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THE SCIENTIST
VOLUME 8, No:20 OCTOBER 17, 1994
(Copyright, The Scientist, Inc.)
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TI : CONTENTS
PG : 3
============================================================
BEHAVIORAL CHALLENGE: The search is narrowing for a director
of the National Institutes of Health's new Office of
Behavioral and Social Sciences Research. Social and
behavioral scientists who have fought long and hard to raise
the status of their disciplines at NIH say the new director
will need to be strong and creative to combat the prevailing
laboratory sciences culture at the agency--including, they
say, the bias of NIH director Harold Varmus
PG : 1
CANCER SCIENCE A VICTIM: Cancer research institutions are
facing an increasingly difficult battle to maintain their
high standards of scientific research in the face of
diminishing federal funding. They are especially falling
victim to the congressional budgetary practice of earmarking
monies for specific high-profile diseases
PG : 1
MORE FOR AGING: Despite a recent infusion of support for
gerontological studies, ambitious investigators of aging-
associated phenomena continue to lament that their field is
underfunded
PG : 1
LASKER WINNERS: The Lasker Foundation's medical research
awards have been bestowed this year upon three investigators
who exemplify "persistence and tenacity, intuition and
intelligence"
PG : 1
NEUROSCIENCE MEETING: The 24th annual meeting of the Society
for Neuroscience, to be held in Miami Beach, is likely to be
largest conference in the society's history, officials say
PG : 3
BIOETHICAL PERSPECTIVES: Arthur Caplan, the nation's
preeminent bioethicist, recently moved his base of
operations from the University of Minnesota to the
University of Pennsylvania, where he has established the
Center for Bioethics. In a candid interview with The
Scientist, Caplan discusses the increasing importance of his
discipline and the ambitious plans he has for the center
PG : 12
COMMENTARY: Science sociologist and historian Robert K.
Merton, now in the 85th year of a notably productive life,
was recently named winner of the National Medal of Science.
In this essay, publisher Eugene Garfield reminisces about
his long relationship with the eminent scholar, noting the
significance of Merton's contributions and urging all
scientists to become acquainted with his work
PG : 13
MATURING FIELD: Like its baby boomer subjects, the branch of
biomedical science that explores the effects of aging is
visibly maturing
PG : 14
HOT PAPERS: Developmental biologist Michael A. Rudnicki
discusses his studies of the functions of myogenic
regulatory factors; astrophysicist Georges Meynet reports on
new grids of stellar models
PG : 16
SEQUENTIAL IMPROVEMENTS: Rapidly advancing DNA-sequencing
technology offers increased speed, power, and sensitivity
PG : 17
INTERVIEW SKILLS: In the second installment of a three-part
excerpt from his book A Ph.D. Is Not Enough!, physicist
Peter J. Feibelman advises those interviewing for a job to
look at the situation from the prospective employer's
viewpoint and prepare accordingly
PG : 23
STEPHEN J. BENKOVIC, a chemistry professor at the
Pennsylvania State University, has received the American
Chemical Society's Alfred Bader Award in Bioinorganic and
Bioorganic Chemistry
PG : 24
NOTEBOOK PG : 4
CARTOON PG : 4
LEADERS OF PG : 10
SCIENCE
LETTERS PG : 13
DNA SEQUENCING DIRECTORY PG : 21
NEW PRODUCTS PG : 22
CROSSWORD PG : 24
(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
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TI : Behavioral Scientists See New NIH Status Enriching
Biomedical Studies
AU : Franklin Hoke
TY : NEWS
PG : 1
A search committee will stop accepting applications for the
directorship of the newly chartered Office of Behavioral and
Social Sciences Research (OBSSR) at the National Institutes
of Health this week. The deadline's passing sets the stage
for the appointment, by year's end, of a leader whose task
will be to effective- ly integrate behavioral and social
sciences research into the traditional biomedical
investigations for which NIH is better known.
Advocates who have long struggled to raise the stature of
these disciplines at NIH succeeded through pressure and
persuasion in getting Congress to write the new office into
the health agency's fiscal 1994 authorization. Now, they say
that if a strong first director is named, OBSSR should be
able to promote in-novative, interdisciplinary re- search
that will significantly extend understandings of basic
processes in disease and health.
Some of these observers voice concerns, however, that OBSSR
may not be easily incorporated into the laboratory sciences
culture that prevails at NIH. The office's most important
potential ally, NIH director Harold Varmus, has expressed,
at best, lukewarm support for the behavioral and social
sciences, they say.
Although the new OBSSR director will have a high profile--
the position will carry the additional title of associate
director of NIH and will reside within the NIH director's
office--how the office fares will depend, in part, on the
welcome it receives from Varmus.
The search committee is expected to forward a short list of
candidates to Varmus by late November or early December; the
NIH chief will then make the final selection, pending
approval of Public Health Service head Philip Lee. Once
installed, the new office's chief will begin the challenging
task of coordinating with various NIH institutes to promote
research linking behavioral and social factors to health and
disease.
Scientists believe that the office's initial funding of
about $2.5 million will probably not be enough to grant
research awards directly. They expect, however, that the
amount should be adequate to sponsor conferences, workshops,
and other projects to catalyze important new scientific
investigations, both within and outside NIH.
"So many of the diseases facing us involve behavioral
patterns participating in their pathogenesis or
perpetuation," says Ira B. Black, chairman of the department
of neuroscience and cell biology at the University of
Medicine and Dentistry of New Jersey at the Robert Wood
Johnson Medical School in Piscataway. Black, a past
president of the Society for Neuroscience, Washington, D.C.,
was also a member of the Institute of Medicine committee
that produced the report AIDS and Behavior: An Integrated
Approach (Washington, National Academy Press, 1994).
"There's an extraordinary need for the behavioral sciences
to crosstalk more effectively with what we might call the
biological sciences--even though those very distinctions
that I'm drawing are artificial. If this office can
contribute to that kind of interaction, it will be
successful."
Although generally optimistic that, with a sufficiently
articulate and scientifically qualified director, OBSSR can
accomplish its goals, some behavioral and social scientists
worry about past statements made by Varmus that they
characterize as disparaging of their disciplines.
The new position is being constructed as, potentially, quite
a visible post," declares Felice J. Levine, executive
officer of the American Sociological Association in
Washington, D.C. "We are concerned that Dr. Varmus has not
seemed to appreciate the real value added of looking at the
social and behavioral dynamics of health and disease. But
we're hoping that this office can be part of the solution,
and that he will be open to the scientific counsel of an
effective director."
Others note what they feel has been an excessively long wait
between congressional authorization for the new office in
June 1993 and action taken to create it, indicating
resistance to OBSSR. Department of Health and Human Services
Secretary Donna Shalala signed the necessary paperwork to
establish the office on July 13 of this year. The delay has
been ascribed by NIH, however, to normal bureaucratic
procedure.
NIH officials say that, whatever tensions may exist, OBSSR
will likely join other congressionally ordered units that
have been productively integrated into the office of the
director--the offices for research on minority health and
research on women's health, for example.
"It's difficult when there are legislative mandates,"
observes Delores Parron, associate director for special
populations in the office of the director of the National
Institute of Mental Health (NIMH)--a job also created by act
of Congress, in 1980--and cochairwoman of the search
committee for the OBSSR director. "But with minority health
and women's health, we've learned how to really make good
use of these offices to do the kind of things that we need
to do, to take the leadership to move us into areas where
we've needed to move for a long time."
Leadership Needed
Because the office will not have a large budget and, hence,
will have limited direct powers, the new director's
leadership capabilities--both scientific and for coalition-
building with other offices in NIH--will be crucial to
OBSSR's effectiveness. A demonstrable understanding of the
scientific methodologies used in the laboratory-focused
biomedical disciplines will also be needed, researchers
agree.
The [OBSSR director] will have to work very closely with all
the institutes at NIH, so there should be a very strong
appreciation for systematic pursuit of knowledge," says Cora
Marrett, an assistant director of the National Science
Foundation in Washington. Marrett, the first head of NSF's
directorate for the social, behavioral, and economic
sciences--an office comparable to OBSSR, established at the
science foundation in 1992--is a member of the search
committee for the OBSSR director. "The person clearly will
have to have a strong ability to communicate ideas and to
bring others together, because the position will not have a
lot of staff or resources initially.
OBSSR, for example, "won't have the budget authority of the
Office of AIDS Research [OAR]," according to Susan Persons,
associate director for government affairs of the Consortium
of Social Science Associations (COSSA) in Washington. OAR
consolidates AIDS research budgets and planning at NIH.
"That's one of the reasons that it's important that the new
director be someone who's respected in the larger community
as well as at NIH. Hopefully, if there's a good, strong
director, that person will be able to get the institutes to
collaborate more." Persons adds that a director interacting
well with all parts of NIH should help ensure that
duplicative research is minimized.
One difficult, early objective of the new director will be
establishing consensus about just what constitutes
behavioral and social science. Different definitions are
used throughout the health agency.
"One of the first tasks for the new person coming in will be
to define precisely how much [behavioral and social science]
there is at NIH right now," Marrett says.
According to Marrett, this will be difficult because of the
breadth and diversity of what has been called behavioral or
social science. For her office to coordinate well with its
NIH counterpart, she says, inter- and intradisciplinary
distinctions will be important.
"There are some areas where most of the support would be at
NSF," Marrett notes. "There is more support for anthropology
at NSF than NIH, for example. But for a number of parts of
psychology--physiological neuropsychology and, to some
extent, cognitive psychology--there is substantially more
support at NIH than at NSF currently."
In many ways, links between biomedical laboratory sciences
and behavioral and social sciences research are only just
emerging. Perhaps for this reason, defining just what types
of studies will lie within the purview of OBSSR may be
difficult. Will, for example, psychosomatic medicine be
included in the category? What about the search for behavior
genes?
"With behavior genes, you're really talking about
straightforward molecular biology," says Louis Sibal,
director of the office of laboratory animal research in the
NIH director's office. Sibal is the official managing the
process of establishing OBSSR and will be asked to help the
office's new leader navigate the bureaucracy at NIH, an
especially important job if the incoming person is from
outside the agency. "Those kinds of [investigations] would
come in the genome program, where people would be mapping
the genes and finding out what their functions are."
NIMH's Parron, however, suggests that work with behavior
genes and psychosomatic medicine probably will both fall
within OBSSR's mandate.
"But coming up with an agreed-upon definition of what's
encompassed is one of the main tasks the new director will
be undertaking, because there has been controversy in
various sectors of NIH about what the appropriate definition
of behavioral science research should be," Parron points
out, noting that the social sciences are more easily
defined. "There are some people who say that much of the
research in the neurosciences should be excluded, for
example, and then others who make the argument as to why it
should be included."
Areas of investigation that most scientists agree will be
addressed by the new office include so-called preventive
research--studies on the persistence of high-risk behaviors
among populations with the potential to be exposed to the
HIV virus, for example, or why young people aware of the
fact that smoking can lead to cancer are still attracted to
cigarettes.
Trouble At The Top?
NIH director Varmus, a Nobel-Prize-winning molecular
biologist, has been accused by behavioral and social
scientists of being unsympathetic to their disciplines, and
their concerns based on this impression extend to their
expectations for OBSSR. The feeling that the NIH director is
less than favorably disposed to behavioral and social
science stems, in part, from a statement that appeared in
The New York Times (N. Angier, Nov. 23, 1993, page C1).
"I begin with the premise that behavior is an incredibly
important element in medicine," Varmus told the newspaper.
"People's habits, their willingness to take steps to avoid
transmission of HIV, are all behavioral questions. But what
I'm looking for are new ideas, real discoveries. When I read
about genetics, I see breakthroughs every day. And while I'm
trying to learn more about behavioral science, I must say
that I don't feel I get tremendous intellectual stimulation
from most of the things I read."
Varmus's defenders insist that his comments have been
misinterpreted and that he was merely expressing his
personal affinity for the methodologies of molecular
biology. Through spokespersons, Varmus declines to respond
directly.
"Dr. Varmus is a molecular biologist at heart," says Sibal.
"And, obviously, he's a brilliant man who has very high
standards. He's a stickler for high-quality research. That's
what was intended by that remark."
Behavioral and social scientists acknowledge that an ability
to challenge the impression--relatively common among
traditional biomedical researchers--that the behavioral and
social sciences lack a rigor comparable to that of their own
disciplines, will be key to the new director's success.
"The scientific depth and acumen [of the new director] will
be core," says Levine, "not just in interaction with Dr.
Varmus but also in being able to play a leadership role
across the agency."
In the view of Denis J. Prager, former director of the
health program at the John D. and Catherine T. MacArthur
Foundation in Chicago and now head of a consulting firm for
foundation planning, "there's room for some strengthening of
the behavioral and social sciences." For most of the past
decade, the MacArthur Foundation supported a research
network for health and behavior headed by psychologist
Judith Rodin, the new president of the University of
Pennsylvania. Says Prager: "Certainly, there's some room for
strengthening the degree to which they're integrated into
the biomedical sciences. On the other hand, it doesn't take
a lot of reading of the literature to become convinced that
some of the most powerful determinants of health in our
society are behavioral and social."
Varmus is also said to be broadening his knowledge of the
behavioral and social sciences as his time in office
lengthens.
"He's on a learning curve and open to hearing," says Anne
Thomas, associate director for communications in Varmus's
office. "And I've heard him express his understanding that
behavioral science is important."
"We've been told that he's educable, that this just isn't
his area of interest, and I can understand that," counters
COSSA's Susan Persons. After Congress authorized OBSSR in
June 1993, she formed the Coalition for the Advancement of
Health Through Behavioral and Social Science Research,
consisting of 12 member societies and organizations, to
monitor NIH progress toward establishing the office.
Persons reports that Varmus failed to mention the behavioral
and social sciences at his confirmation hearings and in
other testimony before Congress. He has also refused to meet
with representatives of her group, while meeting often with
other biomedical researchers, raising fears that the new
OBSSR will be coolly received in his office, she says.
"I'm not inclined to give him the benefit of the doubt any
further," Persons says. "There have been opportunities. As
the NIH director, truly, he represents all of the research
that is done there."
She adds, however: "In spite of the slow progress in getting
this done, I'm really hopeful that, once it is in place and
we have a good [OBSSR] director, things will improve. I
don't think we're going to be able to tackle most of the
health challenges that we have without behavioral and social
science. It's just impossible."
Persons's views--a mix of optimism and cynicism--are shared
by other scientists.
"Behavioral and social scientists are enthusiastic about the
fact that such an office will exist, but skeptical that it
will, in fact, be well integrated into the NIH system and
have much impact," Prager says.
Whatever the start-up problems with OBSSR, most behavioral
and social scientists agree that the questions to be
addressed by the office will be critical ones for biomedical
research and public health in the future.
"The most interesting and most powerful science down the
road is going to be that science which is capable of
integrating the inputs of social, behavioral, and biological
[sciences] in such a way that we get a really detailed view
of how the organism operates in the real world and how it is
affected by the environment within which it lives," Prager
says. "If the NIH people, including Varmus, can be brought
to understand that, then we're going to make much more
progress, much more quickly, in promoting health and
preventing disease."
"I very much hope this office will be a spur for ever-
increasing multidisciplinary efforts," neuroscientist Ira
Black says. "We're in a position now for that to become a
reality, for us to regard the biology of behavior, the
behavioral output, and the behavior of interacting
individuals as different facets of the same pursuit."
Black adds: "Medicine of the 21st century, in large measure,
may well be psychosomatic and somatopsychic medicine."
(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
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WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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TI : Lasker Awards Cite Persistence Of Three Scientists
AU : Barbara Spector
TY : NEWS
PG : 1
The Albert and Mary Lasker Foundation this year has chosen
as the recipients of its prestigious Winged Victory
statuettes three researchers who, according to awards
program director Jordan U. Gutterman, exemplify "persistence
and tenacity, intuition and intelligence."
The New York-based foundation presented its Albert Lasker
Clinical Medical Research Award to John A. Clements, Julius
H. Comroe, Jr. Professor of Pulmonary Biology and a
professor of pediatrics at the University of California, San
Francisco. The Albert Lasker Basic Medical Research Award
was bestowed on Stanley B. Prusiner, a professor of
neurology and biochemistry at UC-San Francisco. The
foundation gave its Albert Lasker Special Public Health
Award--which had been presented only four times previously
in the program's 49-year history--to Maclyn McCarty, an
emeritus professor of bacteriology and immunology at
Rockefeller University.
In addition to the inscribed statues, each winner received a
$25,000 prize. The presentation took place at a luncheon in
New York City on September 30. Health and Human Services
Secretary Donna E. Shalala was the keynote speaker.
"All three are wonderful human stories in science,"
proclaims Gutterman, who is also chairman of clinical
immunology and biological therapy at the University of Texas
M.D. Anderson Cancer Center in Houston.
A Lasker award, believed by many to be the most significant
United States biomedical science prize, is generally viewed
as a "predictor" of the Nobel Prize. Fifty-one Lasker
recipients have gone on to win the coveted Swedish honor.
The Lasker Foundation was established in 1942 by Albert
Lasker, the late owner of the Lord & Thomas advertising
agency, and his wife, Mary, an enthusiastic advocate of
biomedical research. This year's awards were the first to be
given since Mary Lasker's death this past February (B.
Spector, The Scientist, March 21, 1994, page 3).
In her address at the luncheon, Shalala paid tribute to Mary
Lasker: "One of Mary's greatest skills was her ability to
hold public officials to a very high level of service and
excellence. And when it came to the government's commitment
to science and knowledge, she left little room for people to
weasel out of those commitments.
"From Franklin Roosevelt to Bill Clinton, Mary Lasker made
sure that presidents and Cabinet secretaries knew the value
of science to this country."
