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Vol. LVIII, No. 9
May 5, 2006

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NIDDK Director Spiegel Moves To Academia

If ever a career reflected all the potential in the life of an NIH scientist, it was Dr. Allen M. Spiegel's. During 33 years of service, first as a fellow and clinical associate and finally as director of NIDDK, he never ceased being fascinated with the institution and its people, nor they with him.

"And the Oscar goes to . . ." Former NIDDK director Dr. Allen Spiegel's colleagues voted him the best man in a leading role at a farewell party recently.  
"Aside from my family, NIH has been the most important thing in my life," Spiegel says. "I've had fantastic colleagues at every level, and I leave with mixed emotions, knowing I'll miss close friends and colleagues at NIH." He left in March to become dean-designate of Albert Einstein College of Medicine of Yeshiva University in New York, where he will pursue his interests in fostering translational research and in medical education.

NIH director Dr. Elias Zerhouni tapped Spiegel for critical trans-NIH initiatives during his tenure as NIDDK director, and he will be sorely missed, according to the NIH head. "Allen Spiegel does whatever he does with grace, insight and an analytical mind. He has the highest degree of intellectual rigor and integrity of anyone I've met," Zerhouni told the crowd of colleagues gathered for Spiegel's recent farewell reception.

A replay of the events and mentors of Spiegel's scientific life reveals circles overlapping circles. When he assumes the deanship at Einstein, he will be completing a circle begun in 1962, when, as a junior at Yeshiva University High School for Boys, he fell in love with research during an Einstein summer program funded by the National Science Foundation. A second circle of influence began when, as a student at Columbia, Spiegel was mentored at NYU's medical school by researcher Mark Bitensky, who had just come to New York from an NIH lab.

"I was completely hooked on biochemical studies by then," Spiegel remembers. While a Harvard medical student, he published his first paper in 1969 in Endocrinology, on the efficacy of fragments of the hormone glucagon in stimulating formation of the second messenger cyclic AMP. The journal's associate editor then was Dr. Gerald Aurbach, an NIH scientist known for his seminal work on the role of cyclic AMP in the mechanism of action of parathyroid hormone (PTH).

After finishing his internship and residency at Massachusetts General Hospital, Spiegel interviewed for 2 days at NIH. Aurbach, "one of NIH's luminaries," says Spiegel, was a physician-investigator steeped in basic science who never lost sight of research's relationship to clinical medicine. Aurbach's Metabolic Diseases Branch (MDB) seemed a "perfect match" to Spiegel, and the basic research-clinical medicine alliance became a hallmark of Spiegel's career.

By day, he saw patients suffering from excess or deficient hormones on 8 West in the Clinical Center. By night, he worked with cyclic AMP assays in the MDB. "It was extraordinary to be a fellow at NIH in those days," Spiegel recalls. "You were working with giants — it's not a cliché at all — Gerry Aurbach, Phil Gorden, Marty Rodbell, Mort Lipsett, Jesse Roth."

"Allen was a total pleasure, so quick and bright. It was a mutual education to work with him," says Gorden, who preceded Spiegel as director of NIDDK. Spiegel came to NIH intending to leave in 2 years. "He was a super talented clinical associate," adds Gorden. "Fortunately, he decided to stay."

Spiegel's investigative career showed no less talent. He followed Aurbach's lead in parathyroid hormone studies and work done by Nobelist Martin Rodbell, who identified G proteins at the cell membrane level. G proteins are key molecules controlling transmission of information from outside to inside a cell. Increases or decreases in this signaling cause hormone overproduction or resistance.

Spiegel quickly became a leader in defining subtypes of G proteins and their role in pediatric diseases, says NIDDK colleague Bill Simonds. His first memory of Spiegel was seeing him poring over a tray of Western blots in Bldg. 36. Simonds notes that Spiegel cloned human Gs-alpha cDNA while collaborating with Nobelist Marshall Nirenberg. Fascinating stuff, but for Spiegel, bench discoveries always led to the bedside. "He had a real gift for bringing together clinical and basic science," says Simonds.

"Allen was among the first to use biochemical assays to look at red blood cell membranes from patients," says Lee Weinstein, whom Spiegel — then chief of the section on molecular pathophysiology — recruited in 1986. "In an incredibly lucid manner, he explained the whole field of G proteins in about 20 minutes," says Weinstein, who promptly signed on.

