
                      THE SCIENTIST
     (CONTENTS PAGE & FULL ISSUE FOLLOW THIS SHORT MESSAGE)
     ****************************************************** 

Dear Reader:

Many of you have been accessing THE SCIENTIST, free of 
charge, on the Internet for over a year.  We thank you for 
your interest.

Would you please take a moment to let us have your views, 
suggestions, and comments about THE SCIENTIST to enable us 
to better meet your needs?

We would particularly like to know:

1. If you are working in an academic, commercial, or 
   government organization?

2. After you ftp each issue of THE SCIENTIST, how many 
   others do you share it with?

3. Do you usually ftp the file or prefer searching it via 
   Gopher or WAIS?

4. If it can be arranged, would you prefer receiving each 
   issue, automatically, in your electronic mail box?

5. Each file is approximately 150K.  Can you receive a
   file of this size in your mail box?

5. Finally, do you have any suggestions for ways of 
   improving our file or format?


Thanks and best wishes,

Eugene Garfield
Publisher
THE SCIENTIST, 3600 Market Street, Philadelphia, PA 19104,U.S.A.
Phone :(215)243-2205 // Fax: (215)387-1266 

E-mail:garfield@aurora.cis.upenn.edu

                     =================


                          THE SCIENTIST


VOLUME 8, No:20                          OCTOBER 17, 1994
(Copyright, The Scientist, Inc.)

===============================================================
Articles published in THE SCIENTIST reflect the views of their 
authors and not the official views of the publication,         
its editorial staff, or its ownership.                         
===============================================================

    *** THE NEXT ISSUE OF THE SCIENTIST WILL APPEAR ON  ***
    ***                OCTOBER 31, 1994                 ***
    ***                                                 ***
    *******************************************************

Subscription rates for the printed edition are:

In the United States: one year $58, two years $ 94
Canada              : one year $82, two years $142
All other foreign   : one year/air cargo $ 79
                      one year/ airmail  $133


THE SCIENTIST 
(Page numbers correspond to printed edition of 
THE SCIENTIST)

FOR SEARCHING PURPOSES:  
AU   = author
TI   = title of article
TY   = type
PG   = page
NXT = next article

------------------------------------------------------------
TI :                      CONTENTS
PG : 3 
============================================================


BEHAVIORAL CHALLENGE: The search is narrowing for a director 
of the National Institutes of Health's new Office of 
Behavioral and Social Sciences Research. Social and 
behavioral scientists who have fought long and hard to raise 
the status of their disciplines at NIH say the new director 
will need to be strong and creative to combat the prevailing 
laboratory sciences culture at the agency--including, they 
say, the bias of NIH director Harold Varmus     
PG   : 1

CANCER SCIENCE A VICTIM: Cancer research institutions are 
facing an increasingly difficult battle to maintain their 
high standards of scientific research in the face of 
diminishing federal funding. They are especially falling 
victim to the congressional budgetary practice of earmarking 
monies for specific high-profile diseases       
PG   : 1

MORE FOR AGING: Despite a recent infusion of support for 
gerontological studies, ambitious investigators of aging-
associated phenomena continue to lament that their field is 
underfunded     
PG   : 1

LASKER WINNERS: The Lasker Foundation's medical research 
awards have been bestowed this year upon three investigators 
who exemplify "persistence and tenacity, intuition and 
intelligence"
PG   : 1

NEUROSCIENCE MEETING: The 24th annual meeting of the Society 
for Neuroscience, to be held in Miami Beach, is likely to be 
largest conference in the society's history, officials say      
PG   : 3

BIOETHICAL PERSPECTIVES: Arthur Caplan, the nation's 
preeminent bioethicist, recently moved his base of 
operations from the University of Minnesota to the 
University of Pennsylvania, where he has established the 
Center for Bioethics. In a candid interview with The 
Scientist, Caplan discusses the increasing importance of his 
discipline and the ambitious plans he has for the center        
PG   : 12

COMMENTARY: Science sociologist and historian Robert K. 
Merton, now in the 85th year of a notably productive life, 
was recently named winner of the National Medal of Science. 
In this essay, publisher Eugene Garfield reminisces about 
his long relationship with the eminent scholar, noting the 
significance of Merton's contributions and urging all 
scientists to become acquainted with his work   
PG   : 13

MATURING FIELD: Like its baby boomer subjects, the branch of 
biomedical science that explores the effects of aging is 
visibly maturing        
PG   : 14

HOT PAPERS: Developmental biologist Michael A. Rudnicki 
discusses his studies of the functions of myogenic 
regulatory factors; astrophysicist Georges Meynet reports on 
new grids of stellar models     
PG   : 16

SEQUENTIAL IMPROVEMENTS: Rapidly advancing DNA-sequencing 
technology offers increased speed, power, and sensitivity       
PG   : 17

INTERVIEW SKILLS: In the second installment of a three-part 
excerpt from his book A Ph.D. Is Not Enough!, physicist 
Peter J. Feibelman advises those interviewing for a job to 
look at the situation from the prospective employer's 
viewpoint and prepare accordingly       
PG   : 23

STEPHEN J. BENKOVIC, a chemistry professor at the 
Pennsylvania State University, has received the American 
Chemical Society's Alfred Bader Award in Bioinorganic and 
Bioorganic Chemistry    
PG   : 24

NOTEBOOK         PG : 4

CARTOON          PG : 4

LEADERS OF       PG    : 10
SCIENCE

LETTERS         PG  : 13

DNA SEQUENCING  DIRECTORY     PG   : 21

NEW PRODUCTS    PG  : 22

CROSSWORD       PG  : 24



(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  Behavioral Scientists See New NIH Status Enriching                 
        Biomedical Studies

AU   :  Franklin Hoke

TY   :  NEWS

PG   :  1

A search committee will stop accepting applications for the 
directorship of the newly chartered Office of Behavioral and 
Social Sciences Research (OBSSR) at the National Institutes 
of Health this week. The deadline's passing sets the stage 
for the appointment, by  year's end, of a leader whose task 
will be to effective- ly integrate behavioral and social 
sciences research into the traditional biomedical 
investigations for which NIH is better known.

Advocates who have long struggled to raise the stature of 
these disciplines at NIH succeeded through pressure and 
persuasion in getting Congress to write the new office into 
the health agency's fiscal 1994 authorization. Now, they say 
that if a strong first director is named, OBSSR should be 
able to promote in-novative, interdisciplinary re- search 
that will significantly extend understandings of basic 
processes in disease and health.

Some of these observers voice concerns, however, that OBSSR 
may not be easily incorporated into the laboratory sciences 
culture that prevails at NIH. The office's most important 
potential ally, NIH director Harold Varmus, has expressed, 
at best, lukewarm support for the behavioral and social 
sciences, they say.

Although the new OBSSR director will have a high profile--
the position will carry the additional title of associate 
director of NIH and will reside within the NIH director's 
office--how the office fares will depend, in part, on the 
welcome it receives from Varmus. 

The search committee is expected to forward a short list of 
candidates to Varmus by late November or early December; the 
NIH chief will then make the final selection, pending 
approval of Public Health Service head Philip Lee. Once 
installed, the new office's chief will begin the challenging 
task of coordinating with various NIH institutes to promote 
research linking behavioral and social factors to health and 
disease.

Scientists believe that the office's initial funding of 
about $2.5 million will probably not be enough to grant 
research awards directly. They expect, however, that the 
amount should be adequate to sponsor conferences, workshops, 
and other projects to catalyze important new scientific 
investigations, both within and outside NIH.

"So many of the diseases facing us involve behavioral 
patterns participating in their pathogenesis or 
perpetuation," says Ira B. Black, chairman of the department 
of neuroscience and cell biology at the University of 
Medicine and Dentistry of New Jersey at the Robert Wood 
Johnson Medical School in Piscataway. Black, a past 
president of the Society for Neuroscience, Washington, D.C., 
was also a member of the Institute of Medicine committee 
that produced the report AIDS and Behavior: An Integrated 
Approach (Washington, National Academy Press, 1994). 
"There's an extraordinary need for the behavioral sciences 
to crosstalk more effectively with what we might call the 
biological sciences--even though those very distinctions 
that I'm drawing are artificial. If this office can 
contribute to that kind of interaction, it will be 
successful."

Although generally optimistic that, with a sufficiently 
articulate and scientifically qualified director, OBSSR can 
accomplish its goals, some behavioral and social scientists 
worry about past statements made by Varmus that they 
characterize as disparaging of their disciplines.

The new position is being constructed as, potentially, quite 
a visible post," declares Felice J. Levine, executive 
officer of the American Sociological Association in 
Washington, D.C. "We are concerned that Dr. Varmus has not 
seemed to appreciate the real value added of looking at the 
social and behavioral dynamics of health and disease. But 
we're hoping that this office can be part of the solution, 
and that he will be open to the scientific counsel of an 
effective director."

Others note what they feel has been an excessively long wait 
between congressional authorization for the new office in 
June 1993 and action taken to create it, indicating 
resistance to OBSSR. Department of Health and Human Services 
Secretary Donna Shalala signed the necessary paperwork to 
establish the office on July 13 of this year. The delay has 
been ascribed by NIH, however, to normal bureaucratic 
procedure. 

NIH officials say that, whatever tensions may exist, OBSSR 
will likely join other congressionally ordered units that 
have been productively integrated into the office of the 
director--the offices for research on minority health and 
research on women's health, for example. 
"It's difficult when there are legislative mandates," 
observes Delores Parron, associate director for special 
populations in the office of the director of the National 
Institute of Mental Health (NIMH)--a job also created by act 
of Congress, in 1980--and cochairwoman of the search 
committee for the OBSSR director. "But with minority health 
and women's health, we've learned how to really make good 
use of these offices to do the kind of things that we need 
to do, to take the leadership to move us into areas where 
we've needed to move for a long time."

Leadership Needed
Because the office will not have a large budget and, hence, 
will have limited direct powers, the new director's 
leadership capabilities--both scientific and for coalition-
building with other offices in NIH--will be crucial to 
OBSSR's effectiveness. A demonstrable understanding of the 
scientific methodologies used in the laboratory-focused 
biomedical disciplines will also be needed, researchers 
agree.
The [OBSSR director] will have to work very closely with all 
the institutes at NIH, so there should be a very strong 
appreciation for systematic pursuit of knowledge," says Cora 
Marrett, an assistant director of the National Science 
Foundation in Washington. Marrett, the first head of NSF's 
directorate for the social, behavioral, and economic 
sciences--an office comparable to OBSSR, established at the 
science foundation in 1992--is a member of the search 
committee for the OBSSR director. "The person clearly will 
have to have a strong ability to communicate ideas and to 
bring others together, because the position will not have a 
lot of staff or resources initially.

OBSSR, for example, "won't have the budget authority of the 
Office of AIDS Research [OAR]," according to Susan Persons, 
associate director for government affairs of the Consortium 
of Social Science Associations (COSSA) in Washington. OAR 
consolidates AIDS research budgets and planning at NIH. 
"That's one of the reasons that it's important that the new 
director be someone who's respected in the larger community 
as well as at NIH. Hopefully, if there's a good, strong 
director, that person will be able to get the institutes to 
collaborate more." Persons adds that a director interacting 
well with all parts of NIH should help ensure that 
duplicative research is minimized.

One difficult, early objective of the new director will be 
establishing consensus about just what constitutes 
behavioral and social science. Different definitions are 
used throughout the health agency.

"One of the first tasks for the new person coming in will be 
to define precisely how much [behavioral and social science] 
there is at NIH right now," Marrett says.

According to Marrett, this will be difficult because of the 
breadth and diversity of what has been called behavioral or 
social science. For her office to coordinate well with its 
NIH counterpart, she says, inter- and intradisciplinary 
distinctions will be important.

"There are some areas where most of the support would be at 
NSF," Marrett notes. "There is more support for anthropology 
at NSF than NIH, for example. But for a number of parts of 
psychology--physiological neuropsychology and, to some 
extent, cognitive psychology--there is substantially more 
support at NIH than at NSF currently."

In many ways, links between biomedical laboratory sciences 
and behavioral and social sciences research are only just 
emerging. Perhaps for this reason, defining just what types 
of studies will lie within the purview of OBSSR may be 
difficult. Will, for example, psychosomatic medicine be 
included in the category? What about the search for behavior 
genes?

"With behavior genes, you're really talking about 
straightforward molecular biology," says Louis Sibal, 
director of the office of laboratory animal research in the 
NIH director's office. Sibal is the official managing the 
process of establishing OBSSR and will be asked to help the 
office's new leader navigate the bureaucracy at NIH, an 
especially important job if the incoming person is from 
outside the agency. "Those kinds of [investigations] would 
come in the genome program, where people would be mapping 
the genes and finding out what their functions are."

NIMH's Parron, however, suggests that work with behavior 
genes and psychosomatic medicine probably will both fall 
within OBSSR's mandate.

"But coming up with an agreed-upon definition of what's 
encompassed is one of the main tasks the new director will 
be undertaking, because there has been controversy in 
various sectors of NIH about what the appropriate definition 
of behavioral science research should be," Parron points 
out, noting that the social sciences are more easily 
defined. "There are some people who say that much of the 
research in the neurosciences should be excluded, for 
example, and then others who make the argument as to why it 
should be included."

Areas of investigation that most scientists agree will be 
addressed by the new office include so-called preventive 
research--studies on the persistence of high-risk behaviors 
among populations with the potential to be exposed to the 
HIV virus, for example, or why young people aware of the 
fact that smoking can lead to cancer are still attracted to 
cigarettes. 

Trouble At The Top?
NIH director Varmus, a Nobel-Prize-winning molecular 
biologist, has been accused by behavioral and social 
scientists of being unsympathetic to their disciplines, and 
their concerns based on this impression extend to their 
expectations for OBSSR. The feeling that the NIH director is 
less than favorably disposed to behavioral and social 
science stems, in part, from a statement that appeared in 
The New York Times (N. Angier, Nov. 23, 1993, page C1).

"I begin with the premise that behavior is an incredibly 
important element in medicine," Varmus told the newspaper. 
"People's habits, their willingness to take steps to avoid 
transmission of HIV, are all behavioral questions. But what 
I'm looking for are new ideas, real discoveries. When I read 
about genetics, I see breakthroughs every day. And while I'm 
trying to learn more about behavioral science, I must say 
that I don't feel I get tremendous intellectual stimulation 
from most of the things I read."

Varmus's defenders insist that his comments have been 
misinterpreted and that he was merely expressing his 
personal affinity for the methodologies of molecular 
biology. Through spokespersons, Varmus declines to respond 
directly.

"Dr. Varmus is a molecular biologist at heart," says Sibal. 
"And, obviously, he's a brilliant man who has very high 
standards. He's a stickler for high-quality research. That's 
what was intended by that remark."

