Interview with Professor Paul Berg by Joanna Rose, science writer, 8 December 2001.
Professor Berg talks about the development of genetic engineering; the commercial pressure on research (3:26); basic versus applied research (5:41); the Asilomar conferences on the risks of gene-splicing experiments (6:56); and today’s problems (11:44).
Professor Paul Berg, welcome to Stockholm and to the Nobel interview.
Paul Berg: Thank you.
You received another prize in 1980 for your pioneering work on recombinant DNA, the molecule that governs chemical machinery in all living cells, so in some sense one may say that you are the father of bio-technology. Are you happy with the way that genetic engineering has developed since then?
Paul Berg: Well, like most scientific advances, they open the door to new kinds of researches and I don’t carry the title of father of genetic engineering very well, because in fact we made only the first step and everybody else seized immediately on this new technology, new capability and began to use it for their own purposes, which is what it was intended to do. But there are many, many very smart people in this world and they all figured out new ways to be able to use recombinant DNA so that today recombinant DNA is the most important tool and governs almost every question that anybody could ask in biology and even outside biology, which is really interesting because it has affected virtually every way in which people want to investigate living organisms – plants or insects or whatever. Recombinant DNA is the basic tool and so one has to feel very good about the impact of one’s early work, even though we didn’t foresee everything that would happen.
You could only imagine the impact?
Paul Berg: No, many people have asked me did you foresee all the new kinds of things that would develop in the whole industry and the answer is very clearly no. We had in mind to do the experiment that we set out to do and, in the early stages, we increased or widened the range of what we did but it was like an avalanche behind us. Many, many people were developing new approaches and particularly industry.
Yes. This was both industry and science and also enormous commercial success, so of course also commercial pressures, I would say.
Paul Berg: Yes. And it has many very beneficial points and some worsening points because there’s no question that companies sprung up almost like mushrooms, you know, after a rain. I mean, there was just huge, huge excitement about it and then many, many small companies, not just the big pharmaceutical companies, but small biotech companies that were started from people in the universities. I understand here in Stockholm now, for example, that the Karolinska is, almost the whole new industrial part developing around the Karolinska to make use of the technologies that they develop there and that’s true of almost every major research university in the US. If you look around the country of the 15, 1700 biotech companies, they’re mostly close to around the major research universities.
So what is your opinion about the commercial pressure on research?
Paul Berg: I think it’s, well it’s positive in the sense that it brings money to the academic institutions; it provides jobs for the people who are trained in our laboratories, but the universities have themselves become commercialised and I think my university, Stanford University, is probably one of the leaders in large part because it made a lot of money very early from the patents on recombinant DNA. I mean, Stanford probably over 17 years of the patent acquired something like, probably more than $100 million, so other universities see that as a possibility of a way of earning money so they become much more aggressive about seeking patents so now, whereas before when I was growing up in the university, nobody ever asked me to patent anything and I never patented anything in my life. I gave away everything we did.
I gave away everything we ever did because what we did it for was to benefit research, but in fact today universities come into the labs and try to teach people how to look for things to patent, help them to start companies, so we now have a very different kind of mix and I think the openness with which scientists usually talk about their research is compromised to some extent, but it has changed the whole climate about the thing. People think in terms of what they’re doing, will I be able to start a business? Will I be able to patent it? Instead of thinking, getting it published and being excited by the fact that people want to use it.
Yes, the perspective then is very short term.
Paul Berg: Yes. So it today, people tend to be more guarded and the universities have sort of required the faculty to become more focused on commercialisation of their work and from the universities’ point of view, it’s to bring in money to help the research in the university so they see it as being beneficial. Those of us who are in the faculty see it as a kind of disturbing influence.
The part of science that maybe can be influenced in the negative way is the basic research.
Paul Berg: That’s right. And that’s another thing, is I think in the long term it will change the, even slightly, the direction of basic research versus applied research. I think people, as they begin to make choices of what to work on or what directions to follow, may begin to choose more and more frequently those which have commercial possibilities and from the public point of view, that may be very beneficial. It means that a lot of the benefits of the research, which is coming from government funds and people’s monies, is going to benefit the public and the criticism was, many years ago, that much of the work that people did with federal funds or government funds never got into the marketplace, never made commercial things because they didn’t have that interest, so many things were lost. But I think we’re paying a price, so it’s a balance and I think it’s an important balance about how do you define and protect the academic atmosphere without changing it, making it the same as a company?
You’ve really come back to these crucial years, I would say, of the development of genetic engineering. There were, almost from the very beginning, concerns both between the scientists and, don’t know, public, about the possible dangers of this research and you were there. Can you tell us some words about the Asilomar conferences, for example?
