10. BACK TO THE FUTURE FOR PHARMA
What we now know is that pharmaceutical companies took a wrong fork in the road in the 1980s. Instead of following SK&Fs example of the hard yards of drug development, it took the easier, more lucrative alternative. That has led to the supply chain woes we have heard about earlier. The fact is, the Zantac experience put an end to a golden era of drug development. Prior to that, physicians, doctors and healthcare professionals were at the heart of drug development, as we will go on to explore.
The penicillin story is well known. For those that need reminding, the mother of all antibiotics was developed by Alexander Fleming. On his return from holiday in August 1928, he noticed that bacteria had not grown in one of his culture dishes. He obtained an extract from the mold in the dish, naming it ‘penicillium’. The rest is history…or is it?
Not according to Robert P. Gaynes, author of Germ Theory, and the article The Discovery of Penicillin – New Insights After More Than 75 Years of Clinical Use.
In his book, Gaynes states “Due to its importance in medicine, the story of penicillin’s discovery has become shrouded in legend and distorted truths.” Gaynes’ article explains the distorted truths, summarized below. Fleming did not have the wherewithal to properly identify the mold strain or make it. It took a team at Oxford University, headed by a gentleman named Howard Florey, to purify enough penicillin to run pre-clinical (1939) and clinical (1941) studies. The studies were a great success, but they didn’t know how to make sufficient quantities to supply the market.
In 1941, Florey and a fungal expert, Norman Heatley, visited the USA to mull over the problem. The scenario was put to a microbiologist named Andrew J Moyer, an expert in the manufacture of molds, working at the United States Department of Agriculture Northern Regional Research Laboratory in Peoria, Illinois. Moyer and his team came up with the idea to “culture the penicillin in a mixture of corn steep liquor and lactose, thereby greatly increasing the yields and production rate”.
Moyer applied for a patent in May 1945, which was awarded 3 years later. So why did the myth persist? An article in The Times reported the breakthrough in Oxford but failed to mention Fleming or Florey. Fleming’s boss wrote to The Times, extolling his virtues and Fleming talked freely to the press at the time. Florey didn’t say a dicky bird to the press. So, the real account of it was never told.
In a nutshell, the story goes like this.
- Fleming discovered strong evidence penicillium was killing bacteria but was not able to isolate or purify the active ingredient.
- Florey’s team in Oxford isolated and purified enough to make test quantities, which produced even more evidence, but they were not able to manufacture it in more than gram quantities.
- A J Moyer’s team devised the commercial process and supply-chain to make penicillin in exponentially greater quantities and he was awarded the patent.
This led to successful mass production of penicillin to satisfy the demands of the World War II. The article comments, “Unprecedented United States/Great Britain cooperation for penicillin production was incredibly successful.” Moyer applied for a patent of the manufacturing process in 1945, which was granted in 1948.
This myth therefore perpetuated and has become hard coded into the industry psyche. This has created a public illusion that drugs are ‘discovered’ through serendipitous findings. Nothing could be further from the truth.
The important takeaway is that there were 11 lost years while Fleming was looking for someone to help him identify what was active in the mould. He eventually hooked up with Oxford University in 1939. By early 1943, the US Government had entered World War II and facilitated the transfer of Moyer’s process to Merck and other large pharmaceutical companies.
Just imagine if Fleming, Florey, and Moyer had been collaborating in August 1928, when the discovery was made – potentially, four years to get such a ground-breaking compound to market! There are more examples of the power of collaboration in the days prior to the blockbuster era
In 1921, on a shoestring budget at the University of Toronto, several young scientists began investigating a possible treatment for Type 1 diabetes. They found that by grinding up and purifying animal pancreases, and then regularly injecting the material, they could treat Type 1 diabetes in dogs.
