The beginning of the nightmare
A late 1950s advertisement touted a new drug called “Mornidine” (which was another name for Thalidomide). The advertisement said that “Mornidine is a drug with specific effectiveness for treating the nausea and vomiting which occurs in early pregnancy.” Can you imagine? It SPECIFICALLY said to use this drug “In Pregnancy.” It would turn out, as we will see below, that using this drug during pregnancy produced disastrous results!
The late 1950s and early 1960s were the beginning of the nightmare. Mornidine was, in actuality a drug called Thalidomde which had been developed in the mid 1950s by the West German pharmaceutical company Chemie Grünenthal GmbH. It was originally intended as a sedative or tranquilizer but was soon used for treating a wide range of other conditions, including colds, flu, nausea and – worst of all – morning sickness in pregnant women.
A prescription was never required.
Really? How could it be that a doctor’s prescription was never required for people to have access to Thalidomide? Well actually yes. It is unfortunately true. When initially released in Germany in late 1950s, a prescription was not required for people to have access to Thalidomide. Why? Well, it so happened that during early testing of Thalidomide, researchers found that “it was virtually impossible to give test animals a lethal dose of this drug”. What that meant is the they gave Thalidomide to laboratory test animals and that (pretty much) no matter how high a dose of Thalidomide they gave to laboratory test animals, it did not kill them. Therefore, based on this, the drug was felt to be harmless to give to humans. As a result, Thalidomide was licensed in Germany in July 1956 for over-the-counter sale (no doctor’s prescription was needed). Unbelievable but unfortunately true.
By 1958, Thalidomide was being produced and sold in various countries. In the United Kingdom it was produced and sold under various brand names, such as Distaval, Tensival, Valgraine and Asmaval. That means that in 1958 in Great Britain, you could walk up to your local pharmacy and pick up some Thalidomide without a prescription (under the various brand names mentioned above) to treat the nausea, or “Morning Sickness”, which is often encountered in early pregnancy. Advertisements of the time said things like “Distaval (another name for Thalidomide) can be given with complete safety to pregnant women (!) and nursing mothers without adverse effect to mother or child.” Nothing could be further from the truth.
In the USA: Dr. Kelsey saved us!
Here in the USA, we were largely saved this Thalidomide nightmare by a physician/pharmacist at the FDA by the name of Frances Oldham Kelsey, MD, PhD (or “Frankie” as her friends called her). Despite tremendous pressure from the pharmaceutical company that wanted the FDA to approve Thalidomide for use in the USA, Dr. Kelsey stubbornly turned down their many requests for the FDA to approve Thalidomide to be put pharmacy store shelves here in the USA. Dr. Kelsey felt that the companies had not provided enough clinical evidence to refute reports coming to the US from England (and other countries) of adults who developed nerve damage in their limbs after long-term use of Thalidomide. Unbelievably this was Dr. Frances Oldham Kelsey’s only her second case on the job as one of the reviewers for NDAs (New Drug Application) for the FDA. Dr. Kelsey, who passed away on August 7, 2015 at the age of 101, was a rookie at the FDA when a pharmaceutical company applied to the FDA to approve Thalidomide for us in the USA and rookie or not, she largely saved the US (the country as a whole) from the terrible nightmare of what was Thalidomide in the early 1960s! This took tremendous courage on her part.
On September 8, 1960, Dr. Kelsey received an NDA (New Drug Application) from a pharmaceutical company headquartered in Cincinnati called the “Richardson-Merrell” Company” who wanted the FDA to approve for the USA their new sedative which they called “Kevadon”, (but in reality this was Thalidomide under a US tradename). What is even more significant of the courage and sacrifice that Dr. Oldham Kelsey did for all of us is that at the time, a New Drug Application (NDA), by rule, had to be processed within 60 days or the company had the automatic right to market the product in the US! Can you imagine? What if Dr. Kelsey did not defend us as stubbornly as she did? In addition, unbelievable but true, at the time in the late 50s and early 60s, whether or not it was yet approved by the FDA, drug companies were permitted to freely distribute products to doctors if the packaging was labeled “experimental.” These reasons are why, despite Dr. Kelsey’s unbelievably heroic efforts, here in the US we still had a number of children born with birth defects due to Thalidomide.
