Today In Science History – September 6 – John James Richard Macleod and the Discovery of Insulin

J.J.R. Macleod
John James Rickard Macleod (1876-1935) Co-Discoverer of Insulin

September 6 is John James Richard Macleod’s birthday. Macleod was the Scottish biochemist who shares the 1923 Nobel Prize in Medicine with Frederick Banting for the discovery of insulin.

Macleod began his career as a physician. He graduated from Aberdeen University and received his medical degree from Marischal College. He earned a scholarship that allowed him to study at the University of Leipzig’s Institute for Physiology. While here he focused on studying biochemistry. He moved to London to lecture at the Hospital Medical College while attending Cambridge University for a public health degree. He emigrated to the United States to teach at Western Reserve University in Cleveland, Ohio. Macleod began his research into the way the body metabolizes carbohydrates. He investigated the metabolism of salt and urea along with the way the liver processes glycogen. The sum of these investigations lead to his publication of Diabetes: Its Physiological Pathology.  He also wrote his textbook Physiology and Biochemistry in Modern Medicine which went through seven editions during his lifetime. After World War I, Macleod moved to the University of Toronto.

It was here he met Frederick Banting, a Canadian physician who had the idea to treat diabetes with extractions from the pancreas. Scientists knew that diabetes resulted when the pancreas stopped secreting a substance that regulated the levels of sugar in the bloodstream. The problem was exactly which substance performed this function and where in the pancreas it came from. There were several failed attempts at isolating the compound excreted by the pancreas and Macleod doubted Banting would be any more successful. He still allowed Banting to use space in his laboratory and the aid of one of his demonstrators, Charles Herbert Best while Macleod was away in Scotland for the summer. Macleod outlined a procedure for the two to follow and dogs to use as experimental animals.

Macleod returned to his laboratory at the end of the summer. He was greeted to the news that Banting and Best had succeeded in isolating a pancreatic secretion that lowered the blood sugar of a dog whose pancreas was removed. Banting wanted to announce their discovery, but Macleod felt they needed more tests and better controls. While Banting did not like this idea, he continued the experiments while Macleod put the two men on his payroll and gave them more space in the laboratory. The new experiments were successful and the men began to announce the discovery of insulin. Banting and Best published their findings in The Journal of Laboratory and Clinical Medicine. Macleod declined to appear as an author on the paper but continued to present the findings at conferences.

The men needed more insulin for their clinical trials. The amount they were producing from dogs was not nearly enough to be useful. Macleod enlisted the help of Canadian biochemist James Collip to find a better way to obtain their secretion. Collip was instrumental in improving their techniques and managed to obtain insulin from cow pancreas. A much more plentiful and easier to obtain source. They now had enough insulin to conduct human trials.

Banting began to feel Macleod was crowding him out of the discovery. Macleod directed more laboratory space to the insulin studies and took more control of the methodology of the experiments. Macleod was better versed in experimental design than Banting, but Banting felt Macleod was trying to take credit for his discovery. Tensions between the two men began to grow high.

The first human trial in January 1922 was a success.  A young diabetic named Leonard Thompson received injections of insulin that helped control his disease. The results were published with all four men as co-authors. Diabetes was basically a death sentence, but now simple injections could control the disease. Countless lives would be saved by their discovery. The Nobel committee awarded Macleod and Banting the Nobel Prize in Medicine the very next year. Banting was less than happy. He felt Best’s contributions were ignored and Macleod did little more than “leave the keys to the laboratory while he went on vacation”. When they received their Prize money, Banting split his half with Best while Macleod split his half with Collip. While Macleod pursued another line of research into pancreatic tissue of the teleost fish in New Brunswick, Banting began to talk to the press about how he deserved the credit and not Macleod. Banting and Macleod’s working relationship deteriorated enough for Macleod to return to Aberdeen Medical School as a professor. Neither men would speak to the other again.

The controversy did not go away after Macleod left for Scotland. After Banting died in a plane crash in 1941, Best continued to spread the tale of Macleod’s lack of contribution. He seemed determined to remove Macleod and Collip’s name from any discussion of the discovery of insulin. Macleod’s public image was tarnished for decades. It would be 50 years before documentation would surface showing Banting and Best’s version of the events were “distorted” and Macleod’s contributions were important.

Notable Science Events for September 6

1943 – Richard J. Roberts was born.

Roberts is a British molecular biologist who shares the 1993 Nobel Prize in Medicine with Phillip A. Sharp for their discovery of split genes. They discovered introns, which are sections of the DNA molecule that do not carry any genetic information.

1940 – Phoebus Levene died.

Phoebus Levene (1867 - 1940)
Phoebus Levene (1867 – 1940). National Institutes of Health

Levene was a Russian-American biochemist who discovered nucleic acids came in two different forms called DNA and RNA based on ribose and deoxyribose. He identified the components of DNA where it contained adenine, guanine, thymine, cytosine, deoxyribose and a phosphate group. He also determined these components linked together as phosphate-sugar-base units he called nucleotides. He believed the structure of DNA was based on a tetranucleotide where the different components were equally distributed

1939 – Susumu Tonegawa was born.

Tonegawa is a Japanese molecular biologist who was awarded the 1987 Nobel Prize in Medicine for his discovery of the genetic principle for generation of antibody diversity. He discovered how the immune system could genetically change the body’s antibodies to adapt against new antigens.

1908 – Louis Essen was born.

Essen was a British physicist who developed methods to precisely measure the passing of time. He developed the quartz crystal ring clock with an accuracy of one-second loss in three years. He also developed the first atomic clock with Jack Parry. Their clock used the natural resonance frequency of cesium atoms and would be accurate to one second in 2000 years. Clocks based on this design would be used to define the SI standard of the second used today.

1st Cesium atomic clock from 1955 designed by Louis Essen (right) and Jack Perry (left).

1906 – Luis Federico Leloir was born.

Luis Federico Leloir
Luis Federico Leloir (1906 – 1987)

Leloir was an Argentine physician and biochemist who was awarded the 1970 Nobel Prize in Chemistry for the discovery of sugar nucleotides and their role in carbohydrate biosynthesis.

He researched the way the body breaks down and forms lactose and discovered sugar nucleotides. These are important parts of the process the body converts sugar to usable energy.

1892 – Edward Victor Appleton was born.

Edward Victor Appleton
Edward Victor Appleton (1892 – 1965)
Nobel Foundation

Appleton was a British physicist who investigated the physics of the upper atmosphere or ionosphere. He found radio signals are reflected off a boundary in the atmosphere and interfere with the same signal traveling along the ground. This reflective layer is called the Appleton layer and was important in the development of radar. This work would earn him the 1947 Nobel Prize in Physics.

1811 – James Melville Gilliss was born.

James Melville Gilliss
James Melville Gilliss (1811 – 1865)

Gilliss was an American astronomer who was the founder of the US Naval Observatory, the first US research observatory. The original mission of the Observatory was to maintain the Navy’s ship chronometers, charts, and navigational equipment.

1876 – John James Richard Macleod was born.

1766 – John Dalton was born.

John Dalton
John Dalton (1766-1844) Credit: Library of Congress

Dalton was an English chemist and physicist who is best known for his atomic theory and research into color blindness. He proposed elements were made up of individual atoms that could not be broken down into smaller parts. He also said all atoms of an element are identical.

He sought to determine the cause of color blindness since he was color blind himself. He believed it was caused by a discoloration in the medium in the eye.