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Excerpts from "Starting with Serotonin"[Dr. Sjoerdsma’s quotations appear in italics.]

 
 

Prologue, “The Probability of the Improbable”:

Once engaged in the process of medical-scientific experimentation, Al Sjoerdsma says, “things start to pop.” Sometimes the pop is the end-result, but more often, it is a lead that the researcher must pursue and parlay into the next. When the next step is not readily apparent, it sometimes takes contrary thinking—examining data with an eye toward disbelief and improbabilities, not easy conclusions—before research can continue.

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Chapter four, “The Carcinoid Breakthrough and Big-Time Stuff”:

[I]n the spring of 1955, [Sjoerdsma] presented M.C.’s and several other carcinoid patients’ cases at the clinical meetings in Atlantic City. In ten precious minutes, he abstracted his research, and his life changed forever.

This was gut’s ball. It was difficult to even get on the program.

The eagerly anticipated clinical meetings, held annually in May, showcased the crème de la crème in medical research circles, nationally. Three professional societies participated, but it was the American Society for Clinical Investigation (ASCI), whose members were called the Young Turks, that ruled the roost. . . .

Between 1945 and 1955, the number of U.S. physicians trained in clinical investigation increased tenfold. To accommodate growing audiences in Atlantic City, the Young Turks moved in 1951 from the intimate confines of the Haddon Hall Hotel to the Steel Pier Theater, an auditorium that seated more than a thousand. This would be Sjoerdsma’s debut stage. At thirty, he was not yet an ASCI member, so Young Turk, Jim Shannon—who, within months, would be director of the NIH—sponsored him.

I spoke the same day as Jonas Salk. . . . He had a larger audience.

But Salk, a long-winded speaker inclined toward pomposity, had no more confidence. Self-assuredly, Sjoerdsma detailed his research discoveries: the oxidative deamination of serotonin by monoamine oxidase; the clinical and biochemical features of the Malignant Carcinoid Syndrome; and the simplified color diagnostic test for metastatic carcinoid, the 5-HIAA assay.

These were major clinical breakthroughs, he said, “big-time stuff.”

As soon as the question-and-answer portion of his talk began, the Steel Pier audience besieged the young clinician with patient referrals. The National Heart Institute became a Mecca for carcinoid patients, and Sjoerdsma never looked back.

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Chapter seven, “The Journey to Aldomet®”:

Although chemists at the National Heart Institute did not synthesize methyldopa [Aldomet®], Sjoerdsma essentially designed it, or, at least, recognized, rationally, how a compound like methyldopa could act against high blood pressure.

Methyldopa fit into our philosophy of experimenting with the enzymology of pressor amines, using hypertensive patients as our subjects. If something happened to their blood pressure, we were going to see it. The discovery of methyldopa’s therapeutic effect was not serendipitous. But it was unexpected.

The discovery “could only have been made,” John Oates said, “[because] the laboratory, under Al’s direction, had invested very heavily into developing means of studying, in a quantitative way, the biosynthesis and metabolism of aromatic amines in humans.” 

Even before Oates and Gillespie gave patients doses of methyldopa large enough to produce a pressure-lowering effect, Sjoerdsma had to reject conventional medical wisdom and confidently assert his belief that, because of striking differences in response between humans and other species, the drug’s data in animals were misleading. He had to defy Merck scientists and their internationally recognized expert consultants, and, with Udenfriend, fight to resurrect a dead compound.

Max Tischler was smart to supply us with the compound. We just wanted to study biochemistry. After methyldopa, we were a force to reckon with.

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Chapter thirteen, “The Father and Sons of Clinical Pharmacology”:

In November 1965, forty-one-year-old Al Sjoerdsma appeared on the cover of Medical World News. Dressed in standard-issue white, the chief stood beside a patient’s bed, holding a hypodermic shot. The headline trumpeted a “New Breed at the Bedside.” The hyperkinetic kid who capsized outdoor privies had arrived. . . .

According to the article, fewer than sixty clinical pharmacologists practiced in the United States, and Sjoerdsma’s Experimental Therapeutics branch was “the largest clinical pharmacology unit in the world.” The reporter described a clinical pharmacologist as a “man of many parts,” elaborating:

“Above all, he is a skilled clinician who attends patients every day. He is also, in equal measure, part research biochemist, geneticist, molecular biologist or physiologist, a biometrician, a consultant, an expert in specific diseases, and, more often than not, a teacher of medicine and of new clinical pharmacologists. He is not an old-fashioned empirical drug tester, but a scientist who both designs the clinical trials of new drugs by other doctors and conducts drug tests in patients himself. He is, in sum, a major bridge between the worlds of basic biological science and clinical practice.”

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Chapter twenty-three, “Hip, Hip, Hurray! The Seldane® Breakthrough”:

For three or four years in a row at our quarterly research administration meetings with Gorigin, in Cincinnati and sometimes in Strasbourg, Murray Weiner would report on Seldane. He couldn’t prove the efficacy, but he would swear to God it worked. He was studying it against seasonal allergic rhinitis in like a six-day study of drug versus placebo. He would measure things like tearing and nasal congestion.

The problem was Murray was getting a very high-percent response with placebo. About 50 to 60 percent of people on placebo improved, and maybe the drug would be 70 percent. These were just placebo responders. Finally, when I became the senior person, and everyone reported to me, I said, “To hell with this.” I stopped the studies in the U.S., and I moved Seldane to Europe, to guys I trusted, namely John Burke. I put it in the hands of people who I thought would get me an answer. . . .

The company was ready to dump the drug, and Murray kept saying, “I know it works.” But he couldn’t prove it. He couldn’t get a clearcut drug effect. . . . I saved that one from getting thrown in the ashcan.

It would be a billion-dollar rescue.

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Chapter twenty-six, “The Resurrection Drug”:

[Dr. Simon] Van Nieuwenhove flew safely, with his precious stash, back into civil war-torn southern Sudan, retrieved his hidden Land Rover, and traveled the roadless terrain to his makeshift hospital. In July 1981, the full-bearded doctor, described by [Dr. Paul] Schechter “as a cross between a lumberjack and a cowboy,” served the first DFMO cocktail to a patient dying from advanced T. b. gambiense trypanosomiasis. He mixed the powdered drug with fruit juice in a sterilized Gordon’s gin bottle, the only container he had available.

DFMO knocked out the parasites.

People were living, rather than dying.

Soon the bush doctor would initiate DFMO trials in trypanosomiasis, which flourished, in part, because of the Dow [Chemical] merger.

“The businesspeople had their hands full,” Sjoerdsma said. This Third World investment eluded corporate radar.

I was in close contact with Paul on everything that was going on in treating trypanosomiasis. If I’d have gone to the business and said, “Look, are you guys interested in African trypanosomiasis?” the answer would have been no, because it’s a lost cause from a profit point of view. I never filled [the CEO] in very much with trypanosomes because there wasn’t any business aspect to it. . . . [He] knew at some point, but I can’t say when. He just let me go.

Confident in DFMO’s safety, Sjoerdsma and Schechter sidestepped customs and any other regulatory requirements to deliver it to the sick. We went right to Africa. We smuggled it. Absolutely.

To read the updated special report, “AT LAST, DFMO MOVES TO THE FRONT OF THE LINE,” click here.

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