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Daniel Nathans used molecular scissors to map DNA

In 1971 Daniel Nathans showed that a bacterial enzyme cuts DNA into precise, repeatable pieces, and used them to draw the first map of a genome, a technique at the root of genetic engineering.

Daniel Nathans
Daniel Nathans · 1928–1999
Person
Daniel Nathans
Lived
1928–1999
Field
Molecular biology
From
American

The story

In 1969 Daniel Nathans, a microbiologist at Johns Hopkins University, was on sabbatical at the Weizmann Institute of Science in Israel, learning to grow SV40, one of the simplest viruses known to cause tumours. A letter arrived from his Hopkins colleague Hamilton Smith. Smith had found an enzyme in the bacterium Haemophilus influenzae that chopped up foreign DNA, apparently at specific sequences, while leaving the bacterium’s own DNA intact. Bacteria use such restriction enzymes to defend themselves against viruses.

Nathans saw a new use for them. If an enzyme always cut DNA at the same short sequence, it could break a long, featureless DNA molecule into a fixed set of pieces that could be sorted and studied one at a time. Back in Baltimore, with his student Kathleen Danna, he showed that Smith’s enzyme cut the ring-shaped SV40 genome into eleven specific fragments, which they separated by size in a gel. Their 1971 paper predicted that such fragments could be used to map genes, locate mutations, detect differences between DNA molecules and obtain pieces small enough to sequence.

Nathans, Danna and George Sack then worked out the order of the fragments around the viral ring, producing the first cleavage map of any genome. His laboratory used it to find where the virus begins copying its DNA, to locate its genes and to create mutants by removing chosen pieces. Nathans shared his materials generously with other laboratories, and the method spread rapidly.

Within a few years scientists were using restriction enzymes not only to cut DNA but to splice pieces together, the basis of recombinant DNA. His former student Daniel DiMaio wrote that it had become almost impossible to imagine a molecular genetics experiment without restriction enzymes or cloning. In 1978 Nathans shared the Nobel Prize in Physiology or Medicine with Smith and Werner Arber for the discovery of restriction enzymes and their application to problems of molecular genetics.

Why it matters

Cutting DNA at known sites with restriction enzymes became a basic tool of genetic engineering, DNA testing and genome mapping, used in making biotech medicines and diagnosing inherited disease.

About Daniel Nathans

Johns Hopkins biologist who first used restriction enzymes to cut DNA into precise, mappable pieces, a founding tool of genetic engineering, DNA testing and biotech medicine. Nobel Prize 1978.

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Daniel Nathans
1928–1999 · Molecular biology
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Sources

Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.

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