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THE SCIENTIST
VOLUME 8, No:23 NOVEMBER 28, 1994
(Copyright, The Scientist, Inc.)
============================================================
Articles published in THE SCIENTIST reflect the views of their
authors and not the official views of the publication, its
editorial staff, or its ownership.
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*** DECEMBER 14, 1994 ***
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THE SCIENTIST
(Page numbers correspond to printed edition of THE SCIENTIST)
FOR SEARCHING PURPOSES:
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TI : CONTENTS
PG : 3
NEWS
REVIEWING TRIAGE: The expanded use of triage--in which some grant
applications are deemed "noncompetitive" and not discussed in
National Institutes of Health study sections--has drawn praise
from some NIH administrators but has engendered considerable
controversy in the extramural community
PG : 1
NEW LIFE FOR EMBRYO RESEARCH: If NIH accepts recent
recommendations from an advisory panel, some research involving in
vitro human embryos will be eligible for funding for the
first
time in 15 years. But critics of the panel's ethical
rationale--many outside the scientific community--are already
lining up in opposition
PG : 1
ABOUT TIME: Colleagues of the recently announced Nobel laureates
in science say such recognition is long overdue. Meanwhile, the
winners are using their moment in the limelight to lobby for more
governmental support of basic research
PG : 1
JOINING THE FIGHT: Industry has signed on in a major way to the
effort to advance science-education reform, as indicated by
participation in several recent high-profile initiatives. One of
these was a September conference sponsored by Merck and Co. Inc.
PG : 1
A FRESH LOOK: Troubled Biosphere 2, under new management, has
brought in scientists from many fields to help revitalize the most
criticized aspect of its mission--the quality of its science
PG : 3
OPINION
CURIOUS CONVICTIONS: The Clinton-Gore administration rhetoric in
support of science and technology policy is belied by its
anti-technology policies, perhaps best exemplified by its punitive
and often illogical regulation of biotechnology, in the view of
Henry I. Miller, Robert Wesson Fellow of Scientific Philosophy and
Public Policy at the Hoover Institution and a consulting professor
at Stanford University's Institute for International Studies PG
: 12
COMMENTARY: Basic science is in the national interest and is
"strategic" for the future of the United States, facts that are
not appropriately recognized by Congress or the public--to the
detriment of vital investigations as well as America's
students--says Michigan State University associate biochemistry
professor Zachary Burton
PG : 13
RESEARCH
DOMINATING FROM THE DEPTHS: Biological oceanography led a recent
study of the citation records of ecology and environmental
sciences articles, reported in the newsletter Science Watch
PG : 15
HOT PAPERS: Structural biologist Ivan Rayment discusses the muscle
protein myosin; cell biologist Michael Kastan describes steps of
a
signal-transduction pathway in mammalian cells; epidemiologist
Miriam Alter reports on a study of hepatitis C virus patients
PG : 16
TOOLS & TECHNOLOGY
BLOTTING: Blotting technology has recently received widespread
publicity because of its use in forensic cases, but these same
techniques have long been workhorses in life-sciences labs
PG : 17
PROFESSION
JOURNAL JOBS STIMULATING BUT SCARCE: For researchers, editorial
positions in science journals have the advantages of being
stimulating and often quite well-paying, but also a major
drawback--being quite scarce
PG : 23
ADOLFO J. deBOLD AND ERVIN G. ERDOS, research director at the
University of Ottawa's Heart Institute and director of the Peptide
Research Laboratory at the University of Illinois College of
Medicine, respectively, have won the Ciba Award for Hypertension
Research
PG : 24
SHORT TAKES
NOTEBOOK PG : 4
CARTOON PG : 4
LETTERS PG : 13
LEADERS OF SCIENCE PG : 14
BLOTTING APPLICATIONS AND SUPPORT MEDIA DIRECTORY PG : 19
NEW PRODUCTS PG : 21
CROSSWORD PG : 24
(The Scientist, Vol:8, #23, p.3, November 28, 1994)
(Copyright, The Scientist, Inc.)
================================
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TI : Colleagues Laud 1994 Nobelists As Overdue For Coveted
Prize
AU : EDWARD R. SILVERMAN
TY : NEWS
PG : 1
Colleagues of the recently announced winners of the 1994 Nobel
Prizes in chemistry, physics, and medicine or physiology, in
praising the decisions of the Nobel committee, say the coveted
Swedish honor is long overdue for each of this year's recipients.
For their part, the winners are using their newfound recognition
to lobby for greater funding for basic science.
Alfred G. Gilman, chairman of the pharmacology department at the
University of Texas Southwestern Medical Center at Dallas, and
Martin Rodbell, a scientist emeritus in the Laboratory of Cellular
and Molecular Pharmacology at the National Institute of
Environmental Health Sciences in Research Triangle Park, N.C.,
were named to share the prize in physiology or medicine for their
discovery of G proteins and the role of these proteins in signal
transduction.
George A. Olah, director of the Loker Hydrocarbon Research
Institute at the University of Southern California (USC) in Los
Angeles, was selected to receive the prize in chemistry for his
work on carbocations.
The physics laureates are Bertram N. Brockhouse, an emeritus
professor of physics at McMaster University in Hamilton, Ontario,
Canada, and Clifford G. Shull, an emeritus professor of physics at
the Massachusetts Institute of Technology, chosen for their
contributions to the development of neutron-scattering techniques
for studies of condensed matter. Each winner receives or shares a
$930,000 prize, which will be presented next month.
Reflecting on years spent working alongside the five winners in
laboratories across North America, their associates describe the
recipients as dedicated scientists who have not been afraid to
take risks in pursuit of their research.
Recalling his work with Rodbell at the National Institutes of
Health between 1970 and 1985, for example, Constantine Londos,
chief of the membrane regulation section at the National Institute
of Diabetes and Digestive and Kidney Diseases, says: "Marty was an
independent guy who didn't like to restrict people. He'd look at
our work and wasn't concerned with how others might interpret
things. He didn't like to be a conformist. He was a leader by dint
of his nature."
Sweden Signals Approval
Rodbell, 69, and Gilman, 53, discovered G proteins, natural
substances that act as signal transducers, or intermediaries to
relay signals from outside cells to the inside. The G proteins, so
called because they bind guanosine triphospate (GTP), control a
wide range of basic life processes. An excess or deficiency in G
proteins, or alterations in their genetic composition, can lead to
endocrine disorders or tumors. In addition, alterations in
transduction of signals through these proteins may cause symptoms
of diseases such as diabetes and cholera. The two scientists' work
has been the springboard for a flurry of further studies by other
researchers--many of which The Scientist has identified as "hot"
papers--as molecular biologists try to refine their understanding
of the signal-transduction process.
In 1970, Rodbell found that GTP is required in order for glucagon
to stimulate production of cyclic AMP
(adenosine-3_,5_-monophosphate), initiator of the process by which
hormones transmit signals to cells. His two seminal papers--M.
Rodbell et al.,"Glucagon-sensitive adenyl cyclase system in plasma
membranes of rat liver. 4. Effects of guanyl nucleotides on
binding of I-125 glucagon," Journal of Biological Chemistry,
246:1872-6, 1971 and M. Rodbell et al.,"Glucagon-sensitive adenyl
cyclase system in plasma membranes of rat liver. 5. Obligatory
role of guanyl nucleotides in glucagon action," J. Biol. Chem.,
246:1877-82, 1971--have been referenced in more than 400 and 700
subsequent articles, respectively.
Later in the decade, Gilman determined that G proteins are the
signal transducers; they act as mo-lecular switches, shuttling
between the hormone receptor and the amplifier system in the cell
membrane to turn signals on and off. He made this finding while
working with mutated leukemia cells, which lacked a G protein and
thus did not respond to external signals. The Gilman group's
landmark papers, according to the Nobelist's associates--E.M.
Ross, A.G. Gilman, "Resolution of some components of adenylate
cyclase necessary for catalytic activity," J. Biol. Chem.,
252:6966-9, 1977 and E.M. Ross et al., "Reconstitution of
hormone-sensitive adenylate cy-clase activity with resolved
components of enzyme," J. Biol. Chem., 253:6401-12, 1978--have
been cited more than 225 times and 460 times, respectively.
In 1980, Gilman's team purified the first G protein."Rodbell
initiated the study of the G proteins and then Gilman carried it
on," explains Edwin G. Krebs, a professor, emeritus, in the
department of pharmacology and biochemistry at the University of
Washington, Seattle, and a 1992 Nobel laureate who's known both
men for decades. "In fact, Gilman's work was dominant for the past
10 to 15 years."
Krebs and Gilman have shared two Nobel
"predictor" prizes--the 1989 Albert Lasker Basic Medical Research
Award and the 1989 Louisa Gross Horwitz Prize, presented by
Columbia University to honor contributions to knowledge in biology
or biochemistry (The Scientist, Feb. 19, 1990, page 26).
Rodbell and Gilman are likewise no strangers when it comes to
sharing awards: In 1987, they were corecipients of the Richard
Lounsbery Award from the National Academy of Sciences (NAS).
Gilman received a Ph.D. and an M.D. from Case Western Reserve
University in 1969. He has been in his present position at U.
Texas since 1981. He received a Gairdner Foundation International
Award --another Nobel "predictor"--in 1984. He is a member of NAS.
According to Jeremy Levin, CEO of New York-based Cadus
Pharmaceutical Corp., which focuses on research and development in
the G protein area, Gilman is "a worthy recipient because he
conceptualized a completely new field. The man conceptualized an
area that had been thought about but never had the strands all
pulled together."
"This is a wonderful treat," Gilman notes. "All sorts of people
have come out of my past. Even my old Cub Scout leader called to
congratulate me."
Rodbell earned his Ph.D. from the University of Washington,
Seattle, in 1954. An NAS member, he received a Gairdner Award in
1984.
Carbocations
The work of Olah, 67, has led to the development of new fuels
based on petroleum, coal, methane, and other substances, resulting
in higher octane gasoline and liquified coal.
His research centers on carbocations and oxonium ions--highly
reactive, positively charged organic molecules that act as
intermediaries in natural as well as synthetic chemical processes.
In order to determine the structure of these molecules via
solid-state nuclear magnetic resonance spectroscopy and X-ray
crystallography, he modified them using superacids, which are
billions of times more potent than "strong" acids like sulfuric
acid.
Olah and colleagues have demonstrated that in very strong acidic
solutions, hydrocarbons--normally unreactive--can become reactive.
These reactions could be used to convert simple hydrocarbons such
as methane into synthetic fuels.
His most significant paper, according to his colleagues--G.A.
Olah, "Carbocations and electrophilic reactions," Angewandte
Chemie, 12:173-212, 1973--has been
referenced in nearly 200 subsequent articles.
"His contribution is very fundamental in organic chemistry," says
Surya Prakash, an associate professor at USC and Olah's
coauthor
on more than 200 papers. "He's made a major contribution
to
hydrocarbon research and to industry."
Olah, a native of Hungary, earned his Ph.D. from the Technical
University of Budapest in 1949. He worked in Canada from 1957
until 1964, when he came to the United States. He joined the USC
faculty in 1977. An NAS member, he has received numerous awards
from the American Chemical Society.
Structure Of Matter
Shull, 79, and Brockhouse, 76, share the prize for developing
neutron-scattering techniques for analysis of the atomic structure
of solid as well as condensed matter. Neutron beams have, for
instance, facilitated investigations of the structure of
semiconductors, a building block of the electronics industry.
These methods also are used in studying new ceramic
superconductors, catalytic exhaust cleaning, elastic properties of
polymers, and virus structures.
The two Nobelists conducted their prizeworthy research after World
War II--Shull in the 1940s and Brockhouse in the 1950s--at some of
the first nuclear reactors. Shull was cited for developing neutron
diffraction, used in discerning the atomic structure of a
material. His ground-breaking article--E.O. Wollan, C.G. Shull,
"The diffraction of neutrons by crystalline powders," Physical
Review, 73:830-1, 1948--has garnered nearly 70 citations.
Brockhouse pioneered neutron spectroscopy to determine the motion
of atoms. His seminal research was published in a book, Inelastic
Scattering of Neutrons in Solids and Liquids (Vienna,
International Atomic Energy Association, 1961, pages 113-151),
which has been cited 165 times.
"I've known both of them for 30 years, and they were pioneering
contributors," confirms Martin Blume, deputy director of
Brookhaven National Laboratory on Long Island, N.Y., whose High
Flux Beam Reactor is based on the two Nobelists' work. "When you
think that their work began to have a huge effect decades ago,
this recognition is really long overdue," Blume asserts.
Brockhouse received his Ph.D. in 1950 from the University of
Toronto. He has been an emeritus professor since 1984. He holds
awards from physics societies in the U.S., Canada, and the United
Kingdom.
Shull, who re-tired from MIT in 1986, earned his Ph.D. in 1941
from New York University. He is an NAS member and has received
awards from the American Physical Society, the Royal Swedish
Academy of Sciences, and the Russian Academy of Sciences.
A 'Bully Pulpit'
The Nobel winners, while predictably quite happy that their
research was acknowledged, are modest about the accolades being
heaped on them by their colleagues.
"It's very gratifying, but totally unexpected," says Brockhouse.
"Right now, though, I'm still going to lots of luncheons, and
there's various media pursuing us. But this is the icing on the
cake--not the cake, itself."
Still, the sudden notoriety has presented an opportunity that
Gilman is using to call attention to the state of funding for
basic research, a subject that is increasingly causing concern
among scientists who fear that product-oriented research is
crowding out other forms of work.
"I do get a little upset by people who are naysayers and complain
that there isn't enough money, because that sends out the wrong
message. It tells young people that you can't be a scientist
anymore," he remarks. "But it is frustrating for the scientific
community, and it is harder to become a scientist now than when I
was young. Clearly, we could use more money for basic research in
many areas."
Gilman's corecipient is also using his newfound media stardom to
bemoan the current dearth of research funding. In a widely
publicized Associated Press report, Rodbell said he retired in
June because there was no more money for his work. "I think the
attitudes of Congress and the executive branch [have] always been
toward the end goal," he commented. "Underlying all of that is
that they are not willing to take a chance on people like myself,
exploring the unknown."
Physicist Shull echoes these sentiments: "The thing I resent the
most is that students are becoming disillusioned with science as a
field and we're losing the cream of the crop. Students see it's
hard to find positions because science is not supported to the
extent that it would offer opportunities to young people. There's
a general malaise about scientific matters and financial support.
"And it's disturbing that funding for some of these major
facilities has been passed over."
Olah, while noting that funding is still available for top-echelon
researchers, expresses similar worries: "I must say that most of
my friends find a way to get funds and, in comparison with the
rest of the world, things are still good [for scientists]. But
funding is getting limited."
He adds, however, that he hopes the prize will bring recognition
to USC, which is probably best known to Americans for its sports
teams.
"I'm the guy who gets all the recognition, but this prize is for
everyone who worked with me," he asserts. "But there's another
message here, too. And that is that my university is always
improving--and we're much more than a football team!"
Edward R. Silverman is a freelance writer based in Millburn, N.J.
(The Scientist, Vol:8, #23, p.1, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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TI : New Funds Possible For Embryo Research
If controversial studiesare approved for NIHsupport,
investigationswill likely expand beyondprivate laboratories
AU : FRANKLIN HOKE
TY : NEWS
PG : 1
Many researchers in genetics, cancer, and developmental biology
whose studies involve in vitro human embryos will be eligible for
federal support for the first time in about 15 years if the
National Institutes of Health follows an advisory panel's recent
recommendations. At the same time, an ethical boundary on research
set by the panel is being rejected, primarily_but not entirely_by
critics outside the scientific community.
A report produced by the 19-member group, which was convened last
February, has found that research on preimplantation human embryos
is scientifically significant, can be conducted ethically, and
deserves government funding.
Currently, most such research in the United States relies on
private resources, usually in association with clinics performing
in vitro fertilization procedures, and has not been subject to
scientific or ethical peer review.
"There is compelling evidence that research [on human
preimplantation embryos], carried out under appropriately
stringent guidelines, will make important contributions to a
whole
range of medical problems affecting people in all walks of
life,"
said Brigid L.M. Hogan, science cochairwoman of the panel and a
professor of cell biology at Vanderbilt University School of
Medicine, Nashville, Tenn., at a late-September news conference at
which the report was released. "In addition, federal funding will
greatly facilitate collaborations between clinicians and basic
scientists working at the forefront of developmental biology and
mo-lecular genetics, areas in which clearly outstanding progress
is currently being made throughout the world, but particularly in
the United States."
The types of research considered by the panel for funding involve
fertilized human ova, either in vitro or flushed from the womb
before implantation in the uterine wall.
Examples of procedures reviewed include embryo biopsies for
genetic testing, toxicological and nutritional studies, and
various protocols to better understand reproductive processes.
Scientists define the embryo stage as extending into the eighth
week of gestation, at which point the embryo is termed a fetus,
although only very early stage embryos were considered by the
panel for possible use in research.
If the report's guidelines for preimplantation human embryo
research are approved, funding will once again be available for
studies in this area after a hiatus of well over a decade. In
1975, U.S. government regulations were instituted that required
approval by a Department of Health and Human Services (HHS) Ethics
Advisory Board for research proposals involving human embryos. The
first successful outcome of an in vitro fertilization occurred
three years later, in 1978.
In 1979, the ethics board issued a report endorsing federal
funding for research in this area, under explicit guidelines.
However, the HHS secretary allowed the board's charter to expire
in 1980, resulting in a de facto moratorium on funding for human
embryo research until the NIH Revitalization Act of 1993 nullified
the requirement for board approval.
Ethical Obstacles
The moratorium on human embryo research coincided with the
Republican presidencies of Ronald Reagan and George Bush. Both
administrations opposed abortion, with support from some
conservative political and religious groups, based on the view
that human life begins when the ovum is fertilized and that the
resulting embryo has legal rights to protection similar to those
of an infant, child, or adult. In recent years, the Bush
administration also effectively opposed fetal tissue research on
related grounds, a position reversed early in Bill Clinton's
presidency.
Opposition to the NIH panel's recommendations is being voiced by
some of the same forces. For example, in a September 19 letter to
NIH director Harold Varmus, Rep. Robert Dornan (R-Calif.) and
about 30 other members of Congress argued that such
research
should not be funded by the agency. The U.S. election
results
earlier this month, in which Republicans gained control of both
houses of Congress, appear likely to slow NIH progress toward
formulating policy in this area, although panel members and agency
officials decline to speculate on this possibility.
In addressing the ethics of performing research involving embryos,
the panel concluded that "the preimplantation human embryo
warrants serious moral consideration as a developing form of human
life, but it does not have the same moral status as infants and
children."