Behavioral and social scientists acknowledge that an ability 
to challenge the impression--relatively common among 
traditional biomedical researchers--that the behavioral and 
social sciences lack a rigor comparable to that of their own 
disciplines, will be key to the new director's success.

"The scientific depth and acumen [of the new director] will 
be core," says Levine, "not just in interaction with Dr. 
Varmus but also in being able to play a leadership role 
across the agency."

In the view of Denis J. Prager, former director of the 
health program at the John D. and Catherine T. MacArthur 
Foundation in Chicago and now head of a consulting firm for 
foundation planning, "there's room for some strengthening of 
the behavioral and social sciences." For most of the past 
decade, the MacArthur Foundation supported a research 
network for health and behavior headed by psychologist 
Judith Rodin, the new president of the University of 
Pennsylvania. Says Prager: "Certainly, there's some room for 
strengthening the degree to which they're integrated into 
the biomedical sciences. On the other hand, it doesn't take 
a lot of reading of the literature to become convinced that 
some of the most powerful determinants of health in our 
society are behavioral and social."

Varmus is also said to be broadening his knowledge of the 
behavioral and social sciences as his time in office 
lengthens.

"He's on a learning curve and open to hearing," says Anne 
Thomas, associate director for communications in Varmus's 
office. "And I've heard him express his understanding that 
behavioral science is important."

"We've been told that he's educable, that this just isn't 
his area of interest, and I can understand that," counters 
COSSA's Susan Persons. After Congress authorized OBSSR in 
June 1993, she formed the Coalition for the Advancement of 
Health Through Behavioral and Social Science Research, 
consisting of 12 member societies and organizations, to 
monitor NIH progress toward establishing the office. 

Persons reports that Varmus failed to mention the behavioral 
and social sciences at his confirmation hearings and in 
other testimony before Congress. He has also refused to meet 
with representatives of her group, while meeting often with 
other biomedical researchers, raising fears that the new 
OBSSR will be coolly received in his office, she says.

"I'm not inclined to give him the benefit of the doubt any 
further," Persons says. "There have been opportunities. As 
the NIH director, truly, he represents all of the research 
that is done there."

She adds, however: "In spite of the slow progress in getting 
this done, I'm really hopeful that, once it is in place and 
we have a good [OBSSR] director, things will improve. I 
don't think we're going to be able to tackle most of the 
health challenges that we have without behavioral and social 
science. It's just impossible."

Persons's views--a mix of optimism and cynicism--are shared 
by other scientists.

"Behavioral and social scientists are enthusiastic about the 
fact that such an office will exist, but skeptical that it 
will, in fact, be well integrated into the NIH system and 
have much impact," Prager says.

Whatever the start-up problems with OBSSR, most behavioral 
and social scientists agree that the questions to be 
addressed by the office will be critical ones for biomedical 
research and public health in the future.

"The most interesting and most powerful science down the 
road is going to be that science which is capable of 
integrating the inputs of social, behavioral, and biological 
[sciences] in such a way that we get a really detailed view 
of how the organism operates in the real world and how it is 
affected by the environment within which it lives," Prager 
says. "If the NIH people, including Varmus, can be brought 
to understand that, then we're going to make much more 
progress, much more quickly, in promoting health and 
preventing disease."

"I very much hope this office will be a spur for ever-
increasing multidisciplinary efforts," neuroscientist Ira 
Black says. "We're in a position now for that to become a 
reality, for us to regard the biology of behavior, the 
behavioral output, and the behavior of interacting 
individuals as different facets of the same pursuit."

Black adds: "Medicine of the 21st century, in large measure, 
may well be psychosomatic and somatopsychic medicine."


(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : Lasker Awards Cite Persistence Of Three Scientists

AU   : Barbara Spector

TY   : NEWS

PG   : 1

The  Albert and Mary Lasker Foundation this year has  chosen 
as   the  recipients  of  its  prestigious  Winged   Victory 
statuettes  three  researchers  who,  according  to   awards 
program director Jordan U. Gutterman, exemplify "persistence 
and tenacity, intuition and intelligence."

The  New York-based foundation presented its  Albert  Lasker 
Clinical Medical Research Award to John A. Clements,  Julius 
H.  Comroe,  Jr.  Professor  of  Pulmonary  Biology  and   a 
professor of pediatrics at the University of California, San 
Francisco.  The Albert Lasker Basic Medical  Research  Award 
was  bestowed  on  Stanley  B.  Prusiner,  a  professor   of 
neurology   and  biochemistry  at  UC-San   Francisco.   The 
foundation  gave  its Albert Lasker  Special  Public  Health 
Award--which  had been presented only four times  previously 
in  the  program's 49-year history--to  Maclyn  McCarty,  an 
emeritus   professor  of  bacteriology  and  immunology   at 
Rockefeller University.

In addition to the inscribed statues, each winner received a 
$25,000 prize. The presentation took place at a luncheon in 
New York City on September 30. Health and Human Services 
Secretary Donna E. Shalala was the keynote speaker.

"All three are wonderful human stories in science," 
proclaims Gutterman, who is also chairman of clinical 
immunology and biological therapy at the University of Texas 
M.D. Anderson Cancer Center in Houston.

A Lasker award, believed by many to be the most significant 
United States biomedical science prize, is generally viewed 
as a "predictor" of the Nobel Prize. Fifty-one Lasker 
recipients have gone on to win the coveted Swedish honor.

The Lasker Foundation was established in 1942 by Albert 
Lasker, the late owner of the Lord & Thomas advertising 
agency, and his wife, Mary, an enthusiastic advocate of 
biomedical research. This year's awards were the first to be 
given since Mary Lasker's death this past February (B. 
Spector, The Scientist, March 21, 1994, page 3).

In her address at the luncheon, Shalala paid tribute to Mary 
Lasker: "One of Mary's greatest skills was her ability to 
hold public officials to a very high level of service and 
excellence. And when it came to the government's commitment 
to science and knowledge, she left little room for people to 
weasel out of those commitments.

"From Franklin Roosevelt to Bill Clinton, Mary Lasker made 
sure that presidents and Cabinet secretaries knew the value 
of science to this country."

Historic Achievement
The award to McCarty celebrates the 50th anniversary of the 
landmark discovery that genes are made of DNA (O.T. Avery, 
C.M. MacLeod, M. McCarty, Journal of Experimental Medicine, 
79:137-58, 1944). McCarty conducted this research along with 
Rockefeller colleagues Oswald T. Avery and Colin M. MacLeod, 
both now deceased. The trio, originally aiming to find a 
cure for pneumonia, determined that DNA was the substance 
that controlled the reproduction of pneumococcus--a 
breakthrough that launched the modern age of molecular 
biology and genetics. According to the Philadelphia-based 
Institute for Scientific Information (ISI), this paper has 
been explicitly referenced in more than 1,000 subsequent 
articles. It long ago became part of the common wisdom of 
the field.

Joshua Lederberg, University Professor at Rockefeller, has 
called the group's discovery "an outstanding example of the 
feedback of clinically motivated inquiry into the most basic 
issues of fundamental biological science" (J. Lederberg, The 
Scientist, Feb. 21, 1994, page 11).

"It was an authentic discovery of a problem as well as a 
solution," says Lederberg. "It wasn't a problematic issue 
except in the minds of one group." He notes that, at the 
time, it was unclear that one could go about determining 
what genes are made of.

The profound significance of the paper took years to be 
appreciated, partially because it was published during World 
War II, and partially because the journal in which it 
appeared was not widely read by pure geneticists. The 
group's findings were also challenged by several detractors, 
who claimed that there was not enough evidence to support 
the trio's conclusion.

"People didn't get it," marvels McCarty, now 83. He recalls 
being the second presenter at a meeting at Johns Hopkins 
University in 1949, at which he was to discuss the DNA 
research. At the beginning of the event, the room was 
packed. But after the first lecture--on the use of Dramamine 
to treat seasickness--"the sound of people leaving the hall 
was so loud that I had to delay the start of my paper." When 
he finally began speaking, "there were about 35 people 
left."

Another factor hindering widespread acceptance of the work 
was Avery's reluctance to personally promote it. "His view 
of [self-promotion]--practiced for many years before, as 
well--was to get the information published with the best 
possible proof of the point and let the interpretations fall 
where they may," McCarty reminisces. Ironically, although 
Avery received a Lasker award in 1947, he was cited "for 
distinguished service through studies on the chemical 
constitution of bacteria" rather than his DNA work.

McCarty followed the 1944 paper with two articles describing 
his preparation of a purified pancreatic DNase (M. McCarty, 
Journal of General Physiology, 29:123-39, 1946) that, in 
nanogram quantities, would inactivate the transforming 
substance (M. McCarty, O.T. Avery, J. Exp. Med., 83:89-96, 
1946). This evidence backed up the conclusions of the 
original article. In 1946, he left Avery's group to head a 
Rockefeller lab investigating streptococcal infections and 
rheumatic fever.

The Lasker Foundation's Gutterman says the award to McCarty 
is intended "not only to honor the work, but to honor the 
field and publicize what's going on." Although the discovery 
occurred half a century ago, Gutterman points out, only 
recently has an understanding developed of "how cells act, 
how organisms develop, what normal physiology is, and how 
disease develops."

McCarty, a member of the National Academy of Sciences (NAS) 
and the Institute of Medicine (IoM), received his M.D. 
degree from Johns Hopkins in 1937 and came to Avery's 
Rockefeller lab as a research fellow in 1941. He recounts 
his memories of the DNA work in his book The Transforming 
Principle (New York, W.W. Norton & Co. Inc., 1985).

Overcoming Skepticism
Prusiner was cited for identifying a new class of pathogens, 
which he named prions. He has reported that these infectious 
agents are implicated in diseases marked by slow onset with 
progressive deterioration of the brain and nervous system, 
including scrapie, a disease affecting sheep; as well as 
Gerstmann-Strussler-Scheinker disease (GSS), Creutzfeldt-
Jakob disease, and kuru in humans.

Prusiner defined the prion in a 1982 paper, "Novel 
proteinaceous infections particles cause scrapie" (Science, 
216:136-44), which has been cited in more than 425 
subsequent studies. This work was greeted by skepticism in 
certain scientific circles. The pathogen, he maintained, was 
composed only of protein; he did not find DNA or RNA in the 
prion, contradicting the general belief that all living 
organisms contain genes.

Further fueling doubts among some of Prusiner's colleagues 
was his assertion that prion diseases can be inherited as 
well as infectious. Moreover, he concluded that the normal 
prion protein has a different shape from the disease form. 
This, too, was heretical, because it had long been thought 
that each protein has only one natural conformation.

According to Gutterman, Prusiner's award also recognizes his 
"many years of very, very painstaking work [amid] a lot of 
opposition." In the early 1980s, the researcher and his 
prion theory were the subject of uncomplimentary articles in 
the scientific and popular press. His detractors maintained 
that the agent at work in these diseases was a slow-acting 
virus. While some investigators continue to look for a 
virus, the scientific community now generally accepts the 
idea of prions, which are now studied by many former 
proponents of alternative hypotheses.

Prusiner "was all by himself against the world to prove the 
point," comments Pierluigi Gambetti, a professor of 
pathology at Case Western Reserve University School of 
Medicine who studies prion diseases. The copious data 
Prusiner produced ultimately won over the skeptics, says 
Gambetti, noting that he himself originally "had trouble 
understanding the mechanism." The "breakthrough" that 
shifted his perspective, recalls Gambetti, was Prusiner's 
results with transgenic animals.

"The deeper I got into this, the more controversy there was, 
the more people got angry, the more I wanted to figure out 
what this [prion] was," says Prusiner. "I couldn't figure 
out a better problem to work on."

Prusiner, 52, received his M.D. from the University of 
Pennsylvania in 1968 and then moved to UC-San Francisco, 
where he did an internship and a residency in neurology. 
"Today, I believe, it is very unlikely that my initial 
research would have been funded by NIH, because so little 
money is available for basic biomedical research," he said 
at the awards presentation. "The truly innovative proposals 
by young people don't have a chance anymore, at least I 
believe that to be the case."

The general acceptance of the prion hypothesis in the past 
few years has manifested itself in the form of numerous 
significant prizes given to Prusiner, among them a Gairdner 
Foundation International Award, the Richard Lounsbery Award 
from NAS, a Charles A. Dana Award for Pioneering 
Achievements in Health, and a Christopher Columbus 
Quincentennial Discovery Award in Biomedical Research from 
the National Institutes of Health. He was elected to NAS and 
IoM in 1992.

Lifesaving Research
The Lasker Foundation recognized Clements, 71, for 
discovering lung surfactant, a soap-like mixture of 
lipoproteins that coats the lungs and prevents them from 
collapsing, in 1957. The paper reporting on this discovery 
(J.A. Clements, "Surface tension of lung extracts," 
Proceedings of the Society for Experimental Biology and 
Medicine, 95:170-2) has been cited in more than 340 papers; 
like McCarty's seminal DNA paper, it has become textbook 
knowledge.

In 1959, researchers Mary Ellen Avery and Jere Mead of 
Harvard University found that respiratory distress syndrome, 
a leading cause of death in premature infants, develops 
because the babies are born before their lungs start 
producing surfactant. The condition resulted in the death of 
Patrick Bouvier Kennedy, the two-day-old son of President 
John F. and Jacqueline Kennedy, in 1963.

In 1961, Clements and colleagues identified the major lipid 
component of surfactant, which led to attempts by multiple 
groups to synthesize the substance. In 1985, Clements 
developed a synthetic surfactant. The artificial substance, 
called Exosurf, was licensed to Burroughs Wellcome Co. of 
Research Triangle Park, N.C., and received Food and Drug 
Administration approval in 1990. 

"Now it has been demonstrated that surfactant-replacement 
therapy has reduced infant mortality to the lowest it's 
been, in the U.S. and in most industrialized countries," 
says Harvard's Avery, a member of the 1994 Lasker awards 
jury.

Clements acknowledges that science rarely proceeds at a pace 
sufficiently rapid to enable a researcher to see favorable 
clinical results of his basic investigations in his own 
lifetime: "I recognize that fact every day. I think of all 
the people toiling in the vineyards--a lot of them work 
harder than I work; most are a lot smarter. [Therefore] I 
have to consider that Lady Luck played a role."

For example, he notes, it was serendipity that led him to 
study the pulmonary system in the first place. During the 
Korean War, he volunteered for military service and was 
assigned to the U.S. Army Chemical Center in Edgewood, Md. 
At the time, government scientists were studying the effects 
of nerve gases, fearing that the Soviets might use them in 
chemical warfare. "I was assigned the task of figuring out 
how nerve gases affected the lungs. I had no particular 
interest in how the lungs worked up to that point."

Following the war, Clements remained at the Army Chemical 
Center as a staff member until 1959. He has been at UC-San 
Francisco since 1961. An NAS member, he has received a 
Gairdner Award and a Christopher Columbus Discovery Award, 
among other honors.

