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#721 - Engineering Humans -- Part 2, 28-Mar-2001

Human beings can be genetically engineered in three ways: by
inserting genes into the cells of existing people (somatic cell
manipulation, sometimes called "gene therapy"); by trying to copy
an existing person (cloning); or by changing the genes of future
generations (germline manipulation). Here we will examine serious
proposals to modify the human germline to "improve" the human
species, or perhaps even to create an entirely new species of
humans. Researchers have not yet tried to manipulate the human
germline, but proponents would like to convince us all that its a
good idea.

Biologist Daniel Koshland of the University of California at
Berkeley, a former editor of SCIENCE magazine, is a leading
advocate of genetic engineering to improve the human species.
Koshland writes, "If we do go ahead with germline engineering, as
I think we should, I can't see any possible reason for not
allowing enhancement therapy. We are facing monumental problems
with the population explosion, environmental pollution, the
shortage of fossil fuels, and the serious lack of leadership....
Should we turn our back on new methodologies that might bring us
smarter people and better leaders who are more responsible in
their lives? It's going to be tricky, but it seems silly to shut
our eyes to a new technology like this."[1, pg. 29]

In other words, Koshland is urging us to solve social and
environmental problems by redesigning our children.
Unfortunately, there is zero evidence that gene manipulation can
instill "leadership" or "responsibility" in babies. As for making
people smarter, even if it were possible there is no reason to
think "smarter" people are the solution to humanity's problems.
Many of the problems we face were created by some of the smartest
people in the world -- and were then loosed upon the world with
little consideration of the consequences.

The problems of technology and leadership today can both be
traced to a common source: decisions made by elites who don't
engage the people affected by their decisions. What we need is
not "smarter" people groomed to impose decisions on the rest of
us, as happens now; instead, we need more people with common
sense participating in decisions. In other words, we need to make
decisions in new ways, with the democratic participation of
everyone who will be affected.[2]

Some of Koshland's colleagues paint an even more extreme picture
of what genetic engineering could mean for the human race. Lee
Silver, a molecular biologist at Princeton University, writes
about future scenarios in which parents could design embryos to
suit their preferences. He suggests the human race could
eventually divide into two species, one with a normal set of
genes and the other with various expensive genetic
"improvements." The new race of improved humans might be unable
to mate with ordinary humans due to genetic incompatibility,
Silver says.[3] In the future that Silver envisions, the divide
between rich and poor would be permanently coded into our cells,
much as Aldous Huxley foretold in BRAVE NEW WORLD in 1932.

W. French Anderson of the University of Southern California
School of Medicine wants to try engineering the somatic cells of
fetuses as they develop in the womb. Anderson hopes this might be
a way to "cure" inherited diseases;[4] other researchers even
hope to get rid of unwanted traits such as high cholesterol
levels.[5] Almost all attempts to cure disease in adults or
children through somatic cell manipulation have failed, but some
proponents say a consistent record of failure is no reason to
delay experiments on fetuses.[6]

Anderson and others say they plan to leave the future sperm or
egg cells of a fetus intact, but they acknowledge they could
alter sperm and eggs by accident, thus producing changes that
could be inherited by future generations.[4]

It seems unlikely that any of this will ever succeed. Genes
usually do not control just one characteristic, so changing a
gene is likely to have multiple consequences. Furthermore, a
single characteristic may be controlled by several genes. These
facts make it seem unlikely that gene therapy or germline
engineering of humans will ever produce the desired results
without creating new problems.

Researchers recently introduced a gene for a fluorescent
(glowing) protein into the cells of fourteen fetal monkeys,[7]
but the monkeys' cells stopped producing the fluorescent protein
a few months after birth; evidently, they shut off the foreign
genes as they matured.[7, pg. 134]

We know from plant experiments that foreign genes often behave
unpredictably. In one case, petunias were engineered to produce
salmon-red flowers. When the weather turned unusually hot, the
engineered petunias began producing flowers of other colors.
Apparently the stress of high temperatures caused the plants,
unpredictably, to shut down some of the foreign genes.[8] If
monkeys shut off foreign genes as they mature, and if plants shut
down foreign genes in response to stress, should we expect
foreign genes in humans to behave differently?

When researchers genetically manipulate any plant or animal --whether
they are making clones or adding genes to existing
embryos -- they routinely produce organisms that are abnormal in
disastrous ways. It can take thousands of tries before genetic
engineers get the results they want in an engineered plant, and
many engineered plants are discarded because they are deformed or
display an unintended new feature.[9, pg. 3] When researchers
clone animals or manipulate the cells of animal embryos, the
resulting creatures often have severe defects.[10]

Germline engineering in animals, as in plants, can lead to
insertional mutation a change in gene function caused by a
foreign gene inserted into the middle of an existing gene. (See
REHN #716.) In one case, scientists created several generations
of mice with deformities resulting from an insertional
mutation.[11] If researchers introduced an insertional mutation
into a human embryo, they would create a baby with a defect that
could become obvious at birth, later in life, or only when the
victim of the experiment grew up and had children.

In general, problems that have arisen in genetic engineering
experiments on plants and animals can be expected to appear in
experiments on humans. But theres an important difference:
Genetic engineers who work with plants or rodents can breed
multiple generations to test whether an inserted gene performs as
expected in a laboratory setting. With humans, we cannot breed
test generations in a lab.

