SPEAKERS CONTENTS INSERTS
Page 1 TOP OF DOCBIOTECHNOLOGY AND THE ETHICS OF CLONING: HOW FAR SHOULD WE GO?
WEDNESDAY, MARCH 5, 1997
U.S. House of Representatives,
Committee on Science,
Subcommittee on Technology,
The Subcommittee met at 2:08 p.m. in room 2318 of the Rayburn House Office Building, Hon. Constance A. Morella, Chairwoman of the Subcommittee, presiding.
Mrs. MORELLA. The Technology Subcommittee of the Science Committee will now convene.
I would like to promptly start off and introduce and recognize the Chairman of the Full Committee, Congressman Sensenbrenner, for his comments.
Chairman SENSENBRENNER. Thank you very much, Madam Chairwoman and members of the Committee. First of all, let me commend you for conducting this hearing on a very timely and very interesting matter. And, the standing room only crowd in this room is testimony to the fact that this is something that is really tops on the agenda not only of the science community but the public at large.
In the area of cloning embryos, it is obvious that science is ahead of both the law, morals and ethics. And, one of our jobs as Members of Congress is to try to tie the two or three together so that there is a proper balance that is reached so that science can carry forward but that we do not get involved in the deep, ethical and moral issues of cloning human beings.
I am personally opposed to cloning human beings. And, I salute President Clinton for announcing his moratorium on federal research yesterday and also requesting the private sector to stop doing research on the cloning of human beings until we are able to pause and try to tie these ends together.
Page 2 PREV PAGE TOP OF DOC I also specifically endorse and support the two bills that will be introduced today by Congressman Vernon Ehlers of Michigan. One bans federal funding permanently for human cloning research and the second is making it unlawful to clone humans. And, under the bill, cloning would be punishable by a $5,000 fine.
Having said that, let me say that I would hope that the moral and ethical debate that was triggered by the announcement of the cloning of the lamb in Scotland and the monkeys in Oregon will not diminish the public's appreciation of the value of biotechnology research. And, whatever we do as a Committee and as a Congress should allow biotechnological research and genetic engineering research to go forward in a proper, ethical and moral context.
I think it is important to realize that the cloning research that has been done to date is helping to revolutionize the treatment of diseases in human beings such as hemophilia, cystic fibrosis, sickle cell anemia and emphysema. There also is a tremendous impact on the agriculture sector of our economy, which is one of the most productive sectors and which exports a lot of American products abroad; and, we want to make our agriculture more efficient.
We want to be able to lower the cost to our farmers. We want to be able to export more agricultural products overseas.
And, much of the cloning research that has been done has been very beneficial in the agricultural area. So, as we proceed with this very interesting and very timely debate, let's keep in mind that there are good things that happen through biotechnology in the health and agriculture area.
And, we should not let our concerns over the potential of cloning human beings override the fact that we've got to continue biological research in these areas so that we can be healthier and live longer lives, have better food and have a higher quality of life.
Mrs. MORELLA. Thank you, Mr. Chairman. I want to welcome all of you to this hearing today, the first Congressional hearing on the very timely and important issue of cloning and particularly our panelists, who are so expert in the area.
Page 3 PREV PAGE TOP OF DOC It has certainly been called the scientific discovery of the century. And, indeed, perhaps no modern breakthrough in bioscience holds more promise than the possibility of animal cloning, as just announced last week by scientists at Scotland's Roslin Institute.
Animal cloning has the potential to immeasurably improve our human health condition with radical advances in medical research, the speeding up of new drugs and the development of animal organs for human transplantation. Yet, perhaps no other science issue is as dramatically misunderstood and feared, since cloning comes saddled with lingering and troubling concerns about the very dimensions of our human existence.
At the center of the drama is a 7-month-old sheep named Dolly, created in a lab in the Roslin Institute. While the Scottish scientists there, and at other laboratories, had previously cloned animals from embryos, what makes Dolly so unique is that she was cloned from the single cell of an adult mammal--in this case, a 6-year old ewe.
Most experts had previously thought that to be impossible, because they believed cells older than the embryonic stage lost their ability to produce a viable animal. And, although researchers have said this innovative Scottish replication technique is fairly simple, it's far from fool-proof.
The experiment that produced Dolly started with 277 combinations of adult cells with eggs, yet was able to produce just one lamb. This was finally done by taking a cell from an adult donor sheep's udder and then taking an unfertilized egg from a second sheep and removing the part that contains its genetic code. The cell and the egg were then charged with electricity to combine them.
As a result, the egg began dividing like a fertilized egg and became an embryo. The embryo was subsequently implanted in a third sheep, a surrogate mother, who gave birth to Dolly--genetically identical to the sheep that had donated the udder cell and seemingly normal in every way.
Page 4 PREV PAGE TOP OF DOC Shortly following this landmark announcement about Dolly, scientists at the Oregon Primate Research Center announced the results of experiments proving that embryonic cloning procedures are a valid technique for the production of Rhesus monkeys. Although not the same as cloning of an adult animal, by applying nuclear transfer technology to primates--mankind's closest animal relative--for the first time, the scientists at the Oregon Primate Research Center have raised the specter of cloning human beings. And, we will hear more about that today.
The result of these successful experiments with sheep and monkeys, with the potential for the future extension to humans, is not only casting important new light on the biosciences but is also provoking worldwide discussions on the ethics and morality of cloning. Serious questions are now being raised that had once only been theoretical musings when the procedure was considered the stuff of science fiction, such as ''Brave New World'' and ''Jurassic Park.''
As the Chair of this Technology Subcommittee and as the Congressional Representative for Montgomery County, Maryland, which is home not only to the National Institutes of Health but the third largest concentration of biotechnology firms, I am certainly aware of the benefits of animal cloning and genetic research. And, as we move forward with this hearing and discuss possible legislative action, I would urge all of my colleagues to use today's hearing to act wisely and deliberatively on this issue.
We must weigh all of the future opportunities and benefits of cloning technologies to the biosciences. We must be careful not to outlaw or restrict potentially positive scientific developments with overly prescriptive legislation aimed at aspects of cloning which we don't support or condone, such as human cloning.
I certainly am concerned about human cloning. I think we all are.
There are very compelling ethical, moral, religious and psychological reasons not to permit it. The theoretical cloning of human embryos has certainly raised strong concerns and objections throughout the world.
Page 5 PREV PAGE TOP OF DOC The European Union and several countries, including Germany and the United Kingdom, already have laws on the books directly forbidding human cloning, but the United States is not among them. In the United States, the National Institutes of Health will not fund human embryo research. And, there is also a temporary statutory prohibition of federal funding of such research, but there are only limited restrictions on privately funded science.
And, just yesterday, as has been mentioned, President Clinton expressed his support for the current Congressionally-issued prohibition on federal funds for human embryonic research. And, in addition, the President has issued a directive expanding the ban to cover human embryos created by cloning for implantation and extends the ban of funds to cover all federal agencies, as well as calling on privately funded scientists to implement a voluntary moratorium until the National Bioethics Advisory Commission makes its recommendations to the President.
And, of course, that Bioethics Advisory Commission is represented here today. I am certainly pleased to have with us all the members and staff of the National Bioethics Advisory Commission.
The Subcommittee is undertaking the lead--the Genetic Subcommittee is undertaking the lead in providing the thorough review of the legal and ethical issues associated with cloning and will report back to the President in 90 days with recommendations on possible federal actions to prevent its abuse. The Subcommittee has been meeting since, I believe, 7 a.m.--is that right, Dr. Murray--at NIH but felt it was very important to come to Capitol Hill this afternoon to participate.
And, we appreciate that as we, in this Subcommittee hearing, review the breakthrough technology which created the first cloning of an adult mammal; determine how cloning technologies are being used presently, and in the future, for positive, scientific advancements; explore if the technologies can, and should be, used for human cloning; and, discuss the public policy implications that come with cloning.
Page 6 PREV PAGE TOP OF DOC So, I want to welcome this afternoon's very distinguished panel. And, I look forward to a very productive and educational hearing. We need to learn and know more about this.
I want to thank you all for coming. And, I want to now recognize the Ranking Member of the Full Science Committee, Mr. George Brown.
Mr. BROWN of California. Thank you very much, Madam Chairwoman. I want to commend you for calling this hearing today and continuing the record of the Science Committee's involvement in the debates surrounding the development of biotechnology.
It was 20 years ago this month--actually on the 29th of March, 1977--that the Committee held its first hearing on recombinant DNA. The lead-off witness at that time was Dr. Maxine Singer, who was then-head of the National Cancer Institute. And, the witnesses included some extremely noted scientists--Dr. George Wald--since deceased--who was a Nobel Prize winner; Dr. David Baltimore, whose fame is widespread; Dr. Donald Fredrickson, Freeman Dyson--I'm not quite sure what he was doing at the hearings, but----
Mr. BROWN of California. He's a man of many talents; and, Dr. Lewis Thomas, who I have become great friends with over these years. That's only a few, of course.
These hearings--there were about a dozen--stretched out over the next several months. And, they provided the greatest exposure to this new field that it had ever had in the political arena, at least.
This Committee has been part of a broad educational process in society, involving the Congress, the research community and the public in discussions about the legal, ethical and technical implications of recombinant DNA research and the biotechnology industry.
The educational process that the Science Committee underwent in its inquiries into recombinant DNA research was critical in achieving what became a good, working set of guidelines for federally funded research in this area. And, it caused us to curb our instincts to go out and immediately start regulating this new field.
Page 7 PREV PAGE TOP OF DOC And, we did not. And, I think we deserve great credit for not legislating in this area.
Mr. BROWN of California. We left the initial ignorance and anxiety behind, giving way to a process of education and rational discussion. It is significant that we followed the lead of the scientific community in discussing these issues.
Two years later, in 1975, the scientific community--no, 2 years earlier, in 1975, the scientific community had organized the Asilomar conference to discuss the broad implications of their research in this field. This meeting triggered a series of debates at the national, state and local level.
At one of our hearings, we had the elected officials of local government. I think it was the City of Cambridge, which had proposed passing an ordinance prohibiting this kind of research within their city limits. Unfortunately, this broad public dialogue on the social and ethical implications of developments in biotechnology did not continue or did not continue as vigorously as it should have.
Although much of the discussion ceased, science continued to progress. The advent of Dolly has reinvigorated public discussion.
Now, almost 25 years after the initial discussions about the significance and implications of recombinant DNA research for society, we are facing a reality that was once scientific conjecture.
Madam Chairwoman, I will put the rest of my remarks in the record, with your permission----
Mrs. MORELLA. Without objection.
Mr. BROWN of California. And merely comment that one of my contributions is being still alive after all of these years.
Page 8 PREV PAGE TOP OF DOC [Laughter.]
Mr. BROWN of California. No other members of the Science Committee are still in Congress who participated in these discussions.
[The prepared statement of Mr. Brown follows:]
STATEMENT BY REP. GEORGE E. BROWN, JR.
SUBCOMMITTEE ON TECHNOLOGY
COMMITTEE ON SCIENCE
MARCH 5, 1997
I want to commend Chairwoman Morella for calling this hearing today and continuing the record of the Science Committee's involvement in the debates surrounding the development of biotechnology. It was twenty years ago this month that the Science Committee held its first hearing on recombinant DNA. We have been a part of a broad educational process in society, involving the Congress, the research community, and the public in discussions about the legal, ethical, and technical implications of recombinant DNA research and the biotechnology industry.
The educational process that the Science Committee underwent in its inquiries into recombinant DNA research was critical in achieving what became a good, working set of guidelines for Federally funded research in this area. We left the initial ignorance and anxiety behind, giving way to a process of education and rational discussion. It is significant that Congress followed the lead of the scientific community in discussing these issues. In 1975, the scientific community organized the Asilomar conference to discuss the broad implications of their research endeavors in recombinant DNA. This meeting triggered a series of debates at the national, state, and local level. Unfortunately, this broad public dialogue on the social and ethical implications of developments in biotechnology did not continue.
Page 9 PREV PAGE TOP OF DOCAlthough much of the discussion ceased, science continued to progress. The advent of Dolly has reinvigorated public discussion. Now, almost 25 years after the initial discussions about the significance and implications of recombinant DNA research for society, we are facing a reality that was once scientific conjecture.
Although the public has been taken by surprise by the announcement of scientists in Scotland that they had cloned an adult sheep, these results did not happen serendipitously. A review of the scientific literature reveals the steady progress toward this achievement. Only last year, the same research group announced they had cloned sheep from embryo cell tissue. What has happened is that the public and policymakers have been caught flat-footed.
What has changed is that the biotechnology research community and industry are now major segments of our economy and research infrastructure. The discussion surrounding Dolly does not focus on future possibilities, but current probabilities.
Although most public attention has focused on the extreme scientific possibilities such as the cloning of humans, I believe that this recent scientific announcement is a call to review our fundamental understanding of research efforts and public policy.
This cloning research, which is very much applied research, opens up new areas to be explored in basic biological research. It is a strong example of the interrelations and feedback loops that exist in science and points out that there is no clean boundary between basic and applied research, simplistic political statements notwithstanding. Indeed, the announcement of Dolly's existence was delayed until the Roslyn Research Institute had filed its patent application. What will be the impact upon the traditional open flow of research results, let alone the implications of public funding of commercializable research.
Although news accounts and the testimony today speaks of the great promise this research holds, we also need to evaluate the impacts of the practical application of this technology and explore how society will be able to weigh both the potential benefits and drawbacks of this research.
Page 10 PREV PAGE TOP OF DOCI do not expect to find the solutions to the questions Dolly's existence raises. I do hope this hearing marks the beginning of the Science Committee's efforts to renew a national dialogue from which the answers will emerge.
Mrs. MORELLA. I'm sure no others have the kind of wisdom also that you bring to this Full Committee, Mr. Brown.
I would like to now recognize really the senior Ranking Member of the Subcommittee on Technology, the gentleman from Tennessee, Mr. Bart Gordon.
Mr. GORDON. Thank you, Madam Chairwoman. And, my compliments also for calling this hearing.
I think you have stated our position very well. So, I think probably my best contribution to the hearing can be to talk less and to listen more to this panel.
So, I am just going to very quickly say that I support the President's request asking for this Bioethics Advisory panel to make recommendations on cloning research and his additional interim steps to ensure no human cloning research takes place. However, I believe that simply relying on an expert panel to provide advice is not adequate.
The issues raised by the existence of Dolly are so important to so many people that we need a broad, public dialogue. I would hope that this Subcommittee can be a vehicle for bringing in that dialogue.
As I look over the roster of this Committee, I see nine very well educated, very well accomplished scholars. And, I would hope that you would also open up and reach out to get more public dialogue.
I think that if there is going to be positive benefits from cloning, it can only happen with public support. You have a very strong charge, an important charge now to bring that public dialogue in and get that public support for a direction.
Page 11 PREV PAGE TOP OF DOC I feel comfortable that you will be able to do that. And, I know that our Chair will also be a leader in that. And, I look forward to hearing your comments.
Mrs. MORELLA. Thank you, Mr. Gordon. We have all consented that we would have no more opening statements but people can put comments into the record.
[The prepared statements of Ms. Johnson, Ms. Jackson Lee, and Mr. Etheridge follow:]
OPENING STATEMENT OF HON. EDDIE BERNICE JOHNSON
With the recent announcement from the Roslin Institute in Scotland that they had successfully cloned a sheep, the imaginations of people have been fueled with visions of a future where the science fiction of today is the reality of tomorrow.
Not surprisingly, the most troubling aspect of the potential for cloning involves what impact cloning research can have on humanity. Few individuals would likely have serious ethical or moral reservations about cloning research involving animal production of milk that contains new medicines. More people may be troubled about cloning research that involves the use of animals to produce human-compatible organs that can be harvested for transplantation. All of us, I believe, are troubled my the moral, ethical, religious and legal implications of human cloning.
The fact is, Madam Chairwoman, that when it comes to cloning, the genie is truly out of the bottle and cannot be stuffed back in. We should not let our fears and concerns cause us to propose and enact ill-advised and ill-timed restrictions on cloning research. We have the time to give this issue thoughtful and comprehensive consideration.
President Clinton has asked the National Bioethics Commission to look into the troubling ethical and legal implications of human cloning research and he has banned federal funding of such research until the issue is fully examined. However we must be careful not to impose restrictions that are not needed at this time and that have the unintended result of halting cloning research in areas that do not involve the cloning of humans but do involve potential advances in treating or preventing human diseases.
Page 12 PREV PAGE TOP OF DOCOfficials of the government, the scientific community and the private sector must come together to consider the serious questions involving cloning research--not only in the United States, but internationally as well. I look forward to future discussions on this exciting topic.
HEARING STATEMENT BY CONGRESSWOMAN SHEILA JACKSON LEE
HOUSE SCIENCE COMMITTEE SUBCOMMITTEE ON TECHNOLOGY
''BIOTECHNOLOGY AND THE ETHICS OF CLONING: HOW FAR SHOULD WE GO?''
MARCH 5, 1997
Madam Chairwoman, I would like to thank you for bringing this opportunity to the Members of the House Committee on Science to gather more information on the important issue of cloning adult mammals and the possible implications for our broader society.
We were made aware of the successful cloning of an adult sheep two weeks ago, but the details were not available until they were reported in the February, 1997, issue of Nature Magazine, the world renowned scientific publication headquartered in England.
As a Member of the House Committees on Science and Judiciary, I found the news both intriguing and unsettling.
We are fast approaching a point in human evolution where the things of science fiction may be the facts of a far too near future.
There are over 5 BILLION people on this earth--and counting--with 266 million of them here in the United States.
Now, in the waning years of this century, researchers have reached a goal first thought to be impossible, by achieving a clone, of an exact replica of a mammal, in the form of an adult sheep from a cell of its body.
The mammary gland cell was taken and made to halt its natural division, injected into an unfertilized egg, then electricity was used to start the mammary gland cell's normal division inside the egg. The egg was then placed into a surrogate mother.
Page 13 PREV PAGE TOP OF DOCA poll conducted right after the announcement earlier this week, indicated that 87% of the American public believed that human cloning should be banned. The high level of anxiety being experienced by the American public, at the disclosure of this new scientific breakthrough, is understandable.
The concern that I share with many of my constituents regarding this issue is the motivation that spurs this area of research.
Will we find ourselves on the brink of discovery in a new realm of human advancement, which may lead to great legal or ethical calamities or toward untold advances in the understanding of human development, without ever having answered the question: Why are we investing resources into the development of ''cloning technology?''
Therefore, I would like to applaud President Clinton's decision to ask the National Bioethics Advisory Panel to review legal, and ethical ramifications of cloning. They will review this matter with the intent of advising whether we need to watch more clearly the dimension of this scientific and technological development that might pertain to any activity involving its abuse. The President took further steps yesterday, by issuing a directive which bans the use of any federal funds for any cloning of human beings. He also urged the private scientific and medical community, every foundation, every university, every industry that supports work in this area to heed the federal government's example.