Clements stresses that many aspects of surfactant remain to 
be investigated: " 'Surfactant' tends to imply that it is 
something simple, but--no pun intended--we've only scratched 
the surface. We know so little about it at this point." 
Among the knowledge that remains to be gained, he says, is 
the role the substance plays in recovery from injury to the 
adult lung as well as in the lung's response to disease.

At the Lasker awards luncheon, Clements announced that he 
would donate the honorarium to the United Nations 
International Fund for Children's Relief.

In the stories of all three award-winners, Gutterman 
maintains, there runs a common theme: the "spinoff back and 
forth between basic and clinical research."

In order to ensure future breakthroughs, he declares: "We 
have to have environments for these discoveries to be made, 
and we have to have long-term investments."     


(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  Cancer Researchers Fear Impact Of Diminishing Funding
        Support

Redistribution of federal financial backing may have
drastic implications for cancer studies, they warn

AU   : Steven Benowitz

TY   :  NEWS 

PG   :  1

With federal research funds increasingly being earmarked
for such publicly visible areas of biomedical investigation as
AIDS and women's health, cancer research institutions in the
United States are finding themselves in a bind.

Saddled with a shrinking piece of the budgetary pie, heads 
of the nation's basic cancer research centers are struggling 
to maintain their high scientific standards while making 
ends meet. They worry that the frustration of stagnant 
funding levels will drive their best researchers to seek 
greener pastures. And they are concerned that, in the long 
run, the necessity of cutting costs will serve only to
hinder scientific progress.

Last month, the National Cancer Advisory Board told Congress 
that the nation's war against cancer had stalled, and that 
without several changes, cancer would become the country's 
top killer within five years (New York Times, Sept.
3, 1994, page A25). The board suggested, among other things,
additional funding to move new discoveries from the laboratory 
to the bedside.

The National Cancer Institute (NCI), for example,
currently funds only 15 percent of overall grant 
applications -- down from 25 percent only a few years ago, 
says E. Premkumar Reddy, director of Temple University's 
Fels Research Institute in Philadelphia, one of 14 NCI-
designated basic science cancer centers. Moreover, although 
the National Institutes of Health has not significantly 
increased the dollars available for cancer research, these 
monies are being funneled in several different directions, 
especially to more applied areas. In federally funded cancer 
research, the emphasis has shifted to therapeutics, 
particularly for such high-profile conditions as breast 
andprostate cancers, and away from basic science, cancer 
scientists say.

"The money is going to the same tired, unsuccessful drugs," 
Reddy laments. "The only real innovations will come with 
basic research."  Reddy draws an analogy to the advent of 
penicillin, which ushered in a revolution in medicine in the 
1950s and 1960s. "In the next four or five years," he 
forecasts, "basic research in molecular biology may be 
able to achieve the same thing in cancer treatments. But not 
without the money to do it."

Indeed, according to Reddy, NCI has mandated that the basic 
research centers that are affiliated with hospitals -- such
as Fels and Temple -- must make their research more 
"applied."  "Good basic science is hurting," he 
cautions.

A Dying Breed
Some observers fear that the university researcher 
with the resources to command the large, easily renewed 
federal grant that pays for a laboratory full of 
postdoctoral fellows, graduate students, and technicians has 
become a dying breed.

"There's no question that there's a general biomedical 
funding crunch," says Robert Young, president of the Fox 
Chase Cancer Center, also based in Philadelphia. Fox Chase 
is one of 27 NCI-designated comprehensive cancer centers, 
which focus on patient care as well as clinical and basic 
research. "We have more good research projects than are 
adequately funded. In the last 10 years, we've seen an 
increase in the percent of grants that are approved but
not funded."

According to NIH's Division of Research 
Grants, only 15.8 percent of all new R01 investigator-
initiated grant submitted in fiscal year 1993 were funded. 
This represents a drop from 1992 and 1991, in which 20.7 
percent and 21.3 percent of such grants, respectively, were 
funded. Young blames a "stagnant federal research 
budget," combined with earmarking funds for particular 
areas of research, both of which "have been much more 
prevalent in the past five years and [have] affected overall 
funding opportunities."  As a case in point, the NIH 1993 
budget for AIDS research was $1.07 billion. The estimated
1994 figure is $1.3 billion -- an increase of $226 million 
earmarked by Congress-- as reported by the institutes'
Office of Financial Management. 

A significant change in the overall federal budgetary 
outlays is not expected anytime soon. The House of 
Representatives and the Senate have agreed to award NIH an 
overall increase of roughly 3.6 percent for 1995, enough to 
keep up with inflation. Most institutes, including NCI, have 
been granted 3 percent  raises.

Pushing Applications
"There's been an increasing pressure from the federal 
government to justify basic science on the basis of some 
potential clinical application," Young says.

Often, those links are problematic. "That's what concerns 
basic scientists,"he notes. "The fact that there is no 
easily explained application of their research in medicine 
doesn't mean there won't be, but rather that we don't
know what they may be yet."

"People have argued that many of 
the breakthroughs in science and medicine have come at the 
basic-science level," Young points out. 

"An important breast cancer discovery may not specifically 
come from a research project labeled for breast cancer."

As an example, he cites the retinoblastoma gene. It's a tumor 
suppressor gene that's believed to play a role in causing 
some breast cancers. Yet it was discovered as a cause of a 
relatively rare childhood eye cancer.

"Earmarking makes it harder for people to secure funding,"
Young says. "It's produced a feeling of insecurity. Twenty 
years ago good researchers were pretty confident they'd be
able to pursue their goals. Today no one is guaranteed."

Norman Drinkwater, director of the McArdle Laboratory for 
Cancer Research at the University of Wisconsin, Madison, 
worries that the tougher competition for funding will affect 
the next generation of scientists. "I think we'll start to 
lose a number of talented scientists as they become 
frustrated trying to establish top research programs," he 
predicts.

He's particularly concerned about a budget 
shortfall for training programs and grants that include 
support for predoctoral and doctoral students. "As we fail 
to fund these training programs, we'll develop fewer first-
rate scientists for the future," he warns.

The funding crunch may well hinder scientific progress if 
something isn't done, says researcher David Schuller of 
Ohio State University in Columbus. "The problem is, we've 
reached a point today in which the rate of scientific 
discovery in cancer research is resource-driven -- and 
resource-limited."  

"As the level of competition for funding 
gets keener, you can't separate the quality of research 
proposals as easily," maintains Schuller, who is director 
of Ohio State's Comprehensive Cancer Center-Arthur G. James 
Hospital and Research Institute. Greater competition for the 
same research dollars also has made it tougher to secure 
support the first time around. Young investigators are 
competing with more seasoned researchers whose grant 
requests may initially have been turned down, and who are 
already resubmitting revised proposals. "The system tends 
to exclude the entry-level investigator, which affects the 
future of biomedical research," Schuller says.

That message seems to be getting out. A report issued in 
July by the National Research Council (The Funding of Young 
Investigators in the Biological and Biomedical Sciences, 
Washington, D.C., National Academy Press, 1994) showed that 
the number of biologists under the age of 37 applying for 
independent NIH grants dropped by more than 50 percent in 
the past eight years, though applications from older 
colleagues increased by more than a third.Young sees little 
funding relief in sight, with federal budget caps and 
growing public entitlement budgets contributing to keeping 
the biomedical research funding relatively unchanged for the 
next several years.Yet many, like Giovanni Rovera, director 
of the Wistar Institute of Anatomy and Biology in 
Philadelphia, contend that the money is still there. But he 
agrees that greater competition for the same research 
dollars has made it tougher to secure support the first time 
around. The "worthy" projects will get support, Rovera 
forecasts. It just may take two or three grant rewrites 
before the money comes through. And the support may be for 
less time and fewer dollars than expected (see story on page 
4).

"The problem isn't getting the money, but rather, getting it 
promptly, when you want it," Rovera says.

Shelley Berger, an assistant professor who came to Wistar in 
1993 from a postdoctoral position at the Massachusetts 
Institute of Technology, uses baker's yeast to examine how 
genes are turned on and off. Her latest grant application 
was funded by both the National Science Foundation and the 
American Cancer Society, but not by NCI.

Berger acknowledges that many of her friends whose "work 
is just as good and worthwhile of funding" have been 
turned down for federal dollars. "There's plenty of 
science available, but just too many people who want to do 
it." 

Problem With Earmarking

"Earmarking affects the way science
is done in this country," asserts microbiologist Clayton 
Buck, deputy director of Wistar. "By forcing scientists to 
be more competitive, you make them focus on applied areas 
that they may not necessarily have chosen. Now they have to 
because that's where the money is -- you affect their 
choices of research specialties."  

Former NCI director Vincent DeVita, who now is director of 
the Yale University Cancer Center, agrees. "Earmarking is 
dangerous because it takes dollars from the general RO1 
investigator-initiated grant pool and forces investigators 
to redirect their thinking to the direction of translational 
research," he says. "It's not that I'm against translational 
work; I'm just against manipulating the R01 pool."

Such choices may also affect tenure and promotion decisions. 
"Universities [define] successful scientists as whether or
not you have an R01 grant," DeVita observes. "in the old 
days, you could get grants and spend a few years doing 
research and find out whether you were any good as a 
scientist. You're under tighter restrictions and tougher 
demands today."  

While Young, Rovera, and DeVita decry earmarking of federal 
dollars as a potential threat to the future of the United 
States  research base, Congress and the public seem to be 
demanding greater accountability from researchers, according 
to agency officials and other veteran science-watchers. For 
whatever problems scientists choose to address, legislators 
want to be sure tax dollars are resulting in clinical 
payoffs, or at least marketable products. Scientists have 
had to become more attuned to potential clinical 
applications of research, particularly when writing grant 
proposals.

"We're being held more accountable by Congress 
and the public," says Faye Austin, associate director for 
extramural research in NCI's Division of Cancer Biology, 
Diagnoses, and Centers. "We've made a large investment in 
biomedical research in the last 20 years, and the public 
asks, "What are we getting for this?"  

"Things have changed since AIDS came along with the 
empowerment of the AIDS constituency," she notes. 

"They've been  successful in getting resources, and have 
taught similar lessons to other groups." Last year, for 
example, the National Breast Cancer Coalition, along with
other groups, lobbied Congress and persuaded it to double 
the money it spends on breast cancer research.  "The public 
is putting pressure on researchers to show results," 
Austin adds.                              

Steven Benowitz is a science writer for Penn State University
Milton S. Hershey Medical Center in Hershey, Pa.


(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  SLIMMER WISTAR IN TRANSITION

AU   :  STEVEN BENOWITZ

TY   :   NEWS

PG   :   4


The Wistar Institute of Anatomy and Biology in Philadelphia 
shares the woes of other basic science cancer centers: how 
to deal with an uncertain funding environment, given the 
increased push by federal funding agencies to support 
applied research.

Compounding matters, Wistar has had the added burden of a 
three-year legal battle over management issues with former 
director Hilary Koprowski, settled in June 1993. Although 
just three years ago Wistar faced a $2 million budget 
deficit and declining morale, today the staff credits the 
new director, Giovanni Rovera, with streamlining the 
institute--closing unproductive laboratories and reducing 
the work force.

Now, a leaner Wistar seems re-energized, with a fresh sense 
of purpose, according to Robert A. Fox, immediate past 
president of its managing board and president of RAF 
Industries Inc., a private investment company based in 
Elkins Park, Pa. Earlier this year, the institute finally 
celebrated its centennial--albeit three years late.

In singing  Rovera's  praises,  his  supporters  point  to a 
$1 million research grant awarded in 1992 by Philadelphia-
based Pew Charitable Trusts. This support, they say, has 
helped bring in a new wave of young scientists, while 
helping to strengthen scientific initiatives in structural 
biology, molecular genetics, and cell and developmental 
biology. Scientific collaborations have flourished. 
Scientists from Wistar and the University of Pennsylvania--
on whose campus it sits--are studying gene therapy for 
cystic fibrosis and a number of other diseases, for example. 
And Wistar and Children's Hospital of Philadelphia are using 
a five-year, $5.9 million grant from the National Heart, 
Lung, and Blood Institute to establish a pediatric 
cardiology center.

"The institute is clearly now becoming stabilized after 
several turbulent years," says Rovera, a specialist in 
pediatric leukemias. "The focus is clearly on science, 
though we still must keep an eye on financial matters. Our 
precarious economic reality, relying mostly on federal 
grants, and not patient-care revenues, forces us to."

As part of the centennial celebration, honors were bestowed 
upon Koprowski, a Polish-born virologist who headed Wistar 
from 1957 to 1991 and made it a world-class institution. 
Koprowski, who has since moved across town to Thomas 
Jefferson University, was named professor laureate at Wistar 
and given a position on the institute's controlling board of 
managers.

Wistar is known in the research establishment for a century 
of accomplishments. One of 14 basic cancer centers 
designated by the National Cancer Institute, it carries a 
research budget of about $25 million, with some 75 percent 
of its grant funding coming from the National Institutes of 
Health. About 70 percent of its work is devoted to various 
aspects of cancer.

Its many achievements include the development of the first 
line of continuously growing normal human cells, the design 
of vaccines against rubella and rabies, and the creation of 
specialized antibodies to seek out and destroy cancer cells. 
Wistar scientists have identified interleukin-12, an immune 
system regulator that may play a key role in AIDS, and are 
working on perfecting vaccines against rotavirus, which 
causes infantile diarrhea, and cancer.

"Wistar is a unique environment," says Nancy Fogg-Johnson, 
vice president for administration. "It's an academic 
institution without teaching requirements, so the scientists 
can really dedicate themselves to basic science."

She contends that while Wistar has done "relatively well" in 
securing funds for research in the past, it must "step up 
its efforts to get support from private sources." Wistar has 
also been receiving royalties for its numerous discoveries 
over the years, such as rubella and recombinant rabies 
vaccines, as well as the hybridoma method for producing 
monoclonal antibodies for detection and treatment of 
cancers.

Deputy director Clayton Buck, a cell biologist and  
professor of pediatric cardiology who heads the new 
pediatric cardiology center, acknowledges that Wistar has 
had a poor track record in garnering private funding: "An 
institution of our size should have an endowment of some 
$150 to $200 million. We probably have a tenth of that."

The grant funding base at Wistar during the past several 
years had been eroding because of a number of factors. One 
of these was the departure of several senior investigators 
when Koprowski went to Jefferson. "Two program projects that 
he had involving the genetics of cancer and multiple 
sclerosis were not renewed," Rovera notes.

According to Rovera, Wistar scientists have been somewhat 
successful this year--better than expected, in fact--in 
securing new grants. "We've had to make adjustments; weUre 
increasing our emphasis in technology transfer, and being 
more demanding than in the past with upfront money and 
licensing fees. We canUt afford to wait for royalties. 
That's happening at other institutions, too."

--S.B.