The panel counseled that most investigations be discontinued about
14 days after fertilization when the so-called primitive streak
appears, a groove that develops along the midline of the embryonic
disk of cells. The primitive streak is the first morphological
evidence of what will later develop into the nervous system and
is, thus, the earliest suggestion of sentience, according to panel
member Ronald M. Green, a professor of religion at Dartmouth
College, Han-over, N.H. It also establishes the embryo's head-tail
and left-right orientations. In addition, it is the first
developmental point at which the embryo can be called an
individual, he noted at the news conference. Prior to this time,
the embryo, if divided, can give rise to twins.
Critics, however, say the primitive streak may have no special
ethical significance as a stopping point on the developmental
continuum from conception to birth (see accompanying story).
"For the life of me, I really cannot understand why this
specific morphological development, which speaks to where the
nervous system is going to be formed, becomes a landmark," says
Robert J. White, a professor of neurosurgery and a neuroscience
researcher at Case Western Reserve University Medical Center,
Cleveland. White believes fertilization delineates the start of
human life. "There is no neurochemical or electrical event that
speaks to when something becomes human, to when something
equivalent to the soul or spirit_and not so much the mind_is
infused into an embryo."
In forming its recommendations, the panel attempted not to
construct an unassailable moral stance on a controversial subject
but to create defensible public policy, according to panel
chairman Steven Muller, president emeritus of Johns Hopkins
University, Baltimore. That process included public testimony at
panel sessions before the report's release, as well as a
solicitation of public comment leading up to a meeting of the NIH
director's standing advisory committee to be held early next
month. At that meeting, the committee, of which the panel was a
temporary subgroup, will discuss the report's recommendations and
advise director Varmus, who will then make a final decision on
what research in this area the agency will fund. These steps are,
by and large, the usual ones in the development of new policy at
NIH and elsewhere in the government, but may be crucial in
advancing policy in such a controversial area as human
embryo
research, Muller observed at the news conference.
"In a democracy, public policy is not simply imposed on citizens
by a higher authority," he said. "Proper public policy develops
through a public process rooted in public participation. Public
participation involves a multitude of interests, many in conflict
with one another. The public process which produces public policy,
therefore, must strive for a balance among divergent interests, a
balance sufficient to obtain and justify public support."
Muller added, however, that the content of some letters received
by the panel during this process prompted them to request that NIH
undertake a concerted public education effort to explain the
complex scientific and ethical issues involved in human embryo
research. To this end, NIH held an extended special briefing for
science writers a week prior to the report's release and prepared
comprehensive educational materials for distribution with the
report.
Opening Doors
Scientists note that the types of research that NIH may begin
funding if Varmus accepts the panel's proposals are well supported
in a number of other countries and that U.S. investigators who now
must rely on private funding find themselves at a comparative
disadvantage as a result.
"It's very clear that this is all competitive and that countries
like England and Australia are way ahead of us," says Uta Francke,
a professor of genetics and pediatrics at Stanford University
Medical Center in California, and chairwoman of the Institute of
Medicine committee that produced the July 1994 conference report
Fetal Research and Applications (Washington, D.C., National
Academy Press, 1994). "Our colleagues [in other countries] have
sort of looked at [us as] the poor American brothers who couldn't
really do anything because there wasn't any funding for it."
One promising area likely to receive an immediate boost from new
government grant support, according to Francke and other
researchers, is genetic diagnosis of blastomeres_embryos at the
eight-cell stage, in this case_produced through in vitro
fertilization techniques. Currently, prospective parents who know
that one or both of them carry a disease gene are faced with few
options if they wish to have a healthy child with genetic
contributions from both parents. They can test for the gene by
chorionic villus sampling at 10 weeks' gestation or by
amniocentesis at 16 weeks. If the disease gene is present in the
fetus, the couple face the difficult decision of whether to end
the pregnancy.
"People who are at risk and who have done that a few times often
are not willing to do it again," Francke says. "It's a tremendous
emotional burden."
A new experimental procedure, however, allows researchers to
separate a single cell from the eight-cell embryo, amplify
the
genetic material from the cell using polymerase chain reaction
technology, and then analyze the material for the disease gene's
presence. If the gene is not found, the now-seven-cell embryo can
be transferred to the womb where, if it implants, it will develop
normally. In practice, a number of eggs are released from the
ovaries through a hormone-stimulation protocol, fertilized in
vitro, and tested. Multiple embryos that have been screened for
their genetic health are then introduced into the uterus in the
hopes that one will implant.
Worldwide, fewer than 50 pregnancies have resulted from this
diagnostic technique, according to the panel's report, and more
research is needed to extend and refine the procedure.
Genetic disorders successfully tested for, however, already
include cystic fibrosis, Lesch-Nyhan syndrome, Duchenne muscular
dystrophy, and Tay-Sachs disease, as well as a number of
X-chromosome-linked recessive disorders such as hemophilia A,
adrenoleukodystrophy, myotubular myopathy, spastic paraplegia, and
certain forms of mental retardation.
Cancer And Development
Certain areas of cancer research, too, may benefit from federal
funding for preimplantation human embryo research. A number of
genes that play critical roles in the normal development of the
embryo are also suspected to play a part in some cancers.
"The oncogenes that are a part of the cancer situation and the
growth factors that are part of cancer scenarios are also part and
parcel to those that are involved in development," says Neal L.
First, a professor of reproductive biology and biotechnology at
the University of Wisconsin, Madison. First is also a member of
the National Advisory Board on Ethics in Reproduction (NABER), an
interdisciplinary group established in 1992 by the American
College of Obstetricians and Gynecologists and the American
Fertility Society, but now a separate entity funded by private
foundations. "Most often, oncogenes are genes that are useful in
developmental processes when normally regulated, but when the
oncogenes become improperly regulated, the tissues become
tumorous."
First adds: "We would probably enhance our understanding of cancer
if we really understood the gene, growth factor, and cytokine
situations for embryos as they pass through from one
[developmental] stage to the next to the next."
Research on human embryos will be crucial for these studies, First
asserts, because animal studies have demonstrated that important
developmental differences exist between species.
"There's a lot of suspicion that the textbooks are not very
accurate relative to human embryo development," he says. "What are
the things that cause an early human cell to make its
[developmental] changes, to differentiate? We can speculate from
[what we know about] other species, but we wouldn't
actually
know until we were able to study humans."
Studies involving parthenotes_unfertilized eggs that proceed to
either spontaneous or induced early development as embryos_may
lead to important new information about development, according to
Brigid Hogan. Animal studies have shown that there are profound
intrinsic barriers to normal development of parthenotes, which
contain genetic material from only one parent. The reason involves
a little-understood process called imprinting, in which
chromosomes from both parents must be present in the embryo for
normal development. Several tumor forms, relatively benign and
easily treated, now appear to be linked to embryos in which only
maternal or paternal genes are present. One example is a kind of
trophoblast tumor called hydatidiform moles, which can progress to
malignant choriocarcinoma.
"We're not going to be curing anybody of these tumors by doing
research," Hogan says. "On the other hand, the basic biology is
extremely interesting. Studies in mice and in humans show that
choriocarcinoma arises with a particularly high frequency when
there are only paternal genes present. And, so, the question is
why. Presumably, this is because of imprinting problems, in the
sense that certain genes are going to be either active or
inactive, oncogenes are going to be active, or tumor suppressors
are going to be inactive in those cells."
Another potentially significant area of research that may expand
with federal support is in the development of techniques for
culturing pluripotential human embryonic stem cells, according to
Hogan. The creation of so-called immortal lines of
undifferentiated cells might lead to crucial advances in
cell-transplantation therapies.
"A really important [advance] over the last 10 years in mouse
embryo research is the development of these immortal, continuously
proliferating embryonic stem cells from blastocyst-stage
em-bryos," Hogan says.
"You can culture them, and, as long as you continue growing them
under ideal conditions and subculture them routinely, they will
remain undifferentiated. But then you can stimulate them with
various treatments to differentiate into various cells types. You
can get muscle and nerve and bone and cartilage and so forth. So,
the idea would be that maybe, down the line, you could use these
for making blood cells for transplantation, and maybe some
kinds of neuronal stem cells or muscle stem cells."
More than 70 proposals for grants in human embryo research have
already been received at NIH, in anticipation of Varmus's approval
of the panel's recommendations. Most of the new proposals have
been submitted to the National Institute of Child Health and Human
Development at NIH.
(The Scientist, Vol:8, #23, p.1, November 28, 1994)
(Copyright,
The Scientist, Inc.)
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NXT:
--------------------------------------------------------------
TI : ENDURING QUESTIONS
AU : FRANKLIN HOKE
TY : NEWS
PG : 6
The ethical reasoning of the panel advising the National
Institutes of Health on human embryo research was clearly
expressed by its policy cochairwoman at a news conference at which
the group's report was released in September.
"The basic finding of the panel is that it is acceptable public
policy to fund research on the human embryo, subject to stringent
guidelines," said Patricia A. King, who is also a professor of law
at Georgetown University Law Center, Washington, D.C. "There were
three principles that guided us in our determination. First, that
the promise of benefit from doing research on the human embryo was
significant and carried great potential for couples and for
families and for individuals. Two, that the preimplantation embryo
warrants serious moral consideration but does not have the same
moral status as infants and children. And three, that federal
funding and regulation will help bring about consistent ethical
and scientific review of proposals to do research on the human
embryo."
While many--perhaps even most--scientists accept this line of
reasoning, there are critics, primarily outside of research, who
certainly do not. Generally members of conservative religious or
political groups also opposed to abortion, these critics may find
they wield increased influence on federal policies following the
substantial gains made by the Republican party in elections
earlier this month.
For example, the first point made by the panel--that the potential
benefit of human embryo studies provides a justification for such
research--depends on one's view of the second point--that
the
embryo does not have the same moral status as infants,
children,
or adults--according to Richard Doerflinger, associate director
for pro-life activities at the National Conference of Catholic
Bishops in Washington, D.C.
"A utilitarian ethic of human experimentation is going to lead to
enormous abuse," Doerflinger says. "The benefits are one part of
the equation, but if what you're doing is basically unjust use of
a human subject, then the experiment should not be done. And
that's what we feel is being contemplated here."
Some scientists, including those who are basically in agreement
with the panel's findings, note that the appearance of the
primitive streak--the earliest morphological marker of the nervous
system and, thus, sentience--may not, over time, stand as a
significant developmental limit for ethical human embryo research.
"It's a demarcation point," says Neal L. First, a professor of
reproductive biology and biotechnology at the University of
Wisconsin, Madison. First is also a member of the National
Advisory Board on Ethics in Reproduction (NABER), a privately
funded, nonprofit group of 13 professionals in ethics, medicine,
law, religion, and public policy. "That's the most I can say. It
is the point where you can begin to say, yes, this lineage would
be human if it went this way, and it might be something else if it
went another way. I have a suspicion that, as we learn more about
human embryology, we will actually find that that delineation
point comes earlier than the primitive streak."
However, the question of when an embryo becomes uniquely human,
and therefore no longer an appropriate research subject, presents
science with a kind of Catch-22 as far as human embryo research is
concerned, First notes.
"You have to be able to do research to get that answer," he says.
--F.H.
(The Scientist, Vol:8, #23, p.6, November 28, 1994)
(Copyright, The Scientist, Inc.)
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NXT::
------------------------------------------------------------
TI : Science Community Gives Mixed Review To 'Triage'
NIH welcomes expanded use of the study-section procedure--but some
extramural scientistsare less enthusiastic
AU : LIANE REIF-LEHRER
TY : NEWS
PG : 1
The expanded use of triage--under which certain grant applications
deemed to be "noncompetitive" (NC) are not discussed in study
sections--by the National Institutes of Health Division of
Research Grants (DRG) has met with enthusiasic response from many
NIH administrators. The new system, however, has engendered
controversy in the extramural community.
Triage, which has been instituted on a trial basis in an
increasing number of study sections since February of this year,
will be used for all investigator-initiated (R01) and "FIRST
Award" (R29) research grant applications beginning with those
submitted for October/ November 1, 1994 deadlines. NIH expects
about half of all applications to fall into the NC category.
The aim of the measure is to allot more time for study-section
members to discuss applications that stand a chance of getting
funded, as well as to decrease the workload for reviewers and
study-section heads, called scientific-review administrators, or
SRAs (see story on page 8). In addition, modifications in the
review system, designed to reduce paperwork and otherwise
streamline the process, have been put in place (see story on page
9). For example, although all applicants will continue to receive
summary statements about their proposals, these will now contain
primarily the initial reviewers' reports. NC applications will
lack a summary paragraph given for scored applications.
Wendy Baldwin, NIH's deputy director for extramural research,
hopes "triage will help focus the discussion among reviewers.
"All applicants will receive comments about their proposals," she
points out, "and we expect that, by sending the essentially
unedited reviewers' comments, applicants will get faster feedback
and a clearer view of the assessment of the application."
NIH director Harold Varmus says he is pleased with the way triage
is working, and that he has had positive feedback from SRAs.
"Study-section meetings have improved, and that's what the
objective was," he notes. "Applications in the top half [up to the
50th percentile] are getting a fuller and fairer review."
Not all extramural scientists agree that triage is a positive
change. Susan Leeman, a professor of pharmacology at Boston
University School of Medicine, for one, considers it
"inappropriate to ask scientists to spend months writing proposals
and then not afford them discussion time at the study-section
meeting.
"If you want to triage half of all applications," she says,
"perhaps one possibility would be to have scientists write brief
'intention' proposals and then invite only those who stand a
chance of being funded to submit a full application." Some
granting agencies already use this method of sifting proposals.
Leeman is also "concerned that triage may provide an opportunity
for biases to creep into the review process."
Lawrence Grossman, Distinguished Service Professor of Biochemistry
at Johns Hopkins School of Public Health in Baltimore and a former
chairman of the biochemistry department who has served as a member
and chairman of an NIH study section, was disturbed this summer
when an application on which he was listed as a consultant was
designated NC.
"The reviewer apparently dismissed the proposal because of a flaw
he perceived in a particular technique," Grossman says.
The Johns Hopkins researcher contends that "the reviewer's
criticism was based on ignorance of the field. Everyone working in
this area of research is aware of the complication cited by the
reviewer and knows how to circumvent the problem." Although
Grossman currently has a MERIT Award--an eight- to 10-year grant
given by NIH to established investigators with good "track
records" who are working in promising research areas and get
priority scores in the top 20 percent--he is disenchanted with the
peer-review system "because funding decisions are based on
assessment of anticipated results rather than on proven
productivity."
Anthony Demsey, associate director for referral and review at DRG,
comments: "We hear the complaint occasionally that the reviewers
made a basic, elemental error in an assessment, and such a
complaint normally forms the basis for a rebuttal letter on the
grounds that the reviewers lacked appropriate expertise. But this
criticism has nothing to do with triage--it's just inevitable that
in the peer-review system there will occasionally be human error.
"If, however, the implication is that the error was due to casual
review, or sloppiness, or carelessness on the part of a
reviewer--looking for an easy way out of having to do a full
review--well, we just haven't seen that in the triage process. If
anything, the reviewers have been overly cautious."
Demsey thinks "triage is a good streamlining procedure," and many
SRAs and reviewers agree.
SRAs And Reviewers Report
SRAs are supportive of the new review
process, but reviewers'
responses to triage have been mixed. Teresa Levitin, SRA for Human
Development and Aging-1, contends that "time saved by not having
to discuss the NC applications" makes for "richer discussions of
those applications that do get reviewed at the meeting."
Patricia D'Amore, a member of an early "test" study section, is
also positive about triage. In her opinion, "reviewers [should]
spend more time judging the science rather than suggesting
experiments or trying to help rewrite applications."
Thomas Parsons, chairman of the Experimental Virology Review
Group, concurs: "Up to now, proposals were tailored--after three
or four resubmissions--to what the reviewers think should be done
rather than retaining the PI's [principal investigator's] original
aim." Levitin voices a similar feeling: "The study section should
evaluate the quality of the PI's application, not the collective
judgment of the previous study section's critiques."
But a senior professor at Harvard Medical School, speaking on
condition of anonymity, is adamant that "the job of reviewers is
to get good research funded, and reviewers should help PIs. Some
of the best scientists write the worst applications because they
are too close to their own work."
Some study-section members worry that triage will unduly increase
an already disproportionate influence exercised by the primary
reviewers. Edward Zapolski, SRA of the Metallobiochemistry Review
Group, is concerned that the system "may cause reviewers to worry
about getting re-proached by colleague-applicants who know which
reviewers are on a study section and also know that it only takes
one objection [from a study-section member] to bring an NC
application back to full review."
Additional controversy arises from the changes in the summary
statement that have taken place along with triage. A number of
scientists, including some reviewers, think the revised summary
statements will deprive researchers--perhaps those most in need of
advice--of important feedback about their applications. But NIH
officials counter that the new summary statements actually provide
grant applicants with the individual reviewers' reports, and
summary statements for NC applications lack only a summary
paragraph describing the study-section discussion of the
application.
Janet Rasey, a professor of radiation oncology and director of the
Research Funding Service at the University of Washington Medical
Center in Seattle, who has served two four-year terms as a
study-section member, feels conflicted about the new procedures.
She thinks "it's great to have more time to discuss the borderline
proposals--but triaging 50 percent of applications is unrealistic;
there are too many good proposals."
In addition, she worries that "summary statements consisting of
reviewers' reports may be confusing to PIs--especially when the
reviewers disagree with each other."
Moreover, Rasey says, "triage may make more work for conscientious
reviewers who may feel compelled to write a more thorough critique
than they would previously have done." Furthermore, she points
out, "reviewers themselves may 'lose out' under the new system:
Study-section discussion often helps clarify complex issues in the
minds of reviewers, who can then temper their critiques
accordingly."
Rasey maintains, however, that triage and other remedies obscure
"the real problem," which is "that there's not enough money to
fund all the really good grants; tinkering with peer review is
largely cosmetic." Many of her peers concur.
Conflicting Views
A few people contend that much of the negative response to triage
stems from a misunderstanding of the new system. Some SRAs and
reviewers say that triage is nothing more than a formalization of
the way in which study sections already operate, because
applications not likely to be funded are generally given only
brief discussions, anyway.
However, Levitin and other SRAs, as well as some study-section
chairpersons, say applicants will get adequate feedback from the
reviewers' reports despite lack of discussion by the whole study
section, especially because critiques for NC
applications--initially restricted to one page in the February
1994 triage trials--no longer have a page limit, and a number of
reviewers will write longer tutorial reports because they want to
help PIs.
Jane Koretz, a professor of biology and biophysics at Rensselaer
Polytechnic Institute who served as a member of an NIH study
section from 1989 to 1993, believes the new form of the summary
statement is "good for PIs because they get to see conflicts
between reviewers that were sometimes 'papered over' in the
integrated summary statements written by SRAs."
