now answer that question that we could devise
00:07:47.16 the experiments in some way that would markedly lessen the likelihood of escape.
00:07:53.19 So this organism wouldn't be able to live outside the lab.
00:07:57.29 So there were a number...so right in that meeting
00:08:02.20 you could see science taking over, people thinking oh we can do this,
00:08:08.00 LG: And I think you and I would agree, if you are going to have good science policy,
00:08:11.15 it has to be driven by good science.
00:08:14.24 Misunderstanding is not going to get the job done.
00:08:17.08 PB: The turning point of the meeting
00:08:19.14 frankly was the last night when the lawyers had their session
00:08:25.21 and the ethicists. We'd invited a group of lawyers and ethicists.
00:08:29.05 LG: And did the lawyers and ethicists sit through the science as well?
00:08:31.26 PB: They participated in everything, as did the press.
00:08:34.13 The press were free to ask questions, raise points,
00:08:36.27 and in the drinking in the evenings, they milled around and were full members of the meeting.
00:08:45.19 The lawyers pointed out the legal problems, and challenged Jim Watson
00:08:53.25 with the idea, because he had now turned, and he was totally opposed to any kind of regulation,
00:08:59.24 whereas he had been a signer of the original letter.
00:09:03.03 They said people could close down Cold Spring Harbor
00:09:08.12 if there is any danger or anything that happens.
00:09:11.01 And then people's own personal risks were
00:09:14.24 beginning to be played on and eventually I think everybody
00:09:18.27 said we cannot walk out of here tomorrow morning
00:09:22.06 saying we don't have any advice. So that night...
00:09:27.17 LG: Well, especially with the press there.
00:09:28.12 PB: Exactly.
00:09:29.05 LG: Because they were going to cover it, right?
00:09:30.02 PB: And that night, I and Maxine, and Dave and Sydney, we drafted a set of guidelines,
00:09:36.21 and recommended that the NIH use this as a sort of outline
00:09:43.18 for a set of guidelines that would essentially determine the conditions
00:09:48.27 under which this research could be done, and the conditions under which it should not be done.
00:09:53.00 And so the whole thing that came out was very positive.
00:09:56.10 We debated it, and voted on it segment by segment
00:09:59.08 until when noon came when we had to leave.
00:10:03.23 We had an approved list of regulations.
00:10:07.07 LG: Was it unanimous or was consensus?
00:10:08.10 PB: No, no, there were... I would say there was 95% in favor of going forward,
00:10:13.20 even though the language was muddled and things like that,
00:10:17.10 ] but we all agreed that we would smooth things out.
00:10:20.19 So I worked on the language, and Dave did, and Maxine.
00:10:24.17 And we finally got a document, which is now recorded
00:10:28.16 as a famous document out of the Asilomar conference.
00:10:31.16 We look back on it and say, well you know,
00:10:34.22 a bunch of amateurs, we mumbled through a bunch of stuff.
00:10:38.05 We made some decisions that were smart in retrospect.
00:10:41.28 For example, one of the things we did not do and did not include in any way
00:10:46.14 was the ethics. We didn't talk about genetic testing.
00:10:51.14 We didn't talk about any of that.
00:10:52.18 We talked about real experiments.
00:10:55.02 And what the impact of those experiments would be in the field.
00:10:58.14 So there were agriculture, nitrogen fixation, people had all kinds of ideas
00:11:02.29 of what we call the low hanging fruit.
00:11:05.04 LG: The infamous low hanging fruit.
00:11:06.26 PB: What were the things we were going to do right away? Clone insulin gene, clone the growth hormone gene.
00:11:10.01 All of those things were obvious.
00:11:11.26 In retrospect, when you look back, you say
00:11:15.01 most of what has happened, no one could even conceive of it at the time.
00:11:19.13 And so that's the way science goes. You make a slight
00:11:25.01 breakthrough, you've got a lot of very smart people out there.
00:11:27.15 Very smart people figure out very quickly how to use
00:11:30.28 this new notion, this new tool, or whatever
00:11:34.05 and the field explodes, and that is what happened
00:11:37.23 and why recombinant DNA has had the impact that it has.
00:11:40.25 LG: So when did the Congress get into the act?
00:11:43.06 When did the politicians decide that this was something they should worry about?
00:11:46.25 PB: Okay, so, the Asilomar meeting was held in February of 1975.
00:11:54.00 The rest of that year there were small groups that were meeting to
00:11:58.27 devise the guidelines. The guidelines came out
00:12:02.07 in the summer of '76. And that ruled the day.
00:12:08.28 And then sniping occurred. And the sniping occurred from different people
00:12:15.10 who said, "well, these guidelines are not rigorous enough,"
00:12:19.13 or, "we don't trust the scientists or abide by them. "
00:12:22.14 Congress began to respond to these little barbs
00:12:26.24 and they set on a course that they were
00:12:29.27 actually going to prohibit recombinant DNA research in the country.
00:12:33.05 And I remember spending a lot of time in Congress
00:12:35.24 and I can remember vividly one Senator
00:12:39.17 from Arkansas who is normally a liberal
00:12:42.01 and was a pretty good guy getting up and saying on the floor of the Senate,
00:12:45.26 "I never got through high school chemistry,
00:12:49.16 and I don't profess to understand any of this science,
00:12:53.04 but I believe this is the most dangerous work ever undertaken in this country,
00:12:57.20 and I would recommend prohibiting it."
00:13:01.28 There were a lot of people who shared that view,
00:13:04.02 and I am cynical enough to now realize that what changed the whole picture
00:13:09.12 and obliterated the concerns was the founding of Genentech
00:13:15.01 and the first phase stock issue.
00:13:17.25 LG: Ahh, money.
00:13:19.13 PB: Money. Suddenly it became clear that this was going to be
00:13:22.28 a commercial entity and important,
00:13:25.22 and to put any prohibitions on it was like shooting yourself in the foot.
00:13:29.05 And the whole thing disappeared.
00:13:31.00 LG: So the promise of making insulin for kids was not the winning message, you think?
00:13:35.08 PB: It was a message, but when you actually saw something happen
00:13:38.25 that was the, I believe, that was thing that actually was the switch.
00:13:44.14 And the atmosphere changed completely as soon as
00:13:48.10 it became a couple of companies starting up
00:13:50.18 to take advantage of this technology
00:13:52.24 to do this that and the other thing.
00:13:54.28 LG: So ultimately the resolution of this was, if I understand,
00:13:58.17 if I remember correctly, no law was ever passed in the Congress,
00:14:02.16 PB: No law was passed.
00:14:04.04 LG: And it was all done by scientists driving the development of good regulation
00:14:09.17 through the funding bodies, which then spread.
00:14:11.16 PB: Exactly.
00:14:12.23 LG: Amazing. That's a fantastic example.
00:14:14.28 PB: Yeah.
00:14:16.22