(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : Gerontology Investigators Press An Ambitious Agenda

AU   : Karen Young Kreeger

TY   : NEWS

PG   : 1

Despite a substantial increase in the flow of financial 
support for gerontological research during the past several 
years, ambitious investigators of aging-associated phenomena 
continue to lament that their field is underfunded.

One such investigator is Denham Harman, a professor, 
emeritus, at the University of Nebraska College of Medicine 
in Omaha. The 78-year-old Harman for many years has argued 
that aging research deserves far more attention and 
financial support than it traditionally has 
received--especially because the United States population, 
according to demographic statistics, is rapidly getting 
older. "We need to spend more money on basic biomedical 
research on aging to go after its basic causes," he asserts.

Harman acknowledges his gratification at seeing significant 
funding gestures in the past year alone by such private 
sources as the Charles A. Dana Foundation in New York and 
the Glenn Foundation for Medical Research in Santa Barbara, 
Calif. And he was heartened most recently to hear of a $14.3 
million infusion--called the Paul Beeson Physician Faculty 
Scholars in Aging Program--into the gerontology research 
effort from a consortium of three private foundations.

Harman nevertheless in-sists that backing for gerontology 
studies remains inadequate for the important task facing 
researchers in the field. "One should not be deluded," he 
warns.

'A Shot In The Arm'
Last month's show of support through the Beeson program was 
announced by the initiative's three cosponsors: the John A. 
Hartford Foundation and the Commonwealth Fund--both New York-
based private philanthropies--and the Alliance for Aging 
Research, a Washington, D.C., private, nonprofit advocacy 
group that promotes research and policy attention to issues 
of aging.

The program's main purpose is to support young faculty 
members whose research relates to aging and to promote the 
study of aging across disciplines, especially in U.S. 
medical schools. The program is named as a tribute to 
gerontologist Paul Bruce Beeson, a professor of medicine and 
distinguished physician who is now retired from the 
University of Washington and the Veterans Administration 
Hospital, both located in Seattle.

Robert Butler, a geriatrician at the Mount Sinai Medical 
Center in New York and first director of the National 
Institute on Aging (NIA), calls the initiative a "shot in 
the arm" for "young people just on the crest of their 
careers."

Nevertheless, many observers are still calling for more 
funding. Over the last four years, three groups have 
separately proposed substantial increases for aging 
research. In 1990, the Pepper Commission TK, a U.S. 
bipartisan panel looking into comprehensive health care, 
recommended in its final report that the federal government 
move toward a funding level of $1 billion annually to 
finance "a research and development program aimed at 
preventing, delaying, and dealing with long-term illnesses 
and disabilities," including studies on such diseases and 
disorders as Alzheimer's, osteoporosis, and urinary 
incontinence. 

One year later, a committee from the Institute of Medicine 
echoed the Pepper Commission's recommendations. In its 
report, Extending Life, Enhancing Life: A National Research 
Agenda on Aging (Edmund T. Lonergan, ed., Washington, D.C., 
National Academy Press, 1991), the committee said that "a 
major investment in research on aging is needed urgently." 
This support should total "$913 million annually, a figure 
approaching the $1 billion recommended by the Pepper 
Commission," the report stated.

Most recently, a group of 72 nonprofit professional and 
advocacy groups called the 1994 Task Force for Aging 
Research Funding issued a statement urging Congress and the 
president to "enact legislation authorizing $1 billion a 
year for aging research at NIH, and $2 billion a year by the 
end of the decade."
And as Harman stated in a commentary in The Scientist (March 
19, 1990, page 18), "Funding for basic biomedical research 
on aging is meager. Only between $25 and $50 million is 
available per year, largely from the National Institute on 
Aging. In contrast, more than $2 billion is allocated each 
year for two major causes of death--cancer and 
atherosclerosis." In fiscal 1994, close to half of NIA's 
total $420 million budget was devoted to Alzheimer's 
research, with the other half going to fund sociological, 
behavioral, psychological, and basic biomedical research 
(see story on page 14.

Daniel Perry, executive director of the Alliance for Aging 
Research, agrees that there aren't enough funding sources to 
enable scientists to properly study the basic processes of 
aging. What the Beeson program will do, he says, "is bring a 
measure of high-quality science to bear on understanding the 
conditions that afflict older people. It will bring 
understanding the biology of aging into the forefront, and 
it will increase the sophistication of physicians in how to 
diagnose, treat, prevent, postpone, and rehabilitate chronic 
diseases in the elderly."

Harman adds that the program "will increase the visibility 
of aging" as an area of research, so that, he says, more 
attention will be paid by the science community to this 
underrepresented discipline.

Thirty In Three Years
"The goal for the Beeson program," says Perry, "is to have 
30 leaders [in aging research] in place at the end of three 
years. Only a handful of medical students have an exposure 
to geriatrics and gerontology, and these are not exposed to 
the best science on aging at that. [The Beeson initiative] 
is more than a step in the right direction." 

Each year, for three years, the program will select 10 
junior faculty members and provide each with a grant of up 
to $150,000. The application deadline for the first round of 
funding is December 15, with final decisions to be announced 
in April.

A national committee, headed by William N. Kelley, chief 
executive officer of the University of Pennsylvania's 
Medical Center and Health System and dean of Penn's School 
of Medicine in Philadelphia, will review applications and 
select the scholars. The American Federation for Aging 
Research (AFAR), a New York-based group that funds 
gerontology and geriatrics research, and the alliance will 
share administrative and technical support for the program. 

Creators of the program say its main emphasis is to attract 
top-flight young physician-scientists to commit their 
careers to research and training in aging. "The goal is to 
generate more well-prepared and leading junior faculty 
members," states Franklin Williams, scientific director at 
AFAR and a professor of medicine, emeritus, at the 
University of Rochester, New York, "and to give people who 
have promise the opportunity to have some really good free 
time for advancing their research and their careers.

"I think the bulk of the applicants will probably be at the 
interface of biomedical and clinical research." The fields 
that prospective recipients could be from is "really quite 
open," remarks Williams, who was NIA director from 1983 to 
1991. For example, he notes that the chosen scholars could 
just as likely have degrees in genetics, molecular biology, 
or physiology as in psychology or sociology. 

Each scholar will be paired with a senior faculty mentor 
from his or her home institution. The program will stage an 
annual meeting of scholars, mentors, and leaders in academic 
medicine to review and disseminate research findings of the 
scholars.

Sign Of The Times
Almost every cry for more resources for aging 
research --whether for work on its sociological aspects or its 
biomedical underpinnings-- cites the demographic shift in the 
U.S. population to an older majority as the impetus. "In 
this century, with the baby boom, we've established 
departments of pediatrics in every medical school in the 
country and only one in geriatrics [the Mount Sinai School 
of Medicine, New York]," says the alliance's Perry. "It is 
this unprecedented and profound shift to an older population 
that is forcing medical schools to adjust, but they haven't 
been forced quickly enough.

"Efforts by the federal government to induce training of 
faculty have been modest, at best. And what we now are 
seeing are these three nonprofit, philanthropic entities 
committing over $14 million to jump-start the field in the 
space of three years."

And, according to Perry and others in the field, there are 
other places--but not enough--that are starting to commit 
large amounts of money to support research in aging, in 
addition to NIA's commitment.

Non-NIA funding comes from such private groups as AFAR, the 
New York-based Brookdale Foundation Group, and the Sandoz 
Foundation for Gerontological Research in East Hanover, N.J. 
(see story on page 11). Still others like the Charles A. 
Dana Foundation of New York and the Buck Center for Research 
in Aging in Novato, Calif., mount their own research 
initiatives (see story on this page).


(The Scientist, Vol:8, #20, pg.1, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  WHERE GERONTOLOGISTS GET TOGETHER

TY   :  NEWS

PG   :  11

Following  are  some  of the  professional  societies  whose 
memberships include biological, social science, and clinical 
researchers in the fields of geriatrics and gerontology.

American Aging Association  (AAA)
American College of Clinical Gerontology (ACCG)
2129 Providence Ave.
Chester, Pa. 19013
(610) 874-7550
Fax: (610) 876-7715


Arthur K. Balin, executive director of AAA and president  of 
ACCG

American Geriatrics Society
770 Lexington Ave., Suite 300
New York, N.Y. 10021
(212) 308-1414
Fax: (212) 832-8646
Harvey Jay Cohen, president
Linda Hiddemen Barondess, executive vice president


Gerontological Society of America
1275 K St., N.W., Suite 350
Washington, D.C. 20005-4006
(202) 842-1275
Fax: (202) 842-1150
E-mail (via Bitnet): gsa@gwuvm
Linda K. George, president
Carol Schutz, executive director


Society for Neuroscience
11 Dupont Circle, N.W.
Suite 500
Washington, D.C. 20036
(202) 462-6688
Larry Squire, president
Nancy Beang, executive director



(The Scientist, Vol:8, #20, pg.11, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  ACCESSING AGING ASSETS

TY   :  NEWS

PG   :  11

Following  are some of the funding sources for  research  on 
aging,    including  basic  biomedical  research,   clinical 
research, and training:

American Federation for Aging Research (AFAR)

AFAR  Research Grants: awards of up to $40,000 for one  year 
to junior faculty for preliminary research projects.

Merck/AFAR  Fellowships in Geriatric Clinical  Pharmacology: 
awards  of $100,000 over two years, cosponsored by  Merck  & 
Co. Inc., Rahway, N.J., to train physicians.

Glenn Foundation/AFAR Scholarships in the Biology of Aging: 
awards of more than $5,000 for predoctoral students--both 
M.D. and Ph.D.--cosponsored by the Glenn Foundation, Santa 
Barbara, Calif., to conduct three-month  biomedical  
research projects.

For more information on these grants and the Beeson Scholars 
in  Aging  Program, contact Odette van  der  Willik,  grants 
manager,  AFAR, 1414 Ave. of the Americas, 18th  Floor,  New 
York, N.Y. 10019; (212) 752-2327. Fax: (212) 832-2298.
Brookdale Foundation Group (BFG)

Grants of various amounts in the fields of gerontology and 
geriatrics. The foundation requests that prospective 
applicants submit a one-page letter explaining a project's 
concept. These are reviewed at monthly board meetings, 
whereupon some applicants are invited to submit a full 
proposal.


For more information, contact Nora O'Brien, BFG, 126 E. 56th 
St., New York, N.Y. 10022.
Sandoz Foundation for
Gerontological Research

Grants of up to $35,000 for one year in the areas of 
biology, pharmacology, immunology, geriatric medicine, 
psychogeriatrics, and epidemiology. The foundation is 
affiliated with the pharmaceutical company Sandoz Ltd. of 
Basel, Switzerland.

For more information, contact Agnes Sisto, Sandoz 
Foundation, 59 Route 10, East Hanover, N.J. 07936-1080; 
(201) 503-8544. Fax: (201) 503-7185.

--K.Y.K.



(The Scientist, Vol:8, #20, pg.11, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  24th Annual Neuroscience Meeting To Attract A 
        Variety Of Specialists

AU   :  Neeraja Sankaran

TY   :  NEWS

PG   :  3

The 24th annual meeting of the Washington, D.C.-based 
Society for Neuroscience, to be held November 13 to 18 in 
Miami Beach, Fla., is likely to be the largest conference in 
the association's history, according to society officials. 
Almost 15,000 of the society's 23,000 members are expected 
to attend. The event will offer a mixed bag of topics in 
about 17 symposia and 15 lectures, in addition to various 
workshops, courses, panel discussions, and more than 10,000 
posters and slides.

"Our meeting is unique in that it draws a large proportion 
of society members," remarks Larry Squire, the current 
president as well as a professor of psychiatry and 
neuroscience at the University of California, San Diego, and 
a staff research scientist at the San Diego Veterans Affairs 
Medical Center (VAMC). "It would be hard to pick any special 
themes of interest--we have everything from molecular and 
cellular research to cognitive studies." (See accompanying 
list for a sampling of topics.) 

Squire's own area of expertise--the biology of memory--is 
the subject of a special presidential symposium, and by 
itself demonstrates the scope of the neurosciences. The two-
hour session will include discussions on genetic, 
regulatory, and chemical aspects of memory. This year the 
symposium commemorates Walle J. Nauta, a noted 
neuroscientist from Harvard University who died earlier this 
year, shortly after being named the winner of the National 
Academy of Sciences Award in the Neurosciences (N. Sankaran, 
The Scientist, April 18, 1994, page 1). 

In addition to the symposium, there will be three special 
presidential lectures, including one on the evolution of the 
brain by Harvard University evolutionary biologist Stephen 
Jay Gould. Scheduled for 11:15 a.m. on Wednesday, November 
16, this lecture will be simultaneously videocast to a 
second room to accommodate attendees unable to fit in the 
lecture theater.

Death In Development
A particularly "hot" area of neuroscience research nowadays, 
say many scientists, is developmental neurobiology--the 
study of how nerve cells differentiate in the embryo and 
achieve their final form. Several sessions at the meeting, 
including one of the presidential lectures, will discuss 
advances in this subdiscipline. The featured speaker, H. 
Robert Horvitz, a professor of biology and a Howard Hughes 
Medical Institute investigator at the Massachusetts 
Institute of Technology, will discuss the role of programmed 
cell death--also called apoptosis--in development.

"A great number of cells die in the course of normal 
development; the question is why and how," says Horvitz. His 
studies on the phenomenon in the nematode Caenorhabditis 
elegans revealed that the genes and proteins involved in the 
programmed death of nerve cells in this organism were 
similar to certain genes and proteins found in humans (J. 
Yuan et al., Cell, 75:641-52, 1993).

"It is [my] hypothesis that the pathway of programmed cell 
death is highly conserved between nematodes and humans," he 
adds. Horvitz will also talk about the applications of his 
work in understanding such neurodegenerative diseases as 
Parkinson's and Alzheimer's.

Attention On Animals
A regular feature at the society's annual conferences has 
been a forum or panel discussion organized by its Committee 
on Animals in Research. The subject is particularly 
important to the society because of the significant amount 
of neuroscience research that uses animals as experimental 
models, according to committee chairman Stuart Zola-Morgan, 
a professor of psychiatry at UC-San Diego and a research 
scientist at the San Diego VAMC. 

This year the discussions will focus on two issues. One is 
public opinion on the use of animals in research, including 
polling data showing how men's and women's views vary on 
this subject. The other issue is a recent strategy 
implemented by animal rights groups to promote their cause, 
whereby they align themselves with women's groups, targeting 
perceived parallels between the use and treatment of animals 
in research and the exploitation of women. Panelists include 
Mary Woolley, president of Research!America, a research-
advocacy group based in Alexandria, Va.; Sandra Bressler, 
director of scientific and educational activities at the 
California Medical Association; and Andrea Zardetto-Smith, a 
professor of psychology at the University of Iowa, Iowa 
City. Zola-Morgan will act as the moderator for the session.

Animal research will also be touched on during a workshop 
for high school students to be held at the conference. "We 
feel an obligation to explain the importance of animal 
[models] in research, particularly with the resurgence of 
animal rights concerns in schools," says Squire.

