You cannot fit your left glove onto your right hand, nor the right glove on the left hand, because hands and gloves possess a property called chirality; each object cannot be superimposed on its mirror image. The same is true of your feet and your shoes, and the phenomenon applies to many organic compounds –chemicals whose molecules are based on carbon atoms. Organic compounds include limonene, the chemical that gives lemons and oranges their citric taste and smell –but this means limonene is only in what chemists call its R enantiomer, one of the two mirror image forms in which limonene molecules can exist. The opposite mirror image form, known as S-limonene provides a minty, pungent taste in foods that contain it. Similarly, biological catalysts known as enzymes locate and attach to building blocks of proteins, known as amino acids, drawing them close together into chains. But this works because each enzyme has a particular 3-dimensional shape that allows it to bind only to left-handed amino acids. The same enzymes will not recognize right handed amino acids, the mirror image forms of the amino acids that our cells need.
Organic molecules also include medications, which also have R and S forms which can have very different effects in the body. This is the case with drugs that you may have heard of under the trade names Prilosec™ and Nexium™. Known generically as omeprazole, this drug was patented as Nexium™ and as the S form of a molecule, without the R form, whereas Prilosec is a racemic mixture, a combination of both the R and S molecules. There is evidence that esomeprazole (S-omeprazole spelled out) is more effective than omeprazole in people suffering from gastroesophageal reflux disease (GERD), but there is also talk that perhaps the drug company that makes Nexium™ has exaggerated these benefits.
The chirality phenomenon also applies to a drug called thalidomide. In the late 1950s, thalidomide was marketed in Europe as a sedative and anti-nausea drug, particularly good for pregnant women. It was called a “miracle drug” because research and clinical trials showed that it worked really well… and it actually did. It turns out that R-thalidomide, one of the two mirror image forms of the molecule, is effective as a sedative, an anti-anxiety drug, an anti-cancer drug, a drug against leprosy, and a drug against the terrible nausea that often strikes pregnant women. On top of all this, R-thalidomide produces only very minor side effects.
There was just one problem: S-thalidomide, the mirror image form of the molecule, turned out to be teratogen, an agent that causes birth defects. And because the differences in the effects of both forms of the molecule were not investigated carefully, and because it was cheaper to mass-produce the drug as a racemic mixture, S enantiomer of the molecule was included in the industrial product given to pregnant women. Because of the S form of the molecule, which deletes and shortens arms and legs in developing fetuses, many babies were born without appendages, or with shortened appendages.
Of course, the drug was taken off the market (read here the heroic story of Dr. Frances Kelsey, who protected American women from the thalidomide-induced birth defects). By the time that scientists figured out that the beneficial effects came only from the R form of the drug and that the birth defects came only from the S form of the drug, it was too late. Many people were growing up missing limbs, and the name thalidomide had just about the worse reputation that any drug could have.
Many years later, thalidomide was reintroduced to the health market, because it does work very well against leprosy, certain cancers, particularly a kind of cancer called multiple myeloma. For these conditions the pharmaceutical company Celgene now provides thalidomide. I am talking, of course, about R-thalidomide, which is what you are getting in pure form, if you buy the drug.
What is less known, even by some doctors, is that the same drug –R-thalidomide– is also an excellent, safe, sedative and anti-nausea drug that would be excellent to use during pregnancy, much better than the alternatives that are available today. There is no logical reason why the drug should not be approved for pregnancy use, but do you think that drug companies and governments will actually make R-thalidomide available to treat nausea of pregnancy any time soon?
Probably not, at least until they give the public a very good lesson in organic chemistry.