This Talk

Speakers: Larry Goldstein, Paul Berg

Audience:

Educators of H. School / Intro Undergrad
Student
Educators of Adv. Undergrad / Grad
Researcher
Educators

Recorded: March 2011

Talk Overview

Paul Berg tells Larry Goldstein how concerns about an early recombinant DNA experiment in his lab launched him into the science policy arena. He describes organizing the 1975 Asilomar Conference on Recombinant DNA and promoting guidelines that aimed to ensure the safety of recombinant DNA technology. Both the guidelines and the meeting format continue to impact science policy today.

Speaker Bio

Larry Goldstein

Larry Goldstein is Professor of Cellular and Molecular Medicine at the University of California, San Diego and a Howard Hughes Medical Institute Investigator. Goldstein is also a recipient of the ASCB Public Service Award. The Goldstein lab studies how molecular motors interact with axonal vesicles and how this relates to neurodegenerative disease such as Alzheimer’s… Continue Reading

Paul Berg

Paul Berg joined the nascent Biochemisty department at Stanford University in 1959 and has remained there since. Berg’s early work led to the discovery of the aminoacyl tRNA synthetases and tRNAs and their role in protein synthesis. Berg was a pioneer in developing recombinant DNA techniques, work for which he shared the 1980 Nobel Prize… Continue Reading