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The people behind the drug.

In 1981, researchers at Cetus Corporation (which has since become part of Chiron Corporation) under the direction of Dr. David Mark succeeded in cloning the human gene for interleton beta. The group inserted a segment of human DNA into the bacteria known as Eschenchia coli, and coaxed the bacteria to make the human protein.

This was an important step toward getting the bacteria to manufacture enough of the protein to test its effects in clinical trials. Some tantalizing preliminary studies had indicated this protein might be useful in a number of diseases.

The interferon beta produced by the bacteria was purified by Dr. Leo Lin and his team of protein chemists to make it suitable for tests in humans. However, when the scientists began testing it in the laboratory, they hit a wall: the protein made in bacteria had significantly less activity than interferon beta made by human cells.

Dr. Lin and Dr. Mark analyzed the properties and studied the structure of the purified protein. They decided to try a novel approach: to alter the human gene so that the bacteria would replace a single amino acid -- a cysteine at position 17 in the protein -- with a different amino acid, serine. They reasoned that the biological effect of most proteins depends on their shape, and that the unpaired cysteine at position 17 might cause the protein to fold into a different and less active shape when it was made in bacteria than when the molecule was made in human cells.

This procedure -- introducing a mutation at a specific site in a gene to alter the structure and shape of a protein -- was revolutionary in the early 1980s, although it is now a standard part of rational drug design.

The modification of the interferon beta molecule did what the two scientists hoped. When Dr. Lin purified the altered interferon -- now named Interferon beta 1-b, or Betaseron -- extensive testing showed it had the same biological activities as the original human protein. Clinical trials of Betaseton for human diseases, eventually including MS, started shortly thereafter.

In addition to designing the amino acid change in Betaseron and developing the purification process that separates the drug from the bacteria that produce it, Dr. Lin helped guide the steps that led to the recent recommendation for its approval by the FDA. He is currently managing Chiron Corporation's efforts to improve the manufacturing process for Betaseron.
COPYRIGHT 1993 National Multiple Sclerosis Society
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Copyright 1993, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Title Annotation:Cetus Corporation's research on Betaseron
Author:Eastwood, Abe
Publication:Inside MS
Date:Jun 22, 1993
Previous Article:Eleven questions.
Next Article:Coping When a Parent Has Multiple Sclerosis.

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