Although all of the research known of to date has only involved animals and plants we must weight the values of our society in the area of cloning.
It was London born Thomas Henry Huxley, one of the first adherents to Darwin's theory of evolution by natural selection, and who is credited with doing more than anyone else to advance its acceptance among scientist and the public. He said that ''The chess-board is the world; the pieces are the phenomena of the universe; the rules of the game are what we call the laws of Nature. The player on the other side is hidden from us. We know that his play is always fair, just, and patient. But also we know, to our cost, that he never overlooks a mistake, or makes the smallest allowances for ignorance.'' So as we delve further into to this new area of science it may be wise on our part to fully examine to motivation and sound arguments for each step we take along the way. Therefore. I would wholeheartedly support the participation of licensed Ethicist in the decision making process of all public and private cloning projects.
Page 14 PREV PAGE TOP OF DOCI advocate this position based on the experience of the last few weeks regarding the disclosure of the first cloning of an adult mammal in the form of a sheep. Although this cloning technology did not involve a human being, the news of its results affect the peace of minds and sensibilities of millions of people around the world. In my opinion, to consider all aspects of cloning research's impact on people is not unreasonable.
I believe that the President has set the correct tone on this issue and I applaud his leadership.
To say that all cloning should be illegal in the U.S. will not stop research or work on cloning abroad.
The concerns that I have are defining the long-term objectives of genetic research for our Nation's universities and laboratories. Not with the intent of developing a straitjacket approach to the technical intricacies of genetics based research.
If the mind of man can conceive it, should we in Congress make it a part of our National Policy?
We may be fast approaching a time when the philosophical debate regarding this issue recedes to accept the reality of tomorrow's headlines that indeed a team of researchers somewhere on this earth have done the unthinkable--cloned a perfect replica of another human being.
If the ability to clone reached the realm of developing a cloned person would he or she be more than an exact copy of the original person's genetic information?
No, that person would only share the genetic information of the supplier of the material, just as a twin shares the genetic information of his or her brother or sister with only slight genetic anomalies.
But the questions delve deeper than just what is the true meaning of the ultimate unwritten, unspoken research objective of the possible cloning of a human being?
There are many more legal issues to determine than what is a definition of a human being? Parentage, citizenship, civil rights, property rights, and legal rights are only a few.
Many scientist and researchers working in the field of cloning envision no malevolence in their efforts to advance human understanding. They view the possibility of improved organ donation, not by the cloning of the whole human body, but by the cloning of humanized organs for the purpose of transplantation.
Page 15 PREV PAGE TOP OF DOCThe number of individuals stricken by deadly disease and life threatening accidents may find a hope in the future, currently not available to medical science today. The parents of children who are diagnosed with severe birth defects may have the resource of expanded knowledge of our own genetic makeup to correct injuries before they occur or as a part of prenatal medical treatment.
With all of these wonderful medical possibilities remains the true nature of mankind, to seek--to know and--to understand.
Today, I would venture to say that it is not a question of ''if,'' but one of ''when'' will a team of researchers or a single scientist somewhere on the globe find the key to the full physical duplication of a human being?
When that day arrives, will it mean that we will see no more pursuits in the arena of human duplications? Will it mean that once science has attained a cloned human being that the innate curiosity of mankind will stop?
Will scientist and researchers cease to wonder at the next step? Will they dare not ask the next question in the race to create an exact replica of an individual in every respect? Can we silence the next question that would raise like mist from the depths of the human drive to know. Will there be another question? Is it possible to transfer the mind of one person to another?
The questions posed are the ones none of us would like to ponder at this point in the process our scientific exploration of nature, but we must and should seek the answers to the motivation that drives any research.
Are these questions science fiction or just a distant debate for a generation of tomorrow to ponder?
REPRESENTATIVE BOB ETHERIDGE
Thank you, Madame Chairwoman. And I thank all those who will testify before us today.
Page 16 PREV PAGE TOP OF DOCIt is with great excitement and quite honestly considerable astonishment that, as members of the Science Committee, we sit here today to learn more about the new information we have received about ''Cloning.''
There are a lot of unknown and riveting questions which go through my mind just like everyone else's mind when we learn about this news. We can scarcely pick up a newspaper or magazine or turn on the TV news without encountering Dolly the cloned Scottish sheep or the pair of cloned rhesus monkeys in our own country.
For me and the people and businesses of the 2nd Congressional District of North Carolina, there appear to be some enormous benefits from such research.
My District is a unique district of small towns, small businesses, and rural farmland, coupled with high-tech university research facilities and businesses. I think it is the only district in America where tobacco fields sit right next to pharmaceutical companies.
In North Carolina, the synergy of high-tech research and agriculture benefits both. Eastern North Carolina has long been a successful agricultural region, because of the strong work ethic and ingenuity which has made our nation great; we have worked hard and smart, and then some, to provide for our families and our communities so that everyone in the community could have a better opportunity in life.
This same hard work and ingenuity learned in agriculture led to the establishment of the Research Triangle Park in the 1950's. It is the international and North American headquarters for numerous corporations today, like GlaxoWellcome, Northern Telecom, IBM and others. The Raleigh-Durham area also provides a nurturing environment for some of the nation's finest research facilities and institutes of higher learning like Duke University, North Carolina State, UNC-Chapel Hill, and others. This combination of successful agriculture, advanced research and high-tech industries produces an economic climate that allows small businesses to flourish as well.
Madam Chairwoman, Dr. Wilmut's work could have profound and almost immediate implications for advancements for agriculture. In North Carolina, the longstanding cooperative relationship between agriculture and industry encourages us to embrace break-through technology and harness its possibilities. Continuing our investments in research will enhance our ability to retain and recruit cutting edge businesses and give our farmers and agricultural community every advantage they need in the marketplace.
Page 17 PREV PAGE TOP OF DOCYet for all the promise these seeming miracles of research hold, the cloning of species so genetically close to our own touches a raw nerve by forcing the fundamental question of the role mankind plays in God's world. While we grow adept at harnessing the natural world around us, it is quite healthy for us to step back and ask the question, ''Should we?'' before we go roaring off into the future. And if we arrive at the answer of ''Yes,'' then we must ask, ''Under what constraints?'' What guide should we follow as we probe the unknown? Recent events clearly push the envelope of genetic engineering.
These are fascinating and profoundly important questions, and I thank you Madam Chairwoman for convening this hearing so we can begin to ask them. Thank you all for being here, and I look forward to your testimony.
Mrs. MORELLA. We will wait for questioning to hear from others, but I did want to recognize some people who are here today at the hearing.
We have Ms. Stabenow, who was here, who is planning to be on the Subcommittee, from Michigan. Mr. Etheridge from North Carolina is here.
Mr. Ewing is here from Illinois. And, Mr. Capps is here from California.
Thank you very much for joining us, all.
And, now as we go on with our panel, the hearing this afternoon is going to consist of just this one panel of the five experts. Leading off our very distinguished panel of witnesses is Dr. Harold Varmus, the Director of the National Institutes of Health. Dr. Varmus, I know you have been spending a lot of time here on Capitol Hill, but we would really like to hear from you about everything that is happening in the appropriations process as it proceeds.
Our second witness is going to be Dr. Caird Rexroad, who is an animal gene expert for the Department of Agriculture's Agriculture Research Service in Beltsville, Maryland.
And, Dr. M. Susan Smith is the Director of the Oregon Primate Research Center. And, we appreciate your being here, coming from Oregon.
Page 18 PREV PAGE TOP OF DOC The fourth witness is Dr. Tom Murray, the Director of the Center for Bioethics at the Case Western Reserve University in Cleveland. And, in addition, Dr. Murray is also the Chair of the Genetics Testing Subcommittee of the National Bioethics Advisory Commission.
And, finally, rounding out our panel is a gentleman I met this morning, talking about the hearing, Mr. Jim Geraghty, who is the President and CEO of Genzyme Transgenics Corporation, which is perhaps the leading United States company in the field of animal transgenics research. That company is located in Framingham, Massachusetts.
Thank you all for joining us here today. And, we will start off with you, then, Dr. Varmus. Thank you.
STATEMENT OF HAROLD E. VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH, BETHESDA, MARYLAND
Mr. VARMUS. Thank you, Madam Chairwoman. I would like first, on behalf of my colleagues, to thank you for holding this important hearing.
As President Clinton said yesterday, all Americans, including the Clintons, are spending a great deal of time around the dining room table talking about these issues. We see these issues as important topics for conversation so that policy gets set properly. And, we also see it as an opportunity to educate the public about the excitement in biological science.
In my brief remarks, I am going to touch on three things. I would like to review very briefly some of the foundations of the science that allowed the experiment that brought us all together to actually occur.
Secondly, I would like to talk about the future applications of these breakthroughs and to do that in a way that sets the stage for the conversations we will have together with my other panelists.
And, lastly, I would like to speak very briefly about some of the steps that have been taken by the Administration in view of the recent discoveries.
Page 19 PREV PAGE TOP OF DOC The science that we are talking about has a very rich and deep history. Indeed, it was nearly 60 years ago that the famous German embryologist, Hans Spemann, first proposed the notion of nuclear equivalence.
To understand what that phrase means, let us think about a very simplistic view of mammalian development, as shown by the figures on the left side of the chart in the front. After a sperm and an egg, each carrying genes from the mother and father, are fused, a series of cell divisions gives rise to a very primitive embryonic form called the blastocyst, which then develops into an early embryo, and then into a late embryo and then into a fetus, and finally, after several months in the uterus of a mother, produces a newborn and then an adult animal.
During the course of these complex events, which ultimately give rise to a complex organism with many different kinds of cells and tissues, the roughly 80,000 genes that are housed in the nucleus are turned on and off in a series of events that are orchestrated in an extremely complex way. Spemann asked: Could the collection of genes housed within the nucleus of any single cell be competent to give rise to an entire new individual?
Over the course of the last couple of decades, in work with frogs and a variety of animals, that question has been put to a test, using as sources of nuclei at least the four kinds of--or four forms of mammalian organisms shown on the left--that is, cells from very immature embryos, from late embryos, from the fetuses and from adults. Those cells, either directly taken from the blastocyst or grown temporarily in culture, provided the source, the donors, for the nuclear transfer experiments.
The recipient cell in these experiments is an egg from which the nucleus, shown by the pink dot in the center of the drawing, has been removed using a micropipette, a fine needle. That cell, now deprived of its own nucleus, is the place into which the donor nucleus in the donor cell is provided by, first, an injection and then a fusion event that can be initiated, for example, by an electric shock.
Page 20 PREV PAGE TOP OF DOC It's intended that the fused cell then undergo divisions into a multiple cell aggregate that resembles the blastocyst, as normally occurs. And, that blastocyst can then be implanted into the uterus of a surrogate mother in which further developmental events occur and, ultimately, progeny results.
Now, a number of laboratories over the last decade or so have shown--with a variety of animals, including sheep, pigs and most recently, as you will hear soon from Dr. Smith, rhesus monkeys--have given rise to animals from--by nuclear transfer from blastocysts. What, of course, is extremely remarkable about Dr. Wilmot's experiments was the use of later embryos, fetal cells and, in one case, as you have described, Madam Chairwoman, from an adult mammary gland and transferred using some novel technologies was capable of giving rise to a mature animal.
Let me speak briefly to the implications of this science. First, in the area of traditional husbandry, we know throughout the history of man, as an agricultural animal that many techniques have been used to generate optimal forms of plants or animals for feeding the human population. Dr. Rexroad will describe some of those and show how these new techniques could fit into our traditional concepts of husbandry designed, as would be the self-fertilization or corn with the twinning of cows or sheep as a technique for improving the vitality of our agricultural industry.
The second application is in the area of what I would call non-traditional husbandry, husbandry in which the animals that are being used have been modified by genetic technology that Mr. Brown referred to in ways that allow the production of medically useful products or organs that might be suitable for human transplantation.
And, Dr. Geraghty will address some of those applications.
The third application is in the area of research on human disease, in the area of developing models for human disease. As you are well aware, Madam Chairwoman, for many years, investigators have used mice and rats and sometimes other laboratory animals to study a variety of human diseases.
Page 21 PREV PAGE TOP OF DOC Recently, it has been possible to modify the chromosomes of mice using advanced recombinant DNA technology to try to mimic some of the genetic diseases that occur in such animals. While the genetic manipulations are possible, the mice that result from them do not always accurately mimic the disease that one intends to study.
Therefore, the possibility of making such manipulations in other kinds of animals and cloning such animals for the purpose of studying diseases like cystic fibrosis and others is made more possible by some of the technologies we will be discussing. Dr. Smith, in her discussion of the generation of--of genetically identical rhesus monkeys will specifically address this in the context of many diseases, including AIDS, that we are concerned about.
The fourth general area of application addresses questions about fundamental biological principles. I mentioned earlier that during the generation of mature animals, there is a ballet going on in which subsets of our genes are turned on and off in an orchestrated display that underlies many diseases as well as developmental processes.
Understanding how such control occurs, how genes that are told to be off can be once again told to be switched on and vice-versa, will have deep implications for our understanding of mammalian development, aging and many other processes.
Understanding these issues, the answers to such fundamental questions, will, I believe, affect a fifth area of concern; and, that is the reprogramming of human cells to treat certain diseases. We already use such a principle in trying to treat sickle cell disease.
A gene called the fetal globin gene, which is normally turned off in adults, is currently turned on, at least partially, in patients with sickle cell disease using a drug called hydroxyurea. This reduces the frequency of sickle cell crises in such patients by 50 percent.
If we could more efficiently reprogram expression of the globin gene in question, we could have yet more beneficial effects in such patients. But, there are many other situations in which the principles of turning genes on and off may have beneficial effects for patients--in the generation of completely compatible bone marrow; in the generation of skin cells that would not be rejected in bone patients, burn patients; in the generation of nerve cells in patients who have degenerative neurological disorders.
Page 22 PREV PAGE TOP OF DOC The final and sixth area is the one that has attracted the great majority of public attention, even though I would contend that the five I have listed so far are the ones that are of major interest to scientists; and, that is the creation of mature human clones. Now, from everything that you have heard so far, it does seem that this is a possibility although, to my knowledge and to the knowledge of my colleagues here, that has never been successfully attempted.
To do--to make human clones for scientific purposes, to me, is an offensive idea, one that is not scientifically necessary. After all, we already have spontaneously occurring identical twins, reared apart, reared together.
We have animals in whom the questions of interest can be answered. We have cultured cells in which many of the experiments of interest can be carried out.
There is, however, the issue of creating human clones to combat reproductive deficiencies. My own sense is that, if ever to be used, would be used incredibly sparingly.
We prize ourselves as human beings because of our diversity. And, diversity is the product of the mating of sperm and egg.
But, I think in our--in the early stages of this discussion, we need to contemplate whether there might be any rare situations in which it might, indeed, be acceptable to contemplate human cloning under strict conditions of guidance. It's for that reason that I particularly applaud the President's decision to refer the issues of human cloning to the National Bioethics Advisory Commission, which you will hear more about in a moment from Dr. Murray.
As you know, research on human embryos has been restricted in many ways through the NIH. About two and a half years ago, a panel that I commissioned under the leadership of Dr. Steven Meuller, previously the president of Johns Hopkins, reviewed all forms of human embryo research and recommended to the NIH that some be considered for funding, others not and others reserved for further deliberation.
Among those which they recommended not receive federal funding was the cloning of human beings in the manner described here. And, I agree with that conclusion.
Page 23 PREV PAGE TOP OF DOC In addition, we had a presidential order imposed in December of 1994 and amendments to our appropriation bills in the last 2 years that would forbid any experiments that would lead to the cloning of human beings.
As has been said repeatedly now, the President yesterday directed both a government-wide restriction on the use of federal funds for human cloning, extending the ban beyond research and beyond the confines of the Department of Health and Human Services and also asked for a voluntary moratorium in the private sector on human cloning experiments until the Commission has carried out its work. And, again, I applaud the decision to calm the public and reassure them that such work is not going on in the United States to allow the Commission to do its work and for the public to debate these important issues.
And, in that vein, I welcome the opportunity to have spoken to you today and to air these issues further with you. Thank you.
Mrs. MORELLA. Thank you very much. And, before I turn the microphone to Dr. Rexroad, I just want to indicate that Mr. Cook from Utah has joined the panel, as has Ms. Johnson from Texas, who was here just a moment ago; and, Ms. Jackson-Lee from Texas; and, Ms. Rivers from Michigan.
STATEMENT OF CAIRD E. REXROAD, JR., SUPERVISORY RESEARCH PHYSIOLOGIST, AGRICULTURE RESEARCH SERVICE, GENE EVALUATION AND MAPPING LABORATORY, LIVESTOCK AND POULTRY SCIENCES INSTITUTE, UNITED STATES DEPARTMENT OF AGRICULTURE, BELTSVILLE, MARYLAND
Mr. REXROAD. Thank you, Madam Chairwoman and members of the Subcommittee. I am pleased to appear before you today to discuss the technical and scientific aspects of cloning in farm animals and specifically the U.S. Department of Agriculture's biotechnology research.
Page 24 PREV PAGE TOP OF DOC Scientists at the USDA have not been conducting research on cloning using specialized adult cells of farm animals, as we recently heard about from Scotland. However, we are very much involved in biotechnology research with farm animals to improve animal health, production efficiency, food safety, human nutrition and the additional value to animal products.
Cloning of farm animals has been practiced since 1986 when Steen Willadsen first described the technique for the production of cloned sheep using embryonic cells. Subsequently, clones of cattle have been offered on the market for sale, all from embryonic cells.
Dolly has broken a dogma that has long existed in biology--that is that for higher animals, reproduction was limited to the germ cells; that is, the sperm and the egg coming together, fertilization taking place and the reproduction of an embryo, an embryo that would eventually set aside special cells that would enter the testis or ovary and make new germ cells for the next generation. The cloning that we have practiced until now used these embryonic cells collected before germ cells were set aside.
The experiment of Dr. Willmut and his colleagues bypasses the sperm/egg/embryo relationship and indicates that highly specialized cells, even of the adult, can be induced to participate in forming embryos. Their technique was really relatively simple but it is, as of yet, very poorly understood.
Two things they did were to grow these cells--and this is a very important concept--so that their DNA was quiescent, was no longer being synthesized. They joined that to an unfertilized egg which had its DNA removed--and this is the other real important technical point--so to bring these two together to reprogram the genetic code that was in this mammary gland cell to let it know that it can now make an intact embryo.
So, this was quite an accomplishment scientifically. But, what Dr. Willmut and his colleagues and others have been trying to do are to find some cells that they could grow in the laboratory so that we could precisely, genetically engineer those cells and produce clones from these very precisely, genetically engineered cells.