Capitol Neuroscience
A special workshop entitled "Educating your legislators or 
suffering the consequences" is scheduled this year, to 
introduce the society's members to the process of law-making 
and the dispensation of research funds by Congress. "The 
workshop will talk about how Congress deals with various 
scientific and funding issues, and how scientists can affect 
those decisions," says workshop presenter Frankie Trull, 
vice president for government affairs at Capitol Associates 
Inc., a government-relations consulting firm in Washington, 
D.C.

"What kind of funding goes to a particular type of research 
depends on the importance given to it by Congress," she 
notes, "and the best option for a scientist is to speak 
directly to Congress and arm them with relevant knowledge so 
that they can make informed decisions. 

"This workshop will deal with some of the dos and don'ts--
don't argue, do express yourself clearly, and do follow up," 
advises Trull.

For more information on the society's meeting, contact 
Joseph Carey or Julie Ziegler at the Society for 
Neuroscience, 11 Dupont Circle, N.W., Suite 500, Washington, 
D.C. 20036; (202) 462-6688. A computerized Program Search 
System listing the title, author and affiliation for each 
abstract along with the date and time of presentation can be 
obtained ahead of time, for a fee, along with registration. 


(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  AT A GLANCE (SOCIETY FOR NEUROSCIENCE - PROGRAM FOR
        THE 24TH ANNUAL MEETING) 

TY   :  NEWS

PG   :  3

The 24th annual meeting of the Society for Neuroscience will 
run from Sunday, November 13 to Friday, November 18, at the 
Miami Beach Convention Center in Miami Beach, Fla. Following 
is a list of the planned symposia and lectures scheduled du-
ing the conference:

                    Sunday, November 13

Decade of the Brain Lecture, 8:00 p.m.-9:00 p.m.: 
"Consolidating the gains in brain"



                    Monday, November 14

Presidential Special Lecture, 10:00 a.m.-11:00 a.m.: "Cell 
death in development and disease"
History of Neuroscience Lecture, 1:00 p.m.-2:00 p.m.: 
"Evolving concepts of function of the neocortex"


Special Lectures
11:15 a.m.-12:15 p.m.: "Molecular studies of physiological 
functions of glutamate receptor"

4:15 p.m.-5:15 p.m.: "The molecular biology and biophysics 
of prions causing CNS degeneration"

Symposia
8:00 a.m.: "Molecular mechanisms of axon guidance"; "Genes 
with triplet repeats in neuropsychic illness"

1:00 p.m.: "Neuroscience implications of inborn errors of 
metabolism"; "Mo-lecular mechanisms of controlling K+ 
channel diversity and distribution in the nervous system"

Presidential Symposium
8:00 p.m.-10:00 p.m.: "The biology 
of memory: From synapses to systems"


                    Tuesday, November 15

Presidential Special Lecture, 4:15 p.m.-5:15 p.m.: 
"Transient and enduring effects of experience: Functional 
studies of the visual and motor cortex"
Grass Foundation Lecture, 8:00 p.m.-9:00 p.m.: "In your ear: 
Transduction, tuning, and transmission by hair cells"

Special Lectures
11:15 a.m.-12:15 p.m.: "Membrane receptors and ion channels: 
Electron crystallographic studies of their design and action"

1:00 p.m.-2:00 p.m.: "Evolutionary origins of neocortex: 
Reshuffling neurometers to make a new deck?"

Symposia
8:00 a.m.: "New approaches to understanding dendrites";  
"The amygdala: From circuits and synapses to emotional 
memory"

1:00 p.m.: "Cytokines and neural development"; "Autonomic 
integration in the control of food intake"


                   Wednesday, November 16

Presidential Special Lecture, 11:15 a.m.-12:15 p.m.: 
"Adaptation and exaptation in the evolution of the human 
brain"

Special Lectures
1:00 p.m.-2:00 p.m.: "The role of local signals in the 
control of CNS neuronal development"

4:15 p.m.-5:15 p.m.: "Potassium channels"

Symposia
8:00 a.m.: "Early development and molecular plasticity in 
the mouse brain"; "Molecular plasticity in epilepsy and 
ischemia"

1:00 p.m.: 8:00 a.m.: "Early development and molecular 
plasticity in 8:00 a.m.: "Early development and molecular 
plasticity in 8:00 a.m.: "Early development and molecular 
plasticity in Toward a neurobiology of visual 
consciousness"; "Developmental   control  of  electrical  
excitability"


                   Thursday, November 17

Warner-Lambert Lecture, 11:15 a.m.-12:15 p.m.: "Ins and outs 
of programmed cell death"

Special Lectures
1:00 p.m.-2:00 p.m.: "Brain map for movement"
4:15 p.m.-5:15 p.m.: "Muscimol, memory, and motivation in 
the basal ganglia"

Symposia
8:00 a.m.: "Structure, function, and regulation of glutamate 
receptors"; "General anesthetic effects on somatomotor 
processing"

1:00 p.m.: "The cell biology of secretion vesicles"; 
"Neuropeptide regulation of brain development: From cells to 
animals"



                    Friday, November 18

Symposium
8:00 a.m.: "Neural coding of visual space: Visual mechanisms 
of multimodal integration"


(The Scientist, Vol:8, #20, pg.3, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


                          NOTEBOOK

------------------------------------------------------------
TI   : Calling All Taxonomists   

TY   : NEWS (NOTEBOOK)

PG   : 4

The National Science Foundation's division of environmental 
biology recently announced a special grant competition--
called Partnerships for Enhancing Expertise in Taxonomy--to 
stimulate taxonomic research and training. The initiative is 
spurred by concern over dwindling numbers of younger 
scientists taking up taxonomy--the study of the general 
principles of scientific classification--and systematics and 
the limited knowledge that exists about thousands of 
species. Specifically, NSF is seeking applicants to submit 
ideas on how to train future generations of taxonomists and 
how to translate current expertise into electronic databases 
to broaden accessibility of taxonomic data, as well as 
research proj-ects on taxonomy and evolution, especially of 
little-known species. The deadline for applications is March 
1. For more information, contact the division of 
environmental biology at (703) 306-1480. E-mail: 
sysrev@nsf.gov.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  


NXT:

------------------------------------------------------------
TI   :  For Young Experimenters   

TY   :  NEWS (NOTEBOOK)

PG   :  4

Science students and teachers seeking ideas for classroom 
science projects or contests can now turn to the Science 
Experiments and Proj-ects Index. Written and edited by the 
staff of the Columbus (Ohio) Metropolitan Library, the 
source describes 8,400 hands-on, interactive experiments and 
project ideas. The book is published by Fort Atkinson, Wis.-
based Highsmith Press, (800) 558-2110 or (414) 563-9571.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
  
NXT:

------------------------------------------------------------
TI   : Clearing The Air   

TY   : NEWS (NOTEBOOK)

PG   : 4

Beginning this month, the National Institute of 
Environmental Health Sciences (NIEHS) in Research Triangle 
Park, N.C., is establishing a clearinghouse to provide 
information or referrals for questions about health and the 
environment. Users can call EnviroHealth toll-free at (800) 
NIEHS94 (643-4794) to receive information about NIEHS 
research and training programs as well as referrals to other 
NIH offices; clearinghouses; toll-free numbers; federal, 
state, and local agencies; and information sources. 


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

NXT:

------------------------------------------------------------
TI   : In The Name Of Cheeses   

TY   : NEWS (NOTEBOOK)

PG   : 4


In keeping with the age-old link between fermentation and 
religious orders--some of the best wines hail from 
monasteries--Sister Noella Marcellino, a member of the 
Benedictine Abbey of Regina Laudis in Bethlehem, Conn., and 
a graduate student in microbiology at the University of 
Connecticut in Storrs, is conducting research on the 
microbes that flourish in naturally ripened cheeses and how 
those organisms impart their distinctive flavors and aromas. 
Her work gained her a Fulbright grant to travel to France 
for nine months to study the microbes in such specialty 
cheeses as Camembert and St. Nectaire, which are produced in 
the Auvergne region. Sister Noella's microbial studies will 
be conducted in a laboratory in Burgundy, where many 
traditional cheeses are produced. In addition, she will 
investigate traditional methods of ripening cheeses in 
caves.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

NXT:

------------------------------------------------------------
TI   : Natural History Online   

TY   : NEWS (NOTEBOOK)

PG   : 4


Now available free of charge over the Internet is the full 
catalog of Yale University's Peabody Museum of Natural 
History. With more than a million entries, the catalog 
offers information on the New Haven, Conn., collection's 
nearly 11 million specimens, including some of the most 
scientifically significant dinosaur fossils in the world. To 
access the Peabody database, use the gopher command to 
connect to "gopher.peabody.yale.edu" at port number 70. For 
more information, contact Peabody's Lawrence Gall at 
lawrence.gall@yale.edu.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

NXT:

------------------------------------------------------------
TI   :  A Helping Handbook   

TY   :  NEWS (NOTEBOOK)

PG   :  4


The Grant Application Writer's Handbook, by Liane Reif-
Lehrer--a former Harvard Medical School researcher and 
National Institutes of Health study section member--was 
issued earlier this month by Boston-based Jones and Bartlett 
Publishers. The book covers both the psychology and the 
mechanics of proposal writing, taking readers through the 
steps of planning, outlining, drafting, revising, and 
finishing an application. For more information, contact 
Jones and Bartlett Publishers, One Exeter Plaza, Boston, 
Mass. 02116; (800) 832-0034. Fax: (617) 859-7675.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

NXT:

------------------------------------------------------------
TI   :  Cool Comfort   

TY   :  NEWS (NOTEBOOK)

PG   :  4

The Multiple Sclerosis Association of America (MSAA) and the 
National Aeronautics and Space Administration (NASA) have 
signed a "Memorandum of Understanding" that expands their 
collaborative efforts to further develop a spin-off NASA 
technology--known as microclimate cooling--used to produce 
lightweight vests, dubbed "cool suits," worn by MS patients 
who suffer from heat stress. Those donning the suit have 
experienced improvements in their speech as well as relief 
from fatigue and other symptoms associated with the disease, 
according to MSAA. For more information about microclimate 
cooling and other MSAA services, call (800) 833-4MSA.


(The Scientist, Vol:8, #20, pg.4, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


                             OPINION

------------------------------------------------------------
TI   :  ARTHUR CAPLAN DISCUSSES ISSUES FACING THE GROWING FIELD 
        OF BIOETHICS

AU   :  FRANKLIN HOKE
        KAREN YOUNG KREEGER

TY   :  OPINION

PG   :  12

Editor's Note: 

In May 1994, preeminent bioethicist Arthur Caplan moved his base 
of operations from the University of Minnesota, Minneapolis, 
where he had established the Center for Biomedical Ethics, to the 
University of Pennsylvania in Philadelphia. There, he launched 
the Center for Bioethics, hoping to expand the purview of his 
activities through association with the extensive biomedical 
research community at Penn and in the greater Philadelphia area--
initially, for example, sharing temporary offices with the 
university's Institute for Human Gene Therapy. The 44-year-old 
Caplan, who is the author of dozens of scholarly papers, also 
strives to make critical bioethical debates comprehensible to the 
public, most recently in his book Moral Matters: Ethical Issues 
in Medicine and the Life Sciences (New York, John Wiley & Sons 
Inc., 1995). As the fall semester got under way at Penn last 
month, Caplan met with Senior Editor Franklin Hoke and Associate 
Editor Karen Young Kreeger of The Scientist for a wide-ranging 
discussion of his views and plans. Following is an edited 
presentation of the interview.



Q  Why did you decide to move to Penn?
A  Well, Minnesota--the medical school in particular--had 
oriented itself very strongly toward some high-tech forms of 
transplantation, like bone marrow, while Penn has this 
emerging gene therapy, testing, and screening interest and 
was pulling together a group of people to do molecular 
medicine. So, intellectually, that was a big draw for me. 
Also, Minnesota didn't have much of a group doing health 
economics and policy. But Wharton [Penn's business school] 
does, and that was another attraction.


Q  Is Philadelphia a good place to practice your discipline?
A  Surprisingly, Philadelphia has not been a major presence 
on the bioethics front, although it has all these medical 
schools and hospitals--Fox Chase [Cancer Center], the 
[American] College of Physicians, and so forth--and it has a 
lot of pharmaceutical companies. So it looked like a place 
where one could go and make something happen.

Q   What are some of the new things you hope to do here?
A   We'll definitely be moving into the genetics area, and 
we'll try to work with Penn's very good history and 
sociology of science units in the areas of eugenics, 
heredity, and human nature theories. So, we'll go into 
everything from the most practical questions--such as 
insurance implications--to lofty theoretical matters [like] 
what's a disease and whether medicine has, as its mission, 
to improve or enhance as well as repair things.


Q  What bioethical areas are you most concerned about?
A  I'm especially interested in the rationing of health 
care, both at the bedside and in terms of who gets access to 
high-tech treatment--things like that. I'm also interested 
in how to divvy up the health-care budget for the readers of 
The Scientist. Should we spend more money on research or put 
some kind of embolism in the research pipeline to slow down 
cost? And what is the proper incentive system for technology 
transfer?

And then there are end-of-life care decisions--termination-
of-treatment- and assistance-in-dying- type matters. And 
questions of research on children--do we have a system that 
protects their interests? If I tell you that your daughter 
is sick and we can lop off half her pancreas to try to save 
her, and you ask, "What are my options?" and I say, "None," 
and you say, "Okay, you have my consent"--is that good 
enough? Does informed consent mean anything in the context 
of very sick kids? My hunch is that it doesn't--and then how 
do we replace or supplement informed consent?

Q  Do you have a particular technique for exploring this 
   sort of issue?
A  When I was in Minnesota, our center had a reputation for 
trying to integrate descriptive empirical work with 
prescriptive things, and I think we will do that at Penn, 
too. Before I tell people what to do, I'd like to know sort 
of what they're doing first. It may turn out that what 
they're doing is what they're supposed to do, and it may 
waste a lot of time to fish around for what they ought to do 
if you don't know what they're doing already. I have the 
feeling that most people don't read the informed consent 
form, so shaping it into a finely honed document is probably 
not useful for a lot of people.

On the other hand, there may be issues coming up from the 
subjects that are not captured on the informed consent form. 
But if you don't debrief them you'll never know that they 
were mad about this or that nobody ever told them, for 
example, that they were going to be nauseated after a 
certain test. That's the place where I think we can do some 
interesting empirical examination.


Q  What are the origins of bioethics?
A  Well, bioethics more or less started in response to 
scandals over such things as the Tuskegee Study, where 
people were deceived about getting treated for their 
syphilis and not told that they had syphilis; or the 
Brooklyn Jewish Chronic Disease Study, where demented, 
terminally ill elderly patients were given live cancer cells 
with no one's consent; or the Texas Contraceptive Trial, 
where women were given placebos to test the effectiveness of 
birth control pills. In response to these early T60s 
scandals, bioethics shows up in the late T60s and says, 
"We're going to fix this."

