Engineering the Human Germline Symposium

Summary Report June, 1998 This one-day symposium organized by UCLA's Science, Technology, and Society Program at the Center for the Study of Evolution and the Origin of Life was funded through grants by the Greenwall Foundation and the Alfred P. Sloan Foundation

Gregory Stock
Director, Program on Science, Technology, and Society
Center for the Study of Evolution and the Origin of Life
University of California, Los Angeles
 

John Campbell
Symposium co-convener and Professor of Neurobiology, UCLA Medical School
Senior Science Advisor: Program on Science, Technology, and Society

The UCLA Program on Science, Technology and Society at the Center for the Study of Evolution and the Origin of Life would like to express special gratitude to the invited speakers at the Engineering the Human Germline Symposium for their willingness to participate thoughtfully and candidly at the event. These presenters were: W. French Anderson, Andrea Bonnicksen, Mario Capecchi, John Fletcher, Leroy Hood, Daniel Koshland, Jr., Michael Rose, Lee Silver and James Watson. Obviously, the symposium could not have succeeded without them. We would also like to thank William Stubing from the Greenwall Foundation and Doron Weber from the Alfred P. Sloan Foundation for their generous support. Their desire to foster increased public dialogue and awareness of the emerging technology of germline genetic engineering is greatly appreciated. Finally, we’d like to thank the Director, William Schopf, and the staff of the Center for the Study of Evolution and the Origin of Life for their ongoing support and assistance, and Donald Ponturo, Associate Director of Special Projects in the Science, Technology, and Society Program for his many contributions to the symposium and this summary report.

Executive Summary

Symposium Overview

Presentation Abstracts and

Speaker Biographies

Key Points and Highlights

Policy Recommendations
 

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Executive Summary

To assess the potential of human germline engineering over the next twenty years.

To provide a solid scientific foundation for future public policy discussions on this topic.

To examine scientific and ethical arguments for and against germline engineering.

To invigorate and deepen public debate about human germline engineering.

Our hope was that a candid look at this controversial topic by key voices in the academic community would significantly elevate public discussion. Questions about human germline engineering are often parried with the response that the technology is too distant for us to worry about now, though it may be an important issue for our children or grandchildren. This is no longer true. The potential exists to do primitive human germline engineering now, though not with the safety and reliability we demand in human medicine.

Since a goal of this symposium was to catalyze broad discussion of germline engineering, in addition to the individual presentations, there was a free-wheeling panel that for an hour and a half candidly and openly discussed many of the difficult issues surrounding germline engineering. A more august, qualified, and forthright panel is hard to imagine. Of the eight scientists (James Watson, Daniel Koshland Jr., Mario Capecchi, Lee Hood, French Anderson, Michael Rose, Lee Silver, and John Campbell), half are members of the National Academy and hold prestigious prizes including the Nobel Prize, the Kyoto Prize, and the National Medal of Science, some are (or have been) editors of key journals such as Science, PNAS, Mammalian Genome, and Human Gene Therapy. As for the panel’s non-scientists, John Fletcher was the first head of NIH’s bioethics program and Andrea Bonnicksen is on the ethics committee of the American Society for Reproductive Science.

This symposium -- the first broad appraisal of germline engineering -- was free and open to the public. What was most interesting about the attendees was their diversity, not only in walks of life but in age. Middle and high-school students lined up at the door along with undergraduates, research scientists, physicians, writers, journalists, school teachers, and the interested general public. Attendees flew in from around the US, and from overseas. Germline engineering rouses intense interest, and whether one is inclined to embrace its possibilities or to worry about its misuse, this technology could change humanity’s path and deserves serious public discussion.

The UCLA symposium reached far beyond the thousand who filled the hall and the close-circuit-TV overflow room. Thoughtful print and broadcast pieces have discussed the event and human germline engineering itself. Not a single general article about human germline engineering appeared in any of the several thousand publications in the Dow Jones database during the three months before this symposium, in the three weeks following it there were 31 including front page stories in The New York Times and Washington Post.

Engineering the human germline consisted of seven talks, each covering a key scientific aspects of germline engineering, and a moderated panel discussion.

Some points of particular interest were:

That clever design of germline modifications could insure that they are not inherited by future generations and that activation of the genetic changes will require the consent of the recipient.

That germline engineering will be quite gradual in its introduction so we will have considerable time to reflect on its more profound implications.

That germline engineering will likely prove much easier and more versatile than somatic engineering.

That there are two very different approaches to germline engineering in humans: homologous replacement and the use of an artificial chromosome.

That the fundamental discoveries that will lead to germline engineering will occur whether we deliberately pursue them or not, because they will come out of research deeply embedded in mainstream efforts toward other important biomedical goals. So the question is not if, but when and how.

The FDA (Food and Drug Administration) should explicitly assert its authority to regulate human germline engineering.

The RAC (Recombinant Advisory Commission) should revise current policies and agree to entertain germline proposals.

The Human Genome Project’s ELSI (Ethical Legal and Social Implications) should lead an exploration of the challenges and potentials of human germline engineering.

The United States should resist any effort by UNESCO or other international bodies to block the exploration of human germline engineering.

No state or federal legislation to regulate germline gene therapy should be passed at this time.

The National Bioethics Advisory Commission (NBAC) should recommend revisions to US Patent law to address the challenges of germline technology and the widespread patenting of human genes.

A temporary voluntary moratorium on the cloning of humans should be supported by researchers and clinicians.

Any legislation to prevent the act of human cloning should explicitly state that it does not restrict research.

Back to Contents

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Symposium Overview

Welcome and Introduction - Gregory Stock

An evolutionary perspective on germline engineering and the interplay between human biology and technology.

A Vision for Practical Human Germline Engineering - John Campbell

Germline engineering may enable us to obtain the benefits of a century of genetic science. We now have the capacity to develop techniques to reliably and safely introduce DNA constructs into germ cells and could begin to conceive and design genetic therapies to ward off diseases and improve the quality of human life. This talk discusses how a program for human germline engineering might be structured and some of the technical hurdles it would face.

The Human Genome Project, Launch Pad for Human Genetic Engineering - Leroy Hood

Our ability to manipulate our genetics will be profoundly extended by the successful completion of the human genome project. What therapeutic enhancements to our genes might be feasible two decades from now? How close might we be to constructively altering the genes for our immune system, our development, and our nervous system? What role might biotechnology companies play in generating the knowledge and technology for human germline engineering and making it broadly available?

Ethics and Safety - Daniel Koshland, Jr.