Page 25 PREV PAGE TOP OF DOC So, until they show that they can do this genetic engineering in the lab--and we have our suspicions about how far along they are--until they do that, they won't have completed the research. But, if they do find this ability, then they will have a very powerful technique that they will have available, that we will have available.
You will see things like additional proteins being produced in the milk, some of them to be used for human medicine. And, we will be able to remove or to replace genes in farm animals. For us, that's very important.
The Dolly experiment reflects an advancement of the understanding of how the genetic information in DNA programs the development of an animal from a single cell to a complex organism. Such knowledge of the action of genes in farm animals will help us to improve animal productivity and will yield consumer benefits.
There are two areas of research and ARS will benefit greatly from this technology that is being developed by cloning. The ARS now has research on mapping of genes. It's a--compared to the human genome project--very mini project but nonetheless very important to us.
And, we've produced genetic maps for cows, pigs and sheep at the Meat Animal Research Center in Nebraska. Researchers are now using those genetic maps to try to locate regions of chromosomes that are important for health and production traits.
The longer term goal will be to try to find the underlying genes that make these regions of chromosomes important. Then, we will approach--use a second approach, which is the production of transgenic animals to study how those genes function in these animals.
And, we are currently conducting transgenic research--that is, the insertion of genes into farm animals--at the Beltsville Agricultural Research Center in Maryland and looking at ways to modify the amount of fat in meat, enhance animal resistance to viral disease and understand what kinds of genes should be inserted in cows, how to construct those genes to improve the quality of milk as a food for human infants and adults and to improve fluid milk for processing into cheese and new food products.
Page 26 PREV PAGE TOP OF DOC Another avenue that is opened by this particular research. The ability to clone animals from cultured cells is the enhancement of the possibility of preserving a diverse set of genes for our population. Preserving germplasm to maintain and protect genetic diversity is a high priority for ARS. It enables us to meet future needs for livestock production and provides opportunities against such things as emerging diseases.
Cloning of animals from adult or fetal cells is seen by the ARS to be primarily a tool for research that could lead to important advances in biotechnology. ARS believes that this kind of animal research provides a powerful approach to improving the availability, affordability and quality of food and as being in the public and national interest.
Madam Chairwoman and members of the Subcommittee, thank you for this opportunity to participate in this important hearing. And, I will be pleased at the appropriate time to answer any questions that you may have.
[The prepared statement of Mr. Rexroad follows:]
STATEMENT OF DR. CAIRD E. REXROAD, JR, RESEARCH LEADER, U.S. DEPARTMENT OF AGRICULTURE, AGRICULTURAL RESEARCH SERVICE GENE EVALUATION AND MAPPING LABORATORY, LIVESTOCK AND POULTRY SCIENCES INSTITUTE, BELTSVILLE, MARYLAND
BEFORE THE U.S. HOUSE OF REPRESENTATIVES, COMMITTEE ON SCIENCE, SUBCOMMITTEE ON TECHNOLOGY
MARCH 5, 1997
Madam Chairman and Members of the Subcommittee, I am pleased to appear before you today to discuss the technical and scientific aspects of cloning in farm animals, specifically the U.S. Department of Agriculture's (USDA) biotechnology research.
I want to point out at the beginning of my testimony that the USDA Agricultural Research Service (ARS) scientists are not conducting cloning research on specialized adult cells with sheep or other species as recently reported from Scotland. However, we are very much involved in biotechnology research with farm animals to improve animal health, production efficiency, food safety, human nutrition, and add more value to animal products. I will briefly describe ARS research approaches toward these goals.
Page 27 PREV PAGE TOP OF DOCCloning of farm animals has been practiced since 1986 using cells from embryos. What is new about the Dolly experiment in Scotland is that it represents a major scientific breakthrough in the way we think about reproduction. Prior to Dolly, a dogma of biology was that in higher animals the only cells that could participate in reproduction were the ''germ cells,'' the sperm and egg. Reproduction was seen as the joining of sperm and egg at fertilization to form an embryo. The embryo set aside a special set of cells that would enter the testis or ovary and make new germ cells for the next generation. Cloning, until now, used embryonic cells collected before germ cells were set aside.
The experiment of Dr. Ian Wilmut and his colleagues by-passes the sperm/egg/embryo relationship and indicates that highly specialized cells, of even the mature adult, can be induced to participate in forming embryos. Their relatively simple, but as yet poorly understood, procedure grew cells from the mammary gland in the laboratory and treated them so that the genetic material, deoxyribonucleic acid (DNA), was no longer replicated. Then the scientists took a single quiescent cell and joined it to an unfertilized egg which had its genetic material removed. In one attempt of 434, this procedure produced an embryo that would develop in a surrogate mother to become a thriving lamb.
Dr. Wilmut and many others have been trying to find farm animal cells that they could grow and precisely genetically engineer in the laboratory. When they demonstrate that they can genetically engineer cells, a new procedure will be available to produce new or modified proteins in animals. One set of important proteins will be human medicines to be produced in the milk. You will learn more about this in subsequent testimony.
The Dolly experiment reflects an advancement of understanding of how the genetic information in DNA programs the development of an animal from a single cell egg to a complex organism. Such knowledge of the action of genes in farm animals will contribute significantly to efforts to improve animal productivity and consumer benefits through other approaches to genetics research.
Page 28 PREV PAGE TOP OF DOCARS research on livestock species has used two approaches to understanding the role of genes: (1) gene mapping; and (2) the transfer of genes into farm animals to produce transgenic animals.
First, the ARS has an extensive effort in mapping genes in livestock at the Roman L. Hruska Meat Animal Research Center, Clay Center, Nebraska. Mapping research has produced genetic maps for cows, pigs and sheep. Researchers are now using those maps to locate regions of chromosomes carrying genes important for production characteristics and health characteristics in farm animals. The maps will provide DNA markers used to select animals for breeding to produce future generations of superior animals. Longer term goals of this research are to identify genes that substantially affect animal productivity, animal health, and the nutritive quality of meat and milk and contribute to food safety. We will study genes that this mapping effort suggests are important for these traits by the now common tools of molecular biology to ascertain their function. It is important to note that these animal studies use the same sophisticated tools used for the human genome project and are often the progenitor to breakthroughs for human medicine.
Second, one of the most powerful tools of molecular biology has been the insertion of genes into animals to determine the gene's function. The ARS conducts research on gene insertion at the Beltsville Agricultural Research Center in Beltsville, Maryland to determine how biotechnological approaches will be used to reduce the amount of fat in meat, enhance animal resistance to viral disease, and understand what kinds of genes should be inserted into cows to improve the quality of milk as food for human infants and adults, and to improve fluid milk for processing into cheese and new food products.
A tool of molecular biology not heretofore available to scientists who work with the larger farm animals is the ability to remove or replace genes in cells that can be used to produce animals, as has been accomplished in mice. The recent cloning of sheep from cultured cells suggests that these kind of precise genetic changes might now be possible for farm animals as wells as mice. In addition, the ability to clone sheep or other farm animals from cultured cells will enhance the rate of progress in understanding the role of specific genes by significantly increasing the efficiency of inserting genes into farm animals. I should add, however, that it will increase the level of expertise needed to accomplish this task.
Page 29 PREV PAGE TOP OF DOCThe ability to clone farm animals from cultured cells may also enhance our ability to preserve germplasm because the type of cells that produced Dolly can be successfully stored frozen. Preserving germplasm to maintain and protect genetic diversity for future use is an ARS priority because it enables us to meet the needs for livestock production and provides opportunities for resistance to emerging diseases.
Cloning of animals from adult or fetal cells is seen by the ARS to be primarily a tool for research that could lead to important advances in biotechnology. As I stated at the beginning of my testimony, the ARS does not currently have research projects that include attempts to clone animals from adult cells. Nonetheless, ARS believes this kind of animal research provides a powerful approach to improving the availability, affordability, and quality of food and as being in the public and national interest.
Madam Chairwoman and Members of the Subcommittee, thank you for the opportunity to participate in this important hearing. This concludes my prepared statement about the remarkable cloning experiment and its possible impact on livestock production. I also included additional background on this issue in my written testimony. I will be pleased to answer any questions you may have at this time regarding the information I have provided.
--------Additional material on cloned animals in agriculture
What is a clone? A clone is a new animal produced from a single cell of an existing animal. Cloning of farm animals has been around since 1986 when Steen Willadsen first cloned a sheep from the cells of an embryo. The cells of an embryo were thought to be a natural source of cells for cloning experiments because they are unspecialized. The remarkable experiment recently reported by Ian Wilmut and others and subsequently confirmed indicates that now sheep can be cloned from very specialized cells, the cells that make up the mammary gland of an adult ewe (a mature female sheep). During the last 10 years, cows and pigs have also been cloned, but so far, only from the unspecialized cells of embryos.
Page 30 PREV PAGE TOP OF DOCHow was Dolly produced? Dolly was produced by growing cells from an adult ewe's mammary gland in the laboratory. Blood serum was removed from the broth that fed the cells, as a result, the cells quit making new DNA. The single cell that was to be Dolly was joined to an unfertilized sheep egg from which the DNA had been removed. This joining was caused by placing the cell and egg together and giving them a slight electrical shock. The unfertilized egg material ''restarted'' the genetic program in the DNA that was contributed by the very specialized mammary gland cell so that it could grow into a new embryo that could be placed in a surrogate mothers uterus (womb). Dolly was the only lamb produced from over 300 attempts to join a mammary cell with an egg.
What is so remarkable about Dolly? Dolly represents a major scientific breakthrough because she changes the way we think about reproduction. It has been a dogma of biology that in higher animals the only cells that could participate in reproduction were the ''germ cells,'' the sperm and egg. Reproduction was seen as the joining of sperm and egg at fertilization to form an embryo. The embryo set aside a special set of cells that would enter the testis or ovary and make the new germ cells for the next generation. Now we know that with a relatively simple, but poorly understood procedure, other cells can participate in forming embryos. Understanding the procedure that produced Dolly will teach us many things about how cells are caused to be specialized by the genetic program in their DNA. The applications of these findings remain to be determined but they will have important impacts on agriculture and medicine.
Will future food and fiber producing animals be clones of superior animals? Maybe. Animals are superior both because of their genes and because of their environment. Clones may help us decide the relative importance of these two factors because they are essentially genetically identical. Several limitations, however, suggest that the use of clones may be limited. The best animals today may not be the best animals for tomorrow. One of the advantages of sexual reproduction compared to cloning is that sexual reproduction maintains a diversity of genes in a population that can be selected when environments change. Changes such as the type and quality of feed available, global climate changes and emerging diseases threats all suggest that we should not cause genetic stagnation by settling on clonal reproduction of what we now consider to be superior animals. In addition, genetic progress for important characteristics are still ongoing for all livestock species and breeding goals have not necessarily been met. In dairy cows, milk production has increased since 1950 from under 10,000 pounds/cow per year to almost 20,000 pounds per cow per year. There is no indication that optimum production has been achieved. Does this mean that clones will have no role in production agriculture? I believe that it means that we need to develop models to determine what role clones of superior animals could play.
Page 31 PREV PAGE TOP OF DOCWill there be a role for clones in the genetic improvement of livestock? Farm animals were domesticated from wild ancestral stocks and the best were kept to produce subsequent generations. Breeding of ''like to produce like'' is discussed in the story of Jacob and Laban in Genesis of the Christian Bible in which Jacob miraculously makes lambs have different color patterns than their parents. In the last 50 years genetic progress has depended on statistical inference about the relationship between the productive capacity of animals and their ability to pass the traits on. In the United States the Dairy Herd Improvement Association resulted in remarkable genetic progress in the milk production capacity of dairy cows by keeping milk records for cows and using them to predict which bulls should be used in artificial insemination. Unfortunately not all characteristics of animals, especially health characteristics, have such good records nor are they transmitted as dependably. Genetic improvement of animals may now be further enhanced by the methods of molecular biology and is characterized by two developments: gene mapping and transgenic animals.
The genetic maps for livestock animals developed in the last 5 years at places such as the Meat Animal Research Center in Clay Center, Nebraska are tools to help us understand the structure of the genetic information in the DNA of livestock. We are developing genetic fingerprinting techniques that will be used to select superior livestock animals. At the same time we are using these maps to identify the genes that are important for characteristics of animals such as their milk production, fat in the meat, and disease resistance. These maps are sparsely populated with genetic markers and genes compared to the human and mouse maps. Nonetheless, much of the information from the human genome project will be useful in the gene research in livestock.
What do you do with these genes when you find them and what does that have to do with clones? We will try to define the function of the genes that we find. Some of the methods will depend on analytical techniques and comparison to research in other species. In some cases we will want to test the genes in laboratory or farm animals. The techniques used for cloning Dolly provide a clue for how that might be accomplished in livestock. Inserting genes into farm animals was first reported in 1986 by a collaboration among researchers at the University of Pennsylvania, University of Washington, and the ARS of the USDA at Beltsville, Maryland. The technique used was to inject DNA containing the gene into an embryo. This research is costly because less than 1% of the embryos produce newborns that contain the new genetic information, but surrogate mothers must be maintained for all offspring. In the laboratory DNA can be inserted into cells in culture and the cells with the new DNA can be selected for study. The cloning of Dolly suggests that we can find adult, or more likely fetal, cells that can be genetically manipulated in the laboratory and used to produce, by cloning, offspring that all contain the new gene. Indeed because genes can be modified in the laboratory, we will not be limited to studying genes that we find, but we will be able to change those genes. These studies have already been done inefficiently but successfully to produce genes that cause protein medicines to be produced in milk by sheep, goats and pigs. The agricultural use of this technology will be to produce, for example, milk with improved nutritional qualities for consumption by human infants.
Page 32 PREV PAGE TOP OF DOCDoes cloning have a role in germplasm preservation? Possibly. There are techniques for the freezing of semen from sheep, cattle and pigs. The embryos of sheep and cattle can be preserved by freezing. Not all species of potential agricultural interest have been researched for the freezing capacity. Cultured cells are frequently frozen successfully. Culture of somatic cells may be of limited utility for germplasm preservation.
Are these the only implications of Dolly for agricultural science? No! Like any discovery the full impact will be known only after much investigation and after many scientist have considered the range of possibilities.
Mrs. MORELLA. Thank you, Dr. Rexroad. I also notice that in your written statement, which shall be included in its totality in the record, as will the other statements in their entirety, you have also indicated or given us some additional material which is a question and answer response, which is helpful. What is a clone? How was Dolly produced, et cetera.
We appreciate that, too.
Mr. REXROAD. Thank you. I hope that it is helpful, Madam Chairwoman.
Mrs. MORELLA. Yes. I am pleased to turn now to Dr. M. Susan Smith.
STATEMENT OF M. SUSAN SMITH, DIRECTOR, OREGON REGIONAL PRIMATE RESEARCH CENTER, OREGON HEALTH SCIENCES UNIVERSITY, BEAVERTON, OREGON
Ms. SMITH. Thank you, Madam Chairwoman. It's a pleasure to be here and to have this opportunity to speak with you today.
Nonhuman primates, such as monkeys, are valuable animal models because of their genetic and biologic similarity to humans. And, it is because of these similarities that they can be used to answer many questions related to human health and disease.
Page 33 PREV PAGE TOP OF DOC Moreover, the availability of genetically identical monkeys would provide a powerful resource for biomedical research, because it would eliminate genetic variation from research studies. To give one example, this has very important implications for studying the pathogenesis in the treatment of AIDS.
Although researchers have used many methods to produce genetically identical animals, as Dr. Varmus has so nicely outlined, the most powerful technique, which was first demonstrated in frogs over 40 years ago, is called nuclear transfer. For the past 2 years, Dr. Don Wolf and his associates at the Oregon Regional Primate Research Center have performed experiments to determine if nuclear transfer is a valid technique for the production of rhesus monkeys.
To describe this technique in a very general way, rhesus monkey embryos are produced by standard in vitro fertilization techniques, which are similar to those used in infertility clinics around the world. At the earliest stage of embryo development, each cell in the embryo can be separated apart and is capable of developing into an individual offspring.
So, for example, using this technology, an eight-cell embryo could provide eight individual cells that could develop into eight genetically identical monkeys. These embryonic cells are transferred into the reproductive tract of host mothers and a normal pregnancy ensues.
Using this technique of nuclear transfer, we have had two pregnancies that resulted in the birth of a normal, healthy male and a normal female. This happened in August of 1996. I am sure many of you have seen pictures of these youngsters, who appear to be very normal in every aspect.
There is an important distinction between the work at the Oregon Center and that recently described by Dr. Willmut in Scotland. Whereas, both groups are using nuclear transfer techniques, Dr. Willmut was able to transfer a cell from an adult sheep and produce a live offspring. Hence, an adult animal was cloned for the first time. To put it another way, a copy was made of an already existing adult animal.
Page 34 PREV PAGE TOP OF DOC The efforts at the Oregon Center will continue to focus exclusively on the use of embryonic cells to produce genetically identical offspring; that is, individuals who are genetically identical to each other but different from their adult parents. We have no plans, nor is there any rationale present at the time, for cloning adult monkeys.
I also wish to emphasize that despite reports, we have not, as yet, produced genetically identical monkeys. However, Dr. Wolf is in the process of attempting to produce several sets of genetically identical twins. And, hopefully, we will know some more results by the end of the year.
After accomplishing this goal, Dr. Wolf proposes to improve these procedures so that large numbers of identical monkeys can be produced. These animals would be made available to the biomedical community for experimental use.
Genetically identical monkeys would revolutionize the use of nonhuman primates in biomedical research.
First: fewer animals would be required in research studies because of their genetic homogeneity.
Second: the animals would provide new opportunities for testing gene therapy treatments for human disease.
Third: researchers would be able to study the effects of factors such as stress, the environment and nutrition without the confounding influence of genetic variability.
Finally, these techniques can be used to preserve the gene pool of nonhuman primate species in danger of extinction.
I would like to say, in conclusion, that our work at the Oregon Center in developing the capability to produce genetically identical monkeys is very exciting to the scientific community and has great potential to improve human health. I also recognize that we need to go forward carefully as we use these very powerful techniques.
Page 35 PREV PAGE TOP OF DOC However, we should not prevent important new research from being conducted in experimental animals while the public debate on cloning proceeds.
Thank you for your attention.
