April

Although the Affordable Care Act dominated news from the Supreme Court last month, the decision in another case involving this molecule has special importance for clinical laboratories. Can you guess what it is?

6-mercaptopurine

6-mercaptopurine (6MP) and azathioprine (which is converted in the body into 6MP) are inhibitors of purine synthesis used to treat neoplastic disease (such as leukemia) as well as inflammatory disease (such as vasculitis). Prometheus ®, a commercial laboratory in California, patented the use of measurement of 6MP metabolites to guide therapy in inflammatory bowel disease, and sued Mayo Clinic Laboratories ® when they offered their own version of this test. The Supreme Court ruled that because Prometheus had not discovered the metabolites nor their relationship to drug levels, they could not patent these conventional activities. This decision may have significant impact as the field of "personalized medicine" develops and organizations attempt to patent the application of a "law of nature" to a specific clinical scenario.

March

A shortage of this molecule last month threatened the treatment of thousands of children with leukemia. Can you guess what it is?

Methotrexate

This folate antagonist (compare their structures) is used to treat a variety of disorders including acute lymphoblastic leukemia, the most common leukemia occurring in children. One of four U.S. companies producing the drug temporarily closed its manufacturing plant, causing a sudden shortage. The FDA had to quickly approve shipments of methotrexate from abroad. This incident exposed problems with the FDA's backlog of approvals for new applications to manufacture generic drugs of all kinds.

February

This molecule comes from a member of the chrysanthemum family and, although it tastes incredibly sweet, has zero calories. Can you guess what it is?

Rebaudioside A

Rebaudioside A (RebA) and stevioside are the two major glycosides of the diterpene steviol, found in the stevia plant (a member of the chrysanthemum family). Both have a glucose ester at the carbonyl atom (bottom of figure) and either two (stevioside) or three (Reb A) glucoses linked to the top of the molecule as an ester. These glycosides are hundreds of times sweeter than sucrose and are not absorbed. (They are metabolized by bacteria in the colon.) Reb A is marketed as "Truvia", the latest in a series of artificial sweeteners. We hope that your Valentine's Day was genuinely sweet.

January

Ryan Braun, baseball's 2011 National League Most Valuable Player, did not have enough of this molecule in his urine during a recent drug test. Can you guess what it is?

Epitestosterone

An inactive epimer of the androgen testosterone, epitestosterone differs only in the orientation of the hydrogen and hydroxyl at carbon position 17. Although its biological significance is unknown, it appears to be made along with testosterone by the testis at a ratio of 1:1. Measurement of the ratio of testosterone to epitestosterone by gas chromatography/mass spectrometry is the most commonly used method to determine whether there has been abuse of exogenous steroids by athletes. An elevated ratio (as found in Ryan Braun's case) indicates possible steroid doping. This test was the cause of Floyd Landis being stripped of the Tour de France title in 2007.