RACHEL'S ENVIRONMENT & HEALTH NEWS #720 ---March 15, 2001---

ENGINEERING HUMANS, PART 1 by Rachel Massey*

As we saw in our series on genetic engineering of food crops, genetic "engineers" are now moving genes around among plants, animals, and bacteria on a regular basis, but with very little understanding of the possible consequences, and almost no safety testing. Now genetic engineers are starting to modify the genes of humans, using three approaches: 1) cloning, 2) somatic cell manipulation, and 3) human germline manipulation.

Cloning: Cloning uses the DNA of an existing individual to create a new individual. The best-known example is Dolly, a sheep that was cloned using DNA from a sheep that had been dead for six years. A human has not yet been cloned, but a team of researchers including an American and an Italian recently announced they are going to attempt it.[1]

Somatic cell manipulation: Somatic cells are all the cells of the body that do not pass DNA on to the next generation. Somatic cell manipulation is currently practiced in some medical research centers under the name "gene therapy." For example, researchers are experimenting with ways to introduce genes into the blood cells of patients with hemophilia (a blood disorder), and into cells of the immune system in patients with Severe Combined Immune Deficiency (SCID), a rare inherited disorder of the immune system. The idea is to "correct" the genetic component of the disease instead of, or in addition to, treating the disease with drugs. Hundreds of trials have been carried out, but in most cases the patients have not been cured.[2]

Germline manipulation: Germ cells (sperm and eggs) do pass DNA from one generation to the next. Germline manipulation refers to changes in the germ cells changes which will be inherited by successive generations. Designing future generations through germline manipulation is still in the realm of science fiction, but just barely: some influential scientists are arguing that it should be attempted.

Why are scientists pursuing these techniques? Some researchers see somatic cell manipulation as a promising way to treat serious diseases, such as cystic fibrosis. Other genetic engineers may have less idealistic motives. Engineering human cells is technically appealing, and the mere fact that we possess this technology is, for some people, sufficient reason to use it. Some technological optimists are fascinated by the idea of germline engineering as a way to "take evolution into our own hands" by redesigning the genetic information in our children's cells.

Engineering human cells could also be a big money-maker. For example, one company hopes to create a market in "organ repair" generating cloned cells and tissues to insert into existing people's organs.[3, pg. 18] Other companies and researchers simply want to keep open the option to engineer human cells because it could be profitable in the future, even if they have not made investments in doing it right now.[3]

Cloning

There are two main applications of cloning. One is "embryo cloning," which could be used to create new human parts. For example, some scientists are working on methods to produce a new embryo from an existing person's cells and then use the cells from that embryo to produce replacements for failing body parts in the original person.[4] An embryo develops about a week after conception, and in its early stages consists of a few identical cells.

"Reproductive cloning" would produce complete cloned individuals, like Dolly the sheep. Genetic engineers are now able to clone mice and cattle as well as sheep.[5, pg. 45] Human cloning would produce a new person who is a near genetic copy of another person. He or she would, however, be different from the original person because he or she would develop in a different environment and have different experiences.

Many people think both "reproductive cloning" and "embryo cloning" are repugnant and unethical. Other people think embryo cloning could be acceptable in some cases to treat disease but think reproductive cloning is wholly unnecessary and never justifiable.

In the U.S., federal funds cannot be used for reproductive cloning experiments and some states have outlawed it, but there is no federal law against it.[5, pg. 4] A team of researchers recently announced they are going to attempt human cloning in an "unidentified Mediterranean country."[1] These researchers have been widely condemned, but some of their colleagues are primarily concerned that this early attempt at cloning could give the technology a bad name and reduce the public's willingness to allow further cloning research.

Somatic cell manipulation

Somatic cell manipulation adds genes to existing cells in some part of the human body, such as the lungs or the blood. Somatic cell manipulation is only supposed to affect the DNA of the person undergoing the treatment. In theory, it does not produce changes that could be passed on to that person's children and grandchildren.

Somatic cell manipulation was first attempted on humans in 1990.[6, pg. 110] The mechanisms of somatic cell manipulation are poorly understood, and the effects can be lethal. In one case, a teenager died after researchers at the University of Pennsylvania tried to introduce genes into his liver cells, using a modified virus to carry the genes to their destination. The idea was that the virus would "infect" the target cells and insert the desired genes, without being dangerous itself. The researchers are still not certain how they killed their patient, but evidence suggests the virus invaded many organs besides the liver and triggered a severe immune reaction.[7]

According to the U.S. Food and Drug Administration (FDA), somatic cell manipulation also poses the threat of insertional mutagenesis, in which inserting new DNA changes or disrupts the functioning of existing DNA. (See REHN #716. ) FDA also says researchers attempting to alter somatic cells could inadvertently introduce foreign genes into the patient's sperm or egg cells.[8, pg. 4689] If this happened, researchers could accidentally change the genetic information passed from parent to child.

