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ed in making and isolating large quantities of a mutated enzyme in which a predetermined amino acid had been exchanged for another one.
The gestation period of Mullis' PCR idea also had its difficulties. According to an article that appeared last week in the Sunday newspaper supplement Parade, which portrayed him as an unconventional scientist who likes rollerblad-ing and surfing, Mullis' idea at first received a frosty reception from his colleagues at Cetus, and he had trouble publishing his findings. In any case, three days before last week's chemistry Nobe-lists were named, the publication suggested that Mullis could win the prize.
Ron Dagani
/Split genes' discovery wins medicine Nobel Two U.S. researchers who were educated as chemists won the 1993 Nobel Prize in Physiology or Medicine last week for their discovery that genes can consist of two or more well-separated segments of genetic material (DNA).
British-born Richard J. Roberts and American-born Phillip A. Sharp share the $842,000 prize for their independent discovery in 1977 of "split genes." Roberts, 50, is a research director at New England Biolabs, a company in Beverly, Mass., that makes restriction enzymes and related products for molecular biology research. Sharp, 49, is a cancer researcher who heads the biology department at Massachusetts Institute of Technology. Both men earned bachelor's and doctorate degrees in chemistry.
"The discovery of split genes has been of fundamental importance for today's basic research in biology, as well as for more medically oriented research [on] the development of cancer and other diseases," says Stockholm's Karolinska Institute, which awarded the prize.
Before 1977, scientists envisioned a gene as a single segment of double-stranded DNA. The gene's information, they had discovered, is copied into a single-stranded RNA molecule (messenger RNA), which then translates this coded message into a protein.
This simple picture was shattered when Roberts and Sharp found a viral gene that exists as four discrete, well-separated segments of DNA. These gene segments, now known as exons, are sep
arated by introns—so-called nonsense DNA because it apparently bears no protein-coding message. Very soon after this discovery, other researchers showed that such split genes are common—in fact, the most common gene structure in higher organisms.
"This knowledge has radically changed our view of how genetic material has developed during the course of evolution," says the Karolinska Institute. Scientists have long thought that evolution takes place gradually as the result of the accumulation of minor alterations in DNA. Now, says Sharp, scientists know that new genetic variations also can arise through the shuffling of gene segments.
The discovery of split genes revealed the existence of RNA splicing: After a multisegment gene is copied onto messenger RNA, the RNA strand is "edited" to remove the introns. The remaining exons are joined together to form a shortened RNA strand that duplicates the information in the gene. The trimmed messenger RNA leaves the cell nucleus and goes to the ribosomes in the main body of the cell, where the RNA serves as a blueprint for protein assembly.
The importance of splicing became apparent when researchers discovered that exons of the same gene can be used in different combinations to code for different proteins. They also learned that an exon for one protein can be treated as an intron (and thus is snipped out) when the cell's machinery wants to make a different protein. Likewise, introns can become exons for particular proteins. Thus, the DNA instructions themselves do not necessarily specify a specific protein when they are copied into RNA. Rather, it is the splicing pattern—what is snipped out and what
Roberts (left) and Sharp independently discovered 'split genes' in 1977
isn't—that determines the nature of the final protein.
Recent research suggests that this splicing process can go awry, leading to certain hereditary diseases. These include muscular dystrophy, beta-thalassemia (a type of anemia), and chronic myelocytic leukemia (a type of cancer of the blood).
Ultimately, the discovery by Roberts and Sharp could lead to improvements in gene therapy and to a better understanding of the cause of cancer, says Gosta Gahrton, a member of the Karolinska Institute.
Ron Dagani
Hoechst Celanese pays premium for drug firm Hoechst Celanese plans to buy 51% of generic drugmaker Copley Pharmaceutical for $546 million. Hoechst Celanese will pay a premium for the Canton, Mass.-based generic drug manufacturer, hoping to position itself for growth in the drug industry.
Critics expressed amazement that Hoechst Celanese would pay so much for Copley considering the generic drug maker's sales in 1992 were only $52 million. In contrast, Marion Merrell Dow just paid $275 million for generic drug company Rugby Darby, or about the same as Rugby's 1992 sales. And Merck plans to buy generic distributor Medco Containment for $6 billion, or about three times Medco's 1992 sales.
A Hoechst Celanese spokesman points
OCTOBER 18, 1993 C&EN 7