Philip Leder

Making Ourselves Over

VTR Date: November 8, 1987

Dr. Philip Leder discusses the implications of biotechnology.


GUEST: Dr. Philip Leder
VTR: 11/8/1987

I’m Richard Heffner, your host on THE OPEN MIND. And I think that most of us would identify our subject today either as genetic engineering or genetic manipulation depending, perhaps, upon whether our hopes or our fears loom larger. Will scientists learn what there is to know about our genetic makeup – one scientist anticipates that someday “the complete recipe for a human being will be revealed” – essentially to the end that longer and better life, freedom from disease, can be engineered? Or will this incessant nibbling away at forbidden fruit from the tree of knowledge mark our further fall from innocence as, Frankenstein-like, we manipulate ourselves and our progeny into monsterdom? So, there are hopes and there are fears…both growing rapidly, and perhaps without full warrant, as scientists today succeed more and more in breaking the code of life, developing that “complete recipe for a human being”. Unfortunately, so many on the one hand “point with pride” and, on the other, “view with alarm”, that frequently what indeed we can and should do with what indeed we do now is lost sight of. And today I’d like to raise those questions with a distinguished scientist at the very forefront of research into our genetic code. Dr. Philip Leder is Chairman of the Department of Genetics at Harvard University’s Medical School and winner now of the 1987 prestigious Albert Lasker Basic Medical Research Award. The Lasker Award cites Dr. Leder “for his elegant studies of the genetic basis of antibody diversity and the role of genetic rearrangement in carcinogenesis”. And I want to start right off today by asking Dr. Leder about his oath as a physician to “do no harm” and whether this genetic “rearrangement” or “engineering” or “manipulation” is likely to “do no harm”. Fair question?

Leder: Well, you’ve certainly started out with one of the most important, perhaps not one of the most difficult, but certainly the most important questions you can ask. And quite naturally on any medical research voyage that is undertaken, the consideration to “do no harm” has to be uppermost in a scientist’s mind. But on the other hand, sitting idly by, seeking no further knowledge and no further opportunity to gain knowledge in the service of mankind is another way of doing great harm. So, couched in those terms, I think the imperative is to move ahead, seeking new knowledge for the purpose of relieving suffering, diagnosing, preventing and treating disease.

Heffner: What’s the downside in that?

Leder: The downside is to continue the terrible waste that is represented in a whole variety of diseases, both those that we commonly associate with inheritance and those diseases that affect much larger numbers of people that we commonly don’t conventionally think of as genetic disorders. Basically an attempt to understand how genes operate is relevant to problems as serious and diverse as heart disease, hypertension, diabetes and cancer. Those are not issues, not to mention, for example the infectious disease that’s uppermost on many peoples’ minds these days, such as AIDS. To sit idly by and to do nothing because we are concerned about the consequences of new knowledge would indeed be very harmful and very deleterious.

Heffner: What do we know now about AIDS that may be of use in terms of genetic content?

Leder: Well, basically, the virus that causes AIDS is a rather simple creature in a sense, in that it carries around, just as you and I do, in its basic genetic material, in its chromosome, a small amount of genetic information which allows it to perpetuate itself and which allows it to insinuate itself into the host. The new developments in recombinant DNA technology, our new knowledge about the very structure of the genetic material has allowed scientists to isolate and to identify and to determine the structure of the small collection of genes that make up that virus. And that information has been transformed into tests which are being used to diagnose the virus and basically, the whole of the research effort which is directed towards understanding the life-cycle of that particular virus, not to mention others which are tremendously important in human disease, has been really a major thrust and this all has depended upon the revolution that has occurred in genetics in the course of the last decade.

Heffner: Do you know, Doctor, I realize that you put your emphasis upon the positive, as you should. When before I asked you about the downside, e really meant the downside of the efforts that you and other leading scientists are making to discover more about our own…the working of this frail instrument…a human being. Do you see any? Or do you want to stay away from what is going on in the public, an act of continuing concern?

