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Nobel laureate David Baltimore, director of M.I.T.'s Whitehead Institute, was one of the many who feared that such a megaproject would have much the same impact on biology that the shuttle had on the U.S. space program: soaking up so much money and talent that smaller but vital projects would dry up. Others stressed that the technology to do the job in a reasonable time was not available. But by 1986 some opponents realized they were fighting a losing battle. "The idea is gaining momentum. I shiver at the thought," said Baltimore then. Now, however, he approves of the way the project has evolved and has thrown his weight behind it.
What really turned the tide was a February 1988 report by the prestigious ; National Research Council enthusiastically endorsing a project that would first map and interpret important regions of the genome, then -- as better technology became available -- proceed to reading the entire genetic message. Most of the remaining critics were silenced last fall when the NIH chose the respected Watson as project director. Still, some scientists remain wary of the project. Says David Botstein, a vice president at Genentech and a member of the Human Genome Advisory Committee: "We need to test its progress, regulate its growth and slap it down if it becomes a monster. Jim Watson understands the dangers as well as any of us."
The concern, as well as the cost, reflects the complexity of the human genome and the magnitude of the effort required to understand it. DNA is found in the human-cell nucleus in the form of 46 separate threads, each coiled into a packet called a chromosome. Unraveled and tied together, these threads would form a fragile string more than 5 ft. long but only 50 trillionths of an inch across.
And what a wondrous string it is. As Watson and Crick discovered in 1953, DNA consists of a double helix, resembling a twisted ladder with sidepieces made of sugar and phosphates and closely spaced connecting rungs. Each rung is called a base pair because it consists of a pair of complementary chemicals called nitrogenous bases, attached end to end, either adenine (A) joined to thymine (T) or cytosine (C) attached to guanine (G).
Fundamental to the genius of DNA is the fact that A and T are mutually attractive, as are C and G. Consequently, when DNA separates during cell division, coming apart at the middle of each rung like a zipper opening, an exposed T half-rung on one side of the ladder will always attract an A floating freely in the cell. The corresponding A half-rung on the other section of the ladder will attract a floating T, and so on, until two double helixes, each identical to the original DNA molecule, are formed.
Even more remarkable, each of the four bases represents a letter in the genetic code. The three-letter "words" they spell, reading in sequence along either side of the ladder, are instructions to the cell on how to assemble amino acids into the proteins essential to the structure and life of its host. Each complete DNA "sentence" is a gene, a discrete segment of the DNA string responsible for ordering the production of a specific protein.