Historic Achievement
The award to McCarty celebrates the 50th anniversary of the
landmark discovery that genes are made of DNA (O.T. Avery,
C.M. MacLeod, M. McCarty, Journal of Experimental Medicine,
79:137-58, 1944). McCarty conducted this research along with
Rockefeller colleagues Oswald T. Avery and Colin M. MacLeod,
both now deceased. The trio, originally aiming to find a
cure for pneumonia, determined that DNA was the substance
that controlled the reproduction of pneumococcus--a
breakthrough that launched the modern age of molecular
biology and genetics. According to the Philadelphia-based
Institute for Scientific Information (ISI), this paper has
been explicitly referenced in more than 1,000 subsequent
articles. It long ago became part of the common wisdom of
the field.
Joshua Lederberg, University Professor at Rockefeller, has
called the group's discovery "an outstanding example of the
feedback of clinically motivated inquiry into the most basic
issues of fundamental biological science" (J. Lederberg, The
Scientist, Feb. 21, 1994, page 11).
"It was an authentic discovery of a problem as well as a
solution," says Lederberg. "It wasn't a problematic issue
except in the minds of one group." He notes that, at the
time, it was unclear that one could go about determining
what genes are made of.
The profound significance of the paper took years to be
appreciated, partially because it was published during World
War II, and partially because the journal in which it
appeared was not widely read by pure geneticists. The
group's findings were also challenged by several detractors,
who claimed that there was not enough evidence to support
the trio's conclusion.
"People didn't get it," marvels McCarty, now 83. He recalls
being the second presenter at a meeting at Johns Hopkins
University in 1949, at which he was to discuss the DNA
research. At the beginning of the event, the room was
packed. But after the first lecture--on the use of Dramamine
to treat seasickness--"the sound of people leaving the hall
was so loud that I had to delay the start of my paper." When
he finally began speaking, "there were about 35 people
left."
Another factor hindering widespread acceptance of the work
was Avery's reluctance to personally promote it. "His view
of [self-promotion]--practiced for many years before, as
well--was to get the information published with the best
possible proof of the point and let the interpretations fall
where they may," McCarty reminisces. Ironically, although
Avery received a Lasker award in 1947, he was cited "for
distinguished service through studies on the chemical
constitution of bacteria" rather than his DNA work.
McCarty followed the 1944 paper with two articles describing
his preparation of a purified pancreatic DNase (M. McCarty,
Journal of General Physiology, 29:123-39, 1946) that, in
nanogram quantities, would inactivate the transforming
substance (M. McCarty, O.T. Avery, J. Exp. Med., 83:89-96,
1946). This evidence backed up the conclusions of the
original article. In 1946, he left Avery's group to head a
Rockefeller lab investigating streptococcal infections and
rheumatic fever.
The Lasker Foundation's Gutterman says the award to McCarty
is intended "not only to honor the work, but to honor the
field and publicize what's going on." Although the discovery
occurred half a century ago, Gutterman points out, only
recently has an understanding developed of "how cells act,
how organisms develop, what normal physiology is, and how
disease develops."
McCarty, a member of the National Academy of Sciences (NAS)
and the Institute of Medicine (IoM), received his M.D.
degree from Johns Hopkins in 1937 and came to Avery's
Rockefeller lab as a research fellow in 1941. He recounts
his memories of the DNA work in his book The Transforming
Principle (New York, W.W. Norton & Co. Inc., 1985).
Overcoming Skepticism
Prusiner was cited for identifying a new class of pathogens,
which he named prions. He has reported that these infectious
agents are implicated in diseases marked by slow onset with
progressive deterioration of the brain and nervous system,
including scrapie, a disease affecting sheep; as well as
Gerstmann-Strussler-Scheinker disease (GSS), Creutzfeldt-
Jakob disease, and kuru in humans.
Prusiner defined the prion in a 1982 paper, "Novel
proteinaceous infections particles cause scrapie" (Science,
216:136-44), which has been cited in more than 425
subsequent studies. This work was greeted by skepticism in
certain scientific circles. The pathogen, he maintained, was
composed only of protein; he did not find DNA or RNA in the
prion, contradicting the general belief that all living
organisms contain genes.
Further fueling doubts among some of Prusiner's colleagues
was his assertion that prion diseases can be inherited as
well as infectious. Moreover, he concluded that the normal
prion protein has a different shape from the disease form.
This, too, was heretical, because it had long been thought
that each protein has only one natural conformation.
According to Gutterman, Prusiner's award also recognizes his
"many years of very, very painstaking work [amid] a lot of
opposition." In the early 1980s, the researcher and his
prion theory were the subject of uncomplimentary articles in
the scientific and popular press. His detractors maintained
that the agent at work in these diseases was a slow-acting
virus. While some investigators continue to look for a
virus, the scientific community now generally accepts the
idea of prions, which are now studied by many former
proponents of alternative hypotheses.
Prusiner "was all by himself against the world to prove the
point," comments Pierluigi Gambetti, a professor of
pathology at Case Western Reserve University School of
Medicine who studies prion diseases. The copious data
Prusiner produced ultimately won over the skeptics, says
Gambetti, noting that he himself originally "had trouble
understanding the mechanism." The "breakthrough" that
shifted his perspective, recalls Gambetti, was Prusiner's
results with transgenic animals.
"The deeper I got into this, the more controversy there was,
the more people got angry, the more I wanted to figure out
what this [prion] was," says Prusiner. "I couldn't figure
out a better problem to work on."
Prusiner, 52, received his M.D. from the University of
Pennsylvania in 1968 and then moved to UC-San Francisco,
where he did an internship and a residency in neurology.
"Today, I believe, it is very unlikely that my initial
research would have been funded by NIH, because so little
money is available for basic biomedical research," he said
at the awards presentation. "The truly innovative proposals
by young people don't have a chance anymore, at least I
believe that to be the case."
The general acceptance of the prion hypothesis in the past
few years has manifested itself in the form of numerous
significant prizes given to Prusiner, among them a Gairdner
Foundation International Award, the Richard Lounsbery Award
from NAS, a Charles A. Dana Award for Pioneering
Achievements in Health, and a Christopher Columbus
Quincentennial Discovery Award in Biomedical Research from
the National Institutes of Health. He was elected to NAS and
IoM in 1992.
Lifesaving Research
The Lasker Foundation recognized Clements, 71, for
discovering lung surfactant, a soap-like mixture of
lipoproteins that coats the lungs and prevents them from
collapsing, in 1957. The paper reporting on this discovery
(J.A. Clements, "Surface tension of lung extracts,"
Proceedings of the Society for Experimental Biology and
Medicine, 95:170-2) has been cited in more than 340 papers;
like McCarty's seminal DNA paper, it has become textbook
knowledge.
In 1959, researchers Mary Ellen Avery and Jere Mead of
Harvard University found that respiratory distress syndrome,
a leading cause of death in premature infants, develops
because the babies are born before their lungs start
producing surfactant. The condition resulted in the death of
Patrick Bouvier Kennedy, the two-day-old son of President
John F. and Jacqueline Kennedy, in 1963.
In 1961, Clements and colleagues identified the major lipid
component of surfactant, which led to attempts by multiple
groups to synthesize the substance. In 1985, Clements
developed a synthetic surfactant. The artificial substance,
called Exosurf, was licensed to Burroughs Wellcome Co. of
Research Triangle Park, N.C., and received Food and Drug
Administration approval in 1990.
"Now it has been demonstrated that surfactant-replacement
therapy has reduced infant mortality to the lowest it's
been, in the U.S. and in most industrialized countries,"
says Harvard's Avery, a member of the 1994 Lasker awards
jury.
Clements acknowledges that science rarely proceeds at a pace
sufficiently rapid to enable a researcher to see favorable
clinical results of his basic investigations in his own
lifetime: "I recognize that fact every day. I think of all
the people toiling in the vineyards--a lot of them work
harder than I work; most are a lot smarter. [Therefore] I
have to consider that Lady Luck played a role."
For example, he notes, it was serendipity that led him to
study the pulmonary system in the first place. During the
Korean War, he volunteered for military service and was
assigned to the U.S. Army Chemical Center in Edgewood, Md.
At the time, government scientists were studying the effects
of nerve gases, fearing that the Soviets might use them in
chemical warfare. "I was assigned the task of figuring out
how nerve gases affected the lungs. I had no particular
interest in how the lungs worked up to that point."
Following the war, Clements remained at the Army Chemical
Center as a staff member until 1959. He has been at UC-San
Francisco since 1961. An NAS member, he has received a
Gairdner Award and a Christopher Columbus Discovery Award,
among other honors.
Clements stresses that many aspects of surfactant remain to
be investigated: " 'Surfactant' tends to imply that it is
something simple, but--no pun intended--we've only scratched
the surface. We know so little about it at this point."
Among the knowledge that remains to be gained, he says, is
the role the substance plays in recovery from injury to the
adult lung as well as in the lung's response to disease.
At the Lasker awards luncheon, Clements announced that he
would donate the honorarium to the United Nations
International Fund for Children's Relief.
In the stories of all three award-winners, Gutterman
maintains, there runs a common theme: the "spinoff back and
forth between basic and clinical research."
In order to ensure future breakthroughs, he declares: "We
have to have environments for these discoveries to be made,
and we have to have long-term investments."
(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
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TI : Cancer Researchers Fear Impact Of Diminishing Funding
Support
Redistribution of federal financial backing may have
drastic implications for cancer studies, they warn
AU : Steven Benowitz
TY : NEWS
PG : 1
With federal research funds increasingly being earmarked
for such publicly visible areas of biomedical investigation as
AIDS and women's health, cancer research institutions in the
United States are finding themselves in a bind.
Saddled with a shrinking piece of the budgetary pie, heads
of the nation's basic cancer research centers are struggling
to maintain their high scientific standards while making
ends meet. They worry that the frustration of stagnant
funding levels will drive their best researchers to seek
greener pastures. And they are concerned that, in the long
run, the necessity of cutting costs will serve only to
hinder scientific progress.
Last month, the National Cancer Advisory Board told Congress
that the nation's war against cancer had stalled, and that
without several changes, cancer would become the country's
top killer within five years (New York Times, Sept.
3, 1994, page A25). The board suggested, among other things,
additional funding to move new discoveries from the laboratory
to the bedside.
The National Cancer Institute (NCI), for example,
currently funds only 15 percent of overall grant
applications -- down from 25 percent only a few years ago,
says E. Premkumar Reddy, director of Temple University's
Fels Research Institute in Philadelphia, one of 14 NCI-
designated basic science cancer centers. Moreover, although
the National Institutes of Health has not significantly
increased the dollars available for cancer research, these
monies are being funneled in several different directions,
especially to more applied areas. In federally funded cancer
research, the emphasis has shifted to therapeutics,
particularly for such high-profile conditions as breast
andprostate cancers, and away from basic science, cancer
scientists say.
"The money is going to the same tired, unsuccessful drugs,"
Reddy laments. "The only real innovations will come with
basic research." Reddy draws an analogy to the advent of
penicillin, which ushered in a revolution in medicine in the
1950s and 1960s. "In the next four or five years," he
forecasts, "basic research in molecular biology may be
able to achieve the same thing in cancer treatments. But not
without the money to do it."
Indeed, according to Reddy, NCI has mandated that the basic
research centers that are affiliated with hospitals -- such
as Fels and Temple -- must make their research more
"applied." "Good basic science is hurting," he
cautions.
A Dying Breed
Some observers fear that the university researcher
with the resources to command the large, easily renewed
federal grant that pays for a laboratory full of
postdoctoral fellows, graduate students, and technicians has
become a dying breed.
"There's no question that there's a general biomedical
funding crunch," says Robert Young, president of the Fox
Chase Cancer Center, also based in Philadelphia. Fox Chase
is one of 27 NCI-designated comprehensive cancer centers,
which focus on patient care as well as clinical and basic
research. "We have more good research projects than are
adequately funded. In the last 10 years, we've seen an
increase in the percent of grants that are approved but
not funded."
According to NIH's Division of Research
Grants, only 15.8 percent of all new R01 investigator-
initiated grant submitted in fiscal year 1993 were funded.
This represents a drop from 1992 and 1991, in which 20.7
percent and 21.3 percent of such grants, respectively, were
funded. Young blames a "stagnant federal research
budget," combined with earmarking funds for particular
areas of research, both of which "have been much more
prevalent in the past five years and [have] affected overall
funding opportunities." As a case in point, the NIH 1993
budget for AIDS research was $1.07 billion. The estimated
1994 figure is $1.3 billion -- an increase of $226 million
earmarked by Congress-- as reported by the institutes'
Office of Financial Management.
A significant change in the overall federal budgetary
outlays is not expected anytime soon. The House of
Representatives and the Senate have agreed to award NIH an
overall increase of roughly 3.6 percent for 1995, enough to
keep up with inflation. Most institutes, including NCI, have
been granted 3 percent raises.
Pushing Applications
"There's been an increasing pressure from the federal
government to justify basic science on the basis of some
potential clinical application," Young says.
Often, those links are problematic. "That's what concerns
basic scientists,"he notes. "The fact that there is no
easily explained application of their research in medicine
doesn't mean there won't be, but rather that we don't
know what they may be yet."
"People have argued that many of
the breakthroughs in science and medicine have come at the
basic-science level," Young points out.
"An important breast cancer discovery may not specifically
come from a research project labeled for breast cancer."
As an example, he cites the retinoblastoma gene. It's a tumor
suppressor gene that's believed to play a role in causing
some breast cancers. Yet it was discovered as a cause of a
relatively rare childhood eye cancer.
"Earmarking makes it harder for people to secure funding,"
Young says. "It's produced a feeling of insecurity. Twenty
years ago good researchers were pretty confident they'd be
able to pursue their goals. Today no one is guaranteed."
Norman Drinkwater, director of the McArdle Laboratory for
Cancer Research at the University of Wisconsin, Madison,
worries that the tougher competition for funding will affect
the next generation of scientists. "I think we'll start to
lose a number of talented scientists as they become
frustrated trying to establish top research programs," he
predicts.
He's particularly concerned about a budget
shortfall for training programs and grants that include
support for predoctoral and doctoral students. "As we fail
to fund these training programs, we'll develop fewer first-
rate scientists for the future," he warns.
The funding crunch may well hinder scientific progress if
something isn't done, says researcher David Schuller of
Ohio State University in Columbus. "The problem is, we've
reached a point today in which the rate of scientific
discovery in cancer research is resource-driven -- and
resource-limited."
"As the level of competition for funding
gets keener, you can't separate the quality of research
proposals as easily," maintains Schuller, who is director
of Ohio State's Comprehensive Cancer Center-Arthur G. James
Hospital and Research Institute. Greater competition for the
same research dollars also has made it tougher to secure
support the first time around. Young investigators are
competing with more seasoned researchers whose grant
requests may initially have been turned down, and who are
already resubmitting revised proposals. "The system tends
to exclude the entry-level investigator, which affects the
future of biomedical research," Schuller says.
That message seems to be getting out. A report issued in
July by the National Research Council (The Funding of Young
Investigators in the Biological and Biomedical Sciences,
Washington, D.C., National Academy Press, 1994) showed that
the number of biologists under the age of 37 applying for
independent NIH grants dropped by more than 50 percent in
the past eight years, though applications from older
colleagues increased by more than a third.Young sees little
funding relief in sight, with federal budget caps and
growing public entitlement budgets contributing to keeping
the biomedical research funding relatively unchanged for the
next several years.Yet many, like Giovanni Rovera, director
of the Wistar Institute of Anatomy and Biology in
Philadelphia, contend that the money is still there. But he
agrees that greater competition for the same research
dollars has made it tougher to secure support the first time
around. The "worthy" projects will get support, Rovera
forecasts. It just may take two or three grant rewrites
before the money comes through. And the support may be for
less time and fewer dollars than expected (see story on page
4).
"The problem isn't getting the money, but rather, getting it
promptly, when you want it," Rovera says.
Shelley Berger, an assistant professor who came to Wistar in
1993 from a postdoctoral position at the Massachusetts
Institute of Technology, uses baker's yeast to examine how
genes are turned on and off. Her latest grant application
was funded by both the National Science Foundation and the
American Cancer Society, but not by NCI.
Berger acknowledges that many of her friends whose "work
is just as good and worthwhile of funding" have been
turned down for federal dollars. "There's plenty of
science available, but just too many people who want to do
it."
Problem With Earmarking
"Earmarking affects the way science
is done in this country," asserts microbiologist Clayton
Buck, deputy director of Wistar. "By forcing scientists to
be more competitive, you make them focus on applied areas
that they may not necessarily have chosen. Now they have to
because that's where the money is -- you affect their
choices of research specialties."
Former NCI director Vincent DeVita, who now is director of
the Yale University Cancer Center, agrees. "Earmarking is
dangerous because it takes dollars from the general RO1
investigator-initiated grant pool and forces investigators
to redirect their thinking to the direction of translational
research," he says. "It's not that I'm against translational
work; I'm just against manipulating the R01 pool."
Such choices may also affect tenure and promotion decisions.
"Universities [define] successful scientists as whether or
not you have an R01 grant," DeVita observes. "in the old
days, you could get grants and spend a few years doing
research and find out whether you were any good as a
scientist. You're under tighter restrictions and tougher
demands today."
While Young, Rovera, and DeVita decry earmarking of federal
dollars as a potential threat to the future of the United
States research base, Congress and the public seem to be
demanding greater accountability from researchers, according
to agency officials and other veteran science-watchers. For
whatever problems scientists choose to address, legislators
want to be sure tax dollars are resulting in clinical
payoffs, or at least marketable products. Scientists have
had to become more attuned to potential clinical
applications of research, particularly when writing grant
proposals.
