THE SCIENTIST VOLUME 7, No:21 NOVEMBER 1, 1993 (Copyright, The Scientist, Inc.) Articles p
THE SCIENTIST
VOLUME 7, No:21 NOVEMBER 1, 1993
(Copyright, The Scientist, Inc.)
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TI : CONTENTS
PG : 3
NEUROSCIENCE CAREER OUTLOOK: Stunning research advances have
swelled the ranks of neuroscientists. But tight federal funding
and wariness on the part of industry about the economy in general
has made job prospects for these new brain researchers sparse--at
least in the short term
PAGE 1
STEWART-FEDER UPDATE: The long-term future for Walter Stewart and
Ned Feder, two National Institutes of Health scientific fraud
investigators removed from their laboratories and transferred
elsewhere in the agency, is still being negotiated, though two
powerful United States senators have recently lent support to
their fight for reinstatement to their former positions
PAGE 1
MUSEUMS AS CLASSROOMS: The Howard Hughes Medical Institute, known
for its support of productive scientists, also offers an
innovative program aimed at helping to ensure the next
generation's curiosity and wonderment with science--funding
education programs developed by local science museums, with an
emphasis on attracting young women and minorities
PAGE 1
BUILDING MOMENTUM: The National Science Foundation has awarded
$37.1 million to 56 colleges and universities to repair their
deteriorating research facilities in an attempt to make a dent in
what NSF estimates to be a $10 billion to $12 billion "problem"
with such aging infrastructure nationwide
PAGE 3
PATENT PROBLEMS: The patenting of scientific discoveries may be
necessary in order to protect some scientists' intellectual
property, says British immunologist Cesar Milstein; but he also
cautions that the practice of patenting is often unfair and
actually dangerous to the health of curiosity-driven research
PAGE 11
COMMENTARY: A recent photo in The Scientist .MDNM/showing Hillary
Rodham Clinton and Mary Lasker, founder of the Lasker
Foundation's medical research awards, is symbolic of the vital
role basic research can play in providing health care to all
Americans, a message that should not be lost on Congress or the
public, says Eugene Garfield
PAGE 12
CELLULAR MECHANICS: Scientists are converging from many
disciplines in an attempt to unlock the secret of "molecular
motors," the complex mechanisms that drive cells. The task is
daunting, and funding is described as "seat of the pants"
PAGE 14
HOT PAPERS: A cancer researcher discusses her report describing
an antibody that allows examination of p53 expression in solid
tumors
PAGE 15
DIGITAL MICROSCOPY: In many areas, film-based photography is
gradually being replaced by digital imaging amenable to computer
manipulation, transfer, and storage. In microscopy, especially,
new digital cameras and scanners are providing ever-improving
image quality, as well as ease and economy of use
PAGE 19
BRAIN TRUST: Love of learning unites the prestigious membership
of the American Philosophical Society, the U.S.'s oldest honor
society, which celebrates scholarship in the sciences, arts, and
humanities--and whose ranks include some of America's premier
scientists
PAGE 21
DARYL CHUBIN has been appointed division director for research,
evaluation, and dissemination in the education and human
resources directorate of NSF
PAGE 22
NOTEBOOK PAGE 4
CARTOON PAGE 4
LETTERS PAGE 12
CROSSWORD PAGE 13
OBITUARY PAGE 22
SCIENTIFIC SOFTWARE DIRECTORY
PAGE 30
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Neuroscience Is A Booming Field--For Neuroscientists With Jobs,
That Is
Exciting advances in this discipline are attracting far more
researchers than academic and corporate labs currently can employ
AU : SUSAN L-J DICKINSON
TY : NEWS
PG : 1
Working neuroscientists can take heart: Their discipline is
booming. Exciting advances in their field, and a rapidly
broadening environment for the application of these advances,
have placed their specialty at or near the forefront of life
science endeavor during the past decade or so.
Membership in the Society for Neuroscience has nearly doubled
during recent years. At this year's meeting of the organization--
November 7-12 in Washington, D.C.--attendees will be bombarded
with a packed agenda of seminars, short courses, speeches,
workshops, product demonstrations, and a wealth of other events.
The multiplicity of offerings attests to the high level of
energy, activity, and fruitful achievement characterizing the
discipline at this point, midway through the so-called Decade of
the Brain.
But what about the non-working neuroscientists--the advanced-
degree-holding men and women who will be at the meeting primarily
to find work? For them, prospects aren't all that bright.
According to trends observed by the society's placement service,
work-seeking neuroscientists are likely to confront the fact that
their numbers are dramatically on the increase--but job
availability is discouragingly on the decline.
Currently, says David Bredt, who graduated from Johns Hopkins
University this past May with an M.D. and a Ph.D. in
neuroscience, "the job market is extremely competitive. Many of
my colleagues have applied to more than 50 places." Ross Gibson,
director of human resources for Cambridge Neuroscience Inc. in
Cambridge, Mass., concurs. "We've had no trouble finding people
we want," he says. "If we advertise nationally, we get up to 200
applicants per position; 15 to 20 percent of these meet our exact
qualifications."
But industry experts say that as neuroscientists spend more time
copying their resume and interviewing with prospective employers,
they can take heart in the knowledge that their employment
prospects are better than those of their scientific colleagues in
many other fields. Industry watchers say that biotech companies
are still being founded to cash in on neuroscience breakthroughs,
pharmaceutical firms are preserving neuro- science as they pare
down their research and development budgets, and granting
agencies are making a concerted effort to invest in neuroscience
during the '90s' "Decade of the Brain" effort.
"Neuroscience is getting lots of publicity and money, so this
period is probably not as painful for us as for scientists in
other areas," observes Christine Livingston, a Ph.D. graduate of
the neuroscience program at the Marine Biomedical Institute in
the University of Texas Medical Branch at Galveston.
"The glory days of two decades ago are past," adds Jim
Blankenship, president of the Association of Neuroscience
Departments and Programs and director of the neuroscience program
at Galveston, referring to a period of expanded hiring of
scientists in general and neuroscientists in particular. "But the
job market [for neuroscientists] is reasonably stable; there is
no reason to panic."
Market Factors
Statistics compiled by the placement service at each of the past
five Society for Neuroscience meetings reveal a depressing trend
for those entering the job market (see charts on page 7): The
number of candidates registering for interviews has increased
sharply, while the number of position descriptions posted has
leveled off, and the number of employers registering to interview
candidates has decreased.
The result is that, while the average number of interviews each
employer conducts at the meeting has increased, the average
number of interviews each candidate garners has decreased.
Several factors--involving both the supply of neuroscientists and
the demand for them--have converged to create this current tight
market, observers say.
The most significant of these factors is the sharpness with which
the supply of neuroscientists has increased: The Society for
Neuroscience reports that its membership has grown in the past
five years from 11,690 in 1987 to 20,415 in 1992. A small portion
of this increase can be attributed to the burgeoning number of
Ph.D.'s being awarded in neuroscience. Yet it is ironic that one
of the most valuable assets of neuroscience--its
interdisciplinary nature--is also the primary reason there are so
many scientists competing for a few jobs, neuroscientists say.
"Scientists are converging from all different backgrounds into
this field: pharmacology, molecular biology, protein
biochemistry, immunology, and physiology," says Ted Dawson, an
M.D./Ph.D. who has just garnered a joint assistant professorship
in the departments of neurology and neuroscience at Johns
Hopkins. "Neuroscience is probably the most interdisciplinary of
any of the biomedical sciences," concurs U. Texas' Blankenship.
"Molecular biologists are finding that just being able to clone
genes is no longer that unusual or marketable a skill. So they
are starting to focus, and the developments in neuroscience are
probably more exciting, more plentiful, and more rapidly moving
than in any other field of biomedical research," says Solomon
Snyder, director of the neuroscience program at Johns Hopkins.
"So many people are entering the field," he adds, "that NIH
[National Institutes of Health] funding for neuroscience is being
overwhelmed."
Academic Dilemma
Indeed, heightened competition for grant money--almost a
prerequisite for staying in an academic department or obtaining
permanent appointment--is making the academic sector of the job
market tightest for neuroscientists. "Everyone is scared about
the grant situation," says Blankenship, and a brief glance at
some statistics from NIH reveals why.
The success rate of grant applications to the National Institute
of Neurological Disorders and Stroke (NINDS), the source of
nearly one-third of the $1.9 billion NIH granted to Decade of the
Brain projects during fiscal year 1993, has plummeted, from 39.6
percent five years ago to 21.9 percent in 1993. One reason is
that the number of applications is up, from 1,583 in 1991 to an
estimated 1,802 this year. And Constance Atwell, NINDS director
of extramural programs, notes that the institute's annual budget
increase is not keeping pace with either this increase in the
number of applications or the average size of grant awards.
According to students as well as professors of neuroscience, this
situation is creating a lot of stress in academic labs throughout
the country. And Bredt, who will be moving to the University of
California, San Francisco, in January as an assistant professor
of neuroscience, says that getting a job doesn't necessarily
relieve the pressure: "Unless your research is successful and you
are lucky enough to have it be of interest to a granting agency,
then you can't even stay in a department."
"You are much more marketable in looking for a job if you have a
grant," Livingston agrees. She received her Ph.D. from the
University of Texas, Galveston, in 1987, and it was only three
months ago, after two postdoctoral fellowships, that she returned
to a position on the same campus as assistant professor in the
department of humanities and basic sciences. In her words, an
assistant professorship in a liberal arts department is an
"unorthodox position" for a scientist who wants to do serious
work in the lab. She spends much of her time teaching
undergraduate students, and has limited start-up funds and lab
space for her own work. She says that some friends advised her
against taking this position, cautioning that teaching
responsibilities would swallow up her research time. Others felt
that she was selling out.
"But [the job market for neuroscientists] was a pretty
threatening environment," she says. "And I was in a very scary
position, especially as a single parent and the sole provider for
my family."
Now, Livingston says, she is finding her position challenging and
interesting. And she is confident that, with colleagues and
collaborations still in place on campus from her graduate school
days, her research won't suffer. Moreover, bad as her experience
has been, she agrees that in another field of research it could
well have been worse. "[Undergraduate] biology departments love
to have neuroscientists on their faculty," she says. "Big strides
have been made in neuroscience . . . and they want to milk the
field."
With a job market that, at best, can be described as stable, why
do many neuroscientists feel fortunate? "Neuroscience is exciting
right now," says Dawson.
Indeed, recent advances in molecular biology are enabling
scientists to clone receptor proteins and identify subreceptors
that no one knew existed a decade ago. Developments in
neurophysiology are allowing scientists to record activity of a
single ion channel. The gene for Huntington's disease has been
identified, and it is now known that amyotrophic lateral
sclerosis (ALS, or Lou Gehrig's disease) is caused by the loss of
a simple enzyme.
"A whole new category of drugs is being developed to treat
previously untreatable neurodegenerative diseases," notes Kayla
Paul, director of international clinical research at Hoffmann-La
Roche Inc. in Nutley, N.J. And because America's aging population
is making neurodegenerative diseases more prevalent, industry's
investment in neuroscience is expanding.
"Since there are new tools and new avenues for therapeutic
intervention, there is more money being spent in neurology and,
especially, neuropharmacology," observes Thomas L. Copmann,
assistant vice president for biotechnology and biologics at the
Washington, D.C.-based Pharmaceutical Manufac- turers
Association.
"The pharmaceutical industry is having a renaissance of interest
in neuroscience," adds Johns Hopkins' Snyder. "And of course,
this translates into jobs."
Commitment To Research
Although recent layoffs and job cuts at major pharmaceutical
firms have gotten a lot of media attention, several of these
companies indicate that they are not backing away from their R&D
commitments in the neuroscience area. Merck & Co. Inc. in
Whitehouse Station, N.J., reports that it hired 18 people in the
neurosciences in 1993, and plans to continue this expansion in
1994, hiring some 10 to 15 more. SmithKline Beecham,
Philadelphia, won't release hiring numbers, but confirms that it
has hired some Ph.D. neuroscientists in 1993, and that
neuroscience continues to be one of its core programs. Warner-
Lambert Co. public relations representative Lisa Wilder reports
that her Morris Plains, N.J.-based company launched Cognex, the
first United States Food and Drug Administration-approved drug
for Alzheimer's disease, in early September. "Cognex is the most
important drug in the history of our company," she says.