She also thinks the verbatim presentation of the reviewers'
remarks on the summary statements may encourage "a higher and more
objective standard of review than some reviewers, unfortunately,
currently practice."
But Koretz does not like the use of triage. She says that "the NC
classification institutionalizes a trend toward awarding
'fundable' and 'non-fundable' priority scores that began when NIH
funding got tight." She contends that "study sections should be in
the business of assessing scientific merit, rather than trying to
figure out whether a proposal is competitive or not."
Gerhard Ehrenspeck, SRA of the Cellular Biology and Physiology-2
study section, is in favor of triage and thinks "it is working
well." He observes: "I have had no negative feedback from
reviewers in my study section nor from any of the PIs whose
applications were designated NC by my study section in February
or
July."
Others think that, in any case, study sections should stop
spending time on applications that stand little chance of
succeeding at current funding levels. Garrett Keefer, SRA of the
Experimental Virology Review Group, which has used triage since
February, predicts that NC designations are likely to be on
target. In his February study-section meeting, 27 of 90 proposals
were designated NC. Of the 27, one was recalled for full review
but in the end got an NC score, anyway. Parsons further suggests
that "an application designated NC two or three times in a row
should not be permitted to be submitted again in the same form."
Meanwhile, scientists will have to deal with triage. In the long
run, observers believe, it may save time for applicants because
summary statements for NC applications will be returned quickly,
allowing more time to revise or make other plans if an application
is turned down. Also, they point out, writing revisions to an
application that doesn't stand a chance of getting funded is a
waste of precious research time. In any event, NIH officials say
they hope PIs will give triage a fair chance and provide DRG with
objective feedback about the various aspects of the modified
system of peer review.
Liane Reif-Lehrer is president of Erimon Associates, a consulting
firm based in the Boston area, and the author of Grant Application
Writer's Handbook (Boston, Jones and Bartlett Publishers, 1995).
She gives workshops on grant-proposal writing and related
subjects.
(The Scientist, Vol:8, #23, p.1, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : WHAT IS TRIAGE?
AU : LIANE REIF-LEHRER
TY : NEWS
PG : 8
The National Institutes of Health announced in the September 23
NIH Guide for Grants and Contracts that it will extend its use of
a triage system to all investigator-initiated research grant (R01)
and "FIRST Award" (First Independent Research Support and
Transition Award, R29) applications submitted for October/November
1, 1994 receipt dates and reviewed by the NIH Division of Research
Grants (DRG) at the February 1995 study-section meetings.
Under triage, R01 and R29 applications deemed by reviewers to be
"noncompetitive" (NC) at current funding levels are not discussed
at study-section meetings and are not routinely forwarded to the
relevant advisory council, the second level of NIH peer review. To
be categorized as NC, an application must be judged so by at least
two assigned reviewers--but an application can be recalled for
full review by even a single study-section member at any time
before or during the meeting. Members are advised to opt for full
review in borderline cases.
It should be noted that NC is very different from the voting
category "not recommended for further consideration" (NRFC), which
came into use in 1991 and was used for the last time in autumn
1994 in about half of the study section meetings.
Whereas NRFC indicated that an application did not have
substantial scientific merit, NC implies nothing about the quality
of an application but rather indicates that the application is not
likely to be funded in the current budgetary climate.
Although the announcement about expanded use of triage in the
September 23 NIH Guide states that about half of all applications
will be designated NC, the figures to date at the test study
sections have been lower: The average in the four study sections
in the February test group was 36.5 percent (range: 30 percent to
51 percent); the average in 12 study sections in a July test group
was 35.4 percent (range: 27 percent to 43 percent).
NIH hopes the new procedure will allow more time at study section
meetings to discuss applications that stand a chance of getting
funded. The agency also hopes to decrease the workload for
reviewers and scientific review administrators (SRAs) of study
sections. SRAs say that although the reviewers' workload has not
changed appreciably--and in some cases may have even
increased--study-section meetings have been shorter, and their
burden has been eased.
--L.R.-L.
(The Scientist, Vol:8, #23, p.8, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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------------------------------------------------------------
TI : A NEW LOOK FOR SUMMARY STATEMENTS
AU : LIANE REIF-LEHRER
TY : NEWS
PG : 9
Summary statements for National Institutes of Health grant
applications (often referred to as "pink sheets," although they
have not been printed on pink paper since 1991) will be formatted
differently from now on:
* Summary statements will consist primarily of the individual
reviewers' critiques.
* Scientific review administrators (SRAs) will write summaries of
the study-section discussion (including budget recommendations, if
appropriate) only for applications that undergo full review by the
study section. Because "noncompetitive" (NC) applications are not
discussed at the study-section meetings, their summary statements
will not contain a paragraph summarizing the discussion by the
study-section members about the application.
* Summary statements for scored applications will continue to have
a "Description of Project," but NC applications will no longer
contain this paragraph.
* Summary statements for NC applications will contain an
explanation of this designation.
* Summary statements will no longer contain a separate paragraph
about investigators.
* Reviewers will be expected to modify their written critiques
during the review of an application--for example, removing a
criticism that was deemed to be invalid following
group
discussion.
NIH officials contend that SRAs will save appreciable time as a
result of these changes, as they will no longer have to integrate
the reviewers' reports into a cohesive summary statement. Garrett
Keefer, SRA of the Experimental Virology Review Group, reports
that he was able to generate summary statements much faster after
the February meeting than he could under the old system. Principal
investigators will profit by getting the summary statements for
their applications more promptly.
--L.R.-L.
(The Scientist, Vol:8, #23, p.9, November 28, 1994)
(Copyright, The Scientist, Inc.)
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--------------------------------------------------------------
TI : Industry And Educators Team Up
AU : KAREN YOUNG KREEGER
TY : NEWS
PG : 1
Citing a need to replenish and train their own work force, United
States companies are joining academia, government, and communities
in the effort to reform science education, as indicated by several
recent initiatives. Industry officials and others maintain that
their participation can infuse a business perspective, as well as
a "sense of urgency" and focus that is lacking in the national
dialogue on this issue.
Bassam Shakhashiri, a professor of chemistry at the University of
Wisconsin, Madison, who was assistant director for science and
engineering education at the National Science Foundation from 1984
to 1990, contends that industry involvement in this effort is more
than a welcome contribution; it is a necessity. "The
business
community must be involved intimately in the science
education
reform arena because they have expertise that academic communities
can benefit from," he asserts. Shakhashiri says that this
expertise ranges from "technical know-how" in science areas to
management tools, such as strategic planning, that can be applied
to the U.S. educational system.
He warns, however, that for any undertaking to be effective, U.S.
educators have to be receptive to change and that change must be
coordinated among all stakeholders, "not just the participation of
the private sector."
One such effort in this movement took place last September in a
conference entitled "Corporate America's Impact on Elementary
Science Education." Hosted by Merck & Co. Inc. at its Whitehouse
Station, N.J., facility, the meeting was sponsored by the National
Science Resources Center (NSRC), the National Academy of Sciences
(NAS), and the Smithsonian Institution in collaboration with
Bristol-Myers Squibb Co. of New York; Dow Chemical Co.,
headquartered in Midland, Mich.; Hewlett-Packard Co., Palo Alto,
Calif.; and Pittsburgh-based Miles Inc.
Participants in the conference included about 80
delegates--educators, development officers, top-level executives,
and researchers--from industry, government, and academia. Biotech,
pharmaceutical, chemical, publishing, manufacturing, and computer
and electronics firms were all represented. Attendees discussed
ways in which corporations are contributing to science education
reform and how their current and future efforts could be more
effective.
In a luncheon address at the meeting, NAS president Bruce Alberts
summed up the role he feels corporate representatives should take.
"We need advocates in every local region for science. The basic
message I have for you is that we need all of you to be involved
and to spread the word and to take the scientists and engineers
throughout this country who really want to contribute [to
science-education reform] and enable them to be effective
volunteers."
In other high-profile collaborations, the National Aeronautics and
Space Administration, the Department of Education, and the 28
largest U.S. aerospace contractors signed the NASA-Industry
Education Initiative this month. The agreement created a
partnership to work on improving such areas as students' academic
performance in science and mathematics and strengthening the
teacher work force.
And in mid-December, the National Research Council (NRC) is
cosponsoring a two-day symposium to explore ways that corporations
can contribute to reform efforts. Whereas the focus of the Merck
meeting was on elementary science education, the upcoming
NRC-sponsored conference will concentrate on K-12 science as well
as mathematics education, although some overlap is expected, say
NSRC officials.
Conferences like these are, in part, outgrowths of the GOALS 2000
Educate America Act signed last March by President Bill Clinton,
which authorized $400 million in grant funds to state and local
educational agencies to develop and implement reforms.
Experts say that the National Science Education Standards--a
project started in 1991 to formulate a set of curriculum,
teaching, and assessment guidelines (R. Kaufman, The Scientist,
July 6, 1992, page 3)--also account for the heightened corporate
participation in science education. For example, these
specifically articulated goals mirror the mission statements and
goals of the education programs of the five collaborating
corporations at the Merck conference.
Industry Role
Many U.S. firms have been involved in science education in an "ad
hoc way," according to one corporate official, for several years,
but lately their involvement has been stepped up and formalized.
For example, many companies are devoting millions of dollars to
create educational institutes and positions within corporations;
sponsor programs within schools at the local and regional level;
and spearhead national education initiatives through NSRC and
other groups.
No statistics are available that itemize corporate contributions
to K-12 science education. However, according to the Conference
Board, a New York-based nonprofit business research organization,
out of 371 companies surveyed in 1992, the proportion of corporate
contributions to precollege education out of total corporate
charitable giving was 4.3 percent.
"Money is no longer the only thing. It's really the expertise that
we can add to the partnership," says Carlo Parravano, director of
the Merck Institute for Science Education, based in Rahway, N.J.,
"We want to go beyond giving away a check." The corporate
representatives interviewed for this story concur, noting that
their firms' nonmonetary contributions fall into three main
categories: facilitating volunteerism for employees, donating
equipment to schools, and promoting advocacy activities.
"Advocacy, in my opinion, is the most important" of Dow's
contributions, asserts Robert Henson, manager of education affairs
at Dow. For example, voicing opinions on education reform at
school board meetings and writing editorials are ways in which Dow
employees take on an advocacy role, he says.
Systemic Reform
According to Sally Goetz Shuler, deputy director for external
relations, development, and outreach at NSRC, the new initiatives
address systemic reform--the suite of changes in educational
methods that reformers espouse--involving all "stakeholders,"
including children, teachers, administrators, educators at
universities, parents, community leaders, and scientists and
engineers. Shuler, who spent 15 years as a classroom science
teacher and a science specialist for the Fairfax County
Public
Schools in Virginia, says that overhauling curriculum,
establishing professional development programs, creating
educational materials and equipment, conducting performance
evaluations, and devising ways to involve community leaders all
fall under suggested reform measures.
NSRC's official involvement with corporations began about four
years ago with Dow and Hewlett-Packard, she says. The Merck
meeting was spawned by a less formal gathering sponsored by
Hewlett-Packard in 1992. "Both of these meetings had similar
goals: These corporations wanted to share what they were learning
about reform with other corporations in order to get more
communities involved and to engage more corporations in the whole
process," she reports.
Participants in the Merck meeting say, for the most part, that it
did accomplish its goal of increasing awareness, but that the
meeting should be viewed only as a beginning. Dow's Henson adds
that organizers "needed to close the deal. Part of the meeting
could have been [dedicated] to gaining some commitment in the form
of coalitions and alliances."
In the two months since the conference, however, Shuler notes that
about 10 corporations have contacted her for more information on
ways to participate. "I'd like to see us have at least 10 or 15
corporations involved at the same level [as the five sponsoring
corporations at the conference] in the next five years," she says.
"Right now these five corporations are working with 97
communities, representing about 700,000 children in 18 states and
two Canadian provinces."
Corporate Payoff
Corporate representatives cite "big-picture" reasons to explain
why they are devoting more and more resources to educational
reform. They say that developing an informed and diverse work
force for the future is a wise business investment in people and
communities. "It's a work-force issue," maintains Sande Deitch,
executive director of the Pittsburgh-based Miles Inc. Foundation.
"Getting involved will help develop [a company's] own qualified
pool of talented people."
Merck's Parravano agrees, adding: "Another payoff is having a work
force that is well trained" in the skills that firms anticipate
will be needed in the future. Corporate executives list some
general examples of these desired abilities: problem-solving,
assessing data, working in teams, having subject-matter expertise,
and possessing knowledge of and a high comfort level with
technology.
Parravano and others also view their involvement as "an
investment" in the communities in which they are located. "Having
a strong school system spills over into the entire community," he
contends.
Corporate officials emphasize that another long-term payoff
for
society is improved science literacy. "I think in today's
global
economy, whether you're tossing hamburgers on a grill or whether
you're running a process-control system within a plant, more and
more jobs are going to require some deeper level of knowledge of
technology," contends Henson.
Industry representatives assert that businesses can contribute to
education reform in a way that is different from the involvement
of others. "One of the things that really impresses me about
working in a corporation such as Merck is [industry's] ability to
focus on a problem," says Parravano, who, before coming to Merck
in 1993, was a professor of chemistry and chairman of the division
of natural sciences at the State University of New York, Purchase.
"I spent 20 years in academia and I rarely if ever saw that
[ability to focus]. Business is good at sitting back and asking:
'What did we learn from this? How does this improve our next
step?' I think that that's a perspective that corporations can
bring to the educational environment."
Dow's Henson also notes that corporations can contribute "a sense
of urgency" to promoting changes in science education. "If you
talk to educators, they don't [seem to] have a sense of urgency.
They take your ideas, and say: 'Well, we do need to do that, but
it's going to take further research.'"
And Miles' Deitch says that, as far as students are concerned,
corporate America can bring a "business point of view" to
discussions on reform. "[We can show] these kids what they are
going to have to know when they get out of school. I think it's
very important because kids have to have some idea about why
they're learning something."
What Can A Scientist Do?
Corporate and NSRC brochures and representatives circulating at
the meeting offered numerous examples of how researchers can
contribute to science education in their communities. Some
scientists conduct tours of the plants where they work,
participate in student science and math clubs, and serve on school
district curriculum-review committees. Others mentor students,
give classroom presentations, and build demonstration equipment
for teachers. Still others serve on school boards and judge
science fairs.
"The most important thing is to mentor teachers," Parravano
stresses. "If a teacher has a question on a specific topic or is
having trouble with some material, they have somebody [with
subject-matter expertise] that they can call." He adds that this
arrangement is especially important for teachers who have less
experience with hands-on science.
And at Hewlett-Packard, Bess Stephens, manager of K-12 education
relations, says that at the local level, company technical staff
and researchers are assigned to school districts in
communities
where the firm has plants. "That scientist is the
primary conduit"
between Hewlett-Packard and the students, she explains.
But how do scientists make time in their busy research schedules
to help out in schools? Most firms have an informal arrangement
with employees who volunteer, while some others have a more
formalized mechanism to facilitate volunteering.
According to Stephens, Hewlett-Packard has a policy that allows
scientists to use company time to volunteer in schools. "It's not
at all uncommon for some of these individuals to [also] contribute
some of their personal time," she adds.
One of the first things Stephens did when she assumed the newly
established post at Hewlett-Packard was to "create an environment
that encouraged people to volunteer." The standard is roughly four
hours per month, distributed in many possible combinations.
She maintains that it is important for any company that wants to
engage in educational reform to set up formal policies because it
sends a strong message to employees that management is serious
about their efforts to become involved.
(The Scientist, Vol:8, #23, p.1, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : Under New Management, Biosphere 2 Explores Research
Opportunities
AU : NEERAJA SANKARAN
TY : NEWS
PG : 3
Long plagued by logistical problems and dogged by
controversy, the troubled Biosphere 2, under new management,
is attempting to revitalize one of the most criticized
aspects of the program--the quality of its science.
Since the summer, more than a dozen geologists,
biogeochemists, ecologists, and climate modelers have
visited the 3.15-acre Oracle, Ariz., facility--the world's
largest enclosed artificial ecosystem--to evaluate its
potential experimental uses and have made recommendations,
in a series of "white papers," for various investigations
that might take advantage of its unique features. The
evaluation is part of an effort by the new management team
to generate a long-term scientific plan and restructure the
enterprise as a full-scale research center. The scientists'
proposals span three broad areas of possible study within
the facility: biogeochemical cycles; ecology and plant
biology; and modeling systems.
A member of the new team of scientific consultants who is
quite familiar with the enclosure and the program's troubled
past is Walter Adey, director of the Washington, D.C.-based
Smithsonian Institution's marine systems laboratory and the
primary consultant in designing the original miniature ocean
for Biosphere 2. Adey resigned from the project over
scientific differences, but has returned to take part in the
reexamination.
Adey sees unique value to the Biosphere project in the realm
of ecosystem modeling. Biosphere 2 "is not really a new
endeavor," he remarks. "It's just that it is on a much
larger scale than any other model system before."
Built in the late 1980s by a group of environmentalists,
Bio-sphere 2--which includes miniature versions of a
savanna, rain forest, marsh, farm, and ocean enclosed within
glass-and-steel domes--was touted as an attempt to better
understand the workings of the Earth's own biosphere and to
see if an artificial ecosystem could sustain humans entirely
on its own. The $150 million effort was financed by Edward
P. Bass, a Texas multimillionaire with an interest in
ecology and conservation.
The original endeavor at self-sufficient existence within
the interconnected domes commenced in September 1991, when
an eight-member team was sealed inside for two years. Among
a number of problems they experienced were poor crop yields,
leading to inadequate food supplies, and dangerously high
carbon dioxide levels. The so-called Biosphereans often went
hungry, and oxygen had to be pumped in to supplement air
supplies.
More controversy swirled around the administration of the
project. There was considerable criticism from the
scientific community because several of the Bio-sphereans
were not well-credentialed scientists and because of an aura
of secrecy--which was compounded by a lack of published
data--maintained by the nonscientist management. Because of
sharp internal disputes, many of the initial scientific
advisers quit the project last year.
This April, Bass took legal action to dismiss the top
management. A nonprofit consortium--called the Biosphere 2
Research Group--was formed in July by project executives
and Columbia University's Lamont-Doherty Earth Observatory
in Palisades, N.Y., to set a new scientific course of
action. One of its first activities was to commission white
papers from independent scientists in various disciplines
relevant to the areas of research that the facility is
equipped to support.
"A critical aspect of these papers is that they make
suggestions for work that could be done only in Biosphere
2," explains Bruno Marino, a biogeochemist from Harvard
University's department of earth and planetary sciences who
joined as the new scientific director in August. "How could
their [the white paper authors'] current research be
expanded by the unique perspective that these facilities
offer?"
