For years, the hype surrounding genetic engineering and gene therapy knew no bounds. With the Human Genome Project -- publicized at the height of the dot com mania -- things went from bad to worse. The genome was "decoded," then fully decoded. Then a final draft was decoded one more time, fully and finally. That was last spring. And still they didn't know how many genes we have. Twenty thousand? Forty thousand? About as many as roundworms, some guessed.
Something was wrong. But there had been a coronation, and now there was no going back. The genome was the marvel of our age. Knowing the nucleotide sequence of the DNA would allow us to decipher the mysteries of life. Now we could repair the misprints and defects that had brought us disease and misery. Sooner or later, death itself would be overcome.
There was no adversary press. The liberals who had brought us social engineering were not going to dispute the claims of human engineering. The breakthroughs, endlessly touted, constituted the new progressive vision. For the first time in years, it became possible for liberals to believe in progress again. So the journalists formed themselves into a cheering squad. The libertarians were especially enthusiastic.
In part, the conservatives were critical. But they confined their criticisms to the ethical realm. Ought we to be doing these things? The science itself was accepted as a given. Only a few old-fashioned leftists, disapproving a priori of the claim that we are hard-wired products of our genes, provided any balance. A critical review in Harper's by Barry Commoner, examining "the spurious foundation of genetic engineering," was exceptional in challenging the science itself.
The moral qualms of the conservatives only inflamed the utopian passion of the bio-engineers. Were it not for benighted politics, progress would be assured. We had been on the brink of attaining it, and then came George W. Bush! Michael Kinsley howled for increased political support for stem cell research. The scientists had worked their wonders, but the pols were letting us down.
Belatedly, second thoughts about the science are now beginning to surface. There are signs of impatience, verging on disillusionment. The human genome in particular is not delivering as expected.
HUMAN DNA IS A GREAT STRING of four nucleotides, three billion letters long. Some of these sequences -- the "coding regions" -- are called genes. They control the construction of proteins in the body. But far greater stretches of the same DNA are "non coding regions," and for many years they were called "junk." That was the word scientists used. Junk DNA had no function and could be ignored. These enormous sequences, amounting to 98.5 percent of the whole genome, were dismissed as the accumulated rubbish and detritus left behind by the constant trial and error of evolution.
Now the white-coats are beginning to suspect that they made a mistake. Wayt Gibbs reported in November's Scientific American that "journals and conferences have been buzzing with new evidence," contradicting the old idea that genes "are the sole mainspring of heredity and the complete blueprint of life." Included in this "unseen genome" is the 98.5 percent that had been "written off as irrelevant." Some scientists now suspect that the key to understanding what makes one person different from the next is, precisely, "hidden within our 'junk' DNA."
Sooner or later this will make its way to the front pages, and we will realize that the genome project was based on a misconception. Some scientists are already arguing that the gene must be rethought and may have to be abandoned in favor of something more fluid.
"The concept of a gene as an easily recognized single segment of DNA has evaporated," says Art Robinson, who taught biochemistry at U.C. San Diego before launching his own Oregon Institute of Science and Medicine. "The real question is: What is the other 98.5 percent of the DNA used for?" He suggests that "there is an entire new dimension of the molecular structure of life that has been hitherto unknown." Phillip Johnson, the U.C. Berkeley law professor who began a new career some 15 years ago as an articulate critic of evolutionism, thinks that "DNA is vastly less important than we have been led to believe."
No error will be admitted. Political appointees at the National Institutes of Health will call for fatter budgets. "Great strides have been made," they will say. "It is still a young science." The National Human Genome Research Institute's budget (which grew from $28 million in 1988 to $480 million today) will surely be increased. The nation's health and security will be said to depend on it. And more and more young scientists, attracted by the nine-to-five security of government work, will disappear into the labyrinths of federally funded research, never to be heard from again.
THERE ARE TWO SEPARATE problems. One is reading the genome -- not in sight yet. The second is knowing what to do with the information, medically. In the case of some genetic diseases -- sickle cell anemia, for example -- the gene defect was known decades before the genome project was a gleam in James Watson's eye. Still, no cure has been forthcoming. DNA anomalies associated with cystic fibrosis were found in 1989. Again, no cure. The problem is that the genetic error is in every one of the body's 100 trillion cells. How do you get the corrected gene into enough cells to make a difference? That is the unsolved puzzle of gene therapy.
One technique had shown promise. A harmless retrovirus was used to transport the repair gene into the body. A virus infects lots of cells on its own. So it embeds the reformed gene that way. But there is this great difficulty: The body's immune system sees the virus as a foreigner and quickly wipes it out. End of treatment. But with a rare genetic defect that cripples the immune system itself, the treatment did seem to work. Some children in a Paris hospital were claimed cured by this method. The New York Times reported it as the "first success of gene therapy."
Two years later, some of the treated children who were thought cured developed leukemia. On the Washington Post's front page the headline read: "Dream Unmet 50 Years After DNA Milestone. Gene Therapy Debacle Casts Pall on Field." The news came on the 50th anniversary of the double helix.
The idea that the instructions needed to build fantastically complex organisms are contained in a simple linear code appealed to scientists for various reasons. The problem could be digitized. "Errors" in the genome could be found by computers; and perhaps also corrected by them. But almost certainly that is not going to work out.
THE GENE MANIA OF THE LAST generation has had serious consequences. Above all it has led to what is surely the most serious error of modern medical science -- the unproductive 25-year pursuit of the theory that mutations or "spelling errors" in the genome turn normal cells into cancer cells. (Wayt Gibbs also discusses this matter -- more tactfully and politely than I have here -- in an earlier [July] issue of Scientific American.)
I believe the underlying problem is that government funding, which increasingly dominates medical research, demands that a "political" consensus be substituted for the exploration of rival theories by the normal trial and error of scientific method. Government agencies won't fund rival theories.
A year ago, the writer Michael Crichton gave a lecture at Caltech in which he explored the harmful transition from science to consensus. His argument was fascinating. The search for extraterrestrial intelligence somehow morphed into nuclear winter, and from there, from "second hand smoke to global warming." Science and policy have become inextricably mixed, he said. We have seen this most strikingly with AIDS -- turned now into a grossly politicized rationale for the expansion of foreign aid. We have seen it with cancer -- over 100 "oncogenes" have been catalogued, not one of which has been shown to cause cancer. And we have only begun to see it with the Human Genome Project.
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