Watson and Crick

Building a model of inheritance

In 1953, James Watson and Francis Crick used these plates to construct the first correct model of DNA's double-helical structure. The arrangement of complementary base pairs suggested how DNA could be copied and passed on to successive generations.

"The brightly shining metal plates were used to make a model in which for the first time all the DNA components were present. In about an hour I had arranged the atoms in positions which satisfied both the X-ray data and the laws of stereochemistry," said James Watson in The Double Helix.

Victor McKusick

Victor McKusick brought genetics to the forefront of medicine

When Watson and Crick first described DNA's structure, medical genetics hardly existed. Victor A. McKusick helped invent it.

While training in cardiology, McKusick became interested in Marfan syndrome, an inherited disorder that causes a surprising and variable array of symptoms. These include dislocated lenses of the eye, long arms and legs, and a weakened aorta that's prone to sudden rupture.

McKusick recognized that the syndrome could be caused by a gene defect that affected a single element of connective tissue. He proceeded to look for Mendelian patterns of inheritance in other disorders of connective tissue and wrote the definitive book on the subject in 1956.

The following year, McKusick started one of the world's first clinical genetics units at Johns Hopkins University.

Putting the first genes on the map

By 1968, 68 genes had been mapped to the X chromosome. Traits controlled by genes on the X chromosome, like color blindness, show a recognizable pattern of inheritance called sex linkage. The inheritance patterns of traits controlled by genes on the other 22 chromosome pairs, the autosomes, don't indicate which of the 22 carries the gene.

This paper reports the first mapping of a gene to one of the autosomes, by a graduate student of McKusick, Roger P. Donahue. Until this discovery, not a single human gene had been mapped to one of the autosomes.

According to McKusick, Donahue studied his own chromosomes—as all genetics students should—even though it was unrelated to his thesis research. Donahue noticed that one of a pair of his chromosomes had a region, called the uncoiler, that looked distinctive.

Says McKusick, "Donahue had the wit and the gumption to do a linkage study: the wit to sense that this might be a Mendelian character in his family, and the gumption to collect blood samples from his far-flung family and put together a pattern of inheritance."

Creating an essential reference for medical genetics

McKusick may be best known for publishing the "bible" of medical genetics, Mendelian Inheritance in Man, which summarizes facts on every known human trait influenced by a single gene. When the first volume was published in 1966 with 1,500 entries, genes were known only by their phenotypes—their expression as distinct traits inherited in the simple recessive or dominant patterns described by Mendel. Only a few genes had been mapped—all to the X chromosome.

The current volume has more than 9,000 entries. McKusick estimates that the catalogue has about 4,000 genes associated with human genetic disorders. An online version—Online Mendelian Inheritance in Man—gets updated weekly with new discoveries.