He adds that each white paper "might spawn many further
proposals--the investigators could identify other people to
carry on research here. We are not yet 100 percent sure what
we are going to do." Marino, who wrote a paper on the topic
of isotope biogeochemistry, hopes to find some common ground
among the various white papers to help set an agenda for the
future of Biosphere 2.
While there are no set plans for the future, researchers
involved do not anticipate another cycle of isolated
residents at the facility. "I can see no reason to have
'Bio-sphereans' in there," says Wallace Broecker, a
professor of geochemistry at Lamont-Doherty and a member of
the executive committee of the newly formed consortium.
"They've already proved the point [that they can survive]."
Laying The Groundwork
Marino says the first step--even before any new research
projects are initiated--will be to "unpack the data
collected over the past 2H years" and fully understand how
the ecosystems enclosed within the giant greenhouse have
developed. In some cases, the advisers say, errors
incorporated into the design and construction of the
facility need to be rectified. For instance, Adey, who
originally designed the miniature ocean, sees a
"particularly strong need to redesign the model aquatic
system."
In a rush to complete construction, many important features
of the original design were either modified or left out
altogether, he says, resulting in technical difficulties--
such as destruction of pumps by plankton--as well as a
"skewed outcome" in mimicking the natural ecosystem of an
ocean. As a result of the changes, Adey, a marine ecologist,
resigned from the original project but returned to take part
in the reevaluation. He estimates that between six months
and a year will elapse before new projects are set up.
Adey concurs with Marino's view that the present system must
be understood before proceeding with further experiments:
"If we want to understand the effects of perturbing an
environmental parameter within a system, we first have to
understand the [existing] system."
In order to correlate results from Biosphere 2 to Earth's
own bio-sphere, Adey stresses, scientists need to gauge the
modeling effects resulting from the difference in size
extremely carefully. "Because of the dimensional
differences, the other parameters--temperature, humidity,
air composition--must be as close to the wild ecosystem as
possible," he cautions.
Marino and Broecker also point out the need for extremely
rigorous controls in modeling experiments.
"We have to create controls--to see what happens under
'normal' conditions," Broecker explains. Biosphere 2
scientists are not yet decided on whether the controls will
be set up in new units or be incorporated into the existing
facility.
Spheres Of Investigation
The scientists commissioned to prepare the white papers are
calling Biosphere 2 a tremendous intellectual lure.
Broecker's white paper is entitled "Elemental and nutrient
models." In the document, he suggests a number of different
experiments to describe past, present, and perhaps future
processes in the Earth's atmosphere, oceans, and crust. He
offers as one possible course of experimentation a study of
the long-term effects of enhanced levels of carbon dioxide
on various life forms. Another project he envisions is an
attempt to analyze what he calls "the fattening of the bio-
sphere," or "anthropogenic greening."
"If we add up the total amount of carbon in [burned] fossil
fuels and forests, it exceeds the amounts accounted for by
the increases in atmospheric and oceanic carbon dioxide," he
says. "Therefore there must be a carbon sink--which we
believe is the terrestrial biosphere, including soil
organisms and [standing] forests." The closed system of the
biosphere, containing a miniature forest, is an ideal place
to test the hypothesis, he contends.
The artificial ocean has generated many ideas among the
visiting scientists. Francois Morrell, a professor of
environmental engineering at the Massachusetts Institute of
Technology, is proposing studies into the organic and
inorganic chemistry of aquatic systems, while Marino hopes
to expand this into investigations of oceanic flora and
fauna. "The research potential is great," Marino comments.
"Right now [the ocean] is more like a harbor environment
with severe environmental perturbations," observes Adey. "It
could be a useful model of a coral reef." A possible
project, he says, could be a study of the degradation of
reefs in response to increasing carbon dioxide.
One of the major priorities for Bio-sphere 2's patron Bass
is the subject of ecology and the roles of different living
organisms in maintaining an equilibrium, Broecker says. To
this end, the new scientific directors commissioned several
white papers in the areas of ecology and biology. For
example, Graham D. Fahrquar, an environmental biologist at
the Australian National University in Canberra has written a
paper entitled "Plant biology and physiology"; Mary
Firestone, a microbial ecologist from the University of
California, Berkeley, is contributing her ideas in "Soil
biochemistry and microbial ecology"; and Stanford
University's Peter Vitousek, an expert in the area of
biological diversity, has written a paper on "Ecological
approaches to interaction between plants, soils and the
atmosphere."
In addition to basic research, Biosphere 2's new directors
hope to utilize the facility as an educational tool, and
efforts are already under way to establish such a program.
Broecker envisions it as an "outdoor science museum, for
young people to come and learn about the Earth's environment
and ecosystems.
"It is not a perfect analog for the planet," Broecker
concedes, "but [it] comes pretty damn close, all things
considered."
(The Scientist, Vol:8, #23, p.3, November 28, 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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NXT:
------------------------------------------------------------
TI : BLUEPRINTS FOR A GREENHOUSE (BIOSPHERE)
AU : NEERAJA SANKARAN
TY : NEWS
PG :
The reshaping of Biosphere 2 into a fully operational
scientific facility is occurring under the management of the
Biosphere 2 Research Group, a nonprofit consortium of
scientists formed as a result of a collaboration between the
Oracle, Ariz.-based facility and Columbia University's
Lamont-Doherty Earth Observatory at Palisades, N.Y. Members
of the new executive council overseeing the research group
are:
* Bruno D.V. Marino: the new director of science and
research for Biosphere 2. Marino, a biogeochemist, formerly
worked in Harvard University's department of earth and
planetary sciences.
* Wallace S. Broecker: Newberry Professor of Geology at La-
mont-Doherty. He first became involved with the project
during the tenure of the first group of Biosphereans, to
investigate the causes of the dramatic drop in oxygen levels
in Biosphere 2.
* Michael M. Crow: vice provost of Columbia University, a
professor of science policy in Columbia's School of
International and Public Affairs, and the driving force
behind the school's Global Systems Initiative.
* Stephen K. Bannon: an investment banker and administrative
head of Space Biosphere Ventures, the parent company of the
Biosphere 2 project.
In addition, the group consists of a science committee,
responsible for evaluating the current situation at
Biosphere 2 and setting up a long-range scientific plan. The
committee is chaired by Michael B. McElroy, chairman of
Harvard University's department of earth and planetary
sciences. Recently Harold A. Mooney, Paul S. Achilles
Professor in Environmental Biology at Stanford University,
was appointed vice chairman.
One of the main tasks of the committee was to commission
white papers on potential experiments at Biosphere 2.
Following are the white papers that were prepared.
* "Elemental and nutrient models," by Broecker.
* "Experimental agronomy," by Joe Tom Cothern, a professor
of agronomy in Texas A&M University's department of soil and
crop sciences.
* "Environmental science and engineering," by Jay C. Davis,
associate director, division of environmental programs,
Lawrence Livermore National Laboratory.
* "Plant biology and physiology," by Graham D. Fahrquar, a
professor and head of the environmental biology group at the
Research School of Biological Sciences, Institute of
Advanced Studies, Australian National University, Canberra.
* "Soil biochemistry and microbial ecology," by Mary K.
Firestone, chairwoman of the University of California,
Berkeley's department of environmental sciences, management,
and policy.
* "Soil physics and biology," by Eugene F. Kelly, an
assistant professor of pedology at Colorado State
University's department of soil and crop science.
* "Ecological modeling of complex systems," by Christopher
G. Langton, visiting professor, Santa Fe Institute, and John
B. Corliss, a member of the Biosphere 2 Science and Research
Department.
* "Isotope biogeochemistry," by Marino.
* "Organic and inorganic chemistry of aquatic systems," by
Francois Morrell, a professor of civil and environmental
engineering at the Massachusetts Institute of Technology.
* "Trace gas interactions with vegetation," by Karl
Turekian, Stillman Professor of Geology and Geophysics and
founder of the Center for the Study of Global Change at Yale
University's Institute for Biospheric Studies.
* "Ecological approaches to interactions between plants,
soils, and the atmosphere," by Peter Vitousek, Clifford G.
Morrison Professor of Population and Resource Studies at
Stanford University.
Also serving as advisers to the scientific committee are
Walter Adey, director of the marine systems laboratory of
the Smithsonian Institution, Washington, D.C., and John C.
Mutter, acting director and senior research scientist at
Lamont-Doherty.
--N.S.
(The Scientist, Vol:8, #23, p.3, November 28, 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:
NOTEBOOK
------------------------------------------------------------
TI : Musical Chairs
TY : NEWS (NOTEBOOK)
PG : 4
The Republican electoral earthquake that rumbled through Capitol
Hill this month will result in the unseating from committee chairs
of veteran Demo-crats, including Rep. George E. Brown, Jr.,
widely
recognized as Congress' "Mr. Science." Brown has headed the
House
Science, Space, and Technology Committee since 1991. He was
re-elected from his Southern California district but will lose the
chairmanship when the GOP takes charge of Congress in January.
Rep. Robert S. Walker of Pennsylvania, who has served as ranking
minority member of the committee, is in line to take over as
chairman. However, Walker first intends to try for a House
leadership position--majority whip. If he succeeds in that bid,
the committee leadership is likely to go to Rep. Sherwood L.
Boehlert (R-N.Y.) or Rep. F. James Sensenbrenner (R-Wis.). In the
Senate, Sen. Larry Pressler (R-S.D.) is expected to head the
Commerce, Science, and Transportation Committee, replacing Sen.
Ernest F. Hollings (D-S.C.). At press time it was still unclear
who would succeed Sen. Jay Rockefeller (D-W.Va.) as chairman of
the committee's science, technology, and space subcommittee. Among
other Democrats who will be relinquishing committee posts are Sen.
Barbara A. Mikulski, chairwoman of the Senate appropriations
subcommittee that oversees funding of the National Science
Foundation, the Environmental Protection Agency, and the National
Aeronautics and Space Administration; Rep. John Dingell of
Michigan, chairman of the House Energy and Commerce Committee;
Rep. Henry Waxman of California, chairman of the energy
committee's health subcommittee; and Sen. Tom Harkin of Iowa,
chairman of the Senate Appropriations committee subcommittee for
NIH. According to reports, Dingell or Waxman may be replaced by
Rep. Thomas Bliley, Jr. (R.-Va.). The powerful congressional
appropriations committees are expected to be taken over by Sen.
Mark Hatfield of Oregon and either Rep. Joseph McDade of
Pennsylvania, who is under indictment for corruption, or Rep. John
Myers of Indiana. The House appropriations subcommittee for NIH is
expected to be chaired by longtime NIH supporter Rep. John Porter
of Illinois.
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright, The Scientist, Inc.)
================================
NXT:
------------------------------------------------------------
TI : Another Electoral Battle
TY : NEWS (NOTEBOOK)
PG : 4
As defeated members of Congress begin to pack up their offices,
another election battle is heating up in Washington, D.C.
Cornelius Pings, president of the Washington-based Association of
American Universities and the official nominee for president of
the National Academy of Engineering (NAE), will likely be
challenged by Harold Liebowitz, dean emeritus of engineering
at
George Washington University, who garnered an astounding 42
percent of the vote when he bucked the NAE establishment and ran
as an independent in 1991. To run in this March's election, he
needs signatures of 5 percent of the membership, from 10 separate
institutions. Liebowitz asserts : "I think the academy needs
change, and I represent that to a great extent." Pings, by
contrast, comments that the academy is "in very good health" and
that he "would not go in with any reform agenda."
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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U.S.A.
NXT:
------------------------------------------------------------
TI : Job Security
TY : NEWS (NOTEBOOK)
PG : 4
In his weekly "What's New" E-mail broadsheet for November 4,
Robert L. Park, American Physical Society executive director for
public relations, reports that the Department of Energy (DOE)
chief is being considered for other jobs in the White House. "The
administration has been trying to figure out what to do with Hazel
O'Leary," he writes, recounting speculation that she might be made
ambassador to South Africa or head of the Central Intelligence
Agency. As to why something needs to "be done" with the popular
secretary, a source close to DOE, requesting anonymity, says:
"She's generally regarded as not a good team player within the
administration. A little bit of that showed up in this openness
initiative of hers, when she released the results of [past DOE]
radiation testing [experiments on humans]. Nobody objected to her
releasing [that material], but she didn't warn anybody [in the
administration]." As for rumors that O'Leary may be in line for
other work, DOE spokesman Jeff Sherwood says, "She's been denying
that for some time now." He adds that O'Leary is committed to
the
job, at least through Clinton's first term, although "she's
not
promising a second term."
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright, The Scientist, Inc.)
================================
NXT:
------------------------------------------------------------
TI : PCAST Session
TY : NEWS (NOTEBOOK)
PG : 4
In the midst of this year's election turmoil, the White House's
senior outside advisory group on science issues and policy is
reconnoitering the "wide horizon" of its mission after an
inaugural meeting that included a chat with Vice President Al
Gore. The 75-minute, closed-door session with Gore came at the
start of a 1Z\x-day meeting to launch activities of the
President's Committee of Advisers on Science and Technology
(PCAST), consisting of 18 science and technology experts plus
presidential science adviser John H. Gibbons. During the October
25-26 meeting, PCAST members discussed a possible long-term agenda
involving such issues as education, environment, health, R&D
investment, and international affairs. John A. Young, PCAST
co-chairman (with Gibbons) and former president and CEO of
Hewlett-Packard Co., describes the session with Gore as "very
inspiring." Young adds: "He is really quite well grounded in and
obviously loves science and technology issues. I thought he made
an excellent set of challenging points, to stretch our thinking."
Expanding on the direction of the discussion, PCAST member Mario
J. Molina, a professor of environmental sciences at the
Massachusetts Institute of Technology, says, "We wanted to get
some sense of what constraints we had, or what limits. On the one
hand, we have constraints in terms of the economy and what society
can afford, for research and so forth. But we don't have
constraints in terms of possible directions we can take as a
group. From that point of view, we have a wide horizon."
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright, The Scientist, Inc.)
================================
NXT:
------------------------------------------------------------
TI : Online Headaches
TY : NEWS (NOTEBOOK)
PG : 4
Researchers traveling the information superhighway are
contemplating the issues brought out by two recent incidents
involving electronic-mail networks. Last month David Farber, a
professor of computer and information sciences at the University
of Pennsylvania, posted an online notice regarding a news brief in
Information Week (Oct. 31, 1994, page 10) about British physicist
Laurence Godfrey, who reportedly is suing colleague Philip
Halam-Baker for placing derogatory messages about him on the
Usenet. And the Chronicle of Higher Education (41[9]:A24, Oct. 26,
1994) published an item about Grady Blount, an associate professor
of environmental science at Texas A&M University, who reportedly
was the victim of a break-in to his Internet account. The intruder
used Blount's account to post racist messages to approximately
25,000 people, many of whom retaliated with angry notes to the
Texas A&M faculty member. "We're in a period of chaos because the
norms of what's appropriate use [of the Internet] are in the
process of changing," says Robert Kraut, a professor of social
psychology and human computer interaction at Carnegie Mellon
University--a school that recently had its own online troubles
when it tried to shut down sexually explicit Internet discussions.
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright, The Scientist, Inc.)
================================
NXT:
------------------------------------------------------------
TI : New Year's Persecutions
TY : NEWS (NOTEBOOK)
PG : 4
The Science and Human Rights Program of the American Association
for the Advancement of Science (AAAS) has just released the 1994
edition of its Directory of Persecuted Scientists, Health
Professionals and Engineers. The booklet lists 468 individuals
from 42 countries whose human rights have been violated--119 cases
more than appeared in last year's edition. AAAS project
coordinator Elisa Munoz says the rise can be attributed to two
factors: an improvement in the program's data-collection
methods--it is developing its own sources rather than relying
primarily on Amnesty International--and the fact that "most
human-rights organizations have said there is definitely more
repression this year."
(The Scientist, Vol:8, #23, p.4, November 28, 1994)
(Copyright,
The Scientist, Inc.)
----------
WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT
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NXT:
OPINION
------------------------------------------------------------
TI : Administration's Technology Rhetoric Is Belied By Its
Policy Actions
AU : HENRY I. MILLER
TY : OPINION
PG : 12
Nowhere is the disparity between politicians' rhetoric and actions
more pronounced than in United States science and technology
policy. Government officials extol the importance of research
activities to the national economy, jobs, and quality of life,
while their policies tell a quite different story.
One need only contrast the too-often-negative consequences of the
Clinton administration's biotechnology policies with the lofty
goals that are outlined in a slick administration booklet entitled
"Science and the National Interest" (B. Reppert, The Scientist,
Aug. 22, 1994, page 1; C. Macilwain, Nature, 370:317, 1994).
Consider several examples among the document's science-policy
goals. One is to "enhance connections between fundamental research
and national goals," including "stable policies on research
funding." In fact, public-sector funding of research is down.
Budgets for 10 biomedical institutes of the National Institutes of
Health were on the administration's cost-cutting block for fiscal
year 1995. While the NIH budget as a whole rose 3.6 percent, that
increase goes primarily to the Human Genome Project and the office
of the NIH director.
Funding of investigator-initiated basic research at the National
Science Foundation is also in deep trouble. Although funding for
NSF overall increased 14 percent, the increase for research
was
only 5.4 percent, only a percentage point or so above
inflation.
Moreover, much of the NSF research budget is being shifted toward
non-basic research (C. Macilwain, Nature, 370:401, 1994). Overall,
as a percentage of the nation's gross domestic product, the White
House's proposed science budget was the lowest since 1958.
Another goal is to "stimulate partnerships that promote
investments in fundamental science and engineering and effective
use of physical, human, and financial resources." The reality is
that biotech is caught both directly and indirectly by White House
assaults on drug prices and physicians' prescribing, and its
insistence on rebates for government-subsidized drugs. While many
of these proposed changes remain in limbo along with health-care
reform, the expectation that first lady Hillary Clinton; Ira
Magaziner, senior adviser for policy development to the president;
and some members of Congress will exact their pound of flesh from
what they characterize as drug companies' profiteering continues
to make investors wary.
In addition, a climate of increased stringency of regulations,
irrational aversion to any kind of risk, and mistrust of
technology generally--and biotechnology in particular--have
conspired to discourage investment. Not surprisingly, small
biotech firms were harder hit by potential investors than
pharmaceutical giants. These firms have seen investment capital
from public offerings drop more than 80 percent between 1991 and
1993, and stock market valuations have fallen precipitously.
