Greetings. I have a few questions that I hope an obstetrician or medical researcher might be able to answer.
Recently I was reading about the drug thalidomide — an unwitting cause of many birth defects in the early 1960s, when the drug’s danger to fetuses were not yet known. For me this raised some historical and procedural questions that further reading hasn’t yet addressed:
[ol]
[li]Why, specifically, weren’t thalidomide’s effects noticed before it was approved for general use? Were pregnant mammals, the usual rats and monkeys, not tested?[/li]
[li]Or alternatively, does the drug cause birth defects only in humans — hence the rude surprise after its release? (And if that’s the case, I’d be curious to know what quirk of human physiology separates us from other mammals, in this one area anyway.)[/li]
[li]Did the thalidomide scare result in a change in the mechanics or standards of drug studies, either in the US or elsewhere? This FDA page, for example, says merely that it “aroused public support for stronger drug regulation”, but doesn’t say whether that actually amounted to anything.[/li][/ol]
This whole subject is a bit disturbing I realize, but thanks go to anyone who can answer some of these questions.
My understanding was that they tested in some animals overseas and determined that the drug was stopped at the placental barrier, but they didn’t test in other animals.The drug was approved in Europe, but the FDA resisted in the US because of questions about the testing, despite pressure from the European drug manufacturer. Some samples did make it the US, however.
After human birth defects started showing up, they did tests on rabbits, which hadn’t been done before, and found that the drud did pass the placenta barrier. It was yanked off the market. Recently, thalidomide has been making a comeback, although everyone insists it be kept away from pregnant women.
This is fronm my recollections, combined with the story as told in Paradox Press’ "graphic novel(?) The Big Book of Bad.
Thalidomide was one of a number of scandals that threw light onto procedures and protocols surrounding animal testing. In the 60s and 70s the FDA (and later EPA) dramatically tightened the rules on what until then had been actually a sort of slipshod practice. Improved regulations and better methods of testing (including equipment that can measure infinitesimally small traces of chemicals) have led to the banning or stricter controls on the use of many drugs and chemicals.
It appears that thalidomide has only one stereocentre, meaning that there are two versions of the drug depending on how the atoms are oriented around this single carbon atom. It looks like the R enantiomer is “safe” and produces the desired results, while the S enantiomer is the one that causes the birth defects by breaking in half and producing two embryotoxic and tetragenic compounds.
Delivering only the R enantiomer to the patient could theoretically obtain the wanted results while avoiding defects, but the R and S enantiomers are easily interconverted inside the body. So any dose of R only would eventually become R and S. Assuming this is true, the separation of the two is not very easily or inexpensively accomplished, since their differences are very very subtle.