"We're being held more accountable by Congress
and the public," says Faye Austin, associate director for
extramural research in NCI's Division of Cancer Biology,
Diagnoses, and Centers. "We've made a large investment in
biomedical research in the last 20 years, and the public
asks, "What are we getting for this?"
"Things have changed since AIDS came along with the
empowerment of the AIDS constituency," she notes.
"They've been successful in getting resources, and have
taught similar lessons to other groups." Last year, for
example, the National Breast Cancer Coalition, along with
other groups, lobbied Congress and persuaded it to double
the money it spends on breast cancer research. "The public
is putting pressure on researchers to show results,"
Austin adds.
Steven Benowitz is a science writer for Penn State University
Milton S. Hershey Medical Center in Hershey, Pa.
(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
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TI : SLIMMER WISTAR IN TRANSITION
AU : STEVEN BENOWITZ
TY : NEWS
PG : 4
The Wistar Institute of Anatomy and Biology in Philadelphia
shares the woes of other basic science cancer centers: how
to deal with an uncertain funding environment, given the
increased push by federal funding agencies to support
applied research.
Compounding matters, Wistar has had the added burden of a
three-year legal battle over management issues with former
director Hilary Koprowski, settled in June 1993. Although
just three years ago Wistar faced a $2 million budget
deficit and declining morale, today the staff credits the
new director, Giovanni Rovera, with streamlining the
institute--closing unproductive laboratories and reducing
the work force.
Now, a leaner Wistar seems re-energized, with a fresh sense
of purpose, according to Robert A. Fox, immediate past
president of its managing board and president of RAF
Industries Inc., a private investment company based in
Elkins Park, Pa. Earlier this year, the institute finally
celebrated its centennial--albeit three years late.
In singing Rovera's praises, his supporters point to a
$1 million research grant awarded in 1992 by Philadelphia-
based Pew Charitable Trusts. This support, they say, has
helped bring in a new wave of young scientists, while
helping to strengthen scientific initiatives in structural
biology, molecular genetics, and cell and developmental
biology. Scientific collaborations have flourished.
Scientists from Wistar and the University of Pennsylvania--
on whose campus it sits--are studying gene therapy for
cystic fibrosis and a number of other diseases, for example.
And Wistar and Children's Hospital of Philadelphia are using
a five-year, $5.9 million grant from the National Heart,
Lung, and Blood Institute to establish a pediatric
cardiology center.
"The institute is clearly now becoming stabilized after
several turbulent years," says Rovera, a specialist in
pediatric leukemias. "The focus is clearly on science,
though we still must keep an eye on financial matters. Our
precarious economic reality, relying mostly on federal
grants, and not patient-care revenues, forces us to."
As part of the centennial celebration, honors were bestowed
upon Koprowski, a Polish-born virologist who headed Wistar
from 1957 to 1991 and made it a world-class institution.
Koprowski, who has since moved across town to Thomas
Jefferson University, was named professor laureate at Wistar
and given a position on the institute's controlling board of
managers.
Wistar is known in the research establishment for a century
of accomplishments. One of 14 basic cancer centers
designated by the National Cancer Institute, it carries a
research budget of about $25 million, with some 75 percent
of its grant funding coming from the National Institutes of
Health. About 70 percent of its work is devoted to various
aspects of cancer.
Its many achievements include the development of the first
line of continuously growing normal human cells, the design
of vaccines against rubella and rabies, and the creation of
specialized antibodies to seek out and destroy cancer cells.
Wistar scientists have identified interleukin-12, an immune
system regulator that may play a key role in AIDS, and are
working on perfecting vaccines against rotavirus, which
causes infantile diarrhea, and cancer.
"Wistar is a unique environment," says Nancy Fogg-Johnson,
vice president for administration. "It's an academic
institution without teaching requirements, so the scientists
can really dedicate themselves to basic science."
She contends that while Wistar has done "relatively well" in
securing funds for research in the past, it must "step up
its efforts to get support from private sources." Wistar has
also been receiving royalties for its numerous discoveries
over the years, such as rubella and recombinant rabies
vaccines, as well as the hybridoma method for producing
monoclonal antibodies for detection and treatment of
cancers.
Deputy director Clayton Buck, a cell biologist and
professor of pediatric cardiology who heads the new
pediatric cardiology center, acknowledges that Wistar has
had a poor track record in garnering private funding: "An
institution of our size should have an endowment of some
$150 to $200 million. We probably have a tenth of that."
The grant funding base at Wistar during the past several
years had been eroding because of a number of factors. One
of these was the departure of several senior investigators
when Koprowski went to Jefferson. "Two program projects that
he had involving the genetics of cancer and multiple
sclerosis were not renewed," Rovera notes.
According to Rovera, Wistar scientists have been somewhat
successful this year--better than expected, in fact--in
securing new grants. "We've had to make adjustments; weUre
increasing our emphasis in technology transfer, and being
more demanding than in the past with upfront money and
licensing fees. We canUt afford to wait for royalties.
That's happening at other institutions, too."
--S.B.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
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TI : Gerontology Investigators Press An Ambitious Agenda
AU : Karen Young Kreeger
TY : NEWS
PG : 1
Despite a substantial increase in the flow of financial
support for gerontological research during the past several
years, ambitious investigators of aging-associated phenomena
continue to lament that their field is underfunded.
One such investigator is Denham Harman, a professor,
emeritus, at the University of Nebraska College of Medicine
in Omaha. The 78-year-old Harman for many years has argued
that aging research deserves far more attention and
financial support than it traditionally has
received--especially because the United States population,
according to demographic statistics, is rapidly getting
older. "We need to spend more money on basic biomedical
research on aging to go after its basic causes," he asserts.
Harman acknowledges his gratification at seeing significant
funding gestures in the past year alone by such private
sources as the Charles A. Dana Foundation in New York and
the Glenn Foundation for Medical Research in Santa Barbara,
Calif. And he was heartened most recently to hear of a $14.3
million infusion--called the Paul Beeson Physician Faculty
Scholars in Aging Program--into the gerontology research
effort from a consortium of three private foundations.
Harman nevertheless in-sists that backing for gerontology
studies remains inadequate for the important task facing
researchers in the field. "One should not be deluded," he
warns.
'A Shot In The Arm'
Last month's show of support through the Beeson program was
announced by the initiative's three cosponsors: the John A.
Hartford Foundation and the Commonwealth Fund--both New York-
based private philanthropies--and the Alliance for Aging
Research, a Washington, D.C., private, nonprofit advocacy
group that promotes research and policy attention to issues
of aging.
The program's main purpose is to support young faculty
members whose research relates to aging and to promote the
study of aging across disciplines, especially in U.S.
medical schools. The program is named as a tribute to
gerontologist Paul Bruce Beeson, a professor of medicine and
distinguished physician who is now retired from the
University of Washington and the Veterans Administration
Hospital, both located in Seattle.
Robert Butler, a geriatrician at the Mount Sinai Medical
Center in New York and first director of the National
Institute on Aging (NIA), calls the initiative a "shot in
the arm" for "young people just on the crest of their
careers."
Nevertheless, many observers are still calling for more
funding. Over the last four years, three groups have
separately proposed substantial increases for aging
research. In 1990, the Pepper Commission TK, a U.S.
bipartisan panel looking into comprehensive health care,
recommended in its final report that the federal government
move toward a funding level of $1 billion annually to
finance "a research and development program aimed at
preventing, delaying, and dealing with long-term illnesses
and disabilities," including studies on such diseases and
disorders as Alzheimer's, osteoporosis, and urinary
incontinence.
One year later, a committee from the Institute of Medicine
echoed the Pepper Commission's recommendations. In its
report, Extending Life, Enhancing Life: A National Research
Agenda on Aging (Edmund T. Lonergan, ed., Washington, D.C.,
National Academy Press, 1991), the committee said that "a
major investment in research on aging is needed urgently."
This support should total "$913 million annually, a figure
approaching the $1 billion recommended by the Pepper
Commission," the report stated.
Most recently, a group of 72 nonprofit professional and
advocacy groups called the 1994 Task Force for Aging
Research Funding issued a statement urging Congress and the
president to "enact legislation authorizing $1 billion a
year for aging research at NIH, and $2 billion a year by the
end of the decade."
And as Harman stated in a commentary in The Scientist (March
19, 1990, page 18), "Funding for basic biomedical research
on aging is meager. Only between $25 and $50 million is
available per year, largely from the National Institute on
Aging. In contrast, more than $2 billion is allocated each
year for two major causes of death--cancer and
atherosclerosis." In fiscal 1994, close to half of NIA's
total $420 million budget was devoted to Alzheimer's
research, with the other half going to fund sociological,
behavioral, psychological, and basic biomedical research
(see story on page 14.
Daniel Perry, executive director of the Alliance for Aging
Research, agrees that there aren't enough funding sources to
enable scientists to properly study the basic processes of
aging. What the Beeson program will do, he says, "is bring a
measure of high-quality science to bear on understanding the
conditions that afflict older people. It will bring
understanding the biology of aging into the forefront, and
it will increase the sophistication of physicians in how to
diagnose, treat, prevent, postpone, and rehabilitate chronic
diseases in the elderly."
Harman adds that the program "will increase the visibility
of aging" as an area of research, so that, he says, more
attention will be paid by the science community to this
underrepresented discipline.
Thirty In Three Years
"The goal for the Beeson program," says Perry, "is to have
30 leaders [in aging research] in place at the end of three
years. Only a handful of medical students have an exposure
to geriatrics and gerontology, and these are not exposed to
the best science on aging at that. [The Beeson initiative]
is more than a step in the right direction."
Each year, for three years, the program will select 10
junior faculty members and provide each with a grant of up
to $150,000. The application deadline for the first round of
funding is December 15, with final decisions to be announced
in April.
A national committee, headed by William N. Kelley, chief
executive officer of the University of Pennsylvania's
Medical Center and Health System and dean of Penn's School
of Medicine in Philadelphia, will review applications and
select the scholars. The American Federation for Aging
Research (AFAR), a New York-based group that funds
gerontology and geriatrics research, and the alliance will
share administrative and technical support for the program.
Creators of the program say its main emphasis is to attract
top-flight young physician-scientists to commit their
careers to research and training in aging. "The goal is to
generate more well-prepared and leading junior faculty
members," states Franklin Williams, scientific director at
AFAR and a professor of medicine, emeritus, at the
University of Rochester, New York, "and to give people who
have promise the opportunity to have some really good free
time for advancing their research and their careers.
"I think the bulk of the applicants will probably be at the
interface of biomedical and clinical research." The fields
that prospective recipients could be from is "really quite
open," remarks Williams, who was NIA director from 1983 to
1991. For example, he notes that the chosen scholars could
just as likely have degrees in genetics, molecular biology,
or physiology as in psychology or sociology.
Each scholar will be paired with a senior faculty mentor
from his or her home institution. The program will stage an
annual meeting of scholars, mentors, and leaders in academic
medicine to review and disseminate research findings of the
scholars.
Sign Of The Times
Almost every cry for more resources for aging
research --whether for work on its sociological aspects or its
biomedical underpinnings-- cites the demographic shift in the
U.S. population to an older majority as the impetus. "In
this century, with the baby boom, we've established
departments of pediatrics in every medical school in the
country and only one in geriatrics [the Mount Sinai School
of Medicine, New York]," says the alliance's Perry. "It is
this unprecedented and profound shift to an older population
that is forcing medical schools to adjust, but they haven't
been forced quickly enough.
"Efforts by the federal government to induce training of
faculty have been modest, at best. And what we now are
seeing are these three nonprofit, philanthropic entities
committing over $14 million to jump-start the field in the
space of three years."
And, according to Perry and others in the field, there are
other places--but not enough--that are starting to commit
large amounts of money to support research in aging, in
addition to NIA's commitment.
Non-NIA funding comes from such private groups as AFAR, the
New York-based Brookdale Foundation Group, and the Sandoz
Foundation for Gerontological Research in East Hanover, N.J.
(see story on page 11). Still others like the Charles A.
Dana Foundation of New York and the Buck Center for Research
in Aging in Novato, Calif., mount their own research
initiatives (see story on this page).
(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
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TI : WHERE GERONTOLOGISTS GET TOGETHER
TY : NEWS
PG : 11
Following are some of the professional societies whose
memberships include biological, social science, and clinical
researchers in the fields of geriatrics and gerontology.
American Aging Association (AAA)
American College of Clinical Gerontology (ACCG)
2129 Providence Ave.
Chester, Pa. 19013
(610) 874-7550
Fax: (610) 876-7715
Arthur K. Balin, executive director of AAA and president of
ACCG
American Geriatrics Society
770 Lexington Ave., Suite 300
New York, N.Y. 10021
(212) 308-1414
Fax: (212) 832-8646
Harvey Jay Cohen, president
Linda Hiddemen Barondess, executive vice president
Gerontological Society of America
1275 K St., N.W., Suite 350
Washington, D.C. 20005-4006
(202) 842-1275
Fax: (202) 842-1150
E-mail (via Bitnet): gsa@gwuvm
Linda K. George, president
Carol Schutz, executive director
Society for Neuroscience
11 Dupont Circle, N.W.
Suite 500
Washington, D.C. 20036
(202) 462-6688
Larry Squire, president
Nancy Beang, executive director
(The Scientist, Vol:8, #20, pg.11, October 17, 1994)
(Copyright, The Scientist, Inc.)
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3600 Market Street, Suite 450, Philadelphia, PA 19104
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--------
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TI : ACCESSING AGING ASSETS
TY : NEWS
PG : 11
Following are some of the funding sources for research on
aging, including basic biomedical research, clinical
research, and training:
American Federation for Aging Research (AFAR)
AFAR Research Grants: awards of up to $40,000 for one year
to junior faculty for preliminary research projects.
Merck/AFAR Fellowships in Geriatric Clinical Pharmacology:
awards of $100,000 over two years, cosponsored by Merck &
Co. Inc., Rahway, N.J., to train physicians.
Glenn Foundation/AFAR Scholarships in the Biology of Aging:
awards of more than $5,000 for predoctoral students--both
M.D. and Ph.D.--cosponsored by the Glenn Foundation, Santa
Barbara, Calif., to conduct three-month biomedical
research projects.
For more information on these grants and the Beeson Scholars
in Aging Program, contact Odette van der Willik, grants
manager, AFAR, 1414 Ave. of the Americas, 18th Floor, New
York, N.Y. 10019; (212) 752-2327. Fax: (212) 832-2298.
Brookdale Foundation Group (BFG)
Grants of various amounts in the fields of gerontology and
geriatrics. The foundation requests that prospective
applicants submit a one-page letter explaining a project's
concept. These are reviewed at monthly board meetings,
whereupon some applicants are invited to submit a full
proposal.
For more information, contact Nora O'Brien, BFG, 126 E. 56th
St., New York, N.Y. 10022.
Sandoz Foundation for
Gerontological Research
Grants of up to $35,000 for one year in the areas of
biology, pharmacology, immunology, geriatric medicine,
psychogeriatrics, and epidemiology. The foundation is
affiliated with the pharmaceutical company Sandoz Ltd. of
Basel, Switzerland.
For more information, contact Agnes Sisto, Sandoz
Foundation, 59 Route 10, East Hanover, N.J. 07936-1080;
(201) 503-8544. Fax: (201) 503-7185.
--K.Y.K.
(The Scientist, Vol:8, #20, pg.11, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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71764.2561@compuserve.com
The Scientist,
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U.S.A.
--------
NXT:
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TI : 24th Annual Neuroscience Meeting To Attract A
Variety Of Specialists
AU : Neeraja Sankaran
TY : NEWS
PG : 3
The 24th annual meeting of the Washington, D.C.-based
Society for Neuroscience, to be held November 13 to 18 in
Miami Beach, Fla., is likely to be the largest conference in
the association's history, according to society officials.
Almost 15,000 of the society's 23,000 members are expected
to attend. The event will offer a mixed bag of topics in
about 17 symposia and 15 lectures, in addition to various
workshops, courses, panel discussions, and more than 10,000
posters and slides.
"Our meeting is unique in that it draws a large proportion
of society members," remarks Larry Squire, the current
president as well as a professor of psychiatry and
neuroscience at the University of California, San Diego, and
a staff research scientist at the San Diego Veterans Affairs
Medical Center (VAMC). "It would be hard to pick any special
themes of interest--we have everything from molecular and
cellular research to cognitive studies." (See accompanying
list for a sampling of topics.)
Squire's own area of expertise--the biology of memory--is
the subject of a special presidential symposium, and by
itself demonstrates the scope of the neurosciences. The two-
hour session will include discussions on genetic,
regulatory, and chemical aspects of memory. This year the
symposium commemorates Walle J. Nauta, a noted
neuroscientist from Harvard University who died earlier this
year, shortly after being named the winner of the National
Academy of Sciences Award in the Neurosciences (N. Sankaran,
The Scientist, April 18, 1994, page 1).
In addition to the symposium, there will be three special
presidential lectures, including one on the evolution of the
brain by Harvard University evolutionary biologist Stephen
Jay Gould. Scheduled for 11:15 a.m. on Wednesday, November
16, this lecture will be simultaneously videocast to a
second room to accommodate attendees unable to fit in the
lecture theater.
Death In Development
A particularly "hot" area of neuroscience research nowadays,
say many scientists, is developmental neurobiology--the
study of how nerve cells differentiate in the embryo and
achieve their final form. Several sessions at the meeting,
including one of the presidential lectures, will discuss
advances in this subdiscipline. The featured speaker, H.
Robert Horvitz, a professor of biology and a Howard Hughes
Medical Institute investigator at the Massachusetts
Institute of Technology, will discuss the role of programmed
cell death--also called apoptosis--in development.
"A great number of cells die in the course of normal
development; the question is why and how," says Horvitz. His
studies on the phenomenon in the nematode Caenorhabditis
elegans revealed that the genes and proteins involved in the
programmed death of nerve cells in this organism were
similar to certain genes and proteins found in humans (J.
