[MUSIC] So remember, we are at a place where construction of recombinant plasmids had happened. But those plasmids hadn't as yet been transfected into a bacteria, E coli in particular. We're in January of 1973, and at a meeting conceived and run by Paul Berg that also took place at Asilomar. But this isn't the Asilomar meeting that people are talking about when they talk about the Asilomar meeting. That's the second one, which will come up in just a little bit. The first Asilomar meeting was unrelated to the recombinant DNA work, but was rather focused on containment. And in particular due to concerns around cancer viruses, which we talked about in the first section, and new hybrid viruses. There were about 100 scientists there, they were mostly American. There was no press. This is, again, in contrast to the second Asilomar meeting, which I'll talk about in a little bit. And at this meeting, a series of safety precautions were outlined, again, around containment of cancer and hybrid viruses. One attendee at this meeting was Andrew Lewis, who had been generating hybrid adeno-SV40 viruses. And he personally would only share these viruses with people who acknowledged their danger, the potential danger of these hybrid viruses, and agreed to handle them carefully. So he was exerting some sort of governance over the distribution of this reagent. But the broader meeting, the meeting was to talk about what the field generally ought to be doing. A Gordon Conference later that year was meant to, A Gordon Conference later than year was all focused around DNA synthesis, and structure, etc., it was the Nucleic Acids Conference. And on the fourth day, they were going to use that to talk about restriction and the use of restriction enzymes to study DNA. Now, EcoRI had been discovered in the lab of a scientist named Herbert Boyer at UCSF. And following a series of conferences in the early 1970s, Boyer and Stanley Cohen, who was a plasmid guy, struck up a collaboration. And within a few months, the two of them had not only combined two antibiotic resistance genes into a recumbent plasmid using EcoRI, but they had also then inserted that plasmid into E Coli. So they had taken that step that Paul Berg and his colleagues had not yet taken, that was sort of on pause, they had gone ahead and done it. Now, Cohen wasn’t at the Gordon Conference, and Boyer was. In advance, Cohen made Boyer promise not to talk about their work. But he's a scientist, he was excited, and he did. [LAUGH] So Boyer broke his agreement with Cohen, and told the folks assembled at the 73 Nucleic Acids Conference what they had done. Now, first think about this accomplishment, and sort of the questions that might surround it, right? They had conferred multiple antibiotic resistance to a bug, E coli, that lives in the human gut. And again, place that in the broader context of the late 60s and early 70s, and everything that is going on, in particular in the United States. So the exclamation was made, then, following this revelation by Boyer, that now we can combine any DNA. We can do it, it's done. The field has demonstrated the power of this. So the conference chairs, who were Maxine Singer and Dieter Soll, there was only a half day of the conference left, but they said, okay, this is what we're talking about now. [LAUGH] This is all we can talk about now, right, the implications of Boyer's revelation. So Friday morning, last day of the conference, within about 30 minutes, the participants at the Nucleic Acids Conference agreed that first, a letter should be sent to the presidents of the National Academy of Science and the Institute of Medicine, and that that letter should be published. And it was in fact published in July of that year, and noted both the promise of this science and the potential risks of this science, and suggested that the academies establish a committee and recommend actions and guidelines around governance for this science. The letter appeared in Science Magazine later in that fall. Maxine Singer had recommended Paul Berg to lead this recommended committee. He, in fact, did organize a small meeting to figure out what the next steps should be. In April of 74 at MIT, Paul Berg, Jim Watson, David Baltimore, and others met and concluded that first, and most importantly, the scientific community should enact a voluntary moratorium on this science while they deliberated among themselves, primarily, about the benefits and risks of the science and governance for it. They also concluded that the scientific community should carefully weigh experiments to link animal DNA to plasmid or phage DNA, that the NIH should establish an advisory committee, and that there should be an international meeting to, again, discuss benefits and risks and governance. That international meeting is Asilomar II. But it is the Asilomar meeting that people are talking about when they talk about the Asilomar meeting. It took place in February of 75. There were about 90 scientists from the US, about 60 from outside the US, 16 reporters, and several lawyers, who I'll talk about in a little bit. It was three and a half days. There were three discussion panels. And the discussion panels were supposed to meet in advance of the meeting and develop recommendations in their area. Unfortunately, the virologists missed the memo. So the night before the meeting, they got together and wrote up two pages, and that was their working document. The plasmid report, for comparison, was 35 pages. David Baltimore opened the conference, and basically told the scientists there, the buck stops here. We need to figure this out. There is no one else we can turn to. It's our job to sort of self regulate. Paul Berg talked about the effect of the statement and why he brought in the lawyers who, again, I'll talk about in a little bit. The meeting was very, very technical. I mean, it's important to point out that, again, these were all scientists. And while there was a great deal of disagreement among them about various technical issues, there weren't members of the broader society or members of the groups that had come out against recombinant DNA and this area of science. So for example, there was a group called Science for the People. They had written a letter to the group, which was circulated at the meeting, but was not discussed. And that letter argued for a continuation of the