Consider this lead from a front-page story in the September 23
issue of BioWorld Today (L. Piercey, 5:1, 1994):
"The New York biotechnology investment firm D. Blech & Co.
suffered a liquidity crisis on Thursday [September 22] as its
capital reserves dipped below federally regulated levels and it
ceased trading activities on NASDAQ. The news caused the stock
prices of many Blech-financed companies to plummet--a portfolio of
11 of the firm's biotechnology concerns lost more than $168
million in the course of the day, more than 30 percent of their
combined market valuation."
While this collapse cannot be ascribed wholly to administration
policies, to be sure, they have created an investment climate in
which small biotech companies are less viable--and their stocks
less valuable.
Regulatory Rhetoric
An additional goal is "a stable, science-based regulatory system."
The Clinton-Gore report asserts that the administration has "taken
significant steps . . . towards accelerating the development of
technologies critical for long-term economic growth and for
increasing productivity while reducing environmental impact . . .
[via] fundamental science." The reality is that at the same time
that funding is down, biotechnology regulation, the bte noir of
the administration's policies, has become increasingly
anti-innovative, unscientific, and focused on negligible-risk
activities.
The United States Department of Agriculture (USDA) has required
unnecessary permits for more than 1,400 field trials of
genetically modified plants, all of them of negligible risk to
public health or the environment.
The Food and Drug Ad-ministration (FDA), which has a generally
positive 15-year track record on regulating biotech, has been
revising its regulatory approach according to instructions from
the administration. The agency recently announced that it will
soon require food manufacturers to notify FDA before marketing
foods made with high-precision recombinant DNA techniques--while
exempting those crafted with other techniques, regardless of
possible risk.
By exposing these biotech techniques alone to public scrutiny--for
no scientifically sound reason--FDA is casting suspicion on these
products, making them vulnerable to the boycotts, threats, and
accusations of anti-technology groups.
The biotech regulatory policies of the Environmental Protection
Agency (EPA) are the most egregious and arbitrary of all. In early
September, EPA published regulations for biotech biocontrol
agents. Inexplicably, EPA targets only products made with the most
precise and predictable new genetic methodologies, as opposed to
products made with older, cruder techniques of genetic
manipulation (which, in fact, are more likely to exhibit
unexpected traits).
The agency also plans to expand its regulatory dominion to a whole
new category of products--plants that are made resistant to pests
by using the new genetic techniques. These garden and farm plants
will be regulated even more stringently than chemicals similar to
DDT or parathion. Yet plant breeders have been creating and
farmers using genetically improved plant varieties--many with
genes moved across species or genus lines--safely for more than a
century without government regulation.
These rules make neither scientific nor economic sense. USDA, FDA,
and EPA regulatory approaches fly in the face of a broad
scientific consensus that the new biotechnology is an extension,
or refinement, of earlier techniques of genetic manipulation that
often have been subject to no regulation at all. Their regulatory
policies constitute, in effect, a tax on innovation that uses the
new biotechnology. Ineluctably, these anti-innovative policies
will discourage research using the newer, more precise techniques,
denying consumers more varied and nutritious produce grown with
fewer chemicals.
Gore's Antagonism
One might well wonder about the etiology of such actions by those
who extol the importance of technology. The vice president's
long-held antagonistic attitudes provide a clue.
In a 1991 article in the Harvard Journal of Law and Technology
(5:19-30, Fall 1991), Al Gore displayed remarkable lack
of
appreciation of the historically positive linkage between
science
and economic development when he disdainfully described investors'
eager reception of South San Francisco, Calif.-based Genentech
Inc.'s 1980 stock offering as the first sellout of the "tree of
knowledge to Wall Street."
He went on to deride biotechnology research, claiming that "the
decisions to develop ice-minus [bacteria], herbicide-resistant
plants, and bovine growth hormone . . . lent credibility to those
who argued that biotechnology would make things worse before it
made things better" [emphasis added]. Moreover, in Gore's Earth in
the Balance (New York, Houghton Mifflin, 1992), he uses repeatedly
the metaphor that those who believe in technological progress are
as sinister as the perpetrators of World War II's Holocaust. These
views from the government's technology czar are difficult to
reconcile with the recent, upbeat verbiage in the administration's
report.
Whole emerging industrial sectors--bioremediation, agbiotech, food
production, even biopharmaceuticals--have been damaged by
regulatory or other disincentives. The bitter irony in the
administration's policies is that, under the guise of concern for
safety, they have undermined research on precisely the kinds of
low-value-added but societally important products--safer and more
nutritious foods, improved bioremediation agents, alternatives to
chemical pesticides and fertilizers, and other environmentally
friendly innovations--that should have universal appeal. The
administration's record on biotechnology, including the
technology's most environmentally friendly manifestations, has
made a shambles of a success story. The new, rosy rhetoric cannot
remedy that.
Henry I. Miller is the Robert Wesson Fellow of Scientific
Philosophy and Public Policy at the Hoover Institution and a
consulting professor at Stanford University's Institute for
International Studies in California.
(The Scientist, Vol:8, #23, p.12, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
COMMENTARY
------------------------------------------------------------
TI :BASIC SCIENCE IS 'STRATEGIC' FOR THE FUTURE OF THE U.S.
AU : Zachary Burton
TY : OPINION (COMMENTARY)
PG : 13
Basic science is in the national interest and is "strategic" for
the future of the United States. In addition to being very
inexpensive for the services we provide, scientists contribute a
tremendous amount to our culture and communities--a fact that is
not appropriately recognized by Congress or the public. As a
member of an apparently dispensable generation of scientists, I
would like to express my views about congressional micromanagement
of national science policy.
My field is basic biomedical research. In this area, the U.S. is
committing less than half the funds and is funding fewer than half
the grant proposals that are minimally required for healthy
functioning of the enterprise. The problem for scientists who
cannot obtain reasonable or consistent funding for excellent
research is acute. It extends to our students, who realize that
they must be more talented and creative than the people who are
training them to survive in this field in the future.
The most competitive study sections at the National Institutes of
Health and the National Science Foundation have been funding about
10 percent of worthwhile proposals for the last several years.
With the lid screwed down so tightly on funding, we are wasting
much of the productivity of this generation of scientists. We are
also harming the next generation, since they must know that they
will have to be among the top 5 percent to 10 percent of their
colleagues to be funded in the future. I do not believe I would
have taken an academic position if I had known the federal
government would let science slip into this deep recession.
A primary casualty of federal neglect of science has been
education. Research and teaching are natural complements because
involvement in research allows us to teach newer and more
sophisticated material. This makes education more relevant and
applicable when students graduate into the work force. Ironically,
however, I must now spend about half my time writing grant
proposals, and thus have less time to devote to teaching. My
students' vision of what they can become is marred by the travails
of their teacher.
I do basic research on the functions of proteins that bind to RNA
polymerase II in the human and yeast systems. From my point of
view, understanding mRNA synthesis is fundamental to understanding
cancer and viral infection. I expect that within five to 50 years,
information accumulated about the mechanism and regulation of
transcription will contribute to curing a significant number of
now-fatal human diseases. In this endeavor, applied science is not
as practical as basic research at this time.
Yet currently, my re-search enterprise is not so much driven by
the thrill of discovery as it is by the hope of survival in a
desperately competitive field. The idea of scientists correcting
this problem by redirecting basic research to make it more
"strategic" is laughable, as we are already doing what we can to
advance important goals of society.
Industry is also dependent on basic scientists. I train people who
take jobs in the biotechnology industry. I also have interactions
with several biotechnology companies as a consultant and
manufacturer of a product. Industry cannot afford to do basic
research as we can do it in aca-demia. Personnel cost too much in
the private sector, and the free flow of ideas in academic
institutions rarely can be duplicated in industry. In supporting
academic science, society gains big dividends in biotechnology and
medical science for a relatively small federal investment.
Congressional leaders contend that they are unable to provide
additional money for basic research, although it is unclear to me
why this should be so. Basic research is a very important and
practical investment that must be made by the federal government,
since no one else can do it adequately. Without additional funds,
scientists must spill each other's blood to make more money
available for basic research.
In the absence of increased investment, I suggest the following
Draconian measures: (1) Cap overhead on federal grants at 35
percent; (2) cap federal grant awards at $150,000 per year in
direct costs; (3) make the NIH intramural program subject to
competitive, external peer review; (4) end program project grants,
except for research facilities that require shared use of
expensive, specialized instruments; (5) end federal targeting of
research dollars; (6) end "pork barrel" funding of research; and
(7) end federal funding for short-term applied research. These
measures have serious consequences, but they could be applied to
stop the hemorrhaging of the basic research enterprise.
Zachary Burton is an associate professor of biochemistry at
Michigan State University, East Lansing. E-mail:
burton@pilot.msu.edu.
(The Scientist, Vol:8, #23, p.13, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
LETTERS
------------------------------------------------------------
TI : HHMI At Yale
AU : GERARD N. BURROW
TY : OPINION (LETTERS)
PG : 13
We write concerning what we believe are misrepresentations of
Howard Hughes Medical Institute (HHMI) policies that operate at
the Yale School of Medicine, as expressed in the article by Karen
Young Kreeger (The Scientist, Oct. 3, 1994, page 3). Statements in
the article incorrectly imply that HHMI investigators and their
facilities are separate from the rest of the school and that their
equipment is inaccessible to others.
HHMI investigators occupy space in different buildings throughout
the school, including two floors of a newly constructed,
four-floor research building, called the Boyer Center for
Molecular Medicine, which was opened in 1990. Their laboratories
are indistinguishable from those of other Yale faculty in the
building, and their equipment, purchased with HHMI funds, is as
accessible to other Yale faculty and students as any in the
school.
Because HHMI investigators rely heavily on a set of core
laboratories supplying peptides and oligonucleotides and amino
acid sequencing services, HHMI contributes to the support of
technicians who operate these facilities, which are, of course,
open to all investigators. This is just one example of many ways
in which HHMI's support benefits the entire Yale community.
Gerard N. Burrow
Dean
Yale School of Medicine
Vincent T. Marchesi
Director, Boyer Center for Molecular Medicine
Yale University
New Haven, Conn. 06520
(The Scientist, Vol:8, #23, p.13, November 28, 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 : Alternative Perspectives
AU : RODNEY GRANT SEMCHUK
TY : OPINION (LETTERS)
PG : 13
The views expressed by Graeme Fricke (Letters, The Scientist, June
27, 1994, page 13) regarding the integration of alternative
medical approaches with conventional biomedical treatments appear
reasonable, relative to evaluating treatment efficacy and safety.
Where I find these views wanting is in perspective.
Open-minded intellectual curiosity is required to realize that the
broadest possible perspective will yield the best data for
analysis, and lead to greater understanding of a particular
subject. This approach to scientific investigation describes an
unbiased, open perspective, and indicates respect for the
intellectual integrity of those with different viewpoints.
A predetermined or biased approach inhibits the development of
broader knowledge. Bias is unintentional in most instances, and
most often arises from too narrow a perspective, rather than from
some self-serving motivation. Therefore, I would ask what Graeme
Fricke's perspective is when using terms such as "mainstream,"
"so-called medical professionals," "real medicine," and
"purveyors." What are the implied attitudes and apparent judgments
regarding alternative medicine? I ask this so as not to
misconstrue his interest in the development of a more informed
knowledge base.
If profit is being implied or denigrated, who would not
acknowledge that the profit motive is hardly absent among many
"purveyors" of conventional biomedical approaches to health care;
but no call is made for the world to do without the benefits of
conventional medicine based on this fact.
As a research immunologist, I, along with many other scientists
and clinicians, value the common ground found among all medical
approaches, including conventional medicine. All input is welcome
in developing a greater synthesis of knowledge for the benefit of
all. We presume that everyone involved is striving to improve
therapy.
The fulfillment of potential in all areas and on all levels
demands integration of knowledge; this can be achieved only
through interdependence. Let us contribute to a greater
realization of all potential, through open minds and mutual
support.
Rodney Grant Semchuk
The Argus Group
245 W. 25th St.
New York, N.Y. 10001
E-mail: Rodgrant@aol.com
(The Scientist, Vol:8, #23, p.1, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : THE LEADERS OF SCIENCE
THE READERS OF THE SCIENTIST
PG : 14
DONALD P. FRANCIS
Clinical Researcher
Genentech Inc.
South San Francisco, CA.
"THE SCIENTIST covers important research breakthroughs and
summarizes key information in a way that all of use with demanding
schedules can absorb quickly."
While serving with the World Health Organization, Geneva, Donald
Francis was involved in eradicating smallpox from Sudan, India,
and Bangladesh in the early 1970s. He comments: "I can walk in
India now and not see the scarred faces and blind eyes. Completely
eliminating smallpox was an historic public health accomplishment
made possible by the efforts of people working together, despite
very difficult conditions and poor communications."
One of the first scientists to suggest that AIDS is caused by an
infectious agent, Francis directed the Centers for Disease Control
and Prevention's (CDC) AIDS laboratory in Atlanta. His team worked
closely with the Institut Pasteur, Paris, to demonstrate HIV's
involvement in AIDS. Recognizing early on the devastating impact
that HIV would have on the U.S., he has been a tireless advocate
for a federal government response to AIDS that equals the urgency
of the epidemic. During his 20 years with CDC, Francis's
continuing goal was to cure and prevent infectious disease and
promote public health. "When that effort succeeds, as with
smallpox, it is incredibly rewarding. But when progress is slow,
as it is today with AIDS, it can be incredibly frustrating," he
observes.
Drawing on his long research experience with AIDS and vaccines,
Francis is currently developing an HIV vaccine. Looking forward to
success in this effort, he is also founding an organization to
establish a global HIV vaccination program. Working at the
frontiers of biomedical research, Francis feels a need for
information from many different fields. THE SCIENTIST helps to
meet that need.
He states: "THE SCIENTIST covers important research breakthroughs
and summarizes key information in a way that all of us with
demanding schedules can quickly absorb."
(The Scientist, Vol:8, #23, p.14, November 28, 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:
RESEARCH
------------------------------------------------------------
TI : Oceanic Plants Are At The Root Of Ecology's Most-Cited
Studies
TY : RESEARCH
PG : 15
Editor's Note: A little more than a year ago, the newsletter
Science Watch, published by the Philadelphia-based Institute for
Scientific Information (ISI), began conducting analyses of the
citation record of ecology and environmental sciences on a regular
basis (The Scientist, Feb. 7, 1994, page 15). Since then, the
newsletter has found that citation leaders in this burgeoning area
come from a wide array of disciplines, including plant science,
oceanography, bioremediation and pollution ecology, conservation
biology, statistics, and animal behavior.
It is interesting to note that, in a recent analysis--using ISI's
Science Indicators Database--half of the 10 most-cited papers from
1991-92 were from the field of biological oceanography. Following
is the June 1994 Science Watch report, written by Peter D. Moore,
a reader in ecology and chairman of human and environmental
sciences in the Division of Life Sciences, King's College, London.
The report--with an update on the number of citations each of the
10 papers has garnered through September 1994--is presented here
with the permission of Science Watch and ISI.
The swing of this survey of ecological and environmental citations
is distinctly toward the ocean. Papers published during 1991-92
and cited through 1992 show a very strong marine influence, with
five of the top 10 having a phytoplankton focus. (Note, however,
that Nos. 3 and 10, although bearing 1990 publication dates, did
not enter ISI's database until 1991.) The main questions being
asked center on the productivity and nutrient cycling of plankton
and the ways in which these processes might affect global
atmospheric carbon budgets.
Two of the papers on phytoplankton productivity (Nos. 1 and 7)
report results derived from the Research on the Antarctic Coastal
Ecosystem Rates (RACER) program and show that the high
productivity one often associates with Antarctic waters is mainly
confined to the Antarctic Peninsula coastal zone, other areas
being of generally low productivity. The Bransfield Strait,
studied by O. Holm-Hansen and B.G. Mitchell (Paper No. 1), lies
off the northern tip of the Antarctic Peninsula, and here the
greatest phytoplankton biomass was found, especially during the
bloom months of December and January. An understanding of what
limits the productivity of these waters and controls the blooms is
obviously of interest not only to oceanographers, but also to the
fishing industry and even to climatologists who still look
wistfully to the phytoplankton as a possibly influential carbon
sink. But the RACER program, perhaps not surprisingly, fails to
come up with a simple answer.
Nutrient limitations are not favored as an explanation either of
the bloom decline or the low productivity of many Antarctic areas.
Temperature may be involved, but the case is unproven. Light may
be important, but the bloom declines faster than the light
intensities as the Antarctic summer fades. So the answer may lie
in the grazing intensity of the zooplankton, which can account for
more than 50 percent of the productivity in a season.
The significance of grazing is also apparent in the nitrogen cycle
of the oceanic surface layers, as shown by the work of P.A.
Wheeler and S.A. Kokkinakis in the subarctic Pacific. Here they
showed that nitrate (NO3-) ions were between 15 and 40 times more
abundant than ammonium (NH4+) ions. This does not appear to be due
to efficient microbial nitrification (the oxidation of NH4+ to
NO3-), but rather to the preferential uptake of NH4+ by
phytoplankton, followed by grazing and then excretion (or
decomposition to) ammon-ium ions. These ions are quickly
sequestered once more by the next generation of phytoplankton. The
cycle virtually bypasses the nitrate ion.
Iron Fertilization Fantasy
This movement of opinion away from nutrient, or even
trace-element, limitation of phytoplankton productivity takes the
dream of iron fertilization of the oceans to create an unlimited
carbon sink even further into the realms of science fantasy. Two
other papers (Nos. 2 and 6) in the top 10 also assist in this
process. W.G. Sunda and associates (Paper No. 6) use an
experimental approach to examine the iron requirements of
different diatom species, one of which--Thallassiosira
oceanica--is an open-ocean species and the other--T.
pseudonana--an estuarine type. The oceanic species achieved
maximum growth at two moles of iron per mole of carbon, while the
estuarine species required four times this amount of iron for
maximum growth.
The early proposals by J.H. Martin and his colleagues (Science
Watch, 5[2]:7-8, February 1994) concerning iron limitations were
based on the assumption that higher concentrations were optimal
for phytoplankton growth. But this may not prove appropriate for
open-ocean conditions.
Yet one more ferric nail is driven into the coffin of the
fertilization/carbon-sink theory by T.-H. Peng and W.S. Broecker
(Paper No. 2), who have modeled the atmosphere/ocean carbon flux
on the assumption that the iron-limitation hypothesis is correct.
They found that the drawdown of carbon from the atmosphere becomes
limited by the slow process of vertical mixing within the water.
They calculate that in 100 years the atmospheric load of carbon
dioxide could be reduced by 10 percent q 5 percent, as a result of
enhancing phytoplankton productivity. So, even if the iron
limitation proposal is correct (which we have reason to believe is
not the case), the impact of mass oceanic fertilization with
soluble iron would have little impact on the greenhouse effect.
