Genetic Manipulation

THE OPEN MIND
Host: Richard D. Heffner
Guest: Lewis Thomas
Title: “Genetic Manipulation”
VTR: 1/10/83

I’m Richard Heffner, your host on THE OPEN MIND. For some time now the press has reported the concern of many of us in this nation about the ways in which some contemporary scientists seem to us to be playing God. Now only physicists now with their ever-growing nuclear capacity to eliminate mankind, but rather molecular biologists too with their increasing ability to manipulate the very stuff of life, what has always been the genetic continuum from one generation to another. This will be the most important concern to face mankind. Clearly it needs to be examined as carefully and as reasonably as our time on this planet and our wisdom permit.

So that I’ve invited today on THE OPEN MIND the wisest man I know. Maybe we can begin to touch on these concerns. Later do so even more. Dr. Lewis Thomas, Chancellor of the Memorial Sloan Kettering Cancer Institute is also the former Dean of the medical schools at both NYU and Yale University. He’s one of the most highly regarded medical scientists of our times.

Dr. Thomas, thank you for joining me today on THE OPEN MIND. We won’t talk about your new book today, but I would like to talk about – we’ll do that another time – I would like to talk about this matter of genetic manipulation and ask you whether it concerns you as it does so many of the rest of us.

THOMAS: I don’t know. It concerns me, but mostly at the moment because of the misapprehensions about it that are abroad in the press and, forgive me, in the media.

HEFFNER: You mean my misapprehensions?

THOMAS: I wouldn’t want to rank the discipline of molecular genetics, sometimes miscalled “genetic engineering”, as a hazard anywhere at all near the hazard of thermonuclear warfare. I don’t think that there is any resemblance between these two kinds of risk. I believe that the scientific community and indeed the whole community at large ought to be concentrating all of their apprehensions for the future on nuclear bombs. That I think is what will do the species in if anything is going to do it in.

Now, as top the risks of this line of research, they were regarded by the scientists doing the work themselves seven or eight years ago as possible dangers. It was thought that the organism used for, principally used for this kind of work, E. coli, a very ubiquitous kind of bacteria, might if its own genetic machine were altered then get loose from a laboratory and acquire disease-making capacities that it didn’t have before and produce some kind of epidemic. So the scientists themselves declared a moratorium on the research until it could be carefully reviewed and until some guidelines could be drawn up. And in the last several years I think it’s become clear to most if not all of the professional scientists engaged in the work that the dangers were very considerably overblown and overstated at the outset.

And now there’s a new misapprehension about his technology. And it’s being made to seem as though a lot of money can be made out of it. And much of the interest one senses in the press is in the possible applicability of the technology for making one or another product for the marketplace. And this may be true. It may be that some useful things can be made. But it overlooks the real importance of the technology. This is the most important thing that’s happened in biological science in this century. And very possibly the most important thing that’s happened in biology since Darwin. It places in the hands of good scientists a technique for finding out how things work, not for making products or not for selling things, but for penetrating much more deeply into the machinery of life than has ever been conceivable before. It is possible now to sort out the genomes of any number of different species including our own, to map them, to identify the precise molecular configurations of strings of DNA that comprise the genes, and it looks to me, forget about parochial interests, as the best of all possible ways to find out what really is going on in cancer cells. And thereafter, having found out what’s really going on, to begin to think about ways of, really good ways of preventing or reversing the process.

There are applications like that all over the place in the study of disease mechanisms that we’ve never had available to us before. I don’t really see the danger to it. I’m not sure that it’s infinitely possible to change the germ plasm itself. At least it’s not going to be easy. It’s not going to be too difficult to change the genetic machinery inside somatic cells, the body’s already fully formed cells. But the change the germ plasm is another matter, and a much more difficult one. It’s been done in the animals that were persuaded to use a different gene for the preparation of growth hormone. And we’ve got the recent story about very large mice coming from a line of what was really only been normal sized mice. And the generations thereafter had the same large size and the same kind of growth hormone. So it is possible to change the germ plasm. But I don’t really see it happening for applications to medicine in the future.

HEFFNER: I like so much your use of your word “persuaded”. You don’t want to talk about manipulation there. You talk about “persuaded”. Why do you choose that word?

