October 28, 2022 marks the 40th anniversary of when biotechnology became medicine. And it happened here in Indianapolis — not in San Francisco or Boston, as many might suspect. This was a validating technical achievement filled with enormous commercial relevance for an emerging sector of the global pharmaceutical industry. This is the drug Humulin from Eli Lilly and Co., a revolutionary breakthrough for people with insulin-dependent diabetes. Its development and successful registration collectively represent the first step in demonstrating that safe breakthrough drugs could be assembled in microorganisms and then in engineered human cells.
I was a leading scientist in product development and translating technology into commercial production. There were many equally experienced scientists and several who were more eminent. Irving Johnson, now deceased, was the executive scientific director of the project which included all scientific disciplines. Within the chemistry group, Ron Chance, William Bromer, Bruce Frank, LeRoy Baker and Edward Smithwick played prominent leadership roles. It was a company-wide effort to offer this drug to patients as a registered drug. The research at City of Hope associated with Genentech was of the utmost importance in setting the stage for what was subsequently accomplished at Lilly. They assembled the gene that expressed the building blocks that became insulin. They made small quantities that required the most sensitive methods of the time to characterize them. The work in Indiana has advanced science from the lab to the patient, from micrograms to kilograms (a billion-fold increase) to purity and cost that have made it pharmaceutical. This is analogous to the discovery of insulin a century ago in Toronto, where Lilly and Novo-Nordisk were instrumental in developing it for safe and effective therapeutic use.
Here’s the little-appreciated fact: no microorganism has ever produced human insulin. The engineered bacteria made two independent half-blocks of insulin that had to be independently purified, chemically integrated, and then purified into a final product. Emphasis was placed on purity to ensure that this unprecedented insulin source would pose no safety risks beyond those associated with animal-derived insulin. However, this approach was very inefficient. Looking back now as a recognized world expert in the chemistry of insulin, I am simply amazed at the use of this technology from the 1970s and 80s to deliver this revolutionary product. Knowing what I know today about basic chemical ingredients and using state-of-the-art technology, I’m not sure I would try to take on what was started four decades ago commercially. It was so difficult, but the scientific community at Lilly persevered and made it happen.
Were it not for the virtually unlimited amount of insulin that is now possible through this and associated rDNA processes, it is easily conceivable that insulin delivery could have been rationed, given the epidemic diabetes and the associated demand for insulin as a therapy. As profound as that may be, the most important achievement is the validation that this technology was more than a research tool; it was a new method to make revolutionary drugs. This is what has accelerated the interest of the business community and the proliferation of next generation start-ups after Genentech.
Venture capitalists are focused on financial return, and Genentech’s lucrative deal with Lilly and Lilly’s product registration validated financial wisdom for new biotech investments. The evolution of biotechnology to produce more complex proteins and in particular antibodies has a lineage of Humulin as the ancestor of all.
It is important to elevate the seminal role that the Indiana Center, Lilly and an army of Hoosiers have done in converting biotechnology into medicine. No one in the country was exploiting this technology on a commercial scale and there were notable federal restrictions on how to do this. In Germany, the Green Party was notable for its opposition to technology and blocked development in Central Europe throughout the 1980s. In short, commercialization forced Indiana to help Lilly do what was being done locally. It is a great example of progressive public-private economic policy that has created jobs and propelled an industry that saves lives.
As time goes on, I feel an increased obligation to acknowledge what happened and to thank Lilly for giving so many people the opportunity to contribute to something of such fundamental importance. This is a milestone in the delivery of a precedent-setting drug that provided the first validation of the commercial relevance of biotechnology. It occurred largely in Indiana by a large group of inspired Hoosiers, and it had worldwide ramifications.
Richard Di Marchi, PhD is Emeritus Professor of Chemistry and Gill Chair in Biomolecular Sciences at Indiana University. He is a member of the National Academy of Medicine and the National Inventors Hall of Fame. He is a past president of the Peptide Therapeutics Foundation and an international advocate for macromolecular drugs.
#Indiana #biotech #medicine #INdiana #Business