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1/15/10 MARSHALL NIRENBERG, 1968 NOBEL LAUREATE, DIES

Marshall W. Nirenberg, the Nobel Prize-winning NIH biochemist who deciphered the human genetic code, died Jan. 15 of cancer. He was 82.

Dr. Albert Sjoerdsma, a longtime friend of Nirenberg and his late wife, Perola Zaltzman Nirenberg, described Nirenberg as “a kind man, a gentleman,” whom he was always pleased to see at NIH alumni gatherings.

“Marshall always greeted me warmly and enthusiastically,” Sjoerdsma said, “I suppose because I was a link to his wife, Perola, and the good old days.”

Born April 10, 1927, in New York, Marshall Warren Nirenberg received his undergraduate degrees in zoology and chemistry from the University of Florida and his Ph.D. in biological chemistry in 1957 from the University of Michigan. He joined the National Institutes of Health as a postdoctoral fellow and went on to spend his career at the flagship institutes in Bethesda, Md. He reached his peak, however, during the exciting, open-frontier years of the 1960s.

Ann Sjoerdsma contacted Nirenberg at his NIH office early in 2008, to ask him if he would read a review copy of “Starting with Serotonin” and comment for the back jacket. He graciously complied, writing:

“Starting with Serotonin” . . . “is an exciting account of scientific and clinical discoveries by the blunt, tough-talking, iconoclastic Al Sjoerdsma and his colleagues. His daughter brings to life the ideas and personalities behind the experiences, [in particular] catching the flavor of the NIH in the late 1950s and early 1960s. . . . This is a wonderful book.”

Said Ann: “He couldn’t have been more generous and responsive to my request. I’m saddened by his death.”

In addition to the 1968 Nobel prize, Nirenberg received the National Medal of Science in 1966 and the National Medal of Honor in 1968. His wife, Perola Zaltzman, a chemist from Brazil, was an exceptional bioassayist in Sjoerdsma’s Experimental Therapeutics Branch of the National Heart Institute in the ’60s—until biochemist Sidney Udenfriend, Sjoerdsma’s basic-scientist partner, “stole her from me,” Sjoerdsma said.

Perola Zaltzman-Nirenberg died in 2001 after years of suffering from Alzheimer’s disease. Nirenberg is survived by his second wife and four stepchildren.

The following is an excerpt about the Nirenbergs from chapter 16 of “Starting with Serotonin,” pp. 250-51:

§ . . . In 1966, Marshall W. Nirenberg cracked the genetic code in Sid’s lab—where the inconspicuous biochemist unexpectedly landed on the rebound.

Marshall was self-effacing and modest. He was all science, boy, a real dreamer. [Quote by Albert Sjoerdsma]

Herb Weissbach, who had shifted his focus to protein synthesis after a sabbatical at the University of California-Berkeley in the late 1950s, could not have been more pleased. According to Weissbach, Nirenberg, who headed a biochemical genetics section in another institute, was preparing to leave Bethesda when his wife, lab technician Perola Zaltzman, “came in to Sid, crying one day, ‘Marshall doesn’t have the space he needs. He’s going to need to go to [the University of] Michigan.’

“Sid didn’t want to lose Perola,” Weissbach said. “I don’t think he was that interested in Marshall. . . . So he called us all in and said, ‘Listen, if we all cut our space in half—there were four of us then, Gordon Guroff and John Pisano, and Udenfriend and myself—we’ll have enough space for Marshall.’ We said, ‘Fine, no problem.’”

Sjoerdsma and Udenfriend spoke to [Heart Institute research director Robert] Berliner about accommodating the under-appreciated Nirenberg, and he moved into Sid’s lab, next to Weissbach, who went on “a sabbatical,” without leaving town. “Marshall changed my whole life,” he said. 

In 1959, Nirenberg had shown that ribonucleic acid, the messenger to deoxyribonucleic acid, is needed for protein synthesis. He later used synthetic RNA to deduce the chemical codes for nearly all amino acids that make up protein. Nirenberg received the 1968 Nobel Prize in Physiology or Medicine with two other U.S. biochemists who contributed to deciphering the cell’s molecular structure, the ABCs of heredity. The dreamer was just forty-one.4

“Cells will be programmed with synthetic messages within twenty-five years,” Nirenberg correctly predicted at the time. “Man may program his own cells long before he will be able to formulate goals and long before he can resolve the ethical and moral problems which will then be raised.”5

4) The other two Nobel recipients were Robert W. Holley, forty-six, of Cornell University, and India-born Har Glorind Kharana, forty-six, of the University of Wisconsin at Madison. See Victor Cohn, “3 U.S. Scientists Split Nobel Prize,” The Washington Post, Oct. 17, 1968, p. A1.

5) Ibid, A10. §

According to Sjoerdsma, his longtime NIH secretary, Marceline Lee, worked for Nirenberg after Sjoerdsma left the National Heart Institute in the 1970s. Lee told her former boss that she had never encountered anyone as disorganized as Nirenberg, describing him as the stereotypical absent-minded genius scientist. Once, Lee said, Nirenberg arrived at a conference in Copenhagen, for which he was scheduled to speak and Lee had booked timely airplane fare, on the day after the event occurred.

“He simply got on a plane and came home,” Sjoerdsma said, laughing.  

A detailed obituary of Marshall W. Nirenberg appeared in The Washington Post on Jan. 18, 2010, p. B4. He will be missed by all who had the pleasure to know his great intellect, his kindly manner, and his other-worldly character. He was a visionary. 