[The prepared statement and attachment of Ms. Smith follow:]
STATEMENT OF M. SUSAN SMITH, PH.D., DIRECTOR, OREGON REGIONAL PRIMATE RESEARCH CENTER, OREGON HEALTH SCIENCES UNIVERSITY
RHESUS MONKEYS PRODUCED BY NUCLEUS TRANSFER
TESTIMONY PRESENTED TO THE TECHNOLOGY SUBCOMMITTEE OF THE SCIENCE COMMITTEE, U.S. HOUSE OF REPRESENTATIVES
HONORABLE CONNIE MORELLA--CHAIR
MARCH 5, 1997
Because of their genetic and biologic similarity to humans, nonhuman primates are a valuable animal model for answering many questions pertaining to developmental biology and biomedical research. Moreover, the availability of genetically-identical nonhuman primates would provide a powerful resource for biomedical research, because it eliminates genetic variation during experimental manipulation and allows greater statistical validity with fewer animals. Such a primate resource would be analogous to the inbred strains of mice that have greatly facilitated studies on biological mechanisms, disease processes, and the development of new treatments such as gene therapy. Researchers have used several methods to produce genetically-identical animals, including the mouse, rabbit, pig, sheep, and cow. However, the most powerful technique, which was first demonstrated in frogs over 40 years ago, is called ''nuclear transfer.''
For the past two years, Dr. Don Wolf and his associates at the Oregon Regional Primate Research Center performed experiments to determine if nuclear transfer is a valid technique for the production of rhesus monkeys. The enclosed figure (Fig. 1) summarizes the technique. In Step 1 (upper left panel) embryos are produced by standard in vitro fertilization (IVF) procedures analogous to those used in infertility clinics around the world. These embryos are grown in culture to the 6-to-12 cell stage; then one embryo is selected and dissociated into individual cells or blastomeres that serve as the source of donor nuclei. Thus, an X-cell embryo could provide the genome (nucleus) for 8 genetically-identical monkeys. In Step 2 (upper right panel), mature oocytes, or eggs, are collected from another animal and the nuclear material (genome) removed by micromanipulation. A micropipette pierces the zone layer covering the egg cell and the nuclear material is drawn into the pipette, leaving an enucleated egg, or cytoplast. Thus, if one has eight blastomeres as a source of donor nuclei, then eight enucleated eggs are also required. In Step 3 (bottom panel), the blastomere is transferred into the space between the enucleated egg and its zone cover and the blastomere: enucleated egg fused together, using an electrical field. Thus, the embryonic cell provides the nucleus and the egg provides the large amount of cytoplasm needed for growth of the reconstituted embryo. The reconstituted embryos are cryopreserved in liquid nitrogen for up to several months before thawing and transfer into the reproductive tract of host mothers at the optimal time in the menstrual cycle.
Page 36 PREV PAGE TOP OF DOCFifty-nine reconstituted embryos were produced by nuclear transfer; they appeared morphologically normal and underwent early cell division prior to cryopreservation. When selected embryos (typically 2-3) were transferred into nine monkeys, three animals became pregnant. One pregnancy was lost at 30 days of gestation. The remaining two pregnancies resulted in the birth of a normal, healthy male and female in August, 1996. No clinical abnormalities have been observed. The parentage of both nuclear transfer infants was confirmed by genetic typing, using DNA markers.
Thus, we have proven that the technique of nuclear transfer is feasible in nonhuman primates and could be used to produce genetically-identical monkeys. As currently outlined, using dissociated cells from one early embryo, it is possible in theory to produce approximately a dozen identical animals. However, considering the efficiency of the various steps, including pregnancy initiation after transfer of reconstituted embryos, the production of identical twins or triplets is more realistic. However, if one could develop a more robust source of donor nuclei, for example an undifferentiated ''stem cell'' line from a monkey embryo that would provide an unlimited number of nuclei, then the potential exists to produce entire colonies of identical monkeys for research purposes. Moreover, it would be possible to use gene manipulation technology prior to nuclear transfer (such as the addition or deletion of a gene associated with a particular disease) to create, for the first time, transgenic or genetically-altered monkeys for critical studies of direct relevance to human health.
There is an important distinction between this work and that described recently by Dr. Ian Wilmut in Scotland. Whereas both groups are using nuclear transfer techniques, Dr. Wilmut was able to transfer a cell from an adult sheep into an nucleated egg and produce a live offspring; hence, an adult animal was cloned for the first time. The efforts at the Oregon Regional Primate Research Center have and will continue to focus exclusively on the use of embryonic cells as nuclear donors; there are no plans (or rationale) for cloning adult monkeys. I wish to emphasize that despite reports, we have not as yet produced genetically-identical monkeys. We have, however, proven the feasibility of using nuclear transfer techniques for this purpose. To this end, Dr. Wolf recently submitted an application to the NIH requesting funds to produce 5 sets of genetically-identical monkeys in the initial year by the described technique. The proposal is designed to improve the procedures, with the goal of offering these animals to the biomedical community for experimental use while evaluating the efficiency and cost-effectiveness of this evolving approach.
Page 37 PREV PAGE TOP OF DOCGenetically-identical monkeys would revolutionize the use of nonhuman primates in biomedical research by: (1) reducing the number of animals required in treatment groups because of their genetic homogeneity, (2) providing new opportunities for genetic manipulations to study molecular processes and treatments in diseases and human health, 3) enabling the study of factors, such as stress, the environment or nutrition, without the confounding influence of genetic variability, and 4) providing an alternative to using endangered species collected from the wild, as well as preserving the gene pool of species in danger of extinction.
Insert offset folio 1
Mrs. MORELLA. Thank you very much, Dr. Smith.
I would like to now--Dr. Murray, with your indulgence, before you begin your testimony, I have already mentioned that members of your NBAC Genetic Subcommittee are here and I would like to individually recognize them.
We have Ms. Patricia Backlar--maybe she would stand--from the Oregon Health Sciences University; and, Dr. James Childress, who is the Chair of the Human Subjects Subcommittee, from the University of Virginia at Charlottesville. Welcome.
Dr. Ezekiel Emanuel, J. Emanuel, from Dana-Farber Cancer Institute; Dr. Carol Greider, who is from Cold Spring Harbor Laboratory. Thank you.
Mr. Steven H. Holtzman from Millenium Pharmaceuticals, welcome.
Dr. Bernard Lo from the University of California, San Francisco. He's not here now.
Dr. David Cox, Stanford Medical School. Thank you.
Dr. William Raub, who is the Deputy Assistant Secretary for Science Policy. I haven't seen you for a long time.
Mrs. MORELLA. He used to be Acting Director at NIH.
Page 38 PREV PAGE TOP OF DOC Ms. Henrietta Hyatt-Knorr, who is the Acting Deputy Executive Director of NBAC. Fine.
Thank you all very much. Dr. Murray, it's now yours.
STATEMENT OF THOMAS M. MURRAY, CHAIRMAN, GENETICS TESTING SUBCOMMITTEE, NATIONAL BIOETHICS ADVISORY COMMISSION; PROFESSOR AND DIRECTOR, CENTER FOR BIOMEDICAL ETHICS, CASE WESTERN UNIVERSITY, SCHOOL OF MEDICINE, CLEVELAND, OHIO
Mr. MURRAY. Thank you very much, Madam Chairwoman. And, I am delighted that you saw fit to introduce the members and staff of the Commission. They are a superb group of people.
Thank you very much, Madam Chairwoman, for the invitation to speak with you today. Although I am not officially representing the National Bioethics Advisory Commission or its Chair, Dr. Harold Shapiro of Princeton University, I believe I can fairly convey the Commission's gratitude for your interest in the subject of today's hearing and assure you of our determination to make a full and timely response to the President's request.
Dr. Shapiro, in fact, has already spurred the full Commission, not just the Genetic Subcommittee, into action on the issue. Indeed, the bulk of the Commission's meeting scheduled for the 13th and the 14th of March, next Thursday and Friday, will be devoted to the issue of cloning.
At that meeting, we hope to hear a clear explanation of the science and the potential applications of cloning. We are also calling upon leaders of the major religious traditions in the United States to present their views about the ethical issues raised by the prospect of cloning human beings.
We expect to have a frank and vigorous airing of concerns. And, as with all meetings of the Commission, there will be ample time set aside for public testimony as well.
Page 39 PREV PAGE TOP OF DOC I want to speak now not as a member of the presidential commission or as a representative of my institution but as an ethicist, a parent and a citizen with my own concerns about the possibilities of human cloning. If the techniques used to clone Dolly worked in human beings, they could lend new meaning to the desire to ''have a child just like myself,'' though when I mentioned this to my class last week, one of my students said that she had heard her parents say that but they usually didn't mean it as a compliment.
Mr. MURRAY. They said, ''I hope you have a child just like yourself.''
Mr. MURRAY. In any event, we have to cope with the new possibility, technically at least, of the conception and birth of genetic replicas of already existing persons.
Now, as Dr. Varmus pointed out, we are familiar with clones of a sort. Identical twins occur when an embryo divides into two genetically identical ones. If we applied cloning technology to ourselves, we would be substituting controlled, intentional and perhaps decades-delayed cloning for the occasional accident of nature.
But, cloning strikes us as very different from the birth of identical twins. What is it about cloning that seems to trouble us so much?
It's important to understand what this new technology cannot do. If someone were to clone a 40-year old woman, you would not get another 40-year old woman, despite what movies seem to indicate. You would get an embryo that would have to be implanted in a woman's uterus, pass through all the normal stages of fetal development before birth. Then would come infancy, childhood and the throes of adolescence.
It would be 40 years and 9 months before the cloned individual would herself be 40--by which time the genetic source would be 80 or 81. So, there will be no instant copies.
Many people have spoken to me lately about the possibility of cloning human beings. One woman, when I had said I thought we should probably not permit this, she asked if we could make an exception for Mel Gibson.
Page 40 PREV PAGE TOP OF DOC [Laughter.]
Mr. MURRAY. Now, the good news is that the clone may, in fact, look a great deal like Mel Gibson. And, that may be all that matters to some people.
Mr. MURRAY. But, the bad news is that Mel's charm lies in his personality and wit, at least as much as in his good looks. Or, maybe that's just me speaking hopefully.
Mr. MURRAY. Mel's clone would be very different from the original. He would have different parents, different friends, a lifetime of different experiences to shape his character.
He would come of age in a different historical era. The depression and world war shaped my parents' generation. Mine came of age with rock and roll and Vietnam. My children's experiences were different again from mine. Likewise with the clone, any clone, of Mel Gibson.
Our genes are merely the ground plan. Our personalities are made up by the totality of our life experiences--what we learn and whom we love. And, no two lives are identical.
So, why are we uneasy about cloning? We might be worried about the dangers of excessive control over human reproduction, about the dangers of unbounded human pride.
In the public debate that has begun, a great deal hinges on what questions we think are central. Some will want to ask. Who would be harmed by cloning? Whose rights would be violated?
The claim that children are harmed--the children created by cloning would be harmed thereby requires comparing a perhaps much less than ideal existence with non-existence. That's a difficult comparison to make. I mean, to me, it's like trying to divide by zero. You don't get a very useful answer.
Another question is. Whose rights would be violated? And, here we have a similar problem as we did trying to think about harm to the child.
Page 41 PREV PAGE TOP OF DOC If we are talking about violating the child's rights, we have a quandary. Until the child is created, there is no child whose rights we could possibly violate, yet that creation would be accomplished by precisely those actions which we want to say violated those rights. That's a confusing kind of claim to make.
I believe that there are--neither of these arguments, it seems to me, reflect very well the depth of concern, indeed, the revulsion that many Americans feel in response to the prospect of cloning human beings. I share those concerns.
And, so I want to urge us to look for their strongest representations. Certainly, many people will reject cloning based on their religious beliefs.
We will benefit from a full and vigorous airing of those religious objections to human cloning. And, we intend on the Commission to have that.
I believe there are, as well, a set of moral concerns at the heart of our response to cloning that touch the most intimate and important relationships in our lives--the relationships of parents and children, the lives of families. I would like to see us begin by asking questions like. What do we value most about the relationships of parents and children? What is it in the lives of families that we find most precious and most worth preserving?
Cloning, like other reproductive technologies, ought to be judged not just on whether it harms a particular person or violates someone's rights, although those are important concerns. Our response to cloning should ask whether it supports or whether it undermines what we value most about children and about being a parent.
In the realm of family life, choosing the precise genetic composition of your offspring, which is one of the things cloning does, may not be a virtue.
Responsible scientists will, I expect, have the same reaction to human cloning as we have heard from Dr. Varmus and Dr. Wilmot, along with most non-scientists--that it's repugnant and should not be done. It is essential that we do our best to understand those moral objections and to give them their most cogent and forceful form.
Page 42 PREV PAGE TOP OF DOC It is also essential that we keep in view the possible scientific and ultimately the human benefits of research on animal cloning, benefits best described by witnesses you have already heard. It is important that our public policy response to research on the cloning of animals not be swept along by our concern to prevent what we will judge to be the ethical dangers of human cloning.
[The prepared statement of Mr. Murray follows:]
COMMITTEE ON SCIENCE, SUBCOMMITTEE ON TECHNOLOGY, U.S. HOUSE OF REPRESENTATIVES
5 MARCH, 1997
TESTIMONY OF THOMAS H. MURRAY, PH.D., CENTER FOR BIOMEDICAL ETHICS, SCHOOL OF MEDICINE, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO
I want to begin by thanking Representative Morella, Chairwoman of this Subcommittee for the invitation to speak with you today. Although I am not officially representing the National Bioethics Advisory Commission or its Chair, Dr. Harold Shapiro, of Princeton University, I believe I can fairly convey the Commission's gratitude for your interest in the subject of today's hearing, and our determination to make a full and timely response to the President's request for ''a thorough review of the legal and ethical issues associated with the use of this technology,'' and for ''recommendations on possible federal actions to prevent its abuse.''
In that connection, it should be noted that Dr. Shapiro has already spurred the Commission into action on this issue, and that the bulk of the Commission's meeting scheduled for 13 and 14 March, 1997 will be devoted to the issue of cloning. At that meeting we hope to hear a clear explanation of the science and potential applications of cloning. We are also calling upon leaders of the major religious traditions in the United States to present their views about the ethical issues raised by the prospect of cloning of human beings. We expect to have a frank and vigorous airing of concerns. As with all meetings of the Commission, there will also be time set aside for public testimony.
Page 43 PREV PAGE TOP OF DOCI want to speak now not as a member of a Presidential Commission or as a representative of my medical school or university, but as an ethicist, parent, and citizen with my own concerns about the possibility of human cloning. There is a saying in my field that ''good ethics begins with good facts.'' The facts are just now emerging, so what I say today might have to be revised in the light of the better understanding of the facts that will come with time. The ''facts'' here include whether cloning of higher animals using the nuclear DNA of adults of that species can be accomplished efficiently, or whether Dolly was a fluke; whether the technology would work with humans; for what purposes people might want to clone humans.
We also need to see what laws we have in place now that are relevant to human cloning, as well as what current laws might be extended to cover it. It may well be that our laws governing research with human subjects could provide the protections that the American people believe are necessary.
If the techniques used to clone Dolly worked in humans, they could lend new meaning to the desire to ''have a child just like myself.'' (Though, as one of my students reminded me, something very similar is occasionally uttered by frustrated parents when they say ''I hope you have a child just like yourself!'') In any event, we have to cope with a new possibility--the conception and birth of genetic replicas of already existing persons.
We are all familiar with clones of a sort. Identical twins occur when one embryo divides into two genetically identical ones. If we applied cloning technology to ourselves we would be substituting controlled, intentional and perhaps decades-delayed cloning for the occasional accident of nature. But cloning strikes us as very different from the birth of identical twins. What is it about cloning that troubles us?
It is important to understand what this new cloning technology cannot do. If someone were to clone a forty-year-old woman, you would not get another forty-year-old woman, but an embryo that would have to be implanted in a woman's uterus and pass through all of the normal stages of fetal development before birth. Then would come infancy, childhood and the throes of adolescence. If would be forty years and nine months before the cloned individual would be a forty-year-old woman herself-by which time the genetic source would be eighty or eighty-one. So, no instant copies.
Page 44 PREV PAGE TOP OF DOCI've spoken with many people recently about the possibility of cloning human beings. One suggested that if we were to ban human cloning, we should make an exception for Mel Gibson. I like Mel Gibson. The good news is that the clone may look a great deal like Mel Gibson. And that may be all that matters to some people. The bad news is that Mel's charm lies in his personality and wit at least as much as it does in his good looks. And Mel's clone could be very different from the original. He would have different parents, different friends, a lifetime of different experiences. He would come of age in a different historical era. The depression and world war shaped my parents' generation; mine came of age with rock and roll, and then Vietnam. My children's experience is different again from mine. Likewise with the cloned version of Mel Gibson. Our genes are merely the ground plan. Our personalities are made up as well by the totality of our life experiences, what we learn and whom we love. And no two lives are identical.
So why are we uneasy about cloning? We might be worried about the dangers of excessive control over human reproduction, about unbounded human pride. In the public debate that has begun, a great deal hinges on what questions we think are central. Some will want to ask Who would be harmed by cloning? Whose rights would be violated? The claim that children are harmed by cloning requires comparing a possibly less-than-ideal existence with non-existence--a tough comparison to make. It's a bit like trying to divide by zero. In this case, you cannot get a very meaningful answer. Another appropriate question to ask is whose rights would be violated? Here we run into a similar problem as we did in trying to think about who is being harmed. If we are talking about violations of the child's rights, we encounter an interesting quandary. Until the child is created, there is no child whose rights we could violate, yet that creation would be accomplished by precisely those actions which we want to say violate the child's rights.
Neither of these arguments, it seems to me, reflect very well the depth of concern, indeed the revulsion, that many Americans feel in response to the prospect of cloning human beings. I share those concerns, and so I want to urge us to look for their strongest representations. Certainly, many people will reject cloning based on their religious beliefs. We will benefit from a vigorous and complete airing of those religious objections to human cloning.
Page 45 PREV PAGE TOP OF DOCI believe there are a set of moral concerns at the heart of our response to cloning that touch the most intimate and important relationships in our lives--the relationships of parents and children, the lives of families. I would like to see us begin by asking questions like What do we value most about the relationship of parents and children? What is it in the lives of families that we find most precious and worth preserving? Cloning, like other reproductive technologies, ought to be judged not just on whether it harms a particular person or violates someone's rights. Our response to the possibility of human cloning should ask whether it supports or undermines what we value most about children and about being a parent. In the realm of family life, choosing the precise genetic composition of your offspring (which is what cloning effectively does) may not be a virtue.
Last week I heard a man hail the idea of human cloning. He said that he looked forward to the prospect of cloning himself, then raising his child/himself without making all the mistakes his parents had made. I don't envy that child.
Responsible scientists will, I expect, have the same reaction to human cloning as Drs. Varmus and Wilmot, along with most non-scientists--that it is repugnant and should not be done. It is essential that we do our best to understand those moral objections and to give them their most cogent and forceful form.