Spiegel’s NIH career began in the NIDDK intramural
program in 1973. He eventually became NIDDK director.
As his work in cell signaling advanced, so did his role in NIDDK's intramural program. He was appointed chief when the molecular pathophysiology section expanded to a branch in 1988. In 1990, Spiegel became scientific director of NIDDK. Colleagues found him a good leader not only because of his wide knowledge of science — "he has a gigantic memory," says longtime colleague Steve Marx — but also because of his ability to teach others what he had absorbed. The year 1991 marked a highlight of his career, the publication of a landmark paper on McCune-Albright syndrome in the New England Journal of Medicine. Children with the disease suffered from over-secretion of multiple hormones that brought about precocious puberty as well as disordered thyroid, adrenal and growth hormones. Spiegel and colleagues discovered that a malfunctioning G protein was causing the overproduction.

Spiegel's ability to deliver flawless lectures on complex scientific topics at the drop of a hat prompted Simonds to say that his friend seemed to talk in "pre-formed paragraphs that would come tumbling out." Marx, who collaborated with Spiegel on 160 papers, says that during the pursuit of the MEN1 gene, he was famous for giving the team "unscheduled 40-minute lectures synthesizing some new and complex related topic in the literature." These events led co-investigator Francis Collins to assert that those who know Allen only as an administrator have probably not had "the full Spiegel experience."

His penchant for encyclopedic knowledge and the ability to apply it creatively probably guaranteed that administrative duties would not diminish Spiegel's role as scientific investigator. "Allen is a multi-dimensional person," says Gorden. "He very quickly gained the respect of NIDDK intramural scientists and others at NIH." Colleagues found him an accessible leader who had not only intellect but also a sense of fairness and honesty they appreciated.

In addition to functioning as scientific director, Spiegel remained chief of the Metabolic Diseases Branch from 1993, and helped create a trans-NIH collaboration that identified the tumor suppressor gene for multiple endocrine neoplasia, type 1 (MEN1). "He played a central role in mobilizing clinical researchers to gather tumors and patient DNA to go after the gene," says Simonds. "He was like a general, marshaling forces." Spiegel recalls this success as "very satisfying," perhaps on more than one count. Marx says Spiegel saw MEN1 as a paradigm for excess secretion of PTH, harkening back to Aurbach's protocols. It was icing on the cake that the NIH team beat out a European consortium to find the gene.

In 1999, Spiegel scored another kind of coup when he recruited Allen Kirk and Dave Harlan to study islet and kidney transplantation in NIDDK's new Transplantation and Autoimmunity Branch. "I learned that one could accomplish as much or more by encouraging others as by being solely focused in the lab," he remembers.

Later that year, NIH director Dr. Harold Varmus appointed Spiegel director of NIDDK, and his outlook shifted to the beta cell, and broadened to include NIDDK's many constituencies, from children with type 1 diabetes to the country's lawmakers. "It's very poignant," he says, "to field questions about diabetes from children as young as two and half. You see the optimism and realize we need to go further." At the other end, he notes, is the chance to explain the importance of scientific research and its power to members of Congress, which many colleagues feel he has done brilliantly. "He's among the very best," says Dr. Richard Hodes, director of the National Institute on Aging, "not only on the scientific level, but in management. He has real vision, and it transcended NIDDK."

Zerhouni apparently thought so, too. With obesity spiraling out of control in the U.S., he tapped Spiegel to co-chair the NIH task force on obesity in 2003. Spiegel, with NHLBI director Dr. Claude Lenfant, developed a strategic plan for NIH obesity research in a little over a year. Zerhouni further gave Spiegel a key role in helping develop one of the NIH Roadmap initiatives, and relied on his expertise as a member of the NIH stem cell task force.

Now Spiegel's career circles back to Einstein and New York. "It's an extraordinary opportunity to invigorate the medical school and its programs, and Einstein's community, the Bronx, represents the whole spectrum of disease and health," he adds.

Spiegel believes that 21st century research requires an interdisciplinary approach including the computational, the quantitative and rigorous basic science with an understanding of biological systems. "Translation of basic science to systems knowledge must be applied to human health, for individual patients, but also in populations. There's a critical role for the NIH and other groups in this."

