[MUSIC] So you mentioned that the RAC, NIH in this case was regulating that which they were funding, right? And the US is fairly unique in that way, that most of our federal research guidelines, policies, regulations pertain only to federally funded research. The rest of the world generally isn't like that. [LAUGH] >> Yes. So two questions, and you can answer in whichever order you want. How did that play out in the US for non-federally funded research? Like at Lilly, which you've already mentioned once. And what do you know about what the rest of the world was thinking while the RAC was doing it here in the US, doing its work and developing those guidelines. >> The Selmer conference in February of 75 was very decisively international. >> Yes. >> There were people from, I think, at least 20 countries involved there. So that was a time when the best scientists in their relevant fields did get together and talk through the issues. And I think the country that was doing the most in parallel with what the NIH in Iraq was doing, was the United Kingdom. Where there were studied commissions that looked at this whole area and tried to come up with recommendations for public policy in the U.K.. The factor, I think, from mid 1976 on, the NIH guidelines became the standard for most countries in the world. In terms of physical containment and biological containment. But periodically, people like Sydney Brenner for the United Kingdom would come to the United States to consult with people at NIH or with the RAC. And similarly, I would say Donald Fredrickson traveled a great deal internationally to China and to what was then the Soviet Union. And tried to keep abreast with what was happening in this research field internationally. But you're right, I think the standard format for a field of biomedical research in other countries is to have an independent agency overseeing the field. And at least some kind of registration of each study that's going to be done. If I look at a parallel field like research involving human subjects or human participants. I wish that we had a mandatory registration of all studies that are being conducted. But we don't currently have that. In the UK for work involving in vitro fertilization, for example, there's a human fertilization, an embryology authority. That oversees that field of research. And in some ways that's a more rational structure then having a funding agency double as an oversight group. Or perish the thought, a regulatory agency. >> [LAUGH] And going back to the question of in the US, research outside of federally funded research. Can you talk about how that played out with Lilly and other private companies that were doing this research? >> Yes, there was a vote that the RAC took at a certain point when it became clear that industry was becoming more deeply involved. I think the RAC by a narrow margin recommended that there be a program of mandatory compliance by industry. And I think the NIH director felt that that went too far, so what he put forward was a proposal that there be voluntary compliance by industry. That got the RAC into areas that we didn't expect to be in, say in 76. As some companies began to move toward the applications of recombinant DNA research to say producing biosynthetic substances in the lab. >> The RAC then had to deal with proprietary information. The RAC is a federal advisory committee so everything is supposed to be in the sunshine. There are minutes, but I recall that a group from industry came in with a proposal to produce somatostatin in the lab. And they requested that the RAC go into executive session where they would then outline the techniques they were using to produce somatostatin. And some of us had qualms about going into executive session because we prefered to be in the open. But given the alternatives,either no oversight or this kind of oversight with an exception to the rule about openness. I think we came out in favor of going into executive session. By about 1980, the question of laboratory research was basically settled. And we were on the way to having the guidelines become a kind of informal code of practice. For at least all the NIH funded labs around the country. At that point, Eli and Lilly in particular, wanted to scale up to produce biosynthetic insulin. So I was in a small delegation of the RAC that went out to Indianapolis and that visited the laboratory. And saw the huge vats where Lilly was planning to produce biosynthetic insulin. And we heard from, Leaders of the company, what precautions they'd taken to characterize exactly what they were dealing with in vitrum. So that they would know that the biosynthetic insulin would be pure. And I came back from that site visit thinking there's no mystery in this work as there is in a shotgun experiment in the lab. When you don't know what pieces of DNA you're dealing with, this was probably safer. Even though the quantities involved or the volumes were much greater than a shotgun experiment in the lab with unknown pieces of DNA being combined. So, much as I always think one needs to be cautious of when the profit motive is involved. In this case, I thought that the company presented a pretty clear rationale for the safety of what they were doing. But this is a strange role for an advisory committee to the NIH to be site visiting Eli Lilly, doesn't look good there. >> [LAUGH] Do you know of any other examples like this since where an NIH has developed guidelines? And there's been sort of voluntary adherence to those guidelines by industry? >> Well, the closest analogy that I know about came with a subsequent era in the life of the RAC. And that is when it oversaw, and still to some extent oversees, human gene transfer research, or human gene therapy. And there again are Guidelines for human gene transfer research, that NIH and the RAC developed over time. And, at times private companies Have come with proposals to the RAC to have their review. In this case there's a kind of a competition between the Food and Drug Administration, and the NIH RAC. And I think, in some ways, the Food and Drug Administration regrets that it didn't get in on the gene therapy field as early as NIH did. And now the RAC provides a forum for public discussion of what's happening. And in particular, there's been an adverse effect of gene transfer research. And there have been some deaths that have been attributable to gene transfer in clinical trials. And the discussion at the RAC is public. The press is there, they see what's going on. And then FDA can sit in those public meetings, take what they hear under advisement, and then they go behind closed doors. >> Interesting. >> And they make a judgement about whether studies will continue, or whether there will be a clinical hold. A very sad event in that connection is that in the late 90s, the role of the RAC with respect to gene therapy was downgraded. And some researchers either changed their protocols or failed to provide information on adverse effects in a timely manner. In human subjects research, NIH was for a long time the principal oversight group. But now, that function has been transferred to the Department of Health and Human Services. Animal research is, I think in some ways unfortunately the oversight is still located at the National Institutes of Health. And gene therapy, or gene transfer research has been at NIH, and as you pointed out even embryonic stem cell research, is very much tied to NIH rules. And, in some ways, oversight at the present time.