For The Landlubber
Moving to somewhat drier realms, but sticking with the effects of
elevated atmospheric carbon dioxide, R.B. Thomas and B.R. Strain
(Paper No. 4) have examined the idea that plant life will grow
better in a high-carbon-dioxide world. In general, plants are
often limited in their productivity by the availability of carbon
dioxide, but these two researchers find that if root growth is
restricted, the plant does not respond to increased carbon
dioxide. They term this observation "sink-limited feedback
inhibition," which basically means that if the plant cannot grow
adequately it shuts down its carbon dioxide acquisition, even
though gas may be present in higher-than-normal concentrations. It
is conceivable that this effect could result in a greenhouse
world, especially if root competition were severe.
Biotechnology is effectively becoming synonymous with microbial
domestication. Two of the highly cited papers on the list (Nos. 5
and 9) indicate the potential value of our bacterial neighbors in
cleaning up some of the mess we regularly make of the planet. Both
relate to the ability of certain free-living denitrifying bacteria
to degrade such toxic molecules as benzene, toluene, and xylene
that can con-taminate soils and aquifers as a result of gasoline
spills.
Denitrifying bacteria operate in anoxic conditions, in which they
use nitrate ions rather than oxygen in the respiratory breakdown
of organic molecules. These conditions provide bacteria with
energy and result in the release of nitrogen gas along with carbon
dioxide. P.J. Evans, D.T. Mang, and L.Y. Young (Paper No. 9) have
found that a very wide range of soils, sediments, effluents, and
sludges contain de-nitrifying bacteria that are able to use
toluene, some types of xylene, and benzene as substrates; these
bacteria also can completely degrade toluene in culture within
three months. S.R. Hutchins and colleagues (Paper No. 5) have
conducted similar experiments using cultures from aquifers, and
they also conclude that denitrifying bacteria can degrade such
aromatic hydrocarbons as toluene. They, however, express caution
about the value of such bacteria as cleaning agents because
mixtures of aromatic molecules--as found in jet fuels, for
example--may lower biodegradation rates overall, owing to the
inhibitory influence of some of the mixture's components on
denitrification.
(The Scientist, Vol:8, #23, p.15, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : WHAT'S HOT IN ECOLOGY AND ENVIRONMENTAL SCIENCES
TY : RESEARCH
PG : 15
Rank (Through 1992) Paper Citations
Through 1/93-
1992 9/94
1 O. Holm-Hansen, B.G. Mitchell, "Spatial 26 16
temporal distribution of phytoplankton
and primary production in the western
Bransfield Strait region," Deep-Sea
Research, 38:961-80, 1991.
2 T.-H. Peng, W.S. Broecker, "Dynamic 21 9
limitations on the Antarctic iron
fertilization strategy,"
Nature, 349:227-9, 1991.
3 P.A. Wheeler, S.A. Kokkinakis, "Ammonium 21 19
recycling limits nitrate use in the
oceanic subarctic Pacific," Limnology
and Oceanography,35:1267-78, 1990.
4 R.B. Thomas, B.R. Strain, "Root 20 45
restriction as a factor in
photosynthetic acclimation of cotton
seedlings grown in elevated carbon
dioxide," Plant Physiology,
96:627-34, 1991.
5 S.R. Hutchins, G.W. Sewell, D.A. Kovacs, 20 19
G.A. Smith, "Biodegradation of aromatic
hydrocarbons by aquifer microorganisms
under denitrifying conditions,"
Environmental Science & Technology,
25:68-76, 1991.
6 W.G. Sunda, D.G. Swift, S.A. Huntsman, 19 13
"Low iron requirement for growth in
oceanic phytoplankton,"
Nature, 351:55-7, 1991.
7 M. Huntley, D.M. Karl, P. Niiler, 17 1
O. Holm-Hansen "Research on Antarctic
Coastal Ecosystem Rates (RACER):
An interdisciplinary field experiment,"
Deep-Sea Research, 38:911-41, 1991.
8 M. Raymond, A. Callaghan, P. Fort, N. 17 29
Pasteur "Worldwide migration of amplified
insecticide resistance genes in mosquitoes,"
Nature, 350:151-3, 1991.
9 P.J. Evans, D.T. Mang, L.Y. Young, 17 10
"Degradation of toluene and m-xylene
and transformation of o-xylene by
denitrifying enrichment cultures,"
Applied and Environmental
Microbiology, 57:450-4, 1991.
10 L.M. Smith, T.R. Schwartz, K. Feltz, 17 42
T.J. Kubiak,"Determination and occurrence
of AHH-active polychlorinated biphenyls,
2,3,7,8- tetrachloro-p-dioxin and 2,3,7,8-
tetrachlorodibenzofuran in Lake Michigan
sediment and biota: the question of their
relative toxicological significance,"
Chemosphere, 21:1063-85, 1990.
Source: ISI's Science Indicators Database, 1991-94
(The Scientist, Vol:8, #23, p.15, November 28, 1994)
(Copyright, The Scientist, Inc.)
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19104
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NXT:
HOT PAPERS
------------------------------------------------------------
TI : STRUCTURAL BIOLOGY
TY : RESEARCH (HOT PAPERS)
PG : 16
I. Rayment, W.R. Rypniew-ski, K. Schmidt-Base, R. Smith, D.R.
Tomchick, M.M. Benning, D.A. Winkelmann, G. Wesenberg, H.M.
Holden, "Three-dimensional structure of myosin subfragment-1: A
molecular motor," Science, 261:50-8, 1993. (Total citations
through October 1994: 107)
I. Rayment, H.M. Holden, M. Whittaker, C.B. Yohn, M. Lorenz. K.C.
Holmes, R.A. Milligan, "Structure of the actin-myosin complex and
its implications for muscle contraction," Science, 261:58-65,
1993. (Total citations through October 1994: 76)
In the first of this pair of papers, Ivan Rayment, Hazel Holden,
and their colleagues at the University of Wisconsin's Institute
for Enzyme Research in Madison describe the structure of the
muscle protein myosin. The reason this paper is so important to
many other researchers, says Rayment, is that the
"three-dimensional structure [of myosin] gives a molecular
framework that is essential for understanding how [the molecule]
works.
"There is an enormous interest in the way that muscles contract
and a vast amount of literature on this subject. In this paper we
have actually described the three-dimensional configuration of the
motor domain of the protein."
Perhaps one of the most intriguing problems in fundamental biology
is the structural basis of energy transformation in living systems
(N. Sankaran, The Scientist, Sept. 5, 1994, page 14), a point that
is addressed in the second paper, with specific reference to
muscles, where chemical energy in molecules like adenosine
triphosphate (ATP) is converted to movement.
"In this paper we have proposed a hypothesis of how the muscle
proteins accomplish the task of converting chemical energy into
motive energy," explains Rayment. This paper and its hypothesis
are the result of an international collaboration involving
the laboratories of K. Holmes at the Max-Planck Institute in
Heidelberg, Germany, and R. Milligan at the Scripps Research
Institute, in La Jolla, Calif., in addition to the Wisconsin
group.
"The [myosin] protein hydrolyzes ATP to ADP [adenosine
diphosphate] and an inorganic phosphate, and releases chemical
energy, so as to be able to do work," says Rayment. "But in order
to do work you need something to work against, and that something
is actin. The ATP is hydrolyzed before any work is done; the
released energy is first stored in myosin and subsequently used to
move myosin past actin.
"One of the questions we had was how the actin-binding site and
ATP-binding site, which are quite far apart on the myosin
molecule, communicate with each other."
Based on the structures of the muscle proteins detailed in both
papers, as well as new electron microscopic and X-ray diffraction
data from Holmes and Milligan, Rayment believes this molecular
communication occurs through the rearrangement of a series of
domains in myosin. The next step the group will take, he reports,
is to "test the hypothesis by proving the occurrence of the
suggested structural changes by X-ray crystallographic studies on
myosin in the presence of ATP."
One reason Rayment offers to explain the high number of citations
to his articles is that both the data and hypothesis presented in
the papers "influence the way people think about the molecular
basis of motility. All of the [current] work on muscle proteins
and motility will benefit from our information. The structure of
the motor domain is already finding its way into standard
biochemistry textbooks.
"These papers tie together everything we already knew about myosin
biochemistry--it is a capstone on the field and a tribute to the
rest of biochemistry."
(The Scientist, Vol:8, #23, p.16, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : CELL BIOLOGY
TY : RESEARCH (HOT PAPERS)
PG : 16
M.B. Kastan, Q. Zhan, W.S. El-Diery, F. Carrier, T. Jacks, W.V.
Walsh, B.S. Plunkett, B. Vogelstein, A.J. Fornace, Jr., "A
mammalian cell cycle checkpoint pathway utilizing p53 and GADD45
is defective in ataxia-telangiectasia," Cell, 71:587-97, 1992.
(Total citations through October 1994: 246)
This paper is one of a number of publications from the laboratory
of Michael Kastan at the Johns Hopkins Oncology Center in
Baltimore that describe various steps of a signal-transduction
pathway in mammalian cells. It follows up an earlier paper by
Kastan's group (M.B. Kastan et al., Cancer Research, 51:6304-11,
1991) that was also identified by The Scientist as a "hot paper"
(Sept. 20, 1993, page 16).
"We had previously demonstrated that the p53 gene product--the
most commonly mutated gene in human cancer--controls cell-cycle
arrest in response to damage," says Kastan. In this paper the
authors have identified two new participants in the
damage-response pathway, using cells from patients with
ataxia-telangiectasia [AT], a disease characterized by
hypersensitivity to radiation and high susceptibility to cancer.
"In normal cells, when DNA is damaged by ionizing radiation, the
p53 protein levels rise rapidly and arrest the cell cycle,"
explains Kastan. When the cell cycle is not arrested, cells
continue to replicate, which, in the face of damaged DNA, could
ultimately contribute to the development of tumors. The
investigators found that in AT cells the levels of p53 following
radiation were abnormally low, thus indicating an additional
factor--the AT gene--in the pathway.
"While previously it was not known when the cell used p53 to halt
the cell cycle, our data showed that p53 acted in response to the
damaged DNA," reports Kastan. The reason the results are exciting,
he suggests, is that they demonstrated one mechanism by which
cells could be set up for the onset of cancer, such as in a
condition like AT, in which patients are also known to be highly
prone to cancer. The article also reports another participant in
the damage-response signal-transduction pathway called the GADD45
gene, whose induction is dependent upon p53. Though the exact
function of GADD45 is not yet known, Kastan notes that
accumulating data point to its role in DNA repair, replication,
and possibly even apoptosis (M. Smith et al., Science, in press).
Since the publication of this paper, observes Kastan, other
investigators have shown that p53 is involved "not only in
cell-cycle arrest, but in apoptosis or programmed cell death as
well. [S. Lowe et al., Nature, 362:847-49, 1993; A.R. Clarke et
al., Nature, 362:849-52, 1993]. This means that the p53 pathway is
important in determining the fate of the cell following DNA
damage."
This finding, he adds, has implications for understanding
tumorigenesis as well as for improving the outcome of cancer
therapy. "The major focus for the future," he adds, "would be to
find out all the participants in the pathway. We can then
determine what causes a cell to arrest its growth or alternatively
commit suicide and investigate ways to induce one response over
the other."
(The Scientist, Vol:8, #23, p.16, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
------------------------------------------------------------
TI : EPIDEMIOLOGY
TY : RESEARCH (HOT PAPERS)
PG : 16
M.J. Alter, H.S. Margolis,K. Krawczynski, F.N. Judson, A. Mares,
W.J. Alexander, P.Y. Hu, J.K. Miller, M.A. Gerber, R.E. Sampliner,
E.L. Meeks, M.J. Beach, "The natural history of community acquired
hepatitis-C in the United States," New England Journal of
Medicine, 327:1899-1905, 1992. (Total citations through October
1994: 76)
This paper reports the results of a study tracking the onset and
course of hepatitis C virus (HCV) infection in patients over a
four- to six-year period.
"We looked at the natural history of the disease--namely what
happens over time with respect to infection and clinical
symptoms," says Miriam Alter, chief of the epidemiology section of
the hepatitis branch at the Centers for Disease Control and
Prevention (CDC) in Atlanta. "We found that 62 percent of the
patients developed chronic hepatitis and that all of them remained
persistently infected even in the absence of liver disease or
inflammation."
>From an epidemiological perspective, this study proved
significant, Alter explains, since "it showed that the majority of
cases did not contract the disease from transfusions, which are
believed to be the most common mode of spread. Most people get it
[HCV] as a result of community-based exposure--sharing
contaminated needles, for instance, or from having multiple sexual
partners."
Another reason Alter offers for the high number of references to
this study is that "it has been the only follow-up study of
community-acquired HCV, and it showed the extremely high rate of
persistent infections." The studies indicate that HCV may be one
of the major causes of chronic liver disease in the United States.
CDC is continuing to follow up on the original patients to further
track the course of the infection. Determining the natural history
of HCV infection will be important in developing therapeutic and
prevention strategies, according to Alter.
(The Scientist, Vol:8, #23, p.16, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
TOOLS & TECHNOLOGY
------------------------------------------------------------
TI : Blotting Technology's Permanence Is Assured As Its
Applications In The Laboratory Flourish
AU : HOLLY AHERN
TY : TOOLS & TECHNOLOGY
PG : 17
Nearly everyone within earshot of a television or radio has become
familiar with the molecular biology term "Southern blotting,"
thanks to the publicity attached to some highly publicized
forensic cases such as the O.J. Simpson murder trial. Southern
blotting is the technique that may ultimately determine Simpson's
fate, by matching--or not matching--his genetic profile obtained
through DNA fingerprinting with the DNA pattern derived from blood
found at the scene of the murder of his wife, Nicole, and at his
Brentwood, Calif., home.
In Southern blotting, DNA fragments separated by gel
electrophoresis are transferred to a support membrane made of
nitrocellulose, nylon, or some other type of support material. The
process is named after the technique's inventor, biochemist Edward
M. Southern, Oxford University, England. The paper describing this
technique (E. M. Southern, Journal of Molecular Biology, 98:503,
1975) has been explicitly cited more than 25,000 times, according
to the Institute for Scientific Information in Philadelphia.
Northern blots (the transfer of RNA molecules from a gel to a
membrane) and Western blots (the transfer of proteins) were later
developments. Once blotted to a membrane, the bound macromolecules
can be analyzed in numerous ways--probed with labeled
oligonucleotides to detect specific genes for example, or treated
with antibodies to identify a single protein in a cellular extract
from among several hundred.
All three of these techniques quickly became workhorses in the
molecular-biology laboratory and for several other life-sciences
disciplines, such as developmental biology and evolution.
"These types of techniques have basically reached commodity
status," explains Keld Sorensen, senior research scientist at
Pierce Chemical Corp. in Rockford, Ill. "Blots are generally no
longer the focus of a scientist's research, but they are often the
essential tools that allow researchers to get on with their
studies."
Molecular biologists rely on Southern blots in conjunction with
Westerns and Northerns to aid in cloning genes and characterizing
the gene products. Cell biologists and organismal scientists use
blotting assays to study signal transduction or gene expression,
for example, or to analyze the events that occur during
development. Evolutionary biologists perform Southern blots to
study the evolution of conserved genes.
"Assays involving blotting are protected by history," comments
George Dearden, a technical specialist with Schleicher and Schuell
Inc., a company specializing in blotting membranes and equipment
in Keene, N.H. "To get results published, you have to show the
standard Southern and Northern blot results and prove that the
assays are sensitive and repeatable."
The scientific concepts governing all of the various forms of
blotting are essentially the same, with only the starting
material--DNA, RNA, or proteins--as the major difference. The
macromolecules separated in a gel or colonies growing on culture
media in a petri dish are placed in contact with a suitable
support material along with vast quantities of buffer. Capillary
action causes the buffer to flow through the gel toward the solid
support. The macromolecules in the gel are transported along with
the buffer to the support membrane where they bind, producing an
exact replica of the gel or petri plate on the membrane. Using a
labeled probe, researchers can detect their target and localize it
to specific colonies on the plate medium, for instance, or to a
specific molecular weight on the original gel.
Southern, Western, and Northern blots are all performed in the
same general way. In its original and still widely used form,
blotting is achieved via capillary transfer. Gels are overlaid
with the support membrane and then topped by huge stacks of paper
towels or some other absorbent material. The stacks are crowned
with a weighted object, usually the lab's largest and heaviest
molecular biology handbook, and left overnight. Buffer from below
wicks upward through the gel and the membrane, toward the
absorbent paper towels above.
Variations on this standard theme began to evolve shortly after
blotting techniques were developed. Although capillary transfers,
which require very little in the way of equipment, remain popular,
additions and improvements to the standard blot are gaining ground
with researchers who want to decrease the time required to
complete an experiment by speeding the movement of macromolecules
out of the gel and onto the membrane. Systems for vacuum
blotting--in which vacuum pressure literally sucks the
macromolecules out of the gel--and electroblotting equipment that
operate on a principle similar to electrophoresis are available
from a number of companies that specialize in electrophoresis,
such as Bio-Rad Laboratories, based in Hercules, Calif., along
with companies that supply life-sciences research tools, like Life
Technologies of Gaithersburg, Md., and Stratagene Inc. of La
Jolla, Calif.
New designs based on the standard capillary-transfer technique
also increase the efficiency of the method. The Turbo Blotter from
Schleicher and Schuell, for example, is a capillary blot system in
which blots proceed downward with gravity rather than upward. "The
downward blot is a more natural progression of events and the
nucleic acids move out of the gel quickly," says Judith Peter,
marketing manager at Schleicher and Schuell.
"Transferring DNA or protein to a support membrane is absolutely
essential, because most applications such as nucleic acid
hybridization cannot be carried out in gels," says Richard P.
Cunningham, a professor of biology at the State University of New
York, Albany. "Hybridization reactions in solution have been
performed, but the results lack context. With a blot, the
hard-copy results can be analyzed spatially in terms of molecular
weight or relative position."
"There will be a place for blotting membranes in research
laboratories for the foreseeable future," agrees Michael
Mansfield, a consulting scientist with Millipore Corp. in Bedford,
Mass., which specializes in filtration and separation
technologies. "Blotting allows researchers to conduct studies that
simply can't be done any other way."
DNA Fingerprinting
One area of blotting that is attracting the attention of numerous
scientists in clinical and forensic laboratories as well as in
molecular biology labs is RFLP (restriction fragment length
polymorphism) analysis. Known also by its more common designations
of genetic or DNA fingerprinting, this application has advanced
Southern blotting beyond the research lab and into new areas of
forensic science and diagnostic testing. "There were inklings that
Southerns were on their way out because of the development of new
procedures along the lines of PCR that would enhance researchers'
abilities to perform DNA analysis without first blotting to a
membrane," says Mansfield. "However, the standard RFLP procedures
currently in use are the most deeply entrenched right now from a
legal standpoint. As other techniques develop they will have to go
through the same sort of scrutiny before gaining widespread
acceptance within the legal community."