It is also essential that we keep in view the possible scientific, and ultimately the human, benefits of research on animal cloning, benefits best described by the other witnesses before you today. It is important that our public policy response to research on the cloning of animals not be swept along by our concern to prevent what we will judge to be the ethical dangers of human cloning.
Mrs. MORELLA. Thank you very much, Dr. Murray. Mr. Geraghty, I look forward to hearing from you again.
Page 46 PREV PAGE TOP OF DOCSTATEMENT OF JAMES GERAGHTY, PRESIDENT AND CHIEF EXECUTIVE OFFICER, GENZYME TRANSGENICS, FRAMINGHAM, MASSACHUSETTS
Mr. GERAGHTY. Thank you, Madam Chairwoman. I appreciate the invitation to appear before this Subcommittee, particularly with such distinguished fellow panel members.
I am here to discuss transgenic technology and the potential impact and some of the most specific benefits that recent advances in cloning technology may eventually have on the development and production of important therapeutic products. Although I do not officially represent the biotechnology industry, I believe that most of what I will say represents its consensus.
Let me say at the outset that I am confident that everyone in the biotechnology industry shares the unequivocal conviction that there is no place for the cloning of human beings in our society and recognizes that we must work within accepted societal limits. In these brief remarks, I would like to provide information on important research programs currently underway which cloning technology could enhance and which I believe it is equally clear have and merit wide popular support.
Biotechnology provides the ability to provide a wide range of therapeutic products, many of which offer the ability to treat successfully serious diseases not able to be treated any other way. More than a dozen such products have been introduced in the past several years, treating such diseases as heart attacks, strokes, genetic disorders and saving or improving the lives of hundreds of thousands of people.
Transgenic technology represents the area of biotechnology for which animal cloning may offer the greatest benefits and is, therefore, the principal focus of this statement. Transgenic technology involves the transfer of genetic material from one species to another.
Page 47 PREV PAGE TOP OF DOC And, it can be used for a number of different medical purposes. Let me give you some examples.
First. Animals are being bred today whose organs may be transplanted into human patients suffering from organ failure and a lack of availability of human organs for transplantation.
Another example, as has been discussed here, lies in the development of genetically engineered animal models for use in testing potential treatments for various serious diseases.
As a final example, cloning technology may be useful in breeding animals that produce human therapeutic products. This is the focus of my company's work, which I would like to describe very briefly.
Transgenic technology is widely used today to develop therapeutic proteins in the milk of dairy animals. At Genzyme Transgenics, we have expressed more than 25 different proteins in milk of many different kinds.
We are currently developing products for the treatment of cardiovascular diseases, several forms of cancer, diabetes, hereditary disorders and others. We are presently engaged in phase II clinical trials under a US IND with a transgenic form of human antithrombin III, a protein that helps prevent harmful blood clotting in many serious medical conditions.
There are several important benefits to transgenic production. For some very complex proteins, transgenic technology represents the only technically feasible way in which the product can be manufactured. For many others, transgenic technology offers significant and even dramatic economic benefits.
And, finally, milk offers a safer alternative source for products currently derived from sources such as pooled human plasma, which necessarily carries some risk of transmitting infectious human diseases to the recipients.
Genzyme Transgenics has published widely on our work and maintains an open dialogue with and broad support from the scientific community, our local communities and the public. Further information regarding transgenic production has been provided in the monograph submitted along with this statement.
Page 48 PREV PAGE TOP OF DOC I would like now to turn specifically to the potential benefits that so-called animal cloning or nuclear transfer technology, as it has been more broadly described here, may have. The cloning of animals has little application to transgenic production in the near term. This is the case both because large scale cloning is not commercially viable at this time and because transgenic production is highly successful and fully viable without it.
Longer term, nuclear transfer technologies could further enhance the effectiveness of transgenic production in several respects. These include enabling the breeding of a large number of offspring from a female founder animal in a single generation. This could allow the acceleration of herd expansion, clinical trials and product launch.
Second. Ensuring that all offspring bred from a founder are both transgenic and female. This could reduce the number of births and, therefore, the costs required to generate a full size production herd.
And, finally, further ensuring the biochemical identity of material from different animals by eliminating variability in background genetic factors. This factor could be of great value in areas such as the breeding of animals for organ transplantation.
It should be emphasized that these advances would represent only incremental enhancements to more established, if less well publicized, technologies. It is also possible that advances using other forms of nuclear transfer technology will achieve some of these objectives earlier or more effectively than animal cloning.
Finally, I would like to reiterate that all of these advances are fully achievable without any activities in any way involving the cloning of human beings.
In closing, I would like to suggest what I believe could be the most significant opportunity presented by the birth of Dolly. As an event which has clearly captured the popular imagination, this event offers a powerful platform from which to inform people about advances in biopharmaceutical therapies and, in the context of related biomedical advances, in our basic understanding as to how life works.
Page 49 PREV PAGE TOP OF DOC With such a focus, this moment offers the ability to engage an even broader community in a constructive dialogue about the benefits and acceptable limits of the technologies involved. As Congress examines this issue further, we ask that you focus principally on mechanisms for further education and public participation in these fields.
I join with others here in reminding the Congress that a rush to judgment in complex areas can lead to bad policy, and in urging you not to rush to legislation that might restrict widely accepted technology with great potential therapeutic benefits.
Madam Chairwoman, I believe that I speak for the biotechnology industry in thanking you for engaging in a constructive dialogue on these matters. We are always appreciative of the opportunity to update the Congress and the American people about the continuing progress underway in biotechnology.
Our industry is very conscious of the need to maintain an open dialogue on these matters and to engage only in research and medical activities that are ethically responsible and acceptable to our society.
[The prepared statement of Mr. Geraghty follows:]
STATEMENT OF JAMES GERAGHTY, PRESIDENT AND CHIEF EXECUTIVE OFFICER, GENZYME TRANSGENICS, FRAMINGHAM, MASSACHUSETTS
RELEVANCE OF CLONING TO TRANSGENIC TECHNOLOGY
SUBCOMMITTEE ON TECHNOLOGY, COMMITTEE ON SCIENCE
MARCH 5, 1997
Madam Chairman and other members of the Subcommittee, my name is Jim Geraghty and I am president and chief executive officer of Genzyme Transgenics, a biotechnology company based in Framingham, Massachusetts. I appreciate the invitation to appear before this subcommittee, particularly along with such distinguished panel members. I am here to discuss transgenic technology and the potential impact that recent advances in cloning technology may eventually have on biopharmaceutical development and production.
Page 50 PREV PAGE TOP OF DOCCloning technology, like many other important scientific discoveries, poses great potential benefits to society as well as raising important ethical concerns. Let me say at the outset that I am confident everyone in the biotechnology industry shares the unequivocal conviction that there is no place for the cloning of human beings in our society. In these brief remarks, I would like to provide information on important transgenic research programs currently underway, and benefits that animal cloning may add, which I believe it is equally clear have and merit wide public support.
I. The Reality of Transgenic Production
A. Transgenic Technology
Transgenic technology involves the transfer of genetic material from one species to another, and can be used for a wide range of medical purposes. Cloning may offer some potential for improving the efficiency of various applications of this technology. Let me give you some examples:
Animals are being bred today whose organs may be transplanted into human patients suffering from organ failure, presenting some risk of immune system rejection. Cloning technology could potentially be used to make it easier to breed animals with organs that the human immune system would better accept.
Another example lies in the development of genetically-engineered animal models for use in testing potential treatments for various serious diseases. Cloning technology could allow for these animal models to be bred more quickly, which could in turn allow for research into curing a wider range of human diseases.
As a final example, cloning technology may be useful in breeding animals that produce human therapeutic products. This is the focus of my company's work, which I would like to describe briefly.
B. Production of Therapeutic Products
Transgenic technology is widely used today to produce therapeutic proteins in the milk of dairy animals. At Genzyme Transgenics, we have expressed more than 25 different proteins of many different kinds. We are currently developing products for the treatment of cardiovascular diseases, several forms of cancer, diabetes, hereditary diseases, and others. We are presently engaged in phase II clinical trials under a US IND with a transgenic form of human antithrombin III, a protein that helps prevent harmful blood clotting in many serious medical conditions.
Page 51 PREV PAGE TOP OF DOCWe produce these proteins by linking the gene that codes for them to the gene that codes for a naturally-occurring milk protein. This construct is then injected into a one-cell animal embryo, such that the new material can incorporate into the genetic make-up of the resulting offspring. This integration does not occur in every embryo, but about 10% of the animals born following injection will reliably incorporate the new material.
Once a transgenic animal has been born, the transgene will be stably inherited by its offspring. The transgene has no effect on the animals of any kind, except that when female offspring lactate the therapeutic protein is expressed in their milk along with native proteins. This protein can then be purified away for the production of a pharmaceutical product.
There are several important benefits to transgenic production. For some very complex proteins, transgenic technology presents the only technically feasible way in which they can be manufactured. In addition, milk offers a safer alternative for products currently derived from sources such as pooled human plasma, which necessarily carry some risk of transmitting infectious human diseases.
Furthermore, transgenic technology offers significant economic advantages. Our production facility, on a 168-acre farm, can produce products for far lower capital and unit costs than the $100 million facilities often necessary to produce the same proteins using conventional technology.
Genzyme Transgenics has published widely on our work, and maintains an open dialogue with and broad support from the scientific community, local communities, and the public. Further information regarding transgenic production has been provided in the monograph submitted along with the statement.
II. The Potential Benefits of Cloning Technology
The cloning of animals has little application to transgenic production in the near term. This is the case both because large scale cloning is not commercially viable at this time, and because transgenic production is highly successful and fully viable without it.
Page 52 PREV PAGE TOP OF DOCLonger term, cloning technology could further enhance the effectiveness of transgenic production in several respects. These include:
1. Enabling the breeding of a large number of offspring from a female founder in a single generation. This could allow the acceleration of herd expansion, clinical trials, and product launch.
2. Ensuring that all offspring bred from a founder are both transgenic and female. This could reduce the number of births, and therefore the costs, required to generate a full-size production herd.
3. Further insuring the biochemical identity of material from different animals, by eliminating variability in background genetic factors. This factor could be of greater value in areas such as the breeding of animals for organ transplantation.
It should be emphasized that these advances would represent incremental enhancements to more established if less well-publicized technologies. It is also possible that advances using other approaches will achieve some of these same objectives earlier or more effectively in the coming years. Finally, I would like to reiterate that all of these advances are fully achievable without any activities involving human cloning.
In closing, I would like to suggest what I believe could be the most significant opportunity presented by the birth of Dolly. As an event which has clearly captured the public imagination, this event offers a powerful platform from which to inform people about advances in biopharmaceutical therapies, and, in the context of related biomedical advances, in our understanding as to how life works. With such a focus, this moment offers the ability to engage an even broader community in a constructive dialogue about the benefits and acceptable limits of the technologies involved.
Page 53 PREV PAGE TOP OF DOCMadam Chairman, I believe that I speak for the biotechnology industry in thanking you for engaging in a constructive dialogue on these matters. We are always appreciative of the opportunity to update the Congress and the American people about the continuing progress underway in biotechnology. Our industry is very conscious of the needs to maintain an open dialogue, and to engage only in research and medical activities that are ethically responsible and acceptable to our society.
As Congress examines this issue further, we ask that you focus principally on mechanisms for further education and public participation in these fields. I join with others here in reminding the Congress that a rush to judgment in complex areas can easily lead to bad policy, and in urging you not to rush to legislation that might restrict widely accepted technology with great potential therapeutic benefits.
JAMES A. GERAGHTY
PRESIDENT AND CEO OF GENZYME TRANSGENICS
Mr. Geraghty has been the President and Chief Executive Officer of Genzyme Transgenics Corporation since its incorporation in February 1993. Mr. Geraghty joined Genzyme Corporation in September 1992 as Vice President of Corporate Development. He also served as General Manager of Genzyme's transgenics business unit until its incorporation as Genzyme Transgenics Corporation. Mr. Geraghty was previously Vice President of the Prescription Services of Caremark International which was then a unit of Baxter International. Prior to that, he held a variety of general management and strategy consulting positions with Bain and Company and with companies in the Bain venture capital portfolio. He holds a JD degree from Yale Law School, an MS from the University of Pennsylvania, and a BA from Georgetown University.
Mrs. MORELLA. Thank you very much, Mr. Geraghty. What I am going to do is subject each of us to a 5-minute rule for the questioning to make sure we get a round. And, then there will be an opportunity, as time allows, for us to get back for a second round.
Page 54 PREV PAGE TOP OF DOC We also have been joined by Mr. Ehlers from Michigan and Mr. Gutknecht from Minnesota.
And, we are going to go from alternating Republican, Democrat, Republican, in all fairness. So, I will start off with you, Dr. Varmus.
You mentioned that public attention is focused on the most sensational aspects of the cloning research which you deplore. What steps should the scientific community have taken to focus attention on the science and the ethics of cloning, if you think any steps should have been taken?
Mr. VARMUS. Well, of course, the discovery was announced very abruptly. And, needless to say, the public's interest, the journalistic interest in the topic, overwhelmed the ability of the scientific community to refocus attention on other issues.
But, I think as just days have gone by, one can see a change in the newspaper accounts of the discovery--much deeper analyses and discussions of much more substantial issues than the cloning of your favorite movie star. So, I think that one of the advantages of the moratorium and the referral of the matter to the National Bioethics Advisory Commission is that we have a breathing space in which a more expansive dialogue can occur and the issues of greater scientific moment can be aired.
Mrs. MORELLA. I just wonder if we should have--if the scientific community should have prepared the public more for the research that was going on.
Mr. VARMUS. Well, sometimes it's difficult to prepare the public until the public is ready to be prepared. After all, a year ago there was an article featured very heavily in ''Nature'' magazine describing an early step in the cloning process, an experiment in which cells were taken from the early embryo, the blastocyst, placed into culture by Dr. Willmut and then used to--by the technique of nuclear transfer to generate an adult sheep. That was a riveting moment for scientists.
Page 55 PREV PAGE TOP OF DOC Forty years ago, Dr. Gergen and his colleagues took cells from frog skin and other tissues and made a tadpole. That was pretty exciting, too.
But, I think sometimes it's difficult to capture widespread public attention until something extraordinary has occurred.
Mrs. MORELLA. Thank you. Dr. Rexroad, do you think that this will mean that we won't have to worry about endangered species?
Mr. REXROAD. Madam Chairwoman, I think it offers great possibilities for germplasm preservation. One of the things that we are up against in livestock species and zoo animals is that the current technologies that we use for freezing eggs, for freezing sperm, don't work equally well across all species.
Frequently, the types of cells that are described by Willmut and others, and particularly the fetal fibroblast, are quite susceptible to storage and cryopreservation. So, I think it does offer some possibilities, but we will have to see.
Mrs. MORELLA. Because of the scientific breakthrough, do you all have all of the information to be able to put it into the research you are doing to benefit from that part of it that is applicable?
I mean, how does the sharing take place?
Mr. REXROAD. Madam Chairwoman, Dr. Willmut over the years has published rather full details of the work that he has accomplished. And, I think that if we looked at this morning's paper we would note that they did restrain themselves somewhat from publishing this for being concerned about intellectual property rights.
But, nonetheless, when they do publish, they have adequately described their procedures. I feel that we can competently follow many of those procedures at Beltsville and can achieve the same ends.
Mrs. MORELLA. Dr. Smith, in your--well, another question.
Page 56 PREV PAGE TOP OF DOC I noted in your testimony that your monkeys--speaking of timing, your monkeys were born in August 1996; and, yet your research wasn't released until this past weekend. Why did you deny the announcement of it?
Is this typical? Is this standard?
Ms. SMITH. Well, there were a number of reasons. And, I should also point out that we weren't responsible for the release of this information this weekend. That was--sort of got out of our control.
The reason for that is that we wanted to make sure of the genetic analysis of these animals, which took quite a bit of time. We wanted to make sure that the animals seemed to be developing normally.
And, there also was a manuscript that was written and has been submitted for publication. And, our reason for delaying the announcement of this, it's typical with science.
I mean, we wanted to wait until the research article had been accepted for publication. We expect that to happen within the next month.
And, so this was--we did not feel it would be appropriate to release this information until the paper was accepted for publication. We are not quite sure how this information actually leaked out.
So, we--it got--the gun was jumped on.
Mrs. MORELLA. You thought it was prudent--you would have preferred to have waited.
Ms. SMITH. Absolutely.
Mrs. MORELLA. Right. In fact, aren't there some questions about the fact--maybe I will move to Dr. Murray and then in my next round, I will get to you, Mr. Geraghty.
Remembering that we talked this morning about the fact that Dolly doesn't have a father or a mother, so who is the parent? The significant udder.
Page 57 PREV PAGE TOP OF DOC Mrs. MORELLA. Actually, Dr. Murray, last Friday, the ''Wall Street Journal'' had an article entitled, ''How Do We Know Dolly Isn't a Hoax?'' It suggested that the Scottish announcement was such a shock to the scientific community and again got into why did the scientists wait 7 months to deliver the birth announcement.
And, it ties in a little bit. And, I wonder what your comments are.
Mr. MURRAY. About whether we know it's a hoax or not?
Mrs. MORELLA. Yes. What do you think? How would you respond to that article if you had to write the response or rebuttal, as you see appropriate?
Mr. MURRAY. Well, baseball season is about to begin. And, when a pitch is thrown, it's not a ball or a strike until the umpire calls it.
And, I think what Dr. Smith was describing, the finding isn't really a reliable finding until peer review passes on it and says it is. So, I guess we know it's real when a reputable journal like ''Nature,'' in the case of the Dolly piece, says it is and accepts it for publication.
That also is--it's not a perfect guard against the possibility of fraud. But, it's a good one.
Mrs. MORELLA. We also don't know how long she is going to live, do we?
Mr. MURRAY. We have no idea. We don't know if she will continue to develop normally. We don't know if she will be fertile or not.
Mrs. MORELLA. Right, right. Well, my time is up. I will wait for a second round.
And, I will now recognize Mr. Brown.
Mr. BROWN of California. Mrs. Morella raises an interesting question about the possibility of cloning other than mammals or cloning endangered species. Having had considerable experience with the difficulties of protecting a small fly out in my district recently, I would like to know if we could clone that insect and move the clone insect to a more favorable habitat.
Page 58 PREV PAGE TOP OF DOC [Laughter.]
Mr. BROWN of California. But, this raises a more general question. We are talking about mammals here, with Dolly, which is presumed to be the most complex form of animal life.
And, then we go down the scale to birds and snakes and fishes and then on down to insects and worms and so on. Speculate about whether or not this cloning process would be easier or more difficult with other kinds of animals and if there are potential applications like preserving endangered species, any of you. Start with Dr. Varmus, since he's the chief scientist for the government here.