"Neuroscience is a big growth area for us."
And the picture at smaller biotech firms that specialize in
neuroscience is also one of cautious expansion. Neurogen Corp. of
Branford, Conn., hired 15 researchers (including six Ph.D.'s)
during the past year, and estimates it will make five to 10 new
hires in 1994. Regeneron Pharmaceuticals Inc., Tarrytown, N.Y.,
hired 25 new employees in 1993, and projects 1994 new hires will
number about 50.
Cephalon Inc. of West Chester, Pa., has expanded the ranks of its
Ph.D.'s and M.D.'s by 20, an increase of 31 percent since last
December, and plans to continue hiring throughout the coming
year. Cambridge Neuroscience Inc. hired 10 neuroscientists in
1993, and has plans to hire six more in 1994. And Raymond Bartes,
senior vice president of neurobiology at Alkermes Inc., also in
Cambridge, has hired eight neuroscientists in the last eight
months, and says that positions are still open at his company.
This expansion is being fueled not only by the normal growth of
young companies, but also by the unprecedented number of
promising compounds these neuroscience companies are working on,
according to analysts in the biotechnology research division of
Merrill Lynch & Co. in New York. As a group, these firms have at
least 28 neuroscience-generated products (neurotrophic factors,
neurotrophins, and other neurology products) in development. Many
of these, according to Merrill Lynch, address previously
untreatable neurological disorders, such as Alzheimer's, ALS,
Parkinson's disease, stroke, and spinal cord injuries.
Despite this increased activity, all of these companies are
currently operating under economic and political pressure.
Consumers and investors are spending less money, and the
potential results of the current national debate on health care
have top managers at biomedical corporations concerned.
Guarded Optimism
"We are in an anomalous situation now," says John Groom,
president and chief executive officer of San Carlos, Calif.-based
Athena Neurosciences Inc.
"We are making good scientific progress in a negative [economic]
environment. As a result, I am very optimistic about our
technology, but very pessimistic in terms of how to pay for it."
Nevertheless, Groom says, there currently are openings for
Ph.D.'s at Athena--positions that represent expansion, not
just replacement.
Until some of these issues are resolved, neuroscientists counsel
their job-seeking colleagues to be patient. Christine Livingston
recalls the advice of a professor that she has found to be true:
"Just stick it out and you'll make it."
Blankenship also urges calm and perseverance. "The short term
looks a little spooky," he acknowledges. "But openings are there,
and in the long term, things should cycle back around."
Susan L-J Dickinson is a freelance writer based in Philadelphia.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : NIH Fraud Investigators Take On New Roles At Agency, But
Remain Determined To Resume Sleuthing Activity
Stewart and Feder, with support from senators, continue efforts
to have their controversial reassignments reversed
AU : FRANKLIN HOKE
TY : NEWS
PG : 1
Walter Stewart and Ned Feder, the two National Institutes of
Health scientists whose fraud-busting investigations were quashed
by forced reassignments last April, have now--after a summer-long
resistance campaign--taken up their new positions.
Feder is a grants reviewer in the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK), and Stewart is a
science writer in that institute's Office of Program Planning and
Evaluation, writing summaries of the institute's research
activities.
But while the pair may have acceded to their employers' demands
for now, their long-running, controversial case is far from
settled. Determined to resume their investigative roles, they
have proposed creating an Office of Whistleblower Assistance at
the institutes, to be staffed by them. They have also conducted
workshops on their own time to explore sexual and racial
discrimination, scientific misconduct, and retaliation on the NIH
campus, offering to help attendees file official complaints.
Meanwhile, two senators have taken up their cause, pressing the
General Accounting Office (GAO) to investigate their
reassignments as possible violations of the 1989 Whistleblower
Protection Act. Sens. William S. Cohen (R-Maine) and Charles E.
Grassley (R-Iowa), cosponsors of the law, are concerned that the
action at NIH, within the Department of Health and Human Services
(HHS), may amount to retaliation.
"The two whistle-blowers are recognized experts in rooting out
scientific fraud and uncovering waste of government funds," Cohen
said in a statement. "This is work in which all Americans have a
stake because it is their money that may be wasted. We must know
all the facts surrounding the reassignment of these two
scientists."
`Atmosphere Of Fear'
Stewart and Feder say the reassignments are certainly
retaliation, an overt attempt to silence dissenting voices.
"And the sad fact is that suppression sends a message to the
community at large," Stewart says. "It's not necessary to shut
more than a few people up before you create an atmosphere of
shutting up. There certainly is an atmosphere of fear here that
if anyone speaks out, they're going to be retaliated against. And
I think there's an adequate basis for that belief."
NIH originally reassigned Stewart and Feder to begin new jobs in
early May. But the internal personnel move drew national
attention, and, after a 33-day hunger strike by Stewart ended in
mid-June, HHS placed the two on paid administrative leave pending
a review of the case by the department's general counsel (F.
Hoke, The Scientist, May 17, 1993, page 1; June 28, 1993, page
4).
Several alternative job options were discussed during the review,
but these were each rejected by either Stewart and Feder or the
agency. These rejected possibilities included placements within
HHS's Office of Research Integrity (ORI) or Office of the
Inspector General (OIG) or temporary faculty positions with the
Program for Cultural Values and Ethics at the University of
Illinois, Champaign. Positions hardened, and HHS attorneys ended
the negotiations with the late-September order for the two to
return to work.
The dispute between Stewart and Feder and their employers stems
largely from differing characterizations of their work. The two
investigators say they are involved in scientific integrity
research with important implications for biomedical science,
while HHS views their work as unauthorized investigations of
individual scientists with the seeming imprimatur of the
government. Although the investigative work was part of Stewart
and Feder's formal performance assessments, HHS now says such
activities are appropriate only to official investigative
offices.
"They profess that they're doing research, not investigation,"
says Michael Wald, deputy general counsel for HHS. "We find it
hard to understand how they're differentiating it."
He adds: "Whatever work gets done by anybody within the agency on
issues of scientific misconduct--whether it's direct
investigation or research as to the causes of scientific
misconduct--needs to be done in an appropriate manner by people
operating within the structures of the agency. And whenever an
investigation is involved, the privacy rights of people who are
being investigated as well as the thoroughness of the
investigation, both, are important values to be protected."
Stewart and Feder say they are not police but scientists, and, as
such, must be allowed the freedoms traditionally accorded to
scientists.
Sens. Cohen and Grassley have seen sufficient merit in that view
to begin asking questions of HHS officials and to call for the
GAO investigation. The two senators have been involved in a
number of Department of Defense whistle-blower cases in the past.
"While we do not want to unjustly accuse anyone of wrongdoing in
this case," Cohen said in the statement, "the circumstances
surrounding the reassignment of Mr. Stewart and Dr. Feder have
raised troubling questions about NIH practices." Cohen is the
ranking Republican on the Subcommittee on Oversight of Government
Management of the Senate Committee on Governmental Affairs.
A Midwestern Alternative
One employment option with appeal for all parties involved
assigning Stewart and Feder to a university under the provisions
of the Intergovernmental Personnel Act (IPA). The IPA allows
federal employees to be temporarily assigned to nonfederal
organizations for up to four years when it serves "sound public
purpose," according to the federal personnel manual. The salaries
and benefits of such employees continue to be paid by the federal
government.
The federal personnel manual also states, "Assignments
arranged...to avoid unpleasant personnel decisions are contrary
to the spriit and intent of the mobility assignment program."
Still, after consultation with Stewart and Feder's lawyers,
according to Wald, letters were sent from the HHS general
counsel's office to 23 academics who had written in support of
Stewart and Feder earlier, at the time of their reassignment.
"We asked them whether they would take the lead in seeing whether
placement was possible at their university," says Wald, "figuring
that the most likely kind of placements would be where there was
already somebody interested in [Stewart and Feder's] work."
One of the people contacted was Robert Sprague, a professor of
psychology at the University of Illinois, Champaign, and a former
whistle-blower himself. Sprague received support from Stewart and
Feder when he accused University of Pittsburgh psychologist
Stephen Breuning of publishing false claims concerning
psychotropic medication of mentally retarded people. Breuning
pleaded guilty to academic fraud-related charges in United States
District Court in Maryland on Nov. 10, 1988.
Sprague contacted the person in charge of the university's
Program for Cultural Values and Ethics, who expressed an interest
in bringing the two NIH scientists to Illinois. Further
consultations led to specific ideas for work that Stewart and
Feder might undertake once there.
One idea, Sprague says, involved Stewart and Feder using their
so-called plagiarism machine--a computer system for comparing
texts for similarities--to assess the plagiarism "norm" in
science.
"They were going to look into the base rate of plagiarism with
their equipment," says Sprague. "They would take a large database
and try to assess in scientific literature just how much is
duplicated or copied."
The arrangement foundered, however, on misunderstandings over
whether the two NIH scientists would be able to maintain their
homes in Washington and even their offices on the NIH campus.
Stewart and Feder thought, as did Sprague, that they could
fulfill their obligations with a part-time presence on the
Illinois campus.
Wald and HHS, however, expected them to move to the Midwest.
"The purpose of an IPA is for an employee to be placed somewhere
else to gather experiences and do things they couldn't otherwise
do in the department," says Wald. It would "make no sense,"
according to Wald, for the pair to be supervised by the
University of Illinois while physically working at NIH.
When the terms of the IPA could not be agreed upon, Stewart and
Feder were ordered back to work, in new positions chosen for
them.
Even in their new positions, Stewart and Feder have continued to
offer ideas for ways they feel HHS could better use their
talents. These include the formation of an Office of
Whistleblower Assistance, to be initially staffed by them.
Stewart says they have received no response to this suggestion to
date.
Whistle-Blower Assistance
Whistle-blowers in several scientific misconduct cases indicate
that such a role for them would serve an important purpose.
"People who are encountering difficulties and whom the system is
working over have turned to [Stewart and Feder] as a resource,"
says Sprague. "And they've been very, very helpful. They were
very helpful to me. The government ought to have some kind of a
support system [for whistle-blowers]. And, clearly, they do not
have."
Sprague says that young scientists often come to him for advice
and counsel when they feel they have witnessed or been the
victims of scientific misconduct.
"Some of these people are very distraught," Sprague says.
"They've spent years working, and they see it slipping through
their fingers because of some misconduct."
Margot O'Toole, the researcher who charged that central data had
been faked in a 1986 Cell paper coauthored by Nobelist David
Baltimore, emphasized the significance of Stewart and Feder's
counsel to whistle-blowers in an interview with The Scientist
earlier this year.
"They do two very important things," O'Toole said, "and they're
the only two people in science who do them. One is that they
promote debate: They study cases and see how the principles of
science are supposed to apply.... And the other thing they do is
provide evaluation and support for whistle-blowers."
A prime concern of Stewart and Feder's during their conflict with
HHS has been the disposition of their files on scientific
integrity cases. For now, these files remain locked up, as
discussions continue.
One result of the standoff over the files, perhaps unforeseen by
HHS, is that the two investigators are now actively seeking new
cases. They have held two workshops this fall to explore sexual
and racial discrimination, scientific misconduct, and retaliation
on the NIH campus. Fliers publicizing the workshops declare that
"anyone seeking help in formulating or submitting an [Equal
Employment Opportunity] complaint or a complaint to the Office of
Research Integrity would be especially welcome."
"Being deprived of our data," Stewart explains, "we're sort of
wide open for business."
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : HHMI Museum Initiative Woos Youngsters To Science
AU : RENEE TWOMBLY
TY : NEWS
PG : 1
The Chevy Chase, Md.-based Howard Hughes Medical Institute (HHMI)
has a longstanding reputation for funding high-profile
researchers and their important investigations into the crucial
biomedical issues of the day. But a smaller, though substantial,
percentage of the Hughes budget goes toward educating the
researchers of tomorrow.