moratorium that had been going on since the small meeting that Paul Berg ran, and also for public involvement in the decision making. Again, this letter was circulated, but not discussed. The meeting itself was really focused on the science. Each working group presented their findings. There was, again, dissent among the scientists, but no discussion of dissent from outside. And they were at a pretty significant disadvantage here in that, again, they could predict or envision the possibilities of this science. But they had no way of judging the risks. As I mentioned on the last slide, Science for the People, this outside group that was against recombinant DNA, they had concerns about the risk/benefit analysis, about broader social issues. Although no human genetic engineering, obviously, had gone on at this point, in the mid 1970s, they were looking down the road, and were very concerned about that possibility. They were concerned about social justice and transparency. This one quote, I think, is poignant and still highly relevant today. Since the risks and danger of these technologies are borne by the society at large, and not just scientists, the general public must be directly involved in the decision making process. And this is a sentiment that has been echoed time and time again since the 1970s for other areas of emerging technology. So, back to the lawyers. Daniel Singer, Alex Capron, and Roger Dworkin were all there to sort of, as David Baltimore said at the beginning, the buck stops here. But even more than that, to really impress upon the scientists how important it was that they develop some way of regulating this area of science. The scientists had gone to the NIH to convene this meeting. They funded this meeting to develop the committee that they recommended. And they trusted the NIH, because the NIH is made up of scientists. But the lawyers impressed upon them that there were many other federal agencies that could reasonably be expected to have an interest in this science, including the Food and Drug Administration, the Centers for Disease Control and Prevention, the Environmental Protection Agency, the Department of Labor. It was not just the scientists. And if the scientists assembled did not come up with a defensible approach to regulating the science, someone else would, and that it might lead to restrictions on the science. Because the public and government were going to insist on having their say, in particular if the scientists couldn't come to consensus on a way forward. Roger Dworkin talked about not just the sort of societal implications of not coming to consensus, but in fact, legal liability for potential bad outcomes from the science. When the scientists finally came to the point of having to vote, having to make a decision about governance going forward, it was on a draft statement that had been circulated on the last morning of the conference that was drafted by the organizing committee the previous night. And they had to take votes on basically each part of it, right? Figuring out how a group of 150 scientists makes decisions on a draft statement is complicated, some cat herding involved. So they voted on various pieces of the statement. The first vote, or one of the votes, was that the work, in fact, should proceed, but with safeguards. So the pause was over. Remember, up until this point, there had been a voluntary moratorium. The scientists said, okay, we are ready. We feel like we have a handle on this, and the science can now go forward. However, there are some experiments that should not proceed, right? They continued to vote on major statements, which were then fleshed out later in a summary statement. And the provisional statement was released at a press conference on the 28th. The provisional statement was immediately adopted by the NIH Recombinant DNA Molecule Program Advisory Committee, which became the RAC, the Recombinant DNA Advisory Committee, so that they could get to work. Now, the RAC had, in fact, they'd been working on developing the RAC up and to this point, getting people appointed, figuring out what it would look like, so that members of the RAC could in fact be at the meeting and ready to start their work immediately following Asilomar. Their first meeting was on February 28, the day of that press conference and the day after the Asilomar meeting ended. As I was just discussing, the process up to that point, that the RAC was formed in response to that Berg letter from 1974. They had to develop a charter, get it signed, and get people onto the committee. As a national advisory body, it's subject to certain rules in the United States. And the RAC was established as being advisory to the director of the National Institutes of Health. And again, it was important that the committee be seated prior to the Asilomar meeting, so that members of the RAC could attend the meeting. You can see here the first members of the RAC, who were there seated prior to Asilomar. These were all basic scientists. The second wave a few months later were additional scientists. And it wasn't until the third wave in 75 when LeRoy Walters, who is an ethicist, and Emmette Redford, a layperson, were added to the RAC. So the guidelines for the RAC, I mean, the first ten months of their work was really focused on developing the guidelines. They were, in fact, faithful to the Asilomar consensus, leaning to the conservative end, and importantly, trying to match the containment to the risk. So going back to the virus group, who were a bit late with their report, what they ended up producing and presenting on the first day of Asilomar was two pages. One page of guidelines was signed by seven of eight members of that committee, and one page was a dissent by Andrew Lewis. If you remember, Andrew Lewis is this guy who works on hybrid viruses, who would only share his viruses with people he trusted, and who he felt understood the risks. His dissent was about physical containment and biological containment. Meaning, physical containment, only use these viruses in well constructed, secure facilities. And biological containment, using engineered, fragile hosts and vectors that can't survive outside the lab. And in fact, that ended up being sort of the focus of the guidelines and oversight of this science. So Andrew Lewis for the score, very focused on physical and biological containment.