Leder: Yes, I think that genetics, in general, perhaps properly, perhaps not, has been a focus of concern. When one thinks about the reasons why that is true and, for example there’s lesser concerns in other areas of biologic research, I think it relates to the fact that most of us realize that it is our posterity that is involved. And most of us would inevitably share a concern that any alteration that one makes in the genetic makeup of the species, whether it be a human being or whether it be a farm animal or some small organism, might be with us in terms of its consequences for good or possibly for bad for generations to come. But on the other hand, you know the struggle to gain new knowledge is not just a cultural activity, it’s an activity with a real and precise and measurable outcome at the end. Knowledge, in its own sake…for its own sake, has no special value for good or evil. In the end, it’s the uses to which that knowledge is put. One has to weigh that. We really know enough from classical genetics and really the insane and horrific philosophy that guided the regime that rose to power in Germany in the 1930s provides us with ample examples of that, to know that genetics can be used to…as in any science, physical sciences or biologic, to horrendous goals. But on the other hand, and that must certainly be true of modern genetics as it’s true of our modern biochemistries, as it’s true of our modern physics, but in the last analysis, we can’t be frightened by whatever insane use can be made of knowledge because that’s an aberration of which society must always be on guard. But really our purpose is to move ahead because to remain at the point we now see ourselves is to allow this tremendous accumulation of frustration that we see in the face of disease.

Heffner: What responsibility do you take as a researcher, the Lasker Award refers to the “elegant nature” of your researches. What responsibility do you take as a scientist for the use of what you uncover?

Leder: well you take a…I think a major level of responsibility in the end for the use. At least for the near-term purposes of the research. First of all, when you undertake to understand something, let’s say that it’s the fundamental nature of malignancy. You sit down and you think about what possible model you could devise to understand how the process of malignancy or cancer could really arise. You design a reasonable model. You think about an experimental system which would test that reasonable model. You consider the results that you would obtain. You hold them up to testing the validity of your model and further downstream you certainly do think about the consequences that that could have. It can get a little ridiculous at times because, you know, one would have to consider the tremendous impact of eliminating cancer as a disease were this strategy to be successful. I’m not by any means predicting any short-term success in this area. But those implications would be very profound. They would be economic, they would be moral, they would affect the lifespan of the individual, but certainly the would have a tremendous impact on the alleviation of human suffering and would remove from us a scourge of what is a terrible and disabling and painful disease.

Heffner: Once said, then you move on from the positives to the things we fear. What responsibility does the scientist have for those?

Leder: Well, I think that the responsibility for the downside implications of any research undertaking, and I don’t want to really make…limit this to the field of genetics, our knowledge of the human genome, our knowledge, as you put it, of the recipe necessary for the formulation of a human being or any other organism. That responsibility doesn’t rest with the scientist by him or herself. That responsibility is really society’s. That responsibility falls to all of us who are concerned about our fate on this very fragile planet. And so while scientists can be in a position to explain to the layman the fundamentals of the scientific aspects f the field, once those are firmly grasped, it remains the responsibility of all of us to make further decisions. I think one of the major misunderstandings in a sense that we, as geneticists, confront is that a lot of the scenarios that are held up as perhaps uncomfortable or terrifying are really borrowings from fiction. After all, you mentioned Frankenstein at the beginning of this program and somehow we lose sight of the fact that Frankenstein is really a fictional character and is not really a scientific entity at all. And the possibility that genetics could be used to create such a horrendous monster is about as remote as the possibility that a movie could be used to make such horrendous and real-life monster.

Heffner: But, Dr. Leder, then one turns to Brave New World, if you want to stay with fiction and we come a little closer to manipulation, we come a little closer to what people do fear today. So, though I brought up the Frankenstein metaphor, I think one could say fiction, is it that fiction is stranger than truth or truth is stranger than fiction? I think the fear is that what we do may become even more dangerous, stranger than the fiction that has frightened us.

Leder: Well, as I said before, the possibility that genetics could be used in a way that would be inconsistent with humane goals, you know that there is really a scientific basis for conjuring up some kind of solution that would permit us to modify the real…really the fundamental nature of human beings as a species, is a fiction. That’s ridiculous. That’s not something to be feared, that is, I mean, it’s not something that’s within the realm of possibility. Really there are important ethical questions that arise from genetics and these will come in terms of making choices about how we deal with diseases that we can diagnose and diseases that we can treat. But what is really not fully understood is that a lot of our concerns are a reflection of our imperfect understanding of what really we think we can do in the realm of genetics. In other words, we are shadow-boxing with what is part fiction and part reality.

Heffner: What are those moral questions that you refer to?