Efforts to engineer the human germline need to satisfy appropriate ethical and safety requirements. What level of testing should be required before germline procedures are used with humans? How do the individual and global risks from human germline engineering compare with other medical and reproductive risks? Should guidelines be developed to regulate the methods by which the human genome is manipulated or merely the types of genetic changes allowed?

The Genetic Engineer's Tool Box - Mario R. Capecchi

Various procedures have vastly expanded our ability to manipulate the genome and further advances can be expected during the next two decades. This talk examines the techniques used to engineer genetic changes in various organisms and considers their technical potential for refinement into tools for safe, reliable germline engineering in humans. The potential scope of human germline manipulations in coming generations is also considered.

A New Front in the Battle Against Disease - W. French Anderson

Introducing healthy genes into diseased somatic cells is becoming an established medical practice. How big a step would it be to extend such therapy to germline cells? For which categories of disease might germline engineering be superior to such alternatives as somatic cell therapy, embryo selection, and traditional medical treatment? What new approaches to disease diagnosis and treatment might germline engineering offer us in two decades?

Aging: a Target for Germline Engineering - Michael Rose

Aging is multifaceted, affected by individual genes, interacting gene complexes, and environmental influences. This talk reviews our current understanding of the genetic factors which affect aging, considers how this knowledge may increase in the next two decades, and assesses the prospects of germline engineering both for ameliorating the degenerative changes that accompany aging and for retarding the aging process itself.

In-Vitro Fertilization: From Embryo Selection to Genetic Design - Lee Silver

In-vitro fertilization will soon offer many possible new twists to traditional human reproduction, from chimeric babies and children born to their grandparents, to detailed screening of individual embryos. This talk explores these possibilities, looking at how sophisticated such technologies as embryo screening might soon become, and how they might relate to germline engineering.

The Road Ahead: Human Germline Engineering and Society

This panel discussion moderated by Gregory Stock will consider the technical, social and ethical issues raised during the presentations. Panelists will include Andrea Bonnicksen, John Fletcher, James D. Watson, and the symposium speakers.

W. French Anderson is Director of Gene Therapy Laboratories and professor of biochemistry and pediatrics at the University of Southern California School of Medicine. It was Dr. Anderson’s pioneering efforts that led to the first human genetic engineering trials in 1991. Dr. Anderson holds an M.D. from Harvard Medical School. He has published extensively, holds many Board and Editorial positions, and is Editor-in-Chief of Human Gene Therapy.

Andrea L. Bonnicksen is Professor and Chair of the Political Science Department at Northern Illinois University. Dr. Bonnicksen has written various articles on preimplantation genetic diagnosis of human embryos, germline therapy, and other reproductive issues. She is the author of In Vitro Fertilization: Building Policy from Laboratories to Legislatures (Columbia University Press, 1989), co-editor of Emerging Issues in Biomedical Policy, and a member of the Ethics Committee of the American Society for Reproductive Medicine.

Mario Capecchi received his doctorate from Harvard University and is a Distinguished Professor of Biology and Human Genetics in the Department of Biology and Human Genetics at the University of Utah. His techniques for generating mice with specific targeted genes inactivated ("knock-out" mice) established a new way of exploring how genes work in mammals. He is a member of the National Academy of Science and his honors include the Bristol-Myers Squibb Award for distinguished achievement in neuroscience, and the 1996 Kyoto Prize.

John Fletcher received his Ph.D from the Union Theological Seminary (NYC). He researched his dissertation, "A Study of the Ethics of Medical Research", at the Clinical Center of the NIH, where he later served as the first chief of its bioethics program. In 1980, French Anderson and he coauthored an influential article on criteria for any trial of human gene therapy. He was one of the first in bioethics to explore the issues of germline gene therapy. In 1993 he was named Kornfield Professor of Biomedical Ethics at the University of Virginia.

Leroy Hood received his M.D. from the Johns Hopkins Medical School and Ph.D. from Cal Tech. He has been a member of the National Academy of Sciences and the American Academy of Arts and Sciences since 1982, and co-edited The Code of Codes (Harvard 1993). Dr. Hood was the Bowles professor of Biology at Caltech until he joined the University of Washington in 1992 as the William Gates professor of Biomedical Sciences and founding chair of the Department of Molecular Biotechnology.

Daniel Koshland, Jr. received his doctorate from the University of Chicago. A professor of Molecular and Cell Biology at UC Berkeley since 1965, Dr. Koshland was the editor of PNAS from 1980 to 1985 and of Science magazine from 1985 to 1995. He has been a member of the National Academy of Sciences since 1979. Among his many honors are the Waterford Prize from the Scripps Institute and the National Medal of Science.

Michael Rose received his doctorate from the University of Sussex, and is a professor in the Department of Ecology and Evolutionary Biology at the School of Biological Sciences, UC Irvine. He is the author of The Evolutionary Biology of Aging (1991 Oxford Univ. Press), and co-edited Genetics and Evolution of Aging with Caleb Finch. Dr. Rose’s major research focus has been experimental tests of evolutionary theories of aging and fitness.

Lee Silver received his doctorate from Harvard University. He is currently a professor at Princeton University in the Department of Molecular Biology where he conducts research in mammalian genetics, evolution, reproduction, and developmental biology. Dr. Silver is the editor-in-chief of Mammalian Genome and the author of Mouse Genetics: Concepts and Applications (1995 Oxford Univ. Press) and Remaking Eden: Cloning and Beyond in a Brave New World (1997 Avon).

James D. Watson, who shared a Nobel Prize with Francis Crick and Maurice Wilkins in 1962 for the discovery of the structure of DNA, received his Ph.D. from Indiana University. He joined the Harvard faculty in 1956 and became Director of Cold Spring Harbor Laboratory in 1976. From 1988-1992 , Dr. Watson functioned as Director of the National Center for Human Genome Research of the NIH where he established the Human Genome Project. Dr. Watson has won numerous honorary degrees and awards, and has been the President of the Cold Spring Harbor Laboratory since 1994.

Symposium Co-Organizers

John Campbell received his Ph.D. from Harvard University and postdoctoral training at the Institut Pasteur, Paris and the CSIRO in Canberra Australia. He is an elected Fellow of the American Academy of Sciences, first holder of the Robert Wesson Fellowship on Scientific Philosophy and Public Policy, and Professor of Neurobiology at the UCLA School of Medicine. Dr. Campbell’s fields of research are genetics and evolutionary theory.

Gregory Stock received a Ph.D. from John Hopkins University and an M.B.A. from Harvard. In his 1993 book, Metaman: The Merging of Humans and Machines into a Global Superorganism, he examined the evolutionary significance of humanity’s rapid technological progress, and at Princeton’s Woodrow Wilson School looked at the implications of recent breakthroughs in molecular genetics. Dr. Stock is now the Director of the Science, Technology and Society Program at UCLA’s Center for the Study of Evolution and the Origin of Life.

