IV. Expanding the Research
J.J.R. Macleod was cautiously supportive of Banting and Best's work. There had to be “no possibility of mistake,” he wrote Banting, urging him to “continue along the same lines,” multiplying his results in controlling for several complicating variables. “It's very easy often in science to satisfy one's own self about some point but it's hard to build up a stronghold of proof which others cannot pull down.” Banting and Best were already back in the lab trying to do just this when Macleod’s replies to their earlier letters arrived.
After a summer of research that was as often frustrating and discouraging as it was exciting, Banting wanted better facilities. When Macleod returned Toronto late in September, Banting asked him for better lab and operating space, help with the animals, and a salary. By his lights Macleod had already been remarkably generous to Banting. Now he wanted to go slowly, in part because a new building was about to be opened, in part because Banting’s research was still unconvincing.
Banting had a hot temper and Macleod had a well-developed sense of professional authority. Their meeting to discuss the work in its future turned into an angry confrontation. According to Banting,
I told him that if the University of Toronto did not think that the results obtained were of sufficient importance to warrant the provision of the aforementioned requirements I would have to go someplace where they would.
His reply was, ‘as far as you are concerned I am the University of Toronto.’
Best remembered Banting saying of Macleod, “I'll show that little son of a bitch that he is not the University of Toronto.”
In fact tempers quickly cooled, Macleod found ways of improving the facilities, and a friendly third party arranged a University of Toronto appointment for Banting as a special lecturer in Pharmacology. Macleod even found retroactive pay for Banting's summer work and for Best’s extra summer service.
Probably at Macleod’s prodding, Banting and Best began to study the literature on their subject, jotting down notes and ideas on index cards that have survived.
There was little sense in Toronto of being in a race or competition with other investigators. Had Banting and Best’s scientific antennae been more highly tuned, they might have given special thought to the very impressive results that Paulesco, the Romanian, had published in the summer of 1921 just as they were starting work. Paulesco’s pancreatic extracts seemed to have very promising antidiabetic prospects – but whatever attention the pair might have given to his work was nullified when Best seriously mis-translated Paulesco’s French by reading the phrase “non plus” to mean “no good.”
The Toronto investigators knew it was vital to show that their pancreatic extract could do more than reduce glycosuria and hyperglycemia. Others had done and were doing this. Other substances or shocks to the system could do it without restoring the metabolic function. Lowering urinary and blood sugar from time to time was not proof of the discovery of the internal secretion. What should the team do next? Banting continued to be drawn to the idea of pancreas grafting. He was somehow persuaded, probably by Macleod, to stick to his extract.
Banting and Best gave the first quasi-public talk about their research to a meeting of the Physiology Department’s Journal Club on November 14 (Banting’s thirtieth birthday). One of the younger physiologists, Dr. N.B. Taylor, suggested afterwards that it would be a convincing demonstration of the extract’s potency to show that it could prolong the life of diabetic dogs. Macleod agreed, and it was decided to proceed with a longevity experiment.
But there was very little generated pancreas from duct-ligated dogs at hand. Producing significant quantities of it would take several months under the best of circumstances. Banting still believed that he had to have pancreas whose trypsin-producing cells were not active. He learned from his reading that foetal pancreases have large quantities of islet cells and do not at that stage produce an external secretion. On November 16-17 he and Best tried making extract from foetal calf pancreas, obtainable in fairly large quantities from local abattoirs. When it proved as active as the extract of duct-ligated pancreas, the supply problem seemed to be solved. The surgical procedure that had been central to Banting’s original idea was abandoned.
Macleod had now abandoned much of his original scepticism. The work was entering a new stage and thoughts began to turn to the possibility that the extract might be used on human diabetics. “I may say privately that I believe we have something that may be of real value in the treatment of Diabetes,” Macleod wrote to the Boston diabetologist, Elliott Joslin, on November 21, “and that we are hurrying along the experiments as quickly as possible.”
On November 23, Banting made the first actual injection of his extract into a human, trying it out on himself. There was no obvious reaction; no blood or other tests appear to have been done.
On December 2 the original longevity experiment ended abruptly after two weeks when the extract-receiving dog suddenly went into shock and died. A replacement dog began receiving extract. Production of the extract was now being refined, with a filtration stage and a preservative added. On December 7 Banting and Best tried using alcohol rather than Ringers (a chilled saline) solution in making the extract. It proved a better solvent and could be more easily evaporated in preparing the final product. Banting and Best then decided to try an extract of fresh whole beef pancreas ground up in slightly acid alcohol. When it worked as effectively as the foetal pancreas, the supply problem eased still further. From then on the Toronto group made extract from fresh whole beef or pork pancreas.