THOMAS: I forget how I used it.

HEFFNER: Well, you said that the mice had been persuaded.

THOMAS: Ah, yeah. Well, they’d been manipulated, to be sure. And a gene from a larger animal had been inserted, the gene reflecting the capacity to the larger animal’s gene had been inserted for the manufacture of a single gene product, a single hormone, growth hormone.

HEFFNER: Well, of course, in the last few minutes what’s happened is what happens many times. Somebody in the media begins a program by saying what may seem to you as a scientist rather outrageous and alarmist things, talks comparatively about the most this, that, and the other thing, and then my scientific friend begins by saying, not on a scale, but by and large this doesn’t require that much concern on our part, and what requires more concern of course it’s the potential for destroying ourselves with nuclear weapons. But if we could only – and I have that responsibility – separate out the comparatives and the worsts and the bests, let me then just ask again. Are you really sanguine and satisfied that we are not running risks with the persuasion of genetic material to change?

THOMAS: I suppose I’d better back off a little bit, because I have been talking out of what’s called “enlightened self-interest”. I’m deeply concerned that basic biological science be fostered and encouraged, especially in this country.

HEFFNER: You don’t want people like me stirring up a storm that will lead to limiting the knowledge…

THOMAS: Yeah, I don’t want a lot of regulation of a research technology that has such immense promise for the future, and particularly as a physician I would hate to see this approach to research restricted because of hazards that can be imagined up in the face of the possible usefulness of it for understanding human disease mechanisms in the near term.

HEFFNER: Do you reject Murphy’s law that if something can go wrong it will?

THOMAS: Well, it hasn’t gone wrong yet in this technology. There hasn’t been, as far as I know, a single untoward effect or a single, there’s been no disease that has occurred in any species or plant yet as a result of the technology.

HEFFNER: Dr. Thomas, when I’m arguing, discussing the matter with those who are gung-ho for nuclear power and perhaps for the use of nuclear power eventually in weaponry, I hear constantly, “Now, look, nothing untoward has happened as yet. None of these things have gotten out of hand”. I suspect that in the area of nuclear energy that’s an argument that would set your hackles rising, while…

THOMAS: Well, they’re not.

HEFFNER: No?

THOMAS: No. Because I tend to agree with it. I think nuclear power, although hazardous and requiring a much more magnificent kind of engineering than has been applied to it thus far, is not in the same league with nuclear weapons. That, I think, is, I don’t anybody would argue with you about that. The science that is being done and has been done in the past for the development of nuclear weaponry is, I think should be stopped and should have been stopped long ago.

HEFFNER: But there are those of us who feel as though Pandora’s Box in both areas, in biological, molecular biology area too has been opened. And yet you’re really not too concerned about it.

THOMAS: No, I’m not. I don’t really foresee, I can’t manufacture a scenario that scares me as far as genetic, molecular genetics and research along that line is concerned. I understand the feeling that there is something sacred about the genetic apparatus and the germ plasm, and I would hope that before research designed to manipulate the germ plasm was undertaken that that would be carefully scrutinized by the bodies in government that are principally if not entirely responsible for the funding of this kind of science in this country. But I can’t make up a story that scares me. I don’t think anybody’s going to go around cloning eminent politicians. I don’t think…I mean, I think it would cost too much and it wouldn’t get anywhere. I don’t think anybody’s going to try to change human behavior by modifying genes because there isn’t anybody on earth I think who has the ghost of an idea how genes do influence, if they do influence, human behavior. But nobody’s going to fool around with that because the file at large is made up of people who are totally ignorant about it.

HEFFNER: But you know, when you talk about all the safeguards that have been taken, and you have spoken about that, obviously they’ve been taken because there is something that is of concern. The elaborate apparatus for establishing these safeguards has been built up because obviously biologists have been concerned about something happening. Now, if those safeguards have had to have been built, certainly they could have been built in a faulty way. And I use the word “fault” as I think about nuclear contaminants, too.

