TIME: Almanac of the 20th Century

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<text> <title> (Mar. 15, 1993) Happy Birthday, Double Helix </title> <history> TIME--The Weekly Newsmagazine--1993 Mar. 15, 1993 In the Name of God </history> <article> <source>Time Magazine</source> <hdr> SCIENCE, Page 56 Happy Birthday, Double Helix </hdr> <body> Forty years after their discovery of DNA's secret, Watson and Crick celebrate its impact on the world By Leon Jaroff/Cold Spring Harbor--With reporting by Larry Thompson/Washington It was a night to celebrate. Raising their glasses in the Eagle, a pub near the campus of Cambridge University in England, a euphoric Francis Crick, 36, and James Watson, 24, drank to what they had just accomplished. Over the hubbub in the crowded pub, Crick's voice boomed out, "We have discovered the secret of life!" Indeed they had. The year was 1953, and that afternoon in the university's Cavendish Laboratory, the two brash overachievers had at last solved a puzzle that had for years stymied scientists seeking to understand how traits are passed from one generation to the next. By finally discerning the double-helix structure of deoxyribonucleic acid (DNA), the giant molecule of heredity, they had cleared the way for a great leap forward in human understanding of the processes of life. Last week Watson and Crick were euphoric again as they gathered with a brilliant galaxy of scientists, biotech executives and other friends to celebrate the 40th anniversary of the discovery that opened a new era. The site was the century-old Cold Spring Harbor Laboratory on New York's Long Island, where Watson, host of the glittering symposium, has served as director for 25 years. The appearance of the reclusive Crick helped highlight the event; he seldom ventures forth from California's Salk Institute for Biological Studies, where for the past 17 years he has been studying the brain. "Jim is an administrator and manager," Crick explains. "I'm still caught up in research." The setting could not have been more appropriate. Representations of the fabled molecule abound at the campus-like laboratory, which Watson calls "the University of DNA." Twisted, twin-strand, DNA-like designs border the ceiling of the auditorium and circle the lab's ubiquitous CSH insignia. A delicate steel model of the molecule sits in the auditorium lobby, and a DNA rendering hangs from the wall behind Watson's desk. The laboratory's lofty bell tower is not exempt. Each of its four sides is labeled with a letter representing one of the four nucleotides that constitute DNA's code letters: A, T, C and G. And visible through arches in each of the tower sides is a central staircase--spiral, of course. As an added touch, Watson and several of his guests who had investigated DNA's handmaiden, RNA, in the later 1950s wore their RNA Tie Club ties, each bearing the image of the single-strand molecule. DNA was also very much on the minds of the scheduled speakers as they described the events flowing from the Nobel-prizewinning Watson-Crick discovery. In the four decades since, scientists, building on their knowledge of DNA's structure, cracked the genetic code, described the machinery of the living cell, identified and located specific genes and learned to transfer them from one organism to another. Their work has already transformed biology, created the biotech industry and new pharmaceuticals, is beginning to affect business, industry, agriculture and food processing, and promises to change drastically the way medicine is practiced. "In five years the impact on medicine will be big," predicts Crick. "In 10 or 15 years, it will be overwhelming." Key to the rapid progress in genetics is the 15-year, $3 billion Human Genome Project, which Watson headed from its beginning in 1990 until he left last April over differences with Dr. Bernadine Healy, the director of the National Institutes of Health (NIH). The ambitious project, which Watson helped persuade Congress to fund, has as its goal the discovery and mapping of all the estimated 100,000 human genes and the sequencing, or arranging in order, of all 3 billion chemical code letters in the human genome, the long strands of DNA that make up the chromosomes in the nucleus of each* of the body's 10 trillion cells. The genome is in effect a blueprint for the complete human being, containing instructions that not only determine the structure, size, coloring and other physical attributes, but can also affect susceptibility to disease, intelligence and even behavior. "We used to think that our fate was in our stars," says Watson. "Now we know, in large part, that our fate is in our genes." Scientists funded by the genome proj ect have their work cut out for them. As of last week, only about 6,100 human genes had been identified, and only a tiny fraction of the genome sequenced. But the rate of discovery is picking up. Even as the gala event at Cold Spring Harbor was proceeding, news came that a collaborative group of scientists from 13 institutions had identified the gene that, when faulty, is responsible for at least some cases of amyotrophic lateral sclerosis, or ALS, the untreatable degenerative nerve disorder that crippled and eventually killed Lou Gehrig, the New York Yankee first baseman. Victims of "Lou Gehrig's disease" usually die because of fast-spreading paralysis in as little as three to five years. A small percentage of ALS sufferers, including famed British physicist Stephen Hawking, manage to survive for decades, mentally alert but trapped in a completely immobilized body. The new finding, reported in the journal Nature, could someday result in treatment and perhaps even prevention of the disease. Only a week earlier, in another Nature report, scientists revealed that they had found the gene that appears to cause X-linked adrenoleukodystrophy, or ALD, the rare degenerative disease depicted in the movie Lorenzo's Oil. Other researchers have just discovered that at least 23 different mutations in a single gene can lead to the development of type II (adult) diabetes. The identification of disease genes has already resulted in the development of tests for such disorders as cystic fibrosis and muscular dystrophy; people from families with histories of these diseases can now be tested for the faulty gene