This case study, contributed by the Cornell Center for Teaching Excellence, is intended to show that two enantiomers can have different effects on the body, and how the same drug can be used to treat different diseases or symptoms. It is also intended to help students begin to understand the process of FDA approval for drugs. This problem could be used in an organic chemistry class or in a class for non-science majors.
Here is the case study text:
You and your friend are enjoying some food at the local pizza parlor, and you begin to talk about the chemistry exam that you have coming up. Your friend, knowing that you are taking chemistry and biology classes, starts asking you about thalidomide.
Friend: “Hey, you know some stuff about biology and chemistry, right? So have you ever heard of thalidomide?”
Even though you don’t know much about it, you do recall your chemistry teacher mentioning something about it in class earlier in the day. She told you that it caused birth defects in the developing fetus.
You: “Yeah, I think that it’s a teratogen. There were some babies born in Europe and Canada that had missing or shortened limbs in the 1960’s. It was prescribed to pregnant women, and if they took it in the first few months of the pregnancy, they had a much higher risk of having babies with these birth defects.”
Friend (looking somewhat shocked): “What!? My Aunt Pat was told to consider taking it by her doctor. She was talking to us about it at dinner the other night ‘cuz she isn’t sure if she is going to take it or not! It seems awful, is this doctor crazy?”
You: “I wonder why anyone would think of prescribing something that if it causes all those problems? Why does she need to take it?”
Friend: “Well, she has a pretty bad case of leprosy. None of the other treatments that she has tried have worked. She’s in a lot of pain, her doctor said that this might help her. It’s the only thing they haven’t tried and they seem to think it will help.”
You: “You know, now that you mention it, I think I remember being told that people are looking thalidomide for treating other diseases, even cancer. I guess once you have a drug, you just keep looking for diseases that it can help cure. Is your aunt planning on having any kids?”
Friend: “Not right now, she is on birth control right now. Her doctor told her she needed to stay on it while she was taking thalidomide. I guess I know why now.”
You: “You know, I remember my professor telling us about the woman in charge at the Food and Drug Administration who refused to let it be sold in the US because there hadn’t been enough testing done on what the side effects of taking thalidomide were. I wonder how it can be prescribed now?”
Friend: “I don’t know, but there must be a good reason to be taking it, right? Otherwise the FDA wouldn’t let it be used at all. How does the FDA decide what drugs are good and which are bad? How do they even know what the drugs do?”
You finish up your pizza and that night in your room you decide to look up some information on thalidomide. Would you recommend to Aunt Pat that she take thalidomide? What factors would affect your decision? What if Aunt Pat was Uncle Pat? Would that change your recommendation at all?
Here are some things to consider…
1) This is the structure of thalidomide:
2) Is this molecule chiral? If so, circle the asymmetric carbon.
3) Draw any isomers of it (look carefully at the structure)?
4) If there are isomers, do you think that they have the same effects on the body? Why or why not?
5) If you were Aunt Pat, would you take the thalidomide? What your decision be different if you were Uncle Pat?
6) Do you see anywhere in the molecule where there might be resonance? (electron movement?)
----Questions for further thought ----
7) What was thalidomide originally prescribed for?
8) Thalidomide is being used as a leprosy drug. What is leprosy and what causes it?
9) How does thalidomide work? (This is not known for sure, but people have been speculating.)
10) What is the FDA’s procedure for approving drugs for clinical use?
11) If the FDA (who was in charge of determining if this drug should be used in the US?) banned its use, why can we use it now?
Isn’t it odd how a drug that could be so devastating in some cases can be life-saving in other cases? This is why clinical trials with the FDA take so long. A lot of research goes into how a drug will affect our bodies long before human trials are even started.
This activity was contributed by Cornell University.