Back to Contents

The following are some key points and ideas from the symposium. The full text of the presentations and discussion will be available around the end of this year.

Background - Germline engineering definition.

We're talking about significant changes, and that contrasts sharply with the kinds of genetic engineering and genetic therapy that's going on today. Genetic therapy today is somatic therapy, which has to do with particular cells of the soma (or the body), such as those of the lining of the lung mucosa, which are the target of the effort to treat cystic fibrosis. Such interventions are much more limited in scope.

You might ask, "Well, why is human germline engineering so important?" And the reason is that it embodies virtually everything about the powerful new technologies of molecular genetics and molecular biology that are coming back upon us. It touches at the very core of what it means to be human. It touches upon the flow from generation to generation, which is obviously very controversial. And it touches upon our relationship to our genetics because obviously we're talking about altering the genetics of an unborn child.

Germline engineering will likely prove more effective than somatic engineering. Indeed, somatic therapy is very difficult and still not effective.

The efficiency of homologous recombination is extremely low, so if you have to deliver something to do homologous recombination, as with somatic work, this is a Herculean challenge. But, in germline gene therapy, you're looking for single events, and since you can weed out things that didn't work out right, all of a sudden now, you can apply these technologies much more easily than you ever could do with somatic gene therapy.

Leroy Hood: I think the amazing thing is that the manipulations to do these kinds of experiments are actually much simpler in germline than in somatic. In the long run we will essentially be doing -- if I had to project fifty years from now -- everything at the germline rather than in somatic tissues.

John Campbell: Genes are already put into the body cells of adults to ameliorate their cellular diseases. And putting genes in an egg really is just an extension of somatic gene therapy down to the germline. But this is a very important extension because it means that all of the changes can be exactly reproduced in every cell of the body. And these changes can be focused onto particular cells that need them by controlling the expression of the genes. So I see genetic germline engineering as the ultimate form of gene therapy.

Lee Silver: It’s important to realize that germline engineering has very different modalities than somatic cell engineering, because the actual efficiency of the initial process does not have to be very high. In the mouse homologous recombination has efficiencies which are less than one in a thousand, or even one in a hundred thousand. It doesn't matter. If you can select that one cell out of a hundred thousand, and produce the whole embryo from it, that's all you need to do; whereas, with somatic cell gene therapy you have to develop methods that allow you to increase the efficiency with which you get the genes into cells.

French Anderson: The unfortunate fact is that, with the exception of a few anecdotal cases, there is no evidence of a gene therapy protocol that helps in any disease situation. That sentence is expanded in a review I've just written for Nature that looks at this question in six thousand words.

Our bodies have spent tens of thousands of years learning how to protect themselves from having exogenous DNA get into their genomes. So we were all a little naive to think that if we made a viral vector and put it into the human body it would work. The body's done a very good job of recognizing viral sequences and inactivating them.

So the answer to your straightforward question "Does gene therapy work?" is, at this point in time, it does not work. Now, does that mean it's never going to work? Well, no. It will. And there are now some very hopeful signs in a few clinical protocols. There are certainly some very promising new vectors being developed and animal studies that look like they will work. But we have a long way to go.

To look at germline gene therapy in twenty years is probably too early, and to think of artificial chromosomes being used for gene therapy in twenty years I think is definitely too early. But I agree with Mario who said, "We all have a tendency to overestimate what we can do in five years and underestimate what we can do in twenty-five years."

James Watson: One thing that seems pretty obvious is that germline therapy will probably be much more successful than somatic. If we wait for the success of somatic we'll wait until the sun burns out. We might as well do what we finally can to take the threat of Alzheimer's or breast cancer away from a family.

Elucidation of our genetics is proceeding rapidly and will have enormous consequences including the possibility of manipulating extended gene clusters.

…The Human Genome Project is going to do many things for us. It will define all the genes. It will give us the information to let us ascertain all of this fascinating regulatory information. It will give us the ability to actually take the individual genes and their corresponding proteins and de-convolute the lexicon of motifs that are the building block components of genes and proteins. And this is very important because they give us clues both as to what protein structures are and to what protein functions are.

In addition, the Human Genome Project will give us the wherewithal to look at the natural variation that occurs within humans. It is this natural variation that makes us all different from one another -- some tall, some short, some fat, some thin -- but even more important, some predisposed to different types of diseases. So we will be able to characterize and create incredibly dense genetic maps that will let us do genetics in an entirely new way. If the marker distribution is dense enough, we won't have to follow complicated family studies, we will be able to do genetics directly by association.

And even more intriguing, in a new field called molecular epidemiology, we'll be able to look at the variations -- the common variations -- in these hundred thousand genes and ascertain, how differing combinations of these polymorphisms -- these variations -- can cause different physical and mental traits or, predispositions to disease.

But, in a sense, the most important thing the Human Genome Project is going to give us is a vision and the tools to start looking at an entirely new kind of biology -- a biology I'll call systems biology. And, indeed, what the Genome Project and some of the other advances that have occurred in science in the last ten years have done, is lead to a series of really incredible paradigm changes in how we view science.

The demand for genetic enhancement will likely be much greater than that for cloning.

The demand for gene enhancement therapy will probably be very large, to give your children a better chance of success in the world. So outlawing the cloning of one's self seems to me a little like outlawing ballooning around the world. You know, balloons may land in the back yard and do some damage, but the frequency of ballooning around the world really doesn't demand that we pass a law against ballooning around the world. Cloning, I think, of individuals, may be close to that analogy in trying to even outlaw research on human cloning before any indication of widespread use is apparent.

Cloning, in my opinion, is likely to be appealing if one wants to emulate those more clever or more handsome or more athletic than one's self. That will require humility, not egotism. One is saying, "My children will be better with somebody else's genes rather than mine."

Let us imagine an infertile couple faced with the need for artificial insemination. If that's the only way they can get a child would they be better off taking a natural child with a strangers genes, than a clone from a known person who led a commendable life. As we know, children of even the best parents can turn out to be quite peculiar disappointments. Some just don’t care to study and go to college -- the same college that Dad and Grandpa or Mom and Grandma went to. Or some child of a long line of clergymen will decide to go into the theater and disgrace the family and run around with loose people. Or others smoke pot and live a wild life and become President of the United States.

There are two very different approaches to germline therapy – use of the auxiliary chromosomes and homologous recombination.