Researchers are required to submit data to FDA and the National Institutes of Health (NIH) on any adverse effects that occur during somatic cell manipulation trials. After the teenager's death at the University of Pennsylvania, an investigation revealed that many researchers were not reporting adverse effects to NIH, which can make the information public. Some researchers say it would "confuse people" to report every death that occurs during these trials because many participants are seriously ill and could die for reasons unrelated to the treatment.[9]

Right now, most information that researchers submit to FDA on somatic cell manipulation experiments is kept secret.[8, pg. 4688] The agency has issued proposed regulations under which information about somatic cell manipulation trials will be made available to the public, and is accepting comments on the proposed regulations until April 18, 2001.[10]

Germline manipulation

Germline manipulation permanently changes the inheritable characteristics passed from one generation to the next. This can be done by altering sperm or egg cells or by altering an embryo. If an engineered embryo survives and develops into a baby, the changes introduced by germline manipulation will be present in every cell of that baby. If the baby survives to adulthood and has children, the changes will be passed on to future generations, through that person's sperm or egg cells.

Some researchers try to justify germline manipulation by saying it could remove or replace DNA associated with an inherited disease. This is a far-fetched idea and unnecessary; even if both members of a couple have the genes for a hereditary disease, there are other ways to produce a child without the disease, including using donated sperm or eggs. Other researchers say they want to
use germline engineering to give a baby new genetic features it could not have gotten from its parents. This goal cannot be achieved through any other technology. It is also a goal that, by definition, could never be medically necessary because it would not serve to relieve sickness in an existing person. Instead, it would aim to "improve" future generations of human beings.[6, pg. 113]

The attempt to "improve" the human race genetically -- as one might create a specialized breed of horses or dogs -- is known as eugenics. In the early decades of the 20th century, eugenics projects in the U.S. led to forced sterilization of some people who were considered to have undesirable traits. This included prison inmates who were considered to be "hereditary criminals." One forced sterilization was justified by describing a man as "subnormal mentally," with "every appearance and indication of immorality."[6, pgs. 20-21] In Nazi Germany, the systematic extermination of Jews and other people was one part of a eugenic project to breed a "superior race."[6, pg. 17]

Some prominent scientists hope to achieve eugenic goals through genetic engineering instead of through breeding. Molecular biologist Daniel Koshland, formerly the editor of SCIENCE magazine, argues that "if a child destined to have a permanently low IQ could be cured by replacing a gene, would anyone really argue against that?" He continues, "It is a short step from that decision to improving a normal IQ. Is there an argument against making superior individuals?... As society gets more complex, perhaps it must select for individuals more capable of coping with its complex problems."[4, pgs. 115-116]

To be continued.

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*Rachel Massey is a consultant to Environmental Research Foundation.

[1] Jane Barrett, "U.S., Italian Experts Plan to Clone Humans," Reuters (March 9, 2001). Available at http://dailynews.yahoo.- com/ htx/nm/20010309/sc/italy_cloning_dc_2.html

[2] Larry Thompson, "Human Gene Therapy: Harsh Lessons, High Hopes," FDA CONSUMER MAGAZINE (September-October 2000) Available at http://www.fda.gov/fdac/features/2000/500_gene.html

[3] See Sarah Sexton, "If Cloning is the Answer, What was the Question?: Power and Decision-Making in the Geneticisation of Health," THE CORNERHOUSE Briefing 16 (1999). Available at http://cornerhouse.icaap.org/briefings/16.html

[4] Emma Young, "Stem Cell Go-Ahead," NEW SCIENTIST ONLINE (December 20, 2000). Available at http://www.newscientist.com- /nsplus/insight/clone/stem/goahead.html.

[5] Margaret Talbot, "The Cloning Mission: A Desire to Duplicate," NEW YORK TIMES MAGAZINE (February 4, 2001), pgs. 40-45, 67-68.

[6] 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 0807004316]. (Boston: Beacon Press, 1999).

[7] Eliot Marshall, "Gene Therapy Death Prompts Review of Adenovirus Vector," SCIENCE Vol. 286, No. 5448 (December 17, 1999), pgs. 2244-2245.

[8] Food and Drug Administration, "Availability for Public Disclosure and Submission to FDA for Public Disclosure of Certain Data and Information Related to Human Gene Therapy or Xeno- transplantation," FEDERAL REGISTER Vol. 66, No. 12 (January 18, 2001), pgs. 4688-4706. Available at http://frwebgate.access.gpo.- gov/cgi-bin/getdoc.cgi?dbname=2001_register&docid=01-1048-fild

[9] Maggie Fox, "Gene Therapy Under Fire," Reuters (January 31, 2000). Available at http://www.abcnews.go.com/sections/living/- DailyNews/genetherapy_000130.html

[10] See Council for Responsible Genetics Alert, "Tell the FDA that the Public has a Right to Know about Xenotransplantation and Gene Therapy, February 28, 2001." Available at http://www.gene-watch.org/crgalerts.html

. . RACHEL'S ENVIRONMENT & HEALTH NEWS #721 . . ---March 29, 2001--- . . HEADLINES: . . ENGINEERING HUMANS, PART 2 . . ========== . . ENGINEERING HUMANS, PART 2

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 characteri
stic 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://- http://www.gene-watch.org

** Human Genetics Alert: web: http://www.- users.globalnet.co.uk/~cahg/ --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). < /p>

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

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