Yuan et al., Cell, 75:641-52, 1993).
"It is [my] hypothesis that the pathway of programmed cell
death is highly conserved between nematodes and humans," he
adds. Horvitz will also talk about the applications of his
work in understanding such neurodegenerative diseases as
Parkinson's and Alzheimer's.
Attention On Animals
A regular feature at the society's annual conferences has
been a forum or panel discussion organized by its Committee
on Animals in Research. The subject is particularly
important to the society because of the significant amount
of neuroscience research that uses animals as experimental
models, according to committee chairman Stuart Zola-Morgan,
a professor of psychiatry at UC-San Diego and a research
scientist at the San Diego VAMC.
This year the discussions will focus on two issues. One is
public opinion on the use of animals in research, including
polling data showing how men's and women's views vary on
this subject. The other issue is a recent strategy
implemented by animal rights groups to promote their cause,
whereby they align themselves with women's groups, targeting
perceived parallels between the use and treatment of animals
in research and the exploitation of women. Panelists include
Mary Woolley, president of Research!America, a research-
advocacy group based in Alexandria, Va.; Sandra Bressler,
director of scientific and educational activities at the
California Medical Association; and Andrea Zardetto-Smith, a
professor of psychology at the University of Iowa, Iowa
City. Zola-Morgan will act as the moderator for the session.
Animal research will also be touched on during a workshop
for high school students to be held at the conference. "We
feel an obligation to explain the importance of animal
[models] in research, particularly with the resurgence of
animal rights concerns in schools," says Squire.
Capitol Neuroscience
A special workshop entitled "Educating your legislators or
suffering the consequences" is scheduled this year, to
introduce the society's members to the process of law-making
and the dispensation of research funds by Congress. "The
workshop will talk about how Congress deals with various
scientific and funding issues, and how scientists can affect
those decisions," says workshop presenter Frankie Trull,
vice president for government affairs at Capitol Associates
Inc., a government-relations consulting firm in Washington,
D.C.
"What kind of funding goes to a particular type of research
depends on the importance given to it by Congress," she
notes, "and the best option for a scientist is to speak
directly to Congress and arm them with relevant knowledge so
that they can make informed decisions.
"This workshop will deal with some of the dos and don'ts--
don't argue, do express yourself clearly, and do follow up,"
advises Trull.
For more information on the society's meeting, contact
Joseph Carey or Julie Ziegler at the Society for
Neuroscience, 11 Dupont Circle, N.W., Suite 500, Washington,
D.C. 20036; (202) 462-6688. A computerized Program Search
System listing the title, author and affiliation for each
abstract along with the date and time of presentation can be
obtained ahead of time, for a fee, along with registration.
(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com
The Scientist,
3600 Market Street, Suite 450, Philadelphia, PA 19104
U.S.A.
--------
NXT:
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TI : AT A GLANCE (SOCIETY FOR NEUROSCIENCE - PROGRAM FOR
THE 24TH ANNUAL MEETING)
TY : NEWS
PG : 3
The 24th annual meeting of the Society for Neuroscience will
run from Sunday, November 13 to Friday, November 18, at the
Miami Beach Convention Center in Miami Beach, Fla. Following
is a list of the planned symposia and lectures scheduled du-
ing the conference:
Sunday, November 13
Decade of the Brain Lecture, 8:00 p.m.-9:00 p.m.:
"Consolidating the gains in brain"
Monday, November 14
Presidential Special Lecture, 10:00 a.m.-11:00 a.m.: "Cell
death in development and disease"
History of Neuroscience Lecture, 1:00 p.m.-2:00 p.m.:
"Evolving concepts of function of the neocortex"
Special Lectures
11:15 a.m.-12:15 p.m.: "Molecular studies of physiological
functions of glutamate receptor"
4:15 p.m.-5:15 p.m.: "The molecular biology and biophysics
of prions causing CNS degeneration"
Symposia
8:00 a.m.: "Molecular mechanisms of axon guidance"; "Genes
with triplet repeats in neuropsychic illness"
1:00 p.m.: "Neuroscience implications of inborn errors of
metabolism"; "Mo-lecular mechanisms of controlling K+
channel diversity and distribution in the nervous system"
Presidential Symposium
8:00 p.m.-10:00 p.m.: "The biology
of memory: From synapses to systems"
Tuesday, November 15
Presidential Special Lecture, 4:15 p.m.-5:15 p.m.:
"Transient and enduring effects of experience: Functional
studies of the visual and motor cortex"
Grass Foundation Lecture, 8:00 p.m.-9:00 p.m.: "In your ear:
Transduction, tuning, and transmission by hair cells"
Special Lectures
11:15 a.m.-12:15 p.m.: "Membrane receptors and ion channels:
Electron crystallographic studies of their design and action"
1:00 p.m.-2:00 p.m.: "Evolutionary origins of neocortex:
Reshuffling neurometers to make a new deck?"
Symposia
8:00 a.m.: "New approaches to understanding dendrites";
"The amygdala: From circuits and synapses to emotional
memory"
1:00 p.m.: "Cytokines and neural development"; "Autonomic
integration in the control of food intake"
Wednesday, November 16
Presidential Special Lecture, 11:15 a.m.-12:15 p.m.:
"Adaptation and exaptation in the evolution of the human
brain"
Special Lectures
1:00 p.m.-2:00 p.m.: "The role of local signals in the
control of CNS neuronal development"
4:15 p.m.-5:15 p.m.: "Potassium channels"
Symposia
8:00 a.m.: "Early development and molecular plasticity in
the mouse brain"; "Molecular plasticity in epilepsy and
ischemia"
1:00 p.m.: 8:00 a.m.: "Early development and molecular
plasticity in 8:00 a.m.: "Early development and molecular
plasticity in 8:00 a.m.: "Early development and molecular
plasticity in Toward a neurobiology of visual
consciousness"; "Developmental control of electrical
excitability"
Thursday, November 17
Warner-Lambert Lecture, 11:15 a.m.-12:15 p.m.: "Ins and outs
of programmed cell death"
Special Lectures
1:00 p.m.-2:00 p.m.: "Brain map for movement"
4:15 p.m.-5:15 p.m.: "Muscimol, memory, and motivation in
the basal ganglia"
Symposia
8:00 a.m.: "Structure, function, and regulation of glutamate
receptors"; "General anesthetic effects on somatomotor
processing"
1:00 p.m.: "The cell biology of secretion vesicles";
"Neuropeptide regulation of brain development: From cells to
animals"
Friday, November 18
Symposium
8:00 a.m.: "Neural coding of visual space: Visual mechanisms
of multimodal integration"
(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com
The Scientist,
3600 Market Street, Suite 450, Philadelphia, PA 19104
U.S.A.
--------
NXT:
NOTEBOOK
------------------------------------------------------------
TI : Calling All Taxonomists
TY : NEWS (NOTEBOOK)
PG : 4
The National Science Foundation's division of environmental
biology recently announced a special grant competition--
called Partnerships for Enhancing Expertise in Taxonomy--to
stimulate taxonomic research and training. The initiative is
spurred by concern over dwindling numbers of younger
scientists taking up taxonomy--the study of the general
principles of scientific classification--and systematics and
the limited knowledge that exists about thousands of
species. Specifically, NSF is seeking applicants to submit
ideas on how to train future generations of taxonomists and
how to translate current expertise into electronic databases
to broaden accessibility of taxonomic data, as well as
research proj-ects on taxonomy and evolution, especially of
little-known species. The deadline for applications is March
1. For more information, contact the division of
environmental biology at (703) 306-1480. E-mail:
sysrev@nsf.gov.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
NXT:
------------------------------------------------------------
TI : For Young Experimenters
TY : NEWS (NOTEBOOK)
PG : 4
Science students and teachers seeking ideas for classroom
science projects or contests can now turn to the Science
Experiments and Proj-ects Index. Written and edited by the
staff of the Columbus (Ohio) Metropolitan Library, the
source describes 8,400 hands-on, interactive experiments and
project ideas. The book is published by Fort Atkinson, Wis.-
based Highsmith Press, (800) 558-2110 or (414) 563-9571.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
NXT:
------------------------------------------------------------
TI : Clearing The Air
TY : NEWS (NOTEBOOK)
PG : 4
Beginning this month, the National Institute of
Environmental Health Sciences (NIEHS) in Research Triangle
Park, N.C., is establishing a clearinghouse to provide
information or referrals for questions about health and the
environment. Users can call EnviroHealth toll-free at (800)
NIEHS94 (643-4794) to receive information about NIEHS
research and training programs as well as referrals to other
NIH offices; clearinghouses; toll-free numbers; federal,
state, and local agencies; and information sources.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
NXT:
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TI : In The Name Of Cheeses
TY : NEWS (NOTEBOOK)
PG : 4
In keeping with the age-old link between fermentation and
religious orders--some of the best wines hail from
monasteries--Sister Noella Marcellino, a member of the
Benedictine Abbey of Regina Laudis in Bethlehem, Conn., and
a graduate student in microbiology at the University of
Connecticut in Storrs, is conducting research on the
microbes that flourish in naturally ripened cheeses and how
those organisms impart their distinctive flavors and aromas.
Her work gained her a Fulbright grant to travel to France
for nine months to study the microbes in such specialty
cheeses as Camembert and St. Nectaire, which are produced in
the Auvergne region. Sister Noella's microbial studies will
be conducted in a laboratory in Burgundy, where many
traditional cheeses are produced. In addition, she will
investigate traditional methods of ripening cheeses in
caves.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
NXT:
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TI : Natural History Online
TY : NEWS (NOTEBOOK)
PG : 4
Now available free of charge over the Internet is the full
catalog of Yale University's Peabody Museum of Natural
History. With more than a million entries, the catalog
offers information on the New Haven, Conn., collection's
nearly 11 million specimens, including some of the most
scientifically significant dinosaur fossils in the world. To
access the Peabody database, use the gopher command to
connect to "gopher.peabody.yale.edu" at port number 70. For
more information, contact Peabody's Lawrence Gall at
lawrence.gall@yale.edu.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
NXT:
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TI : A Helping Handbook
TY : NEWS (NOTEBOOK)
PG : 4
The Grant Application Writer's Handbook, by Liane Reif-
Lehrer--a former Harvard Medical School researcher and
National Institutes of Health study section member--was
issued earlier this month by Boston-based Jones and Bartlett
Publishers. The book covers both the psychology and the
mechanics of proposal writing, taking readers through the
steps of planning, outlining, drafting, revising, and
finishing an application. For more information, contact
Jones and Bartlett Publishers, One Exeter Plaza, Boston,
Mass. 02116; (800) 832-0034. Fax: (617) 859-7675.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
NXT:
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TI : Cool Comfort
TY : NEWS (NOTEBOOK)
PG : 4
The Multiple Sclerosis Association of America (MSAA) and the
National Aeronautics and Space Administration (NASA) have
signed a "Memorandum of Understanding" that expands their
collaborative efforts to further develop a spin-off NASA
technology--known as microclimate cooling--used to produce
lightweight vests, dubbed "cool suits," worn by MS patients
who suffer from heat stress. Those donning the suit have
experienced improvements in their speech as well as relief
from fatigue and other symptoms associated with the disease,
according to MSAA. For more information about microclimate
cooling and other MSAA services, call (800) 833-4MSA.
(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com
The Scientist,
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U.S.A.
--------
NXT:
OPINION
------------------------------------------------------------
TI : ARTHUR CAPLAN DISCUSSES ISSUES FACING THE GROWING FIELD
OF BIOETHICS
AU : FRANKLIN HOKE
KAREN YOUNG KREEGER
TY : OPINION
PG : 12
Editor's Note:
In May 1994, preeminent bioethicist Arthur Caplan moved his base
of operations from the University of Minnesota, Minneapolis,
where he had established the Center for Biomedical Ethics, to the
University of Pennsylvania in Philadelphia. There, he launched
the Center for Bioethics, hoping to expand the purview of his
activities through association with the extensive biomedical
research community at Penn and in the greater Philadelphia area--
initially, for example, sharing temporary offices with the
university's Institute for Human Gene Therapy. The 44-year-old
Caplan, who is the author of dozens of scholarly papers, also
strives to make critical bioethical debates comprehensible to the
public, most recently in his book Moral Matters: Ethical Issues
in Medicine and the Life Sciences (New York, John Wiley & Sons
Inc., 1995). As the fall semester got under way at Penn last
month, Caplan met with Senior Editor Franklin Hoke and Associate
Editor Karen Young Kreeger of The Scientist for a wide-ranging
discussion of his views and plans. Following is an edited
presentation of the interview.
Q Why did you decide to move to Penn?
A Well, Minnesota--the medical school in particular--had
oriented itself very strongly toward some high-tech forms of
transplantation, like bone marrow, while Penn has this
emerging gene therapy, testing, and screening interest and
was pulling together a group of people to do molecular
medicine. So, intellectually, that was a big draw for me.
Also, Minnesota didn't have much of a group doing health
economics and policy. But Wharton [Penn's business school]
does, and that was another attraction.
Q Is Philadelphia a good place to practice your discipline?
A Surprisingly, Philadelphia has not been a major presence
on the bioethics front, although it has all these medical
schools and hospitals--Fox Chase [Cancer Center], the
[American] College of Physicians, and so forth--and it has a
lot of pharmaceutical companies. So it looked like a place
where one could go and make something happen.
Q What are some of the new things you hope to do here?
A We'll definitely be moving into the genetics area, and
we'll try to work with Penn's very good history and
sociology of science units in the areas of eugenics,
heredity, and human nature theories. So, we'll go into
everything from the most practical questions--such as
insurance implications--to lofty theoretical matters [like]
what's a disease and whether medicine has, as its mission,
to improve or enhance as well as repair things.
Q What bioethical areas are you most concerned about?
A I'm especially interested in the rationing of health
care, both at the bedside and in terms of who gets access to
high-tech treatment--things like that. I'm also interested
in how to divvy up the health-care budget for the readers of
The Scientist. Should we spend more money on research or put
some kind of embolism in the research pipeline to slow down
cost? And what is the proper incentive system for technology
transfer?
And then there are end-of-life care decisions--termination-
of-treatment- and assistance-in-dying- type matters. And
questions of research on children--do we have a system that
protects their interests? If I tell you that your daughter
is sick and we can lop off half her pancreas to try to save
her, and you ask, "What are my options?" and I say, "None,"
and you say, "Okay, you have my consent"--is that good
enough? Does informed consent mean anything in the context
of very sick kids? My hunch is that it doesn't--and then how
do we replace or supplement informed consent?
Q Do you have a particular technique for exploring this
sort of issue?
A When I was in Minnesota, our center had a reputation for
trying to integrate descriptive empirical work with
prescriptive things, and I think we will do that at Penn,
too. Before I tell people what to do, I'd like to know sort
of what they're doing first. It may turn out that what
they're doing is what they're supposed to do, and it may
waste a lot of time to fish around for what they ought to do
if you don't know what they're doing already. I have the
feeling that most people don't read the informed consent
form, so shaping it into a finely honed document is probably
not useful for a lot of people.
On the other hand, there may be issues coming up from the
subjects that are not captured on the informed consent form.
But if you don't debrief them you'll never know that they
were mad about this or that nobody ever told them, for
example, that they were going to be nauseated after a
certain test. That's the place where I think we can do some
interesting empirical examination.
Q What are the origins of bioethics?
A Well, bioethics more or less started in response to
scandals over such things as the Tuskegee Study, where
people were deceived about getting treated for their
syphilis and not told that they had syphilis; or the
Brooklyn Jewish Chronic Disease Study, where demented,
terminally ill elderly patients were given live cancer cells
with no one's consent; or the Texas Contraceptive Trial,
where women were given placebos to test the effectiveness of
birth control pills. In response to these early T60s
scandals, bioethics shows up in the late T60s and says,
"We're going to fix this."
Q You say that "descriptive empirical work" is important to
you. Is that approach new to bioethics?
A Yes, it's definitely new. The scope could be anything
from what happens to someone who's signing up as a subject
for a research project all the way out to how a doctor
decides who gets access to a CAT scan. You just come in and
interview a dozen or so people at length, almost like a
journalist would, and sort of follow them over time and
paint the picture. Now, I'm not sure that anybody can say,
statistically, what number of case studies is enough to
generalize out to. But we are not interested in
generalizing--we're not interested in saying we understand
the whole population. Our empirical approach lets us pick up
what the problems are. I don't care if only one person
encounters a problem or 10 do; even if it's a problem of one
person, it's still a problem.
Q Does the use of an empirical approach help make bioethics
a science?
A The goals of ethics research aren't the same as those of
scientific study. The scientist may want to know how common
a problem is or, if you change variables, will it go away. I
am more interested in finding out simply what problems exist
out there. I sometimes think of this as "moral systematics."
It's like doing taxonomy. I talk this way in part because I
grew up as an evolutionary biologist, but it seems to me
that I'm closer to moral ethology in a sense of how an
animal behaviorist might study what's going on out in nature
and look for problem identification and classification.
The other type of empirical work involves what I could call
historical-sociological studies. We might, for example, be
looking at genetics as part of a historical review of what
happened in eugenics. Does anybody really know what the
Nazis did? Has anyone really looked at their arguments about
why they did it? And do we really understand enough about
the German or American experience with eugenics? I am
interested in looking at old laws, old policies, old ethics
arguments. What did the scientist in Germany say about
working in the camps?
Q And what are the present-day applications?
