A Tale from the Sea to Ara C

. . . what sponges have to do with saving the lives of children with ALL

The year was 1945. A young organic chemist named Werner Bergmann collected sponges in the shallow waters off Elliot Key, Florida, and on close examination, found that they belonged to a theretofore unidentified species. [1,2] A few years later, Bergmann and the "eminent taxonomist Dr. M. W. de Laubenfels" found more of the same species of sponge in the waters off Bimini Islands in the Bahamas. Dr. de Laubenfels named the sponges Cryptotethia crypta. Bergmann took the sponges back to his lab.

The Cryptotethia crypta were put into boiling acetone in an apparatus called a Soxhlet extractor. At the time, Bergmann was studying sterols, a sub-class of steroids. (Cholesterol, for instance, is a sterol.) He did not expect it, but a "rather copious amount of a nicely crystalline material" separated from the boiling acetone. Crystals - nothing like great crystals to get an organic chemist jumping up and down and then on the move to figure out what new compound they have isolated.

So began the saga that resulted in one component in a mixture of drugs for the treatment for childhood acute lymphoblastic leukemia (ALL). In 2005, this drug is still in use in ALL treatment. This past decade has seen a resurgence of interest in drugs from the sea, and new drugs inspired by Cryptotethia crypta have entered the chemotherapy pipeline. But for now, let's get back to Bergmann.

Werner Bergmann characterizes the new compound

Bergmann determined that the pure crystalline material was not a sterol, since sterols consist solely of carbon, hydrogen, and oxygen and have a characteristic ring backbone. Analysis showed that the new compound contained nitrogen, was optically active, and exhibited an ultraviolet (UV) absorption spectrum that was similar to that of thymidine, a nucleotide (see below). Other studies on the molecule verified that it was similar to but not thymidine. Bergmann named this new compound spongothymidine in honor of the sponges from which it was isolated.

Over the next several years Bergmann and his group continued to study the sponge extracts. [3] They identified another compound that they named spongouridine. They determined the chemical structures and the scientific names of each compound:

spongothymidine is "3-beta-D-arabofuranosylthymine"

spongouridine is "3-beta-D-arabofuranosyluracil"

I am somewhat reverent of the work and perseverance of mid-twentieth organic chemists like Bergman. They did not have the spectroscopic instruments of today's chemists: IR, GC MS, and NMR, the computer-interfaced tools of the organic chemist (more on this on my organic chemistry web site). Still, Bergmann's group was able to correctly identify spongothymidine and spongouridine. They were excellent and dedicated chemists.

At the time of this discovery, thymidine was known to be a nucleoside, a building block of DNA (more on this in section two). Spongothymidine was just slightly different from thymidine: there is a hydroxyl (-OH, alcohol) group instead of a hydrogen (-H) in the molecule, and that makes all the difference between thymidine and spongothymidine. Bear with me for a short chemistry lesson in the next section - it's the only way to really explain this difference.

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