Mr. VARMUS. I'm not sure that my colleagues who study frogs and fish would agree with your assessment that mammals are necessarily the most complex. But, there are, in fact, methods already available for preserving really embryos or germ cells from some of the species you mentioned or for freezing whole animals.
For example, the experimental worm can be frozen in its adult state and reactivated. So, there are freeze species methods that have generally been developed--not for all but for most.
Mr. BROWN of California. You don't need to clone them?
Mr. VARMUS. Well, it depends a little bit on the purpose of cloning. I think we don't want to over-determine the usefulness of cloning as an experimental strategy.
For example, if one makes a genetically altered mouse, it's perfectly possible, as many of us do in our laboratories, to continue to procreate that mouse by conventional male/female matings.
Mr. BROWN of California. Right.
Mr. VARMUS. We would not jump to use nuclear transfer and cloning for that purpose because we have perfectly good methods already available.
Mr. BROWN of California. Now, getting to my rare and endangered, sand-loving fly, is it possible that we could reproduce that by cloning or any other method and transfer that fly population to another suitable habitat that isn't right in the middle of a busy industrial development?
Page 59 PREV PAGE TOP OF DOC Mr. VARMUS. Well, there has been a problem in preserving Drosophila mutants, for example. Generally, they are kept alive by simply growing generation after generation. But, one has to adapt the preservation of the species to that species of beast.
And, cloning wouldn't necessarily be the avenue for preservation. In some cases, for example, with certain viruses, you can preserve the virus by simply freezing the DNA away.
I think it needs to be adapted to the specific----
Mr. BROWN of California. I can see we are going to have to explore this in more detail, Dr. Varmus.
I am looking here at an article from the ''New York Times'' of February 25th dealing with this subject. It's written by Gina Kolata, who has been a respected writer for some time, or at least some people respect her. I don't know how you feel about it.
Mr. VARMUS. I do.
Mr. BROWN of California. But, the question that she raises incidentally in this discussion is that we have, what she calls, a parallel universe, that of animal science, which Dr. Willmut represents, and that of molecular biology, which is a different field, and that the two don't communicate very well. Now, that's a problem in science which I have been intrigued by for some time, that different fields of science don't have respect for each other or they don't feel that there is an area that is common to both that is worthy of attention by the best people in the field.
Is it possible that we are talking about a parallel universe here in which there is a lack of respect on either side for the work that the other is doing?
Mr. VARMUS. Mr. Brown, I don't think it's a lack of respect. I do think that there is at least a semi-separation of communities that--for example, the work that Dr. Rexroad does is more clearly situated in the community of agricultural scientists and less in the area of medical science. And, because the funding sources are different and the structure of the scientific community is somewhat different, meetings are held with different objectives in mind, there isn't as much overlap of the communities as perhaps there ought to be in some circumstances.
Page 60 PREV PAGE TOP OF DOC Mr. BROWN of California. They are just not communicating adequately.
Mr. VARMUS. Perhaps. I mean, we have a lot of people to communicate with and a lot of information.
So, excuse us for not being totally conversant with each other.
Mr. BROWN of California. Well, I have to deal with both of these. For a number of years, I chaired the Research Subcommittee on the Agriculture Committee. And, I developed a lot of respect for agriculture research.
And, I think there ought to be more communication between, we will say, the molecular biologist or the cell biologist and the agricultural researchers. And, I thought maybe there would be here a hook that we could use to help build some of that respect.
But, I'm just looking for comments at this point.
Mr. VARMUS. Well, I think this is one of several recent hooks. I think the general interest in manipulating the genetic constitution of mice has brought many molecular biologists more in tune with some of the other disciplines that they may have been semi-neglecting over the years, including husbandry and early development and histology in other fields.
Mr. BROWN of California. Thank you. Thank you, Madam Chairwoman.
Mrs. MORELLA. Thanks, Mr. Brown. I agree with you in trying to get the various facets of the scientific community together.
I am pleased to recognize Mr. Ehlers from Michigan.
Mr. EHLERS. Thank you, Madam Chairwoman. First of all, just a comment about your question which, I think, was an excellent question, Congresswoman Morella. And, that is, can we prepare the public better for events such as this? And, I would have to answer no.
From my standpoint as a scientist, I have tried a number of times on issues. And, it seems that until an attention-grabbing event comes along, the public simply is not interested in considering it.
Page 61 PREV PAGE TOP OF DOC An example is, some years ago when it became apparent to me that surrogate parenting was going to become an issue, I approached a number of ethicists, theologians, scientists and talked to them and said, ''We should get a public discussion on this before it happens so that we can consider it in a reasoned, unemotional atmosphere and establish some guidelines.'' I simply could not get even the experts interested in doing that. And, if I couldn't interest them, I don't think we can interest the public.
It was absolutely no surprise to me to hear the announcement about the sheep. I think that was--that development was inevitable once we discovered the molecular basis of life.
But, I do--I apologize to the panel that I was not able to hear their testimony. Unfortunately, I was called into service to press another meeting. And, I got away as quickly as I could, but it was too late.
But, rather than ask questions, I would simply like to comment on something that I've done and ask your response to that. And, what I've done is, a few hours ago, introduced two bills, one of which would follow up on the President's moratorium and simply prohibit the use of federal funding for human cloning research. That is, I suspect, identical to the bill introduced by Senator Bond in the Senate last week. I also have introduced a bill to ban research on human cloning.
Now, this may seem an unusual thing for a scientist to do. After all, shouldn't I be interested in pursuing this to the maximum?
But, I think it's very important for us to draw the boundary at experimentation on human cloning. You have seen what has already happened in Britain as a result of the announcement the British government cut off funding for the research.
I saw the President's rapid action. If you talk to the public at large, they somehow seem to think we have to stop all cloning research.
And, I think if we don't ban immediately research on cloning of humans, we are likely to see a strong movement to ban research of cloning in general. And, I think that's why it's very important to delineate the limits immediately on human cloning so that we will be able to continue further work in this issue of cloning of other species, and simply point out to the public we now have a golden opportunity, as Congresswoman Morella was stating, we have a golden opportunity to educate the public. We have their attention now.
Page 62 PREV PAGE TOP OF DOC There are many potential benefits to cloning research conducted on animals. Perhaps, you know, we can't envision the results, but things that have been mentioned as perhaps somehow being able to permit an organism to develop new arms or legs or fingers or feet or what have you, eventually perhaps allowing humans to do that; perhaps also regeneration of the spinal cord in some fashion, which would be a marvelous development for anyone who is paralyzed due to a spinal injury.
I am just speculating. And, I have no idea if those will ever happen.
But, those are certainly within the realm of possibility. And, I think it's extremely important to pursue research so that those possibilities may perhaps become real at some point in the future.
I would very much appreciate your comments on my line of thought, because I have not had time to meet with members of the scientific community. I happen to be a physicist, not a life scientist.
I would appreciate any comments you might have on my thoughts and on my approach in this issue and particularly negative comments. Thank you.
Oh, incidentally, I was just asked to give the bill numbers of the bills--House Bill 922 and 923. Senator Bond's bill is S.368. That's House Bill 922 and 923 and Senate Bill 368.
Thank you. I would appreciate your response.
Mr. VARMUS. If I could, Madam Chairwoman, make a couple of comments.
The President's actions, in my view, were intended to give us a period of deliberation and a time to be sure that any legislation that was crafted was only crafted after the Commission has had its time to deliberate and we've thought through all the possible applications of cloning, as it's currently envisioned in light of recent discoveries. The way in which any bill that limits federal funding for research is crafted can, in my view, impede our ability to do many of the things you were suggesting in the area of spinal cord injury or other kinds of medical treatments, which I tried to address briefly in my opening comments.
Page 63 PREV PAGE TOP OF DOC Unless a bill is written in a way that places a very tight fence around that which the public and the Congress want to forbid, the possibility of closing off research that is related to or required for the development of an unwanted goal can also, in my view, cut off research intended to advance us towards a wanted goal. So, I would--it seems to me that, as you've pointed out, you haven't had a chance to confer with all the individuals who you might want to confer with, the Commission hasn't yet done its business.
Human cloning is not going to happen overnight. I don't believe there is actually substantial interest in the scientific community.
If there are outliers, they can go to an offshore island and do it anyway if they--we are not sure it's actually possible. In any event, there are many preliminary steps before it could happen.
And, my concern is that we not act in conformity with what I think the President has intended; namely, that we have a period in which we absorb and discuss the new findings and think through the implications before there is legislation on this topic. That's a duly, respectfully submitted comment from one scientist to another, Mr. Ehlers.
Mr. EHLERS. If I may just clarify, I certainly appreciate your comments. And, they are accurate.
But, at the same time, even though human cloning will not occur immediately, the cutoff of funding for all cloning research could occur immediately if one doesn't treat the subject carefully. And, that's my goal.
Ms. SMITH. I just wanted to comment on your experiences with trying to kind of engage the public in the debate. It is difficult.
I am reminded--I don't know how many years ago it was now when the first announcement was made of the first IVF baby, Louise Brown, I think her name was. It has been, I don't know, 25 years ago. I mean, at that point--at that time, I mean, the public, I think, reacted in a similar vein to what they have reacted to this.
Page 64 PREV PAGE TOP OF DOC And, I think that the government and NIH reacted very responsibly in sort of dealing with the issues related to that. But, I don't really feel there has been a public debate on the issues that have evolved out of that.
I mean, some of these issues end up in the court. But, there has not been what I would consider to be a public debate on all of the things we are dealing with now or who is--is this a surrogate parent or who is the biological parent or all of these issues that are coming up.
I mean, in one way, I think it's reassuring that it was a startling announcement; and, yet, here we are 20 years later. We use that technology to the benefit of many people. It has become accepted.
And, yet there wasn't, I don't think, really a public debate on that issue. So, when we get to this, I think there are some interesting lessons that come from that.
But, the point that you raise, I think, still remains a challenge. And, I'm not quite sure how we address that.
Mrs. MORELLA. I know Dr. Murray would like to respond. So, I would like to give you a chance.
Mr. MURRAY. Thank you. Congressman Ehlers, I was taken by your story about surrogacy and would----
Mr. EHLERS. If I may, just to amplify. It's not only surrogacy but also IVS. I posed both of those at the same time.
Mr. MURRAY. I've learned a rough lesson in bioethics--be careful about making up what seemed to be ridiculous hypothetical examples; they are likely to be true. That has happened more often than not.
I would want to say, though, I look forward to reading the text of the two bills you have offered. Speaking now as a member of the National Bioethics Advisory Commission, I would hope before any irreversible action is taken on those bills that we are given our 90 days to try to encourage a public--a vigorous public debate and to make a report of whatever findings we can reach.
Page 65 PREV PAGE TOP OF DOC Thank you.
Mrs. MORELLA. Thank you. I would like to recognize Mr. Gordon, but I want to also point out that we have been joined also by Mr. McHale from Pennsylvania.
Mr. GORDON. Thank you, Madam Chairwoman. It seems to me that Dolly, to some extent, let the genie out of the bottle on advanced cloning similar to the Manhattan Project on producing atomic weapons.
And, Dr. Varmus, you have maybe even broke the bottle by saying that even though you opposed human cloning that
--I think you used the term ''it might be used sparingly in the future in certain circumstances.'' You know, just as there are national prohibitions against proliferation of nuclear weapons, we are finding, you know, rogue nations doing this around the country.
And, I guess, maybe--and, Dr. Rexroad, you said that you thought that you could reproduce this experiment at your shop. And, I guess my question is: Let's assume that we have all kinds of prohibitions by the major nations, by the major industry concerning human cloning. Yet, you have a couple of wealthy folks that are following George Bernard Shaw's script and trying to determine whether or not it is heredity or environment that is going to affect adult conduct and decide to hire a rogue scientist and go off to Dr. Varmus' island and conduct these experiments.
Mr. VARMUS. Not mine.
Mr. GORDON. Now, what really is--I mean, what would be necessary?
What are the resources that would be necessary for this rogue outfit to proceed with these human cloning experiments?
Page 66 PREV PAGE TOP OF DOC Dr. Rexroad, since you said you could do it yourself, at least----
Mr. REXROAD. Maybe I shouldn't have offered that suggestion at all. The components of a cloning experiment are the unfertilized eggs. That might be difficult to come by.
In cattle, we collect slaughterhouse ovaries to get unfertilized eggs. So, we need a source of eggs that can reprogram whatever cells are to be cloned.
Mr. GORDON. But, that would be--I mean, that's not that difficult.
Mr. REXROAD. I can't say what--you know, how difficult that would be in humans. It might be cadaver eggs. It would have to be fresh cadavers. It could be super-ovulated, certainly not practices that we think acceptable, of course.
It takes some form of cell culture. I don't see that as being prohibitive.
It takes the ability to join those cells, the unfertilized egg and the cell that you would like to clone. But, it takes some micromanipulation techniques and skills.
If the cells are very small, you might need a $30,000 microscope and a set of manipulators. You need a culture cabinet. That's $4,000 or $5,000.
The thing you need more than anything is some technical expertise. So, given speculation that it would work in the same way or even with the same efficiency that it does in the sheep and other species, it would not be an impossible task. I think it's----
Mr. GORDON. Science is the--
Mr. VARMUS. One other thing that one needs is surrogate mothers. And, this is not a trivial issue.
So, I think in any rogue scenario, one has to remember at this point all that can be done in the laboratory is to generate those blastocysts, the early embryos, and one would need a willing or unwilling cadre of surrogate mothers. We don't know what the----
Mr. GORDON. Aren't they already available? Not for this experiment but, I mean, how would a surrogate mother know the difference between a cloned, you know, egg and a naturally fertilized egg that they were going to----
Page 67 PREV PAGE TOP OF DOC Mr. VARMUS. That's a possibility.
Mr. GORDON. So, it's really--I mean, the resources are not much of a bearer. It's obviously the science is still----
Mr. REXROAD. The physical resources, the intellectual resources might be limited. It's possible.
Mr. GORDON. So, I mean, what--assuming that you come up with the policy that it is the proper course to stop all types of human cloning, how is that going to be enforceable?
Mr. VARMUS. It would be like any other law, I would assume. This is something that you folks are better equipped to answer than I am.
Mr. GORDON. Well, we have a law against robbing banks, but you still--banks are still robbed.
Mr. VARMUS. That's correct. I think that's--I agree with that point.
Mr. GORDON. Yes, Dr. Smith.
Ms. SMITH. I was just going to make the comment that, I mean, some of the reason--the example you gave why someone would want to clone another human being had to do with the question of like performing an experiment, for example. I mean, I would argue that if you had animals available in which you could do a lot of these experiments that you are driving at, which is kind of the nurture versus nature kinds of issues, for example, that you could do in monkeys, you could get the answers and then people would know the answers, so they wouldn't need to think about doing human cloning for those kinds of reasons.
Now, to do human cloning to clone yourself because you think you are so great, I mean, those are different kinds of issues. But, I think issues related to health or disease issues, I think by doing more research we can prevent the need for people to want to do that.
Mr. GORDON. Well, you know, if someone wants to have a steak, they can go and kill a cow and have a steak. But, we often hear of these exotic dinners where people don't want to eat beef, they want to eat some endangered species.
Page 68 PREV PAGE TOP OF DOC Ms. SMITH. Yeah, I understand.
Mr. GORDON. So, you know, it obviously doesn't take those kind of resources to be able to do this. And, there are people that might have other thought processes than yourself.
I don't know whether--is my----
Mrs. MORELLA. Go ahead.
Mr. GORDON. Dr. Murray, could you outline for us some of your thoughts on how you can reach out for this public dialogue and public comment?
Mr. MURRAY. Certainly, Congressman. Dr. Shapiro, as I said, has already begun our activities on this regard. We are--I think people have already been in touch with leaders of at least four major religious traditions in the United States and asked representatives of those traditions to come to our 13 and 14 March meeting.
And, they would be American Protestantism, Roman Catholicism, Jewish tradition and Islam. And, we expect to devote a significant portion of the full meeting to conversation with those scholars and representatives.
We are also going to commission a pro/con. It's hard to find anybody who is flatly in favor of human cloning, but there are some people who at least aren't ready to say it's a closed case. We will have a couple of such people, we hope.
We will also have a couple of people who represent very strong views that it's a bad idea and always would be a bad idea. That's how we will begin the debate, sir.
Mr. GORDON. Well, I would encourage you to have as broad a base discussion. As I've said earlier, I think the broader base discussion, the larger the consensus and the more maybe the potential to--as you bring in a wide base to be able to stop the--you know, the human cloning, that's going to be a very difficult thing to do other than by slowing down science.
Mr. MURRAY. Yes, sir.
Mrs. MORELLA. Thank you, Mr. Gordon. I would now like to recognize the very patient, interested Mr. Cook from Utah.
Page 69 PREV PAGE TOP OF DOC Mr. COOK. Well, I find this most fascinating and have really enjoyed listening to what you have been saying. I know, in an answer to a previous question, you have indicated that you believe the peer review process really still needs to take place before you really know what happened in Scotland or what was announced--let me--or could you clarify maybe that?
Mr. REXROAD. Yes. Let me add something about that.
Mr. COOK. Yes.
Mr. REXROAD. As a scientist, the important point is that you be able to replicate the experiment. We do, indeed, expect the peer review process to make the first pass at saying that this is valid, that the data looks all right. But, you are still relying on an individual work, investigator or set of investigators, to produce that data.
So, replication, the ability to do this in another environment makes it science. That means that it's repeatable, that it's a deterministic phenomena, that somebody else can do it.
And, if we can believe sources other than ''Nature,'' the journal, then we understand that this particular experiment has been replicated at least once.
Mr. COOK. Oh, it already has?
Mr. REXROAD. I think----
Mr. VARMUS. Excuse me. Mr. Cook, to recognize that this has occurred in the context of a series of scientific steps, although it's a revolutionary finding at one level it is within the body of scientific knowledge and advances previous experimental strategies. And, from that point of view, it's not a bombshell in a totally different direction, upsetting all previous notions of how biology works.
Mr. COOK. Well, I'm from Salt Lake City, Utah. And, a number of years ago, a very spectacular announcement of coal fusion was brought----
Page 70 PREV PAGE TOP OF DOC Mr. COOK. (continuing) --forward. Now, I was skeptical even at the time, because my father happens to be a scientist who--it didn't add up in his mind at the time.
But, I guess what I'm really--one thing I did want to ask you as far as this peer review process, are there any of you on this panel that is expecting that this won't be quite the way it was announced; or, are you quite confident that the peer review will establish this as a fact?
Are you all--I take it you all seem quite confident in this.
Mr. REXROAD. I am quite confident. There was a news release from New Zealand that the laboratory of Robin Tervit had used the same set of cells and produced clones that were obviously identical to Dolly. I haven't seen that in a scientific article.
