Sickle-cell anemia hemoglobin: the molecular biology of the first “molecular disease”—the crucial importance of serendipity

VM Ingram - Genetics, 2004 - academic.oup.com
VM Ingram
Genetics, 2004academic.oup.com
IN the spring of 1952 I sent 32 letters to England, note, needed a protein biochemist to place
a “heavy atom” in a specific location in his hemoglobin (Hb) trying to find a job in academic
research. I was finishing my second postdoctoral year in the United States, crystals. This
approach would enable him to determine the phases of most of the X-ray reflections, the big
working in Joseph Fruton's Biochemistry Department at Yale University. My topic was
peptide chemistry, in particu- problem in X-ray crystallography at that time. Freddie said “do …
IN the spring of 1952 I sent 32 letters to England, note, needed a protein biochemist to place a “heavy atom” in a specific location in his hemoglobin (Hb) trying to find a job in academic research. I was finishing my second postdoctoral year in the United States, crystals. This approach would enable him to determine the phases of most of the X-ray reflections, the big working in Joseph Fruton’s Biochemistry Department at Yale University. My topic was peptide chemistry, in particu- problem in X-ray crystallography at that time. Freddie said “do apply” and I did, not expecting much. To my lar the development of a novel end-group method by reductive methylation of the N-terminal-amino group, surprise, I was accepted for September 1952 and I was happily on my way back to England. followed by paper chromatography of the hydrolysate to detect a “basic” derivative of the end amino acid. The The laboratories of the MRC Unit were modest, but modern. We had one large biochemistry room for about method worked and was published (Ingram 1950). To four people. Next door was a large office for Francis my knowledge, my method was never used by anybody, Crick and, later, for Jim Watson and Sydney Brenner. but of course I did not know this at the time! I was The suite also contained a modest office for Max Perutz an organic chemistry Ph. D. with an interest in animal and John Kendrew, both X-ray crystallographers workphysiology developed through an excellent undergrading on the structure of hemoglobin and myoglobin, uate course by Alistair Graham at Birkbeck College, respectively. There also was a well-equipped machine
Oxford University Press