In Pursuit of the Gene

282 ¨ EPILOGUE
After some timely advice from his crystallographer office mate, Jerry
Donahue, about the location of the hydrogen atoms in thymine and guanine,
on the morning of February 28, 1953, Watson saw that adenine (A)
could be paired with thymine (T), and guanine (G) with cytosine (C). Further
support for this scheme was provided by the recent work of the Austrian
biochemist Erwin Chargaff, who had shown that the amount of A and
T in DNA samples was roughly equal, and that the same was true for C and
G. 11 Using cardboard cutouts, Watson showed that the two pairs had almost
identical shapes. In this new scheme, a pair of complementary strands reproduced
itself, each strand serving as a template for its complement. That
is, during the process of DNA replication, the helix was peeled apart and
complementary bases were laid down on each of the two complementary
strands (later called “Watson” and “Crick”), resulting in two new DNA
molecules. When he arrived at the lab later that morning, the ordinarily
skeptical Crick was quickly won over. 12
Watson and Crick announced the double helical structure of DNA in
the April 25, 1953, issue of Nature. 13 As the structure famously made clear,
the specificity of the gene was determined by the order of the nucleotide
bases, and mutations amounted to changes in their order. The two-layered
structure also illustrated both how the molecule could be self-replicating
and how variations in particular genes could be inherited, the two properties
that Muller had long insisted were fundamental to the hereditary particles.
The gene’s ability to reproduce its own variation was simply a reflection
of the fact that the particular order of the bases did not affect the
copying mechanism.
¨ THE DISCOVERY of the structure of DNA catalyzed the development
of molecular biology and led to spectacular advances in the knowledge of
genetics and cell biology. Nevertheless, more than two decades would pass
before this knowledge was brought to bear on the human genome. Fifteen
years after Watson and Crick’s discovery, the only genes that had been
mapped in humans were X-linked, revealed by their characteristic inheritance
patterns—affected fathers producing normal daughters half of whose
sons, on average, again showed the trait. Not a single gene had been
mapped to the 22 pairs of other (non-sex) chromosomes called autosomes.