But, knowing these people personally, which is something that also in the science community adds cache to the claims. And, I know these people personally. I have all the research over the years, seen parts of it replicated in other labs.
I think we fully expect that this is, indeed, verifiable and valid science.
Mr. COOK. Okay. Just one final question. Is it your belief that the American people are taking this with unhappiness, for want of a better word, that maybe science is just too close now to the realm of what--I mean, do you see--you know, this group of religious leaders that you are going to be convening, I take it--what I mean is at a time when we just need more of our young people to be so more interested in science and math training and all this, what implications does this sense of unease that we have to raise so many ethical questions, what's that--what is that going to mean as far as the--and this is a very general question, but the future of science just--I wanted to get a feel for how you feel about that.
Mr. VARMUS. I think, for us, this is an opportunity to take an event that has attracted the attention of virtually everybody in the country and explain the remarkable features of it at a scientific level. We have their attention.
Page 71 PREV PAGE TOP OF DOC And, I think to point out that great discoveries frequently impose moral dilemmas upon society, that the fundamental scientific principles that work here offer tremendous opportunities in medical research and agricultural research and other areas and that the deep principles of biological behavior that are illuminated here can be means of attracting new talent into biological science.
Mr. COOK. Thank you.
Mrs. MORELLA. Thank you, Mr. Cook. I would now like to recognize Mr. Capps from California.
Mr. CAPPS. Thank you very much. I find this discussion very, very interesting.
And, I have to say that before about two and a half months ago, I was a professor of religious studies at the University of California. So, I am going to ask some questions about religion, you know, because I think--you have addressed some of these and some of the bioethical implications of this but, you know, just as a starter, when one looks at the religious traditions--and I recognize you are going to be talking with members of the dominant traditions in this country--when one looks at the literature in those traditions, it's really remarkable how often language like ''cycle of birth'' and ''rebirth'' will appear. I mean, ''salvation'' is even described in some traditions as having to do with the transcending of birth and rebirth.
We talk about new birth. We tend to talk about a relationship with God, as Dr. Murray has already pointed out, in terms of--he didn't point this out quite, but I'm going beyond it a little bit, in terms of relationship of parents and children. And, I understand when you say that there are moral and ethical implications here that really have to do with how we understand family life and how we understand children and still, by way of preface, all the religious traditions would attest that human beings are something more than the constellation of cells but there's something like spirit, there's something like soul.
We also talk in these traditions that we are not cloned but we are created. And, we don't come into this life being cloned, but we are created.
Page 72 PREV PAGE TOP OF DOC Now that we have that possibility--now, I am finally to the question--it just seems to me that this is going to affect rather pervasively, rather thoroughly how we look at a whole bunch of things. I mean, I don't know if this is like the Copernican Revolution, but I just think, you know, I think that it's--that it would be a mistake to underestimate the power of these discoveries on how we now understand ourselves and how we look at the world.
And, I think the first reflex action there is to generate fear. To think that we may lose a moral sense, we may lose something that we have ethically because of these new discoveries, I want to turn that around.
And, I know this is exploratory and we can't do it all today, and I am hoping we will have more discussions of this, but can you see positive moral and ethical implications coming from these scientific discoveries? Thank you.
Mr. MURRAY. I take it that was addressed to me.
Mr. MURRAY. It was a wonderful prelude to a question. I think wonderful things might happen in the basic science and in applied clinical science of animal cloning.
But, Congressman, was your question whether human cloning would also lead to----
Mr. CAPPS. I would be happy if you took on the--you know, took on the subject itself. If you want to get into human cloning, it's okay but----
Mr. VARMUS. Could I try your point, Mr. Capps?
Mr. CAPPS. I'm trying to find something--you know, some positive foothold here.
Mr. VARMUS. I would like to try something on you.
Mr. CAPPS. Okay.
Mr. VARMUS. I think your question is extremely interesting. One of the things that characterizes the public response to these experiments is, I think, informed by an overemphasis on the importance of genes and a loss of belief in the importance of experience in the generation of a mature individual.
Page 73 PREV PAGE TOP OF DOC Before we knew about genes, we recognized that life history--who raised you, who your friends are, what you did in life--created, whether it's a life history or spirit. In recent times, due to the focus that we've all placed upon DNA and genes and how they influence a disease and life, genes have become, in my view, seen by the public as over-determining who we are and how we behave.
I think this is an opportunity for us to set that balance in a better perspective. Think about identical twins.
Mr. Gordon raised earlier this issue of would someone want to carry out the Shavian experiment of asking about nurture versus nature. That experiment actually already goes on.
It is a fantasy to think that someone who has the same genes that you have is you. It's somebody else who happens to have the same sequence of DNA.
I think those distinctions are things that we can bring up in this debate that will make us respect life history as much as we respect our genes.
Mr. CAPPS. I think my time is up. Well, Dr. Murray, did you----
Mr. MURRAY. Well, leave it to a scientist to put the ethical point better than the ethicist, but----
Mr. MURRAY. The point I was trying to make with the Mel Gibson example, if you wanted to recreate Mel Gibson you are probably going to be frustrated. You might get somebody who looks like him but may not be him.
There is even a second benefit, I think, that might come out of this conversation. And, it would be, I think, a highly focused and intense public discussion about what really is important in the lives of families, what really is important in the relationships between parents and children.
And, I think that could be a very positive conversation to have in this country.
Page 74 PREV PAGE TOP OF DOC Mr. CAPPS. I appreciate your comments very much. And, I hope that I have communicated my disposition here, which is to welcome the consequences of this research and, you know, not unilaterally, not without discernment.
But, I think it does create a new day. And, I am hoping we can see that new day in positive and constructive terms.
So, I wanted to wish you well and want to cooperate to the extent that I can now as a new Member of Congress. Thank you.
Mrs. MORELLA. Thank you, Mr. Capps. I am pleased that you brought up that particular focus, which I think is important.
I am pleased to recognize Mr. Ewing from Illinois.
Mr. EWING. Thank you, Madam Chairwoman. And, to all the panelists, thank you for your presentations. They were very interesting.
And, it may take some of us, at least this member, awhile to digest it all. And, so if my questions are a little elementary, bear with me. I am not a scientist.
Dr. Smith, would you explain just very quickly again the difference between cloning and when we fertilize an egg and transplant it into a surrogate mother?
Ms. SMITH. Well, basically the techniques that we've used and the techniques that Dr. Varmus described earlier with embryos, I mean, those techniques of in vitro fertilization where you take an egg and a sperm and combine them are used routinely in infertility clinics throughout the world.
You know, what's different about this is that when the embryo begins to divide into several cells, the technique we are using then is to dissociate that very young embryo into individual cells. Now, each of those cells are sort of equally potent in terms of being able to develop into an adult individual.
So, for example, in the technique we are using now on a theoretical basis, you might be able to take a single embryo, dissociate it into maybe 12 cells. Each of those cells, if everything went perfectly, could be implanted into a host mother and you could get 12 genetically identical animals.
Page 75 PREV PAGE TOP OF DOC The reality is, on the efficiency of the technique, we would be lucky to get twins probably or triplets. So, it's quite different.
And, in fact, it's not very much different than what goes on normally in nature now in which twins and even occasionally triplets are produced. What we are trying to do is to sort of expand that somewhat so that we have larger cohorts of genetically identical animals which can then be used for various aspects of research.
So, we are not cloning adult animals. And, we really have no intention at this time to do that, because we can't think of a rationale frankly why one would want to clone an adult monkey.
Mr. EWING. So, when you have a normal fertilization, you have a whole different being that's just one being. And, this way, by dividing it, you could have multiples that would be alike?
Ms. SMITH. Yes.
Mr. VARMUS. I think you are getting at a somewhat different point, if I may, just quickly.
Mr. EWING. Yes.
Mr. VARMUS. You and I each have two copies of every gene. One set of copies comes from our dad; one set comes from our mom.
When in vitro fertilization is used to generate a new child, again one set comes from dad and one set comes from mom. In the case of the cloning experiments, where they were using cloning in which the donor is an adult cell or the donor is an embryonic cell, both sets of genes come from the same, if you will, parent or predecessor.
Mr. EWING. The concern, I think, that I hear people raise is what's this animal or, if it was a human, human going to be like. Like, if we cloned a dog, is it going to be a quiet, gentle dog or a barking dog or a biting dog?
Page 76 PREV PAGE TOP OF DOC That doesn't--that's not necessarily predetermined, is it, I mean, in any of the research?
Ms. SMITH. Well, I think one of the interesting things one would be able to do with--particularly, I think, with rhesus monkeys since they have a very complex behavior is you could begin to ask questions like that and get at the issue that was being discussed earlier, because you could take genetically identical twins and you could rear them under different conditions and show just exactly how different their personalities and so on would be like. And, I think it would get at this issue in a very nice way.
Although, as Dr. Varmus pointed out, there are lots of data in the literature about identical twins that are either raised in the same environment and are different or who are separated at birth and raised in separate environments and they do have some similarities and they have a lot of differences that are clearly environmentally determined.
Mr. EWING. I'm a little concerned about the President's order to prevent human cloning research. And, I don't disagree with it.
I guess I'm concerned in the sense that do we really anticipate that the scientific community will say, ''We won't do that?'' Do you believe that as scientists, at least in this country, we won't do that?
Mr. GERAGHTY. If I might comment on that for a moment? I think we can have a high degree of confidence in that.
There have been examples, some of which were described earlier, of the scientific community on its own initiative recognizing that because of ethical concerns and societal concerns it was appropriate to recognize a moratorium on certain kinds of work.
I would also say, although there was some discussion earlier about how relatively inexpensively perhaps in terms of capital this work could be done, I don't think we should lose sight of the fact that today it represents cutting edge research which there are only a handful of laboratories in the world capable of doing. And, as Dr. Rexroad said earlier, many of us in this field know most of the individuals capable of doing that work personally.
Page 77 PREV PAGE TOP OF DOC And, I think those of us who do work in it have a high degree of confidence that there is certainly no one looking to do any of that kind of work today or certainly with any inclination to try to circumvent the kind of process that has just been initiated.
Mr. EWING. But, it wouldn't take a scientist with maybe the degrees and experience that our panelists have to do the work.
Mr. VARMUS. It's hard.
Ms. SMITH. It's hard.
Mr. REXROAD. Very hard.
Mr. EWING. Very hard? All right. I just----
Mr. VARMUS. Dr. Willmut has spent his life working on this problem. He had one successful cloning out of 277 tries.
We don't--it may be actually even less efficient than that.
Ms. SMITH. Exactly.
Mr. VARMUS. If he did 5,000, he might get another one. I mean, I think we shouldn't underestimate the difficulty of this work and the limited number of people who are actually capable of carrying it out.
Mr. EWING. Well, you know, in--and I know there is a great difference, but you can build a bomb from what's on the Internet. They will tell you just step by step how to do that.
I hope that this isn't the way we will be going with this research also. Thank you very much for your comments.
Mrs. MORELLA. Thank you, Mr. Ewing. I want to recognize Ms. Johnson from Texas.
Ms. JOHNSON. Thank you, Madam Chairwoman. I guess my questions--I've listened with great interest and am pleased that I've had the opportunity.
My concern, frankly, is not whether or not we can influence the reproduction of people that look alike. I feel certain that there is no real fear of that coming any time soon.
Page 78 PREV PAGE TOP OF DOC We had some of the same kind of concerns when in vitro fertilization came along. But, rather whether or not we can get some of them to act alike.
It seems to me that we suffer more with erratic behavior in this country than we do with people looking alike. So, perhaps you can research how we can inject behavior or have some immunizations for those behaviors that are considered antisocial.
Now for the question. When I first heard about Dolly, I could visualize many benefits of having that type of research. We still have a situation where we are still wondering whether or not we can reproduce brain tissue and whether or not we might be able to correct some of the blood dyscrasia. And, it seemed that there is real value in that kind of research.
I know there is a real ethical consideration. And, I don't fear, however, that we are going to have people on the Internet developing their own lab and producing people.
If so, I hope they are all females so we can equalize things around here.
Ms. JOHNSON. But, the fact that the research results were held up until after an application for a patent was submitted, I really do wonder whether or not this is going to have impact on how we have operated as a research environment around the world and would like your input on that.
And, if, in fact, that there were some limitations of this type of research, how then would it affect research and the techniques in this country for attempting to arrive at some of the benefits of this kind of research here in terms of the diabetes or organ transplantation and that sort of thing?
Mr. VARMUS. Ms. Johnson, I don't think we should take the--overemphasize the delay between the time of the discovery in this case and the publication. It really wasn't all that long.
It's common practice in many fields of research for there to be some delay--until a paper is written and reviewed. As you know, in this country, there is public disclosure if the company has a patent application. So, in general, the tendency to submit a patent application is a device that requires public disclosure of scientific findings.
Page 79 PREV PAGE TOP OF DOC We have worked quite well as a biomedical community and a scientific community with existing patent laws. And, I don't think that the scientific community was unduly inconvenienced by what may have been a month or two of delay before publication of the paper.
Mr. REXROAD. One of the things that we probably should know is that the patent law is somewhat different in Europe than it is in this country and probably more prohibitive in terms of exchange of scientific information. Where we have a year from first disclosure to the filing of a patent, there is no disclosure allowed in Europe.
Mr. GERAGHTY. If I could address for just a moment the second half of your question, I think there is some concern that if we were to rush into some kind of legislative actions, it actually could impede or end some of the valuable kinds of medical research that were described earlier. And, it's for exactly that reason that Dr. Varmus and others and many people have urged that we take the opportunity that this moment provides to spend at least the 90 days in a process of education and communication and not do something irrational that could wind up inadvertently having exactly the impact you described.
Ms. JOHNSON. Thank you. Thank you, Madam Chairwoman.
Mrs. MORELLA. Thank you. I would now like to recognize the Vice Chair of the Technology Subcommittee, Mr. Gutknecht, from Minnesota.
Mr. GUTKNECHT. Thank you, Madam Chairwoman. And, I really want to express my appreciation for holding this hearing.
This is a very interesting subject, not only to us here in Congress but I think the American people.
It is interesting to me that several weeks ago I was invited to tour a facility in my district. And, it's not quite as--well, I guess it is fairly scientific, but it's called ''21st Century Genetics.''
And, at that facility, they have almost 500 bulls, most of them holsteins. And, it was curious at that time--I mean, somehow when this whole thing was announced, it was not such a surprise to me when we talked at that meeting about how much is going on right now in terms of genetic research.
Page 80 PREV PAGE TOP OF DOC In fact, one of the things that surprised me at that meeting, I think they had a picture there of one bull, whose name, I am sorry, I do not remember. But, I think he had fathered, before he was ultimately sent on to the Great Beyond, something like 1,000,000 calves here and around the world.
And, it struck me at the time though that--and I think they made the point--and perhaps, Dr. Rexroad, you can fill me in on this, because my memory is not as good as it should be--that a relatively small number of bulls in this country sire a disproportionately large number of all the calves that are born. And, one of the concerns that I have--and it really becomes even more complicated as we go forward--and I do want to ask you what level of research is really going on at USDA under USDA sanction in terms of cloning of--whether it be beef calves or dairy cattle or whatever other kinds of livestock.
But, one of the concerns I have is that as you go down that path, it seems to me we are developing strains of livestock in the United States and perhaps around the world that really lack genetic diversity. Is that of any concern to you in the USDA?
Mr. REXROAD. Congressman, I think that is, indeed, an appropriate concern. Each year in this country, about 2,000 dairy bulls are tested for the ability to transmit milking characteristics to their daughters. And, so that's a rather limited gene pool.
But, of those, a much smaller percentage--a small percentage is selected to do large amounts of breeding that produce the 9,000,000 or so dairy cows that we have in this country. We don't have precise estimates on how much we have restricted our genetic base by this approach of artificial insemination and continuous selection of the best animals.
I think it is, and should be, of some concern. I think we need some effort to have a better grasp on just how much genetic diversity we have in this population.
And, indeed, I would suggest that some of the research in my lab is making a small contribution by looking at the genetic maps of holstein bulls, how much variation--some information on how much variation we have. But, we need some more.
Page 81 PREV PAGE TOP OF DOC So, I think the concern about preservation of germplasm in animals and our dairy animals is appropriate. I think we need to be thinking very seriously about how to do that, how much of a genetic base we need to meet changing environments in the future, changing beef stuffs that we may be feeding the animals, changing demands and the way--the practices, the husbandry practices that we have.
In USDA, of course, there are two areas that fund research. One is the National Research Initiative and one is our own internal in-house research conducted by the Agricultural Research Service.
Most of the cloning work or related work is done in my laboratory, though there have been embryo splitting studies in the past conducted in other areas. We have--most of that work has been focused primarily not on the production of large numbers of clones but on using this as a scientific tool to evaluate in animals the genetic effects versus the environmental effects. And, I think we will continue to use it in that way as a tool.
Now, cloning is another tool that would--if one would desire to use cloning in a widespread fashion in farm animals, I think you would have to be very concerned about reduction in the genetic base. And, we would have to have models developed as to how we could use them effectively and efficiently without causing more concern about loss of genetic diversity.
Mr. GUTKNECHT. Just a follow-up to that. I am not really clear.
What is the USDA doing right now in terms of cloning research?
Mr. REXROAD. Okay. In terms of cloning research, I would say we are not concerned about cloning at all. We are concerned about the introduction of new genes into farm animals.
And, the cloning, particularly as described by Ian Willmut, may be the premier tool for doing that. Heretofore, the kind of work that we have been doing in farm animals has been to insert genes using a technique that has much more serious limitations perhaps than the technique that is being described here.
Page 82 PREV PAGE TOP OF DOC Mr. GUTKNECHT. So, there is cloning research being done?
Mr. REXROAD. Yes. It's part of a tool to do a broader concept of genetics research.
It is a tool. And, it is being used that way.
Mr. GUTKNECHT. I think my 5 minutes just expired. I did want to get to a couple more, but I want to let everybody else have a chance.
Thank you very much.
Mr. REXROAD. You are quite welcome.
Mrs. MORELLA. I can't help but think about those cows that produce that million, the million animals.
Mrs. MORELLA. I would like to recognize Ms. Rivers from Michigan.
Ms. Rivers, would you defer to Ms. Jackson-Lee? I think she was next in line.
Ms. RIVERS. All right.
Mrs. MORELLA. Thank you.
Ms. JACKSON-LEE. Thank you, Madam Chairperson, very much. And, thank you for the hearing on a very important topic.
I might just briefly not give an opening statement or a closing statement but ask if I could submit a statement in the record by unanimous consent?
Mrs. MORELLA. Yes. Without objection, so ordered.
Ms. JACKSON-LEE. Thank you very much.
There are many questions. I looked at a calendar that I had in my office and it indicated that this was a judiciary technology committee. And, I thought we had jumped ahead of our thinking and that you were cloning people and I was coming here to discuss the legal ethics of it.
