The importance of insulin cannot be overstated to any person who is himself a diabetes patient or has a family member suffering from that. And it's lifesaving value cannot be attributed to the price tag. India is often called the diabetes capital of the world with about 9% of its population suffering from the ailment. India has more than 70 million adult diabetes patients and some studies indicate diabetes reaching the scale of a potential epidemic in India.
How was life of a diabetic patient before insulin was discovered? Considering the fact that even in 2015 we had 1.6 million deaths directly attributed to diabetes, it can easily be understood the importance of insulin. Before the discovery of insulin shots, the only known way to treat diabetic patients was to put them on a low calorie diet. However, that often led to death by starvation. Children diagnosed with diabetes rarely lived; more than 80% died within 10 years of first detection. Having Type 1 Diabetes was effectively a death sentence.
The discovery of bio-synthetic insulin currently in use is a process which took more than 100 years to achieve its ultimate objective. It contains years of hard work and toil from hundreds of researchers working across the world. As many as 4 Nobel prizes were awarded for work directly related to discovery of insulin and many more with indirect association.
Édouard Laguesse a French pathologist continued work on these cell clusters and in the year 1893 named them 'Islets of Langerhans' in honor of the person who first discovered those. Insulin originates from insula which is the Latin for island / islet. Laguesse suggested that these islets performed some regulatory role in the digestion process but nothing more was achieved till the arrival of two German surgeons Oskar Minkowski and Joseph von Mering. These surgeons removed the pancreas of dog to identify the impact of its presence. The dog became thirsty and began to urinate frequently. They tested the dog's urine which was found to be high in sugar; the dog had turned severely diabetic. Thus they concluded that pancreas help to regulate sugar in the body and could have a direct relationship with diabetes.
In 1901 an American pathologist while still being a medical student Eugene Opie at John Hopkins Medical School was investigating pancreatic diseases by studying the pancreas removed at autopsy from people who had died from diabetes or other diseases. In the course of this investigation he established that the 'Islets of Langerhans' secreted a hormone which played a role in regulating blood sugar level and hence diabetes.
Identification of the hormone resulted in a race to extract and purify the hormone for human use. In 1920 another surgeon named Frederick Banting in Ontario, Canada approached John McLeod at the University of Toronto with the proposal to derive the hormone from pancreatic extracts. McLeoad agreed to provide Banting with lab space and an assistant, Charles Best, for the research. In 1921 the researchers from Toronto, Banting, Best and McLeod were the first to announce the successful extraction of secretions from dog pancreas which when injected into diabetic dogs was able to quickly bring down the sugar levels in blood.
Towards the end of 1921 a biochemist James Collip from the University of Toronto joined the team at the invitation of McLeod to help them purify the extract suitable enough for human trials. Collip succeeded to purify sufficient amount of extracts from cow pancreas to start the clinical trials.
Leonard Thomson a 14 year old diabetic boy admitted to the Toronto General Hospital was the first to receive a dose of insulin. The first dose helped to lower the sugar level but there were associated side effects. Collip worked hard to further purify the extracts and subsequent doses had reduced side effects. Soon after pharmaceutical giant Eli Lilly collaborated with the Totonto team and provided them with additional chemists who could help them in the purification process. And subsequently first started producing insulin at a commercial scale.
There were many researchers in Europe and elsewhere who were also working towards extracting insulin from dog pancreas and use them to treat diabetes. But the Toronto team's research was more conclusive in all aspects. In 1923 when Banting and McLeod were awarded the Nobel prize in Medicine many others also laid claims to have first extracted insulin. In fact, within the Toronto team there was some conflict with Banting expressing displeasure on McLeod being named the joint awardee instead of Best. According to Banting, McLeod didn't had any contribution in the actual research; he only helped to get the infrastructure. Banting shared his award with Best while McLeod shared his award with Collip.
The production of insulin from animal pancreas was tough task to achieve and involved many complications in the production and storage. Around the middle of twentieth century another branch of life science was making its foray, one that would change the way we know our world. Genetics was slowly gaining momentum and soon assumed the importance of a foremost branch for research and study among scientists.
One revolutionary event in the field of genetics was the discovery of 'recombinant DNA' which are simply DNA molecules formed by copying and pasting sequences from different sources and create a DNA molecule with a completely new sequence. In 1973 Herbert Boyer at the University of California (UCSF) became one of the first scientists to achieve this. In 1976 a venture capitalist Robert Swanson approached Boyer with the objective of putting this new technology into commercial use. Swanson was a serial entrepreneur whose most of the previous ventures had failed miserably but saw opportunity in this new technology. Boyer agreed to the proposal as he also saw the possibilities of creating a growth hormone as his own son was suffering from growth disorder.
Genentech edged out Biogen where another scientist Walter Gilbert was also in the race to synthesize proteins for insulin. However, Gilbert employed a different technique which was more subject to regulatory prohibitions; Gilbert was trying to clone genes while Boyer wanted to create them from their base chemicals. In 1978 Genentech produced created the human insulin from E. Coli and beat Biogen in the race. In 1982 they partnered once again with pharmaceutical company Lily to start production of biosynthetic insulin at commercial scale under the name ‘Humulin’. Genentech was one of this finest examples where scientific knowledge shook hands with business acumen for the betterment of human life. It was one of the first biotechnology corporations in the world and owns the eponymous internet domain ‘gene.com’.
Boyer (left) and Swanson (right)
More than hundred years after Langerhans initiated the study of pancreases, insulin became the first genetically engineered therapeutic agent.
References:
- The Gene by Siddharth Mukherjee
- Wikipedia
- http://centennial.rucares.org/index.php?page=Linking_Diabetes_Damage_Islets_L
- https://www.sciencehistory.org/historical-profile/frederick-banting-charles-best-james-collip-and-john-macleod
- http://www.who.int/diabetes/en/
- The writer of this blog doesn't claim ownership or copyright of the images.
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