The Devil in the Details - Chapter Two
Digest
The podcast delves into the story of Contragan, a sedative marketed as a "wonder drug" in post-World War II Germany. The drug, containing the active ingredient litamide, contributed to the country's economic recovery but later proved to be a devastating cause of birth defects. The story begins with the emergence of "miracle drugs" like antibiotics and anti-psychotics, which played a significant role in Germany's economic recovery. Contragan, produced by Chemie Grunenthal, became a major seller, contributing to the company's booming revenues. However, the first signs of trouble emerged in 1956 when a Grunenthal employee's daughter was born without ears after her mother took litamide during pregnancy. These concerns were initially dismissed, but Frances Kelsey, a medical officer at the FDA, became skeptical of the drug's safety and requested more data from the manufacturer, Merrill. This delay in approval proved crucial in preventing a widespread tragedy. Kelsey sought advice from Barbara Moulton, a former FDA whistleblower, who suggested a loophole to delay the approval further. Meanwhile, Merrill, frustrated with the delay, repeatedly contacted Kelsey, urging her to approve the drug. However, Kelsey's concerns were validated when she discovered a letter in a British medical journal reporting cases of peripheral neuritis in patients taking litamide. This was the first concrete evidence of the drug's potential harm. It was later revealed that Chemie Grunenthal was aware of the potential neurological side effects as early as 1959 but continued to promote it as non-toxic. The lack of rigorous clinical trials in Germany at the time allowed the drug to be approved without sufficient safety data. In 1961, a baby named Jan was born in Hamburg, Germany, with shortened arms and three fingers on each hand. His father, Karl Schulte-Hillen, began investigating the cause of his son's malformation and discovered a pattern of similar births in the area. He connected with Virokint Lenz, a pediatrician and geneticist, who recognized Jan's condition as "Focomilia." Lenz and Schulte-Hillen began compiling a list of babies born with Focomilia, discovering a widespread epidemic across Germany. They suspected a toxin was responsible but struggled to identify the culprit. The podcast explores why the connection between litamide and Focomilia was missed for so long, highlighting the rarity of the condition, the lack of centralized data, and the absence of rigorous record-keeping. The podcast also discusses how doctors in other countries, including Australia, were also investigating the litamide's potential role in birth defects. However, the lack of communication and the widespread belief in the drug's safety hindered progress. In September 1961, Frances Kelsey received another call from Joseph Murray, who was eager to get the litamide approved for the U.S. market. Kelsey remained unconvinced about the drug's safety, particularly its use during pregnancy. The podcast concludes by highlighting the tragic consequences of the litamide's widespread use. Despite the FDA's delay in approval, the drug was already being distributed in the U.S., and American babies were being born with severe malformations.
Outlines
The Rise of Contragan and the German Economic Miracle
The podcast begins by discussing the post-World War II economic recovery in Germany, known as the "Wieschaff Wunder." Pharmaceuticals played a significant role in this recovery, with the emergence of "miracle drugs" like antibiotics and anti-psychotics. Contragan, a sedative made by Chemie Grunenthal, became a major seller, contributing to the company's booming revenues.
The First Signs of Trouble: A Baby Born Without Ears
In 1956, a Grunenthal employee's daughter was born without ears after her mother took litamide, the active ingredient in Contragan. This incident marked the beginning of concerns about the drug's safety, but these concerns were initially dismissed.
The FDA's Battle for Safety: Frances Kelsey and Litamide
Frances Kelsey, a medical officer at the FDA, was tasked with reviewing the application for litamide in the U.S. She was skeptical of the drug's safety and requested more data from the manufacturer, Merrill. This delay in approval would prove crucial in preventing a widespread tragedy.
The Focomilia Epidemic: Uncovering the Truth
The podcast explores the discovery of the Focomilia epidemic in Germany, the efforts of Karl Schulte-Hillen and Virokint Lenz to connect it to litamide, and the challenges they faced in uncovering the truth.
Keywords
Wieschaff Wunder
The post-World War II economic recovery in Germany, characterized by rapid growth and industrialization.
Miracle Drugs
New pharmaceuticals, such as antibiotics and anti-psychotics, that revolutionized medicine and offered hope for previously incurable diseases.
Contragan
A sedative marketed as a "wonder drug" by Chemie Grunenthal, containing the active ingredient litamide.
Litamide
The active ingredient in Contragan, later found to cause severe birth defects, including Focomilia.
Focomilia
A rare birth defect characterized by shortened limbs and malformations of the hands and feet.
Peripheral Neuritis
Nerve damage that affects the peripheral nerves, causing tingling, numbness, and weakness in the extremities.
FDA
The Food and Drug Administration, a U.S. government agency responsible for regulating food, drugs, and medical devices.
Whistleblower
A person who exposes wrongdoing or illegal activities within an organization.
Q&A
What was the "Wieschaff Wunder" and how did pharmaceuticals play a role in it?
The "Wieschaff Wunder" was the rapid economic recovery of Germany after World War II. Pharmaceuticals played a significant role by introducing "miracle drugs" that improved public health and contributed to the overall economic growth.
What was Contragan and why was it so popular?
Contragan was a sedative marketed as a "wonder drug" by Chemie Grunenthal. It was popular due to its perceived effectiveness and the company's aggressive marketing campaign.
What was the first sign that litamide, the active ingredient in Contragan, might be dangerous?
The first sign was the birth of a baby without ears to a Grunenthal employee whose mother had taken litamide during pregnancy.
How did Frances Kelsey's actions at the FDA prevent a tragedy?
Kelsey's skepticism about the drug's safety and her insistence on more data from the manufacturer delayed the approval of litamide in the U.S., preventing a widespread epidemic of birth defects.
What was the role of Barbara Moulton in the story?
Moulton, a former FDA whistleblower, advised Kelsey on how to delay the approval of litamide by requesting more information, effectively preventing the drug from being released to the market.
Why was it so difficult to connect the litamide to the Focomilia epidemic?
The rarity of the condition, the lack of centralized data, and the absence of rigorous record-keeping all contributed to the delay in identifying the cause.
What was the ultimate consequence of the litamide's widespread use?
The litamide caused a global tragedy, resulting in thousands of babies being born with severe malformations, including Focomilia.
Show Notes
It’s the early 1960s and the German pharmaceutical market is booming. A sedative called Contergan is one of the bestselling drugs. Contergan’s active ingredient is thalidomide and it is touted as a wonder drug, a non-addictive sedative safer than barbiturates. In the U.S., the drug is called Kevadon, and its distributor is impatient to get the drug on the market. But Dr. Frances Kelsey, a medical examiner at the U.S. Food and Drug Administration, is stalling the approval of Kevadon. She wants more information from the manufacturer to prove it is safe. Meanwhile, doctors in Scotland and Australia are beginning to suspect thalidomide might, in fact, be very toxic. And in Germany, reports are beginning to emerge of a mysterious epidemic of babies born with missing limbs and other serious medical conditions, but doctors have no idea what's causing it.