Amid the prestigious graduate fellowships and university-based
programs the institute awards is a year-old initiative that
reaches out to elementary and high school students beyond the
classroom, students like Johnetta Thomas of North Carolina. Until
last year, the 16-year-old Thomas was terrified of science.
Normally shy, she says that having to discuss the evolution of a
tornado funnel or the properties of light petrified her, until
she joined an innovative, HHMI-funded program at the North
Carolina Museum of Life and Science in her hometown of Durham.
Now, Thomas is working as an "explainer" at the museum--
expounding on the principles behind the exhibits to visitors.
"There is so much neat stuff here to see and do, and I know
people want to know what's going on," says the soft-spoken high
school student. "At first it was hard for me to talk to people.
But then I found out that everyone else is a person, just like
me, and sharing information is a way to come together."
Bringing children, especially minorities and young women, into
science by way of museums and similar science-related
institutions is the focus of the HHMI program that last year
granted Thomas's North Carolina museum $175,000 over five years.
Through the museum's "Biolinks" program, dozens of disadvantaged
African American students spend up to 10 hours a week at the
museum, picking up job skills and scientific information by
guiding the museum's visitors, many of whom are also minorities.
This year, the HHMI program awarded $4.2 million in five-year
grants to 22 museums, botanical gardens, aquaria, and zoos large
and small across the United States. Last year, in its first
round, it gave $6.4 million to 29 natural history, science, and
children's museums.
Small Program, Big Goals
Although the museum initiative is one of the smallest of Hughes'
education programs--which award-ed a total of $51.4 million in
fiscal year 1993, the majority of which went to graduate,
postdoctoral, and M.D. students in the form of research
fellowships, as well as support for undergraduate education
programs--it rounds out the institute's mandate to improve the
quality of science education at all levels, from primary school
to postdoctoral science. It is the largest private effort to
support educational programs in science museums in the U.S.,
according to HHMI officials.
The institute started the program to tap youngsters' inherent
interest in science, says Joseph G. Perpich, HHMI's vice
president for grants and special programs. "Kids have all the
natural attributes of scientists. They are full of questions, and
are very excited by nature. But they seem to lose that in the
fourth or fifth grade if not stimulated."
But, Perpich adds, the institute wants to do more than fund
short-lived "gee whiz" exhibits that offer a spark of interest
that dies the moment kids leave the museum. Their goal, hashed
out in two years of planning, is to create well-designed
educational programs, directly connected to teachers and pupils,
that go beyond the museum walls to have an impact in the
community. Says Perpich, "We ourselves are not able to master and
run programs that support local schools. We want to fund the ones
in the business of exciting kids."
The institute also has a social agenda: to largely steer the
programs to minority and female children. "In the proposals, we
paid a lot of attention to how museums were trying to reach out
to underrepresented groups and to women," he says. "It's a case
of what the science rich can do for the science poor."
Yvonne Merrill, education director of the Imaginarium, a science
museum in Anchorage, Alaska, has already seen a payoff. After
receiving a $225,000 HHMI grant last year, the small, six-year-
old museum set out to reach rural Alaskans in "roadless
communities." In September a small group from the museum flew in
a cargo plane to Barrow, on the Arctic coast, the first of nine
far-flung destinations, carrying an array of insects from around
the world. They trained local teachers in the biology of the
insects, and the use of interactive props such as models,
puzzles, and audio devices that support the presentation. And
then they left the exhibit for three weeks in the village's
community room for everyone to see.
"In Alaska there are a large number of insects, but only a few
species, and they are dull, not showy," says Merrill. "Many of
the insects brought to Barrow were from the rain forest. The
whole tropical story was mind-boggling to the students."
In Memphis, Tenn., the goal of the Pink Palace Museum is to reach
youths in two of the city's most impoverished communities, the
Foote and Cleaborn Homes public housing projects. The "Memphis
Science Alliance" initiative, funded by a $200,000 HHMI grant, is
a series of programs that follows students from fourth through
eighth grade.
One part of the program is Science Saturdays, a six-week program
of highly interactive activities offered at a church in the heart
of the projects. The Saturday program uses hands-on
experimentation, such as building terrariums and aquariums out of
plastic bottles and biological materials. Another component is a
labs program offered four to six times a year in schools serving
project residents. The program offers an earth sciences lab, for
example, where students test for such things as the physical
properties of minerals.
Long-Term Commitment
"Most museum programming is a one-shot visit. It is a most
gratifying experience to reach a child in the community that has
never gotten a chance to come here, and to maintain consistent
contact," says Joyce Godfrey, the museum's programming director.
Godfrey, Merrill, and other program directors say that the
hallmark of the HHMI grants is its five-year funding--an unusual
com- mitment for museums, which often struggle year to year for
donations. "In the current economic climate, it
is hard to raise money for anything but a highly visible, neat
project that may last only one year," says Bonnie Van Dorn,
executive director of the Association of Science-Technology
Centers, which has almost 300 science museum members in the U.S.
"The HHMI approach to sustained funding for five years is a real
breath of fresh air. It gives museums time to develop serious
projects, and to get the bugs out."
Van Dorn adds that member museums were surprised that such an
august foundation for biomedical research as HHMI "now wants to
focus on education in the public arena for young kids," she says.
"They gave a lot of careful attention to equity, to understanding
what quality teacher education is. We are delighted."
Teachers are equally grateful to be given some help, says Wendell
Mohling, retiring president of the National Science Teachers
Association. "Classrooms are generally poor. Some only get $25 a
year for lab materials," he says. "The HHMI program will make
sure that museums will not just give the kids a `yah-ha' field
trip, but will reinforce what they learn in the classrooms."
In Durham, an evolving connection between the museum and local
schools and universities may succeed in providing an enriching
boost to students from kindergarten through college and beyond.
Program director Georgiana Searles is talking with Duke
University and with HHMI investigators at its medical center to
ensure that young students who thrive at the museum will have a
shot at other Hughes initiatives, such as its precollege,
undergraduate, and postgraduate pro- grams.
As desirable as that would be, Perpich wants the goals of HHMI's
museum initiative to be reachable. He says the final outcome of
the funding is not to funnel kids into a lifelong commitment to a
science profession, but to keep their enthusiasm for life's
wonders alive. "No matter what careers the kids ultimately
choose," he says, "we just want them to know more about science
and nature."
Renee Twombly is a freelance writer based in Durham, N.C.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : MUSEUM SCIENCE FIGURES IN EDUCATION REFORM IN NEBRASKA
AU : RENEE TWOMBLY
TY : NEWS
PG : 18
Both content and logistics are critical to Judy Diamond, who is
trying to bring the world of science to students in 982
independent, far-flung, mostly rural school districts in
Nebraska.
The challenge to Diamond, assistant director for public programs
at the University of Nebraska State Museum: Make a difference in
each district--many of which include a single K-12 school of
fewer than 50 pupils--by teaching the fundamentals of science in
a new and entertaining way. Adding to the challenge was the
necessity do it in the midst of a statewide educational reform
movement that strives to highlight a multicultural approach to
science.
The solution: Use a five-year, $500,000 Howard Hughes Medical
Institute grant to work with Nebraska public television in
producing a series of videotapes that shows real scientists
talking about their love of research while performing
experiments--then build curricula around it and incorporate it
into the state's package.
For example, one of the first of 15 "Science on the Run" kits
features a female botanist talking about her life in science as
she works with pollen. "This is a glimpse into the real person
doing real science," says Diamond. "The aim is to bring in the
minority and female perspective in role modeling while helping
teach basic science concepts." The accompanying curriculum
teaches students how pollen triggers the immune system.
In order to make sure that the kits will be used to their full
potential, the museum staff spent a year researching the needs
and resources available throughout state elementary schools.
Project funds will also be used to teach fourth- through sixth-
grade teachers how to integrate the kits and videos into their
classroom. The videos will also air on Nebraska public television
station NETV.
Diamond says the HHMI grant could not have come at a better time
for the 122-year-old museum. Assimilation of its science
resources into Nebraska schools is a major goal of the facility,
and because the HHMI grant was awarded at the start of a
statewide effort to draft uniform curricula, the museum had a
chance to work "Science on the Run" into a future common lesson
plan.
--R.T.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : NSF Helps Schools Spruce Up Their Research Facilities
AU : EDWARD R. SILVERMAN
TY : NEWS
PG : 3
The National Science Foundation, seeking to halt the
deterioration of research facilities in educational institutions
around the United States, has awarded $37.1 million to 56
colleges and universities for renovation work.
When combined with $41 million in matching funds, more than $78
million will have been dedicated to repair and renovate
laboratories and other facilities used for scientific and
engineering research.
This round of funding marks the third consecutive year that NSF
has made monies available for this purpose. The current awards,
announced in September, were the result of a competitive process
in which 189 institutions submitted proposals. Schools that grant
doctoral degrees must match 50 percent of the NSF award, while
other institutions must match 30 percent to 50 percent. In some
cases, state and local governments have contributed to the
matching funds.
The awards range in size from $100,000 to $2 million. Renovation
projects are scheduled to vary from less than 12 months to as
long as five years in duration; on average, the facilities being
revitalized are 42 years old.
`A Problem Out There'
"There is a recorded $10 billion to $12 billion problem out there
in regard to facilities needs nationwide, and it crosses small
colleges and large universities," says Nathaniel Pitts, director
of NSF's Office of Science and Technology Infrastructure, which
administers the awards.
"And there's been a lot of pressure on Congress to respond.
Congress has been lobbied pretty hard. But this doesn't begin to
come up against the problem out there."
The amount of money that NSF is awarding for renovations is on
the rise, even if it is capable of addressing only a small part
of the problem. The awards given in 1992 totaled $16.5 million,
and the combined total for 1990-91--the fiscal year in which
NSF's Academic Research Infrastructure Program began awarding the
grants--was $39 million. Next year, Pitts expects the program to
hand out $50 million in funding.
"We're always saying that we're concerned about attracting
Americans into math, science, and engineering, and you can't do
that without the proper facilities," Pitts says. "Well, this
helps retain their interest."
Bonnie Sherman and Howard Thorsheim would agree. They are
psychology professors at St. Olaf College in Northfield, Minn.,
who submitted a successful proposal and received $190,000 from
NSF to renovate their school's 69-year-old psychology research
and training facility.
"We'd be stuck without it," says Thorsheim. "We're using an
apprenticeship model here, in which research is conducted with
students. It's collaborative work with professors. And without
the upgrade, this active learning approach wouldn't be feasible.
We'd be set back."
Of course, winning funds from NSF isn't a snap. Sherman and
Thorsheim, assisted occasionally by seven departmental
colleagues, spent well over a month preparing their proposal.
"It's a lot of work, but I don't think anything was
unreasonable," says Sherman. Thorsheim adds: "One of our
colleagues commented that even if we [had] lost, we won, because
we all worked so closely together. It was a great experience."
Thanks to their efforts, the psychology department expects to be
able to conduct more lab studies when the three-year renovation
is completed. And by then, the animal lab, a so-called wet area
because dissections take place there, will be separated from
"dry" areas, where computers reside.
`Crucial' Money
Similarly, the chemistry and biochemistry department at Old
Dominion University in Norfolk, Va., looks forward to using
$870,000 from NSF to upgrade its research labs, which have
asbestos problems and need electrical work.
Department chairman Frank Scully says the funds have an impact
beyond improvement of the physical facilities. "It's crucial
money, let me tell you," he says. "We've had faculty turn down
positions because of inadequate research facilities. This can
only help us recruit faculty. It'll be a major overhaul, but we
were in sore need of it."
Indeed, the department's building, which was built 25 years ago
as part of a teaching college, was never properly equipped for
today's needs, faculty say. Consequently, professors who were
required to develop research in order to achieve tenure have been
working in less-than-ideal converted teaching labs.
After a few faculty members retire in several years, the
department will finally be in a position to replace them with
research people because the facilities will be in place, Scully
says. "This definitely came at the right time," he says.
According to Pitts, the deadline for applications for the 1994
awards will most likely be in early April. For information, call
the NSF Office of Science and Technology Infrastructure at (202)
357-9808.
