Solving a 50-Year Mystery: How Thalidomide Causes Birth Defects

By Rachel Cernansky | May 12, 2009 3:51 pm

thalidomideResearchers may have finally figured out the mechanism of the tragic birth defects caused by thalidomide, the drug taken by pregnant women in the late 1950s as a remedy for nausea: It is thought to have inhibited development of new blood vessels at a crucial stage in the pregnancy.

Women usually took the drug at about five to nine weeks into their pregnancy to combat morning sickness, a specific window that lead researcher Neil Vargesson says “is crucial as that is when the limbs of babies are still forming…. The blood vessels involved in this process, at this stage of pregnancy, are still at an immature stage when they rapidly change and expand to accommodate the outgrowing limb” [BBC]. The most common birth defects caused by thalidomide were babies born with stunted or malformed limbs.

The drug has been difficult to study until now because the compound has to be metabolically activated in the liver, where it is broken down into potentially more than 100 different compounds. Each of those — or some combination — could be the cause of deformed limbs [Nature News]. But the research team found a way to isolate the drug’s metabolites and identified one compound, CPS49, that causes severe limb defects and blocks growth of new blood vessels.

When CPS49 was given to chicks (chosen because chickens are one of few lab animals in which thalidomide causes birth defects) at a stage of development corresponding to that at which thalidomide was often used in pregnant women, the compound selectively affected limb development, leaving the rest of the embryo untouched. This is because at that time blood vessels in the body of the embryo are relatively mature, says Vargesson, whereas vessels in the limbs are just beginning to form [Nature News]. Additionally, the team found that the embryos died when the compound was administered at an earlier developmental stage, while the limb defects were less severe when administered later on in development.

Pulled from the market in 1961, thalidomide caused approximately 10,000 children to be born with deformed limbs, brain defects, or other developmental deformities. Because use of thalidomide has picked up again to treat leprosy and multiple myeloma (a type of cancer), it is hoped that the new study, published in the Proceedings of the National Academy of Sciences, could contribute to the development of a similar drug that does not have the same side effects.

Related Content:
80beats: Chemicals That Warp Male Reproductive System Should Be Studied as a Group
DISCOVER: Works in Progress looks at thalidomide’s uses in fighting leprosy and other diseases

Image: Flickr / otisarchives3

CATEGORIZED UNDER: Health & Medicine
  • Roy Shastid

    I seem to recall that this mystery was solved some time ago. I had heard/read somewhere that the effect of this drug was to block one of the B vitamins and that with supplements of this nutrient the effects could have been avoided. Anyone else have more information on this?

  • Stephanie

    what in the heck… how is someone suppose to unterstand this…:’-(

  • Lynn

    In 1960-1961 I was pregnant with my first child, and suffering HORRIBLE non-stop “morning-sickness”. My husband was in the Army and I was receiving “pre-natal care” at our Base Hospital, in Fairbanks, Alaska. I was put in the hospital and given thalidomide and later compazine for the sickness. I could not keep the thalidomide down, and vomited almost instantly each time I swallowed it. The compazine ended up giving me a paralysis of the facial muscles, and swallowing of my tongue! I had no idea how LUCKY I was, until 2 or 3 years later, when we returned to our home, in the lower 48…and I saw the LIFE magazine article describing the effects of Thalidomide. I had actually KEPT the bottle with the remaining pills…and I rushed to the medicine cabinet to see if the medicine I had taken…(and vomited) was indeed, the same. IT WAS!!! Thankfully, my daughter was born healthy, BEAUTIFUL…though VERY tiny. In her early teens, she began losing her hearing…and is completely deaf today. She is STILL very, VERY tiny….about 4’10. But, she is healthy, smart, so lovely…. and a miracle in my eyes. My pregnancy was a physical nightmare for me, and I weighed 20 lbs less when my daughter was born…than I had when my pregnancy began. But, I realize how very fortunate I was…and thank GOD for my prolonged, 9 month “morning sickness”.

  • Mara

    I had a great Aunt who’s mother recived thalidomide shots during her pregnancy. Her baby was born and never grew up (she couldn’t walk,talk, eat, or go to the bathroom by herself) she looked older but never got bigger then a 8 month old, she died at the age of 40 in the late 90′s. I have been looking through websites and it looks like none of the effects of thalidomide caused that certain birth defect. I want to know if her birth defect was actually caused by thalidomide.

  • Ed

    I was born missing my right arm. It only goes to my elbow. It was 1970 and this was a well known problem with Thalidomide but for some unexplained reason, my mothers doctor gave her this medicine to fight nausea. It is a shame that one person had such a decision in my life. I grew up self conscious, mental suffering, bullying, felt angry towards everything. But as I grew up and matured, I have taken it for what it is. I play all sports, drive, ride dirt bikes, shoot, everything that “normal” people do. I have a beautiful wife of 18 years and two healthy beautiful kids. I wish there was a lawyer that I could have sued that dr.

  • http://www.facebook.com/people/William-Mount/100002350322308 William Mount

    Tge actual numbers effected actually may range in the hundreds of thousands.

    Undrmer developed kidneys, liver lobes, Pancreas are just a few results I have encountered here in America.

    Last count over a milliin people here in America were orescribed this toxic drug, and the Big Pharma prescribed it knowing the effects.

    Dr William B. Mount

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