A change can be made in an existing gene in one of the chromosomes of the germline cell.

A new gene can be introduced into one of the cell’s existing chromosomes.

A new gene can be introduced into a newly added chromosome.

A chromosome design suitable for human germline engineering has no genes of its own, but instead, a series of "docking" sites where extra genes can be inserted. The chromosome would thus serve as a sort of universal delivery vehicle for modules of genes that disparate collaborators had fashioned to achieve various therapeutic purposes. Such modules would be integrated into the docking sites using enzymes. The diagram shows an auxiliary chromosome with three inserted modules. Initially, only a few genetic modules will have been shown to be safe and effective, but eventually hundreds might be incorporated, each offering its own particular extension of the genome. Technicians might inject the loaded chromosome into an egg using a micro-syringe, which could be done in a laboratory similar to an infertility clinic. Today, eggs are collected from a woman, fertilized in vitro, and implanted in the womb. Germline engineering would require an extra step before implantation in which the extra chromosome would be injected into the fertilized egg.

Mario Capecchi: Modalities we would never think possible with somatic gene therapy actually would be quite easy with germline gene therapy. An example is homologous recombination.

The efficiency of homologous recombination is extremely low and if you have to deliver something which requires homologous recombination, this becomes a Herculean challenge. In germline gene therapy, you're looking for single events, so you can weed out things that didn't work out right. This allows you to apply these technologies much more easily than you could ever do with respect to somatic gene therapy.

Our genes already know how to work in the context of many, many other genes. If we modify a particular gene in some context, then we're going to have much smaller perturbations, things that are much less disastrous. One thing we must appreciate is that interactions of genes are going to change all the existing information. We have to become wise enough to know how the interaction is appearing. And that's a very complicated process and it's going to take a lot of research. And a lot of chips. Chip technology is going to go up, so, modifying existing information is actually much easier and a much safer route, initially.

(slide) Here is a schematic outline of homologous recombination. The top line represents the exogenous information, the asterisk a modification. On entering the cell, the machinery actually takes that piece of DNA, searches the entire hundred thousand volumes, finds the same sequence, and then exchanges information. It replaces the sequence that was already there with the modified sequence that you created in the test tube. And this takes place with enormous accuracy so that, in essence, at the point of the recombination there's no change in sequence.

And the asterisk, remember, can be one base pair, ten base pairs, or megabases. That asterisk can be anything we want. So I think that's the power, essentially, of homologous recombination.

There are significant safety issues to be addressed with this technology.

But on the other hand, if you think it over, the whole process of conception and birth is really a very risky and dangerous proposition. For example, if the criterion is that the children should turn out to be at least as good as their parents, my guess is that germline engineering will compete very well with those conceived the natural way. And if we make this criterion that the children should be up to their parents' expectations, then I think the engineered child may have a good edge over the child conceived the normal way.

…Safety issues will require, first of all, that there be extensive experiments on animals to be sure that the techniques which we would use to cure, say, a defective gene are done so that the risks and side effects and failure are known and, for example, would not create any real problems to the mother, certainly before the event, and then see what the after-events are. We should sort of expect, then, that the child has a better chance of living a longer and more disease-free life than a natural child who, say, has inherited a defective gene.

French Anderson: In one sense this gives me an easy out every time I get interviewed about whether I am for or against germline gene therapy. In principle I'm absolutely for it on the most fundamental of grounds. And that's the grounds of human nature. Germline gene therapy is going to be done, assuming that we have experience from somatic cell that it is, in fact, safe. Germline gene therapy will be done because of human nature.

None of us want to pass on to our children lethal genes if we can prevent it. And that's what's going to drive germline gene therapy. In the last analysis, when you really sit down and think about the things really important in your life -- your loved ones, your family, what you're going to do for your family, those things which really touch our core as human beings -- you're not going to pass on a lethal gene to your child if you can have a simple, safe treatment that prevents it. So germline gene therapy is going to happen. The issue is: When is it safe? When is it ethical to have it? So, this is the first criteria.

We need, and do not have now by a long shot, a reliable, reproducible, safe procedure that works in primates. Transgenic animals, knockout mice, are all done in inbred strains of animals. Livestock becomes more difficult to do because, even though they are partially inbred, there's still a touch of outbreeding.

Human beings are, of course, outbred. And there are very strict laws. You can't marry your cousins and so on. The reason for this is because of the problem of having a genetic disease gene in one parent match up with that of the other.

We all carry five to ten lethal genetic diseases in our genes. But by staying very outbred we basically don't see as heavy a dose of lethal genetic diseases as we would if we were marrying our sisters, our cousins, and so on.

But there is not a procedure that's reliable, that's reproducible, and that's safe yet, even in mice where the majority of eggs that are injected do not give you healthy animals. They're aborted. They're deformed. There are various problems.

Now, the efforts in in vitro fertilization are becoming such that the procedure of actually taking one cell out from a four-cell zygote, analyzing it, and then perhaps putting a gene into one of the other cells -- that is becoming more and more reproducible and reliable. And if, when that time comes -- which might not be within a twenty-year period but could be within a twenty-year period -- that it is, in fact, safe and can be shown to produce healthy baby monkeys, then it would be ethical to transfer that procedure to human beings.

…We know so little about the human body. We know so little about life itself, that we should not try to dedicate engineering to try to improve anything. What our society does fifty years from now is its business. It doesn't care what we think, and we don't care what people of fifty or a hundred years ago thought we should do. But it is our duty to go into the era of genetic engineering in as responsible a way as possible. And that means to use this powerful technology only for the treatment of disease and not for any other purpose.

The idea that restrictions on basic research to prevent germline engineering or cloning would have broad and serious consequences.

In actuality, research is extremely slow. For example, somatic gene therapy is an example where over a decade of work has gone into it by countless very talented people, and yet the products are fairly dismal, I think. I mean, if I have to be realistic. Certainly, progress is being made but it's not staggering. And yet, that's over a decade's worth of research by many, many labs and many, many practitioners.

Leroy Hood: I think science succeeds by doing. What we're talking about here are incremental advances that have enormous implications. And I think if they're shackled by "you can't do fetal research. You can't do this; you can't do that …"

Some of the proposed cloning laws would ban everything that has anything to do with the word "clone." That's DNA as well as cells. I think that's something we can't afford to have in society. What you have to be is reasonable and rational. I think you should do animal testing. How far you have to carry that I'm not exactly certain.

The well-known model systems might give us an awful lot of the information we need, but I think it would be a shame if -- and that is the purpose of this symposium -- if we were really inhibited by society. What is great about American society is its enormous diversity. I think it's the equivalent of what Mario was talking about in the genes. And I think an implication of that is people have to have the right to make decisions based on what their diversity is all about.

