Mapping the human DNA sequence is a dream come true for many scientists, but the possible consequences are giving bioethicists nightmares. Meanwhile, some observers think Darwinian assumptions cause researchers to place too much emphasis on genes.
Biology's version of the Book of Life is being written, in part, on the 14th through 16th floors of a gleaming medical tower at Baylor College of Medicine in Houston, Texas. Jeans朿lad biotechnicians peer at computer screens, poke with sterilized toothpicks at spot朿overed gel in trays, and cart racks of test tubes down gray hallways to and from labs filled with banks of thermo朿yclers, sequencers, and other equipment.
Most workers are under 30 and hold "entry杔evel" positions. Few hold graduate degrees, and some haven't finished college. It seems an unlikely setting for what President Bill Clinton in March called "the scientific breakthrough of the century, perhaps of all time."
The technicians are nearly finished "sequencing" the entire human genome; that is, determining the order of the three billion pairs of nucleotides that make up human DNA. The Human Genome Sequencing Center at Baylor is one of five major sequencing centers in the United States, with another in Britain and minor centers scattered around the world. Together they make up the decade杘ld Human Genome Project, an international consortium directed by the National Institutes of Health (NIH) and the Department of Energy.
The $250 million Project plans to release its first draft by summer, having sequenced 90 percent of the genome with 99.9 percent accuracy. The sequence is on a publicly available database, allowing researchers to hunt for all 80,000 to 100,000 genes杝ections of DNA that are believed to control cell development and operation杋n a typical human cell. Scientists use this genetic map to try to figure out what each gene does and how it works with other genes. They then associate mutations in particular genes with specific diseases.
The sequence of human DNA has been called a periodic table of the elements for human biology, or as a recent Newsweek story gushed, the "blueprint of human life, the code of codes, the holy grail, ... what it means to be human." Many believe that this project will revolutionize modern medicine. The media are jumping on the bandwagon; all the attention over the last few years has sent biotech stocks soaring. The final version, expected two years ahead of schedule in 2003, will be, according to NIH National Human Genome Research Institute director Francis Collins, a professing Christian, a "phenomenally significant event in human history."
Enthusiasts predict that in a few more decades genetic research stimulated by the Human Genome Project will lead to cures and more effective treatments for diseases ranging from cancer to schizophrenia. Involvement in the Human Genome Project "is a work of discovery which can also be a form of worship," wrote Dr. Collins in 1997. "It is part of our mandate as Christians to pursue such medical advances, attempting to emulate Christ in his healing role," he said.
In 30 years, predicts Dr. Collins, genetic technology will be so advanced that your physical exam will include a complete genetic profiling. The doctor will swab a few cells from inside your cheek and insert them into an analyzer. A computer will compare your genome to the thousands of disease genes identified by then, pin杙ointing the illnesses you already have or may develop.
Doctors will also use genetic technology to prescribe preventative measures, like specialized diets for those at increased risk of heart disease and regular screening for those with a genetic predisposition for colon cancer. Some presently incurable diseases will be defeated with "gene therapy," the technique of using viruses to insert healthy genes into cells with defective genes.
Eventually, goes the claim, once scientists understand how particular genes cause diseases, they will design drugs accordingly, instead of using the current trial朼nd杄rror method. Scientists will know why some drugs and therapies work so well for some patients but put others in the hospital. Doctors will prescribe medications with the least unpleasant side effects for a given patient. Some scientists predict designer babies杘r at least the ability to influence hereditary traits like height and intelligence and eye color. In addition, genetic science will produce a host of industrial and agricultural breakthroughs, like toxin杄ating bacteria and more pest杛esistant crops.
That's the optimistic assessment of the impact of genetic science.
But Celeste Condit, a communications professor at the University of Georgia who writes regularly on ethics and genetics, offers a nightmare scenario that includes:
- routine prenatal genetic screening, with stringent standards for determining which babies live and die;
- the ready availability of genetic testing generating a sort of public hypochondria, with fears of disease far exceeding the actual risks;
- genetic discrimination, with jobs and health insurance denied to those at risk of serious disease;
- the sorting of young children into career tracks and social classes based on their "genetic potential."