Q  You say that "descriptive empirical work" is important to 
   you. Is that approach new to bioethics?
A  Yes, it's definitely new. The scope could be anything 
from what happens to someone who's signing up as a subject 
for a research project all the way out to how a doctor 
decides who gets access to a CAT scan. You just come in and 
interview a dozen or so people at length, almost like a 
journalist would, and sort of follow them over time and 
paint the picture. Now, I'm not sure that anybody can say, 
statistically, what number of case studies is enough to 
generalize out to. But we are not interested in 
generalizing--we're not interested in saying we understand 
the whole population. Our empirical approach lets us pick up 
what the problems are. I don't care if only one person 
encounters a problem or 10 do; even if it's a problem of one 
person, it's still a problem.

Q  Does the use of an empirical approach help make bioethics 
   a science?
A  The goals of ethics research aren't the same as those of 
scientific study. The scientist may want to know how common 
a problem is or, if you change variables, will it go away. I 
am more interested in finding out simply what problems exist 
out there. I sometimes think of this as "moral systematics." 
It's like doing taxonomy. I talk this way in part because I 
grew up as an evolutionary biologist, but it seems to me 
that I'm closer to moral ethology in a sense of how an 
animal behaviorist might study what's going on out in nature 
and look for problem identification and classification. 

The other type of empirical work involves what I could call 
historical-sociological studies. We might, for example, be 
looking at genetics as part of a historical review of what 
happened in eugenics. Does anybody really know what the 
Nazis did? Has anyone really looked at their arguments about 
why they did it? And do we really understand enough about 
the German or American experience with eugenics? I am 
interested in looking at old laws, old policies, old ethics 
arguments. What did the scientist in Germany say about 
working in the camps?

Q  And what are the present-day applications?
A  I would call that an analogical examination. Does the 
analogy hold up? Is it tight enough? Do you see the same 
arguments today that you saw in the camps? Are the empirical 
circumstances different from what they are today? We want to 
see if the analogies, metaphors, and similes hold up in 
relation to current issues. If someone compares abortion to 
the Holocaust, for example, is that because fetuses are a 
target of government policies intended to eliminate inferior 
genetic human beings? If they mean that what the Germans did 
in their genocidal activities is like what we have as a 
policy about terminating pregnancies, we know, through our 
analogical examination, that this comparison is not correct. 
So, that argument against abortion falls away--even though 
you still  might  think  there  must  be  moral  standing 
for the fetus.

I am interested in knowing if the ethnic arguments from the 
past are convergent, divergent, homologous, or analogous so 
as to understand whether I'm looking at a real phenomenon or 
an accidental similarity. It's important to do this; if you 
just start from your armchair to come up with ethical 
theories, you may arrive at something very interesting, but 
something close to what a mathematician does, or a math 
modeler.

Q  Like people who would model an ecosystem without ever    
   stepping into nature?
A  Right, they don't step in the lake, and they don't care 
to. But that's not my bent--my bent is to step into the 
lake, to be sort of a moral naturalist and look for 
phenomena. That's why I like being around the hospital; 
that's why I like tying in to the people who do the work 
with social science tools.

Q  What influences led you to bioethics?
A  Actually, those go all the way back to my early days, at 
Columbia University, where as a graduate student I spent a 
year at its medical school. So, I got interested in health-
care ethics by hanging around the hospital and the clinic. 
That's how the idea of using the hospital as the laboratory 
began, and out of that came my strong belief that if you're 
going to be credible to doctors and scientists, you must 
understand their world, their limits, their time 
constraints, the financing that they're up against, and how 
they talk.

Q  You mean that before laying down ethical laws to people,    
   you have to understand what really influences what they can    
   and can't do?
A  You shouldn't set your morality beyond what's possible. 
Sometimes, a limit on morality is human nature, fallibility, 
mistakes, a certain amount of egoism and greed. In order to 
take that into account, you don't want to pretend that it's 
a world of saints with infinite resources and unlimited time 
and that we should all act in this way.

Q Returning to the subject of gene therapy, will there be an 
  organizational relationship between your group and Penn's 
  institute?
A The tie is really through me. I have an appointment in the 
department of cellular and molecular engineering, as a 
professor. I'm written into many of their grants, to sort of 
watch that the gene therapy protocols meet the requirements 
of the human subjects' study. So, it's not a center-to-
center marriage; it's more of a faculty-to-faculty marriage.

Q But doesn't the National Institutes of Health's 
Recombinant DNA Activities Committee [RAC] already have a 
very developed pattern of thinking about the ramifications 
of gene therapy before the protocols are in place?

A  To tell you the truth, while I'm not against having a 
national RAC, the NIH committee may have outlived its 
usefulness at this point in time in terms of the level of 
review necessary for protocols relative to the risks. Most 
of the people who are on RAC do gene therapy; they want to 
do it right--but they also want to do it. I'd like to think 
we can come at gene therapy at Penn with a little bit more 
of an objective eye in terms of saying, "We don't care 
whether it proceeds or not, we're just interested in looking 
at the ethical issues."

Q What type of issues?
A  Remember the incident in California involving gene 
therapy for brain cancer? Basically, RAC had all these rules 
about what you had to do to get gene therapy, and then they 
threw them out the window when a woman who knew a senator 
made an appeal. That's the kind of thing we'd like to look 
at and say, "Don't let politics override the system." It's 
not a good idea. It's not compassionate, necessarily, to 
grant a terminally ill person access to a gene therapy 
intervention that's not on a protocol. But it was hard for 
them to say it, because they were getting influenced by 
national politics. It's easier for us, at Penn, to say it; 
we're not accountable to NIH or Congress or anything like 
that.

Q  Where does the Human Genome Project [HGP] office for 
   ethical, legal, and social implications [ELSI] fit into the 
   spectrum?
A  ELSI is interesting, because it is the only area of NIH 
that has been set up with a specific allocation of money to 
look at ethical issues. And that's good. On the other hand, 
I think that they have spent a lot of their time committing 
themselves on issues identified by people who weren't in 
close contact with what was going on in genetics. I will 
tell you, flat out: Bioethics, in my view, is weak in 
genetics. There are not a lot of philosophers, theologians, 
and lawyers who know anything about it--I mean anything! I'm 
talking about, do they know a chromosome from a gene from an 
aardvark? It's an area where bioethics has not intersected 
well with the scientific community.

Most of the people who come into bioethics have much more of 
a clinical focus than a basic science focus. It's hurt the 
ELSI program in a lot of ways. And I lobbied [HGP official] 
Francis Collins pretty hard about this, saying I think it's 
time we sort of get past the declarations of morality into 
the nitty-gritty of it.

Q  Don't you think a lot of researchers fear that bioethical 
   influences will impose too many constraints on their work?
A  There's a common equation between ethics and saying no. 
But my argument is that sometimes the job of ethics is to 
say yes. I'll give you an example. I'm working on an article 
that you'll probably hear about because people will be 
streaming down the street to lynch me. It's called "What's 
wrong with eugenics?" or "What's wrong with germ-line 
engineering?" I happen to think the answer to both those 
questions is, nothing, intrinsically. The question of 
whether I should be able to pick blue eyes or brown or tall 
people or short--I don't think there's anything wrong with 
that, fundamentally.

Q  It's a matter, then, of when to say yes or no?
A  There may be reasons we ought not practice eugenics that 
have to do with politics and the fear that some people may 
go down the slippery slope, as the Germans did. If you're 
worried about coercion--and the Chinese force that kind of 
stuff--you oppose it. But if it's a pure question of, if I 
turned on gene X and made my child grow another two inches, 
and there was no risk to the kid, and nobody made me do it, 
I don't see the problem. You know, you make children play 
the piano an hour a day, seven days a week, for 10 years, 
and you understand that you've imposed a lot of views on 
them of what they should become. You start to think about 
it, it's like, cripes, making him two inches taller may be 
the least of his worries. It's more whether you make him 
study in the yeshiva seven hours a day after school. That's 
imposing a much more cognitive type of thing on a kid.

So, I don't buy the idea that the mission of ethics is to 
say no or go slow or don't do it. That's an oversimplified 
view. My idea is, sometimes it means yes and go faster and 
you ought to do it, so why aren't you doing it? It seems to 
me if you could do germ-line therapy to eliminate killer 
diseases, not only should you do it, you must do it. If you 
could eliminate sickle cell or Tay-Sachs by a safe form of 
altering sperm or egg or embryo, I think it's morally 
incumbent upon you to do it. 

Q  In connection with AIDS research, what are some 
   significant bioethical considerations--for instance, those 
   connected with arriving at an adequate experimental protocol 
   that could be used by AIDS researchers in developing a live 
   attenuated-virus vaccine?

A  If it looked like some lines of vaccine research were 
promising but were limited by the absence of an animal 
model, then I'd be surprised if we wouldn't take the proper 
steps. Specifically, we might try vaccines on people who are 
brain dead and who are about to have their life support 
disconnected. We might decide that we could add a provision 
to their living will or their transplant donor card that 
said, "You could use me for a limited period of time to test 
a vaccine." You might get some information that would make 
you feel more secure before you went to a living human. It 
seems, as a reasonable place to turn, you may find 
individuals who are terminally ill who want to volunteer as 
human models.

The other population that's likely to be morally appropriate 
for this are those groups in high-risk categories whose 
behavior can't be changed. Of course, there's always an 
obli-gation to try to get somebody to stop doing what puts 
them at risk. But there's some truth in the idea that if you 
go to a group of, let's say, sex workers in Thailand and 
say, "You've got to get out of this business," and you come 
back in two months and say, "You've got to get out of this 
business and you've got to use condoms," and they're still 
working there, that probably is the population  you  want  
to  go  to  for  your  vaccine trials. You've done 
everything you can, and you continue to do it throughout 
your entire study, to get them out of the business, even if 
it hurts the study. But if you know they're going to do it, 
and you're not going to get them out, that's where you go 
for vaccine development.

Q  You're aware how radical these ideas are.
A  The intuitive thing is to say, "Well, you can't do this 
and, I don't know, we just have no vaccines." I think the 
right answer is, "Well, let's think more carefully about how 
could we do this and feel comfortable that we haven't hurt 
anybody or made them worse off." We've got an epidemic, and 
we've got to do something.

Q  Another area of considerable debate is technology 
   transfer between universities and industry. What are the 
   ethical considerations that must be addressed in the push to 
   commercialize research results from academic labs?

A  There are really serious issues there. At one level, it's 
been a fight about conflict of interest and disclosure, and 
NIH is still struggling to come out with guidelines. They 
basically rely on disclosure, the assumption being if you 
tell people that you have this technology-transfer 
arrangement, it'll be okay because they'll know how to read 
your data or interpret what you say about whatever gizmo or 
drug it is that you're working on. The other argument is, 
you have to restrict how much scientists and doctors can 
work outside the university. A day a week is a common rule 
about how much outside work you can do. I think those 
provisions are nice, but they're not getting down to the 
real nitty-gritty questions. What's the impact of 
privatization on basic vs. applied research?

If a university is supposed to be a place that pursues basic 
research more than a company would do, and yet companies 
underwrite more and more research or commercialization, will 
we find ourselves richer in the short run but poorer in the 
long run because we spent so much time developing this 
generation of technology that we don't have anybody working 
on the basic science for the next one? Also, what happens to 
the graduate students who work in the labs of people who are 
involved in corporate ventures? They can't do their thesis 
because they've got to do work for a guy who's making money, 
and they're a kind of cheap labor for that person.

But if a company has a gizmo that you can't get at the 
school lab and if the company provides in-kind services 
worth hundreds of thousands of dollars that you could never 
get from your school, is that enough to pull your lab in an 
unacceptable direction? Remember, this is basically a subtle 
kind of a bribe to get you to do things. There are many, 
many interesting questions about how commercialization and 
for-profit motives are shaping biological and medical 
science.

What you may need to do is teach that senior professor that 
you don't push the graduate students around, and you can't 
exploit them to do your work on the side, and you're not 
going to get promoted for how many inventions you make. 
You're still going to get promoted on the basis of how many 
students put out good papers from this lab.

Q  Why does bioethics seem to be such a hot area now?
A  I think bioethics is especially of interest these days 
for a couple of reasons. One, the cost of health care, the 
cost of medical research, the cost of certain medical 
innovation is up. So people always take an interest in what 
they're getting for all this money. There is still a kind of 
cornucopia of new technologies. Investments in the T50s and 
T60s are now paying off with different kinds of devices, so 
there are a lot of technology-driven questions: turning it 
on, turning it off, when to use it, who gets it, that sort 
of stuff.

I think bioethics is of interest because we don't have any 
other place to turn. To some extent, our religious and 
political leaders fail us in terms of understanding enough 
about science to allow us to talk about what's going on. And 
to some extent, science has taken on the guise of secular 
religion. You may say that people go to the doctor with the 
same hopes that they once brought to the minister: Save me, 
prepare me, redeem me. In the Middle Ages, you used to see 
cathedrals; now, what you see are towering medical centers 
dominating the landscape. 

Q  In your new book, Moral Matters, you make a strong case 
   for the enduring value of ethical thinking.A  I think a lot of scientists have the view that ethics is 
subjective--that it's all a lot of talking and yakking and 
blather that amounts to nothing--and that science is 
concrete. A computer scientist said he once asked the 
faculty at [the Massachusetts Institute of Technology], "How 
many people think that 1,000 years from now people will 
believe that the speed of light is 186,000 miles per 
second?" Half the faculty raised their hands. Then he asked, 
"How many people will believe 1,000 years from now that the 
road to hell is paved with good intentions?" Everybody 
raised their hands.

The point is that ethics is more concrete in the long run 
than the physical stuff, which is contingent. And I believe 
that.                                      


(The Scientist, Vol:8, #20, pg.12, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


                           COMMENTARY

------------------------------------------------------------
TI   :  A Tribute To Robert K. Merton
        On Receiving The National Medal Of Science

AU   :  EUGENE GARFIELD

TY   :  OPINION (COMMENTARY)

PG   :  13

Last April 28, I had the pleasure of hearing my good friend 
Robert Merton, the eminent sociologist and historian of science, 
deliver the American Council of Learned Societies' 1994 Haskins 
Lecture. The talk, presented at the American Philosophical 
Society in Philadelphia, centered on Bob's "life of learning"--
the subject addressed each year by a notable "humanist" invited 
by ACLS to deliver the prestigious lecture.

As Bob spoke about his boyhood in Philadelphia, his coming 
of age as a young Harvard intellectual, and the factors that 
fueled his preoccupation with the history of science and the 
behavior of scientists, I was touched by a variety of 
emotions. As often during the 30 years or so that I've known 
him, I was fascinated by his capacious intellect and his 
knack for originating concepts and expressing them in clear, 
evocative terms. (Whether writing or speaking, he knows how 
to hold his audience.) I was also proud, since he has worked 
closely with me as mentor, colleague, and coauthor. I must 
confess as well to a certain amount of civic pride, since 
The Scientist--like Bob Merton--has its roots in the City of 
Brotherly Love.