A I would call that an analogical examination. Does the
analogy hold up? Is it tight enough? Do you see the same
arguments today that you saw in the camps? Are the empirical
circumstances different from what they are today? We want to
see if the analogies, metaphors, and similes hold up in
relation to current issues. If someone compares abortion to
the Holocaust, for example, is that because fetuses are a
target of government policies intended to eliminate inferior
genetic human beings? If they mean that what the Germans did
in their genocidal activities is like what we have as a
policy about terminating pregnancies, we know, through our
analogical examination, that this comparison is not correct.
So, that argument against abortion falls away--even though
you still might think there must be moral standing
for the fetus.
I am interested in knowing if the ethnic arguments from the
past are convergent, divergent, homologous, or analogous so
as to understand whether I'm looking at a real phenomenon or
an accidental similarity. It's important to do this; if you
just start from your armchair to come up with ethical
theories, you may arrive at something very interesting, but
something close to what a mathematician does, or a math
modeler.
Q Like people who would model an ecosystem without ever
stepping into nature?
A Right, they don't step in the lake, and they don't care
to. But that's not my bent--my bent is to step into the
lake, to be sort of a moral naturalist and look for
phenomena. That's why I like being around the hospital;
that's why I like tying in to the people who do the work
with social science tools.
Q What influences led you to bioethics?
A Actually, those go all the way back to my early days, at
Columbia University, where as a graduate student I spent a
year at its medical school. So, I got interested in health-
care ethics by hanging around the hospital and the clinic.
That's how the idea of using the hospital as the laboratory
began, and out of that came my strong belief that if you're
going to be credible to doctors and scientists, you must
understand their world, their limits, their time
constraints, the financing that they're up against, and how
they talk.
Q You mean that before laying down ethical laws to people,
you have to understand what really influences what they can
and can't do?
A You shouldn't set your morality beyond what's possible.
Sometimes, a limit on morality is human nature, fallibility,
mistakes, a certain amount of egoism and greed. In order to
take that into account, you don't want to pretend that it's
a world of saints with infinite resources and unlimited time
and that we should all act in this way.
Q Returning to the subject of gene therapy, will there be an
organizational relationship between your group and Penn's
institute?
A The tie is really through me. I have an appointment in the
department of cellular and molecular engineering, as a
professor. I'm written into many of their grants, to sort of
watch that the gene therapy protocols meet the requirements
of the human subjects' study. So, it's not a center-to-
center marriage; it's more of a faculty-to-faculty marriage.
Q But doesn't the National Institutes of Health's
Recombinant DNA Activities Committee [RAC] already have a
very developed pattern of thinking about the ramifications
of gene therapy before the protocols are in place?
A To tell you the truth, while I'm not against having a
national RAC, the NIH committee may have outlived its
usefulness at this point in time in terms of the level of
review necessary for protocols relative to the risks. Most
of the people who are on RAC do gene therapy; they want to
do it right--but they also want to do it. I'd like to think
we can come at gene therapy at Penn with a little bit more
of an objective eye in terms of saying, "We don't care
whether it proceeds or not, we're just interested in looking
at the ethical issues."
Q What type of issues?
A Remember the incident in California involving gene
therapy for brain cancer? Basically, RAC had all these rules
about what you had to do to get gene therapy, and then they
threw them out the window when a woman who knew a senator
made an appeal. That's the kind of thing we'd like to look
at and say, "Don't let politics override the system." It's
not a good idea. It's not compassionate, necessarily, to
grant a terminally ill person access to a gene therapy
intervention that's not on a protocol. But it was hard for
them to say it, because they were getting influenced by
national politics. It's easier for us, at Penn, to say it;
we're not accountable to NIH or Congress or anything like
that.
Q Where does the Human Genome Project [HGP] office for
ethical, legal, and social implications [ELSI] fit into the
spectrum?
A ELSI is interesting, because it is the only area of NIH
that has been set up with a specific allocation of money to
look at ethical issues. And that's good. On the other hand,
I think that they have spent a lot of their time committing
themselves on issues identified by people who weren't in
close contact with what was going on in genetics. I will
tell you, flat out: Bioethics, in my view, is weak in
genetics. There are not a lot of philosophers, theologians,
and lawyers who know anything about it--I mean anything! I'm
talking about, do they know a chromosome from a gene from an
aardvark? It's an area where bioethics has not intersected
well with the scientific community.
Most of the people who come into bioethics have much more of
a clinical focus than a basic science focus. It's hurt the
ELSI program in a lot of ways. And I lobbied [HGP official]
Francis Collins pretty hard about this, saying I think it's
time we sort of get past the declarations of morality into
the nitty-gritty of it.
Q Don't you think a lot of researchers fear that bioethical
influences will impose too many constraints on their work?
A There's a common equation between ethics and saying no.
But my argument is that sometimes the job of ethics is to
say yes. I'll give you an example. I'm working on an article
that you'll probably hear about because people will be
streaming down the street to lynch me. It's called "What's
wrong with eugenics?" or "What's wrong with germ-line
engineering?" I happen to think the answer to both those
questions is, nothing, intrinsically. The question of
whether I should be able to pick blue eyes or brown or tall
people or short--I don't think there's anything wrong with
that, fundamentally.
Q It's a matter, then, of when to say yes or no?
A There may be reasons we ought not practice eugenics that
have to do with politics and the fear that some people may
go down the slippery slope, as the Germans did. If you're
worried about coercion--and the Chinese force that kind of
stuff--you oppose it. But if it's a pure question of, if I
turned on gene X and made my child grow another two inches,
and there was no risk to the kid, and nobody made me do it,
I don't see the problem. You know, you make children play
the piano an hour a day, seven days a week, for 10 years,
and you understand that you've imposed a lot of views on
them of what they should become. You start to think about
it, it's like, cripes, making him two inches taller may be
the least of his worries. It's more whether you make him
study in the yeshiva seven hours a day after school. That's
imposing a much more cognitive type of thing on a kid.
So, I don't buy the idea that the mission of ethics is to
say no or go slow or don't do it. That's an oversimplified
view. My idea is, sometimes it means yes and go faster and
you ought to do it, so why aren't you doing it? It seems to
me if you could do germ-line therapy to eliminate killer
diseases, not only should you do it, you must do it. If you
could eliminate sickle cell or Tay-Sachs by a safe form of
altering sperm or egg or embryo, I think it's morally
incumbent upon you to do it.
Q In connection with AIDS research, what are some
significant bioethical considerations--for instance, those
connected with arriving at an adequate experimental protocol
that could be used by AIDS researchers in developing a live
attenuated-virus vaccine?
A If it looked like some lines of vaccine research were
promising but were limited by the absence of an animal
model, then I'd be surprised if we wouldn't take the proper
steps. Specifically, we might try vaccines on people who are
brain dead and who are about to have their life support
disconnected. We might decide that we could add a provision
to their living will or their transplant donor card that
said, "You could use me for a limited period of time to test
a vaccine." You might get some information that would make
you feel more secure before you went to a living human. It
seems, as a reasonable place to turn, you may find
individuals who are terminally ill who want to volunteer as
human models.
The other population that's likely to be morally appropriate
for this are those groups in high-risk categories whose
behavior can't be changed. Of course, there's always an
obli-gation to try to get somebody to stop doing what puts
them at risk. But there's some truth in the idea that if you
go to a group of, let's say, sex workers in Thailand and
say, "You've got to get out of this business," and you come
back in two months and say, "You've got to get out of this
business and you've got to use condoms," and they're still
working there, that probably is the population you want
to go to for your vaccine trials. You've done
everything you can, and you continue to do it throughout
your entire study, to get them out of the business, even if
it hurts the study. But if you know they're going to do it,
and you're not going to get them out, that's where you go
for vaccine development.
Q You're aware how radical these ideas are.
A The intuitive thing is to say, "Well, you can't do this
and, I don't know, we just have no vaccines." I think the
right answer is, "Well, let's think more carefully about how
could we do this and feel comfortable that we haven't hurt
anybody or made them worse off." We've got an epidemic, and
we've got to do something.
Q Another area of considerable debate is technology
transfer between universities and industry. What are the
ethical considerations that must be addressed in the push to
commercialize research results from academic labs?
A There are really serious issues there. At one level, it's
been a fight about conflict of interest and disclosure, and
NIH is still struggling to come out with guidelines. They
basically rely on disclosure, the assumption being if you
tell people that you have this technology-transfer
arrangement, it'll be okay because they'll know how to read
your data or interpret what you say about whatever gizmo or
drug it is that you're working on. The other argument is,
you have to restrict how much scientists and doctors can
work outside the university. A day a week is a common rule
about how much outside work you can do. I think those
provisions are nice, but they're not getting down to the
real nitty-gritty questions. What's the impact of
privatization on basic vs. applied research?
If a university is supposed to be a place that pursues basic
research more than a company would do, and yet companies
underwrite more and more research or commercialization, will
we find ourselves richer in the short run but poorer in the
long run because we spent so much time developing this
generation of technology that we don't have anybody working
on the basic science for the next one? Also, what happens to
the graduate students who work in the labs of people who are
involved in corporate ventures? They can't do their thesis
because they've got to do work for a guy who's making money,
and they're a kind of cheap labor for that person.
But if a company has a gizmo that you can't get at the
school lab and if the company provides in-kind services
worth hundreds of thousands of dollars that you could never
get from your school, is that enough to pull your lab in an
unacceptable direction? Remember, this is basically a subtle
kind of a bribe to get you to do things. There are many,
many interesting questions about how commercialization and
for-profit motives are shaping biological and medical
science.
What you may need to do is teach that senior professor that
you don't push the graduate students around, and you can't
exploit them to do your work on the side, and you're not
going to get promoted for how many inventions you make.
You're still going to get promoted on the basis of how many
students put out good papers from this lab.
Q Why does bioethics seem to be such a hot area now?
A I think bioethics is especially of interest these days
for a couple of reasons. One, the cost of health care, the
cost of medical research, the cost of certain medical
innovation is up. So people always take an interest in what
they're getting for all this money. There is still a kind of
cornucopia of new technologies. Investments in the T50s and
T60s are now paying off with different kinds of devices, so
there are a lot of technology-driven questions: turning it
on, turning it off, when to use it, who gets it, that sort
of stuff.
I think bioethics is of interest because we don't have any
other place to turn. To some extent, our religious and
political leaders fail us in terms of understanding enough
about science to allow us to talk about what's going on. And
to some extent, science has taken on the guise of secular
religion. You may say that people go to the doctor with the
same hopes that they once brought to the minister: Save me,
prepare me, redeem me. In the Middle Ages, you used to see
cathedrals; now, what you see are towering medical centers
dominating the landscape.
Q In your new book, Moral Matters, you make a strong case
for the enduring value of ethical thinking.A I think a lot of scientists have the view that ethics is
subjective--that it's all a lot of talking and yakking and
blather that amounts to nothing--and that science is
concrete. A computer scientist said he once asked the
faculty at [the Massachusetts Institute of Technology], "How
many people think that 1,000 years from now people will
believe that the speed of light is 186,000 miles per
second?" Half the faculty raised their hands. Then he asked,
"How many people will believe 1,000 years from now that the
road to hell is paved with good intentions?" Everybody
raised their hands.
The point is that ethics is more concrete in the long run
than the physical stuff, which is contingent. And I believe
that.
(The Scientist, Vol:8, #20, pg.12, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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--------
NXT:
COMMENTARY
------------------------------------------------------------
TI : A Tribute To Robert K. Merton
On Receiving The National Medal Of Science
AU : EUGENE GARFIELD
TY : OPINION (COMMENTARY)
PG : 13
Last April 28, I had the pleasure of hearing my good friend
Robert Merton, the eminent sociologist and historian of science,
deliver the American Council of Learned Societies' 1994 Haskins
Lecture. The talk, presented at the American Philosophical
Society in Philadelphia, centered on Bob's "life of learning"--
the subject addressed each year by a notable "humanist" invited
by ACLS to deliver the prestigious lecture.
As Bob spoke about his boyhood in Philadelphia, his coming
of age as a young Harvard intellectual, and the factors that
fueled his preoccupation with the history of science and the
behavior of scientists, I was touched by a variety of
emotions. As often during the 30 years or so that I've known
him, I was fascinated by his capacious intellect and his
knack for originating concepts and expressing them in clear,
evocative terms. (Whether writing or speaking, he knows how
to hold his audience.) I was also proud, since he has worked
closely with me as mentor, colleague, and coauthor. I must
confess as well to a certain amount of civic pride, since
The Scientist--like Bob Merton--has its roots in the City of
Brotherly Love.
ACLS couldn't have made a more appropriate selection for the
1994 Haskins lectureship. That was also my reaction to the
recent news that Bob was among the eight individuals
selected by President Clinton to receive the 1994 National
Medal of Science. As we reported in our coverage of the
event (N. Sankaran, "Eight To Receive National Medals Of
Science," The Scientist, Oct. 3, 1994, page 1), he is the
first sociologist to be so honored. Evidently, I am not
alone in holding my good friend in high regard. Indeed, as I
listened to his lecture, the thought ran through my mind
that, if there were a Nobel Prize category for the sociology
of science, Bob Merton would have to be a recipient.
I am pleased by the honors this Nobel-class thinker is
receiving, as the international community of historians and
sociologists of science must also be--not that there has
been a dearth of recognition of this great mentor, now in
the 85th year of an incredibly productive life.
His record is indeed impressive. His masterpiece of
theoretical sociology, Social Theory and Social Structure
(New York, The Free Press, 1949; enlarged editions, 1957,
1968) has gone through 30 printings and ranks among the most
cited books in the social sciences. Two other seminal works,
The Sociology of Science: Theoretical and Empirical
Investigations (University of Chicago Press, 1973) and On
the Shoulders of Giants: A Shandean Postscript (University
of Chicago Press, 3d ed., 1993), should be, in my opinion,
required reading for all scientists.
While treating matters of serious consequence, Bob Merton
maintains a sense of irony, self-deprecating humor, and a
fondness for wordplay that has seasoned and humanized his
writings. In a recent note to me, he commented on a close-
to-hand example of a phenomenon he first described in an
article titled "The Matthew effect in science; the reward
and communication systems of science" (Science, 159:56-63,
1968). His neologism, "the Matthew effect"--named after a
passage in the Gospel of St. Matthew--holds that patterns of
biased peer recognition of authors of collaborative papers
are often "skewed in favor of the more established
scientist."
And so it is, he wryly observed, that papers written jointly
by him and his colleague, companion, and wife, sociologist
Harriet Zuckerman--now vice president of the Mellon
Foundation--were often mis-cited as having been written by
"Merton and Zuckerman"--even though, as he noted, "Harriet
is explicitly designated as the first author."
He went on: "It is ironic, of course, inasmuch as I am here
the dubious 'beneficiary' of the Matthew effect"--a
phenomenon that he had identified, named, and harshly
criticized.
The conceptual impact of the Merton oeuvre has been vast;
however, while he has profoundly influenced many aspects of
20th-century science, or at least our ways of thinking about
it, the influence has not been confined to the scientific
realm. Such Merton concepts as "the self-fulfilling
prophecy" and such Merton innovations as "the focused
interview" have found their way into our everyday lives. And
many of his visionary notions concerning the clockworks of
human behavior, while often pertaining originally to the
world of research, have been extended in application to
matters of family, business, and religion.
I congratulate my old friend Bob Merton on receiving the
National Medal of Science. And I encourage young scientists
who have not yet studied with this master to get to the
library or bookstore as soon as possible. A valuable treat
is in store for you.
(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
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--------
NXT:
LETTERS
------------------------------------------------------------
TI : NIH Triage
AU : HUGH STAMPER
TY : OPINION (LETTERS)
PG : 13
Jose Musacchio's commentary, entitled "Triage at NIH: A Smoke
Screen Concealing The Real Problems Facing American Science" (The
Scientist, Sept. 5, 1994, page 13), contains several
misperceptions. While it is true that the use of triage in peer
review would relieve some pressure on review staff at the
National Institutes of Health, it has never been suggested, as
Musacchio implies, that it would "solve the problems undermining
American science."
As now applied at NIH, triage focuses on reducing time spent at
review meetings by eliminating discussion on applications whose
scores would fall below the committee's midpoint (50th
percentile) and are unlikely to be changed by further discussion.
These noncompetitive applications, however, are carefully
reviewed in advance of the meeting. In fact, reviewers report
spending the same amount of time evaluating applications that are
ultimately deemed noncompetitive under triage as they did when
triage was not used. Reviewers prepare written comments in
advance of the meeting, as they have always done.
Contrary to Musacchio's perception, under triage, all applicants
receive summary statements. Furthermore, the use of triage has
facilitated the move from summary statements composed of
carefully integrated comments to those in which reviewers'
prepared comments are released intact and virtually unedited.
Thus, contrary to the suggestion that reviewers are no longer
accountable to applicants receiving a noncompetitive rating,
reviewers are more accountable, since their actual comments are
received by applicants.
Finally, Musacchio confuses the issue of triage by intertwining
it with funding aspects. Triage is not a culprit that prevents
worthy research from being supported. The primary objective of
peer review--and triage is consistent with this--is the
identification of the best research so that reasonable funding
decisions can be made. Availability of funds and the making of
funding decisions must continue to be assiduously separated from
peer review.
Certainly, triage will not cure all the ills related to obtaining
research support. It does, however, permit reviewers and NIH
staff to spend time more efficiently, while allowing the outcome
of review to be communicated more forthrightly to both successful
and unsuccessful applicants. Staff at NIH will continue to seek
improvements that will ensure fair, equitable, and efficient peer
review.
Hugh Stamper
Director, Division
of Extramural Activities
National Institute
of Mental Health
Parklawn Building, Room 9-105
5600 Fishers Lane
Rockville, Md. 20857
E-mail: Hugh_Stamper@nih.gov
(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
--------
NXT:
------------------------------------------------------------
TI : Conduct Meeting
AU : Charles W. McCutchen
TY : OPINION (LETTERS)
PG : 13
The article entitled "Meeting On Science Conduct Seen As A Noble
Attempt That Fell Short" by Franklin Hoke (The Scientist, July
25, 1994, page 1) says that "many of the attendees [at the
'Convocation on Scientific Conduct'] note with some dismay that
active research scientists were largely absent from among the
approximately 250 people [in the audience]." Did they really
think that many would come?