At the moment the nightmare seems more real than the dream. Melanie Andrews朇asal, a genetic counselor with Applied Genetics Inc., in Austin, Texas, does mostly prenatal counseling ($120 per session). She is a member of the National Society of Genetic Counselors, which supports abortion and fetal tissue research. "I see myself as an educator," she said, supplying "non杁irective facts and statistics related to the options."
Most of her clients whose unborn babies have the gene for diseases severe enough to require life support choose to abort them, she reported. About half of parents with Down syndrome babies kill them in the womb. Several dozen commercially available tests discern diseases like cystic fibrosis and hemophilia, but as the number of tests increases, the demand for prenatal screening could escalate accordingly. Already, reported the London Daily Telegraph last month, a British government agency is calling for genetic screening for all pregnant women, in case "abnormalities" prompt them to seek an abortion.
Some see prenatal genetic screening as modern eugenics. C. Ben Mitchell, assistant professor of bioethics at Trinity International University in Deerfield, Ill., said that it "targets fetuses for destruction, since we don't have cures or treatments for most genetic anomalies."
At present, genetic testing can provide only a range of probabilities杋t can't specify when or even if the patient will develop a given disease. Thus, women who test positive for BRCA1 may never suffer breast or ovarian cancer, but "feel like they're walking around with a time bomb," said Ms. Andrews朇asal.
Many more bombs, real or not, will be uncovered when genetic testing becomes readily available and people start ordering their own. Already a Houston company has a national ad campaign for DNA paternity testing. Commuters in 30 major U.S. cities see large, dark billboards with "Who's the father𢴖00朌NA朤YPE" in bold lettering. For $475, Identigene Inc. does a standard DNA paternity test from a cheek swab.
The company has grown rapidly since its 1993 start, said President Caroline Caskey: "It's a peace杘f杕ind issue. A lot of our clients just want to have the answers." Results are mailed within a week. Firms like Applied Genetics offer tests for single杇ene diseases for as little as $250. Complicated tests that must check several areas of the genome, like the one for BRCA1, may cost $2,700 or more, and insurance companies may or may not cover the cost.
Genetic discrimination is presently uncommon, but a series of horror stories prompted federal legislation discouraging the practice in health insurance plans in 1996 (insurance companies may not consider disease genes a "pre杄xisting condition"). Last February President Clinton signed an executive order prohibiting it in federal hiring and promotion practices.
But Mr. Mitchell believes that if the technology is there, people will find a way to abuse it. "All of us have some genetic problems," said Mr. Mitchell, "and as the tests become more sophisticated it's unlikely that we'll find anybody without any mutations."
The ethicist is also concerned that economic pressure to get genetic tests and therapies to market are tempting scientist朇EOs and their venture capital backers to ignore or marginalize once杋nviolate research principles and hide information that would drive down the stock prices of their biotech firms.
In the most damning incident so far, last fall Jesse Gelsinger, 18, died in a gene therapy experiment for his genetic liver disorder at the University of Pennsylvania. The Food and Drug Administration shut down the program indefinitely, blasting researchers for failing to halt the study when several patients suffered serious side effects, failing to report these incidents to the NIH, and failing to obtain proper consent from patients. The NIH later discovered that gene therapy researchers across the country had not filed reports on 650 "adverse incidents" in a timely fashion.
The dispute over ownership of genetic data is also troubling. Celera Genomics Corp., a private firm from Rockville, Md., is racing the publicly funded project to finish the first genetic map. It developed a powerful new "shotgun" sequencing method that is still controversial because it leaves large gaps杔ike having all the pieces of a jigsaw puzzle but not being able to assemble them. Celera has already produced its first "draft" of the human genome. Celera and HGP officials were negotiating a collaboration that might have produced a final version by the end of this year. Talks broke down in March over whether the sequence would continue to be freely available or whether Celera could control the data, turning biology's Book of Life into a for杙rofit lending library. Celera now sells its genetic data to subscribers, mostly pharmaceutical and genomics firms.