Edward R. Silverman is a freelance writer based in Millburn, N.J.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
NOTEBOOK
-----------------------------------------------------------------
TI : Alzheimer's Grants
TY : NEWS (NOTEBOOK)
PG : 4
The Chicago-based Alz- heimer's Association has announced four
competitive, peer-reviewed research awards programs for 1994. The
proposals are solicited for biological, clinical, and
social/behavioral research relevant to degenerative brain
diseases such as Alzheimer's. One batch of grants--called
Investigator-Initiated Research Grants--is designed to continue
the work of established scientists; the maximum award for the
grants is $50,000 per year for two or three years. Another set of
grants--Faculty Scholar Awards--is intended to provide salary
support to experienced junior-faculty-level investigators
committed to Alzheimer's or related studies. Award recipients are
funded at a maximum of $50,000 for three years. The deadline for
these two programs is January 14. A third grant group, Pilot
Research Grants, is designed to provide small, one-year grants
for research proposals, with preference given to scientists new
to Alzheimer's research. The application deadline for the $30,000
awards is June 30. Finally, Zenith Awards will go to scientists
who have already made substantial contributions to Alzheimer's
research. The grants are funded at $100,000 per year for two
years, with a possibility for renewal. Applications must be
received by next August 12. For information, contact Medical and
Scientific Affairs, Alzheimer's Association, 919 N. Michigan
Ave., Suite 1000, Chicago, Ill. 60611-1676; (312) 335-5779.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
================================
NEXT:
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TI : NABR News
TY : NEWS (NOTEBOOK)
PG : 4
The October 8 edition of the National Association for Biomedical
Research's Update newsletter held some grim reminders of the
potential dangers facing scientists who use animals in their
research; any group that, like NABR, supports such research; or,
for that matter, anyone who uses animals for just about anything.
According to the newsletter, a recent NABR conference at a
Washington, D.C., hotel was suddenly interrupted by an
anonymously phoned-in bomb threat. A District of Columbia police
bomb squad cleared the hotel ballroom of conference attendees and
searched it thoroughly. No bomb was discovered, and the meeting
continued. But so have the threats of violence, the newsletter
reported: Six mail bombs, it said, were recently discovered in a
British post office--all addressed to animal sports enthusiasts
in southern England. British police suspect that animal rights
activists were the culprits in this case, as well. Meanwhile,
revealing that NABR's heart is really in the right place when it
comes to animals, the newsletter ran an appropriately mournful
obituary marking the passing of canine marketing superstar Spuds
MacKenzie at the age of 10 in North Riverside, Ill. Bud Light
beer's "Original Party Animal," star of commercials and
promotions, died of kidney failure last spring, according to the
newsletter, but Stan and Jackie Oles, the bull terrier's owners,
apparently had grown so tired of the constant media hounding of
the long-retired Spuds that they did not release the information
until recently.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
================================
NEXT:
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TI : Eine Kleine IQ Booster
TY : NEWS (NOTEBOOK)
PG : 4
Researchers at the University of California, Irvine, report that
students who listened to 10 minutes of Mozart before taking a
standard test of spatial intelligence significantly raised their
test scores. A group of 36 students completed three tasks of the
Stanford-Binet test following 10 minutes of three different
listening conditions: Mozart's Sonata for Two Pianos in D major,
a tape of relaxation instructions designed to lower high blood
pressure, and silence. The average score after Mozart was 119,
compared with 111 after the relaxation tape, and 110 after
silence.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
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TI : New Uses For Old Genes
TY : NEWS (NOTEBOOK)
PG : 4
While hardly the stuff of which movies are made, recently
discovered genes of microorganisms predating the Jurrassic period
might well produce commercial "box-office hits" in their own
right. The genes can redesign host cells by instructing them to
make microscopic, air-filled vesicles that create a cellular
flotation system. Potential applications for the newly discovered
genes include bioengineering of oil-eating bacteria to clean
spills, better and cheaper sewage treatment, pharmaceutical
production, even improved beer brewing. Hidden millions of years
ago inside a bacterium called Halobacterium halobium, they were
discovered by University of Massachusetts, Amherst,
microbiologist Shil DasSarma and his then-grad students John
Halladay and Wai-lap Ng, while conducting basic research using as
their model common Halobacterium taken from San Francisco Bay.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
================================
NEXT:
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TI : Dual Postdocs
TY : NEWS (NOTEBOOK)
PG : 4
The National Research Council and the Alexander von Humboldt
Foundation have announced the opportunity to apply for linked
postdoctoral fellowships to be held in Germany and the U.S.
Winners of the fellowships would hold a Humboldt Research
Fellowship for a year in Germany, and then take up an NRC
Research Associate position at a federal laboratory for one, two,
or three years. The offer is open to U.S. citizens who have held
their degrees for less than five years and are under the age of
40. Applicants must apply to and be awarded postdocs from both
NRC and the von Humboldt Foundation for the offer to apply. For
information, contact National Research Council, Associateship
Program (AvH-NRC), 2101 Constitution Ave., N.W., Washington, D.C.
20418; (202) 334-2760; Fax: (202) 334-2759; and the Alexander von
Humboldt Foundation, North American Office, 1350 Connecticut
Ave., N.W., #903, Washington, D.C. 20036; (202) 296-2990; Fax:
(202) 833-8514.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
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TI : A Good Hair Day
TY : NEWS (NOTEBOOK)
PG : 4
With biotech researchers and companies feverishly working to
fight devastating diseases afflicting populations around the
world, two firms have teamed up to engineer a genetic solution to
one of the most dreaded conditions of all--androgenic alopecia,
or common baldness. Researchers at Sequana Therapeutics of La
Jolla, Calif., plan to identify, map, and clone both mouse and
human genes associated with abnormal hair growth and baldness.
Ridgewood, N.J.-based Alopex Pharmaceuticals will then use the
molecular targets identified by Sequana to discover and develop
treatments for androgenic alopecia and other hair disorders. The
two companies will focus on genetic disorders associated with
hair follicles. Scalp hair follicles normally produce hair for
two to six years and then shut down for a resting period,
followed by a shedding of hair, after which the growth cycles
begin anew. For those with androgenic alopecia, hair follicles
grow hair for progressively reduced periods and remain in the
resting period for longer times than they grow hair.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
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TI : CLARIFICATIONS
TY : NEWS
PG : 7
The article "University Of Virginia Appoints Biologist To Vice
Provost For Research Position" in the People section of the Oct.
18, 1993, issue of The Scientist (R. Kaufman, page 22) misstated
the background of Gene D. Block, new vice provost for research at
Virginia.
Block received his bachelor's degree in 1970 from Stanford
University and his Ph.D. in 1975 from the University of Oregon.
He was a postdoctoral fellow at Stanford University from 1975
until 1978, when he joined the faculty at the University of
Virginia.
Also, the article "Research-Scale Perfusion Systems Aid
Neuroscience Studies" in the Tools section of the same issue (F.
Hoke, page 18) incorrectly identified the patch-clamp perfusion
system designed with the technical assistance of
electrophysiologist Robert S. Eisenberg of Rush Medical College
in Chicago, and commercially available from Adams & List
Associates, Westbury, N.Y.
The system to which Eisenberg contributed his expertise is the
Whole-Cell/Patch Pipette Perfusion Kit.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Patents On Scientific Discoveries Are Unfair And
Potentially Dangerous
AU : CESAR MILSTEIN
TY : OPINION
PG : 11
Many of us still remember a time when the idea of taking out a
patent was far from foremost in our minds. In those days,
scientists working in universities and government-sponsored
institutions were driven not by the patentability of their ideas,
but rather by pure scientific considerations. Patents were rare,
more an afterthought than a preliminary consideration.
The advent of modern biotechnology has brought about a
considerable change, so that now, even among the most curiosity-
driven scientists, the question "Should I take out a patent?"
becomes an issue whenever a new discovery or a new procedure
becomes experimentally successful. If the scientist in question
is better acquainted with current business practices, he or she
may well be tempted to take out a patent even before the results
of the experiments are certain. Otherwise, there is a very real
risk that someone else will patent the idea, and that the
experiments will be used only to validate the other person's
patent.
Recent developments in connection with the controversies
surrounding the patenting of DNA sequences go even further. It is
becoming a matter of high priority for the scientific community
to take a careful look at the issues involved. A recent
pronouncement of the International Council of Scientific Unions
(ICSU) urging the patenting authorities to consider the danger in
allowing pat-ents of nucleic acid sequences per se is a good
start in the right direction.
And yet the problem goes deeper. Different countries have
different concepts in terms of patenting principles--for example,
first to "invent" (United States) vs. first to patent (Europe); a
period of grace (U.S.) vs. no disclosure rules (Europe). Worse
still, lawyers and scientists do not speak the same language or
use the same criteria: What is an obvious extension of previously
established facts (as far as scientific judgment is concerned)
can also be construed as novel (in legalistic terms), and thus
merit patenting. At the other extreme, leaps in scientific
knowledge that do not present any obvious practical implications
today may be the foundation for further developments and lead to
innumerable patents in the future. Good examples are the
discoveries of somatic cell hybridization and of restriction
phenomena in bacteria, both major advances in basic science
whereby eventual developments could not be predicted and were
therefore unpatentable. Without these advances, biotechnology
would not be what it now is.
So, patents are basically unfair. But perhaps they are necessary
for the development of products that will ultimately benefit
society. Without them (we are told) companies would not be
prepared to spend the amount of money required for such
developments. The new element in this equation, however, is that
the complexity and multiplicity of overlapping pat-ents in the
field of biotechnology is creating such havoc that the
counterargument--that patents are beginning to inhibit the
development of new products--should begin to be considered with
the seriousness it deserves. It remains a fact that the specter
of patents is not only introducing new tensions in the scientific
community, but also having serious and undesirable effects on
basic developments that largely rely on curiosity-driven
research.
Cesar Milstein is an immunologist at the Laboratory of Molecular
Biology, Cambridge, England.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
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TI : ICSU STATEMENT ON GENE PATENTING
TY : OPINION
PG : 11
The International Council of Scientific Unions (ICSU) is a Paris-
based, international, nongovernmental organization whose mandate
includes the promotion of cooperation in the basic sciences, and
the safeguarding of the principle of the university of science
and of the free flow of scientific knowledge.
The council is aware of the tremendous potential benefit of
genetic research for humanity and realizes that new ethical and
social dimensions arise from this. Accordingly, ICSU strongly
believes that efforts to patent genetic information should not
jeopardize either progress in the basic sciences or access to the
information that is necessary for such progress to continue.
ICSU asserts its view that information about nucleic acid
sequences cannot be patented per se. Such sequences should be
patentable solely within the context of their demonstrated
significance and/or application (for example, regulatory signals,
antisense RNAs, probes)--and not of their potential products (for
example, proteins)--and provided that this can be shown to be
"novel," "non-obvious," and "useful."
Under such circumstances, patenting of complementary DNA
sequences (cDNA) would distort the patent process, which is
designed to protect applications, methods, and products, on the
basis of proven facts and not mere expectations, and normally
serves society by stimulating the investments and developments
necessary to provide useful products and services. Any deviation
from such patenting principles would run counter to the best
interests of science and hinder international collaboration in
such endeavors. ICSU, therefore, cautions against decisions that
may be irreversible, such as those possibly emerging as a result
of recent patent requests concerning cDNA sequences corresponding
to portions of unknown messenger RNAs.
ICSU urges the relevant authorities, particularly in countries
where patent applications in this field have been or are soon to
be filed, to consider such applications taking due account of the
possible implications and to ensure a strict application of
established patenting principles, thereby setting an example for
other countries in which similar cases may arise in the future.
ICSU would welcome a formal international agreement on this
subject.
Milstein's essay and the ICSU statement appeared previously in
the March/April 1993 issue (Vol. 1, No.2) of The Immunologist,
a bimonthly journal of the International Union of Immunological
Societies, and are used with permission.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Hillary Clinton And Mary Lasker: A Photo In Proper Focus
AU : EUGENE GARFIELD
TY : OPINION (COMMENTARY)
PG : 12
The front page of The Scientist's October 18 issue was graced by
a photograph of two remarkable women: Hillary Rodham Clinton
together with Mary Lasker. The photo accompanied our coverage of
the Albert and Mary Lasker Foundation awards, given to three
scientists--Gnter Blobel, Donald Metcalf, and Nancy Wexler--whose
outstanding efforts in basic research over the years are likely
to yield, directly or indirectly, significant gains in human
health.