Leder: Well, for example, if we do have the possibility of recognizing genetic susceptibilities to certain diseases, which we do…a couple who is at risk for that disease now has an additional option, for example, as to whether or not they want to proceed with a pregnancy that might result in an affected individual, let’s take some disease like cystic fibrosis or Duchenne’s muscular dystrophy – these are tragic disorders of childhood that have an inevitable downward and fatal outcome in the end. Such a couple, having such a child might be concerned with an additional pregnancy. Now the tools are available for allowing a physician and a family to make the diagnosis of such a disorder, intra utero, and allowing the couple involved to make the very difficult decision as to whether they would a) wish to proceed with a pregnancy and b) if they have an affected fetus whether they would like to continue with the pregnancy. And that’s a question that many of us would deal with in many different ways. And it is a real moral and ethical dilemma, but one that we face now, today, every day.

Heffner: As a medical person, do you find…you say “we face those dilemmas every day” are we in any organized fashion, learning to deal with them?

Leder: Well, the physicians who are in a position to encounter patients at this level do, in fact, deal with them and they are presented to the families that are concerned in a way that allows them, first of all, to understand the risks that are involved and further to understand the procedures that are involved, before going forward, so indeed there is. And I’m sure I don’t have to tell you that religious bodies and governmental bodies have considered and continue to consider the questions that are involved. There are many different answers as we all also know to these questions, depending upon our philosophical and religious orientation.

Heffner: We used to laugh at the idea of the self-made man, we seem to be about to be a self-made species.

Leder: Well, I think we can still continue to laugh about the self-made man in terms of a self-made species. That’s not in the cards. Minor modifications in animals that are used for…in the world of agriculture, perhaps. But dramatic changes, indeed changes in the human species that will be perpetuated, that’s not in the cards at this point.

Heffner: Why isn’t it in the cards?

Leder: it’s just…it could be for many reasons. But the first and foremost reason is that the technology now is not sufficiently effective or predictable to allow the alteration of the human germ line, which is essentially that part of your posterity which is passed on from parents to offspring. The technology isn’t there, let alone the ethical underpinnings of such an undertaking.

Heffner: If you had to make a bet, a straight and honest one, how long will it take before the technological information is there?

Leder: Well, I’m too much of a scientist to say “never” and too timid to really make a prediction regarding something that I don’t see the rough outlines of. It’s over the horizon, for sure, a part of scientific achievement which is difficult to write down with pen and paper as to exactly how it will come about and therefore, not possible really to make a prediction about how long it will take us to arrive at that point.

Heffner: Are you satisfied that there are enough institutional controls, governmental, university-wide, on experimentation? Are you satisfied that they are…

Leder: Well, as you know, a very unique feature about the development, the recent developments in genetics has been the fact that scientists, about ten years ago, really came together at the dawn of what was a very new field, at the dawn of what was essentially a revolution in biology, to consider the implications of their work. To consider them so that they could undertake the proper safeguards and undertake the proper precautions necessary to go forward, safely. And I think they bent over backwards because of a concern as to how the public really would react to these new developments in science.

Heffner: And yet some of us are aware that there have been some instances in which those regulations have not been followed. Is that a fair statement?

Leder: There are certainly isolated instances in which the regulations have not been followed. In those cases principally, for example, the agricultural experiments which were done on the infection of trees and so on. And the release of organisms into the environment. The fundamental experiments that were done were basically safe and that’s the very fortunate thing, although no one could really condone the flaunting of regulations that were put in place both for the purposes of safety and for the purposes of addressing public concerns.

Heffner: Dr. Leder, what can we do now? And what can we anticipate that we will be able to do in the next generation by way of making those fundamental changes that will make for a better life, greater health?