Lee Silver: An interesting analogy is a story from the fertility field, because up until 1992 men who could not produce motile sperm were completely infertile and there was nothing that could be done.

In 1992 a completely untested technique was tried, which was to inject sperm directly into the oocyte; and it worked. It had never been tested on other animals but it worked. You got babies out. And within three years, not knowing anything about long-term effects, eighty percent of the fertility clinics in the United States were using this technique.

And I think that it's important to understand what was the driving force here. There was a demand. There was this whole population of individuals who were infertile. The only way they could have a child is by using this technique and the fertility clinics met their demand by using an untested technique. And the children born from this technique, the oldest ones are not more than five years old right now. I think that's going to give you a sense of what's going to drive this technology. They had a sense this was going to work; that it shouldn't be bad. And that was what allowed them to do it in the first place.

James Watson: We're in the position of passing regulations without anything bad happening. I think that is a very different situation, and a very dangerous one, because you really don't know your enemy and yet you're passing laws against them. And biology is so complicated, I think it's a very misguided way to go.

…I think we can talk principles forever, but what the public wants is not to be sick. And if we help them not be sick they'll be on our side.

With germline modifications, heritability is undesirable both for safety reasons and because of the eventual obsolesence of the germline constructs, but there are technical approaches for blocking their heritability.

At every generation, a parent will presumably want to endow his or her child with the newest and the best modifications and improvements that are possible, instead of relying on the chromosome that was given to that person, to the parent, a whole generation ago. So, it'll be important not to have this problem of inheritance.

If geneticists were to scatter gene changes throughout the genome, it would be very hard to handle this problem. But that does not have to be the case. All of the changes could be confined to one disposable, dispensable, extra chromosome, and we could make that chromosome so it wouldn’t be inherited.

If a person has one copy of an extra chromosome instead of the two copies we have of our own chromosomes, that single chromosome would be expected to be transmitted to only one-half of the person's progeny if it follows the rules of Mendel.

We have to go to our genetic engineers and say, " You have to develop a module for the chromosome that will not get through to the sexual cycle. You have to build a module that will break the rules of Mendel." And this, I think, is possible.

Mario Capecchi: One thing that's difficult to appreciate is that when you're doing germline gene therapy you're creating a permanent record. And being a human enterprise, sometimes there will be mistakes. If you have a permanent record, then you're passing that on to the next generation, the next generation, and so on. Also, if we, for example, as a society, decide in twenty years to apply human gene therapy, that the procedures that we'll be working out at that point will appear very primitive fifty years from now. And those procedures, in turn, will appear very primitive a hundred years from now.

So there's no way we should create a system where it is a permanent record. But even with today's technology it would be very simple to make it reversible. This isn't theoretical. Here are vectors [refers to slide] we are making right now with mice for different purposes, in which the human artificial chromosome, for example, would have this pre-recombinase. It's capable of mediating homologous recombination between certain sequences. And if you were to flank those with sequences called lox, so that you had one at each end of this artificial chromosome, when you activated the cre recombinase by a cocktail of two or more, depending on how sure you wanted to make it, of drugs. At that point, the gene addition would be cleared, essentially, from all germ cells from then on. What you would be left with is a small piece of DNA that has no information, no way to replicate itself, no way to propagate itself and, therefore, would be lost in the next generation

… So it's important to remember that there are ways, if we jump into this technology, there are ways to reverse it. It's simply not something we are writing in stone and whatever mistakes we make we're going to have to live with from then on. There are very simple ways to make it reversible.

Germline engineering has been criticized because it does not allow "informed consent" but such consent might be designed to be possible.

In my examples, a change is made that is genetic and of absolutely no consequence at all. The only thing that would happen would be a particular transcription factor produced in a particular cell type. The patient has to choose whether to activate this particular cassette.

I think if people are really concerned about consent we could take a human chromosome or a segment of it and put on a lock. None of those genes would have any effect until a person took an artificial hormone pill to unlock the cassettes and give him or herself the new engineered phenotype.

I don't see that germline engineering does not allow a person to have choice. If that's important, then it’s a technical issue. We’ll say to our genetic engineers, "This is a constraint you have to work with. A person must have a choice before he has any change made to his physical body."

Leroy Hood: The other point one can make is, as Mario pointed out, there has been a lot of genetic engineering practiced in terms of therapeutic selective abortions and things like that. There isn't any prior choice there. It's something that's been done for a long time in society. So these are complicated issues and I don't think you can categorically say we should always require and/or need informed consent. The other thing I would say is that, although you can design these reversible kinds of things (as John Campbell and Mario Capecchi mentioned), it's quite clear that if we get into engineering more complicated traits, it’s not going to be possible to make them all simply reversible. So we are going to have to face up to this question. I think it really is an important one.

Daniel Koshland, Jr.: I'm not sure informed consent is always necessary. When I was a kid I didn't really have an option about whether I should go to school or not. My parents told me to go. And I told my children. My children didn’t have a vote on who their mother was when we decided to have children. So I think, sometimes, to extend informed consent to the embryo is really sort of a theoretical construct.

There might be significant numbers of people who would be interested in meaningful germline therapies if they were safe.

My question is: Who in the audience would absolutely not want to do that? I would like people to raise their hands; those who would not. That's interesting. There are about a dozen or so raised hands. The question is: If you could safely and reliably add an artificial chromosome to a child that you were conceiving, by in vitro fertilization, who would not want to add one that would increase their life expectancy by some ten or twenty years? A few people said that they wouldn't, now how many would, given adequate safety and reliability, do that? Well, look around. That's a large fraction of the audience <about 70%>. It's interesting to reflect on what such interest will lead to when germline engineering becomes practical, whenever that may be.

There are many possible long-term targets for germline – Aging – AIDS, etc.

Now, I know it is very fashionable for genetic engineers to say, "Ah, yes, but we will only turn on those genes later." Well, indeed, you may only turn on transcription at high levels later, but the fact is you're likely to get some amount of genetic action at early ages despite the fact you tried to shut everything down. Then you have the problem of evolutionary instability and having chronically in your germline an artificial chromosome, which is simply not going to be as stable as a regular chromosome. Finally, you have the problem of possible homogenization which is like all of us driving a Toyota Camry. If we all have exactly the same anti-aging chromosome and, as it turns out, that gives us a weakness to a virus which none of us have yet experienced -- which we've not yet seen epidemiologically -- and that virus comes in and kills all of us? Well, bummer.