ACLS couldn't have made a more appropriate selection for the 
1994 Haskins lectureship. That was also my reaction to the 
recent news that Bob was among the eight individuals 
selected by President Clinton to receive the 1994 National 
Medal of Science. As we reported in our coverage of the 
event (N. Sankaran, "Eight To Receive National Medals Of 
Science," The Scientist, Oct. 3, 1994, page 1), he is the 
first sociologist to be so honored. Evidently, I am not 
alone in holding my good friend in high regard. Indeed, as I 
listened to his lecture, the thought ran through my mind 
that, if there were a Nobel Prize category for the sociology 
of science, Bob Merton would have to be a recipient.

I am pleased by the honors this Nobel-class thinker is 
receiving, as the international community of historians and 
sociologists of science must also be--not that there has 
been a dearth of recognition of this great mentor, now in 
the 85th year of an incredibly productive life.

His record is indeed impressive. His masterpiece of 
theoretical sociology, Social Theory and Social Structure 
(New York, The Free Press, 1949; enlarged editions, 1957, 
1968) has gone through 30 printings and ranks among the most 
cited books in the social sciences. Two other seminal works, 
The Sociology of Science: Theoretical and Empirical 
Investigations (University of Chicago Press, 1973) and On 
the Shoulders of Giants: A Shandean Postscript (University 
of Chicago Press, 3d ed., 1993), should be, in my opinion, 
required reading for all scientists.

While treating matters of serious consequence, Bob Merton 
maintains a sense of irony, self-deprecating humor, and a 
fondness for wordplay that has seasoned and humanized his 
writings. In a recent note to me, he commented on a close-
to-hand example of a phenomenon he first described in an 
article titled "The Matthew effect in science; the reward 
and communication systems of science" (Science, 159:56-63, 
1968). His neologism, "the Matthew effect"--named after a 
passage in the Gospel of St. Matthew--holds that patterns of 
biased peer recognition of authors of collaborative papers 
are often "skewed in favor of the more established 
scientist." 

And so it is, he wryly observed, that papers written jointly 
by him and his colleague, companion, and wife, sociologist 
Harriet Zuckerman--now vice president of the Mellon 
Foundation--were often mis-cited as having been written by 
"Merton and Zuckerman"--even though, as he noted, "Harriet 
is explicitly designated as the first author."

He went on: "It is ironic, of course, inasmuch as I am here 
the dubious 'beneficiary' of the Matthew effect"--a 
phenomenon that he had identified, named, and harshly 
criticized.

The conceptual impact of the Merton oeuvre has been vast; 
however, while he has profoundly influenced many aspects of 
20th-century science, or at least our ways of thinking about 
it, the influence has not been confined to the scientific 
realm. Such Merton concepts as "the self-fulfilling 
prophecy" and such Merton innovations as "the focused 
interview" have found their way into our everyday lives. And 
many of his visionary notions concerning the clockworks of 
human behavior, while often pertaining originally to the 
world of research, have been extended in application to 
matters of family, business, and religion.

I congratulate my old friend Bob Merton on receiving the 
National Medal of Science. And I encourage young scientists 
who have not yet studied with this master to get to the 
library or bookstore as soon as possible. A valuable treat 
is in store for you.


(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


                             LETTERS

------------------------------------------------------------
TI   : NIH Triage

AU   :  HUGH STAMPER

TY   :  OPINION (LETTERS)

PG   : 13

Jose Musacchio's commentary, entitled "Triage at NIH: A Smoke 
Screen Concealing The Real Problems Facing American Science" (The 
Scientist, Sept. 5, 1994, page 13), contains several 
misperceptions. While it is true that the use of triage in peer 
review would relieve some pressure on review staff at the 
National Institutes of Health, it has never been suggested, as 
Musacchio implies, that it would "solve the problems undermining 
American science."

As now applied at NIH, triage focuses on reducing time spent at 
review meetings by eliminating discussion on applications whose 
scores would fall below the committee's midpoint (50th 
percentile) and are unlikely to be changed by further discussion. 
These noncompetitive applications, however, are carefully 
reviewed in advance of the meeting. In fact, reviewers report 
spending the same amount of time evaluating applications that are 
ultimately deemed noncompetitive under triage as they did when 
triage was not used. Reviewers prepare written comments in 
advance of the meeting, as they have always done.

Contrary to Musacchio's perception, under triage, all applicants 
receive summary statements. Furthermore, the use of triage has 
facilitated the move from summary statements composed of 
carefully integrated comments to those in which reviewers' 
prepared comments are released intact and virtually unedited. 
Thus, contrary to the suggestion that reviewers are no longer 
accountable to applicants receiving a noncompetitive rating, 
reviewers are more accountable, since their actual comments are 
received by applicants.

Finally, Musacchio confuses the issue of triage by intertwining 
it with funding aspects. Triage is not a culprit that prevents 
worthy research from being supported. The primary objective of 
peer review--and triage is consistent with this--is the 
identification of the best research so that reasonable funding 
decisions can be made. Availability of funds and the making of 
funding decisions must continue to be assiduously separated from 
peer review.

Certainly, triage will not cure all the ills related to obtaining 
research support. It does, however, permit reviewers and NIH 
staff to spend time more efficiently, while allowing the outcome 
of review to be communicated more forthrightly to both successful 
and unsuccessful applicants. Staff at NIH will continue to seek 
improvements that will ensure fair, equitable, and efficient peer 
review.

Hugh Stamper
Director, Division
of Extramural Activities
National Institute
of Mental Health
Parklawn Building, Room 9-105
5600 Fishers Lane
Rockville, Md. 20857
E-mail: Hugh_Stamper@nih.gov


(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                            --------
NXT:

------------------------------------------------------------
TI   : Conduct Meeting
AU   : Charles W. McCutchen

TY   : OPINION (LETTERS)

PG   : 13

The article entitled "Meeting On Science Conduct Seen As A Noble 
Attempt That Fell Short" by Franklin Hoke (The Scientist, July 
25, 1994, page 1) says that "many of the attendees [at the 
'Convocation on Scientific Conduct'] note with some dismay that 
active research scientists were largely absent from among the 
approximately 250 people [in the audience]." Did they really 
think that many would come?

Displaying an interest in misconduct is not a path to advancement 
in science. Remember what happened to Walter Stewart and Ned 
Feder. Only scientists who have already sacrificed their careers 
would dare to come, and why should they swell the audience for 
this latest show put on by the biomedical science establishment 
to give an appearance of action?

If the establishment ever decides to do anything real to halt 
scientific misconduct, it will use the same subterranean methods 
it now employs in the service of cover-ups. There will be no 
fanfare.

Charles W. McCutchen
5213 Acacia Ave.
Bethesda, Md. 20814


(The Scientist, Vol:8, #20, pg.13, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


WHERE TO WRITE:
Letters to the Editor
The Scientist
3501 Market Street
Philadelphia,  PA 19104
Fax:(215)387-7542
E-mail:
Bitnet: garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

              =====================================

NXT:


                            RESEARCH

---------------------------------------------------------------
TI   : Biomedical Researchers Step Up Efforts To Probe 
       Mysteries Of Aging

AU   : Karen Young Kreeger

TY   : RESEARCH

PG   :  14

The population of the United States is aging. According to 
the U.S. Census Bureau, the proportion of Americans aged 65 
and older is expected to increase from about 12 percent 
today to about 20 percent in 2030. By then, the average baby 
boomer--those born in the years immediately following World 
War II--will be upwards of 80 years old. And, like its 
subjects, the field of biomedical science that explores the 
physical, psychological, and sociological effects of the 
aging phenomenon is visibly maturing.

As the  baby boomer generation gets older, increased 
attention is being focused upon geriatrics (the study of 
illness in older people) and gerontology (the basic science 
of aging processes). For scientists in these fields, the 
demographic sea change has conceptually affirmed the need 
for a more aggressive approach to aging research and, 
consequently, has fueled growth in funding for it in recent 
years (see story on page 1).

NIA's Broad Mission
Immunologist Richard Hodes is addressing the challenges of 
this broad field of scientific study in two venues: the 
director's office of the National Institute on Aging (NIA), 
where he's responsible for administering the efforts of 
about 6,000 intramural and extramural investigators and a 
budget of more than $420 million; and at the bench of his 
NIA lab, working with a team of investigators on the 
relationship of the immune system to the biology of aging.

NIA, which was formed in 1974, is the primary source of 
financial support for aging research in the U.S. According 
to Hodes, the institute "evolved to provide a perspective 
that was different from each of the organ- or disease-
specific institutes. It developed into an institute with a 
very broad mission, which is based on the biomedical, 
behavioral, and social aspects of the quality of life of 
older citizens."

Hodes explains that the research sponsored by the institute 
looks at a blend of the molecular and cellular mechanisms 
that influence aging and longevity; behavioral factors, such 
as diet and exercise, which play a role in mediating the 
aging process; and the sociological implications of 
providing care for an aging U.S. population.

NIA researchers agree that the dramatic shift in the makeup 
of the population toward an older majority is the impetus 
for the growth in their field. "The demography is really  
the  driving  force,"  says Zaven Khachaturian, associate 
director  of  the  of  aging  program in neuroscience and 
neuropsychology.

"It's been happening since the turn of the century. People 
are living longer, and the older age group--85 and over--is 
growing at a much faster rate than other age groups."

These demographic changes have had a direct impact on NIA 
funding almost from the time the institute was formed. "When 
I came here 15 years ago, the whole institute had a $28 
million budget. And now our budget for fiscal year T94 is 
over $400 million," notes Richard Sprott, associate director 
for the biology of aging extramural program. "That would not 
have happened without the demographic imperative.

"Aging and AIDS have been the largest growth areas in health 
sciences for the last decade." 

According to George Martin, science director of the 
intramural program, a significant avenue of NIA research is 
identifying risk factors such as diet and exercise habits 
for certain age-related diseases.

Sprott adds that NIA's research mission "is not to produce 
100-year-old people, but to improve the quality of the 
terminal third of the lifespan that we've got."

And it seems that goal is starting to be realized. A recent 
National Research Council report funded by NIA and entitled 
Demography of Aging (L.G. Martin, S.H. Preston, eds., 
Washington, D.C., National Academy Press, 1994) states that 
the prevalence of disability among the older population in 
the U.S. decreased during the 1980s.

Focus On Alzheimer's
One major area that NIA funds--both intramurally and 
extramurally--is the study of Alzheimer's disease. "Research 
relevant to Alzheimer's is the single largest investment 
currently at the institute," Hodes says. 

Khachaturian heads the largest extramural program at the 
institute--neuroscience and neuropsychology--which primarily 
funds basic and applied Alzheimer's disease research. Just 
over $190 million--half of the total NIA extramural budget--
is devoted to this program, with about 80 percent going to 
fund Alzheimer's-related work. 

Khachaturian says that research supported by the 
neuroscience program, which he set up in 1978, ranges from 
molecular-level basic research to epidemiological studies 
involving many human subjects. "The notion is," he explains, 
"that the study of the aging nervous system should not only 
be done at the basic science level, but that it should be 
done at the systems level, starting at very molecular, basic 
areas like genetics and protein chemistry, moving up to 
neurons and neural systems, and on to behavior and effects 
on society.

"This approach has proved to be very fruitful, as 
demonstrated by the success of the Alzheimer's program," 
Khachaturian adds. "There was very little known about the 
disease in 1978. But in a short time, we have moved 
Alzheimer's out of the dark ages to the cutting edge of 
neuroscience because we integrate basic scientists with the 
clinicians.

"In fact, I went out of my way to recruit people from other 
disciplines--like protein chemistry, medicinal chemistry, 
molecular biology, and genetics. If you look at the history 
of many of the people who are in the field now, five to 10 
years ago they weren't studying aging nervous systems or 
Alzheimer's. They're all converts."

According to Hodes, it is with good reason that mounting 
attention has been paid to Alzheimer's disease: "The genes 
that appear to be responsible for some of the rare, 
familial, early-onset forms have been identified, although 
the mechanisms by which they influence disease remain to be 
elucidated. And most recently, a lot of excitement has been 
generated in the last year about the identification of the 
ApoE gene, which has been identified as an epidemiological 
risk factor for disease. 

"This is an important first step. It will ultimately allow 
an avenue by which we can understand the biology [of 
Alzheimer's] and, hopefully, eventually the cause of the 
disease, thus leading to diagnostic and, most importantly, 
therapeutic intervention."


The Biology Of Aging
Another extramural program focuses on trying to unravel the 
nature of longevity and aging from a biological perspective. 
"The main thrust of almost everything we fund is aimed at 
trying to understand the basic processes that go on at the 
cellular and molecular levels that underlie the aging 
phenomenon," says Sprott, referring to the biology of aging 
program he heads. 

The "aging phenomenon" has two parts, explains Sprott: 
"those things that might be the aging processes themselves 
as well as those which have an influence on age-related 
phenomena, such as hip fractures and Alzheimer's."

Elucidation of the underlying mechanisms of aging processes 
has become possible because of recent advances in molecular 
biological techniques, he says: "In the last eight to 10 
years, modern molecular biology grew up and provided us with 
techniques that began to allow us to get answers."

As an example, Sprott cites a recent NIA-funded study 
concerning the possible relationship between the telomere--a 
part of the human chromosome--and the lifespan of certain 
populations of cells. "There's been this recent discovery 
that every time the cell divides the telomere gets shorter. 
It's as if you're knocking off a little piece and the 
telomere length is in fact a counter and it can count how 
many times a cell line has doubled, and when it runs out the 
line dies."

He says this finding is significant because of the 
possibility that there is a physical "counting mechanism" 
that would explain human mortality.

Another aspect of research in Sprott's program is 
understanding the relationship among cell maintenance, 
aging, and genetics. "Inside the cell the job of certain 
genes is to maintain a very, very delicate balance between 
senescence, which must happen, vs. immortality. If the 
senescence genes become too active, they kill off cells, and 
if they aren't active enough, [the cells] become immortal, 
or cancerous, and the whole organism dies anyway," Sprott 
explains.

NIA-funded investigators have found single genes that are 
responsible for maintaining this control over senescence. 
They call them longevity-assurance genes, or LAGs, according 
to Sprott. He also mentions that colleagues at the National 
Cancer Institute have found tumor-suppressor genes that are 
very similar in composition to LAGs. 

"What it looks like is that they may be the same genes 
arrived at from two different directions," says Sprott. "I 
think that what this says is that, as we understand the 
basic processes of aging, we're going to understand the 
basic processes of a lot of other things."