To my knowledge, no other national publication ran a photo of
these two women, bonded as they were at an event underscoring the
increasingly important link between biomedical investigation and
social enrichment. Since she and her husband moved into the White
House last January, Clinton has gained sharp visibility for her
advocacy of a new and equitable system for ensuring the good
health of all Americans; for the past half-century, the Lasker
Foundation has been foremost among United States organizations
honoring researchers whose work ultimately is directed toward the
same estimable goal.
The support of basic research is fundamental to the well-being of
our society, and an event like the Lasker Awards ceremony makes
for, in our opinion, compelling front-page news. I find it
troublesome to think that such publications as the New York Times
and the Washington Post would opt to bury coverage of it in their
back pages and ignore the symbolism of Clinton and Lasker's
encounter. This is a moment in history, after all, when the
nation's scientific community is struggling to produce, through
the endeavors of basic research, remedies for AIDS, cancer, and
other diseases--and while, ironically, federal support for
untargeted laboratory investigation is persistently threatened.
Let us hope that Clinton's appearance at the Lasker Awards
gathering signifies an implicit endorsement of basic research.
Although I've been a guest at many of the Lasker ceremonies over
the years, I was not present at the recent ceremony. However, The
Scientist's managing editor, Barbara Spector, did attend, and her
report on the event is heartening in this respect.
In her article ("Lasker Awards Celebrate Biomedical Scientists
For Their Advances In Health-Related Research," The Scientist,
Oct. 18, 1993, page 1), Spector quotes Clinton as saying in her
keynote speech: "These winners join a remarkable group . . . men
and women whose work has found cures for disease, who have aided
the kind of breakthroughs that we've only been able to dream
about in the past but now take for granted.... This is a time
when the past and the present in medical research join together
to point us to a new future." To me, this sounds like a strong
endorsement indeed!
Today, basic research and National Institutes of Health funding
have become big, bureaucratic matters, not easily susceptible to
influence by a single individual like Mary Lasker. But her
pioneering advocacy efforts are being carried on by dozens of
lobbying groups--such as Research!America--that remind Congress
regularly of the high priority that medical research holds, or
should hold, for most Americans.
Nearly 20 years ago, I proposed in an essay (Current Contents,
Jan. 23, 1974, pages 10-12) that Congress establish a National
Institute for Preventive Medicine. I wrote: "With the energy
crisis upon us, and the `crisis management' reaction to it, most
physical and chemical scientists can look forward to another
decade of generous funding. So be it; but we must make certain
that it is not accomplished by sacrificing the biomedical
research effort because it is now politically popular to support
energy, environmental, or other forms of research."
It is discouraging that Congress or NIH has still not elevated
preventive medicine--and the research activity that goes with it-
-to that status. On the other hand, it is heartening to see such
diverse personalities as Hillary Rodham Clinton and Mary Lasker
united in recognizing the value and immense importance of the
nation's basic research community.
The picture of them, together, is pertinent; let's hope that the
prospect for basic research is as inspiring.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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NEXT:
OPINION SECTION
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TI : Benefits Of Animal Use
TY : OPINION (LETTERS)
AU : CARLOS H. SCHENCK
MARK W. MAHOWALD
Your July 12, 1993, article (R. Kaufman, page 1) on the reasons
behind biomedical scientists' choice of their experimental
subjects--animals, tissue cultures, and others, including humans-
-quoted sleep researcher Adrian Morrison as working "just to
understand basic biological mechanisms."
Such understanding is, of course, fundamental to the eventual
clinical advances that allow us to help our patients. However,
you missed an interesting story in not probing Morrison further,
for it was his studies of a fascinating phenomenon in cats with
brain damage that exhibit elaborate behaviors during REM sleep--a
state when they and all mammals (including humans) are ordinarily
paralyzed--that led to our understanding of a serious, dangerous
sleep disorder we can now treat: REM sleep behavior disorder
(RBD).
Patients with RBD act out their dreams rather than remaining
safely paralyzed. This can result in injury to themselves or
their bed partners, which can be life-threatening, such as when
cervical vertebrae are fractured. Fortunately, RBD is controlled
by medication. Thus does the research that seeks to understand
the basic workings of the body lead to unforeseen benefits to our
patients. Clinical medicine is highly dependent on basic
research, as exemplified by RBD.
CARLOS H. SCHENCK
Assistant Professor of Psychiatry
University of Minnesota
Medical School
Minnesota Regional
Sleep Disorders Center
Hennepin County Medical Center
Minneapolis
MARK W. MAHOWALD
Associate Professor of Neurology
University of Minnesota
Medical School
Director
Minnesota Regional
Sleep Disorders Center
Hennepin County Medical Center
Minneapolis
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Of Morality And Animals
AU : MARTIN L. STEPHENS
TY : OPINION (LETTERS)
PG : 12
Ron Kaufman reports that biomedical researchers tend to use
science, not morality, in deciding between animal-based methods
or non-animal alternatives (The Scientist, July 12, 1993, page
1). While this may be true, morality should not be ignored.
Animals are more than just another research tool for scientists
to pick and choose. In cases in which alternatives are not yet
superior to their animal-based counterparts, the research
community has a moral obligation to seek to expand the
capabilities of the alternative methods.
Instead, what often happens is that the available alternatives
are dismissed as not as good as the animal-based methods, and no
effort is made to improve them.
Some non-animal alternatives are improvements over their animal-
based counterparts. Where they are not, they should be advanced
through targeted efforts and programs. Morality demands that we
not leave the advancement of these methods to serendipity or
something as vague as the inexorable tide of scientific progress.
For its part, the Humane Society of the United States works
closely with progressive members of industry, academia, and
government to help advance the science of alternative methods.
MARTIN L. STEPHENS
Vice President
Laboratory Animal Programs
Humane Society
of the United States
Washington, D.C.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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Letters to the Editor
The Scientist
3501 Market Street
Philadelphia, PA 19104
Fax:(215)387-7542
E-mail:
Bitnet: garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com
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TI : Molecular Motors Drive Multidisciplinary Research Quest
AU : MYRNA E. WATANABE
TY : RESEARCH
PG : 14
In a major career move, molecular biophysicist Steven M. Block is
leaving Cambridge, Mass., where he has been associated with the
Rowland Institute for Science and Harvard University since 1987.
This coming January, he'll be installed as an associate professor
in the molecular biology department at Princeton University,
where he'll join forces not only with other biologists, but also
with physicists and chemists, in a pursuit that Block believes is
as exciting as anything going on in the world of science today.
Block and his colleagues will be studying molecular motors,
minute energy-conversion machines that reside within cells and
yield a locomotive power peculiar to living organisms. This field
of investigation has dominated the 41-year-old Block's research
activities in recent years, playing a significant part in his
productive tenure at Rowland, where he has put out more than 20
scientific papers in the past five years, coauthoring many of
them with his mentor, biophysicist Howard Berg, also of the
Rowland Institute and Harvard.
The lure of Princeton, says Block, is that he will hold a joint
appointment with the new Princeton Materials Institute (PMI), an
interdisciplinary research center, where physicists, chemists,
engineers, and biologists will combine their intellectual
understandings of how microscopic structures behave, with the
goal of offering better approaches to the study and fabrication
of materials for nanotechnology--small-scale technology in the
sub-micron range. As Block notes, molecular motors are the
smallest motors known to science.
An `Outstanding Puzzle'
"This looks to be an unbeatable combination for the future,"
Block says, referring to the interdisciplinary approach to the
challenges facing PMI researchers. To make clear why the study of
molecular motors is of great importance, Block explains that in
elementary biology classes, students are taught three major
qualities that differentiate living organisms from non-living
matter: sensory perception, repro- duction, and movement. The
biochemistry of sensory perception, he points out, is known from
work that has been done on sensory transduction in bacteria.
Reproduction also has been well studied, and the mechanisms for
DNA duplication are now understood. But what, essentially, causes
movement? "That question remains unanswered," says Block. "If you
solve this, you solve one of the great outstanding puzzles of
life."
Once this puzzle is solved, some scientists believe, the
understanding of molecular motors may foster new techniques for
conducting biomedical research and fighting disease. Ambitious
speculation has gone so far, for example, as to envision the
introduction of microscopically tiny motors--programmed to carry
out therapeutic missions--injected into the human bloodstream.
Although Block agrees that "if a mechanism for molecular movement
can be established, the insights that come from such a mechanism
may inspire man-made molecular machines with similar mechanisms,"
he does not envision injectable machines for curing cancer or
cleaning out clogged arteries. But some futurists, such as
molecular nanotechnologist K. Eric Drexler, a research fellow at
the Institute for Molecular Manufacturing in Palo Alto, Calif.,
suggest that such "nanomachines" are at least theoretically
possible. And self-assembling, self-perpetuating biomolecular
machines may be an outgrowth of this specialized research,
according to Block.
Myosin Vs. Kinesin
Molecular motor researchers are, in the main, looking at two
different motor proteins: myosin, which is present in muscle
cells; and kinesin, which attaches to vesicles within the cell
and moves these vesicles along microtubules. Investigators in
this field are also studying the motor protein dynein, present in
sperm tails, cilia, and cytoplasm, but myosin and kinesin are
clearly the chief focus of current studies. All of these enzymes
are referred to as motor proteins because their enzymatic
activity results in energy release leading to motion.
Myosin is the oldest known of these proteins, first isolated from
muscle well over a century ago. Until recently, however,
scientists' ability to study the molecule was limited. But with
the advent of laser technology, such modern tools as optical
tweezers--a laser device capable of manipulating minute objects--
and computerized video enhancement of light microscopy enable
researchers to study individual molecules of myosin on a
microscope slide as they hydrolyze molecules of adenosine
triphosphate (ATP) to release energy.
Myosin is a large molecule, its head needing approximately 890
amino acid residues to obtain movement in vitro. Kinesin's head,
by comparison, needs only 350 or so amino acid residues. Johns
Hopkins University biophysicist Scott Kuo likens the difference
of studying them to the comparative challenges of studying an
eight-cylinder Cadillac engine and studying a lawn mower. If the
myosin motor is the Cadillac, Kuo says, the kinesin motor has two
cylinders. The principles involved in making both engines work
are the same, but the lawn mower is much easier to take apart and
understand.
Because of its size and relative slowness of motion, Block
studies kinesin. Recently, he and fellow researchers Karel
Svoboda, Christoph Schmidt, and Bruce Schnapp have focused on the
size of the step the kinesin molecule takes as it moves up a
microtubule, and the force generated with each step. The group
recently found that one step for the kinesin molecule was equal
to approximately 8 nm with a force of approximately 4 picoNewtons
(pN). The team of researchers did not, however, determine how
many ATP molecules are hydrolyzed per step, an important question
in understanding the efficiency and molecular dynamics of the
movement.
Other laboratories in the U.S. are pursuing similar research with
kinesin molecules. Johns Hopkins' Kuo and cell biologist Michael
Sheetz of Duke University School of Medicine in Durham, N.C.,
have been measuring the force generated by kinesin movement. Joe
Howard, a neurobiologist turned cell biologist at University of
Washington, Seattle, demonstrated that kinesin can function as a
single motor in vitro. He did this work along with cell biologist
Ron Vale, one of the codiscoverers of the kinesin molecule, who
is at the University of California, San Francisco. Both Howard
and Vale have been investigating kinesin step size and how the
molecule moves down the microtubule.
Still other groups are working with the larger myosin molecule.
Most prominent among these is the University of Osaka's Toshio
Yanigida, who has done work on myosin step size. Yanigida's work,
according to Block and other researchers, is considered to be
controversial because the step sizes his group has reported--60-
600 nm with each ATP--do not appear to correspond to recent X-ray
crystallographic evidence from the laboratory of Ivan Rayment at
the University of Wisconsin, Madison. Rayment's group showed that
the myosin head is only 16 nm long. Thus, researchers such as
Block question whether Yanigida sees myosin acting as a "wind-up
toy," carrying out multiple moves in succession, or whether
Yanigida's interpretations of his measurements are correct.