Some people still argue that somatic cell manipulation on
consenting individuals could be justified to treat serious
disease, if it could ever be shown to work the way it is supposed
to. Germline manipulation, in contrast, can never be justified as
a medical treatment, unless we redefine medicine to include
"curing" people who have not yet been conceived. For this and
other reasons, many people consider germline manipulation wholly
unacceptable. Altering the genes of future generations would
amount to a dangerous experiment carried out on subjects who have
no choice about participating. The United Nations' International
Covenant on Civil and Political Rights, which the U.S. ratified
in 1992, prohibits medical or scientific experimentation on
individuals who have not consented freely to participate.[12]

Whether they want to insert foreign genes into adult cells,
"enhance" an embryo, or redesign a fetus, proponents of human
engineering often talk as though genes were the key to
controlling health and disease. In fact, few diseases are
strictly determined by genes. In the vast majority of cases,
disease is produced or prevented through interactions between
genes and our social and physical environments.[13] For example,
certain genetic mutations may increase the likelihood of breast
cancer, but women with these mutations will not necessarily
develop breast cancer. Furthermore, 90% of women who do develop
breast cancer do not have a family history of the disease and
therefore probably did not develop it because of a gene.[14, pgs.
168-170]

Focusing on the genetic elements of sickness and health diverts
attention away from the social and environmental causes of
disease and makes it easy to blame preventable illnesses on "bad
genes." If our goal is healthier, smarter, or otherwise
"improved" future generations, there are obvious ways to achieve
that goal, such as protecting pregnant women and their babies
from toxic exposures and making sure all women have opportunities
for good nutrition and health care during pregnancy.

To learn more or to join the effort to prevent dangerous and
unethical genetic engineering of humans, contact:

** Exploratory Initiative on the New Human Genetic Technologies
(San Francisco, Calif.): (415) 434-1403; E-mail:
humanfuture@publicmediacenter.org. To sign up for the Exploratory
Initiative's E-mail newsletter, GENETIC CROSSROADS , or to
request a free briefing packet on human cloning and genetic
manipulation, send E-mail to teel@adax.com.

** Council for Responsible Genetics (Cambridge, Mass.): (617)
868-0870; E-mail crg@gene-watch.org; web: http://www.gene-watch.org

** Human Genetics Alert: web: http://www.users.globalnet.co.uk/~cahge/

--Rachel Massey and Peter Montague

=====

[1] Gregory Stock and John Campbell, editors, ENGINEERING THE
HUMAN GERMLINE: AN EXPLORATION OF THE SCIENCE AND ETHICS OF
ALTERING THE GENES WE PASS TO OUR CHILDREN [ISBN 0195133021]
(N.Y.: Oxford University Press, 2000), pgs. 29, 67-71.

[2] See, for example, Benjamin R. Barber, STRONG DEMOCRACY:
PARTICIPATORY POLITICS FOR A NEW AGE [ISBN 0520056167] (Berkeley,
Calif.: University of California Press, 1984).

[3] Lee M. Silver, REMAKING EDEN: HOW GENETIC ENGINEERING AND
CLONING WILL TRANSFORM THE AMERICAN FAMILY [ISBN 0380792435]
(N.Y.: Avon Books, 1998).

[4] Jennifer Couzin, "RAC Confronts in Utero Gene Therapy
Proposals," SCIENCE Vol. 282, No. 5386 (October 2, 1998), pg. 27.

[5] Joanna Marchant, "Generation Game," NEW SCIENTIST Vol. 168,
no. 2267 (December 2, 2000) pgs. 16-17.

[6] Holm Schneider and Charles Coutelle, "In Utero Gene Therapy:
The Case For," NATURE MEDICINE Vol. 5, No. 3 (March 1999), pgs.
256-257.

[7] Alice F. Tarantal and others, "Rhesus Monkey Model for Fetal
Gene Transfer: Studies with Retroviral-Based Vector Systems,"
MOLECULAR THERAPY Vol. 3, No. 2 (February 2001), pgs. 128-138

[8] Peter Meyer and others, "Endogenous and environmental factors
influence 35S promoter methylation of a maize A1 gene construct
in transgenic petunia and its colour phenotype," MOLECULAR GENES
AND GENETICS Vol. 231, no. 3 (Febr. 1992), pgs. 345-352.

[9] Michael K. Hansen, "Genetic Engineering is Not an Extension
of Conventional Plant Breeding; How Genetic Engineering Differs
from Conventional Breeding, Hybridization, Wide Crosses and
Horizontal Gene Transfer," report produced by Consumers Union.
Available at http://www.consumersunion.org/food/widecpi200.htm.

[10] Rudolf Jaenisch and Ian Wilmut, "Don't Clone Humans,"
SCIENCE Vol. 291, No. 5513 (March 30, 2001), pg. 2552. Also see
Lorraine E. Young and others, "Large Offspring Syndrome in Cattle
and Sheep," REVIEWS OF REPRODUCTION Vol. 3 (September 3, 1998),
pgs. 155-163.

[11] Chao-Nan Ting and others, "Insertional Mutation on Mouse
Chromosome 18 with Vestibular and Craniofacial Abnormalities,"
GENETICS Vol. 136, No. 1 (January 1994), pgs. 247-254.

[12] United Nations High Commission for Human Rights,
INTERNATIONAL COVENANT ON CIVIL AND POLITICAL RIGHTS (December
16, 1966). Available at
http://www.unhchr.ch/html/menu3/b/a_ccpr.htm

[13] David E. Larson, editor, MAYO CLINIC FAMILY HEALTH BOOK
[ISBN 0688144780], 2nd Edition (N.Y.: William Morrow, 1996), pg.
42.

[14] Ruth Hubbard and Elijah Wald, EXPLODING THE GENE MYTH: HOW
GENETIC INFORMATION IS PRODUCED AND MANIPULATED BY SCIENTISTS,
PHYSICIANS, EMPLOYERS, INSURANCE COMPANIES, EDUCATORS, AND LAW
ENFORCERS [ISBN 0807004312] (Boston: Beacon Press, 1999).

Thanks to Marcy Darnovsky of the Exploratory Initiative on the
New Human Genetic Technologies for reviewing portions of this
series.