Lycheeit2021-6-2 08:29 /
In 1940s, when the doughboy landed on the island in Pacific, the most violent enemy waiting for them was not the Asian little guys with an arisaka rifle but a kind of microorganism that had threated people for a long period in the tropical, plasmodium. The plasmodium caused malaria and infected thousands of the soldiers.
To deal with this hygienic problem that was threating the army, a group of microbiologists, physicians and other scientists were called to research on the plasmodium in order to defeat malaria, including a young female pharmacologist named Frances Kelsey who was serving for University of Chicago. As a specialist in pharmacology, Kelsey’s job was mainly about the drug for malaria like quinine. During the animal testing, Kelsey found that a pregnant rabbit had less ability to break down the drug while others had a rapid metabolism of quinine. And the embryonic rabbits that still in their mother’s uterus even had no ability to metabolize the drug.
Finally, no more valuable finding about new means to cure malaria was found, but the different metabolism among animals left a deep impression for the young researcher, leaving a seed in her mind then.
Kelsey carried on her academic and was awarded her M.D in 1950 during her career as a professor. After that, she served as a lecturer, a physician as well as a columnist for a medical journal, and in 1960, she was hired by the FDA where her most famous achievement was recorded.
Synthesized by the Swiss pharmaceutical corporation CIBA in 1950s, thalidomide was researched furthermore in the West Germany and was first released into the local market in 1957. Thalidomide was applied as a kind of sedative-hypnotic which can bring people quick and natural sleep. During the initial research, thalidomide was thought to be safe in pregnancy and showed great efficiency on curing morning sick. As a result, thalidomide was then used as a prescription for those who were pregnant in more countries.
In Sept. 1960, American pharmaceutical company Richardson-Merrell submitted the application to FDA, intending to import thalidomide into USA. Kelsey, then a fresh man who had joined FDA and worked as a medical officer for just a month, received that as her first drug review assignment. Having checked the application, Kelsey and her colleague all showed concerns about the drug since the chronic toxicity studies as well as the absorption-excretion data were still in adequate. The drug was considered to change its absorption according to some special condition, which made the Kelsey and her colleagues worried. The clinical reports of the drug were more from the testimonials rather than results of well-designed nor well-executed studies. Richardson-Merrell was eager to get the permission so that their drug might catch up with the Christmas when sedatives and hypnotics would be sold the best in a year, but the officers who were in charge of the application asked for more data to show the drug’s safety.
3 months after Richardson-Merrell summited application, a medical journal published a letter from a physician named Leslie Florence, reporting that patients who have taken thalidomide for long period suffered from peripheral neuritis painful tingling of arms and feet. Kelsey noticed the report and contacted Richardson-Merrell immediately. The report reminded her of the experiment of rabbit, and she began to consider whether thalidomide would have some side effect if used during pregnancy, which comes to a suspicion that since thalidomide had some negative effect on nerves, it might also affect a developing fetus. Unfortunately, she almost foresaw what would happen in the near future.
In the coming year, some European physicians reported a disturbing phenomenon that a growing number of women were giving birth to terribly deformed babies who born with abnormally short limbs, toes sprouting directly from hips or flipper-like arms, formally diagnosed as phocomelia. Some other young victims might have malformed internal organs like eyes or ears, and many of those infants died shortly after birth. Finally, in Nov. 1961, a German pediatrician named Widukind Lenz made an epidemiological statistic and found that around 50% of victims’ mother had taken thalidomide during pregnancy, which determined that it was thalidomide that cause a series of tragedies.
Up to then, FDA was still holding on the application of thalidomide and Richardson-Merrell withdrew the application soon. More than 10,000 children in 46 countries were estimated to have been born with deformities due to the use of thalidomide. Even though FDA finally didn’t pass the application for the market in USA, about 2.5 million of thalidomide tablets still had been distributed to more than 1,000 doctors, which eventually caused 17 victims around USA. After all, thanks to the FDA, no more potential accident due to the thalidomide happened.
As the director for the assignment, Kelsey did nothing else but fulfill her duty as a medical officer. The pressure from the manufacturer did not knock down Kelsey and her colleague. None of them thought they did anything heroic and it was only their job as a scientist saved thousands of American families from the terrible nightmare.