Molecular cell biologist James Spudich, a former postdoctoral
student of Block's, now at Stanford University School of
Medicine, also is studying step motion in myosin. These and other
researchers need to clarify the size of each step, and whether
less than one, one, or more than one ATP molecule is hydrolyzed
per step.
Duke University's Sheetz puts the work into perspective,
explaining the importance of determining the number of ATP
molecules hydrolyzed per step. "The reason that this is an
important issue," he explains, "is not that it's stopping every 8
nm. It's that we need to understand how ATP is converted into
mechanical energy in these systems with the efficiencies in
muscles at 50 percent conversion." Sheetz further explains that
these discoveries "will potentially help us in designing other
motor systems on a larger scale." He points out that nanoscale
motors currently being fabricated by silicon chip makers work at
only 10 percent efficiency. Scientists agree that even the most
efficient automobile engine does not work at anywhere near the 50
percent efficiency of these natural molecular motors.
Supporting The Effort
Although the basic research being conducted by Block and others
around the U.S. may well lead to applications in microfabrication
of motors, U.S. funding agencies are not agog. While the National
Institutes of Health funds what Sheetz calls a "significant
fraction" of this research, he adds that "NIH considers this too
basic to be applied to many of the problems that are out there."
Although not extraordinarily expensive as research goes--the
equipment, according to Sheetz, costs between $50,000 and
$100,000 --Sheetz laments, "The funding is typically by the seat
of one's pants.
"Almost everybody I know who has such systems got a little bit
from here, a little bit from there," with NIH coming in "after
the feasibility has been shown," he says.
Block--whose work was fully funded by the Rowland Institute, but
now, with his move to Princeton, must apply for NIH funding--
says, "The NIH has shown a certain reluctance to fund innovative
research that is instrumentation-intensive."
This is not what is happening in Japan, according to Palo Alto
futurist Drexler. Drexler states that the Japanese Ministry of
International Trade and Industry (MITI) is funding a large-scale
project to develop nanotechnology. Part of this project will
focus on molecular machines. Drexler points out that "on the
nanoscale, we've seen a considerable amount of attention to
electronics ... and we've seen microfabri- cation of molecular
components." But the missing piece of the molecular machinery
puzzle, he adds, is the study of biological molecular machines.
Drexler sees molecular motor research leading in the short term
to more efficient instrumentation for sequencing DNA, for
example. In fact, Sheetz points out, the nano-scale measurement
techniques established in the course of this work can already be
applied in automated DNA sequencing. He also foresees molecular
motor research as leading to more efficient nanoscale motors for
the computer chip industry.
Meanwhile, Block and his coworkers are cooperating with the
National Nanofabrication Facility at Cornell University in
Ithaca, N.Y., on micromachining microscope slides so that their
glass surfaces will be irregular in shape and will, themselves,
without use of any separate attachments, be able to hold
molecules such as kinesin for more direct studies of movement and
force. And at Stanford, Spudich and his colleagues are working on
coating micromachined slide surfaces with myosin in order to
study the interactions between actin and myosin.
But no matter what the future applicability of this line of
research, the basic premise, as Sheetz points out, is that "it's
extremely important for us to understand whether nature has found
some fundamentally different way of converting chemical to
mechanical energy than we have utilized in our machines."
The next step will be to apply what has been learned to make more
efficient micromachines.
Myrna Watanabe is a biotechnology consultant based in Yonkers, N.Y.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : HOW TO STUDY KINESIN
AU : MYRNA E. WATANABE
TY : RESEARCH
PG : 14
Karel Svoboda and his colleagues in Steven Block's laboratory at
the Rowland Institute use a technology-laden in vitro setup to
study the movement of the motor protein kinesin on microtubules.
They are able to visualize microtubules through a light
microscope using, what Block refers to as "some tricks." The
"tricks" are use of video-enhanced differential interference-
contrast (DIC) microscopy, allowing visualization of structures,
such as microtubules--1/20 of a light wavelength across--that are
too narrow in diameter to be seen without computer-assisted
enhancement.
They attach a kinesin molecule to a silica bead and, using
optical tweezers, deposit the bead onto the microtubule. The
optical tweezers, developed originally by Arthur Ashkin and
associates at Bell Laboratories check, Holmdale, N.J., in 1985 in
order to study single atoms, is constructed by bringing light
from a laser--in this case near-infrared--to a sharp focus. Block
explains that the tweezers focuses a single beam of light on a
single spot, pulling small objects into the area where the light
is strongest. The silica bead that attaches the kinesin to the
microtubule can be held in place with the optical tweezers.
ATP is added to the system, but in order to measure the movement
of the kinesin molecule and the force of that movement, a dual-
beam interferometer is used along with the optical tweezers. This
is called an optical trapping interferometer. Two photodetectors,
Block explained in a recent product review of the optical
tweezers in Nature (360:493-5, 1992), "can measure the
displacement of a trapped object down to distances as small as
ngstroms, thousands of times per second, using polarized light."
Using this setup, Svoboda--who is Block's graduate student and
the person Block refers to as "the linchpin" of this research--
and his coauthors measured an 8 nm step along the microtubule,
and a force of about 4 picoNewtons.
Joe Howard from the University of Washington, Seattle, and Duke
University School of Medicine's Michael Sheetz explain that the 8
nm steps correspond to stopping points at the alternating alpha
and beta subunits of the microtubule. The width of each subunit
is 4 nm so there is one binding site per each tubular dimer.
Although other researchers, such as Johns Hopkins University
biophysicist Scott Kuo and Sheetz, have come up with different
numbers for force or step length, they admit that there may be
differences in sensitivity of their instrumentation, or
differences in the way the experiment is set up. Kuo, for
example, who measured a force of 2 pN for kinesin movement, says,
"I think Steve is pulling it better than I can."
--M.E.W
SUGGESTED READING
S.M. Block, Modern Cell Biology, Vol. 9, pages 375-402, eds. J.K.
Foskett and S. Grinstein, New York, Wiley-Liss, 1990.
K.E. Drexler, Engines of Creation: The Coming Era of
Nanotechnology, New York, Anchor Press, 1986.
K.E. Drexler, Nanosystems: Molecular Machinery, Manufacturing and
Computation, New York, John Wiley & Sons, 1992.
J. Gelles, et al., Nature, 331:450-3, 1988.
S.C. Kuo, M.P. Sheetz, Science, 260:232-4, 1993.
S. Ray, et al., Journal of Cell Biology, 121:1083-93, 1993.
R. Taylor, Journal of NIH Research, 5:58-62, 1993.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : CELL BIOLOGY
TY : RESEARCH (HOT PAPERS)
PG : 15
M.J. Solomon, T. Lee, M.W. Kirschner, "Role of phosphorylation in
p34cdc2 activation: Identification of an activating kinase,"
Molecular Biology of the Cell, 3:13-27, 1992.
Marc W. Kirschner (Department of Biochemistry and Biophysics,
University of California, San Francisco): "Work from several labs
had shown that phosphorylation might be involved in the
activation of the mitotic kinase, cdc2, or its inhibitors. The
story was naturally confusing for a while until it became clear
that there were two types of phosphorylation that occurred
simultaneously upon binding of cyclin to the inactive cdc2
protein, one that activated and one that inactivated the protein.
Initially, most attention was directed to the inactivating
phosphorylation, particularly since candidate genes had already
been identified in Schizosaccharomyces pombe as negative
regulators of mitosis. When the activating site was identified,
it was thought that it might be phosphorylated by cdc2 itself. If
this were the case, the only regulation of the entry to mitosis
would have been negative regulation.
"In this paper Mark Solomon, Tina Lee, and I showed that a new
kinase existed and could be partially purified--called CAK (for
cdc2 activating kinase)--that is separate from the cdc2-cyclin-
type kinases, and which phosphorylated cdc2 on the activating
phosphorylation site. This finding opened up a new site of
regulation of cdc2. It is likely that CAK regulation exists not
only at G2/M transition but also at G1/S transition for cyclin-
dependent kinases. Purification and identification of CAK and its
regulation are now an active area of research in the cell cycle
field."
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : BIOCHEMISTRY
TY : RESEARCH (HOT PAPERS)
PG : 15
R.A. Heyman, D.J. Mangelsdorf, J.A. Dyck, R.B. Stein, G. Eichele,
R.M. Evans, C. Thaller, "9-Cis retinoic acid is a high affinity
ligand for the retinoid X receptor," Cell, 68:397-406, 1992.
Richard A. Heyman (Ligand Pharmaceuticals Inc., San Diego):
"Metabolites of vitamin A (for example, all-trans retinoic acid)
modulate several important life processes, including cellular
proliferation, differentiation, and metabolism. These actions are
thought to be exerted through specific intracellular receptors.
The retinoid receptors are members of a superfamily of proteins
that function as ligand-dependent transcription factors. These
intracellular receptors regulate expression of their target genes
after binding to small lipophilic ligands, including steroid
hormones, thyroid hormones, vitamin D, and retinoic acid.
"In addition to the receptors that bind to the known hormones,
there are members of the superfamily for which a hormone is not
known; these proteins are referred to as orphan receptors. In
1990, members of our research team published a paper identifying
one family of these orphans as receptors for a novel vitamin A
derivative, which was called retinoid X (D.J. Mangelsdorf, et
al., Nature, 345:224-9, 1990; Hot Papers, The Scientist, Nov. 25,
1991, page 16). These retinoid X receptors (RXRs) activated
transcription in cells exposed to all-trans retinoic acid but did
not bind all-trans retinoic acid directly as a ligand. It was
therefore postulated that in cells all-trans retinoic acid was
being converted to the RXR ligand.
"This observation led to a hunt for the RXR ligand, which
combined the scientific efforts of researchers at Ligand
Pharmaceuticals, the Salk Institute, and Baylor College of
Medicine. In the present work, a novel ligand for the RXR family
has been identified as 9-cis retinoic acid, making this the first
hormone to be described for the intracellular receptor
superfamily in more than 20 years. Interestingly, 9-cis retinoic
acid is a high-affinity ligand not only for RXRs, but also for
the retinoic acid receptors (RARs) (E.A. Allegretto, et al.,
Journal of Biological Chemistry, in press; G. Allenby, et al.,
Proceedings of the National Academy of Sciences, 90:30-4, 1993).
"The RARs were originally identified for their ability to bind
and be activated by all-trans retinoic acid. Thus, while all-
trans retinoic acid serves as a ligand for only the RARs, 9-cis
retinoic acid is a bifunctional ligand for members of both the
RXR and RAR subfamilies. The experimental techniques developed
and used to identify this new hormone provide a potential
approach to identify new hormones for other orphan receptors. In
addition, the identification of 9-cis retinoic acid has yielded a
lead structure for the design of synthetic retinoids with unique
receptor activity profiles.
"Recently, we have synthesized a series of synthetic retinoids
that selectively bind and activate members of the RXR subfamily
and have no cross-reactivity with the RARs. These unique tools
are being used to examine the physiological and pharmacological
consequences of selectively activating different gene pathways
and may provide novel therapeutic compounds for the treatment of
disorders that involve abnormal growth or differentiation, or
both."
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : CANCER RESEARCH
TY : RESEARCH (HOT PAPERS)
PG : 15
C.A. Midgley, C.J. Fisher, J. Bartek, B. Vojtesek, D. Lane, D.M.
Barnes, "Analysis of p53 expression in human tumours: An antibody
raised against human p53 expressed in Escherichia coli," Journal
of Cell Science, 101:183- 9, 1992.