Displaying an interest in misconduct is not a path to advancement
in science. Remember what happened to Walter Stewart and Ned
Feder. Only scientists who have already sacrificed their careers
would dare to come, and why should they swell the audience for
this latest show put on by the biomedical science establishment
to give an appearance of action?
If the establishment ever decides to do anything real to halt
scientific misconduct, it will use the same subterranean methods
it now employs in the service of cover-ups. There will be no
fanfare.
Charles W. McCutchen
5213 Acacia Ave.
Bethesda, Md. 20814
(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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--------
NXT:
WHERE TO WRITE:
Letters to the Editor
The Scientist
3501 Market Street
Philadelphia, PA 19104
Fax:(215)387-7542
E-mail:
Bitnet: garfield@aurora.cis.upenn.edu
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=====================================
NXT:
RESEARCH
---------------------------------------------------------------
TI : Biomedical Researchers Step Up Efforts To Probe
Mysteries Of Aging
AU : Karen Young Kreeger
TY : RESEARCH
PG : 14
The population of the United States is aging. According to
the U.S. Census Bureau, the proportion of Americans aged 65
and older is expected to increase from about 12 percent
today to about 20 percent in 2030. By then, the average baby
boomer--those born in the years immediately following World
War II--will be upwards of 80 years old. And, like its
subjects, the field of biomedical science that explores the
physical, psychological, and sociological effects of the
aging phenomenon is visibly maturing.
As the baby boomer generation gets older, increased
attention is being focused upon geriatrics (the study of
illness in older people) and gerontology (the basic science
of aging processes). For scientists in these fields, the
demographic sea change has conceptually affirmed the need
for a more aggressive approach to aging research and,
consequently, has fueled growth in funding for it in recent
years (see story on page 1).
NIA's Broad Mission
Immunologist Richard Hodes is addressing the challenges of
this broad field of scientific study in two venues: the
director's office of the National Institute on Aging (NIA),
where he's responsible for administering the efforts of
about 6,000 intramural and extramural investigators and a
budget of more than $420 million; and at the bench of his
NIA lab, working with a team of investigators on the
relationship of the immune system to the biology of aging.
NIA, which was formed in 1974, is the primary source of
financial support for aging research in the U.S. According
to Hodes, the institute "evolved to provide a perspective
that was different from each of the organ- or disease-
specific institutes. It developed into an institute with a
very broad mission, which is based on the biomedical,
behavioral, and social aspects of the quality of life of
older citizens."
Hodes explains that the research sponsored by the institute
looks at a blend of the molecular and cellular mechanisms
that influence aging and longevity; behavioral factors, such
as diet and exercise, which play a role in mediating the
aging process; and the sociological implications of
providing care for an aging U.S. population.
NIA researchers agree that the dramatic shift in the makeup
of the population toward an older majority is the impetus
for the growth in their field. "The demography is really
the driving force," says Zaven Khachaturian, associate
director of the of aging program in neuroscience and
neuropsychology.
"It's been happening since the turn of the century. People
are living longer, and the older age group--85 and over--is
growing at a much faster rate than other age groups."
These demographic changes have had a direct impact on NIA
funding almost from the time the institute was formed. "When
I came here 15 years ago, the whole institute had a $28
million budget. And now our budget for fiscal year T94 is
over $400 million," notes Richard Sprott, associate director
for the biology of aging extramural program. "That would not
have happened without the demographic imperative.
"Aging and AIDS have been the largest growth areas in health
sciences for the last decade."
According to George Martin, science director of the
intramural program, a significant avenue of NIA research is
identifying risk factors such as diet and exercise habits
for certain age-related diseases.
Sprott adds that NIA's research mission "is not to produce
100-year-old people, but to improve the quality of the
terminal third of the lifespan that we've got."
And it seems that goal is starting to be realized. A recent
National Research Council report funded by NIA and entitled
Demography of Aging (L.G. Martin, S.H. Preston, eds.,
Washington, D.C., National Academy Press, 1994) states that
the prevalence of disability among the older population in
the U.S. decreased during the 1980s.
Focus On Alzheimer's
One major area that NIA funds--both intramurally and
extramurally--is the study of Alzheimer's disease. "Research
relevant to Alzheimer's is the single largest investment
currently at the institute," Hodes says.
Khachaturian heads the largest extramural program at the
institute--neuroscience and neuropsychology--which primarily
funds basic and applied Alzheimer's disease research. Just
over $190 million--half of the total NIA extramural budget--
is devoted to this program, with about 80 percent going to
fund Alzheimer's-related work.
Khachaturian says that research supported by the
neuroscience program, which he set up in 1978, ranges from
molecular-level basic research to epidemiological studies
involving many human subjects. "The notion is," he explains,
"that the study of the aging nervous system should not only
be done at the basic science level, but that it should be
done at the systems level, starting at very molecular, basic
areas like genetics and protein chemistry, moving up to
neurons and neural systems, and on to behavior and effects
on society.
"This approach has proved to be very fruitful, as
demonstrated by the success of the Alzheimer's program,"
Khachaturian adds. "There was very little known about the
disease in 1978. But in a short time, we have moved
Alzheimer's out of the dark ages to the cutting edge of
neuroscience because we integrate basic scientists with the
clinicians.
"In fact, I went out of my way to recruit people from other
disciplines--like protein chemistry, medicinal chemistry,
molecular biology, and genetics. If you look at the history
of many of the people who are in the field now, five to 10
years ago they weren't studying aging nervous systems or
Alzheimer's. They're all converts."
According to Hodes, it is with good reason that mounting
attention has been paid to Alzheimer's disease: "The genes
that appear to be responsible for some of the rare,
familial, early-onset forms have been identified, although
the mechanisms by which they influence disease remain to be
elucidated. And most recently, a lot of excitement has been
generated in the last year about the identification of the
ApoE gene, which has been identified as an epidemiological
risk factor for disease.
"This is an important first step. It will ultimately allow
an avenue by which we can understand the biology [of
Alzheimer's] and, hopefully, eventually the cause of the
disease, thus leading to diagnostic and, most importantly,
therapeutic intervention."
The Biology Of Aging
Another extramural program focuses on trying to unravel the
nature of longevity and aging from a biological perspective.
"The main thrust of almost everything we fund is aimed at
trying to understand the basic processes that go on at the
cellular and molecular levels that underlie the aging
phenomenon," says Sprott, referring to the biology of aging
program he heads.
The "aging phenomenon" has two parts, explains Sprott:
"those things that might be the aging processes themselves
as well as those which have an influence on age-related
phenomena, such as hip fractures and Alzheimer's."
Elucidation of the underlying mechanisms of aging processes
has become possible because of recent advances in molecular
biological techniques, he says: "In the last eight to 10
years, modern molecular biology grew up and provided us with
techniques that began to allow us to get answers."
As an example, Sprott cites a recent NIA-funded study
concerning the possible relationship between the telomere--a
part of the human chromosome--and the lifespan of certain
populations of cells. "There's been this recent discovery
that every time the cell divides the telomere gets shorter.
It's as if you're knocking off a little piece and the
telomere length is in fact a counter and it can count how
many times a cell line has doubled, and when it runs out the
line dies."
He says this finding is significant because of the
possibility that there is a physical "counting mechanism"
that would explain human mortality.
Another aspect of research in Sprott's program is
understanding the relationship among cell maintenance,
aging, and genetics. "Inside the cell the job of certain
genes is to maintain a very, very delicate balance between
senescence, which must happen, vs. immortality. If the
senescence genes become too active, they kill off cells, and
if they aren't active enough, [the cells] become immortal,
or cancerous, and the whole organism dies anyway," Sprott
explains.
NIA-funded investigators have found single genes that are
responsible for maintaining this control over senescence.
They call them longevity-assurance genes, or LAGs, according
to Sprott. He also mentions that colleagues at the National
Cancer Institute have found tumor-suppressor genes that are
very similar in composition to LAGs.
"What it looks like is that they may be the same genes
arrived at from two different directions," says Sprott. "I
think that what this says is that, as we understand the
basic processes of aging, we're going to understand the
basic processes of a lot of other things."
The Baltimore Study
Although much of NIA-funded work is devoted to basic
biomedicine, another important facet of the NIA mission is
to conduct holistic studies of human aging. One intramural
program centered at NIA's Gerontology Research Center in
Baltimore--the Baltimore Longitudinal Study--is the longest
continually running scientific study on human aging.
The study started in 1958 with 58 male subjects and was
directed by the former National Heart Institute. It now
includes more than 1,100 men and women ranging in age from
20 to 96. Its overall purpose is to follow individuals
throughout their lifetimes in order to understand the
process of aging in the human mind and body.
Hodes describes the study as an "insightful venture that
recognizes the importance of evaluating aging by studying
individuals as they age over time rather than by comparing a
given group of people who are young at a specific time with
a group of people who are old at the same time."
He says that the study has dramatically altered what
researchers consider "normal aging." The study has dispelled
stereotypes of what it means to grow old, such as the
commonly held scientific notion that the amount of blood
pumped per minute, or cardiac output, always decreases with
advancing age. Now, according to information from the
Baltimore study, gerontologists have revised their
description of the aging heart. They have found that
disease-free hearts in older individuals have a comparable
cardiac output to that of younger people.
So far the study has generally concluded that there is no
single, simple standard to describe human aging.
For more information on research grants offered by NIA,
contact Miriam Kelty, associate director of NIA and director
of the office of extramural affairs, NIH-NIA, Gateway 218,
Bethesda, Md. 20892; (301) 496-9322. Fax: (301) 402-2945.
The electronic mail address is:
kelty@nihniagw.internet.gov.
(The Scientist, Vol:8, #20, pg.14, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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--------
NXT:
------------------------------------------------------------
TI : NIA: COMING OF AGE
AU : KAREN YOUNG KREEGER
TY : RESEARCH
PG : 14
The National Institute on Aging (NIA) is celebrating its
20th anniversary this year. It was established in 1974 when
Congress passed the Research on Aging Act, charging the
institute to conduct and support biomedical, social, and
behavioral research as well as training and education on the
process of aging and the diseases and special needs of older
individuals.
"Our research is very far-ranging, from basic research into
cell regulation and cell death, to aging and cancer, to the
social and behavioral aspects of aging," says Miriam Kelty,
associate director of NIA and director of the office of
extramural affairs.
Some current NIA statistics:
NIA's appropriated budget for fiscal year 1994 is $420
million, of which $38 million went to fund intramural
research. For fiscal year 1995 the total appropriated budget
is $434 million, with almost 9 percent of that assigned to
the intramural program.
The extramural program supports more than 900 research
project grants in four main areas--the biology of aging;
geriatrics; neuroscience and neuropsychology; and behavioral
and social science--totaling nearly $250 million.
The majority of intramural researchers work at the
Gerontology Research Center in Baltimore, while the rest
work on the NIH campus in Bethesda, Md.
The intramural program covers 11 areas of research,
including cardiovascular science, molecular genetics, and
cognitive studies.
--K.Y.K.
(The Scientist, Vol:8, #20, pg.14, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com
The Scientist,
3600 Market Street, Suite 450, Philadelphia, PA 19104
U.S.A.
--------
NXT:
HOT PAPERS
------------------------------------------------------------
TI : DEVELOPMENTAL BIOLOGY
TY : RESEARCH (HOT PAPERS)
PG : 16
T. Braun, M.A. Rudnicki, H.H. Arnold, R. Jaenisch, "Targeted
inactivation of the muscle regulatory gene
Myf-5 results in abnormal rib development and
perinatal death," Cell, 71:369-82, 1992.
M.A. Rudnicki, T. Braun, S. Hinuma, R. Jaenisch,
"Inactivation of MyoD in mice leads to up-regulation of the
myogenic HLH gene Myf-5 and results in
apparently normal muscle development," Cell,
71:383-90, 1992.
M.A. Rudnicki, P.N.J.
Schnegelaberg, R.H. Stead, T. Braun, H.H. Arnold, R.
Jaenisch, "MyoD or Myf-5 is required for the formation of
skeletal muscle," Cell, 75:1351-9, 1993.
Michael A. Rudnicki (Institute for Molecular Biology and
Biotechnology, McMaster University, Hamilton, Ontario,
Canada): "Gene targeting has allowed the genetic dissection
of the roles played by the myogenic regulatory factors
(MRFs) in the development of skeletal muscle. The
introduction of null [loss-of-function] mutations in Myf-5,
MyoD, and myogenin into the germline of mice has revealed
insights into the hierarchical relationships existing among
the MRFs and established that functional redundancy is a
feature of the MRF regulatory network.
"Mice lacking a functional MyoD gene were found to have
no overt abnormalities in skeletal muscle and are altogether
viable and fertile (M.A. Rudnicki et al., Cell, 71:383-90,
1992). RNA and histological analysis could not detect any
difference between wild type and mutant MyoD mice. The
amount of Myf-5 mRNA is increased in mutant MyoD mice, which
suggests that Myf-5 may substitute for the absence of MyoD
in the development of skeletal muscle.
RAs with MyoD mutant mice, histological and northern-blot
analyses of newborn Myf-5-deficient animals did not reveal
any abnormalities in skeletal muscle. Muscle development is
delayed until the MyoD is expressed. As an indirect
consequence of this delayed development, Myf-5 mutant mice
have rib abnormalities that prevent normal respiration (T.
Braun et al., Cell, 71:369-82, 1992) and therefore die soon
after birth. The onset of MyoD expression, however, occurs
normally, followed by the expression of myogenin and other
differentiation-specific markers (T. Braun et al.,
Development, in press). These results suggest that the
activation of MyoD occurs independently of Myf-5 and that
MyoD can substitute for the absence of Myf-5 in the
development of skeletal muscle.
"The potential ability of Myf-5 and MyoD to substitute for
one another led to the hypothesis that Myf-5 and MyoD have,
at least to some degree, functionally redundant roles in the
development of skeletal muscle (M.A. Rudnicki et al., Cell,
71:383-90, 1992). To test this hypothesis, Myf-5 and MyoD
mutant mice were interbred. Newborn mice deficient for the
two MRFs are totally devoid of skeletal myoblasts as well as
muscle (M.A. Rudnicki et al., Cell, 75:1351-9, 1993). Mutant
pups are born alive but are immobile and die within minutes.
The spaces normally occupied by muscle are filled with
amorphous connective and adipose tissues, and desmin-
containing myoblast cells are absent.
"Other investigators have targeted the remaining MRF genes.
Mice lacking a functional myogenin gene are immobile and die
perinatally owing to deficits in skeletal muscle
differentiation (P. Hasty et al., Nature, 364:501-6, 1993;
Y. Nabeshima et al., Nature, 364:532-5, 1993). The skeletal
muscle in mice lacking myogenin display a marked reduction
in myofibers. However, myoblasts are present, and these are
organized in groups similar to wild-type skeletal muscle,
suggesting myogenin is not involved in patterning. Myogenin-
deficient mice also display a relatively mild rib deformity.
These results indicate an essential in vivo role for
myogenin in terminal differentiation of myoblasts into
myotubes.
"The absence of myoblasts in mice lacking both Myf-5 and
MyoD places these two factors upstream of myogenin in the
regulatory pathway. Moreover, this result suggests that Myf-
5 and MyoD are involved in the determination of myoblasts,
as these cells are absent when these factors are missing.
However, it is important to note that these results do not
preclude a role for Myf-5 and MyoD as differentiation
factors. For example, while myoblasts lacking myogenin fail
to differentiate efficiently in vivo, they form normal
multinucleated myotubes in vitro (Y. Nabeshima et al.,
Nature, 364:532-35, 1993). This suggests that in arrested
myoblasts in vitro MyoD can substitute for the role myogenin
plays in differentiation. The fourth myogenic factor MRF4
may function late in the myogenic pathway, as has been
implied by its expression pattern in cultured cells.
Alternatively, MRF4 may have a vital role early in the
development of the dorsal subdomain of the dermamyotome, as
suggested by its expression in vivo (T.H. Smith et al.,
Journal of Cell Biology, in press).
"The ability to target specific genes for inactivation in
the mouse has proved to be an extremely powerful tool to
genetically dissect complex biological phenomena. In the
near future, targeted inactivation of other important
players involved in skeletal myogenesis will certainly
provide much information as well as a few surprises."
(The Scientist, Vol:8, #20, pg.16, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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71764.2561@compuserve.com
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U.S.A.
--------
NXT:
------------------------------------------------------------
TI : ASTROPHYSICS
TY : RESEARCH (HOT PAPERS)
PG : 16
G. Schaller, D. Schaerer, G. Meynet, A. Maeder, "New grids
of stellar models from 0.8 to 120M; at Z=0.020 and Z=0.001,"
Astronomy & Astrophysics Supplement Series, 96:269-331,
1992.
Georges Meynet (Geneva Observatory, University of Geneva):
"The evolution of galaxies is intimately related to the
evolution of one of their main components--the stars.
Stellar evolution is responsible for the different colors of
galaxies. When the galaxy presents no sign of recent star
formation, most of its luminosity is due to red giant stars.
Inversely, a young stellar population manifests itself
through the presence of numerous blue stars as O-type and/or
Wolf-Rayet stars. In starburst galaxies, one can even
observe stellar populations that are completely dominated by
very young stars born a few million years ago.
"The chemical composition of the galaxies is also mainly due
to the enrichment of the interstellar gas by new material
synthesized in stars. Again, the metallicity of a galaxy
(the fraction of the mass of a galaxy in the form of
elements heavier than hydrogen and helium) is an indication
of its past stellar formation history.