So I think there are problems with that, and what I would suggest, and this isn't, I hope you understand anything I'm proposing we do immediately. But I think a compromise might be appropriate. The compromise I would suggest is from various types of stem cells, supplying these additional artificial chromosomes to the body before it really gets aging, in the hope of alleviating a lot of the damage of the aging process, so that when you do hit sixty-seven or sixty-eight you don't have to absolutely panic. You could be in relatively decent shape.

Not all disorders that are associated with aging will be preventable using this kind of intervention, because certainly some things arise from growth patterns established in the fetus, such as patterns of vascularization. However, this does leave the germline free. It does leave deleterious effects during childhood avoided and, therefore, it probably right now would be my first choice.

Leroy Hood: In gene therapy, we can think about simple genetic traits, and we can think about complicated genetic traits. So the simple genetic traits are those that might manifest themselves as the expression, primarily, of a single gene. Now, I don't mean that the system still isn't complicated, but a single gene could have a large effect. And I think resistance to infection, as John Campbell has suggested; I think resistance to AIDS; I think resistance to at least a limited number of cancers are a real possibility. And another interesting possibility is longevity.

The second kind of trait -- these complex traits that we're going to have to do the systems analysis on -- are a lot further downstream, but they are the traits that are, by far, the most interesting. In the first category were things we'd like to fix up. In the second category, if humans are ever to take in hand their own evolution, it will be using traits of the second type. Emotional stability, intelligence, the ability to learn, physical attractiveness -- these are all very complicated traits of this second type that I think we have the tools, over the next ten to twenty years to begin deciphering in a really profound way.

There is great disagreement about the distinctions between therapy and enhancement.

Panel Discussion excerpt:

French Anderson: …What is a disease and what is not a disease is a major question. We can all recognize what is a major disease, because if it causes severe suffering and premature death then that can be recognized as a major disease. But once you leave that category and you hit minor disease, what's a minor disease? What's a cultural inconvenience? What really is disease? What really is normal?

…When the time comes that it [germline engineering] is truly safe, that we understand how human cells work, how the brain works, and so on, which I think will take centuries -- when that time comes, I have no objection to enhancements. But the fundamental point I'm trying to make is that we don't know enough about what the consequences would be, from a medical point of view, to attempt anything at this point but treatment of serious disease. That's my fundamental point.

…The normal aging process I would not consider disease. The consequences of aging; namely, cancer, heart disease, stroke -- those degenerative processes that take place -- those are diseases.

Lee Silver: One of the ways of getting over the problem that French mentions is also a question of what you mean by enhancement. When parents want to give something to their children which already exists in other individuals in society, you know how that will operate, at least in other individuals. That’s an alternative allele that parents could give to their children naturally, but not if they don't have it themselves. So that's a situation where you already have the information <about what will happen>. Nobody wants to have an average child, of course. Is it enhancement to give your child something that other children get naturally? It's very difficult to stop parents from doing that particular kind of treatment.

Michael Rose: I think you're tying yourself into all kinds of knots that arise from the medical model, which is basically inherited through Hippocrates from Plato and Aristotle. It's a model that's twenty-five hundred years old. I would suggest that if you reconsider your basic biology, in terms of concepts like quantitative genetics and fitness, selection, genetic variance, environmental variance, you would find your way out of a lot of these problems.

French Anderson: Is breast cancer normal?

Michael Rose: Aging is totally normal. Breast cancer is dramatically age-dependent, like innumerable other disorders. For example, you talked about having premature mortality. If you're alive over a hundred you're overdue for mortality in terms of the normal aging pattern, to which I say: Fine. If we find something that enables us to live to be two hundred, even if I'm an M.D. I'm not going to say no to it, even if it's abnormal. I mean, what can be abnormal can be fantastic.

French Anderson: Is breast cancer normal?

Michael Rose: In terms of the age-dependent profile, to get cancer is very normal. It's difficult to find a person over ninety who, on autopsy, does not show some signs of cancer, some signs of tumor.

French Anderson: So that you would say that breast cancer is normal?

Michael Rose: So are all cancers. The older you get the greater chance of getting Alzheimer's, the older you get the greater your chance of cardiovascular disease and, to me, all of those things reflect the failure of natural selection to operate at those ages. The functions that we have when we are young do not betoken normality, which is a meaningless concept in biology, they instead betoken the action of natural selection to make our bodies work well.

French Anderson: I would say that if you think that Alzheimer's, breast cancer, and so on are normal, then you are tied up in philosophical knots that you need release from.

We are seizing control of our own evolution.

Lee Silver: What IVF does is to bring the embryo out of the darkness of the womb and into the light of the day. And in so doing, IVF provides access to the genetic material within. And it's through the ability to read, alter, and add genetic to the embryo, that the full force of IVF will be felt.

…As the editors of the preeminent journal Nature put it, "We now have the power to 'change the nature of our species.'" We now have the power to seize control of our evolutionary destiny. I would suggest also that someday we'll be able to use these genetic differences as a way to discover exactly what are the genes that allow humans to have a higher level of consciousness than chimpanzees. I don't agree that we'll have to understand how the brain works to know this. When the Huntington's disease gene was first cloned nobody knew how the mutant gene caused the disease; but we knew people who had the mutant gene got the disease and people who had the normal gene did not get the disease, even though there was a black box between one and the other. And I suspect that this might happen in the future.

I think it's important not to make the mistake of thinking that technology is always going to stay the same as it is now. Technology always goes forward. There are radical new technologies that surprise us all the time. And we've got a long time in the future to go. This is my conclusion: Human evolution will be self-driven.

Religion will continue to be a strong ingredient in discussions of genetic engineering.

On the whole, religion plays a very conservative role in response to genetics. And it actually, in its worst features, makes people afraid and passive in the face of the terrible things that nature can do to children and that genetic roulette does to children.

I think that one of the greatest harms of religion in the world is the doctrine that unprotected sex is sanctified. Some religious movements teach that unprotected sex is the holiest way to produce a baby -- or to try to produce a baby. Unprotected sex is the greatest threat to women in the world. It's also a threat to men, but it's certainly a threat to women

There are a variety of approaches to germline regulation in Europe.

There are other nations, too, that are permissive by default, by not having a national law on embryo research, and that would include Belgium. There are some, also, that are restrictive. And I would say that there are two kinds of restrictive voices: one would be countries that have embryo research laws that are very broad, so broad that they would, in effect, include germline manipulations. And that would include Norway, Austria, Switzerland, that forbid all kinds of embryo research. Still, that leaves the door open because if embryo research has reached the point where it would be safe, then germline manipulations would not longer be research and maybe the application would be appropriate.

