This story might feel like movie script, but it is entirely true. People entering the civil service or any responsible position should probably learn it by heart. This is the story of a female scientist who was able to resist the pressure of a pharmaceutical corporations and save thousands of children from disability, and it reminds us how far-going the consequences of our decisions can be.
Here at Bright Side we believe that some stories don’t get old. The memory of lessons taught by history should be refreshed often enough to prevent us from repeating the same mistakes.
Frances’ life before the “thalidomide scandal”
Frances Oldham Kelsey dreamed of becoming a scientist from her childhood, which was not easy for a woman at that time. At the age of 21 she had already received her degree in pharmacology. Then she got lucky: a well-known researcher from the University of Chicago, when looking through candidate resumes, assumed that Francis was a man’s name and accepted Kelsey to his team.
The irony is that here Kelsey managed to find the cause of a mass poisoning of people by an antibiotic solution that wasn’t properly tested before being released to market. 30 years later, when she joined the FDA, she will partially repeat this experience: not as a scientist, but as an official — to prevent a drug called thalidomide from entering the US market.
Thalidomide was first synthesized in the middle of the 20th century in a course of research by an antibiotic company called Chemie Grünenthal. After several years of work, the company came to conclusions, which later became fatal.
- Even when overdosed, thalidomide did not kill any of the test animals. From this, a conclusion was made about the harmlessness of the drug, and the manufacturer sent free samples to doctors from Germany and Switzerland for the treatment of patients.
- The drug had a significant sedative (calming) effect.
A harmless effective sedative, which, as it turned out, also helped with insomnia and morning sickness, is this not a dream come true? Under different names (more than 37 of them!) thalidomide went on sale in 46 countries in Europe, Scandinavia, Asia, Africa, and South America. A year later, a large-scale advertising campaign for “the best and safest medicine for pregnant and lactating mothers” began despite the fact that neither the manufacturer nor the distributors had conducted any research on the effect the drug had on a fetus. Reports of side effects (like, neuritis) were denied and swept under the rug.
What happened in 1960?
In September 1960, thalidomide reached the United States. Richardson-Merrell brought it to the FDA (the US Food and Drug Administration) under the name Kevadon. The approval seemed only a formality. However, a new employee, Frances O. Kelsey unexpectedly rejected the application for everyone.
What alarmed her?
- Studies of the safety of the drug showed strange results: absolute absence of toxicity. But what if the test animals simply could not absorb the drug? No one tested this version. On the contrary, when the first experiments showed that animals did not calm down when taking thalidomide, the scientists changed the test conditions so that they produced the desired result because they wanted to be able to release the drug to the market as soon as possible. Frances found this proof of safety inadequate.
- Richardson-Merrell was aware of the risk of developing neuritis (these reports began arriving a year before), but did not mention this in their report to the FDA. In February 1961, there were more of these reports.
- Nobody conducted tests on the effect of the drug on a developing fetus, even though at that time the permeability of the placental barrier was already discovered. Francis derived a theory that thalidomide caused paralysis of the peripheral nerves, and suggested that damage caused to the embryo could be even greater.
“Stand your ground.”
Francis asked for more information, which started a conflict. She received responses from the manufacturer in the US. The William S. Merrell Company waited 60 days, made new requests and the pharmacists put her under pressure, tried acting through her superiors, reproached her for incompetence, and complained about the bureaucracy. Kelsey insisted that the safety evidence was inconclusive and requested Merrell to conduct her research.
“Richardson-Merrell were at the edge,” — Kelsey noted. — “They were very disappointed, since Christmas is high season for sedatives and sleeping pills. They kept calling me and making visits, saying: We want to get this drug on the market before Christmas, because that is when our best sales are.”
She stood her ground until the end of 1961, when scientists from Germany and Australia finally found a link between taking thalidomide and numerous cases of malformations in children born after mothers took it during pregnancy. Once the results were published and only under pressure from the press did Chemie Grünenthal begin the withdrawal of the drug from the market, also notifying its American counterparts.
What did this decision cost Kelsey?
In order to assess how difficult it was for this woman to make this decision, you need to realize several facts.
- At that time, thalidomide had been selling for several years in more than 40 countries and an aggressive marketing campaign was being conducted. It seemed that the signature on the permit needed to be able to sell it in the US was just a formality.
The only requirement under American law was the safety of the drug. In addition, a trial application was already conducted: Richardson-Merrell managed to distribute more than 2.5 million tablets through therapists, and most doctors found it effective and useful, which was confirmed by their reports. Tons of ready-to-sell “Kevadon” were already laying in warehouses.
At that time, Kelsey had been working at the FDA for about a month and this was one of her first assignments. We can only guess how strong she had to be to withstand numerous accusations of incompetence. The pressure on Kelsey was enormous.
What happened afterward?
- On August 8, 1962, President John F. Kennedy presented Frances O. Kelsey with the award for outstanding civil service, the highest non-military award in the United States. She became the second woman in history to receive this award.
The thalidomide tragedy caused many countries to review their licensing policy for many drugs and toughen it. For example, requirements for providing evidence of the effectiveness of a licensed drug have been added and careful monitoring has been introduced both for patients receiving the drug and for the prescribing physicians.
The total for the 6 years of the drug’s sales, according to approximate estimates, are that up to 12,000 children with abnormalities were born because their mothers were prescribed and took this “harmless sedative.” About 40% of these kids did not live to be one year old. To understand how hard life was for survivors, you can look at the photos of the most famous victims — the star of German documentary, Niko von Glazow, and the bass baritone from Germany, Thomas Quasthoff.
- Chemie Grünenthal and its partners in various countries have received many lawsuits from the victims. The first charges began to come in 1961, but the proceedings dragged on for decades. In most cases, the results were monetary compensations to the families of the victims and the creation of special aid funds.
Frances O. Kelsey didn’t leave her job for the rest of her long life. She retired at the age of 90 and returned to her home in Canada. In addition to the big award in 1962, she received many other awards, and in addition to that, an asteroid was named after her. Kelsey died in August 2015 at the age of 101, less than 24 hours after receiving the rank of Honorary Member of the Order of Canada from the hands of the Lieutenant-Governor of Ontario.
- And thalidomide, strangely enough, came back in the late 1990s, when it was proven effective for serious diseases — like leprosy and some malignant tumors that are immune to chemotherapy. Naturally, it is now prescribed under the strictest control and only in cases where pregnancy is excluded. And this once again proves that every coin has 2 sides.
Have you ever encountered any decisions that were hard to make because of the pressure others were putting on you?