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.
"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.
|"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.
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
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
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 NIH career began in the
program in 1973. He eventually became NIDDK director.
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.
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
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.
|Charles S. “Charley” Carter
Jr. was a 24-year veteran of the Clinical Center’s department
of transfusion medicine.
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.