Refence:
Wikipedia: Frances Oldham Kelsey
Wikipedia: Thalidomide & Thalidomide Scandal
Frances Oldham Kelsey: FDA Medical Reviewer Leaves her Mark on History Linda Bren <U.S Food and Drug administration>2001 Mar.
To deal with this hygienic problem that was threating the army, a group of microbiologists, physicians and other scientists were called to research on the plasmodium in order to defeat malaria, including a young female pharmacologist named Frances Kelsey who was serving for University of Chicago. As a specialist in pharmacology, Kelsey’s job was mainly about the drug for malaria like quinine. During the animal testing, Kelsey found that a pregnant rabbit had less ability to break down the drug while others had a rapid metabolism of quinine. And the embryonic rabbits that still in their mother’s uterus even had no ability to metabolize the drug.
Finally, no more valuable finding about new means to cure malaria was found, but the different metabolism among animals left a deep impression for the young researcher, leaving a seed in her mind then.
Kelsey carried on her academic and was awarded her M.D in 1950 during her career as a professor. After that, she served as a lecturer, a physician as well as a columnist for a medical journal, and in 1960, she was hired by the FDA where her most famous achievement was recorded.
Synthesized by the Swiss pharmaceutical corporation CIBA in 1950s, thalidomide was researched furthermore in the West Germany and was first released into the local market in 1957. Thalidomide was applied as a kind of sedative-hypnotic which can bring people quick and natural sleep. During the initial research, thalidomide was thought to be safe in pregnancy and showed great efficiency on curing morning sick. As a result, thalidomide was then used as a prescription for those who were pregnant in more countries.
In Sept. 1960, American pharmaceutical company Richardson-Merrell submitted the application to FDA, intending to import thalidomide into USA. Kelsey, then a fresh man who had joined FDA and worked as a medical officer for just a month, received that as her first drug review assignment. Having checked the application, Kelsey and her colleague all showed concerns about the drug since the chronic toxicity studies as well as the absorption-excretion data were still in adequate. The drug was considered to change its absorption according to some special condition, which made the Kelsey and her colleagues worried. The clinical reports of the drug were more from the testimonials rather than results of well-designed nor well-executed studies. Richardson-Merrell was eager to get the permission so that their drug might catch up with the Christmas when sedatives and hypnotics would be sold the best in a year, but the officers who were in charge of the application asked for more data to show the drug’s safety.
3 months after Richardson-Merrell summited application, a medical journal published a letter from a physician named Leslie Florence, reporting that patients who have taken thalidomide for long period suffered from peripheral neuritis painful tingling of arms and feet. Kelsey noticed the report and contacted Richardson-Merrell immediately. The report reminded her of the experiment of rabbit, and she began to consider whether thalidomide would have some side effect if used during pregnancy, which comes to a suspicion that since thalidomide had some negative effect on nerves, it might also affect a developing fetus. Unfortunately, she almost foresaw what would happen in the near future.
In the coming year, some European physicians reported a disturbing phenomenon that a growing number of women were giving birth to terribly deformed babies who born with abnormally short limbs, toes sprouting directly from hips or flipper-like arms, formally diagnosed as phocomelia. Some other young victims might have malformed internal organs like eyes or ears, and many of those infants died shortly after birth. Finally, in Nov. 1961, a German pediatrician named Widukind Lenz made an epidemiological statistic and found that around 50% of victims’ mother had taken thalidomide during pregnancy, which determined that it was thalidomide that cause a series of tragedies.
Up to then, FDA was still holding on the application of thalidomide and Richardson-Merrell withdrew the application soon. More than 10,000 children in 46 countries were estimated to have been born with deformities due to the use of thalidomide. Even though FDA finally didn’t pass the application for the market in USA, about 2.5 million of thalidomide tablets still had been distributed to more than 1,000 doctors, which eventually caused 17 victims around USA. After all, thanks to the FDA, no more potential accident due to the thalidomide happened.
As the director for the assignment, Kelsey did nothing else but fulfill her duty as a medical officer. The pressure from the manufacturer did not knock down Kelsey and her colleague. None of them thought they did anything heroic and it was only their job as a scientist saved thousands of American families from the terrible nightmare.
Refence:
Wikipedia: Frances Oldham Kelsey
Wikipedia: Thalidomide & Thalidomide Scandal
Frances Oldham Kelsey: FDA Medical Reviewer Leaves her Mark on History Linda Bren <U.S Food and Drug administration>2001 Mar.