To produce a DNA fingerprint, DNA from a sample of blood or a
forensic specimen is extracted and treated with a restriction
enzyme, which cuts the genomic DNA derived from the cells in the
specimen into millions of small fragments. The fragments are
separated by gel electrophoresis, and then Southern-blotted to a
support membrane. After the bound DNA is denatured by alkaline
treatment, a labeled probe is added to the blot. The probe may be
specific for regions in the DNA that occur frequently (multi-locus
probes) or for sequences found singularly within specific genes
(single-locus probes). The bands that appear following the
detection steps are compared. Matches in the band patterns
indicate that samples came from the same source. A DNA fingerprint
made from a tissue sample left at the scene of a crime can
identify the perpetrator with virtual certainty.
Forensic scientists are not the only group benefiting from the use
of Southern blots in genetic fingerprinting. Scientists can study
the evolution of genes across species and ecologists can study the
parentage of animals in selected niches using RFLP applications.
Human geneticists use RFLPs to track diseases through families,
with the potential for identifying sequences that can be used as
genetic-disease markers. Add these to the large numbers of
researchers currently involved in the Human Genome Project and you
find lots of individuals interested in the Southern blot.
Gene mappers who are sorting through the millions of nucleotide
bases that make up the 23 pairs of human chromosomes are
developing technologies aimed at speeding up and miniaturizing the
DNA-sequencing process. DNA sequence data are already available
for a sizable portion of the human genome. "Ultimately, however,
all of the data obtained from sequencing will have to be related
back to what's really going on in the tissues," Mansfield says.
"And that will probably be accomplished using standard Southern
blot technology."
Developers and users of Western blot technology maintain that it,
too, is here to stay. One area in particular that is keeping this
market moving forward comes as an outgrowth of work done with HIV.
"With HIV, suddenly there was a disease that was approachable only
by Western blot," for mass screening purposes, according to
Mansfield. "With that model out there, it seems likely that other
diagnostic applications will be taking off in the near future."
Mansfield notes the appearance of a Western blot screening test
within weeks of the recent hantavirus outbreak in the Southwest
(K.Y. Kreeger, The Scientist, July 11, 1994, page 14; July 25,
1994, page 15). "The real hurdle now appears to be improving the
technology to make it applicable to viral outbreaks in Third World
countries, where the worst diseases continue to prevail," he adds.
In these and most types of Western blot assays, looking for a
single protein in an extract of cells can be likened to a search
for a needle in a haystack. Just as employing a magnet in the
needle search would quickly localize the needle, using a specific
antibody expedites the search for a target protein on a Western
blot. Companies such as Pierce Chemical, Upstate Biotechnology
Inc. in Saranac Lake, N.Y., and St. Louis-based Sigma Chemical Co.
provide antibodies as well as the reagents required to detect
antibody binding to scientists in search of a protein.
Enzyme-antibody conjugates bearing an isotopic or enzymatic tag,
buffers and blocking reagents, and detection systems for
visualizing the antibody-bound target are available alone or
together in kit form, depending on a user's individual
preferences.
"Researchers are asking more of manufacturers in terms of
higher-quality biochemicals, such as cleaner enzyme-antibody
conjugates and better-defined reagents," says Pierce Chemical's
Sorensen. "They are also relying more on provided protocols.
Rather than working up their own Western blot systems, the trend
is toward purchasing kits that supply the reagents along with a
protocol in a system that is guaranteed to work."
One of the most commonly used applications of Western blotting is
immunodetection of a target protein using a labeled antibody.
Although there are other methods, such as ELISA (enzyme-linked
immunosorbent assay) and immunoprecipitation, that can provide
essential information about the presence of a protein in a mixed
sample, these procedures lack a feature that many researchers find
important. "A Western blot of electrophoretically separated
proteins provides spatial resolution that no other method
provides," says Sorensen of Pierce Chemicals. "A major reason for
performing a Western blot analysis of a cell extract is to first
confirm the presence of a protein and then characterize it by
molecular weight," SUNY-Albany's Cunningham adds.
Sequencing proteins by mass spectroscopy is a recent addition to
the Western blot's repertoire of applications. Performing protein
analysis by mass spectroscopy is a procedure that requires
equipment that is not found in most laboratories because of the
expense. Although scientists interested in protein chemistry may
not have access to a mass spectrometer, they are likely to have
standard blotting equipment available in their labs. "Once the
proteins are blotted, the membrane can be transported to someone
with a mass spectrometer who can perform the mass analysis," says
Mansfield. "This looks like the wave of the future for protein
sequencing."
Hot Or Not?
As in many other areas of science, blotting technology is moving
away from radioactivity. "The trend away from radioactivity is
nearly universal," says Sorensen. "Blotting is an area where it
has been shown that you can get the same sensitivity without the
use of radioactivity." For Southern and Western blot techniques,
nonisotopic labeling and detection systems based on chromogenic or
chemiluminescent substrates are widely available from suppliers
like Boehringer Mannheim Biochemicals of Indianapolis, Madison,
Wis.-based Promega Corp., Bio-Rad, Pierce, and many others.
Labeling systems for RNA, such as Life Technologies'
Nonradioactive RNA Labeling system used in conjunction with their
BluGene or PhotoGene detection system, are emerging. Nonisotopic
detection systems for Southern and Western blots are in many cases
easier to use than isotope-based systems, and they virtually
eliminate the complications associated with the disposal of
radioactive waste. Sensitivity with nonisotopic detection systems
is reportedly as good as the sensitivity achieved with
radioisotopes.
The backbone of the blot is the support membrane that holds the
transferred molecules. Membranes made of nitrocellulose, nylon,
polyvinylodine fluoride (PVDF), and even copier paper have
occupied different niches within the blotting world. Membrane
suppliers such as Scheicher and Schuell and Millipore generally
have a selection of membranes available to meet the preferences of
individual users whose choice of membrane hinges on the
application. For proteins, nitrocellulose appears to be the
membrane of choice for blotting because proteins are inherently
attracted to the polymer and remain permanently attached. For
nucleic acids, which carry a negative charge, PVDF and nylon
membranes are more widely used. "There are a lot of different
types of membranes available," says Sorensen. "Researchers may try
one and find that it works in their application. If they like it,
they stick with it."
Developing new polymers or chemically treating old ones in new
ways are areas under consideration within the blotting membrane
industry. "As more polymer chemistries are searched out where the
interactions between the biomolecule and the membrane are more
than simply an affinity, it should be possible to do things that
we could not have been done in membranes in the past," Mansfield
observes. An example is studies of small molecules and peptides.
These small substances do not stick well to the supports currently
available. Changing the qualities of membranes to allow these
molecules to attach more securely will open the door to a host of
new research applications.
According to the manufacturers and users of blotting equipment,
there is no reason to view blotting membranes as simply an inert
support to which proteins or DNA can be applied. In newer
procedures the membrane is involved in the application. For many
of the PVDF-based applications, the membrane is used first as a
vehicle for purification. Once the macromolecules are anchored on
the membrane, biochemical analysis can be performed right on it.
This circumvents the need to elute the protein off of a membrane
or out of a gel before the chemical analysis can take place.
Using membranes, it is possible for researchers to look at
reactions between different proteins or between a protein and some
ligand such as GTP. To study DNA-binding proteins, for instance,
proteins on a blotting membrane can be probed with a fragment of
DNA containing a possible recognition sequence (a Southwestern
blot). Other small biologically active substances such as signal
molecules can also be studied this way. "Activity blots such as
the Southwestern blot can be used to look at physiologically
relevant reactions," Mansfield explains. "These types of assays
are of interest to many researchers, especially in the area of
development."
Southwestern blots and the potential to perform specialized
chemistries right on blotting membranes are indications of
blotting's permanence in the lab. "It is unlikely that blotting
technology will be completely superceded by another technology,"
says Mansfield. "Procedures will be changed and different
technologies will be allied with it, but blotting will continue to
have an important place in research and diagnostic laboratories."
Predicts Sorensen: "The future of blotting is evolution, not
revolution."
Holly Ahern is a science writer and an assistant professor of
biology at Adirondack Community College in Queensbury, N.Y.
(The Scientist, Vol:8, #23, p.17, November 28, 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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NXT:
------------------------------------------------------------
TI : Blotting Applications And Support Media Suppliers
Directory
TY : TOOLS & TECHNOLOGY
PG : 19
Advanced Biotechnologies
Inc.
Columbia, MD
Circle No. 100 on Reader Service Card
Advanced Genetic
Technologies Corp.
San Diego, CA
Circle No. 101 on Reader Service Card
Ahlstrom Filtration Inc.
Mount Holly Springs, PA
Circle No. 102 on Reader Service Card
American Bioanalytical Inc.
Natick, MA
Circle No. 103 on Reader Service Card
Boehringer Mannheim
Corp.
Indianapolis, IN
Circle No. 104 on Reader Service Card
P.J. Cobert Associates
St. Louis, MO
Circle No. 105 on Reader Service Card
Crescent Chemical Inc.
Hauppauge, NY
Circle No. 106 on Reader Service Card
DuPont NEN
Boston, MA
Circle No. 143 on Reader Service Card
Fluka Chemical Corp.
Ronkonkoma, NY
Circle No. 107 on Reader Service Card
Gallard-Schlesinger
Industries Inc.
Carle Place, NY
Circle No. 108 on Reader Service Card
Hoefer Scientific
San Francisco, CA
Circle No. 109 on Reader Service Card
ICN Biomedicals
Costa Mesa, CA
Circle No. 110 on Reader Service Card
Innotech Biosystems
International
Lansing, MI
Circle No. 111 on Reader Service Card
Intermountain Scientific
Corp.
Kaysville, UTCircle No. 112 on Reader Service Card
Life Technologies Inc.
Gaithersburg, MD
Circle No. 113 on Reader Service Card
Micron
Separations
Inc.
Westboro, MA
Circle No. 114 on Reader Service Card
Midwest
Scientific
St. Louis, MO
Circle No. 115 on Reader Service Card
Millipore
Bedford, MA
Circle No. 116 on Reader Service Card
Novex
San Diego, CA
Circle No. 117 on Reader Service Card
Oncor Inc.
Gaithersburg, MD
Circle No. 118 on Reader Service Card
Pierce
Chemical Co.
Rockford, IL
Circle No. 119 on Reader Service Card
Sartorius Corp.
Bohemia, NY
Circle No. 120 on Reader Service Card
Schleicher &
Schuell Inc.
Keene, NH
Circle No. 121 on Reader Service Card
Thomas Scientific
Swedesboro, NJ
Circle No. 122 on Reader Service Card
VWR Scientific
West Chester, PA
Circle No. 123 on Reader Service Card
Whatman Lab Sales Inc.
Hillsboro, OR
Circle No. 124 on Reader Service Card
(The Scientist, Vol:8, #23, p.19, November 28, 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:
NEW PRODUCTS
------------------------------------------------------------
TI : NEW PRODUCTS
TY : NEW PRODUCTS
PG : 21
Stratagene Releases New DNA Markers
Three new DNA markers have been developed to allow sizing and
quantitation of linear and supercoiled, double-stranded DNA. The
Kb DNA Ladder contains 15 linear fragments from 250 bp to 12 kb.
Bands are produced in 1,000-bp increments from 1 kb to 10 kb. The
ends of each fragment have 5_ overhangs and may be radiolabeled
with a-labeled dATP, dTTP, or dUTP. Alternatively, the ladder may
be radiolabeled by exchanging the 5_ phosphate using T4
polynucleotide kinase and g-labeled rATP. The Illuminator Kb DNA
is a version of the Kb DNA Ladder that has been prelabeled with
fluor-12-dUTP for use with the Illuminator nonradioactive
detection system. The Supercoiled DNA Ladder produces bands from 2
kb to 10 kb at 1-kb increments.
Stratagene, La Jolla, CA
Circle No. 126 on Reader Service Card
------
Balance Draft Shield From Airfiltronix
The DS-1 Balance Draft Shield is designed to protect samples from
air currents during weighing with sensitive balances. The shield
encloses the balance and is equipped with a hinged front door for
direct access to the weighing pan and controls. A 3-inch hole on
the top lid allows for sample dispensing when the lid shield is in
place. A collar on the back of the shield is available for exhaust
ventilation.
Airfiltronix Corp., Clifton, NJ
Circle No. 127 on Reader Service Card
------
Electrophoresis Gel Visualization, Documentation System
The FP 1000 Visualization System incorporates a high-resolution
charge-coupled device (CCD) camera with a 600 nm filter, a 256
gray-scale thermal printer, a monochrome 9-inch monitor, and a
low-profile darkroom with a viewing port for electronic, instant
photography of stains, wet gels, and audioradiograms. The
companion PHD 2000 Documentation System allows digital storage and
archiving of photographed images on a 3.5-inch floppy diskette. It
also provides for serializing and dating stored images as well as
image enhancement.
Ultra-Lum Inc., Carson, CA
Circle No. 128 on Reader Service Card
------
Sun BioScience's Compact Microcentrifuge Debuts
The Personal Microcentrifuge, measuring 6H** x 6H**, reportedly
achieves a full operating speed of 14,000 x g within three
seconds. Designed for quick spins at any workstation, including
the coldroom, the centrifuge can be used for nucleic acid
preparation, protein separation, polymerase chain reaction product
sedimentation, binding studies, and a variety of microchemical
determinations. It is available in three capacities (6 x 1.5 ml,
12 x 1.5 ml, and 24 x 0.5 ml) and a selection of
fixed-angle
rotors.
Sun BioScience Inc., Branford, CT
Circle No. 129 on Reader Service Card
------
VWR Scientific Unveils Sterile Syringe Filter
The VWRbrand sterile syringe filter uses a surfactant-free
cellulose acetate membrane in a modified acrylic housing. Its
applications include sterilization of aqueous solutions,
biological and immunological samples, and cell-culture media
components as well as filtration of sera, antibodies, buffers, and
tissue-culture media. The filter is available in 0.2 mm and 0.45
mm pore sizes and is certified sterile, noncytotoxic, and
nonpyrogenic.
VWR Scientific, Philadelphia, PA
Circle No. 130 on Reader Service Card
------
ATI Unveils Its New Line Of PerpHecT pH Meters
The PerpHecT line of pH meters and electrodes gives users fully
temperature-compensated pH measurements without a separate
temperature probe, according to the manufacturer. The meters
feature LED displays and tactile keypads as well as auto-buffer
recognition. Three models are available. Model 310 provides basic
pH and temperature measurements. Model 330 adds an mV mode for ORP
measurement and RS232C output capability. Model 370 gives direct
ISE (ion) concentration measurement plus mV and relative mV
capabilities. With the PerpHecT ROSS electrodes, the meters can
compensate pH measurements for both Eo and Nernstian temperature
effects.
Analytical Technology Inc., Boston, MA
Circle No. 131 on Reader Service Card
------
Hitachi OffersHPLC System
The ConcertChrom Series HPLC System includes an isocratic and
quaternary pump system, a diode array, UV-Vis and fluorescence
detectors, autosamplers, an integrator, and a PC-based data
station. The system's four modules are designed to be stacked in a
10-inch-wide tower configuration. Its software runs on the Windows
NT operating system, providing a security logbook and networking
capabilities.
Hitachi Instruments Inc., San Jose, CA
Circle No. 132 on Reader Service Card
------
Forma Scientific's Non-CFC Freezers
The Model 8500 Series ultra-low-temperature freezers use
nonchlorofluorocarbon (CFC), nonhydrochlorofluorocarbon (HCFC),
non-flammable refrigerants to maintain _867C tem-peratures.
Both
the chest and upright models incorporate a variety of new
enhancements, including the internal PEAK Control System to
protect compressors; 50 percent larger condensers for heat
removal; front-to-back airflow through the compressor housing; and
a reusable polyester foam filter.
Forma Scientific Inc., Marietta, OH
Circle No. 133 on Reader Service Card
------
Hewlett-Packard's Multitechnique Instrument Software
The HP ChemStation software package is a Windows-based program
that provides control, automation, and data handling for up to
four instruments, including the company's gas chromatograph (GC),
liquid chromatograph (LC), and capillary electrophoresis (CE)
systems. An analog-to-digital (A/D) interface option is available
for acquiring data from non-HP instruments. The software enables
users to both acquire and analyze data from HP GC, LC, CE, and A/D
systems. The software is a standard reporting package; researchers
with custom requirements can use the ChemStation custom report
generator or Dynamic Data Exchange to export data to other
Microsoft Corp. packages for reporting. The ChemStore software
package for sample organization and results storage is optional.
Hewlett-Packard Co., Palo Alto, CA
Circle No. 134 on Reader Service Card
------
Promega Launches mRNA Isolation Systems
PolyATtract Series 9600 mRNA Isolation Systems provide a means to
isolate amplification-quality mRNA for developmental and
tissue-specific screening purposes from milligram quantities of
plant and animal tissues or less than 105 cells per sample. The
systems facilitate the simultaneous isolation of polyadenylated
mRNA from up to 96 tissue extracts or cell lysates. A 96-pin
magnetic separation array is used in the purification process. Two
systems are available: One contains M-MLV Reverse Transcriptase
and other reagents for conversion of the mRNA to cDNA directly in
the wells of the plate; the other lacks these reagents to
accommodate researchers who prefer to synthesize cDNA by other
means.
Promega Corp., Madison, WI
Circle No. 135 on Reader Service Card
------
Eppendorf Microcentrifuge Available From Brinkmann
The Eppendorf Micro Centrifuge Model 5417, now available through
Brinkmann Instruments, offers a choice of three interchangeable,
autoclavable rotors with lid: a standard, 24-place, fixed-angle
rotor; a 24-place aerosol-tight rotor; and a 12-place swing-bucket
rotor. The 24-place models hold tubes from 0.25 ml to 2 ml or 12
aerosol-tight capsules. For use in the lab or coldroom, the
centrifuge has a programmable selection of speeds up to 14,000 rpm
and g-force settings up 20,800 x g.Brinkmann Instruments Inc.,
Westbury, NY
Circle No. 136 on Reader Service Card
------
Molecular Probes' One-Step Bacterial Viability Kit
The LIVE/DEAD BacLight Viability Kit uses fluorescent dyes that
distinguish bacteria with intact plasma membranes from dead
bacteria with compromised membranes. Live bacteria fluoresce
green, while dead cells fluoresce red. Bacteria can be viewed
directly after the dye mixture is applied without washing or
destaining steps. The stained bacteria retain staining specificity
and intensity after treatment with glutaraldehyde or formaldehyde
fixatives. The kit may be used to determine viability of bacteria
in mixed-cell populations and in samples that contain other cell
types, including eukaryotic cells. The proportion of live and dead
bacteria in a suspension may also be quantitated with a
fluorometer, fluorescence microplate reader, or flow cytometer.