The pressure on Dr. Kelsey was tremendous
The pharmaceutical company, Richardson-Merrell, expected to officially launch their Thalidomide medication onto US store shelves within 6 months of when they applied to the FDA for approval. They thought that they would have this medication on store shelves by March 6, 1961! In fact, they had already started to freely distribute samples of this Thalidomide formulation here in the USA and they were telling doctors and patients that their new sedative which they called Kevadon, (but in reality, this was Thalidomide under a US tradename) was supposedly “extremely safe, even for children” and – said even worse – that it was supposedly “safe and effective against the morning sickness of pregnancy”! (which it most definitely was NOT safe!).
Kelsey and her team repeatedly rejected the application for FDA approval for Thalidomide by the Richardson-Merrell Company, thereby angering the company tremendously. Richardson-Merrell submitted to the FDA and to Dr. Kelsey so-called “additional data” to try to compel the FDA to approve Thalidomide for over-the-counter use in the USA, but again Dr. Kelsey and her team rejected Richardson-Merrell’s application noting that their application was, again “incomplete and inadequate”. As expected, the Richardson-Merrell Company became very angry with Dr. Kelsey’s repeated rejections of Thalidomide for US store shelves. In about 18 months, unbelievably, they made approximately 50 visits to Dr. Kelsey’s office trying to get her to approve Thalidomide for the US store shelves – to give to pregnant women for “morning sickness”! Can you imagine the disaster if Dr. Kelsey would have buckled under this pressure and would have approved Thalidomide for US store shelves?
During the time when Dr. Kelsey was rejecting the repeated applications by the Richardson-Merrell Company to approve Thalidomide for United State store shelves, the US started to receive reports from doctors in the UK, Australia, Europe, Japan and West Germany, noting an alarming rate of malformed babies from mothers who were taking Thalidomide when they were pregnant (remember, there was no Internet in those days so these reports had to wait for regular mail). These reports noted that women who were taking Thalidomide during pregnancy were either miscarrying their pregnancies or their babies were being born without arms, without legs, sometimes without eyes and with many other horrible deformities. Other countries therefore began pulling Thalidomide from their markets and, after learning of all of these serious side effects in other countries, on March 8, 1962 the Richardson-Merrell company withdrew from the FDA their application for the approval of their formulation of Thalidomide for the USA!. Dr. Kelsey’s refusal to approve thalidomide for sale in the US prevented the births of thousands of seriously malformed babies.
By the time that it was all said and done, by late 50s and early 60s more than 10,000 children in 46 countries were born with deformities as a consequence of their mothers taking thalidomide during their pregnancies. It was determined that the severity, and even the location of the birth defects, depended on how many days into the pregnancy the mom took Thalidomide:
20 days: If the mom took Thalidomide on or before the 20th day of pregnancy, it caused brain damage in the newborn.
21 days: If the mom took Thalidomide around the 21st day of pregnancy, it caused damage the eyes, the ears and face of the newborn. Some newborns were even born without eyes!
24 through 28 days: If the mom took Thalidomide from the 24th through the 28th day of pregnancy, Thalidomide caused damage to the arms and legs of the newborn. Some newborns were born without arms or legs!
In August 1962, President John F. Kennedy awarded Dr. Frances Oldham Kelsey the President’s Medal for Distinguished Federal Civilian Service for her exceptional judgment in evaluating the drug Thalidomide and rejecting it for US store shelves. Dr. Kelsey was only the second woman ever to receive this award—the highest honor that can be bestowed upon a US civilian. As noted above, sadly Dr. Kelsey passed away on August 7, 2015 at the age of 101, We owe her so much. It is like what Winston Churchill said of the pilots who defended Britain from the Nazi onslaught during the Battle of Britain. “Never have so many, owed so much, to so few!”
