Cosmetic "Gene Therapy"

Gene Enhancements' Thorny
Ethical Traits

Rapid-Fire Discoveries Force
Examination of Consequences

By Rick Weiss
Washington Post Staff Writer
Sunday, October 12, 1997; Page A01
The Washington Post

First in a series of occasional articles

As a medical researcher, Scott McIvor never
suspected that his efforts to develop new cures
would lead him to the edge of a brewing
bioethical storm. Then, a few months ago, he
got an e-mail message from a doctor who
wanted McIvor to help him change a patient's
skin color.

McIvor oversees the University of Minnesota's
program in gene therapy, in which researchers
inject healthy new genes into patients in an
attempt to treat genetic diseases. The doctor
knew that genes affecting skin pigmentation had
already been identified, and he had a patient
who wanted to change his racial appearance.
Would McIvor please treat his patient with
those genes?

A similarly disconcerting request recently came
to Christopher Evans at his office at the
University of Pittsburgh. Evans is helping to
devise a genetic therapy for muscle diseases
such as muscular dystrophy, in which genes will
be added to dying muscle cells to help those
cells grow. A sports medicine doctor "put two
and two together," Evans said, and asked
whether he could get access to the treatment to
help healthy athletes grow bigger muscles.

Evans answered with a definitive "no," and
McIvor didn't even respond to the skin change
request. Changes in skin color and muscle mass
probably could be accomplished with current
technology, they and others said. But the
possibility of harm would be difficult to justify
for a cosmetic procedure and, more important,
genetic enhancement of healthy people raises a
host of difficult ethical questions.

Would cosmetic gene therapy exacerbate racial
or other prejudices, for example,  creating a
market in preferred physical traits? Might it
lead to a society of DNA haves and have-nots,
and the creation of a new underclass of people
unable to keep up with the genetically fortified
Joneses?

The troublesome questions being raised 
genetic enhancement are among many now
arising as scientists break through long-standing
barriers in various fields, such as human
reproduction, genetic engineering and
animal-to-human organ transplants.

Advances in farm animal cloning, for example,
have stirred fears that human adults may also
someday be cloned. And the mass production of
gene-altered animals with "humanized" organs
may bring not only an end to the shortage of
transplantable organs but also new epidemics,
as deadly animal viruses gain their first entry
into people.

Some of these issues remain mostly hypothetical
for now, but many are surprisingly close at
hand. Given the accelerating rate of scientific
advancement, experts said, it's not too soon to
consider what limits, if any, ought to be placed
on even some seemingly remote possibilities.

Until a few years ago, human genetic
enhancement was one of those. But with the
rapid-fire identification of genes affecting
physical characteristics, such as height and skin
color, and behavioral traits such as aggression
and sociability -- and recent improvements in
the art of injecting genes into people -- many
scientists now believe that modest genetic
makeovers could become a reality within the
next few years.

"Certain types of enhancement will probably be
upon us sooner than we'd like to realize," Evans
said.

The federal government is taking that prospect
seriously. The National Institutes of Health and
the Food and Drug Administration convened a
meeting last month to consider for the first time
what regulations may be appropriate for
cosmetic gene therapy. NIH officials organized
the meeting so they might be prepared for the
first such experiments, instead of reacting to
them afterward, as happened when news broke
in February that scientists had for the first time
cloned an adult mammal.

"We all know it's coming," said Theodore
Friedmann, a professor of medicine at the
University of California, San Diego.

Public opinion polls suggest that the demand for
genetic enhancements may be substantial.
Surveys in 1986 and 1992 showed that 40
percent to 45 percent of the American public
approved of the concept of using genes to
bolster physical and intellectual traits.

Those polls also suggested, however, that the
science had gotten ahead of the public
understanding about the possible consequences
of a free market in genes. Few people realize,
for example, that although gene therapy holds
promise against inherited diseases and cancer,
none of the approximately 2,000 patients treated
so far has been cured  the still experimental
technique. Meanwhile, the procedure -- which
generally uses special viruses to inject new
genes into peoples' cells -- has the potential to
cause cancer or other problems.

Because of those risks, federally funded
scientists who want to put new genes into
patients must first convince the NIH and the
FDA that the potential for harm is outweighed
 potential benefits. Privately funded
researchers generally submit their proposals for
review as well, although they don't have to.