8/21/09 FDA APPROVES VIGABATRIN FOR SPASMS, EPILEPSY

The FDA has approved vigabatrin (Sabril®), the antiepileptic designed and developed in Dr. Albert Sjoerdsma’s Strasbourg, France, research center in the 1970s-’80s, for treatment of infantile spasms in children ages one month to two years and for use by adults who suffer from complex partial seizures that have not responded adequately to previous drug therapies. (See the 1/9/09 News item for background details.)

Sabril Oral Solution is the first drug in the United States approved to treat infantile spasms, a devastating seizure disorder that typically manifests in infants between the ages of four and eight months. According to the FDA: “Infantile spasms consist primarily of a sudden bending forward of the body with stiffening of the arms and legs; some children arch their backs as they extend their arms and legs. Spasms tend to occur upon awakening or after feeding, and often occur in clusters of up to 100 spasms. Infants may have dozens of clusters and several hundred spasms per day.”*

A tablet form of Sabril will be available for use by adults in combination with other medications to treat intractable epilepsy.

Because of the risk of vision damage, the drug will be distributed with a box warning alerting physicians to the potential for progressive loss of peripheral vision, and patients will be required to undergo periodic vision testing. Sabril, designated by the FDA as an orphan drug, will be administered only through a restricted distribution program.

Sabril’s manufacturer is Lundbeck Inc., a Denmark company that acquired Ovation Pharmaceuticals of Deerfield, Ill., earlier this year. Lundbeck plans to launch Sabril during the third quarter of 2009.

*See http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm179855.htm

AwardMAY 2009 "STARTING WITH SEROTONIN" WINS DOUBLE GOLD AND MORE IN NATIONAL INDIE BOOK AWARD CONTESTS

SjoerdsmaAnn Sjoerdsma's wondrous book about her pioneering father has received two gold medals and twice placed as a finalist in several 2009 national independent book award competitions, whose results were announced this month.

"Starting with Serotonin" won a gold medal for biography in the Independent Publisher Book Awards, which are known as IPPYs and sponsored by Independent Publisher magazine and the Jennings Publishing Group and a gold medal for science in the Next Generation Indie Book Awards. The book also placed as a finalist in the biography category of the Indie Book Awards and a finalist in the medical category of the National Indie Excellence Awards.

Judges in these contests evaluated thousands of entries from small publishers and academic presses nationwide, and we could not be more pleased about the honors they gave "Starting with Serotonin." Congratulations to our deserving author and her history-making subject.

1/9/09 VIGABATRIN GAINS FDA COMMITTEE APPROVAL

The U.S. Food and Drug Administration’s Peripheral and Central Nervous System Drugs Advisory Committee unanimously recommended on Jan. 7-8 that vigabatrin (Sabril®) be approved as both an adjunctive treatment for adults with refractory complex partial seizures and a monotherapy for infantile spasms. Vigabatrin irreversibly inhibits the enzyme, GABA-transaminase. Drs. Brian Metcalf and Michel Jung designed and synthesized the antiepileptic compound thirty years ago under Dr. Albert Sjoerdsma’s direction at the Merrell institute in Strasbourg, France. (See “Starting with Serotonin” for all of the fascinating details.)

The committee’s endorsement came in response to two New Drug Applications filed by Ovation Pharmaceuticals of Deerfield, Ill., which acquired North American rights to vigabatrin from Sanofi-Aventis, the successor, after multiple mergers, to drugs that came out of Sjoerdsma’s operation. Vigabatrin is already on the market as Sabril® in at least fifty other countries.

There are currently no FDA-approved drugs for infantile spasms, a severely debilitating condition also known as West syndrome. Besides recommending vigabatrin’s approval for this indication, 23-0, the FDA committee voted, 25-0, that Ovation, despite limited data, had provided substantial evidence of its efficacy. It further recommended that Ovation conduct a post-marketing study to determine the appropriate duration of vigabatrin treatment for infantile spasms.

Long-term use of vigabatrin has reportedly been associated with a loss in peripheral field vision in some patients. Besides endorsing vigabatrin’s adjunctive use in refractory epilepsy, 24-0, the FDA panel also voted 14-7, with three abstentions, that Ovation had proved that a visual loss could be detected before it is clinically meaningful, but not that discontinuation of vigabatrin would halt progression of the loss. The panel generally agreed with the risk evaluation and mitigation strategy (REMS) proposed by Ovation, which would require patients who receive vigabatrin to have periodic ophthalmologic monitoring.

Briefing documents for the Peripheral and Central Nervous System Drugs Advisory Committee’s Jan. 7-8, 2009, meeting about the vigabatrin NDAs are available online at http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4396b1-00-FDA-index.htm. For background on Ovation, its NDAs, and the FDA’s previous actions, see the News Archive for 10/26/08, 7/30/08, and 7/10/08.

2008 BEST BOOKS AWARDBook Award Ribbon

“Starting with Serotonin” earned honors as a finalist in both biography categories (general and historical) of USABookNews.com’s national “Best Book 2008” contest, which is open to print and audio books from mainstream and independent publishing houses. To find out more about the awards, see http://www.USABookNews.com.

 

FOR THE SPECIAL REPORT, “AT LAST, DFMO MOVES TO THE FRONT OF THE LINE,” click here.

To read older news items, including a tribute to Dr. Victor A. McKusick, click here.

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