After first testing the drug for safety by injecting themselves, the scientists treated a 14-year-old boy with Type 1 diabetes. His recovery was almost miraculous, going from death’s door to good health in a matter of weeks. By 1923, the scientists had won the Nobel prize and the treatment had entered mass production in collaboration with Eli Lilly and Company and the Swedish organisation Nordisk. The scientists patented the drug and sold it to the University of Toronto for three dollars (one dollar for each researcher), thinking that this was the best way to ensure that affordable treatment would be available to everyone who needed it.
With a fast forward into the future, fast-acting ‘analog’ insulins were pioneered with Lilly’s Humalog in 1996, but when Novo Nordisk entered the market four years later with its own analog insulin, NovoLog, prices did not decrease due to competition. Instead, Lilly and Nordisk followed each other closely in an exponential price increase. When Humalog was first introduced, it cost $21. At the time of writing this book in 2014, HumaLog and NovoLog were around $295 per vial.
The older ‘human’ insulins like Humalin are less expensive, but far less effective in treating Type 1 diabetes— yet even these primitive insulins have increased dramatically in price since their introduction in 1982.
The HPR article: ‘How insulin became unaffordable’ recounted the tragic case of Alec Raeshawn Smith, whose body stopped producing insulin when he was 24—he had become a Type 1 diabetic. The article goes on: “For two years, Smith managed his condition relatively well. But it wasn’t easy financially. On May 20, 2017, Smith turned 26, “ageing out of his parents’ insurance.” He didn’t qualify for government assistance with his insulin payments, and when he went to pick up his insulin in early June, the bill was over $1300 without insurance.
He couldn’t afford the medicine that day and decided to ration his remaining insulin until he was paid. He didn’t tell his family. On June 25, Smith went to dinner with his girlfriend, where he complained about stomach pains.
It was the last time anyone saw him alive. He called in sick to work the next day. On June 27, Smith was found dead in his apartment.
RIP Alec Raeshawn Smith: many hearts went out to his mother, Nicole Smith-Holt, his family, and all those who knew and loved him.
A shocking story, and the pricing issue still goes on today.
The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later the results were published.
Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. On April 12, 1955, Edward R. Murrow asked Jonas Salk who owned the patent to the polio vaccine. “Well, the people, I would say,” Salk responded. “There is no patent. Could you patent the sun?”
By the time of his chat with Murrow, which aired on the day the polio vaccine was announced as safe and 90 percent effective, Salk was already more messiah than virologist to the average American.
Polio paralysed between 13,000 and 20,000 children annually in the last pre-vaccine years, and Salk was the face of the inoculation initiative. Appearing on television to present the vaccine as a gift to the American people was a public relations masterstroke. One critic of Big Pharma called Salk “the foster parent of children around the world, with no thought of the money he could make by withholding the vaccine from the children of the poor.”
Takeaways from the above
There are three important takeaways from the above. Firstly, if Fleming, Florey’s team and Moyer’s team had been together when that initial discovery was made, it would have taken less than 4 years from start to finish, instead of the 15 years it actually took—cutting the time to market to one quarter of what it actually took.
Secondly, Fleming was a physician as well as being a microbiologist. As a healthcare professional, he was looking for new medicines that could cure conditions he was very familiar with in his day-to-day work.
Sir Frederick Banting, famous for his work to isolate insulin in the case above, was similarly qualified as a physician (as was Edward Jenner, who brought the smallpox vaccine to the world).
Jonas Salk, who famously refused to patent his polio vaccine, was a virologist who choose to do medical research instead of becoming a practicing physician. He was, never-the-less, a medical expert in the disease, carrying out the development work personally along with his team.
The final takeaway from penicillin, and from each of the medical breakthroughs above, is the degree of evidence that was assembled on the safety, efficacy and manufacturability of the compound PRIOR to moving into a scaled up supply chain. They effectively created prototypes before exposing any more than handfuls of patients to the medicine. Some even tested for safety on themselves when confidence levels were sufficiently high. It should not surprise you to learn that SK&Fs Sir James Black was also a physician.
Then it all changed
The move to focusing on discovery research to find patented molecules changed all that. Physicians had to move aside to let the scientists take over the show; and wait for sales & marketing to get in touch with their latest breakthrough many years later!