No regulations specifically preclude the use of
genes for cosmetic purposes, and until recently
none seemed necessary. But in March, after
months of internal debate, NIH officials
changed the equation  approving for the first
time a gene therapy experiment in people who
were not sick.

The gene being added will not benefit the
participants; it's part of a larger effort to find a
cure for cystic fibrosis. But scientists and
ethicists immediately expressed concern that it
might serve as a precedent for other gene
modifications in healthy individuals. A slippery
slope might ensue, some said, with doctors
eventually offering elective enhancements in
people's genetic makeup.

But as researchers and regulators discussed at
last month's meeting, the line between treatment
and enhancement won't be easy to draw.

"The central question is, `What is a disease?' "
Friedmann said. "Disease is a spectrum,
spanning from what we all clearly believe to be
disease . . . to someone like me who would
clearly benefit from a hair transplant."

Friedmann, at least, may be in luck. A San
Diego company that specializes in getting genes
into hair follicles already is developing a
gene-laden lotion that would be rubbed into the
scalp to reverse baldness. It's also
experimenting with genes that will make gray
hair grow dark again and to make straight hair
grow curly -- a truly permanent permanent.

"Genetic enhancement is going to happen," said
University of Southern California gene therapist
W. French Anderson. "Congress is not going to
pass a law keeping you from curing baldness."

Anderson is one of many scientists urging the
government to postpone for as long as possible
that inevitability. But the ethical arguments
against cosmetic gene therapy are not open and
shut. After all, no one is against improvements
in diet to help children grow taller, or better
schools to help them learn. What's wrong with
using genes to accomplish those goals?

Moreover, cosmetic gene therapy would not
affect eggs or sperm (that kind of gene therapy,
in which acquired traits could be passed to
children, is technically more difficult and is
widely considered to be a decade or more in
the future), so arguments against engineering
future generations do not apply. And
old-fashioned cosmetic surgery has been around
for decades with little apparent damage to the
social fabric.

Some experts suggest that genetic enhancement
bothers people because it represents a kind of
"cheating" more fundamental than that of
cosmetic surgery. For example, scientists
already know that a gene called IGF-1, which
makes muscles grow, could be valuable to an
athlete heading for an Olympic meet -- and
would be virtually impossible to test for, since
IGF-1 occurs naturally in the body. But as with
steroid use and "blood doping," gene
enhancement would undercut the Olympic spirit
of earning rewards through hard work and
training, said Case Western Reserve University
ethicist Eric Juengst.

Others note that one person's cosmetic concern
is another person's medical problem. Obesity,
for instance, is a serious medical condition as
well as an unpopular aesthetic. How should
regulators view gene therapy for weight loss?

That question may soon be more than
hypothetical, said Case Western researcher
Hunt Willard. Scientists already have identified
a gene that, when mutated, causes Prader-Willi
syndrome, a disease characterized  a huge
appetite and extreme overeating.

"If one copy of that [normal] gene keeps people
from overeating, maybe two or three copies of
this gene will be the new Jenny Craig," Willard
said, referring to the popular weight-loss plan.

In fact, only rarely will cosmetic gene therapy
be that simple. Very few traits are encoded  a
single gene, and many genes do more than one
thing. Researchers announced two weeks ago,
for example, that IGF-1 enhances the growth of
prostate tumors -- a big price to pay for bigger
biceps. Similarly, children with the
Prader-Willi mutation are not only obese but
also are uniformly extremely cheerful. That
suggests the gene plays a role in mood as well
as appetite, and that injections of the normal
gene may change more than a person's weight.

"The question is," Evans asked, "will you then
have people who are very thin but miserable?"

That would run counter to the American
Medical Association's position on genetic
tinkering, which states that genetic enhancement
of traits should be considered only when there
is "no trade-off with other characteristics or
traits." Those guidelines are subjective and
nonbinding, however, leading some to suggest
that professional self-policing is an inadequate
regulatory option.

Another option is to restrict reimbursement, as
Medicare already does, to the "treatment of
illness or injury or to improve the functioning of
a malformed body part." That would probably
limit enhancement procedures, but would not
preclude the wealthy from simply paying for the
traits they want.

Yet another option is to rely on the FDA, which
regulates gene therapy as a biological therapy,
said Maxwell Mehlman, director of the
law-medicine center at Case Western Reserve.
But that agency generally requires less proof of
safety and efficacy -- not more -- for cosmetic
products, Mehlman noted. For example, the
agency ultimately gave up its demands for proof
of efficacy of liposuction, concluding that the
benefits of the fat removal system are probably
best characterized in terms of "patient
satisfaction."

