Skunkworks

Skunkworks+ defy easy analysis. Undoubtedly many more skunkworks went nowhere. By definition we’ll never know. Successful skunkworks make for compelling narrative: overcoming insurmountable odds, etc. But of course the hurdles themselves drive the passion and the commitment of the skunkworks denizens. There’s the thrill of the deceit and the secret handshakes. There’s the common bonds and language of team members as they conspire to overcome the devil in his bureaucratic incarnation. Institutionalize the skunkworks and you lose the thrill. You definitely start to see today’s hidden failures and start to understand why there’s much more to skunkworks that meets the eye.

Famous examples of successful skunkworks in the life sciences industry include (the first two are excerpted from Drug Discovery, Walter Sneader):

In the late 1800’s Arthur Eichengrün prepared a series of esters of phenolic compounds looking for a substitute for salicylic acid, then popular as an internal antiseptic, at a time when it was widely believed many diseases came from pathogenic bacteria in the gut. Felix Hoffmann was given the task of preparing the ester acetylsalicylic acid. Heinrich Dreser, the company pharmacologist in 1897, tested this compound and rejected it. Acting on his own initiative, Eichengrün tested the compound on himself and then arranged for it to be clandestinely evaluated by physicians in Berlin. Acetylsalicylic acid turned out not only to be a superior substitute for salicylic acid but also it had unexpectedly relieved pain in a patient with a toothache. The two colleagues went above Dreser and brought the results to the attention of Bayer management. Management marketed the drug under the proprietary name Aspirin®.

In 1955, chemists at Benger Laboratories in Cheshire synthesized potential bronchodilators, screening them against guinea pigs exposed to aerosols of egg white to induce asthmatic attacks. Altounyan, a physician working with the company, had reservations about the validity of these animal tests and took the unprecedented step of testing the compounds on himself by first inhaling guinea pig hair, which he knew would induce an asthmatic attack. He found compounds that for animals had no bronchodilating activity and afforded no protection, and yet somehow protected him from the effects of the guinea pig hair. Difficulties with the compounds led the company to abandon the project. Those working on the projected decided to continue investigations surreptitiously; Altounyan, the human guinea pig, was only able to test two compounds a week. In 1963 it was discovered one of the compounds had been contaminated with a highly active material – a bischromone. A series of bischromones were prepared for Altounyan to inhale, resulting in the asthma drug sodium cromoglycate (Intal).

Sankyo's brass was unenthusiastic about Dr. Endo’s discovery because there was no precedent for it. They preferred instead to develop refinements of existing cholesterol drugs. With only the support of his boss at the research labs, Dr. Endo embarked on a secret experiment at Osaka University. Dr. Endo recalls phoning the university hospital from home at night so colleagues wouldn’t learn about the experiment. He personally prepared the samples of the drug and carried them to Osaka. The result was compactin, one of the first cholesterol lowering drugs on the market. Insights from Dr. Endo's work led to Mevacor, and to the spectacular rise of the pharmaceutical firm Merck & Co.


Drug Discovery

Stalking Cholesterol - Feat of Japan's Dr. Endo

Editor's Picks for October, 2010

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