"Stars may also deeply affect the dynamic and physical
properties of the interstellar medium. These few examples
show that in many active areas of astrophysics research--
such as the evolution of the galaxies, origin of the
elements, stellar-formation processes one needs information
on the way the stars evolve.
"At the Geneva Observatory, we have recently computed
extended grids of stellar models covering a wide range of
parameters such as initial mass and initial metallicity. We
have also investigated the effects of a change of the mass
loss rates on the outputs of massive stars models. This
article is the first of a series of five papers presenting
the whole set of stellar models (D. Schaerer et al., Astron.
& Astrophys. Suppl., 98:523-7, 1993; C. Charbonnel et al.,
Astron. & Astrophys. Suppl., 101:415-9, 1993; D. Schaerer et
al., Astron. & Astrophys. Suppl., 102:339-42, 1993; G.
Meynet et al., Astron. & Astrophys. Suppl., 103:97-105,
1994). The homogeneity of these data, computed with the same
physical ingredients and the same code for a great range of
important physical parameters, make them attractive for
people interested in stellar populations and the chemical
evolution of galaxies. Moreover, for many years we have
continuously improved the physical ingredients incorporated
in our stellar evolutionary code, taking into account recent
advances in stellar opacities calculations, measurements and
computations of nuclear cross-sections, and neutrino-
emission processes.
"Some of the physical ingredients of the stellar models
cannot be obtained with sufficient accuracy from experiments
alone or from purely theoretical considerations. In these
cases, we tried to constrain these quantities with detailed
comparisons between some theoretical predictions of the
stellar models and some well-established observed properties
of stars. In this way, we concluded that the mass loss rates
of massive stars during the periods when the stellar winds
are essentially driven by radiation pressure must be higher
than those given by the commonly used semi-empirical laws.
"At present our stellar models can account quite well for
many observed properties of the stars, and we hope that they
will represent a good starting point to go ahead in the
fields of stellar and galactic evolution."
(The Scientist, Vol:8, #20, pg.16, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
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U.S.A.
--------
NXT:
TOOLS & TECHNOLOGY
------------------------------------------------------------
TI : DNA Sequencing: Today's Technology And Beyond
AU : Scott Veggeberg
TY : TOOLS & TECHNOLOGY
PG : 17
Since the basic chemistry for DNA sequencing was developed
in the 1970s by Frederick Sanger of the Medical Research
Council, Cambridge, England, this technology has become a
ubiquitous tool in genetics, molecular-biology, and
microbiology labs. But the fastest-growing application of
DNA sequencing today is in clinical diagnostics. Also, rapid
advances in DNA sequencing have pushed the technology beyond
its conventional base in polyacrylamide slab gel
electrophoresis. These new approaches involve capillary gel
electrophoresis and even glass-plate DNA "chips" made with
photolithography processes.
The current market in automated DNA sequencers is a well-
ordered one, dominated by a handful of manufacturers. The
leading companies making these products all currently use
Sanger's basic chemistry for producing nested sets of
progressively longer DNA fragments. These sets of DNA
fragments are tagged with fluorescent dyes and then
separated by gel electrophoresis and automatically scanned
for identification of base-pair sequences.
"A DNA sequencer is nothing but an automated DNA
electrophoresis detection and analysis system," explains
Jack Ball, vice president of molecular biology systems at
Pharmacia Biotech Inc. in Piscataway, N.J., which markets
the ALF (automated laser fluorescence) DNA sequencer. From
Ball's description, this may sound like a simple enough
instrument, but sequencers are not cheap. Prices range from
$55,000 for an aggressively priced system introduced this summer
by Molecular Dynamics Corp. of Sunnyvale, Calif., to
$110,000 for the market leader, made by Applied Biosystems
Inc., a division of Perkin-Elmer Corp. in Foster City,
Calif.
The Major Players
Researchers interested in purchasing a DNA-sequencing system
have a basic choice. They may select a device from Applied
Biosystems, whose sequencer offers the highest throughput--
that is, the most number of bases that can be read in a day.
Alternatively, they may choose one of several other
manufacturers' systems, which cannot offer the same
throughput but are lower priced and offer higher sensitivity
as well as, in at least one case, longer read length--
referring to the base-pair length of DNA fragments. In fact,
one system, available from Lincoln, Neb.-based LI-COR Inc.,
can routinely read DNA fragments up to 800 and even 1,000
bases in length, compared with the 500 bases typically read
by its competitors. But in the final analysis, all of the
commercially available automated sequencers, and the
supporting reaction chemistry, are quite similar.
The current market in sequencers, dominated by a few major
manufacturers, may begin to fragment, however, as new
technologies--and the companies developing them--start
breaking onto the sequencing scene. The Human Genome
Project, with its ambitious goal of mapping the entire human
genome in a matter of years, has increased demand for far
faster, less cumbersome sequencing methods than are
available at present. This has catalyzed the development of
a number of new and unconventional approaches that could
allow a single scientist to sequence up to 10 million bases
per year. At this rate, the entire human genome, with its 3
billion bases, could be sequenced in a single year by just
300 workers.
"Everything that spins off the Human Genome Project will
[also] require confirmatory sequencing," says Ball. That is,
sequences derived rapidly will have to be confirmed, and
thus "the market for DNA sequencers will be absolutely
huge," he predicts.
New applications for DNA-sequencing technology, most notably
in the clinical diagnostic arena, will also expand the
market for sequencers, bringing new technologies and lower-
priced instruments to commercialization, say many industry
observers.
Alternative approaches--such as capillary gel
electrophoresis, hybridization, and time-of-flight mass
spectrometry--may bear fruit before the end of the decade.
But until then, the current technique of using slabs of
polyacrylamide gel to separate DNA fragments will remain the
method of choice. And, at least for now, the Applied
Biosystems technology is predominant.
Applied Biosystems claims to have about 85 percent of the
market in automated DNA sequencers in the United States,
leading Steve Lombardi, product manager for the AB 373 DNA
sequencer, to boast, "We own the market." One of the main
reasons for the company's market dominance is that it was
the first to come out with a sequencer, introducing the AB
373 in June 1986. Another reason is throughput. With its
unique four-dye technology, Applied Biosystems sequencers
read all four nucleotides in a single lane. Other systems
require four parallel sequencing reactions for a single DNA
strand. This multiplexing approach quadruples Applied
Biosystems' output over competing manufacturers, according
to the company.
Applied Biosystems, as well as Molecular Dynamics, also
sells automated robotic systems that perform the pre-
separation reaction chemistry developed by Sanger, which is
still the basis for DNA-sequencing technology. "Our goal is
to automate the molecular biology lab and all the different
applications in that lab," says Lombardi. "We don't just
sell sequencers anymore. We sell genetic analyzers." In
addition to DNA sequencing, these systems can be used to
perform DNA fingerprinting, mutation screening, linkage
mapping, and microsatellite analysis.
Sequencing The Sanger Way
The chemistry used to prepare samples for the currently
available automated sequencers is based on the tried-and-
true method developed in the 1970s (F. Sanger, Proceedings
of the National Academy of Sciences, 74:5463-7, 1977). In
this reaction, DNA is fragmented with restriction enzymes
into single-stranded lengths that readily pass through gels,
with the preferred length about 500 bases. The single-
stranded fragment is then mixed with DNA polymerase, and
with free nucleotides. The DNA polymerase runs along the
strand, "repairing" it by building a complementary strand.
If left alone, the reaction would end when the entire double
strand was completed. However, this would provide no
information on the sequences within the strand.
The trick used in the Sanger method is to force DNA
polymerase to occasionally terminate the reaction at base
number 1, then base number 2, number 3, and so on, resulting
in sequential DNA strands up to 500 base pairs in length. To
do this, a small amount of aberrant nucleotides, called
dideoxynucleotides, is mixed in with the normal
deoxynucleotides. These aberrant nucleotides lack the usual
free 3*-OH, which is needed to continue the polymerization
reaction. Whenever the DNA polymerase picks up an aberrant
nucleotide and incorporates it into the complementary
strand, the reaction halts. In the end, the test tube is
filled with a series of fragments ranging from one to 500
bases in length.
This is the point at which the manufacturers' technologies
diverge. AB utilizes four dyes, each of which is specific to
a particular dideoxynucleotide. One dye would react only
with dideoxyguanosine, another would react only with
dideoxyadenosine, and so on, so that each base fluoresces at
a characteristic wavelength, allowing all four bases to be
read in the same lane of the gel.
In the next step, the fragments are loaded manually onto a
DNA sequencer gel, which separates the fragments into
discrete bands that differ in length by one base. These
fragments will then migrate down the gel at a rate
proportionate to their length, with the shortest passing
through the most quickly. The length is thus determined by
its time of migration, and the base is determined by which
of the four wavelengths it fluoresces at.
The other manufacturers use a single-dye approach. At the
chain-termination step, the DNA fragment is put into four
separate reaction tubes, each one having only one of the
four possible aberrant nucleotides. The four separate
reactions are then loaded into four separate lanes on the
gel, with each lane corresponding to a different nucleotide.
The lower throughput obtained on these systems is simply a
consequence of needing four separate lanes, instead of just
one, to run one DNA strand.
The single-dye approach has advantages, however, explains
James Nelson, product manager for the Vistra line of
sequencers from Molecular Dynamics: "Because it's a single-
dye system, it's selected for much less expensive optics and
laser systems." The Applied Biosystems technology uses a
fairly complex argon laser, which is designed to produce
excitation wavelengths matched to the four different dyes.
As such, its output is not optimized for each individual
dye's absorption maxima, says Nelson. The single-dye system
used by Molecular Dynamics allows use of an inexpensive
helium-neon laser optimized for the company's dye.
The LI-COR system uses a simple infrared (IR) laser, the
same type of laser used in compact disc players. According
to Abraham Oommen, an applications scientist at LI-COR, the
IR laser system is far more sensitive than other detectors,
allowing less sample to be loaded. Plus, he notes, "most
biological molecules don't fluoresce in the infrared, so
background [interference] is negligible." Less interference
translates to longer read lengths, with LI-COR claiming that
researchers can routinely read out to 800 bases with "base
calling," or the identification of the bases, accomplished
automatically by the computer software. Longer read lengths
mean that fewer subclones have to be generated, which can be
a great cost and time advantage for university
investigators.
But LI-COR does not claim to be competitive with AB when it
comes to throughput. "Massive sequencing facilities would
not benefit from our machine," Oommen says. "We get out to
1,000 bases, but not with thousands of samples. So, if you
want to process 100 samples a day, go with an Applied
Biosystems machine."
Falling Prices
As is true of any lab equipment, price is always a powerful
consideration for researchers considering the purchase of a
sequencer. The $110,000 price tag for an Applied Biosystems
machine is something only the most dedicated user or core
facility can afford. For those on a tighter budget,
Pharmacia offers a sequencer that lists at $90,000 but can
usually be discounted into the $75,000 to $80,000 range,
says Ball. "And that's a significant [reduction] in prices."
Besides being a laser-excited, single-fluorescent dye system
with computer-based, automated base calling, the ALF
sequencer has a thermally jacketed gel plate, allowing
precise temperature control of the separation process. Also,
sequencing and data analysis are controlled by a 486
computer running under an OS/2 operating system. The OS/2
system was selected because it is truly multi-tasking,
meaning that data from one run can be manipulated, stored,
or printed with a completely different application while the
computer is running the separation and data analysis for the
current run.
The LI-COR system, which also takes advantage of the
multitasking capability of OS/2, is significantly less
expensive than Applied Biosystems' sequencer, however.
Priced at about $79,000, it has the advantage of longer read
lengths and higher sensitivity over other systems.
The Applied Biosystems and Molecular Dynamics sequencers run
on a Macintosh-based system. And, as Molecular Dynamics'
Nelson points out, "If you look out into the marketplace,
all the software [for genomic analysis] has been written for
the Mac. That's not because it's superior. It's just
history." Apple aggressively marketed its Macintosh systems
to colleges and universities, and much of the DNA software
written by professors and students is Mac-based, he says. In
light of this, Molecular Dynamics' sequencer allows the user
to easily interface with the extensive repertoire of
existing Mac-based programs by running on an Apple Quadra
610. But the real advantage of Molecular Dynamics' Vistra
system is its comparatively low price, listing at just
$54,900, half the cost of an AB 373. A robotic system, also
available from Molecular Dynamics, that can be used for
automating sequencing and PCR reactions may be added for
$59,000. Thus, for the price of an AB 373, a lab can get
both an automated sequencer and reaction system.
Will this competitive price put Applied Biosystems at a
market disadvantage?
Lombardi contends that Applied Biosystems has no intention
of dropping its prices to compete with the newcomer. "As the
market leader, you don't really like to respond," he
explains. "We just say that for $110,000, you're going to
get a well-respected instrument that's going to do the work
that needs to be done."
Instead of competing head-to-head with Applied Biosystems,
Molecular Dynamics is focusing on a different market. "The
AB system has been targeted at core labs and genome
sequencers with high throughput requirements," says Nelson.
"We're focusing on a different market niche, where
throughput is not as much an issue."
Throughput is relatively immaterial to Lonnie Ingram, a
professor in the microbiology and cell science department
at University of Florida, Gainesville, who has a LI-COR
sequencer in his lab. He confirms that the LI-COR will give
a longer read length than an Applied Biosystems sequencer,
and for his lab that's an advantage, since there are fewer
subclones and less wasteful overlapping of sequences. His
lab was doing all its sequencing manually before getting an
automated system. One big advantage of going from a manual
to an automated system was getting the radioactive isotopes
used in manual processes out of the lab--and the radiation
safety department off his back.
Capillary-Based Sequencing
A number of new sequencing approaches are under active
development, with some of them possibly coming onto the
market within the next few years. Chief among these
technologies is multiple-capillary gel electrophoresis.
Molecular Dynamics and Beckman Instruments Inc. of
Fullerton, Calif., are both reportedly working on such
systems, though neither company's representatives would
comment on exactly what stage of development it has reached
nor when the units might become available.
Capillary gel electrophoresis differs from the conventional
method in that the polyacrylamide, instead of being poured
out as a slab, is pumped into a 100-micron (internal
diameter) capillary. This narrow-bore capillary permits the
use of a much higher field strength, allowing separations
to be completed in about an hour, instead of the usual six
hours or more.
With currently available systems, only one capillary can be
run at a time, so throughput is not very high. Under
development, though, is a capillary array in which 24, 48,
or even 96 capillaries can be bundled and run in parallel,
allowing more sample lanes than a slab gel and a six-fold
increase in throughput over the current Applied Biosystems
technology.
One of the drawbacks with such a system is that the price of
the capillaries does not lend them to disposability. And
once the polyacrylamide gel is cross-linked it cannot be
scraped out as is done to recycle conventional gel plates.
But Barry Karger, a chemist at the Barnett Institute of
Northeastern University in Boston, says he is close to a
solution: "What we're pushing pretty hard is replaceable
matrices for capillaries." In this approach, the linear
polyacrylamide is not cross-linked and can thus be blown in
and then blown out of capillaries at the end of each run. In
a commercial system, the capillary preparation steps could
even be automated, he says. Better yet, unlike gel slabs,
which require tedious manual loading of samples, the sample
loading in a multiple-capillary system can be automated by
simply dipping the capillaries into sample wells and letting
the electric field draw in the DNA.
When will a multiple-capillary system be available? Karger
says that Molecular Dynamics has already debuted a 48-
capillary system at a recent trade show. While the company
didn't actually demonstrate the separation of DNA samples
with this system, it showed that it has solved some of the
design issues, such as how to scan the array of capillaries
with the laser. Karger thinks it could be as soon as "a year
or so" before such a system hits the market.
Sequencing On A Chip
Also just over the horizon is the hybridization approach,
such as the one being developed at Affymetrix Inc. in Santa
Clara, Calif. According to Robert Lipshutz, a mathematician
and director of bioinformatics at Affymetrix, the company is
developing a "DNA chip," which takes advantage of the
propensity of single-stranded DNA to complex with
complementary strands of DNA. A set of probes, consisting of
oligomers from eight to 20 nucleotides in length, can be
generated that will adhere to the target DNA. In the
Affymetrix approach, these oligomers are attached to glass
plates using the process of photolithography, widely used in
making computer chips and nano-machines.
In this application, a 1.28 x 1.28 cm region of a glass
surface is chemically prepared so that linker molecules,
terminated with a photolabile compound, are attached. Next,
using a photolithographic mask, a stripe of light is beamed
across a quarter of the plate's width, thus removing the
photolabile compounds in that area. Then, adenosine, for
instance, can be covalently bound to the glass through the
linker molecule. The free end of the nucleotide is capped
with a photolabile group to prevent any further reaction
until it is next exposed to light.
The process is repeated until there are four stripes: one
with adenosine (A), one with guanosine (G), one with
cytosine (C), and one with thymine (T). Afterward, the mask
is turned 90 degrees to form a cross hatch of stripes with
A, G, C, and T attached to the first set of nucleotides so
that all 16 possible nucleotide dimers are formed. Using
successively finer stripes of light, the oligomers can be
built up to a chain with a length up to 20 nucleotides,
which are attached to the glass plate at known positions,
says Lipshutz. "We can make a high-density chip with over
65,000 probes in 30 to 60 steps, taking about 10 minutes per
step." And the company can make 16 identical DNA chips at
the same time.
Fluorescently labeled DNA strands can then be washed over
the DNA chip, whereupon the DNA will hybridize with the
complementary sequences in the probes. The fluorescence is
determined by reading the chip with a confocal microscope
linked to an automated image scanner. For sequencing, this
approach could be extremely rapid, but there is still the
"ambiguity problem" to overcome, explains Lipshutz. That is,
DNA occasionally will form mismatches when complexing with
the oligomers.