Carol Midgley (Cancer Research Campaign Laboratories, Departments
of Biochemistry and Anatomy & Physiology, Medical Sciences
Institute, University of Dundee, Scotland): "The protein p53 is a
member of the rapidly expanding family of so-called tumor
suppressor proteins. These are present in all normal cells, and
their function is linked to the control of cell division. In
cancer cells, where mutation in the p53 gene leads to expression
of an altered mutant p53 protein, the suppressing activity is
lost, contributing to the uncontrolled growth of the tumor. In
normal cells, p53 protein is present at too low a level to be
detected, but it has recently become apparent that many tumor
cells contain high levels of mutant p53 because the mutant form
of p53 protein is far more stable (J. Bartek, et al., Oncogene,
6:1699-1703, 1991; Hot Papers, The Scientist, May 3, 1993, page
16), thus providing us with a new marker for tumor development.
"The importance of this paper is that it described the first
antibody (a polyclonal antibody called CM-1) that is capable of
staining p53 protein in the fixed paraffin-embedded samples used
by most clinical researchers. This opens up a whole spectrum of
conventional tumor preparations and archive material to analysis.
Our paper described a system for making bacteria produce p53
protein in quantities that were previously unavailable and has
provided an excellent immunogen that has allowed us to produce
not only CM-1 but also a whole panel of monoclonal antibodies
with similar properties (B. Vojtesek, et al., Journal of
Immunological Methods, 151:237-44, 1992). As a result, we have
also developed a technique for the quantitative detection of p53
in tumor samples using an immunoassay format (B. Vojtesek, et
al., British Journal of Cancer, 67:1254-8, 1993).
"The availability of these reagents has generated enormous
interest among clinical researchers and has allowed us and
collaborators to examine the pattern of p53 expression in many
types of solid tumors. Overall, p53 staining corresponding to
mutant p53 protein is seen in 70 percent of malignant lesions,
and there is evidence that p53 staining is a marker of poor
prognosis in certain tumor types, such as gastric and breast
tumors (D.M. Barnes, et al., Human Pathology, 24:469-76, 1993).
Essentially, it seems that the accumulation of mutant p53 is the
most common change detected in tumor cells. Perhaps even a
proportion of p53 `negative' tumors are in fact mutants that have
lost the ability to make any p53 at all, which would also result
in a loss of growth control. Important developments are now
taking place in our understanding of the underlying mechanism of
normal p53 function. The accumulation of mutant protein in tumor
cells not only may provide us with diagnostic and prognostic
data, but also may represent a target for chemotherapy. We may
even be able to find drugs that can alter the mutant p53 protein
sufficiently to restore some of its growth-suppressing properties
(T.R. Hupp, et al., Nucleic Acids Research, 21:3167-74, 1993)."
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Digital Imaging In Microscopy Offers Greater Control, More Options
AU : FRANKLIN HOKE
TY : TOOLS & TECHNOLOGY
PG : 19
For researchers who have traditionally worked with photographs,
the conversion of images into digital forms has been gradually,
but steadily, replacing film over the past decade and more. In
microscopy, the cameras and scanners that capture digital images-
-based on the semiconductor technology of charged couple devices
(CCD)--have put scientific imaging within reach of computer
manipulation (image analysis, most prominently), communications,
and archiving.
Neuropathologist Lauren A. Langford at the University of Texas
M.D. Anderson Cancer Center in Houston, for example, now keeps
her indexed digital-image files on a hospital network and carries
prepared presentations to meetings on a disk.
"After years of work," Langford says, "I have filing cabinets
filled with Kodachromes, and I get tired of sorting and labeling
and filing. Once they're digitally captured, I don't have to do
any of that. And if I want to go somewhere--to another university
to give a lecture, for example--I just take my digitally captured
images on a disk. They provide me with a Macintosh and a
projector, and that's it."
Langford consults, via computer lines, with colleagues at other
hospitals using the same images of brain and spinal cord
biopsies--especially important to her because there are fewer
than 500 practitioners in her subspecialty. She also writes
interactive training programs incorporating digital images.
"And you don't have to have a darkroom," Langford says, "you
don't have to have a technician, and you don't have to run a
photography lab." A recent addition to her laboratory toolkit is
the Kodak Professional DCS-200 digital camera from Eastman Kodak
Co., Rochester, N.Y., which carries a list price of $9,995.
Langford's camera is only one of a number of new digital-imaging
products--some originally designed for professional publishing
and other nonscientific uses--that can make such image
acquisition easier and, sometimes, cheaper for researchers. Other
high-resolution cameras also are available that, like hers, mount
on most microscopes and facilitate direct capture of digital
images nearly indistinguishable from photography. And scanners
can be purchased that allow the user to convert existing 35 mm
slides into a digital form for transfer to a computer system.
The advantages for the researcher are clear enough, but for the
institution, too, digital miscroscopy has benefits. Not having a
"wet darkroom" means that disposal of photographic chemicals is
no longer an issue, according to Michael Berke, service engineer
for the Kodak DCS-200 camera. Some of the effluents from
traditional darkroom chemistry--the thiocyanates in fixers, for
instance--can be toxic, he says. Especially in localities with
stringent environmental laws, digital technologies can obviate a
difficult problem.
Johns Hopkins University School of Medicine in Baltimore has
moved almost entirely to a digital-image acquisition and
management system. According to Raymond Lund, an assistant
professor of pathology and director of photography at Hopkins,
researchers and physicians now integrate images with text for
presentations and publications, and images are transferred
routinely from place to place via the hospital network. His
department supports laboratories throughout the school and
hospital, he says.
Lund just purchased a Nikon LS-3510AF digital scanner, from Nikon
Inc. in Melville, N.Y., for his department. The full-color
scanner, which lists at $9,535, has a resolution of 3,185 pixels-
-the tiny square visual units that make up the image--per inch;
each pixel is 8 microns on a side. The scanner also provides an
autofocus feature and, with an accessory, unattended batch-
scanning.
Full-featured, institution-wide systems such as the one Lund has
helped build at Hopkins are not inexpensive, he notes. While
high-quality digital-acquisition cameras and scanners are
becoming more affordable, once the accompanying microscopes,
computers, and output devices are factored in, the system costs
can easily exceed six figures.
Still, given the greater control over acquisition and
manipulation of the images, this is the direction in which many
researchers and their institutions are headed, according to
Charles Berger, president of Image Systems Inc., a Columbia, Md.-
based dealer of digital-imaging accessories and Nikon
microscopes.
"Over the years, I've watched as electronic imaging has slowly
crept into traditional photography, to the point where now it's
virtually replacing it," says Berger. Most manipulation of
images--whether adding something to them or taking something away
--can now be done electronically, he says. "You used to have to
do that in a darkroom. It was very time-consuming, and it was
more art than science."
He adds: "Scientists now have far more control over the visual
medium that they're going to use to communicate to their fellow
scientists."
Acquisition By Silicon
Key to digital microscopy is semiconductor-based CCD acqui-
sition technology. CCD devices capture images in arrays of
pixels, the digital information units of the image.
"If you were to look at film at very high magnification, you'd
see grain," says Michael M. Kersker, national technical marketing
manager for microscope manufacturer JEOL USA Inc. in Peabody,
Mass. The grain, he says, is derived from actual silver halide or
other particles in the film emulsion, and the resolution of the
image cannot be finer than the size of those grains. "Those are
essentially the pixels of film. Each one represents a little
packet of information. Now, you can create packets like that in a
very orderly fashion using semiconductor technology, using CCDs."
When light hits the active silicon areas of a CCD, Kersker says,
it will create a charge. The charge level depends on the amount
of light hitting the silicon and is converted to a so-called gray
scale--although the scale can be displayed in any color. Color
images are created with multiple CCDs sensitive to different
wavelengths in register with each other.
Typically, gray scales resolve 256, 1,024, or 4,096 levels,
Kersker says, even though the eye can perceive only about 70. But
the large number of scale levels is important for successful
image enhancement and analysis. An overexposed image might appear
black to the eye, but electronically discernible contrast can be
converted to a visually discernible contrast using computer
software. The success of the procedure is directly related to the
number of scale levels present in the apparent blackness.
Despite the growing advantages of digital imaging, some
microscopists will continue to use film for their documentation
for some time to come. This is because the image quality of film
is still superior, according to Kodak's Berke.
But even for microscopy systems based on film, CCD technology is
playing a part. Microscope manufacturer Olympus America Inc. in
Lake Success, N.Y., for example, offers the automated PM30
Photomicrographic System, which uses a CCD with 400 individual
detectors to calculate precise exposures. The system's special
emphasis, according to the manufacturer, is fluorescence.
Integrated Systems
Some microscope manufacturers offer integrated digital-image
acquisition and analysis systems. Their capabilities and costs,
depending on available options and user needs, can include image
processing, analysis, and archiving.
For example, Carl Zeiss Inc. of Thornwood, N.Y. introduced the
AxioDoc Image Archiving Workstation in October, to complement the
company's Axioskop, Axioplan, or Axiovert microscopes. The system
runs on a 486-processor personal computer under the Windows 3.1
operating system and is intended to be a comprehensive image-
processing, measurement, annotation, archiving, and retrieval
system.
Using a coding accessory, the AxioDoc system automatically
references the magnification that was used to create the image.
Additional dimensional and statistical information can be linked
to the image and other data.
"So, a digitized image will be stored with all its pertinent
data," says Seth Miller, marketing representative for Zeiss.
"Then, using computer technology, you can go through, sort, and
find anything related to that topic."
Leica Inc. in Deerfield, Ill., offers the Quantimet 570 Image
Processing and Analysis System, which provides many of the same
features for users of its microscopes.
For researchers working in smaller laboratories, who may be
daunted by the costs and complexity associated with such full-
scale systems, there are lower-cost, easier-to-use options.
Nikon, for example, offers the Coolscan, or LS-10, film scanner,
a version of which can be mounted in a personal computer disk
drive bay. With a minimum of technical expertise required from
the user, Coolscan converts color or black-and-white 35 mm slides
to a digital format at a resolution of 2,700 pixels per inch. The
disk-drive-bay version lists for $2,300, while an external
version is available for $2,600.
Despite its relatively low cost, Coolscan provides many of the
advantages of more expensive digital-image-acquisition devices,
accord- ing to Stan Schwartz, confocal imaging manager for Nikon.
"And slides can fade," Schwartz adds. "But once the image is
digitized, the numbers are incorruptible."
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : DIGITAL IMAGING IN MICROSCOPY
TY : TOOLS & TECHNOLOGY
PG : 19
The following companies are among those supplying digital
cameras, scanners, integrated digital-image handling and storage
systems, and/or microscopes that support these products.
Products, capabilities, and costs vary, depending on available
options and user needs, and manufacturers should be contacted
directly for details.
Eastman Kodak Co.
Advanced Imaging Technology Group
901 Elmgrove Rd.
Mail Code: 35405
Rochester, N.Y. 14653-5405
(800) 242-2424
Fax: (716) 726-9868
Image Systems Inc.
8835 Columbia 100 Pkwy., Suite A
Columbia, Md. 21045
(410) 995-0748
Fax: (410) 995-1335
JEOL USA Inc.
11 Dearborn Rd.
P.O. Box 6043
Peabody, Mass. 01961-6043
(508) 535-5900
Fax: (508) 536-2205
Leica Inc.
111 Deer Lake Rd.
Deerfield, Ill. 60015
(800) 248-0123
Fax: (708) 405-0147
Nikon Inc.
1300 Walt Whitman Rd.
Melville, N.Y. 11747-3064
(800) 52-NIKON
Fax: (516) 547-0299
Olympus America Inc.
Precision Instruments Div.
4 Nevada Dr.
Lake Success, N.Y. 11042
(800) 446-5967
Fax: (516) 222-7920
Carl Zeiss Inc.
One Zeiss Dr.
Thornwood, N.Y. 10594
(800) 233-2343
Fax: (914) 681-7446
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Elite Society Celebrates Scholarship In All Disciplines
AU : STEVEN BENOWITZ
TY : PROFESSION
PG : 21
Not every club can boast a membership that has included such
scientific luminaries as Marie Curie, Charles Darwin, Thomas
Edison, and Albert Einstein. The American Philosophical Society
can.
In the true philosophical spirit--the term actually means "love
of learning"--the organization celebrates scholarly achievement
in the sciences, arts, and humanities.