Another restrictive type is one that has an embryo research law and, in it, specifically mentions germline interventions. Germany would be an example here of a highly restrictive law. It, too, has been in effect since about 1990. Here, there's concern for individual rights; there's more of a distrust for the ability to draw lines on technological change than in the countries such as Britain. There's also a concern for genetics as a common heritage.

On the regional level, the Council of Europe was formed at the end of World War II. There are forty nations now. And in 1982 it came up with the idea that maybe there's a right to inherit a genetic inheritance that has not been interfered with except following principles.

So what might those principles be? Over time, the people in the Council of Europe, different ministers and committees, have worked with this, and last year they came up with a Bioethics Convention. And this is now out for the signature of the states. Twenty-two nations have signed it already, and it calls for trans-national harmonization: looking for principles that would guide the deliberate intervention in such things as the human genome. And there's a key phrase that says: "An intervention seeking to modify the human genome may be undertaken for prevention, diagnostic, or therapeutic purposes and only if its aim is not to introduce modification in the genome." This indicates probably a more or less closed door, but still only half of the nations have signed this.

Another that I will mention is UNESCO, which is an international organization. A hundred and eighty-six nations have signed an agreement -- a declaration -- that, again, was issued last year. Last year was a busy year for national and international conventions. It was four years and nine drafts in the making, and it is conducive to scientific inquiry. It suggests that if scientific inquiry comes about there is a need to balance individual rights with it. And, therefore, it is rather open and permissive; it does not close the door.

Everything we do that affects reproduction alters the gene pool in one way or another, so arguments about the sanctity of the human gene pool are difficult to sustain.

Further, if they are, for moral reasons, unable to participate in abortion they can go the much more expensive route of selective implantation, in which the early embryo is dispersed into single cells and then one of the cells is analyzed with respect to its genome. If you find the mutation, you don't plant that embryo. If you find it's free of that particular mutation, you go ahead and implant.

Daniel Koshland, Jr.: We should start, perhaps, with the question raised by some who say we shouldn't tamper with the germline. I frankly don't understand these people. Where are they living? We are already altering the gene line right and left. When we give insulin to a diabetic who then goes on to have children, we are increasing the number of defective genes in the population. No one is seriously suggesting we refuse to give life-saving drugs to genetically disadvantaged people.

We discussed here the cystic fibrosis problem; yet we are damaging the germline every day by doing so [treating cystic fibrosis]. Are we doing something terrible by simply ameliorating the illnesses that our compassionate policies of the present and past have created?

James Watson: I just can't indicate how silly I think it is [the sanctity of the human gene pool]. I mean, sure, we have great respect for the human species. We like each other. We'd like to be better, and we take great pleasure in great achievements by other people.

But evolution can be just damn cruel, and to say that we've got a perfect genome and there's some sanctity to it. I'd just like to know where that idea comes from. It's utter silliness. What we want to do is treat other people the way that maximizes the common good of the human species. And that's about all we can do.

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Medicine is entering unfamiliar territory on many fronts, and people are uneasy about the strange possibilities that are emerging. It is still too early to discern the full challenge and potential xenotransplantation, genetic testing of embryos, psychotropic drugs, human somatic gene therapy, cloning, and human germline therapy embody, but controversy about how to handle the fruits of modern biology and medicine is not new.

In the early 1970s, anxiety about the escape of genetically engineered organisms brought a voluntary moratorium on recombinant DNA research and subsequent adoption by the scientific community of a carefully thought out framework of self-imposed restrictions (Assilomar, 1975). This February, the Association of American Medical Colleges and other groups proposed a pre-emptive 5-year voluntary moratorium on cloning in response to a flurry of legislative efforts to ban cloning, but the harsh condemnations of cloning and various ill-considered measures to stop it have not been a good model for how to approach these challenging new technologies wisely. Human germline therapy will be a far more significant and complex matter than cloning; what must done to insure that its arrival will be handled more judiciously?

At the symposium, there was general agreement that human germline procedures will eventually be used. The real question is not whether the technology will come about, but when and how it will. One way of approaching the matter is to look at the three key activities associated with human germline engineering: research contributing to it, discussion of the issues surrounding it, and its use on humans. Their optimum sequence might seem to be discussion, then research, then use. But this is unrealistic because meaningful, concrete discussion of how to handle the technology isn't possible without the insights provided by research. Research must provide the basis for the evolving discussion and should be strongly supported as we try to decide how best to handle the powerful procedures that are taking shape.

What has been missing is serious discussion of germline engineering. To avoid the sort of the public surprise and dismay that attended cloning, it is important to begin our discussions about the advantages and disadvantages of various approaches to germline engineering before it reaches the stage where its application to humans can be seriously contemplated. Germline engineering, like the rest of medicine, will need to be regulated, but only after we understand more specifically its extraordinary therapeutic potential.

At present, any legislation attempting to influence how the technology unfolds by restricting biomedical research would be misguided. First, it would be less likely to delay the basic research developments that will enable germline engineering than to disrupt other uncontroversial medical research. The fundamental discoveries that will lead to germline engineering will occur whether we deliberately pursue them or not, because they will come out of research deeply embedded in mainstream efforts toward other important goals. Second, it would breach America's cherished tradition of free scientific inquiry to restrict medical research merely because it might open up difficult possibilities. Third, it would set a dangerous precedent for other promising future medical technologies. To our knowledge the Federal government has never banned a particular line of basic medical research, and at present, no impending threat warrants such extreme action.

It is useful to look back twenty-five years to the menacing possibility recombinant-DNA research raised – the accidental release of some new life form that would wreak havoc on us or the environment. Even so grave a threat as this was met largely by voluntary controls that could be easily relaxed as safety concerns were answered. The wisdom of this course is evident in the great strides made subsequently, when progress might have been blocked by earlier legislative excesses.

Recent fears and misconceptions about human cloning provide a clear example of the problems that arise when a new technology arrives unexpectedly. Arguments to ban research that might lead to this possibility employ an entirely different logic than those about recombinant-DNA in the 1970s. Those who seek to block cloning invoke images not of catastrophic accidents, but of technological success. They argue that use of the technology would be unwise or even immoral, and propose stopping it by preemptively blocking both its use and the research that might lead to its development. But in our view, loose speculation about the possible misuse of a technology or its imagined corrosive social influences are not reason enough to stifle research.