Spiegel served NIDDK as director for the past 6 years. He becomes dean of Albert Einstein College of Medicine on June 1.

Blood Bank's Carter Dies Suddenly

Charles S. "Charley" Carter Jr., 52, a 24-year veteran of the department of transfusion medicine in the Clinical Center, died of a heart attack Mar. 27 at home.

"Charley Carter was a big man by almost any measure, and he cast a giant shadow," said DTM chief Dr. Harvey Klein. "He was a wizard in the laboratory where he had an uncanny ability to commune with cells in culture and to solve the most vexing laboratory instrument problem."

Charles S. “Charley” Carter Jr. was a 24-year veteran of the Clinical Center’s department of transfusion medicine.  
Born in Olney, he attended Rockville High School and went on to earn a B.S. degree in microbiology at the University of Maryland. In 1978, he volunteered as a summer technician in the National Institute of Dental Research, which ignited an enduring interest in medical research. The following year he joined NIDR as an entry-level technician in the laboratory of Dr. J.J. Oppenheim. There he learned rigorous laboratory technique and a love of cell biology and clinical investigation.

In 1982, Carter joined DTM, where he later met his future wife, Laura, who was training as a specialist in medical technology.

"Charley was one of the original members of a small R&D team known as the Special Services Laboratory, which evolved over two decades into the cell processing section," said Klein. "Charley helped to build this laboratory into a central resource for NIH intramural investigators and one of the world's leading facilities for preparing novel biologics for clinical trials."

In 1990, Carter was part of a team that prepared the first therapeutic gene-corrected cells that were used to treat a child with severe combined immune deficiency disease, a feat that landed his picture on the November 1991 cover of U.S. News and World Report. "Charley's special genius lay in devising innovative methods for preparing novel cellular components suitable for clinical trials protocols, everything from engineered stem cell grafts to dendritic cells and pancreatic islet cells," Klein recalled. "Most of these skills were self-taught, although he learned from and improved upon the work of numerous colleagues at NIH, in academia and in industry. They invariably became lifelong friends and debate opponents."

Carter was a passionate fan of the Washington Redskins, the Baltimore Orioles and any University of Maryland athletic team; he died while watching the Maryland women's basketball team compete in the NCAA tournament. He was also a volunteer coach and played on a number of local softball teams.

Carter authored or co-authored more than 75 original publications. He also trained and educated a generation of technologists, scientists and regulators in good laboratory practices. He received numerous performance awards as well as the Clinical Center Director's Award and the NIH Director's Award.

He is survived by his wife Laura, daughter Katelyn, brothers Earl and John, and his mother Marjorie.

Freshman NIH Scientist Is Profiled For BET

Dr. Tshaka Cunningham, a health disparities postdoctoral fellow working at NCI, will be profiled by Black Entertainment Television for an upcoming episode of its news show, The Chop Up. A Silver Spring native, Cunningham has been conducting research in Dr. Jay Berzofsky's Vaccine Branch laboratory since February, when he returned from a 1-year immunology fellowship at the Pasteur Institute in France. The postdoc is no stranger to NIH or NCI. His grandmother, Alfreda DeGraff-Simmons, spent more than 30 years conducting small cell lung cancer research for an NCI study at Navy. Several other relatives have also made careers here. Cunningham, a graduate of Princeton and Rockefeller universities, did his Ph.D. work on two aspects of HIV infection — species- specific restriction factors and nuclear import of the virus. He says his interest in medical science was inspired in part by his grandmother's career, but also as a result of a couple of cancer deaths in his family. He hopes his interview with BET will "help other minority students look at research as a viable career and demystify the process." A weekly 60 Minutes-style news magazine, The Chop Up dissects current issues and events in a conversational tone aimed at young people. Cunningham's episode is scheduled to air sometime in May.

NIEHS's Stokes Honored By Toxicology Society

Public Health Service Capt. William Stokes, director of the Interagency Center for the Evaluation of Alternative Toxicological Methods, was honored at the 2006 annual Society of Toxicology meeting Mar. 5-9 in San Diego. He received the Enhancement of Animal Welfare Award for his contributions to the "marked reduction in the use of experimental animals for research." Stokes, PHS chief veterinarian, heads an interagency coordinating committee based at NIEHS that looks at ways to reduce the number of animals used in research.

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