Leder: The kind of fundamental changes that we are talking about, at least that we can foresee, will come in our ability to understand in more precise molecular terms a variety of disease entities. I could use almost any example, I think. But certainly now we have the ability to make the diagnosis of several clearly genetic diseases, and from these we can diagnose, for example, the carrier state, we can identify individuals who might have their offspring at risk for the development of these disorders and that’s very clear. But I think the great promise lies in the area of diseases as I said earlier, which we don’t conventionally think of as genetic disease. For example, the problem of malignancy, the problem of cancer. Cancer is fundamentally a disease which often involves damage occurring to genes. That doesn’t mean that it is a disease which you inherit the propensity of from your parents. Rather, it is a disease that involves, very often, a fundamental and discrete damage occurring at the level of a gene that probably controls the way a cell grows. And once that gene or collection of genes is damaged, those growth controls are released or perturbed and the net response is that cells grow wildly and out of control. A disease that affects one out of five people in our population, it’s not a minor disorder at all. Genetics now allows the scientist to reach in to the tumor, to reach into its fundamental genetic chemical and pull out precisely those genes that are involved in changing its growth pattern. And why is that an advantage? Well, it’s an advantage because you can determine then with great precision, the product of that gene and from it, begin to guess about what it does chemically in the cell. And once one learns what it does chemically in the cell, what the basic chemistry of the product of that gene is, one can begin to design rational forms of treatment that could effectively re-institute the regulation which is lost through that genetic damage. Before this revolution occurred in genetics, that remained an entirely unapproachable area of investigation, it was a pure black box. And now one can actually reach in and understand it, determine its structure in concrete terms. And that’s a tremendous, tremendously powerful ability.

Heffner: And you anticipate the development of this ability?

Leder: Oh yes, I mean it is the major force now guiding us in the area of cancer research. It is also a major force in understanding coronary artery disease. So, genetics, as a technology and as a way of thinking about problems now becomes the most…probably it’s not an exaggeration to say…it’s the most potent vehicle for advance in understanding in a variety of biological fields. And in a variety of disease states.

Heffner: Dr Leder you know someone wrote somewhere that we were talking about a molecular mistake at times in talking about certain diseases, or a genetic mistake. And I keep coming back to the thought that if god or nature’s god could make such mistakes, what we must be able to make by way of mistakes.

Leder: Well, actually we’re pikers by comparison to the mistakes that can be made in nature. Our ability to design genes is insignificant in the framework of all of evolution that has occurred to date. As you and I sit here, literally millions of cells inside each of us are turning over, resynthesizing their DNA and each and every one has the opportunity to make a mistake every time it’s duplicated. And it happens very often. But fortunately evolution has placed in each of our cells an ability to correct in large measure those mistakes. So it’s very likely that any alteration in the structure of the genome that is within our humble ability to undertake, it’s been done already in evolution. It’s been thought of already, it’s probably occurred many, many times already and been fitted into the equation.

Heffner: Do you really feel that easy about it? Seriously.

Leder: As I said, knowing the strengths and the ability and the power of the technology, I’m not concerned really at all. I think that basically what one has to appreciate is that when one deals with a dangerous organism, hepatitis virus, AIDS virus, what have you, that’s obviously a very hazardous, lethal virus and has to be treated with immense respect. Other aspects of genetics are really beyond our…virtually beyond our capacity to inflict further harm, that is harm that has not been quote/unquote thought of by the evolutionary process itself.

Heffner: Is the medical profession, we just have a couple of minutes let…is the medical profession doing what you think it ought to do by way of preparing its practitioners to deal with whatever abilities we do develop?

Leder: The fruits of this revolution in biology are only now beginning to reach the level of medical practice. And for example, the use of certain pharmaceutical reagents that can be developed using recombinant DNA techniques are now available. Let’s just take one example, growth hormone. Other examples would be the use of ant hemophilia factors which will be used in that tragic disorder. But I think that we have a problem in that regard in that we have many, many generations of physicians to which this is all very new. But physicians are very scrupulous about learning what’s going on in their field and undergo a process of continuous education, and that probably represents one of the major goals towards which we will have to strive.

Heffner: Dr. Leder I do appreciate you joining me today, I think I brought in every cliché of fear available to mankind and I must say your response makes one feel a lot more comfortable. Thank you so much for joining me today on The Open Mind.

Leder: A pleasure, pleasure.

Heffner: And thanks, too, to you in the audience. I hope you’ll join us again next time. And if you care to share your thoughts about today’s program, please write to THE OPEN MIND, P.O. Box 7977, FDR Station, New York, NY 10150. For transcripts send $2.00 in check or money order. Meanwhile, as another old friend used to say, “Good night and good luck.”

Continuing production of this series has generously been made possible by grants from: The Rosalind P Walter Foundation; the M. Weiner Foundation of New Jersey; the Mediators and Richard and Gloria Manney; the Richard Lounsbery Foundation; Mr. Lawrence A. Wein; and the New York Times Company Foundation.