An Elegant Triumph

Using the humble pea, an obscure Austrian monk named Gregor Johann Mendel proved that living things pass their characteristics to later generations with mathematical regularity--almost as if the formula for each trait were conveyed in a separate little package. Last week, more than a century later, a team of young Harvard researchers reported that they had finally zeroed in on that Mendelian package. For the first time, science had isolated a single gene.

Viral Assistance. Although the gene has long been recognized as the basic unit of heredity, it has been only 26 years since molecular biologists learned that the gene is actually composed of deoxyribonucleic acid (DNA) a complex molecule that forms the chromosomes in every living cell. The DNA molecule is shaped like a spiral staircase--a double helix connected by steps, or links. Each of the thousands of links consists of a pair of mutually attracting chemical bases. Although only four different kinds of such bases are found in DNA, they can be arranged along the helix in an enormous variety of sequences. Each of these sequences contains genetic information that determines, for example, whether a child will have blue eyes or whether a plant will produce wrinkled seeds. But where along the length of the DNA molecule does one gene end and another begin? How can a single gene be isolated so that its characteristics and processes can be studied?

To answer such questions, a Harvard team led by Jonathan Beckwith, 33, turned to the virus, which consists simply of a single DNA molecule sheathed in a thin coating of protein. Most viruses multiply by entering a living cell, taking control of it and then ordering it to produce carbon copies of the invading virus. Eventually the cell bursts, releasing a host of new viruses. Some strains of invading viruses, however, incorporate several of the cell's genes into their own DNA molecule before they depart. There are two different viruses, the Harvard researchers knew, that invade an intestinal bacteria called E.coli and make off with several of its genes. But the two viruses capture only one bacterial gene in common: the one that enables E.coli to digest lactose, a sugar. Furthermore, the direction in which this so-called lac gene is inserted into the DNA molecule of one virus is opposite to its direction in the other virus.

Stray Tails. Therein lies the key to the elegant experiment reported last week in Nature. Once the two strains of virus had finished raiding the bacteria, the experimenters dissolved their protein sheaths, exposing their raw DNA molecules (Step 1 in diagram). Next, the scientists heated the dissimilar DNA molecules, causing each double helix to unwind and separate into one lighter and one heavier strand. Taking only the heavier strand from each virus, the researchers placed them in the same test tube, reheated them and then cooled them slowly, a process that causes two chemically complementary strands of DNA to combine in a double helix. But the two strands were complementary only along the segments that had been parts of the original bacterial lac gene. Thus, only these segments could combine (Step 2). The remainder of the viral strands, unable to find properly matched partners, were left dangling. After these stray tails were chemically dissolved, only the single gene remained (Step 3).

Now that they can experiment with a single gene, scientists may well learn how it orders the cell to produce vital proteins, and what substances cause the gene to "turn on" or "turn off." Ultimately, this could lead to the repair or replacement of defective genes and the cure of hereditary diseases.

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