Below is the transcript of your testimony before the Morella's Science
Committtee hearing on March 5, 1997, called "Biotechnology and the
Ethics of Cloning: How Far Should We Go?

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.

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.

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 recentiy, 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-fartilization 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.

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, chat
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.

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.
In addition, we had a presidential order imposed in December of 1994
and amendments to our appropriation bills in the last 2 years chat
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 peyond 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.