Would people be satisfied with cosmetic gene
therapy? Or would enhancement just lead to a
never-ending escalation of bigger and better?

The example of short stature may provide a
clue. Researchers suspect that daily injections
of human growth hormone throughout childhood
may help many short children attain average
heights. The treatment is controversial,
however, in part because the enormous number
of injections can leave a child feeling even
more convinced that short stature is a serious
disease. A single dose of growth hormone genes
might overcome that problem  providing a
lifelong supply of the hormone without the need
for shots. But in the end it would simply raise
the average height, leave a new group of kids at
the bottom of the curve, and perhaps strengthen
-- rather than weaken -- bias against shorter
people.

To avoid such scenarios, some believe there
may be a need for a ban on federal funding of
genetic enhancement experiments -- or even a
broader legislative ban to include the private
sector, as has been proposed for human cloning.
Even if gene therapy research were somehow
restricted to bona fide medical applications,
however, companies might still wend their way
into the cosmetic market.

That's the hope among scientists at Anticancer
Inc., the San Diego company developing a
genetic cure for baldness. Andrew Perry,
president of the company's consumer products
division, said the company will apply first for
FDA marketing approval for hair regrowth in
cancer patients who have become permanently
bald as a result of chemotherapy treatments.
Once it's approved for that medical condition,
he said, they will see if they can broaden the
market.

Similarly, McIvor said, imagine a company that
wants to offer a permanent tan -- a feat that
might be accomplished  adding the gene for
tyrosinase, an enzyme involved in the
production of the skin pigment melanin.
"Sunburns can lead to skin cancer, so it could
be seen as sort of a melanoma vaccine," McIvor
said. "But it may also be seen as a cosmetic
thing. Is that enhancement or treatment? Well,
it's a little of both."

The reverse example, in which people of color
may someday consider the possible social
benefits of genetically lightening their skin,
carries even greater ethical freight, said ethicist
Juengst, who is a member of the NIH committee
that examines gene therapy proposals.

"Self-improvement and wanting the best for
your children is acceptable and encouraged in
this culture," Juengst said. "But would I be
complicitous with some unfair cultural values if
I chose to change my skin color" to one that
offers the best chances of societal acceptance?

That question concerns not only racial
minorities but also people who suffer from rare
genetic conditions -- many of whom also face
discrimination and worry that the field of gene
therapy is abandoning them for more profitable
cosmetic endeavors.

"There will be many wealthy people willing
and eager to pay the price of making their child
taller and more beautiful," said Michael S.
Langan, a vice president of the National
Organization for Rare Disorders. "Eventually
there will be discrimination against those who
look `different' because their genes were not
altered. The absence of ethical restraints means
crooked noses and teeth, or acne, or baldness,
will become the mark of Cain in a century from
now."

POTENTIAL GENE THERAPY FOR
BALDNESS

A cream could carry hair growth genes in
laboratory-made bubbles called "liposomes."

1. Cream would be rubbed into the scalp.

2. Liposomes would be absorbed into the skin,
where they bind to dormant hair follicle cells
and release their genetic payload.

3. Genes would enter follicle cells and turn on
hair growth machinery. Hair would continue to
grow for as long as the new genes continue to
function inside cells.

SOURCE: Anticancer Inc.

ABOUT THIS SERIES

Biomedical research is proceeding at
breathtaking speed.

Geneticists are gaining new insights into how
genes work. Biologists are unmasking the
mysteries of how a tiny clump of cells develops
into a fully formed human. Immunologists are
deciphering the complexities of the body's
defense systems.

The research is yielding many potential
benefits. Doctors can identify people at risk for
genetic diseases and fashion strategies to save
their lives. Reproductive biologists can help
infertile couples have children. Researchers can
engineer animals with organs that may be
transplanted into humans.

But as science speeds ahead, it often pushes the
edges of society's readiness to cope with its
consequences. Increasingly, research creates
possibilities before the accompanying ethical
ramifications have been resolved. In an
occasional series of articles, The Washington
Post will explore these issues. Today, the first
article in that series examines the possible
benefits and problems raised  the prospect of
"cosmetic gene therapy."

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