John Jacob Abel
John Jacob Abel (1857-1938) Abel was one of the most distinguished biological chemists of his day and the founder of pharmacology in America. His contribution to diabetes is that he was the first to crystallize insulin and show that it was a protein.
John Jacob AbelIn 1883 he graduated in physiology and chemistry from the University of Michigan. The next year he went to Europe and in Leipzig from 1884 to 1886 studied physiology under Ludwig and von Frey, histology under His, pharmacology under Boehm, pathology under Strumpell, and inorganic and organic chemistry under Wislicenus. The winter of 1886-7 saw him in Strassburg doing internal medicine with Kussmaul and he received his MD there in 1888. He also, in his own words, ‘walked the wards with von Recklinghausen’. This extremely broad education gave him the background for his wide-ranging chemical research of the next 50 years. In 1890 he was offered a chair at the University of Michigan to establish a department of pharmacology but in 1893 was headhunted to join the outstanding faculty at Johns Hopkins as the first full time professor of pharmacology where he remained for the next 45 years.
His interest in the isolation of hormones began around 1895 and he worked on adrenal extracts for the next 10 years. Between 1917 and 1924 he tried to purify the active principle(s) of the posterior pituitary but progress was discouraging and he switched to insulin in the aftermath of its discovery in 1921. In 1924 he went to the California Institute of Technology where a $10,000 grant was available from the Carnegie Foundation for insulin research. Starting with Lilly’s preparation Iletin, he worked out a way of achieving a four or five fold purification. Sulphur was known to be a constituent of crude insulin and serendipitously Abel hit on the idea of measuring the sulphur content of his fractions and soon found that the higher the sulphur content, the greater the physiological activity. This enabled him to do away with time consuming rabbit bioassays and also provided the first major piece of information about the structure -- that sulphur was an integral part of the molecule. Abel was intrigued by the possibility that diabetes might be due to deficiency of an unknown sulphur compound and wrote an article in 1925 entitled ‘Is insulin an unstable sulphur compound?’.
First insulin crystals: 1926In December 1925 his mindset changed completely when he was rewarded with ‘one of the most beautiful sights of his life’, glistening insulin crystals forming on the sides of a test tube. Bioassay of these indicated a 10-15 fold purification of the starting material. His preliminary report appeared in the Proceedings of the National Academy of Sciences in February 1926 in which he reported that his crystals gave ‘a beautiful biuret reaction’ and reacted in other tests as a protein. The idea that a protein could have the unique pharmacological properties of insulin was unthinkable at the time and it is not clear when Abel accepted it.
Opponents claimed that the protein was simply a carrier for the active part of insulin (the adsorption theory) and a major problem for Abel in countering these criticisms is that between March 1926 and January 1927 he inexplicably lost his ability to crystallise it. He initially attributed this failure to the fact that Lilly had supplied him, without his knowledge, with a beef pork insulin mixture; in retrospect, the most likely explanation is that Lilly’s insulins were too pure and did not contain enough of the natural zinc of the pancreas. This became apparent in 1934 when David Scott (1892-1971) of the Connaught Laboratories in Toronto found that crystalline insulin contains zinc and that crystals from which the zinc has been removed cannot be recrystallised.
Able is regarded as one of the fathers of the artificial kidney. In 1913, he became interested in removing substances from the blood of living animals by dialysis and made an elaborate apparatus with which he could remove salicylic acid and other substances as efficiently as the native kidney. He also found amino acids in his dialysates, the first proof that they were present in the blood. He also did experiments with ‘plasmaphaeresis’ in which red cells were separated from the plasma and then reinjected. In the paper on this (1914) he suggested the possibility of blood banks.
From the many affectionate tributes of his pupils, it is clear that Abel was the archetype of the absent minded professor. After noting that he was ‘a most lovable man’, Leonard Rowntree, wrote that he ‘slept, ate and drank research’, while to Paul Lamson, “it seemed that Professor Abel lived in the clouds rather than in this world. However, he was an extremely practical person when his attention was focussed on something…everything having to do with the laboratory, his work and science had a supernatural interest for him.”
^ Murnaghan JH, Talalay P.,John Jacob Abel and the crystallization of insulin. Persp Med Biol 1967;10: 334-380.
^ His artificial kidney is described in Leonard G Rowntree. Amid Masters of Twentieth Century Medicine. Springfield, Illinois. Charles C Thomas 1958 p115-116.
^ Lamson PD. John Jacob Abel: a portrait. Bull Johns Hopkins Hosp 1941; 68:119-157.