long before any symptoms show up. But little testing has been done so far because the diseases are relatively rare and the results are merely informative; no cure is yet available, and if the test is positive, there is little action the recipient can take, except to avoid having children, who might inherit the gene. "That kind of diagnosis does not influence the present generation, except in an indirect fashion," says Walter Gilbert, a Harvard molecular biologist who spoke at the Cold Spring Harbor meeting. But Gilbert, awarded a Nobel Prize for his method of sequencing DNA, foresees more massive screening as tests become available for genes that simply predispose people--that is, make them susceptible--to more common illnesses such as heart disease and cancer. In these cases, he believes, people will seek out the tests because they will have some control over their fate. Depending on their genetic susceptibility, they can watch their diets, exercise, have frequent checkups, avoid the sun or practice other forms of behavior that may ward off the onset of disease. The first genes of this kind will be diagnosed as early as 1995, Gilbert predicts. Then, "by the year 2000 we will have genetic profiles, with 20 to 50 disease genes identified on them." Ten years later, genetic profiles will display between 2,000 and 5,000 potential disease genes, he says, "and by 2020 or 2030, you'll be able to go to a drugstore and get your own DNA sequence on a CD, which you can then analyze at home on your Macintosh." By that time, Gilbert believes, genetic testing will be commonplace and medicine will have drastically changed. Instead of emphasizing treatment with surgery or drugs, it will have become largely predictive and preventive. Yet medicine of the future will undoubtedly be complemented by a technique that is still in its infancy, but suddenly shows signs of taking off: gene therapy, which, simply stated, involves the transfer of beneficial genes into the human body. Encouraged by the apparent success of the first approved use of the procedure--on two young girls being treated for an immune-deficiency disease--the NIH and biotech companies have begun channeling funds to medical researchers eager to apply variations of gene therapy to a host of diseases. "The number of investigators getting involved has mushroomed over the past year," says Dr. W. French Anderson, a molecular biologist at the University of Southern California and a pioneering advocate of gene therapy. At Cold Spring Harbor last week, he reported that the number of approved trials of gene therapy, designed to treat diseases ranging from cystic fibrosis to cancer to AIDS, has now reached 47, involving 92 patients. It was Anderson who took gene therapy out of the realm of science fiction when he got approval for the transfer of a beneficial gene into a sickly five-year-old Ohio girl who suffered from an immune deficiency. Because of a faulty gene, her body could not manufacture an enzyme called adenosine deaminase (ADA). Without it, toxic substances accumulated in her bloodstream and destroyed the white cells, specifically T cells, inactivating her immune system and making her, like AIDS victims, vulnerable to many diseases. Anderson, then at the NIH, with colleagues Dr. R. Michael Blaese and Dr. Kenneth Culver, extracted T cells from the little girl's blood and exposed them to a mouse-leukemia retrovirus that had been rendered harmless and endowed with a normal ADA gene. Invading the T cell, the retrovirus acted as a vector, depositing its genetic material, including the ADA gene, in the cell nucleus. After the re-engineered T cells were cultured, a process that produced billions of them, they were infused back into the child's bloodstream, where their new gene began producing the ADA enzyme. Now, 2 1/2 years after that historic experiment, Anderson reported to the Cold Spring Harbor symposium, both this child and another young Ohio girl who began the same treatment a few months later have acceptable levels of the ADA enzyme and are leading normal, healthy lives, needing only to return every six months for repeat treatments. This study, and one conducted by the University of Michigan's Dr. James Wilson on a woman with familial hypercholesterolemia, represent the only gene-therapy treatments to date with beneficial results. But Anderson expects more success from other projects getting under way. "Short term," he says, "I think that gene therapy will be applied to a broader and broader range of diseases, with more and more clever approaches." He points to one brain-cancer trial that received initial approval just last week. Researchers will splice a herpes simplex gene into a mouse-leukemia virus that has been rendered harmless by genetic engineering, and insert the altered virus directly into the brain tumor. The virus, as is its nature, will promptly invade the nucleus of the tumor cells, endowing them with the herpes gene and making them susceptible to ganciclovir, an anti-herpes drug. The patient will then be given the drug, which should kill both the virus and the tumor cells. Another, more startling strategy, not yet approved, would use the AIDS virus itself as a vector to deliver antiviral genes to white blood cells infected with the AIDS virus. After incapacitating the virus so that it cannot reproduce and splicing a therapeutic gene into its genetic material, researchers would inject it into an AIDS patient's bloodstream. It could be the ideal vector for treating the disease, zeroing in on the T cells normally infected by the AIDS virus. Other methods are more straightforward. In a forthcoming cystic fibrosis trial, Anderson says, doctors will simply "infuse the vector right down into the lungs. And there are even enemas of vectors for colon cancer." Eventually, Anderson told his fellow Cold Spring Harbor celebrators, he looks to the day when "any physician can take a vial off a shelf and inject an appropriate gene into a patient." Like the others gathered to mark the anniversary, Anderson paid tribute to Watson and Crick, whose accomplishment made all that followed possible. Watson was equally appreciative. "I just wish to thank everyone for being here," he said, "to help Francis and me celebrate what was really a very wonderful birthday party." </body> </article> </text>