Page 83 PREV PAGE TOP OF DOC But, thank goodness, I've been saved by the Chairwoman, who is certainly well to have this hearing and to help us explore can people be cloned, who would be considered the parents of the clone and, finally, is it legal to clone people. I do know that there are representatives here from more than the people issue.
There is research obviously going on dealing with genetic cloning that deals with animals and falls in certain categories. But, let me formulate some general concerns and then questions.
I certainly think we are nowhere near having the wisdom to make the cloning of human beings the next scientific discovery, albeit we may know how to do it. And, I happen to support, though I have not read extensively and will do so, the President's position on this.
I note that there are several European countries that have already gone ahead.
My understanding about Scottish researchers is that their focus was less on the ultimate product--and you correct me if I'm wrong--but to see if we could do it. And, I would like some comment on that.
Secondly, I think that as we look at the question of cloning, help me understand--as I have been in meetings where I have argued that the space station, for example, provides an outstanding opportunity for medical research and, therefore, will have some ultimate good for those who may not be totally in agreement that we should be building a space station and living in space. Can we expect that the cloning of humans or the continued research around cloning gives us such a world of medical research opportunity or opportunities for cure, if you will, that this is something that should be part of our thinking as we proceed through this quagmire?
Then, let me, Dr. Varmus, see if I've captured some words that you had clearly; in that in doing this kind of research, there are genetic switches and that we may find or scientists may find themselves doing the research and going along an even train track and the work may be going well, but then the genetic switches may switch on and off. And, what they thought they were going to get would be the complete opposite or worse than what they started out with.
Page 84 PREV PAGE TOP OF DOC With that three questions, I think, the last being is that true and can we wind up with the horror stories that many of us have watched late into the night on stations unmentioned?
Ms. JACKSON-LEE. Can we find some good in continuing to discuss--my last clean-up question--this concept of cloning, knowing that as I've listened to many of my colleagues we have great apprehension? And, I think there are religious and legal ethics as it relates to humans.
But, I would appreciate if you would comment on the concerns that I've raised with respect to these questions. I hope there has been some collective taking of notes.
I will start with Dr. Varmus.
Mr. VARMUS. Let me try to do this as succinctly as I can, Ms. Jackson-Lee. I think you heard a consensus here that there is no evidence at this point of scientific merit to the cloning of humans and that any discussion that occurs, I believe, at the Bioethics Commission will probably be focused largely on the issue of whether or not human cloning is ever appropriate under any circumstances in the context of reproductive choice.
But, what the experiments you have heard described raise is, first of all, a description of a technique which may have a number of uses in animal husbandry. I rush to say, though, that there are other techniques that can be used in animal husbandry, as Dr. Rexroad and others, Dr. Smith and others, have pointed out that may serve the same function with less expense and less trouble.
The key point, from the point of view of a medical scientist like myself, is the extraordinary opportunity demonstrated here for trying to understand how genes are turned on and off. What has been done in this experiment is to take a cell from an adult that has gone through many divisions, it has experienced a turning off and a turning on of some of its genes and yet put into a new environment after being exposed to certain growth conditions.
That cell, the nucleus and the DNA from that cell, has the potential to go through, once again, all of those switches of on and off that are required to make a complete adult animal.
Page 85 PREV PAGE TOP OF DOC We know that in many diseases, the misfiring of switches is extremely important. If we could learn exactly
what factors are required to turn off those subsets of genes and turn them on again, we might have much deeper insight into new strategies for treating a variety of human illnesses and for generating tissues for transplantation and other kinds of things that would be applicable in a wide variety of illnesses.
Mr. GUTKNECHT. I would like, if I might, respond to one thing you said almost in passing which I think actually touches on a very fundamental issue, which is you suggested that perhaps they had done it just to see if they could do it. And, actually, I think that is a very important point, because again if you know the people who are doing this work and why they are doing it, that's fundamentally not true.
People do these things for reasons. And, I think the value of the kind of educational process we have talked about here is to help understand the context in which it is done.
And, that context is exactly as we have talked about here before--in some cases agricultural, but particularly in many cases medical improvement. So that it is done as part of a plan of trying to develop medical therapies.
And, there is a saying actually in the biotech industry that relates to this in terms of when people do things like this that, you know, we are not interested in playing God, we hope to play doctor. And, it's that----
Mr. GUTKNECHT. (continuing) --perspective on why people do this work that I think helps people understand why it is being done.
Ms. JACKSON-LEE. Right. Are you suggesting that the--and, Dr. Smith, I would like to hear from you--suggesting that the Scottish researchers--I don't know whether we have their full report and you all have reviewed it. It is my understanding there was some thought that they were trying to get the A, B, C's of doing it.
Page 86 PREV PAGE TOP OF DOC Is there some other evidence that suggests out of what they have done with Dolly that there is some greater good that is coming out of that process?
Mr. GUTKNECHT. I will let Dr. Smith comment. But, I would just say----
Ms. JACKSON-LEE. Yes.
Mr. GUTKNECHT. Again that the people who are doing that work are definitely doing it, in significant part, to try to provide a better means of producing animals who can, in turn, produce therapeutic human drugs. And, that is, in large part, what the research is oriented toward.
Mr. VARMUS. It is true that the experiments described in the paper just published include some technical innovations that are extremely important. So, the ability to say, ''We did it,'' yes, that's extraordinarily important, but it is one step in a road that leads to goals that I think all of us would agree are humanitarian.
Ms. JACKSON-LEE. Yes, Dr. Smith.
Ms. SMITH. The reason that we have pursued this research at the Primate Center is because the questions arose first. I mean, for example, let's say that you are interested in studying the onset of diabetes and maybe particularly even adult onset diabetes, which is a very common disease; or, maybe you are interested in the onset of cardiovascular diseases in the human population.
Well, if you look at all the research that has been done on that and the studies, I mean, you are always left a little bit unsatisfied by the data, because you never really can sort out which of those issues that are effecting the onset of that disease are really genetically based versus how does the environment and behavior and stress and nutrition play a role in that so you can really get a handle on those factors. Those are the kinds of questions that would prompt you to say, ''Well, if we had monkeys that were all genetically identical, then the genetic variability would no longer be an issue and we could now design our experiments with very few animals and get very clear cut results.''
Page 87 PREV PAGE TOP OF DOC Another example would be in studying AIDS. In studying why something like HIV or HIV-like viruses, why do they do what they do? What are the common things they do?
Well, in the people who study this in primates--and I'm sure it's true in humans--there is some much genetic diversity that many of the responses you get, you don't know whether they are specific or not or common to the disease. And, so arrive at that commonality, you may need to use very, very, very large numbers of animals.
And, so our goal in doing this is to meet very specific research needs that relate to issues involving specific health or disease problems.
Ms. JACKSON-LEE. Thank you very much, Madam Chairperson, for your kindness. As I close out, may I get just a show of hands so that I won't take up the time of my colleague of how many believe there should be legal restraints first on cloning----
Ms. JACKSON-LEE. On human cloning?
[A show of hands.]
Ms. JACKSON-LEE. All right. So, on the generic issue, no response. And, on human cloning, I do have some support.
All right. Thank you.
Mrs. MORELLA. But, from testimony I heard earlier, they don't think there should be legislation yet, that we should hold off until we certainly get the Bioethics Committee----
Ms. JACKSON-LEE. Thank you for clarifying that. Thank you.
Mrs. MORELLA. The NBAC. Right. And, thank you, Ms. Rivers, for your patience and perseverance.
Ms. RIVERS. Thank you, Ms. Chairwoman. And, actually I would have liked to have asked this question immediately following Mr. Ehlers. But, that didn't work out that way.
Because as I was listening to the discussion, I mean, it's almost trite to say this has moved us to a brand new place scientifically, but it has also moved us to a brand new place legislatively. I think it is bringing us to a philosophical watershed.
Page 88 PREV PAGE TOP OF DOC And, I would be very interested in knowing, not just around this issue but as to others that we will surely encounter, whether we should legislate around the acquisition of certain kinds of knowledge or around the application of that knowledge. In other words, should we, as policy-makers, forbid certain kinds of inquiry and never let questions be asked; or, should we wait until the questions have been asked and answered and then regulate how the answers are applied across the Nation?
Each of you.
Mr. VARMUS. I would like to bring this back to the historical analogy that Mr. Brown raised at the start of this hearing. Twenty years ago--a little over 20 years ago when it first became possible to use another kind of cloning technique, molecular cloning in bacteria, there was apprehension. There were all kinds of bizarre scenarios of what might happen.
Fortunately, legislation was not imposed on the scientific community. The scientific community, to its credit, met and set up a moratorium until some guidelines could be proposed.
The NIH and other institutions maintained surveillance over the research. With time, it became clear that the dangers had been overemphasized.
The consequence for the nation now is that we have a biotechnology industry which you see in part displayed before you. This is an industry that employs hundreds of thousands of people and generates many dollars and most importantly, from my perspective, has produced human insulin, various growth factors for treatment of patients with serious illnesses and a variety of other substances that have already proven to be of medical value.
I am worried about legislation that occurs in a preemptive fashion before the scientific community has had a chance to respond itself.
Ms. RIVERS. So, would you be arguing that it's the application of new knowledge that should be regulated as opposed to the acquisition of new knowledge?
Mr. VARMUS. Well, it depends on what you mean by regulated. I think legislation regulating of such matters is--I think I would have to take it on a case-by-case examination.
Page 89 PREV PAGE TOP OF DOC Ms. RIVERS. Okay. Dr. Murray?
Mr. MURRAY. I would like to make a couple of general comments in response. My understanding is that contrary to the United States response which permitted the responsible going forward of research in biotechnology, Germany shut down some of that research early on and now is scrambling to catch up. That industry is simply behind because of sort of a hasty and ill-considered legislative response.
We do, in the United States, forbid certain kinds of research but not because of the subject but because of the mistreatment of either the--that might be involved with animals. We don't permit research that is cruel to animals, and we don't permit research that is not respectful of human beings, that does not protect their privacy and confidentiality and that does not--we only approve research which has substantial benefit without undue risk to the human subjects of that research.
But, that is not regulating the content. That's saying we must behave as morally responsible beings in pursuit of that knowledge.
Ms. RIVERS. Would you say that taking a position right now, which is that cloning has gone as far as we will allow it to go, crosses that line?
Mr. MURRAY. You mean, with animals?
Ms. RIVERS. With anything?
Mr. MURRAY. No, no, it hasn't. I think the research that Dr. Willmut has reported and that we look forward to seeing from Dr. Smith's laboratory and others strikes me as quite responsible and thoughtful and scientifically valuable research.
Ms. RIVERS. And, does anyone else want to speak to that?
Ms. RIVERS. Thank you all. Thank you, Madam Chairwoman.
Mrs. MORELLA. Thank you, Ms. Rivers. Actually, it kind of raised another question in my mind.
Page 90 PREV PAGE TOP OF DOC Other than the recent announcement by the Scottish research group, what are other countries doing in the area of transgenic research and in cloning?
And, if you think that the United States is ahead in these fields, are there some governmental policies that have put us in that place?
Mr. GERAGHTY. I can speak to part of that.
Mrs. MORELLA. Mr. Geraghty.
Mr. GERAGHTY. And, perhaps Dr. Smith and others can speak to other parts. I would say, first of all, you know, science is one of the most global of fields, of business or any other endeavor, because it is so universal in nature.
As a result, the biotechnology industry and related fields are truly worldwide, at least in the developed world, in their pursuit. I think the United States is a real leader in these fields, in part because of our scientific base and in part because of the support for this kind of work.
I think the example that Dr. Murray offered is a very real example, that because of some hasty decisions that were taken based on years that were not fully explored some countries have allowed research to lag significantly. I think today we do have a leadership position in the world in this, although the fact that this work was done in Scotland and there is work being done like this in other areas does suggest that if we are not thoughtful about it, there are certainly other countries looking to move forward actively and continuing to advance the field.
Mrs. MORELLA. Dr. Smith?
Ms. SMITH. I was just going to comment that in terms of the abilities of other non-human primate facilities to do this work, it would be unlikely. And, I think it's because the National Institutes of Health and the National Center for Research Resources which, you know, over 30 years ago staked out a position to support primate centers that we are able to do this work.
I think it would be extremely difficult for most facilities to do this. It takes a lot of resources and a lot of technology, a lot of very well trained people.
Page 91 PREV PAGE TOP OF DOC It's not something that could just be done anywhere someone happens to have four or five monkeys housed. It can't be done.
So, I think certainly our center is where we are without a doubt because of NIH----
Mrs. MORELLA. So, you feel----
Ms. SMITH. (continuing) --research support. There is no question.
Mrs. MORELLA. Right. Good. Dr. Rexroad, with the advent of this new animal cloning technology, do you think that super animals could be created in the laboratory to meet human goals that would push aside animals in the wild; therefore, kind of creating or actually destroying really the genetic diversity that would be needed in a healthy environment?
I mean, can you see some problems in that?
Mr. REXROAD. That's a commonly expressed concern. And, it's not real clear what the answer is.
One of the examples that I frequently use are dairy cows in the United States. In 1944, we had about 26 million dairy cows that produced, on the average, about seven million pounds--4,572 pounds of milk per cow. Forget the earlier numbers.
Currently, we have about nine or nine and a half million cows that produce more than 16,451 pounds of milk per cow. So, over this time, we have actually seen a significant reduction in the number of animals that are engaged in dairy practice.
In many ways, you might suspect that they have a lower impact on the environment. So, it's not real clear that there is a singular model to what will happen with the number of animals.
Actually increasing the productivity per animal should reduce the environmental load that we place by growing animals in the environment. I think that's more likely the direction that research will take us.
Mrs. MORELLA. So, you don't see any real downside in that?
Page 92 PREV PAGE TOP OF DOC Mr. REXROAD. Well, I think that we should be aware of potential and look at it. And, I think that we certainly shouldn't back off from doing research on these kinds of animals because we fear that that might happen.
We really need to develop models to say what will happen. And, we have scientific basis for doing that based on, for instance, the dairy cow model of some things that have already happened.
Mrs. MORELLA. Right. I would like to ask, Mr. Geraghty, we know from the O.J. trial that DNA degrades.
What happens if you clone? How can you be sure that it's done with good DNA instead of degraded DNA?
Is there any protection?
Mr. GERAGHTY. Well, again, I will speak to part of it. And, I am sure there are other people, Dr. Varmus and others, who can speak to broader aspects of it.
The one thing that we know very well actually is within the field of the transgenics production that we are focused on that when you take a gene that produces the therapeutic protein and you produce that in the milk of an animal, that is very stably inherited. We have tested that out over more than a dozen generations in the laboratory animals like mice and we have now demonstrated it over at least four generations of dairy animals.
And, we have found there is--as in the case, of course, of most of our genes, most genes which are inherited throughout generations are inherited very stably without degradation. And, these genes appear to be inherited about as stably.
Mrs. MORELLA. Yes. Dr. Varmus?
Mr. VARMUS. These experiments are not done by extracting DNA from the cell and then putting it back in. Like Dr. Watson, one of the discoverers of DNA, pointed out in the newspaper just this week in Bill Safire's column, these experiments were proposed and could easily have been done long before we knew that DNA was the source of our genes. The whole nucleus is transferred.
Page 93 PREV PAGE TOP OF DOC But, you do raise an interesting point that has not received much public attention. That is that when you take a cell from an adult animal, even from an advanced embryo, it has been through a number of generations.
In each cell division, there's the potential for errors. And, it's possible that errors are occurring in the generation of a cell that is--that comes from a fetus or from an adult animal that would not be found in the germ line of that animal.
In addition, there may be changes in the ends of chromosomes, the so-called telomeres, that are important in determining the life span of the animals. So that when the DNA is--when the nucleus is being transferred into an enucleated egg, to an egg without a cell nucleus, it's possible that we are not actually carrying out cloning in the strict sense.
There are already changes in the DNA that occurred due to natural cell biological processes. That's obviously one of the questions that can now be addressed with this technology in animal models. And, it's a very interesting question, indeed.
Mrs. MORELLA. You could also transmit diseases at the same time, couldn't you, through that process?
Mr. VARMUS. It's conceivable.
Mrs. MORELLA. Conceivable? Mr. Gutknecht, I would like to turn to you for the last questioning.
Mr. GUTKNECHT. Madam Chairwoman, I don't--in fact, the one question that I wanted to ask was what other countries are doing currently. And, I think you asked that question.
And, I hope that as this 90 day Commission goes forward that those will be important issues to be addressed, because this is not just an American issue. Obviously, it is an international issue. And, I think in the end it may well have to be addressed by some international group, whether it's the United Nations or some special panel that is put together.
But, I do think--again, I would thank you for having this hearing today. I think this is a very important issue.
Page 94 PREV PAGE TOP OF DOC And, as I said earlier, I think we, in Congress, and the American people, in general, have an intense interest right now. And, the more we can learn about it, I think the better.
Mrs. MORELLA. I couldn't agree with you more. The more we can learn, the better. And, then we can move ahead with any public policy considerations that are appropriate.
May we ask that members of the Subcommittee submit any questions to you that we would like to have your expert response on?
[The panel members nodded in the affirmative.]
Mrs. MORELLA. I want to thank you for coming and for sharing with us. I know it was a little longer than we had actually anticipated, but it's a subject that is so important. And, you have been just wonderful.
I thank you very much. And, the Subcommittee is now adjourned. Thank you.
[The hearing was adjourned at 4:35 p.m., Wednesday, March 5, 1997.]
BIOTECHNOLOGY AND THE ETHICS OF CLONING: HOW FAR SHOULD WE GO?
COMMITTEE ON SCIENCE
Page 95 PREV PAGE TOP OF DOCSUBCOMMITTEE ON TECHNOLOGY
U.S. HOUSE OF REPRESENTATIVES
ONE HUNDRED FIFTH CONGRESS
MARCH 5, 1997
Printed for the use of the Committee on Science
C O N T E N T S
March 5, 1997:
Harold E. Varmus, Director, National Institutes of Health, Bethesda, MD
Caird E. Rexroad, Jr., Supervisory Research Physioligist, Agriculture Research Service, Gene Evaluation and Mapping Laboratory, Livestock and Poultry Sciences Institute, Department of Agriculture, Beltsville, MD
M. Susan Smith, Director, Oregon Regional Primate Research Center, Oregon Health Sciences University, Beaverton, OR
Thomas M. Murray, Chairman, Genetics Testing Subcommittee, National Bioethics Advisory Commission; Professor and Director, Center for Biomedical Ethics, Case Western University, School of Medicine, Cleveland, OH
Page 96 PREV PAGE TOP OF DOCJames Geraghty, President and Chief Executive Officer, Genzyme Transgenics, Framingham, MA