Paul Berg: Yes. Well, the concerns about the recombinant DNA or genetic engineering came from the scientists, so that was a very crucial fact which I think historically people now identify as a very major and important stage in the development of science, and that is scientists who developed the new technology themselves began to worry about whether there were any dangers and therefore took a major step to make a public announcement saying that this research is very, very important, very powerful but it also has certain risks and we need to examine these risks and determine whether the research should go forward or whether we have to develop new ways to do the research and protect the public and I think we gained an enormous amount of public admiration, if you will, and tolerance and so we were allowed to actually begin to deal with the question of how can we prevent any dangers, things coming out of our work? And so this led to the Asilomar conference. The Asilomar conference was called to bring scientists who wanted to work using recombinant DNA …
The first one?
Paul Berg: The first one, to bring everybody together.
Paul Berg: This is 1975. There was one conference in 1973 and that was to deal with people who were working with animal viruses, to just determine whether there was any danger to the scientists of working with these viruses, and that developed into some very simple recommendations of how to work with dangerous viruses and then that passed and most people did not know. I’m usually the only one who refers to Asilomar 1, but Asilomar 2, which was in 1975, dealt with the issue of recombinant DNA and it brought together about 150 or 130 scientists from all over the world who came together because they wanted to use the technology and they had to be able to develop the guidelines of how we could do this safely.
And out of that Asilomar conference came a strong consensus on the part of everybody there that we should ask the government to establish guidelines or regulations, if you want to call them that, by which you had to proceed with any kind of recombinant DNA permits and they were very, very good. But I think now, as I look back on that period, we made some very, very fundamental decisions which were important but we were so naïve we didn’t understand when we made those decisions and the first one was the focus, the discussion at the Asilomar conference, which was three days, on just the question of safety. Is there anything dangerous in doing these kinds of experiments? And which kinds of experiments are the most dangerous? Which kinds of experiments are less dangerous? Which kinds of experiments are not dangerous at all?
And then to come out of that with a scheme that says for the most dangerous experiments, these are the requirements that you must do; for the next ones, these are the requirements and for the other ones there are no requirements and we put in place a mechanism to review the guidelines periodically so they could change so today there are no more guidelines because the experience and experiments that have been done have shown that the original concerns which we really believed were possible were in fact, didn’t exist and so there are no more guidelines except for a very, very few experiments, but the smart thing was to focus it on only public health. That is danger. We didn’t discuss biological warfare, we didn’t discuss gene therapy, we didn’t discuss gene …
It had never occurred to you …
Paul Berg: … or genetically modified foods because those were, we foresaw that they would come, but they were so far in the future that there was no point to spend time to debate. Today, many people have criticised the Asilomar conference because it didn’t consider ethical and moral issues of the work. We focused on the science. Was it dangerous? Could we find the way to do this safely? And that’s why it was so successful.
So do you think it should be time now for Asilomar 3?
Paul Berg: Well, we had an Asilomar 3 and it was to discuss whether an Asilomar model, whether that way of approaching problems could be applied to today’s problems and different people had different views.
When was it?
Paul Berg: This was in, about 2,5 years ago and in my view, which I said at the conference, I don’t think that the model that we used in 1975 would work with any of the major problems today.
Paul Berg: Because today you have very, very strongly entrenched views and constituencies. They have hardened their views so one of them, for example, if you just take stem cells which today you have a very strong religious movement. You cannot come together in a meeting of two or three days and convince each other that it is ok to work with stem cells or it’s forbidden to work with stem cells. People talk right past each other.
Do you think that some parts of research or of science should be forbidden?
Paul Berg: I think when there is clear evidence of inflicting damage or danger, then I think there’s a strong argument that things should be forbidden but I think they should only be forbidden for specific time intervals, so for example if there’s a moratorium on a particular line of research, or even if you pass legislation to forbid certain kinds of research, it should only last, say, five years and in five years to re-examine the issue again. Maybe the agreement is it is still something that shouldn’t be done and so you go forward this way; but in many cases in our country, if the government passes a Bill and makes it law, sometimes it’s exceedingly difficult to change it and so you’re locked into a situation which, five years later, doesn’t look the right decision. Just if you have a minute, I just want to mention one interesting anecdote.
This year, the Alaska Foundation, which was a major award giving foundation in the US, gave the award to a man named Robert Edwards. Robert Edwards was the man who invented in vitro fertilisation. 25 years ago, when he was doing the preliminary experiments, I can tell you that the huge protests were the same as they are today for stem cells. People thought he was going to make monsters, that the was going to produce children who were going to be deformed and very incapacitated. So today we have a million, more than a million live births, many people who have had children they could not have had before, so 25 years later we recognise that this was a major health and medical benefit and we give him a big prize. Alaska Award often comes just before the Nobel Prize, and yet if you think back at that time, if we would’ve passed the law which says IVF is forbidden, against the law, we would’ve shut down a whole very important advancement and I think we can point to recombinant DNA as another.
Recombinant DNA came very close in our country and I know in Sweden also, to being forbidden. We would’ve lost the entire bio-technology revolution, so we have to think very clearly before you pass laws that forbid scientific work and so the question you asked is are there some lines of science that should be forbidden? Temporarily perhaps, but certainly not forever.
Thank you very much for taking your time. Thank you.
Paul Berg: You’re welcome.
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