THOMAS: Well, I don’t think it‘s the same sort of matter. The safeguards that were proposed very early on were proposed by the scientists themselves. Gradually over the last ten recent years it has been found some of them are unnecessary, and some of the restrictions on this kind of research have therefore been taken away. There is still a great deal of care that goes into the work in the laboratories where the work is going on. And I think that will continue. This is field where, it’s the only field I know of in biomedical science where there are standing committees in Washington and people within the NIH whose principal responsibility it is to make sure that the existing guidelines are not violated.

HEFFNER: Does that make you unhappy or uneasy, government involvement?

THOMAS: Oh, no. I think the government has every right to be involved in this. The government’s paying for most of the research, if not all of it. The people of the country really are the ones who have to decide what is to go on in the furtherance of science. The scientific community has an obligation to the government and to the people and responsibilities to it. And I’m not objecting to regulation. But I would object if the regulation were done in an atmosphere of unreality where hazards are being imagined up that don’t really exist. And I’d object very strongly if the regulation as we feared might happen early on, eight or nine, eight years ago, might bring a halt to this research altogether. I don’t think the scientists, you know, are really as interested in changing the genomes and in meddling with nature as they are in using recombinant DNA technology for finding out how cells work, and especially finding how they go wrong. This is clearly at the moment the technology is used is producing more information at a deep level about cancer. And we could have dreamt that just five or six years ago. It’s now known for example that there are strings of DNA that look like viruses, behave like viruses, but they are normal parts of normal cells. And it’s possible now to find out how they’re switched on and the switching mechanism can be examined just as if you had it between your fingers, although it’s a switching mechanism that involves just a short string of molecules. Work like that, I think, really can’t be regarded as in any way hazardous. And if it’s not done we’re not going to find out how cancer works. But you can’t write any scenario for the laboratories that are studying cancer biology, using recombinant DNA technology, and even make a guess at a possible hazard. There isn’t any, quite clearly.

The bacteria part of it is another story. I think that there are still hazards to changing the genetic apparatus of bacteria carelessly or frivolously. I would think it would be a mistake to insert genes for lethal toxins in bacteria that might then get loose and cause a different kind of disease. But I think it’s quite unlikely.

HEFFNER: Didn’t we read something about that recently in terms of, what was it, diphtheria?

THOMAS: Diphtheria toxin can be produced by these technologies from bacteria that normally don’t make it. The bacteria that are being used for it are bacteria that rally can’t live on their own. If they escape from the laboratory they would drop dead. They’re very carefully contained. I’m not altogether happy about that experiment, by the way. I don’t know why it was necessary to do it. I suppose there was a good reason. We’ve got diphtheria bacilli in the business of making toxin already and I don’t quite understand that.

HEFFNER: Well, why aren’t you happy, or why are you unhappy about it?

THOMAS: Well, I’d like to know more than I do about it, and I don’t know enough about it to make a sensible comment. But I’m a little worried by that one.

HEFFNER: But if you are worried, given what you’ve just said, about the low levels of concern, your threshold of concern in this area is very high, and yet it’s been ticked off, if thresholds are ticked off here. What about the rest of us who are so naïve and frightened?

THOMAS: As I said, I’d like to know more about what the reasons for that line were. I know what the investigators are after. They’re after a better supply of highly purified diphtheria toxin. And the reason they want it is that it now looks as though it’s possible if you have the diphtheria toxin in highly purified form to attach it to a new kind of antibody that’s been discovered in the last few years called monoclonal antibody, having antibody reactive with cancer cells antigens at their surfaces and not with any other kind of cells. And then you have a kind of a time bomb. You give the antibody to an animal with cancer. It will go straight to the cancer cells and lodge there but nowhere else in any other tissue, than release diphtheria toxin which will kill all the cancer cells selectively. It’s a neat, theoretically anyway, an eat approach to a kind of chemotherapy for cancer that hasn’t been thought of before. And that I think must be the justification for wanting to get a larger supply of, under controlled conditions, of diphtheria toxin. And if the technology were to wok and we had then a new form of immunotherapy or cancer, I think it would have been worth what I would guess is really a very, very small risk. That is a risk of having he new bacteria with the new genes for diphtheria toxin get loose out into the environment.