Defenders of public access say that the human genome is the common property of humanity. Charging for access to the sequencing data will stifle genetic research, they say, and there's too much at stake to allow that. Moreover, the drive to patent genes is a turning into a modern杁ay gold rush. The chemical sequence of human DNA may not be patented, but individual genes may if the gene's function is known. Billions of dollars are at stake.
The companies that identify gene functions and patent them will claim a share of any medical applications produced from that knowledge. Tens of thousands of preliminary patent applications have been filed. The U.S. Patent and Trademark Office is tightening up its rules to try to prevent firms from, in effect, staking out the whole Klondike before they know where the gold is.
Christians should start now to influence the public debate over genetic ethics, says John Kilner, director of the Center for Bioethics and Human Dignity, a think tank at Trinity International University. The main issues involve privacy of genetic information (should your employer or the government know you're susceptible to hypertension?) and how much genetic manipulation is appropriate. The ethical bottom line, said Mr. Kilner, is that medicine must respect the fact that humans are made in the image of God. "We should not go beyond correcting problems to shaping people the way we want them to be," he said.
Questions abound. What's morally wrong with giving your child a better memory? Would you marry someone with a genetic predisposition to Alzheimer's? Should you ask for premarital testing? It's also difficult to come up with ethical guidelines when nobody knows what therapies will be possible or when they will be available.
Less may be possible than the promoters of genomics predict, and the answers and cures further off. Scientists announce links between genes and diseases almost weekly; some of the more recent are for stomach, cervical, and testicular cancer. But after a decade of research in gene therapy, individual patients have been helped in trials, but there is still scant evidence that gene therapy can effectively treat any disease. Researchers have been stymied by the body's immune system, which attacks the viruses attempting to insert the "healthy" genes.
Nobody knows which human characteristics are genetically determined and which are affected by environment or other factors. "I think people will be very surprised at what is genetically determined and what isn't," predicted Richard Gibbs, a Baylor molecular biology professor and director of Baylor's Sequencing Center.
Jonathan Wells, a molecular biologist with the Discovery Institute, argues that genes, environment, and cell structure all affect development. DNA controls the production of proteins that affect development, but the cytoskeleton (a network of microscopic fibers) and certain features in the cell membrane determine what happens to these proteins after they are made.
This helps explain why, when the "developmental genes" from a fruit fly are inserted into a mouse embryo, it continues to develop along conventional mouse杄mbryo patterns until the lack of the correct proteins kills it. "It would be more accurate to say that a developmental program is written into the structure of the entire fertilized egg, in a language of which we are still largely ignorant," he said.
"The notion that genes control development is a fallout from neo朌arwinian evolutionary theory," Mr. Wells added. Evolutionists use genetic mutations to explain how organisms could change gradually over time. But if development involves the entire egg, then its complexity is much stronger evidence that a Creator designed life.
Mr. Wells also questions whether genes determine most diseases. Some single杇ene disorders, like cystic fibrosis, clearly are mainly genetic, he said. But the only way researchers can now connect a disease with a particular gene is by statistical correlation studies杢hat is, they hunt for common genetic patterns in people with the disease. "But correlation is not cause," he pointed out, "and the correlations aren't even very good in many of these cases."
If many factors杋n addition to DNA杁o affect diseases, this would help explain why only some of the people with the gene for a given disease actually develop it, and why severity varies wildly among people with the same gene. The claim that diseases are the result of interactions between genes that have yet to be discovered "is still only a theory," he said. The correlations between genes and behaviors, like alcoholism and homosexuality, or genes and psychological characteristics, like intelligence, are "even dicier than the connection with disease." The implication is that fighting disease is a far more complex problem than simply getting healthy genes into sick tissue.
If cancer is not genetic, said Mr. Wells, "then a cure for it might be found sooner if researchers would stop looking in the wrong place. As for designer babies, what this world needs is not more people with good looks or athletic ability, but more people with moral fiber and high principles. Whatever else might be said, sequencing the human genome is a much smaller advance than its promoters claim."
Reprinted by permission of World Magazine, copyright 2000.