Banning the act of cloning humans would be less disturbing, but it is our opinion that prior regulation of this sort is also unwarranted. The FDA, the RAC, and Ethical Review boards already have ample oversight in place to prevent broad misuse of such technologies, and any isolated violations could be dealt with like any serious malpractice or reckless human experimentation would be. In any event, biomedical advances take many years, and resultant clinical procedures remain difficult and expensive for even longer, so our society will have adequate time to debate the implications of cloning before it impacts more than a handful of people.

This last point is especially important in the context of human germline engineering, because it means that we have the luxury of seeing what possibilities emerge from this nascent technology before making decisions about how to define and restrict them. The challenges germline engineering will create are profound: How much are we willing to intervene in life's flow from generation to generation? How much do we want to control the genetics of our children? But we must not answer such questions too quickly. Germline engineering may prove a valuable tool in fighting cancer, AIDS, infectious diseases, and even aging, so society will best be served by first broadly and intelligently appraising these possibilities. We believe that the most effective way of accomplishing this is to move forward – in the public light --with the basic research that will disentangle fantasy from reality. The birth of Dolly, for example, led to more vigorous debate about public policy in this arena than all previous panel discussions, meetings, and writings combined.

Toward this end, UCLA's STS Program offers the following specific recommendations about human germline engineering:

The RAC (Recombinant Advisory Commission) should indicate that it will now consider germline proposals. Such proposals probably will not arise for several years, but a believable public process for examining potential early clinical applications of this challenging technology should now be put in place. It is important to have public scrutiny of germline possibilities right from the beginning to insure that issues of safety, propriety and reliability in germline procedures are fully aired. In 1990, the RAC stated that it would "not at present entertain proposals for germ line alteration," but that policy should now be changed. The RAC, by virtue of the excellent job it has done in reviewing somatic therapy protocols, is the logical body to review early human germline proposals when they are offered.

The FDA (Food and Drug Administration) should explicitly assert its authority to regulate human germline engineering. The FDA recently asserted its authority to regulate human cloning, an action applauded by PhRMA (Pharmaceutical Research and Manufacturers Organization), BIO (Biotechnology Industry Organization), and ASRM (American Society of Reproductive Medicine). We agree with that action and call on the FDA to further extend its authority to germline engineering, so that it is clear that this important technology is not without oversight.

The human genome project’s ELSI (Ethical Legal and Social Implications) should lead an exploration of the challenges and potentials of human germline engineering. Germline manipulation may well be the most far-reaching technology to emerge from the Human Genome Project and therefore should be the focus of considerable attention from ELSI. It is important to begin to thoroughly explore its implications. Issues such as the distinction between human enhancement and human therapy embody deeper dilemmas when they relate to the germline. Issues like the importance of heritability and consent are unique to germline discussions. The advantages and disadvantages of various technical approaches to germline engineering should be compared and issues of safety and reliability explored. Finally, ELSI should fund a serious effort to gauge public attitudes about germline engineering in-depth. This is very important. One of the reasons that human germline engineering had not until recently been seriously explored is that the topic was viewed as too sensitive. But our UCLA symposium demonstrated that the public is thirsting for mature, intelligent discussion of such future possibilities. Solid data about public attitudes and perceptions, rather than short newspaper and television polls about controversial questions, should be an important ingredient in future public policy decisions in this arena.

The United States should resist any further effort by UNESCO or other international bodies to block the exploration of germline engineering.  Various attempts have been mounted in Europe and elsewhere to prevent germline genetic engineering.  While such policies do minimal damage when they exist only at a national level, internationally they must be avoided.  In any event, it is far too early to seek a cross-cultural consensus about this difficult and complex technology, and it would be unwise for the US to unnecessarily hamper its future policies in a realm so important and so unformed. Large legislative assemblies are simply not an appropriate arena for regulating provocative new research.

No state or federal legislation to regulate germline gene therapy should be passed at this time. Legislation should be contemplated only if oversight by the FDA, RAC, and Local Review Boards proves unable to prevent serious misuse of the technology. Any research prohibition, in addition to being contrary to our traditions of free inquiry, would drive research overseas or underground, would disrupt unrelated biomedical research, and might foreclose as-yet-unseen therapeutic possibilities. As to attempting to block the use of germline technologies, such action at this time would not serve our interests or the interests of future generations. We do not yet know even what the most important possibilities of germline engineering will be. In addition, our courts have been loathe to allow infringement of our fundamental liberty to procreate. The right to bear children was first constitutionally protected as a right to privacy in 1965, and it has been repeatedly reaffirmed and extended to include the right to have access to contraceptives and to medical procedures such as IVF (Lifchez v.Hartigan, 1991). Critics of cloning contend that cloning is not protected because it is replication rather than reproduction, does not involve a cooperating male and female, and does not involve the transmission of genes from one generation to the next, but such arguments would be unlikely to be sustained about germline therapy.

The National Bioethics Advisory Commission (NBAC) should recommend revisions to US Patent law to address the challenges of germline technology and the widespread patenting of human genes. Increasing difficulties and uncertainties have arisen in the application of patent law to the rapidly evolving arena of biotechnology. As we move towards human germline engineering and the patenting of genetic constructs that could potentially be transmitted from one generation to the next, a comprehensive review is essential. Such a review would also provide an excellent opportunity to re-examine the difficult issue of human-gene patents, since they exhibit many novel characteristics not anticipated by existing patent law. NBAC was charged in 1996 with the task of reviewing gene patenting, and it is well positioned to outline a viable approach for this important issue.

 

A temporary voluntary moratorium on the cloning of humans should be supported by researchers and clinicians. We support the 5-year moratorium proposed in February (1998) by AAMC (Association of American Medical Colleges). It is in alignment with similar calls by NBAC (National Bioethics Advisory Commission), SDB (Society for Developmental Biology), FASEB (Federation of American Societies for Experimental Biology) and others and is an excellent response to public sensitivities on this controversial research. A voluntary moratorium avoids the pitfalls of legislation while allowing a pause for discussion. Such a moratorium should be extended to human germline engineering as well, since it also is at so early a stage of development that its clinical application to humans would be exceedingly reckless.

Any bills to register opposition to human cloning should be crafted to minimize subsidiary damages they might cause. Specifically, they should:

Apply only to the act of cloning a human child identical to an existing adult.

Explicitly state that they do not seek to limit biomedical research.[ Any ban of the cloning of DNA, cells, or tissues could disrupt vital areas of medical research such as stem-cell research.]

Contain a sunset provision.

 
 

Contact:

Dr. Gregory Stock

UCLA Program on Science, Technology and Society

Center for the Study of Evolution and the Origin of Life

405 Hilgard Ave.

Los Angeles, CA 90024-1567

(310) 825-9715

gstock@ess.ucla.edu

www.ess.ucla.edu/huge

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