Affymetrix is currently working out how to detect and deal
with these mismatches. "It's still a ways off until people
can do de novo sequencing," he says. But high-speed genome
sequencing is not the company's first goal. Affymetrix would
like to see the DNA chips applied to the rapid determination
of mutations in HIV, for example. When the virus is
challenged with a drug like AZT, which targets the reverse
transcriptase (RT) enzyme, the virus develops resistance via
mutations in the RT gene. What the DNA chip could provide is
information on when that mutation has taken place so that an
alternative drug regimen can begin. Lipshutz says the
company hopes to commercialize the DNA chip technology by
1996.
Clinical Diagnostics
The fastest-growing application for traditional DNA
sequencing today is in clinical diagnostics. Take, for
example, the well-known oncogene p53--mutations of this gene
play a role in a growing list of cancers. The p53 gene
consists of 11 exons, and it encodes for a 53,000-dalton
phosphoprotein that regulates cell proliferation.
What's been found, says Pharmacia's Ball, is that there are
dozens of different mutations that the p53 gene can undergo.
For researchers to discriminate among these mutations, the
p53 gene from a patient's tumor is sequenced to see whether
it is an aggressive type or one that is more treatable.
Another application is in diagnosing retinoblastoma (RB), a
rare inherited eye tumor that can cause blindness but, if
detected early, can be eradicated with laser surgery. To
date, more than 300 mutations of the RB gene have been
documented. The Eye Research Institute of Canada, affiliated
with the Hospital for Sick Children in Toronto, is using a
Pharmacia system to rapidly identify members of families
that carry a mutation of the RB gene. This allows the
researchers to exclude the unaffecte
Despite the promise of newly emerging capillary- and chip-
based technologies, users shouldn't expect that conventional
sequencing will vanish any time soon, says Pharmacia staff
scientist Anthony Murray. "I don't think the slab is dead,"
he asserts. Detectors capable of reading narrower lanes will
allow higher lane densities to be read on conventional gel
systems, which will extend the life span of the existing
technology. "I think in the near term, the gel approach is
going to be pretty hard to displace," he says.
Scott Veggeberg is a freelance science writer based in
Swarthmore, Pa.
(The Scientist, Vol:8, #20, pg.17, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
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--------
NXT:
------------------------------------------------------------
TI : SUPPLIERS OF DNA SEQUENCERS, SYSTEMS, AND SOFTWARE
TY : TOOLS & TECHNOLOGY
PG : 21
American Bioanalytical Inc.
Natick, MA
Circle No. 101 on Reader Service Card
Amersham Corp.
Arlington Heights, IL
Circle No. 102 on Reader Service Card
Applied Biosystems
Division of Perkin-Elmer
Foster City, CA
Circle No. 103 on Reader Service Card
Beckman Instruments Inc.
Fullerton, CA
Circle No. 104 on Reader Service Card
Biomed Instruments Inc.
Fullerton, CA
Circle No. 105 on Reader Service Card
Biomedical Research &
Development Labs Inc.
Gaithersburg, MD
Circle No. 106 on Reader Service Card
Bio-Rad Laboratories
Life Science Group
Hercules, CA
Circle No. 107 on Reader Service Card
Boehringer Mannheim Corp.
Indianapolis, IN
Circle No. 108 on Reader Service Card
C.B.S. Scientific Co.
Del Mar, CA
Circle No. 109 on Reader Service Card
DNA ProScan Inc.
Nashville, TN
Circle No. 110 on Reader Service Card
DNASTAR Inc.
Madison, WI
Circle No. 111 on Reader Service Card
EG&G Berthold
Nashua, NH
Circle No. 112 on Reader Service Card
Fisher Scientific
Pittsburgh, PA
Circle No. 113 on Reader Service Card
Hoefer Scientific Instruments
San Francisco, CA
Circle No. 114 on Reader Service Card
Inotech Biosystems
Lansing, MI
Circle No. 115 on Reader Service Card
Integra BioSciences Inc.
Woburn, MA
Circle No. 116 on Reader Service Card
IntellliGenetics Inc.
Mountain View, CA
Circle No. 117 on Reader Service Card
Intermountain Scientific Corp.
Kaysville, UT
Circle No. 118 on Reader Service Card
Jordan Scientific Co. Inc.
Bloomington, IN
Circle No. 119 on Reader Service Card
Laboratory & Research
Products
New Haven, CT
Circle No. 120 on Reader Service Card
Li-Cor Inc.
Lincoln, NE
Circle No. 121 on Reader Service Card
Life Technologies Inc.
Gaithersburg, MD
Circle No. 122 on Reader Service Card
Marsh Biomedical Products Inc.
Rochester, NY
Circle No. 123 on Reader Service Card
Midwest Scientific
St. Louis, MO
Circle No. 124 on Reader Service Card
Molecular Biology Resources Inc.
Milwaukee, WI
Circle No. 125 on Reader Service Card
Molecular Dynamics
Sunnyvale, CA
Circle No. 126 on Reader Service Card
National Biosciences Inc.
Plymouth, MN
Circle No. 127 on Reader Service Card
Owl Scientific
Woburn, MA
Circle No. 128 on Reader Service Card
Perkin-Elmer
Norwalk, CT
Circle No. 129 on Reader Service Card
Pharmacia Biotech Inc.
Piscataway, NJ
Circle No. 130 on Reader Service Card
Promega Corp.
Madison, WI
Circle No. 131 on Reader Service Card
Scanalytics
Billerica, MA
Circle No. 132 on Reader Service Card
Stratagene
La Jolla, CA
Circle No. 133 on Reader Service Card
Textco Inc.
West Lebanon, NH
Circle No. 134 on Reader Service Card
Time Logic Inc.
Moorpark, CA
Circle No. 135 on Reader Service Card
UVP Inc.
Upland, CA
Circle No. 136 on Reader Service Card
Zymark Corp.
Hopkinton, MA
Circle No. 137 on Reader Service Card
(The Scientist, Vol:8, #20, pg.21, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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U.S.A.
--------
NXT:
------------------------------------------------------------
TI : NEW PRODUCTS
TY : TOOLS & TECHNOLOGY
PG : 22
Hamamatsu Introduces Low-Light CCD Camera
The C4880 dual-mode, cooled charge coupled device (CCD)
camera is designed for use in measurements requiring low
light and high dynamic range as well as in photometry and
precision still-image acquisition. It has a sensitivity of
10 lx to 10-7 lx and a resolution of 1 million pixels (1,000
x 1,018 pixels). The C4880 offers both fast- and precision-
scan modes. It has an analog-to-digital conversion rate of
up to 10 MHz per pixel. Its digital output of up to 16 bits
is compatible with most frame-grabber and display hardware
on the market. The camera may also be
controlled by computer through its RS-232C serial
interface.
Hamamatsu Corp., Bridgewater, NJ
Circle No. 138 on Reader Service Card
-----
ScanalyticsU RFLPscan Package For Protein, DNA Analysis
Version 2.0 of RFLPscan is a Windows-based software package
for performing genetic analyses derived from DNA restriction
fragment patterns, DNA fingerprints, protein typing
patterns, and other identity-profiling gel images. It is
able to analyze images obtained from film densitometers,
flatbed scanners, CCD video cameras, storage phosphor
devices, and radiometric detectors. The software offers
comprehensive databasing capabilities that permit the
comparison of lane profile data from gels as well as
pairwise and simultaneous matching of individuals.
Scanalytics, Billerica, MA
Circle No. 139 on Reader Service Card
-----
ImageSpace Software Available As Stand-Alone Product
ImageSpace 3.1 software was previously available only as a
part of Molecular DynamicsU CLSM systems. The confocal
package offers an integrated environment for rendering,
processing, analysis, and display of confocal images, using
an intuitive graphical user interface. Running on a Silicon
Graphics workstation, ImageSpace software allows
investigators to perform quantitative image analysis on
three-dimensional data. Advanced analytical capabilities
include automated object counting, seeding, and segmention;
the program features tools for quantitative co-localization
studies. The different 3-D analysis and 3-D visualization
tools can be combined.
Molecular Dynamics, Sunnyvale, CA
Circle No. 140 on Reader Service Card
-----
Gilson Announces Robotic Liquid Handler
The 215 Liquid Handler is an XYZ coordinate system robot that
automates various manual liquid-handling procedures and sample-
preparation protocols. It has the capability to pierce thick tube
septa to reduce the risk of exposure to potentially hazardous or
infectious samples. Non-piercing probes for open-tube sampling
are also available. The system is fully programmable and performs
with a positional accuracy of 1 0.5 mm in the X and Y axes. It
features a built-in dilutor for autodilution tasks, a large
selection of syringe sizes, 15 standard and thermostatic racks,
and several tube options.
Gilson Inc., Middleton, WI
Circle No. 141 on Reader Service Card
-----
New Electroporation System From BTX
The Electro Cell Manipulator (ECM) 600 for electroporation
of prokaryotic and eukaryotic cells features two voltage
ranges (2.5 kV/500 V), an additive capacitor bank, and
resistance timing, and makes possible instantaneous
monitoring within a single unit. It is equipped with
internal monitoring that measures true peak voltage and
pulse length. The system includes a safety stand, cuvette
rack, and a package of 50 sterile, disposable cuvettes in 1
mm, 2 mm, or 4 mm gap sizes.
BTX Inc., San Diego, CA
Circle No. 142 on Reader Service Card
-----
Storage And Reaction Tubes
Offered For PCR Applications
HotStart 100 storage and reaction tubes are 0.5 ml thin-wall
polymerase chain reaction (PCR) tubes with a wax bead
preadhered on the interior surface. The wax forms a uniform
convective vapor barrier, which is said to reduce mispriming
and primer oligomerization. The convective barrier also
allows for separation of reaction components until the
annealing temperature of the PCR reaction has been reached.
The wax barrier seals the PCR product or prealiquotted
master mixes for long-term storage in a lab freezer or
standard refrigerator.
Molecular Bio-Products Inc., San Diego, CA
Circle No. 143 on Reader Service Card
-----
Bio-Rad Unveils Vertical Electrophoresis Cell
PROTEAN II xi cells perform a variety of separations,
including SDS-PAGE, native, preparative, gradient, and high-
resolution nucleic acid agarose electrophoresis. In
addition, with the two-dimensional electrophoresis
technique, they are able to separate in both the first and
second dimension. The cells enable users to run one, two, or
four slab gels, or up to 16 IEF tube gels simultaneously.
They are available in 1 cm or 2 cm gel lengths with a
selection of combs and spacers.
Bio-Rad Laboratories, Hercules, CA
Circle No. 144 on Reader Service Card
-----
Double-Stranded, Site-Directed Mutagenesis Kit
The Chameleon kit is designed for single- and multiple-base
substitution, insertion, and deletion mutations in virtually any
double-stranded plasmid. Its site-elimination mutagenesis
procedure introduces a new mutnS host strain, XLmutS, which is
EndAQ. The endA mutation removes an endonuclease that degrades
miniprep DNA. The kit can be used with almost any plasmid
template containing a unique, nonessential restriction site and
does not require CsCl-purified DNA.
Stratagene, La Jolla, CA
Circle No. 145 on Reader Service Card
-----
WhatmanUs SMART Colorimeter
The SMART Colorimeter and SMART Reagents offer menu-driven
operation for analysts measuring a variety of water-quality
parameters. The SMART Colorimeter uses a tungsten lamp to
deliver colorimetric analysis of absorbance readings from 1
to 2A and %T readings from 0 to 100 percent. In the
laboratory or field, the alphabetical test selection plus 39
prepackaged reagents are designed to reduce analysis time
and save on reagent time and preparation.
Whatman LabSales Inc., Hillsboro, OR
Circle No. 146 on Reader Service Card
-----
Mettler-Toledo's Volumetric Evaluation Printer Debuts
The LC-PVolume is a compact printer designed for evaluating
the performance of volumetric equipment by means of
gravimetric analysis. The single-balance system, based on
guidelines from the National Committee for Clinical
Laboratory Standards, automatically performs complex
calculations and prints them in a user-defined report.
Features of the system include storage of 60 programs,
password protection, alphanumeric input, and a verification
report for International Standards Organization and Good
Laboratory Practices requirements.
Mettler-Toledo Inc., Hightstown, NJ
Circle #147
-----
MathWorks Releases MATLAB Update For Windows
A new feature of MATLAB version 4.2c for Windows is the
MATLAB Notebook, which integrates the softwareUs Technical
Computing Environment with Microsoft Word 6.0. The Notebook
Suite also provides an intuitive front-end for MATLAB
through a dynamic link with Microsoft Word 6.0. This enables
users to incorporate MATLAB graphics and commands directly
into reports via a word-processing application interface;
make changes in one portion of the document or any
underlying data; and recalculate graphic and data results
throughout the entire document.
MathWorks Inc., Natick, MA
Circle No. 148 on Reader Service Card
-----
(The Scientist, Vol:8, #20, pg.22, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
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U.S.A.
--------
NXT:
PEOPLE
------------------------------------------------------------
TI : Penn State Researcher Chosen To Receive American
Chemical Society's Bader Award
AU : NEERAJA SANKARAN
TY : PROFESSION (PEOPLE)
PG : 24
Stephen J. Benkovic, a professor of chemistry at the
Pennsylvania State University at University Park, has been
named as the winner of the American Chemical Society's 1995
Alfred Bader Award in Bioinorganic and Bioorganic Chemistry.
He will receive the award at ACS's national meeting next
spring in Anaheim, Calif.
Benkovic's research over the years has focused on
understanding how enzymes catalyze chemical reactions. "My
early work involved looking at the mechanisms of organic
reactions of small molecules that mimic biological
processes, and extrapolate that information to how an enzyme
might work," he explains.
During his years as a graduate student at Cornell
University, Ithaca, N.Y.--where he received a doctorate in
1963--and a postdoctoral fellow at the University of
California, Santa Barbara, he coauthored a two-volume set of
books defining the subject of bioorganic chemistry along
with his research supervisor, Thomas Bruice (Bioorganic
Mechanisms, Vols. I and II, New York, Benjamin, 1966).
"Over the years my work evolved to the study of the enzymes
themselves," adds Benkovic, who now does research on a
variety of enzymes and catalytic antibodies, and recently
reported an antibody that catalyzes peptide synthesis. (R.
Hirschmann et al., Science, 265:234-7, 1994).
Benkovic, 56, conducted his undergraduate studies in both
literature and chemistry at Lehigh University, Bethlehem,
Pa., before going on to Cornell.
The chemist, who has been at Penn State since 1967, serves
as Evan Pugh Professor and holds the Eberly Family Chair in
the chemistry department there. He was elected to the
National Academy of Sciences in 1985.
--Neeraja Sankaran
(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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U.S.A.
--------
NXT:
------------------------------------------------------------
TI : Illinois Congressman Honored For Devotion To
Biomedical Research
AU : NEERAJA SANKARAN
TY : PROFESSION (PEOPLE)
PG : 24
The American Association of Immunologists presented Rep.
John Porter (R-Ill.) with a Public Service Award during a
special ceremony held at the United States Capitol on
September 20. Porter is the first recipient of an award that
the 6,000-member, Bethesda, Md.-based scientific society
established to recognize individuals from the lay community
who have demonstrated the im-portance of basic biomedical
research to the public.
The congressman was honored for promoting the importance of
the National Institutes of Health and its research on
Capitol Hill. As a member of the House Appropriations
Committee, and the ranking Republican on the committee's
Labor, Health and Human Services subcommittee--which funds
NIH research--Porter has made basic biomedical research a
priority. Last year, he played a leading role in ensuring
that the 1994 budget supported NIH research with a 6 percent
increase, rather than the 1 percent recommended in President
Clinton's first budget.
"That level of funding would have proved devastating to
biomedical research," Porter maintains, adding that the
budgetary increase to NIH was appropriated without spending
additional money.
Porter, 59, received his J.D. degree from the University of
Michigan Law School in 1961, and practiced law in Evanston,
Ill., until his election to Congress in 1980. He says that,
in supporting basic research, "it is very, very important
that politicians don't put themselves in the position of
managing science. Our role is to give it the tools for
advancement."
--Neeraja Sankaran
(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
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U.S.A.
--------
NXT:
------------------------------------------------------------
TI : Torrey Botanical Club Elects New President
AU : NEERAJA SANKARAN
TY : PROFESSION (PEOPLE)
PG : 24
The Torrey Botanical Club, one of the oldest professional
societies in the United States, has elected a new president,
Steven N. Handel, an associate professor of plant ecology in
the department of biological sciences at Rutgers University
in Piscataway, N.J. Handel, who will serve a one-year term
during the 1995-96 academic year, was installed as
president-elect last month. Handel succeeds Margaret Basile,
a botanist who is currently a research associate at the City
University of New York's Lehman College in the Bronx.
Named after 19th-century botanist John Torrey, the club was
initially founded in 1866. Current worldwide membership
stands at about 650. Although it has no official
headquarters, it holds monthly meetings at the Bronx (N.Y.)
Botanical Gardens and hosts a symposium at the annual
meeting of the American Institute of Biological Sciences, a
Washington, D.C., organization of professional societies.
"One of the things I hope to do as president is to arrange a
symposium on restoration ecology that gets academics, city
officials, and public-policy regulators together in one
place to talk about what can be done in big cities like New
York," says Handel, 49, who specializes in reproductive
ecology in plants and the evolution of pollination systems.
He currently is involved in a project--jointly funded by the
National Science Foundation and New York City's sanitation
department--to see how plant ecology can help in restoring
native vegetation in landfill sites in the New Jersey and
New York area.
He is a visiting professor at Macquarie University in
Sidney, Australia, where he studies pollination in orchids.
--Neeraja Sankaran
(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
----------
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