Late in the summer of 1978*, researchers using recently developed gene-splicing techniques created a new form of insulin.
They built on a technique that Herb Boyer and Stanley Cohen developed with colleagues at Stanford University and the University of California San Francisco.
The Cohen-Boyer team successfully combined DNA from two species of bacteria in 1973, creating a recombinant DNA (rDNA) molecule. Then they “demonstrated that the recombinant DNA could be used by bacteria. The team had created the first genetically modified organisms.”
A year later, they would use this technique to insert a gene from a frog into bacteria, proving that it was possible to transfer genes between two very different organisms.
A San Francisco biotech startup, Genentech, partnered with the City of Hope National Medical Center, Los Angeles, to began the work of creating synthetic insulin, “a relatively simple and well-studied protein used to treat diabetes.”
A team of four scientists at the University of Toronto had discovered how to extract and purify insulin, first from dogs and then from cattle, in 1921. Researchers sold their U.S. patent for $1 (archive link) in 1923. Sir Frederick G. Banting reportedly said, “Insulin belongs to the world, not to me.”
The University allowed Eli Lilly “to produce insulin in exchange for a one year distribution monopoly.” The first patient was treated in January 1922.
Eli Lilly got a jump on insulin production. In 1941, a grand jury would indict three companies involved with insulin manufacturing and distribution — Eli Lilly, Sharp & Dohme and E.R. Squibb & Sons — for violating the Sherman Antitrust Act. This would not be the last time the Department of Justice found Eli Lilly guilty.**
Genentech entered into a research and royalty agreement with Eli Lilly shortly after the successful experiment in 1978. Eli Lilly began clinical trials in July 1980.
On 28 October 1982, FDA approved Humulin, the first biosynthetic human insulin, after only five months of review. That’s an incredibly short review period; in 1982, 30.5 months was the average approval time.
Moreover, according to CODA, that approval was “based on trials conducted on fewer than 400 participants.” In 1992, researchers were calling for “a large randomised trial.”
Although this was the first drug produced using rDNA technology, “recombinant DNA techniques were viewed as an extension, or refinement, of long-used and familiar methods for making drugs” (archive link).
Was the synthetic human insulin more effective than insulin derived from pancreas glands? Not according to either FDA or Eli Lilly: “tests thus far have not found the synthetic human insulin to have any therapeutic advantage over the most highly purified forms of animal insulin.”
Despite no therapeutic advantage, Eli Lilly marketed the drug extensively. Whether or not the supply of pancreas glands (beef and pork) was truly being constrained, as argued by Eli Lilly, the pharmaceutical giant used that line in convincing doctors to prescribe synthetic rather than animal-based insulin.
Note that in 1982, the Washington Post shared Eli Lilly’s claim that the costs should be comparable and then less expensive:
Theoretically, the new method should be cheaper in the long run. But an Eli Lilly spokesman said that the human insulin would initially cost about 50 cents a day, a cost comparable with that of highly purified pork insulin. A commonly used beef-and-pork combination form of insulin is cheaper (emphasis added).
Since 2006, there has been no animal-based insulin available in the United States.
The cost of insulin basically tripled from 2002 to 2013 in the US. According to a 2019 article in Vox, the top four types of insulin tripled in price over the prior 10 years. In addition, “out-of-pocket prescription costs patients now face have doubled.”
Only two countries allowed direct-to-consumer marketing in 2017: the US and New Zealand. In 2015, John Oliver found that “nine out of 10 big pharmaceutical companies [spent] more on marketing than on research.”
No surprise, then, that the United States accounts for about half of big Pharma’s revenue from insulin, while accounting for only 15% of the global insulin market.
We have no true generic insulins. There are biosimilars but they have barriers to entry; three companies control global insulin production: Eli Lilly, Novo Nordisk, and Sanofi.
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*The announcement that Genentech had successfully produced a genetically-engineered insulin may have happened on 06 September 1978. Based on news reports, the announcement was in early September. One source claims the date the team achieved success as 21 August 1978 and another as 24 August 1978.
**That would not be the last case filed against Eli Lilly. For example (not exhaustive)
- 2022. Trulicity (diabetes drug)
False claims on Instagram. - 2019-2022. Eli Lilly plant in Branchburg, NJ
In June 2022, a former employee sued Eli Lilly, “alleging she was terminated after pointing out poor manufacturing practices and data falsification involving one of its blockbuster diabetes drugs.” In 2021, the DOJ began a criminal investigation into “alleged manufacturing irregularities and records tampering.” In 2019, an FDA inspection had uncovered serious violations. - 2009. Zyprexa (antipsychotic drug)
Eli Lilly agreed to plead guilty and pay $1.415 billion in fines (~$1,990,000,000 in current dollars). It included a misdemeanor criminal fine of $515 million (~$723,000,000 in current dollars), the largest ever in a health care case. - 1985. Oraflex (arthritis drug)
Lilly did not to tell the FDA about four deaths and six illnesses and pleaded guilty to misdemeanor criminal charges. The fine, $25,000 (~$69,000 in current dollars).
Less than a week later, the DOJ released its findings. Eli Lilly officials knew Oraflex was linked to at least 28 deaths overseas but “did not disclose them while seeking Government approval to sell the drug,” per the DOJ report. In the US, Oraflex was linked with at least 26 deaths and more than 200 cases of nonfatal kidney and liver failure.
#scitech, #science, #medicine (229/365)
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