Last spring, when the elite organization--the United States'
oldest honor society--turned a robust 250 years old, it threw
itself a four-day fete, paying homage to founder Benjamin
Franklin's ideal of "promoting useful knowledge." It even invited
a king--Juan Carlos I of Spain--to keynote the anniversary bash
at its Philadelphia headquarters next to Independence Hall.
While the society prefers a low public profile, its talented
membership needs no introduction. Its eclectic roster includes
more than 200 Nobel laureates, nearly half of whom joined before
winning the prize. The list has swelled to an all-time high of
711 members (126 foreign), and includes British physicist Stephen
Hawking, former Surgeon General C. Everett Koop, Harvard
University ecologist E.O. Wilson, and Nobel physicist Leon
Lederman.
Scholarship And Relevance
Although the group's members wield a great deal of practical
influence over the affairs of society and state, the
organization, as a body, has none itself. Whereas the National
Academy of Sciences serves as a national scientific advisory
board, the philosophical society's mission is to "assemble the
top people in a wide variety of disciplines in sciences,
humanities and arts and set the standards of excellence in those
areas," says 80-year-old executive officer Herman Goldstine, a
retired Princeton University mathematician and holder of the
National Medal of Science as one of the inventors of the
electronic computer.
"This is one of the few places in the world where scientists and
humanists meet on equal grounds and discover that scholarship is
scholarship, whether in nuclear physics or history," said former
philosophical society president Eliot Stellar in an interview
just before his death last month at age 73. Stellar said he
especially enjoyed the semiannual meeting in Philadelphia, when
the society holds two days of talks and lectures directed at the
nonspecialist and often leading to vigorous debate. A meeting
earlier this year, for example, featured talks on such topics as
the Big Bang and black holes, the molecular genetics of heart
disease, and the utility of pure mathematics, particularly the
role of prime-number theory in banking codes. The society's
autumn gathering, to take place November 11-12, will include
discussions of astronomy as well as slavery and the Civil War.
"That's an important aspect of the society's members," said
Stellar, a one-time University of Pennsylvania provost who headed
its department of cell and developmental biology at the time of
his death and was known for his pioneering work in behavioral
neuroscience. "Great minds coming together to talk and listen to
a variety of topics."
The society first drew international notice in 1769, when
Philadelphia member David Rittenhouse first described the path of
Venus crossing the sun, attracting the attention of scientists
around the world, including the illustrious Royal Society of
London, after which the philosophical society is loosely modeled.
In its early days, it served as a library of Congress, national
archives, patent office, and national science foundation, until
special government agencies took over these roles.
After its early national prominence, its influence and finances
waned. A generous bequest in 1931 rescued the society from fiscal
ruin and helped it regain prestige. Today it carries a healthy
$67 million endowment and operates out of a three-building
complex.
Part of the philosophical society's charm lies in its vast
library of some 6 million manuscripts, which includes librarian
Martin Levitt's favorite: a handwritten 1859 letter addressed to
evolutionist Charles Lyell, imploring the British scientist to
review an early draft of a treatise tentatively titled "The
Origin of the Species."
"Imagine Charles Darwin asking Lyell to look over what many
consider the second most important book ever written [after the
Bible]," Levitt says, noting that the letter is part of the
largest repository of Darwin papers outside of Cambridge,
England.
Yet for all its bluster about intellectualism, the organization
is surprisingly relevant. "There are some- times advantages to
having a politically powerless group with no particular axe to
grind making comments about society," notes cancer geneticist
Alfred Knudson of Fox Chase Cancer Center in Philadelphia.
In addition to April and November gatherings, the organization
publishes books and monographs and hands out some $600,000
annually in grants, mostly small awards of a few thousand dollars
each for scholarly research and travel. (In fact, it's the U.S.'s
oldest existing private research grant program, begun in 1933,
when it gave $3,000 to the second Byrd Antarctic expedition.) The
society's vast Library Hall holds some 180,000 volumes, including
more than two-thirds of Franklin's papers, and one of only two
Thomas Jefferson-penned versions of the Declaration of
Independence, congressional editing included. Most of Meriwether
Lewis and William Clark's journals are housed there (President
Jefferson sent his intrepid explorers-to-be to Philadelphia for
crash courses in the sciences before embarking westward), as is a
first edition of Newton's Principia.
Exclusive Membership
Getting into this highbrow club isn't easy. There are five
classes of members: biological scientists; social scientists;
mathematical and physical scientists; humanists; and a loosely
defined fifth category for those in "the arts, learned
professions, and public affairs," which was added slightly more
than a decade ago to appease complaints about the group's heavy
academic composition. Approximately 25 new members are elected
each year by the existing members, mostly to replace those who
have died.
Its membership is mostly male. Although its first woman member--
Princess Dashkova, who headed the Russian Imperial Academy of
Sciences--was elected to the society back in 1789, female
membership has remained small, today numbering 48. Former
president Stellar acknowledged as much last April when he noted
in a speech that women, minorities, and Third World scholars were
grossly underrepresented. Out of 27 newly elected members in
April of this year, only six were women. In the interview this
fall, Stellar contended that the shortfall isn't confined to his
group; it's reflected in academia and society.
"We need to make greater efforts to recruit women and minorities
into the society," he said. "But universities have had a hard
time recruiting them, as well. You see that in the lack of
Ph.D.'s. Before we can elect them to the society, they need to
have some standing in their fields, which takes time to develop."
"It's like any other organization," says Penn biochemist Mildred
Cohn, Benjamin Rush Professor of Biochemistry, emerita. "I don't
think it's particularly anti-women. I think they are trying to
remedy the situation, but there simply haven't been many women in
the pool." Cohn, who also is a member of the National Academy,
contends that the "lack of women is probably more striking" in
that organization, given its public visibility.
"The average age of [philosophical society] members is high--at
least 60. People don't get considered until they acquire quite a
body of work," says Cohn. "These things take time."
Robert K. Merton of Columbia University, who specializes in the
sociology and history of science, observes that the relative lack
of women members has to be seen in historical perspective, and
that changes must be viewed over time. "Every society, like
American society, has underrepresented women in the upper
reaches," he says. "The pool of potential members [in the
philosophical society] has been growing, but it's still smaller
than that of men."
Appreciating Diversity
For such a busy bunch--college presidents, Nobel laureates,
international heads of state and industry, and otherwise over-
committed academicians and scholars, for whom the prestige of yet
another society membership means little--why bother?
Knudson, like many other members, delights in the diversity of
the topics discussed at the meetings and the opportunity to hear
about and reflect on disciplines other than his own. The society,
Knudson says, is "the one place I can go that I can contemplate
the question, what is history going to say about us when we're
gone? What have we contributed?
"We learn in school about the grandeur of ancient Greece and
Rome. They weren't about conquests--they were about human
creation. We've made enormous contributions to the history of
man, in science, and how to govern. I'm worried that in these
modern times we sometimes get so preoccupied about immediate
problems that we'll forget about the human effort on a grander
scale."
Steven Benowitz is a freelance science writer based in Hershey,
Pa.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : Ex-OTA Staffer Brings `Fresh Eyes' To NSF Division Director's
Post
AU : PHIL BECK
TY : PROFESSION (PEOPLE)
PG : 22
Sociologist and science policy analyst Daryl E. Chubin has been
appointed division director for research, evaluation, and
dissemination in the education and human resources directorate of
the National Science Foundation. His appointment follows seven
years at the congressional Office of Technology Assessment (OTA),
which he left in the position of senior associate.
The move from the legislative to the executive branch has given
him a new perspective on the challenges of implementing
congressionally mandated education initiatives at NSF, Chubin
says, but also gives the agency a pair of "fresh eyes" in
evaluating its educational programming.
The responsibilities of the year-old division, Chubin says, are
twofold: It administers several primarily research-based
education programs and evaluates and monitors the entire
portfolio of the agency's 200-plus educational initiatives, ex-
ercising a sort of "quality control."
One example of a program Chubin's division administers is
Application of Advanced Technologies (AAT). AAT's general
mission, says Chubin, is "to bring technology to bear on as many
NSF educational programs as possible."
On a broader scale, Chubin says, his division looks at all of the
agency's education programs with an eye toward whether they
fulfill performance objectives and NSF's overall educational
goals.
"When NSF lends its imprimatur to something that can be used in
the classroom, what does that mean?" he says, as an example of a
central question his division tackles. "What kind of `back-end'
quality control has it received?" More specifically, he says, his
division tries to determine: "What difference are the programs
making? How do you measure outcomes? What have been the targeted
objectives of various programs?"
In taking the lead in determining science education goals and
methods, Chubin says, NSF is in a "good news-bad news" position:
the good news is that the agency is an "important player," in the
eyes of Congress and others, in setting educational priorities;
the bad news is that this is "very often done within current
budget constraints."
He adds: "I happen to think that Congress asks very pertinent
questions. But they sometimes have unrealistic expectations of
time and of magnitude. `Well, if you can do this in 10 states,
why can't you do it in 40? If you can find this out in three
years, why can't we do it in two?'
"Education does not fit those kinds of time frames ... or scale
questions."
Chubin says his experience with OTA and Congress will help him in
dealing with their demands, but also has given him the ability to
look at NSF's programs critically.
"New leadership brings new opportunities," he says. "I come here
with fresh eyes.... It behooves us to take a hard look at ...
what needs to be expanded, what needs to be consolidated, and
what needs to be let go. We can't do everything."
Because of the challenges NSF faces, Chubin says, he left OTA to
help: "The central motivation for my moving into the position is
that this is a critical time for the foundation ... and the
work that I had done in science education and science policy
convinced me that I could make a difference."
Chubin, 46, received his Ph.D. in sociology from Loyola
University in Chicago in 1973. He became a sociology professor at
Georgia Institute of Technology in 1977. He joined OTA in 1986 as
a senior analyst.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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TI : ELIOT STELLAR
TY : PROFESSION (OBITUARY)
PG : 22
Eliot Stellar, a physiological psychologist and former provost of
the University of Pennsylvania, died of cancer October 12 in
Philadelphia. He was 73 years old.
Stellar's research focused on the physiological processes of the
brain that affect human behavior, especially appetite and
obesity.
Stellar was the author or coauthor of numerous highly cited
papers. His most cited work was "Palatability, food intake, and
obesity in normal and hyperphagic rats" (Journal of Comparative
Physiology, 58[1]:63, 1964), which had garnered 235 citations as
of 1990. His 1954 paper "The physiology of motivation"
(Psychological Review, 61[1]:5-22, 1954), which had received 180
citations as of 1992, is considered by many to be a seminal work
in his field.
In addition, he was the author or coauthor of several books,
including Physiological Psychology (New York, McGraw-Hill, 1950),
considered a standard text in the field; Eating and Its Disorders
(New York, Raven Press, 1983); and The Neurobiology of Motivation
and Reward (New York, Springer Publishing Co., 1985), co-written
with his son James. He also edited the Journal of Comparative and
Physiological Psychology (now the Journal of Behavioral
Neuroscience).
Stellar graduated from Harvard University in 1941 and earned
master's and doctoral degrees from Brown University. After
graduating from Brown, he joined the psychology department of
Johns Hopkins University and moved to Penn in 1954 as an
associate professor of physiological psychology in the School of
Medicine. While at Penn, he served as director of the Institute
for Neurological Sciences, provost during a controversially
extensive restructuring of the university, and Joseph Leidy
Professor of Neurological Sciences. At the time of his death, he
was chairman of the department of cell and developmental biology-
-formerly the anatomy department--and University Professor of
Physiological Psychology in Anatomy.
In addition to his research and administrative duties, he was a
founder of the Society for Neuroscience, a member of the National
Academy of Sciences and the American Academy of Arts and
Sciences, and a member and former president of the American
Philosophical Society--the United States' oldest general learned
society (see story on page 21).
Stellar was an active member of NAS's Committee on Human Rights,
which persuades U.S. and foreign diplomats to intervene on behalf
of political prisoners, especially scientists. Russian physicist
Andrey Sakharov was among the prisoners the committee helped.
(The Scientist, Vol:7, #21, November 1, 1993)
(Copyright, The Scientist, Inc.)
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