Molecular Probes Inc., Eugene, OR
Circle No. 137 on Reader Service Card
------
HEMCO Offers Modular Enclosure Systems
The UniLab Cleanroom, capable of achieving Class 100 air quality,
is available in hard wall or soft vinyl curtain models in a
selection of standard sizes or custom configurations. The UniMax
Hazardous Containment Enclosure is designed to isolate toxic and
hazardous substances from the work area or lab. It features
ventilation and filtration systems in conjunction with grated
flooring and secondary containment basins.
HEMCO Corp., Independence, MO
Circle No. 138 on Reader Service Card
------
Power Supply For Electrophoretic Applications
The Bio-Rad PowerPac 3000 has an output of 3,000 V, 400 mA, and
400 W. It offers three modes of operation in constant voltage,
current, or power: manual mode for timed, volt-hour, or continuous
runs; program mode for more demanding methods with up to nine
separate steps; and temperature mode for electrophoresis at a set
constant temperature. Each mode is programmable via menu-driven
user interface and graphics LCD.
Bio-Rad Laboratories, Hercules, CA
Circle No. 139 on Reader Service Card
------
Drummond Introduces Microinjection Pipette
The Nanoject Auto/Oocyte Injector is microprocessor-controlled and
equipped with a nonrotating plunger. It is available in a standard
46-nanoliter fixed-volume model or a 16-step, 4.6- to
73.6-nanoliter variable-volume design. Attachable to most
micromanipulators, the Nanoject is supplied with enough glass
capillaries to pull 300 tips.
Drummond Scientific Co., Broomall, PA
Circle No. 140 on Reader Service Card
------
New England Biolabs Releases Phagemid Cloning Vectors
The LITMUS Cloning Vectors are phagemid vectors for cloning,
mutagenesis, and in vitro transcription. They feature universal
sequencing primer sites; a pUC-derived plasmid backbone; M13
origin for single-stranded mutagenesis template production;
blue/white selection; ampicillin resistance; and polylinkers
containing 32 unique restriction sites that represent all
commercially available 4-base extensions. They also contain a
system for generating RNA probes in either direction using only T7
RNA polymerase.
New England Biolabs, Beverly, MA
Circle No. 141 on Reader Service Card
------
Cohesive Biotechnologies' Prepacked Columns For Bioseparations
Bio-S and Bio-RP are two new prepacked columns and chemistries
from the Bio-Protocol line. The columns are available in 10 mm, 20
mm, and 50 mm particle sizes. Bio-S is a strong cation exchange
media that provides high dynamic capacity, resolution, and
throughput for protein purification. Bio-RP is a mildly
hydrophobic reverse-phase media for use in initial capture steps
and in final polishing processes. The mild hydrophobicity
reportedly minimizes use of organic solvents while retaining a
high degree of selectivity and resolution.
Cohesive Biotechnologies, Acton, MA
Circle No. 142 on Reader Service Card
(The Scientist, Vol:8, #23, p.21, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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NXT:
PROFESSION
------------------------------------------------------------
TI : Competition Is Intense For Jobs In Science Journal
Publishing
AU : PAUL MCCARTHY
TY : PROFESSION
PG : 23
These days, with funding for research far from assured, scientists
are seeking alternative careers that provide opportunities for
them to continue using their scientific training and remain in
touch with their fields. One such alternative is journal
publishing, a natural venue for those researchers who have a way
with words.
Generalizations about editorial jobs are risky. While some
journals rely on part-timers or even volunteers to handle editing
tasks, others--particularly those in medicine--remunerate their
editors handsomely: Several of them offer salaries in the hundreds
of thousands of dollars.
Still, it's only the weekly and biweekly medical journals that
have a need for full-time scientific editors, as opposed to the
monthlies and quarterlies, which use part-timers. The Journal of
the American Medical Association (JAMA), for instance, has five
full-time positions and the New England Journal of Medicine (NEJM)
has seven. But these are the United States' largest medical
journals and are the exception, not the rule. Edward Huth, who
served as edit or-in-chief of the Annals of Internal Medicine for
19 years, says that, in all of the world's English-language
medical journals, there are only 25 or 30 physicians editing
full-time.
Understandably, the competition for full-time slots is stiff.
Recently, when NEJM advertised for a deputy editor, 60 physicians,
all prominent in their fields, applied.
How They Got There
Researchers come to publishing through a variety of routes. Huth,
who started at the Annals in 1965 as an associate part-time editor
and moved up to editor-in-chief in 1971, calls his career switch
"one of those accidents of life."
While Huth was conducting kidney-function investigations at the
University of Pennsylvania, a colleague was tapped to be
editor-in-chief at the Annals and asked him to sign on, too. Huth
had written for a college magazine and decided to give it a try.
He retired from the Annals in 1990 but recently came out of
retirement to "hold things together" when his successors, Robert
and Suzanne Fletcher, took positions at Harvard Medical School.
NEJM editor-in-chief Jerome Kassirer had a long track record in
publishing before taking his present job. He had coedited the
monthly "Nephrology Forum" for 14 years at the journal Kidney
International, edited a column called "Clinical Problem Solving"
for the Journal of Hospital Practice, and served as
editor-in-chief of a textbook, Current Therapy in Internal
Medicine (St. Louis, Decker, 1991).
In 1974 Peter Newmark, a chemist in the United Kingdom who felt
stuck in a tedious area, left a lecturer's position to become the
biology editor at Nature. Now he is managing director of Current
Biology Ltd. in London. The company publishes nine journals;
Newmark personally edits and publishes Current Biology. In
addition, the company produces books and databases and will soon
be putting out CD-ROMs.
Editors Of All Stripes
Editors of life-sciences journals can network and get assistance
from the Chicago-based Council of Biology Editors (see
accompanying story). Some journals use deputy and associate
full-time editors to supervise the scientific side of editing
research papers. They make certain that the syntax is clear, the
research designs are adequate, and the conclusions are
justifiable. In addition, they sometimes write editorials.
And most journals have a copy editor--NEJM has seven. These
individuals have extensive editing backgrounds, some with a little
science thrown in, but most with undergraduate credentials. They
dot the is and cross the ts and get paid on a baccalaureate scale.
Because there are so few jobs available, "earning a living at
journal editing is a long shot," says George Lundberg, who is in
his 13th year as JAMA's editor-in-chief. But it is a good living
for some, notes NEJM's Kassirer.
Salary depends on experience and the candidate's previous income,
he points out. "If I brought in a cardiologist who was making
$130,000, I'd pay him that, where I would pay an endocrinologist a
little less." Adds Lundberg: "It's all a matter of negotiation
based on supply and demand." Huth guesses that the pay ranges from
$100,000 to $250,000 per year and parallels what physicians in
diverse specialties with wide-ranging experience could earn
teaching.
Various arrangements exist for the part-timers who occupy the vast
majority of editorial positions. Most have university jobs and
edit, too. Some part-timers are paid on top of their university
salaries, while the journal picks up a share of the university
salary for others. Still others edit gratis, to learn and obtain
experience.
Even though there are a lot of part-time positions, getting one
is
not easy. One reason, according to Lundberg, is that there may be
only a handful of journals in a re-searcher's specialty. On top of
that, editors may stay for five to 10 years.
Society Journals
Journals that are published by scientific societies are able to
keep staffing costs low, according to William J. Whelan,
editor-in-chief of the FASEB Journal, a publication of the
Federation of American Societies for Experimental Biology. Whelan,
a full-time professor of biochemistry and molecular biology at the
University of Miami School of Medicine, works part-time out of his
academic office for the journal and has 20 percent of his
university salary paid by FASEB.
Such an arrangement is economical "because generally the
institution is not demanding any overhead for space [and other
costs], and many of these journals are subsidized in that way,"
notes Whelan, who also was involved in starting FEBS Letters, the
European Journal of Biochemistry, and several other publications.
"I must say that, in comparison with private journals like Nature,
we have much smaller and leaner staffs."
He adds that a way to reduce costs and thus keep subscription
costs low is to "limit the number of people you need in the
central office and then spread your work out to the other
[outside] editors. We pay the editors a small fee for each
manuscript they handle--we are paying for the mail or faxes [and
so forth], but nobody makes a dime out of it."
The World Beyond Biomedicine
The take from outside biomedicine is a little different. J.P.
Keener, who edits the SIAM Journal of Applied Mathematics, is a
volunteer. Keener, a professor of mathematics at the University of
Utah, notes that the math community is small and has little money.
In mathematics "I don't see the opportunity for anyone to make a
living editing," he says.
More promising is Physical Review Letters (PRL). Although the
chief editor is part-time, there are six full-time senior editing
positions for people with Ph.D.'s in physics, according to Stanley
Brown, a senior editor at the journal. Starting salaries are
competitive with postdoctoral stipends in the field.
Still another way of allocating editing chores is found at the
Journal of the American Chemical Society (JACS), which publishes
25 journals. Twelve part-time editors, all of whom have full-time
teaching positions, keep the wheels turning. According to Charles
Bertsch, who heads up ACS's journals department, ACS's part-time
editors are paid anywhere from $1,000 to $30,000 per year,
depending on the journal's circulation, size, and number of
associate editors.
Allan Bard, the part-time editor-in-chief, has presided over JACS
for 13 years, although the term is usually five years. JACS looks
for people with a demonstrated record of scholarship. These
individuals do not apply for jobs at the journal but are tapped by
a search committee.
Having What It Takes
Of course, not everyone is suited to editing. Huth says the most
important qualities to have are a firm grasp of the nature of
scientific evidence, a broad knowledge of the field, and a
journalistic instinct to know when to publish something "that may
not stand up, but is substantial and provocative enough to merit
an airing." Kassirer, on the other hand, emphasizes administrative
ability and past editing experience.
There are drawbacks, too. Lundberg cautions that editors attract
controversy: While they are considered the friend of those whose
papers they accept, they are often viewed as the enemy of those
they reject.
And then there's the isolation, says Huth. Although
editors-in-chief are sometimes quite visible, they spend most of
their time cooped up in an office. People accustomed to the
activity of a large academic center often are not prepared to deal
with the solitude, he warns.
"You have got to recognize that it is a tyranny--that it goes on
almost 365 days a year," cautions FASEB Journal's Whelan. "If you
are away for a few days you are constantly in touch by fax because
you can't hold manuscripts up--you always have to meet deadlines.
"You have to accept that it is very demanding and you can't put it
down even for a short time, otherwise things are going to go
wrong. You are a vital link between the authors and the production
office, and the production office is always screaming politely to
meet their deadlines."
Still, for an editor-in-chief, the job can be pretty heady. Huth
points out that it's a chance to be visible. It also provides a
forum to say what one thinks almost without contradiction and an
opportunity to develop national positions on issues in ways that
the average academic can't. Not insignificantly, the job carries
considerable clout. "If you are with an important journal, you
decide what information is provided to large numbers of readers
and to a substantial extent set the agenda for medicine and health
care in the country," comments Lundberg.
One drawback to editing, according to PRL's Brown, is rejecting
papers from scientists one knows personally. When he signed on
during the job crunch of the 1970s, he recalls, he was immediately
faced with rejecting a former office-mate, but had someone else
write the letter. "Since then I've become more calloused," he
says.
Editing isn't all rejection, however. Brown reports that he gets a
good overview of physics, is involved in publishing important
research, and gets to rub shoulders with smart and interesting
people. "And it's a way to keep in touch with physics and still
get paid for it," he notes, something he wasn't sure he would be
able to do because of the tight job situation when he finished his
dissertation in the 1970s.
The biggest negative for JACS's Bard is the time editing takes
from his other work. When he's busy, he acknowledges, "I am less
than happy to spend time on other people's papers." He has also
found that, while most scientists accept how the system works, now
and then a simple rejection ends up straining personal
relationships.
Even so, Bard likes the work. Through editing he sees the big
picture in chemistry: "I get to learn a lot about modern frontier
science and the people doing it."
Advice For Aspirants
Current Biology's Newmark says his chemistry training has helped
him enormously because it has given him a feeling for science and
has enabled him to "talk the talk" with the scientists whose work
he publishes. But he says that the power of persuasion, or the
ability to develop it, is the most important quality for a
would-be editor to have. Whether it's editing journals, writing
books, or reviewing papers, he says, "a lot of publishing is
persuading busy academics to do things that they really don't have
time to do."
For the researcher who wants to make the switch, Newmark thinks
the most important thing is to send a grammatically correct
application letter. He also wants to see some evidence that the
applicant has previously shown an interest in publishing.
JAMA's Lundberg recommends first getting on an editorial board to
learn about the journal and "so they can learn about you."
Competition for jobs with physics journals is arduous because
there is currently a job crunch in the discipline, according to
PRL's Brown. He reports that he has seen several hundred
applications in recent months. He advises job-seekers not to get
their hopes up about a job at his journal.
On occasions when he does have a job open, Brown says, he looks
for someone with at least some postdoctoral experience and some
writing inclination, even as little as having worked on a student
newspaper. "It shows they have an interest in communication and
words," he comments.
Academics sometimes come up short in two areas, according to
Newmark. First, they often don't have a bottom-line mentality,
thinking that a journal will sell automatically because it is good
or important. "You can produce a wonderful [publication] and not
sell it," says Newmark, "because you neglect the marketing."
The other mistake, he cautions, is to assume that a publishing job
carries with it employment security. "You don't come here and get
a job for life," he says. "You succeed or you don't."
Paul McCarthy is a freelance science writer based in Honolulu.
(The Scientist, Vol:8, #23, p.23, November 28, 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 : WHERE BIOLOGY EDITORS GET TOGETER
TY : PROFESSION
PG : 23
The 1,200-member, Chicago-based Council of Biology Editors,
established in 1957 by a joint action of the National Science
Foundation and the American Institute of Biological Sciences,
provides resources for journal editors in the life sciences,
offers a means for them to collaborate, and fosters "effective
communication practices," according to its mission statement.
The group sponsors an annual meeting (next year's gathering,
scheduled to take place in Kansas City, Mo., in May, will focus on
the challenges of the electronic aspects of publishing) and
publishes a style manual for life-sciences journals, as well as a
newsletter.
Council of Biology Editors
11 S. La Salle St., Suite 1400
Chicago, Ill. 60603
Phone: (312) 201-0101
Fax: (312) 201-0214
* President: Bradley Hundley
* Managing Director: Cindy Clark
(The Scientist, Vol:8, #23, p.23, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE
FOLLOWING ADDRESSES:
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NXT:
PEOPLE
------------------------------------------------------------
TI : Pair Of Eminent Peptide Biochemists Receive 1994 Ciba
Award For Hypertension Research
AU : NEERAJA SANKARAN
TY : PROFESSION (PEOPLE)
PG : 24
Adolfo J. deBold, a professor of pathology and physiology at the
University of Ottawa and director of research at the University of
Ottawa Heart Institute in Ontario, Canada, and Ervin G. Erdos, a
professor of pharmacology and anesthesiology and director of the
Peptide Research Laboratory at the University of Illinois College
of Medicine, Chicago, have received the Ciba Award for
Hypertension Research.
Cosponsored by the Houston-based American Heart Association's
Council for High Blood Pressure Research and the Ciba-Giegy Corp.
Pharmaceuticals Division, Summit, N.J., this annual
award--including a cash prize of $20,000 to be shared by the
winners--recognizes contributions toward the improved
understanding of hypertension. The award was presented during the
American Heart Association's annual meeting, held in Chicago in
September.
DeBold was the first to demonstrate that the heart has an
endocrine function in addition to its role as a pump in the
circulatory system. He discovered and isolated a hormone called
atrial natriuretic factor (ANF), named thus because it is produced
in the heart's atria and has very powerful diuretic and
hypotensive properties. In general, deBold explains, ANF
counteracts the renin-angiotensin-aldosterone system in the body,
which increases blood pressure and blood volume.
"The characterization of this hormone led to numerous insights at
the physiological level about water and electrolyte balance," he
says. Currently, the peptide, which acts by "improving perfusion
of blood into the kidneys and their filtering capacity," is being
tested in clinical trials for the treatment of acute kidney
failure.
DeBold's original paper describing the hormone--A.J. deBold et
al., Life Sciences, 28:89-94, 1981--was designated a Current
Contents "Citation Classic" in 1991 and has been explicitly
referenced in more than 1,800 subsequent articles.
DeBold received his undergraduate degree in clinical biochemistry
from the National University of Cordoba in his native Argentina in
1968. He attended graduate school at Queens University, Kingston,
Ontario, in Canada, where he received M.Sc. (1972) and Ph.D.
(1973) degrees in pathology. He held various appointments at
Kingston from 1972 through 1985, when he moved to the University
of Ottawa. Since 1989 he has also been a Distinguished Research
Professor at the Heart and Stroke Foundation of Ontario.
Erdos was recognized for his role in defining the critical enzymes
involved in the metabolism of peptides that regulate blood
pressure, particularly for finding that the enzymes angiotensin I
converting enzyme (ACE) and kininase II are identical.
"We discovered that this enzyme exerted a dual effect on blood
pressure--by controlling two oppositely acting peptides," recalls
Erdos. "It activates the vasoconstrictor angiotensin, which raises
blood pressure, while also inactivating bradykinin, which is a
vasodilator."
His seminal paper discussing this work--"Angiotensin I converting
enzyme," Circulation Research, 36:247-55, 1955--was featured as a
"Citation Classic" in Current Contents in 1986 and has received
more than 200 citations. This work was an important stepping stone
in the development of the class of drugs called ACE-inhibitors.
"Besides blocking ACE, these inhibitors also act by prolonging the
half-life of bradykinin, and that has beneficial effects on the
heart and blood pressure," Erdos explains. Examples of such drugs
include captopril and enalapril, which are used for the treatment
of such conditions as hypertension and congestive heart failure,
in addition to preventing complications that can lead to stroke.
A native of Hungary, Erdos graduated in 1950 from the University
of Budapest Medical School, and obtained an additional M.D. from
the University of Munich Medical School in Germany in the same
year. He first came to the United States in 1954, and taught at
several universities before moving to Chicago in 1985. His work on
peptides and enzymes has garnered him other prestigious
awards,including a gold medal in 1988 from the Frey-Werle
Foundation of the University of Munich.
--Neeraja Sankaran
(The Scientist, Vol:8, #23, p.24, November 28, 1994)
(Copyright, The Scientist, Inc.)
----------
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E-Mail Fredric L. Rice / The Skeptic Tank