The Tragedy of Thalidomide
Safety Assessment
Alan Hoberman

The Tragedy of Thalidomide

On Sept. 14, employees from 18 Charles River sites will work together to painstakingly assemble 305 prosthetic hands for amputees in developing countries. There are an estimated 6-7 million below-elbow amputees worldwide. Many have no financial means to acquire prosthetics. With the creation of the Helping Hands program by Odyssey Teams Inc. in conjunction with their non-profit partner, the Ellen Meadows Prosthetic Hand Foundation, hands are provided to recipients for free. Odyssey Teams created this unique teambuilding process in 2008 and its clients, like Charles River, have funded and built nearly 35,000 hands which are distributed in over 70 countries. Many of the victims were injured in land mines, industrial accidents or electrocution. But some of the recipients were born with deformed limbs caused by congenital defects. Cases like this are pretty rare, but Alan Hoberman, Executive Director of Charles River’s Reproductive and Juvenile Toxicology Program and President of the Teratology Society, talks about a time when cases like this were not so rare, and how the tragedy led to major changes in our  testing guidelines for drugs.    

Before the era of modern warfare and the introduction of land mines, which have been dismembering children in war-torn countries with horrific regularity lately, thousands of children became afflicted with deformed arms and legs for a very different reason. During the 1950s and 1960s, the widespread use of the drug thalidomide, taken by thousands of pregnant women in Europe for morning sickness and thought to be safe when it was marketed in 1957, turned out to be harmful to the fetus. The drug caused over 10,000 cases of a limb reduction defect called phocomelia—from the Greek for seal fin—with only 50% of these babies surviving. By the 1970s, the drug was banned from most markets.

This tragedy led to a major change in our testing guidelines for drugs. It also prompted the establishment, in 1960, of The Teratology Society, a scientific group that encourages multi-disciplinary research and regular communication among health professionals to prevent birth defects. (One of its current preoccupations is the Zika outbreak, which has caused the brain deformity microcephaly in hundreds of infants exposed to the virus in utero.)

 One of the guiding principles in the field of teratology is Karnofsky’s law, which states that any substance given at the right time and right dose can cause birth defects. Based on Karnofsky’s law it became clear that all drugs could be potentially hazardous and that our testing of new drugs must identify when and how we can use a new drug both effectively and safely.  

Charles River has the world’s largest group of teratologists available to the pharmaceutical and chemical industry to design and conduct studies that help prevent another thalidomide tragedy. Many of them are also part of the Teratology Society . Since 1960 we have marketed drugs that are known teratogens, but we have been able to define the hazard and still use the drug in the most efficacious way possible. Thalidomide is even back on the market as an immunomodulatory drug and the prototype of the thalidomide class of drugs. It’s used mainly as a treatment for certain cancers (multiple myeloma) and for a complication from leprosy.

The thalidomide crisis ended years ago, but cases of phocomelia still occur. Surprisingly, some of the defects have been traced to thalidomide, which is still available in South America due to poorly regulated or uncontrolled use of the drug. The causes of other cases of phocomelia remain a mystery. Research studies estimate phocomelia occurs anywhere from 0.3 per 100,000 births to 4.6 per 100,000 births, In the US about 1,500 babies are born with upper limb deformities, which includes a handful of cases of phocomelia. Children are also being born with other kinds of arm and leg deformities.

So the needs for prosthetics isn’t over yet, and I’m gratified that Charles River will be doing its part on Thursday and lending a hand to help people have a basic function we all take for granted.

It is a privilege to be able to help ensure that research in the study of birth defects continues to hopefully eliminate defects caused by genetic and nutritional factors. We owe it to the kids.