HEFFNER: That’s a vision the rest of us have, of course, those of us who are quite so naïve, we do see something escaping from the scientist’s laboratory, and we don’t have to think of it as a mad scientist, either.

THOMAS: Well, the thing that makes it seem much safer than it used to is that the strains of, strain of E. coli that’s used for this kind of work has itself been selectively altered by picking up spontaneous mutants to become a more and more fragile organism incapable of living except under highly artificial laboratory conditions. It has nutritional requirements that can’t be met in any other environment than the Petri dishes and flasks that are used in the labs. So it’s not a hazard itself.

HEFFNER: You said a moment ago that of course you accept the notion of governmental, if the word were not “controls”, at least government involvement in setting standards and safeguards. You think this is true universally over the scientific community?

THOMAS: Yeah, I think so. I think so. I think the scientists worry a lot about coming under regulatory controls by huge faceless bureaucracy, having decisions run through committee after committee in Washington. I think what the scientists want and need for this line of work is a set of guidelines, which they now have from the NIH. And they also want to be sure that those guidelines are continually under review and can be changed in one direction or another as the scientific evidence comes in. I think the scientists are as worried as anybody else about having regulatory agencies looking over their shoulder and cooking up new rules for the way science should be done, or worse still, cooking up new notions about what should or should not be inquired into. As a, I suppose as a group – this may not be true, this is my own view – is that there really aren’t any questions about nature that can be asked by science that should not be asked because of dangers to humanity that might come from those questions. I’m talking now about the kinds of questions that are raised in basic research; not at all about questions like can we make an ABM system work or can we destroy missiles with lasers in space. That’s a different kind of science.

HEFFNER: Yes, but Dr. Thomas, no one has ever protested against the raising of questions. What has been the concern of many is what physical acts take place in the answering of those questions.

THOMAS: Well, your worry is simply the dangers involved in the research itself. You’ve got another worry, which is you might learn some things about how genes work and about how cells work. It might then place in our hands techniques for changing plants and animals and bacteria and human beings and change human behavior. That’s really the anxiety. I think, in the public mind about this. But not so much that E. coli will escape from the laboratories. That was a fear several years ago. I think the fear now is that scientists are really becoming mad scientists and they’re about to change the species.

HEFFNER: Dr. Thomas, is that so strange when the most extraordinary scientific development, if I may call it that, in this century is now posing what you’ve described as the permanent threat to mankind? Is there, aren’t you a little concerned that at times this pure science, this pure research will result in, let us say, a weapon that can be used as we are fearful that nuclear energy will be used in a weapon?

THOMAS: I just can’t imagine such a weapon. I don’t know very much about biological warfare, but my impression of it in the past has been that it’s a very poor way to conduct military affairs. The tendency is to back fire against the users, and it rarely accomplishes what it’s supposed to accomplish, and it’s impossible to do it in secrecy and so forth. I don’t have any reservations at all about what happens when a ten-megaton nuclear bomb is exploded over Manhattan or Zurich or wherever. That’s not a matter of guess work. I know for a certainty that if an exchange of nuclear bombs were begun between us, say, and the Soviets or any other system, that civilization would be destroyed, society would be destroyed. Some humans would survive, but society would be not just devastated, it would be, I think, destroyed. And medicine, by the way, would have no contribution to make to mend things. This other, biological science approach does not…in my wildest stretches of my imagination I can’t imagine turning that into weaponry. And I really can’t imagine doing harm under the kinds of guidelines that now exist for this research.

HEFFNER: Okay, I think that’s fair enough. And as we reach the end of the program it’s quite clear we have to go on and come back to this other area of much – well, not of much greater concern to you – but of real concern to you, where this doesn’t seem to disturb you very much…the matter of nuclear destruction is so imminent perhaps?

THOMAS: Yeah, perhaps…well, in a world that contains as many nuclear bombs as this one contains at the moment, all ready to go, I just can’t worry about biological science and its dangers.

HEFFNER: Dr. Lewis Thomas, then come back again and join me on THE OPEN MIND to talk about the other danger.

And thanks, too, to you in the audience. I hope that you will join us here again on THE OPEN MIND. Meanwhile, as an old friend used to say, “Good night, and good luck”.