post, especially as a woman and relatively young, but she knew the task before her was a difficult one. Malaria can develop resistance to drugs faster than new ones can be created, and nearly a quarter-million compounds had already been tested by scientists around the world. Not making things any easier for Tu was the fact that her husband had been “sent down to the countryside” on a mandatory exchange program for “reeducation,” leaving her a single parent; she would often be separated from her daughter for long periods of time.
Tu and her team traveled from village to village to talk to traditional medicine practitioners and scoured libraries for every medical text they could find. In the end, they collected over 2,000 recipes for herbal, animal, and mineral-based compounds, choosing from these 640 with the most potential. Back in Beijing, her team began distilling those best bets into 380 herbal extracts they could test on mice. One challenge was overcoming the primitive conditions of their own lab, which was poorly ventilated against the harsh solvents the team used and had only household pots and pans as equipment.
By 1971, the researched began to zero in on the herb quinghao, or sweet wormwood. It first appeared in a silk scroll from the Han Dynasty two thousand years ago entitled Prescriptions for 52 Kinds of Diseases and was mentioned frequently in texts throughout the centuries as a remedy for intermittent fevers, a symptom of malaria. That still left the team with many questions: Which species of quinghao did the texts refer to? Where did it grow? Which part of the plant do you use and how should it be prepared? Other research groups joined the quest and after an exacting process of elimination, Artemisia annua L. was found to be the only variety of quinghao containing antimalarial properties. Despite this, disappointingly, no extract of it had produced a consistent effect on the lab mice.
The miraculous sweet wormwood.
Frustrated, Tu began rereading the ancient texts, searching for clues. A medical manuscript from the East Jin Dynasty, written in 340 CE, advise, “A handful of quinghao immersed in two liters of water, wring out the juice, and drink it all.” It was so simple! The team had been boiling samples and the heat had damaged the active ingredients. Tu immediately modified their methods and on October 4, 1971, they found a formulation that proved 100 percent effective in curing malaria-infected mice, though it would take an additional six years to isolate the drug’s molecular structure. Tests in infected monkeys were also successful. The next step was testing humans. To move the process along as quickly as possible, Tu and her team volunteered themselves as test cases. By August of 1972, Tu was able to perform clinical trials of artemisinin on thirty malaria patients. Tu presented the drug at a World Health Organization meeting on malaria in 1981 and the Chinese Ministry of Health finally officially approved artemisinin in 1986, fifteen years after Project 523 began.
In the 1990s, artemisinin gradually began replacing previous generations of medicines that had lost their effectiveness. Artemisinin was effective against even the most stubborn strains of malaria. In severe cases where patients were hospitalized, artemisinin cut the mortality rate in half. World Health Organization statistics for 2013 showed that malaria deaths had fallen from about two million per year a decade earlier to an estimated 584,000.
There was some controversy attached to Tu’s 2015 Nobel Prize in Physiology or Medicine, as hundreds of scientists had been involved. However, it was Tu herself who brought in the sweet wormwood plant and created a method for extracting the active ingredient, as well as leading the first human trials.
Frances Oldham Kelsey
A medical crisis need not be germ-based to spread dangerously. Beginning in 1960, tens of thousands of babies were born with improperly developed limbs, and, in some cases, malfunctioning eyes, ears, or other organs. It was a tragedy as had never been seen before, catastrophically striking families in more than forty countries, including Germany, Japan, and England. The cause of these birth defects was a new sedative called thalidomide, which had been approved to treat pregnant women for morning sickness. It seemed like a godsend, especially for women with hyperemesis gravidarum, which is like morning sickness gone nuclear, and can become a serious health problem. The studies done on this drug were limited in scope and did not reveal its devastating side effects. It was quickly taken off the market, but for the many babies who were hurt or killed, the damage was done.
So why were thalidomide birth defects rampant in Europe but rare in America? It was largely because of one woman, new drug reviewer Frances Oldham Kelsey. Born in 1914 in British Columbia, Kelsey earned both a bachelor and master of science from McGill University. In the mid-1930s, Kelsey wrote to Eugene Geiling, a researcher at the University of Chicago, asking to work in his lab and study for a doctorate. Dr. Geiling replied with an offer of a scholarship for “Mr. Oldham.” Thankfully, he still honored his offer when Ms. Oldham arrived.
In 1938, Oldham earned her PhD from the University of Chicago and would later join the faculty there. She married Dr. Fremont Ellis Kelsey, a fellow professor, in 1943 and the couple had two daughters, all while Frances Kelsey earned her medical degree. Kelsey moved to Washington, DC, to begin her long, distinguished career with the Food and Drug Administration, where she became chief of the Division of New Drugs, director of the Division of Scientific Investigations, and deputy for Scientific and Medical Affairs Office of Compliance.
Kelsey was assigned to review applications from pharmaceutical companies for drug approval. It was a job she was well-suited to, have already proven herself to be masterful detective. While earning her PhD in pharmacology, Kelsey helped pinpoint a toxic ingredient in another drug called elixir sulfanilamide. Elixir sulfanilamide was marketed as something of a cure-all, which should always raise an eyebrow. The drug was very bitter, so the manufacturer added a sweetener. That sweetener, Kelsey discovered, was antifreeze. The drug had already killed more than a hundred people by the time the FDA got it off the market.
Do not drink this.
While it’s imperative to keep antifreeze away from children and pets, it’s a wives’ tale that cats will drink it because of its sweet taste. Cats can’t taste sweet at all.
When the paperwork for thalidomide, sold under the brand name Kevadon, hit Kelsey’s desk in the fall of 1960, she was expected to approve it automatically, since it was already popular in Europe. Her critical eye, however, quickly spotted holes in the data “proving” that thalidomide was safe, and she rejected the application. The “results” in their application were more testimonials than quantifiable science, and the developers had failed to do a placental barrier test to show whether the drug would reach the fetus when taken by a pregnant woman. A chemist working under Kelsey who spoke German also pointed out a higher-than-acceptable number of translation errors in the English copy of the application. In something of a baptism by fire, the thalidomide application was the first Kelsey handled in her new position. There was significant push-back as the drug company lodged complaints against Kelsey with her superiors. Nevertheless, for the next fourteen months, she did not budge. In November 1961, Dr. Kelsey’s careful vigilance was vindicated when Kevadon was taken off the market in its native West Germany and in other countries soon after.
In the aftermath of thalidomide’s European release, thousands of children in Europe were born with partial limbs, blindness, deafness, and/or cognitive impairment. Those who did not die in utero, that is, which is thought to be four times as many. Thalidomide’s effects on fetal development are so dramatic and predictable that doctors can pinpoint in which week of pregnancy the mother took it by which fetal body system was affected. Kelsey’s steadfastness prevented the same from happening in the US. Sadly, this does not mean there were
