From the record
Real cases, written from the published record. Predict first; the record and its sources come after.
1949 · Pasadena
A molecular disease
Sickle-cell disease was first described in a medical journal in 1910. In 1949 Linus Pauling's lab put haemoglobin from people with and without it in an electric field and watched which way each drifted.
A protein has a pH at which its charges cancel. Above it the protein is negative and drifts toward the + end; below it, positive, toward the − end. The lab measured that pH as about 6.87 for haemoglobin A and 7.09 for haemoglobin S, then ran both at pH 6.9.
At pH 6.9, which way did each one drift?
What happened. They went opposite ways: A drifted toward + as a negative ion, S toward − as a positive one. The two proteins differ in charge by about two units per molecule. Pauling called it a molecular disease, the first one. In 1956–57 Vernon Ingram cut both proteins into pieces and found the single difference: at one position of the β chain, glutamate (negative) is replaced by valine (no charge), on each of the two β chains. Biochemists call it position 6; databases that count the first methionine call it 7. Same change.
One changed letter in a gene, one changed charge in a protein, and a disease people live with.
1958 · Cambridge
Who solved it
Proteins do their jobs by their shapes, but for a long time nobody had seen one. John Kendrew's group grew crystals of myoglobin, the oxygen store in muscle, and shot X-rays through them.
Dorothy Hodgkin first photographed insulin crystals with X-rays in 1935.
How long did it take Hodgkin's group to go from those photographs to insulin's full shape?
What happened. Insulin's structure was published in 1969, 34 years later. Kendrew's myoglobin in 1958 was the first protein shape anyone saw. Crambin was solved in 1981 from the faint signal of its sulfur atoms. In 2020–21 AlphaFold 2 predicted most shapes from sequence alone, and its builders shared the 2024 Nobel Prize in Chemistry with David Baker.
Every structure you rotate here was somebody's years of work.