The Baltimore Study
Although much of NIA-funded work is devoted to basic 
biomedicine, another important facet of the NIA mission is 
to conduct holistic studies of human aging. One intramural 
program centered at NIA's Gerontology Research Center in 
Baltimore--the Baltimore Longitudinal Study--is the longest 
continually running scientific study on human aging. 

The study started in 1958 with 58 male subjects and was 
directed by the former National Heart Institute. It now 
includes more than 1,100 men and women ranging in age from 
20 to 96. Its overall purpose is to follow individuals 
throughout their lifetimes in order to understand the 
process of aging in the human mind and body.

Hodes describes the study as an "insightful venture that 
recognizes the importance of evaluating aging by studying 
individuals as they age over time rather than by comparing a 
given group of people who are young at a specific time with 
a group of people who are old at the same time." 

He says that the study has dramatically altered what 
researchers consider "normal aging." The study has dispelled 
stereotypes of what it means to grow old, such as the 
commonly held scientific notion that the amount of blood 
pumped per minute, or cardiac output, always decreases with 
advancing age. Now, according to information from the 
Baltimore study, gerontologists have revised their 
description of the aging heart. They have found that 
disease-free hearts in older individuals have a comparable 
cardiac output to that of younger people.

So far the study has generally concluded that there is no 
single, simple standard to describe human aging.

For more information on research grants offered by NIA, 
contact Miriam Kelty, associate director of NIA and director 
of the office of extramural affairs, NIH-NIA, Gateway 218, 
Bethesda, Md. 20892; (301) 496-9322. Fax: (301) 402-2945. 
The electronic mail address is:
kelty@nihniagw.internet.gov.


(The Scientist, Vol:8, #20, pg.14, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:


------------------------------------------------------------
TI   :  NIA: COMING OF AGE

AU   :  KAREN YOUNG KREEGER

TY   :  RESEARCH

PG   :  14

The National Institute on Aging (NIA) is celebrating its 
20th anniversary this year. It was established in 1974 when 
Congress passed the Research on Aging Act, charging the 
institute to conduct and support biomedical, social, and 
behavioral research as well as training and education on the 
process of aging and the diseases and special needs of older 
individuals.

"Our research is very far-ranging, from basic research into 
cell regulation and cell death, to aging and cancer, to the 
social and behavioral aspects of aging," says Miriam Kelty, 
associate director of NIA and director of the office of 
extramural affairs.

Some current NIA statistics:
NIA's appropriated budget for fiscal year 1994 is $420 
million, of which $38 million went to fund intramural 
research. For fiscal year 1995 the total appropriated budget 
is $434 million, with almost 9 percent of that assigned to 
the intramural program.

The extramural program supports more than 900 research 
project grants in four main areas--the biology of aging; 
geriatrics; neuroscience and neuropsychology; and behavioral 
and social science--totaling nearly $250 million.

The majority of intramural researchers work at the 
Gerontology Research Center in Baltimore, while the rest 
work on the NIH campus in Bethesda, Md.

The intramural program covers 11 areas of research, 
including cardiovascular science, molecular genetics, and 
cognitive studies.

--K.Y.K.

(The Scientist, Vol:8, #20, pg.14, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

                         HOT PAPERS

------------------------------------------------------------
TI   : DEVELOPMENTAL BIOLOGY

TY   : RESEARCH (HOT PAPERS)

PG   : 16

T. Braun, M.A. Rudnicki, H.H. Arnold, R. Jaenisch, "Targeted 
inactivation of the muscle regulatory gene
Myf-5 results in abnormal rib development and
perinatal death," Cell, 71:369-82, 1992.

M.A. Rudnicki, T. Braun, S. Hinuma, R. Jaenisch,
"Inactivation of MyoD in mice leads to up-regulation of the 
myogenic HLH gene Myf-5 and results in
apparently normal muscle development," Cell,
71:383-90, 1992.

M.A. Rudnicki, P.N.J.
Schnegelaberg, R.H. Stead, T. Braun, H.H. Arnold, R. 
Jaenisch, "MyoD or Myf-5 is required for the formation of 
skeletal muscle," Cell, 75:1351-9, 1993.

Michael A. Rudnicki (Institute for Molecular Biology and 
Biotechnology, McMaster University, Hamilton, Ontario, 
Canada): "Gene targeting has allowed the genetic dissection 
of the roles played by the myogenic regulatory factors 
(MRFs) in the development of skeletal muscle. The 
introduction of null [loss-of-function] mutations in Myf-5, 
MyoD, and myogenin into the germline of mice has revealed 
insights into the hierarchical relationships existing among 
the MRFs and established that functional redundancy is a 
feature of the MRF regulatory network.

"Mice lacking a functional MyoD gene were found to have 
no overt abnormalities in skeletal muscle and are altogether 
viable and fertile (M.A. Rudnicki et al., Cell, 71:383-90, 
1992). RNA and histological analysis could not detect any 
difference between wild type and mutant MyoD mice. The 
amount of Myf-5 mRNA is increased in mutant MyoD mice, which 
suggests that Myf-5 may substitute for the absence of MyoD 
in the development of skeletal muscle. 

RAs with MyoD mutant mice, histological and northern-blot 
analyses of newborn Myf-5-deficient animals did not reveal 
any abnormalities in skeletal muscle. Muscle development is 
delayed until the MyoD is expressed. As an indirect 
consequence of this delayed development, Myf-5 mutant mice 
have rib abnormalities that prevent normal respiration (T. 
Braun et al., Cell, 71:369-82, 1992) and therefore die soon 
after birth. The onset of MyoD expression, however, occurs 
normally, followed by the expression of myogenin and other 
differentiation-specific markers (T. Braun et al., 
Development, in press). These results suggest that the 
activation of MyoD occurs independently of Myf-5 and that 
MyoD can substitute for the absence of Myf-5 in the 
development of skeletal muscle.

"The potential ability of Myf-5 and MyoD to substitute for 
one another led to the hypothesis that Myf-5 and MyoD have, 
at least to some degree, functionally redundant roles in the 
development of skeletal muscle (M.A. Rudnicki et al., Cell, 
71:383-90, 1992). To test this hypothesis, Myf-5 and MyoD 
mutant mice were interbred. Newborn mice deficient for the 
two MRFs are totally devoid of skeletal myoblasts as well as 
muscle (M.A. Rudnicki et al., Cell, 75:1351-9, 1993). Mutant 
pups are born alive but are immobile and die within minutes. 
The spaces normally occupied by muscle are filled with 
amorphous connective and adipose tissues, and desmin-
containing myoblast cells are absent.

"Other investigators have targeted the remaining MRF genes. 
Mice lacking a functional myogenin gene are immobile and die 
perinatally owing to deficits in skeletal muscle 
differentiation (P. Hasty et al., Nature, 364:501-6, 1993; 
Y. Nabeshima et al., Nature, 364:532-5, 1993). The skeletal 
muscle in mice lacking myogenin display a marked reduction 
in myofibers. However, myoblasts are present, and these are 
organized in groups similar to wild-type skeletal muscle, 
suggesting myogenin is not involved in patterning. Myogenin-
deficient mice also display a relatively mild rib deformity. 
These results indicate an essential in vivo role for 
myogenin in terminal differentiation of myoblasts into 
myotubes.

"The absence of myoblasts in mice lacking both Myf-5 and 
MyoD places these two factors upstream of myogenin in the 
regulatory pathway. Moreover, this result suggests that Myf-
5 and MyoD are involved in the determination of myoblasts, 
as these cells are absent when these factors are missing. 
However, it is important to note that these results do not 
preclude a role for Myf-5 and MyoD as differentiation 
factors. For example, while myoblasts lacking myogenin fail 
to differentiate efficiently in vivo, they form normal 
multinucleated myotubes in vitro (Y. Nabeshima et al., 
Nature, 364:532-35, 1993). This suggests that in arrested 
myoblasts in vitro MyoD can substitute for the role myogenin 
plays in differentiation. The fourth myogenic factor MRF4 
may function late in the myogenic pathway, as has been 
implied by its expression pattern in cultured cells. 
Alternatively, MRF4 may have a vital role early in the 
development of the dorsal subdomain of the dermamyotome, as 
suggested by its expression in vivo (T.H. Smith et al., 
Journal of Cell Biology, in press). 

"The ability to target specific genes for inactivation in 
the mouse has proved to be an extremely powerful tool to 
genetically dissect complex biological phenomena. In the 
near future, targeted inactivation of other important 
players involved in skeletal myogenesis will certainly 
provide much information as well as a few surprises."


(The Scientist, Vol:8, #20, pg.16, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : ASTROPHYSICS

TY   : RESEARCH (HOT PAPERS)

PG   : 16

G. Schaller, D. Schaerer, G. Meynet, A. Maeder, "New grids 
of stellar models from 0.8 to 120M; at Z=0.020 and Z=0.001," 
Astronomy & Astrophysics Supplement Series, 96:269-331, 
1992.

Georges Meynet (Geneva Observatory, University of Geneva): 
"The evolution of galaxies is intimately related to the 
evolution of one of their main components--the stars. 
Stellar evolution is responsible for the different colors of 
galaxies. When the galaxy presents no sign of recent star 
formation, most of its luminosity is due to red giant stars. 
Inversely, a young stellar population manifests itself 
through the presence of numerous blue stars as O-type and/or 
Wolf-Rayet stars. In starburst galaxies, one can even 
observe stellar populations that are completely dominated by 
very young stars born a few million years ago. 

"The chemical composition of the galaxies is also mainly due 
to the enrichment of the interstellar gas by new material 
synthesized in stars. Again, the metallicity of a galaxy 
(the fraction of the mass of a galaxy in the form of 
elements heavier than hydrogen and helium) is an indication 
of its past stellar formation history. 

"Stars may also deeply affect the dynamic and physical 
properties of the interstellar medium. These few examples 
show that in many active areas of astrophysics research--
such as the evolution of the galaxies, origin of the 
elements, stellar-formation processes one needs information 
on the way the stars evolve.

"At the Geneva Observatory, we have recently computed 
extended grids of stellar models covering a wide range of 
parameters such as initial mass and initial metallicity. We 
have also investigated the effects of a change of the mass 
loss rates on the outputs of massive stars models. This 
article is the first of a series of five papers presenting 
the whole set of stellar models (D. Schaerer et al., Astron. 
& Astrophys. Suppl., 98:523-7, 1993; C. Charbonnel et al., 
Astron. & Astrophys. Suppl., 101:415-9, 1993; D. Schaerer et 
al., Astron. & Astrophys. Suppl., 102:339-42, 1993; G. 
Meynet et al., Astron. & Astrophys. Suppl., 103:97-105, 
1994). The homogeneity of these data, computed with the same 
physical ingredients and the same code for a great range of 
important physical parameters, make them attractive for 
people interested in stellar populations and the chemical 
evolution of galaxies. Moreover, for many years we have 
continuously improved the physical ingredients incorporated 
in our stellar evolutionary code, taking into account recent 
advances in stellar opacities calculations, measurements and 
computations of nuclear cross-sections, and neutrino-
emission processes. 

"Some of the physical ingredients of the stellar models 
cannot be obtained with sufficient accuracy from experiments 
alone or from purely theoretical considerations. In these 
cases, we tried to constrain these quantities with detailed 
comparisons between some theoretical predictions of the 
stellar models and some well-established observed properties 
of stars. In this way, we concluded that the mass loss rates 
of massive stars during the periods when the stellar winds 
are essentially driven by radiation pressure must be higher 
than those given by the commonly used semi-empirical laws. 

"At present our stellar models can account quite well for 
many observed properties of the stars, and we hope that they 
will represent a good starting point to go ahead in the 
fields of stellar and galactic evolution."

(The Scientist, Vol:8, #20, pg.16, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

                     TOOLS & TECHNOLOGY

------------------------------------------------------------
TI   :  DNA Sequencing: Today's Technology And Beyond

AU   : Scott Veggeberg

TY   : TOOLS & TECHNOLOGY

PG   : 17

Since the basic chemistry for DNA sequencing was developed 
in the 1970s by Frederick Sanger of the Medical Research 
Council, Cambridge, England, this technology has become a 
ubiquitous tool in genetics, molecular-biology, and 
microbiology labs. But the fastest-growing application of 
DNA sequencing today is in clinical diagnostics. Also, rapid 
advances in DNA sequencing have pushed the technology beyond 
its conventional base in polyacrylamide slab gel 
electrophoresis. These new approaches involve capillary gel 
electrophoresis and even glass-plate DNA "chips" made with 
photolithography processes.

The current market in automated DNA sequencers is a well-
ordered one, dominated by a handful of manufacturers. The 
leading companies making these products all currently use 
Sanger's basic chemistry for producing nested sets of 
progressively longer DNA fragments. These sets of DNA 
fragments are tagged with fluorescent dyes and then 
separated by gel electrophoresis and automatically scanned 
for identification of base-pair sequences.

"A DNA sequencer is nothing but an automated DNA 
electrophoresis detection and analysis system," explains 
Jack Ball, vice president of molecular biology systems at 
Pharmacia Biotech Inc. in Piscataway, N.J., which markets 
the ALF (automated laser fluorescence) DNA sequencer. From 
Ball's description, this may sound like a simple enough 
instrument, but sequencers are not cheap. Prices range from 
$55,000 for an aggressively priced system introduced this summer 
by Molecular Dynamics Corp. of Sunnyvale, Calif., to 
$110,000 for the market leader, made by Applied Biosystems 
Inc., a division of Perkin-Elmer Corp. in Foster City, 
Calif.

The Major Players
Researchers interested in purchasing a DNA-sequencing system 
have a basic choice. They may select a device from Applied 
Biosystems, whose sequencer offers the highest throughput--
that is, the most number of bases that can be read in a day. 
Alternatively, they may choose one of several other 
manufacturers' systems, which cannot offer the same 
throughput but are lower priced and offer higher sensitivity 
as well as, in at least one case, longer read length--
referring to the base-pair length of DNA fragments. In fact, 
one system, available from Lincoln, Neb.-based LI-COR Inc., 
can routinely read DNA fragments up to 800 and even 1,000 
bases in length, compared with the 500 bases typically read 
by its competitors. But in the final analysis, all of the 
commercially available automated sequencers, and the 
supporting reaction chemistry, are quite similar.

The current market in sequencers, dominated by a few major 
manufacturers, may begin to fragment, however, as new 
technologies--and the companies developing them--start 
breaking onto the sequencing scene. The Human Genome 
Project, with its ambitious goal of mapping the entire human 
genome in a matter of years, has increased demand for far 
faster, less cumbersome sequencing methods than are 
available at present. This has catalyzed the development of 
a number of new and unconventional approaches that could 
allow a single scientist to sequence up to 10 million bases 
per year. At this rate, the entire human genome, with its 3 
billion bases, could be sequenced in a single year by just 
300 workers.

"Everything that spins off the Human Genome Project will 
[also] require confirmatory sequencing," says Ball. That is, 
sequences derived rapidly will have to be confirmed, and 
thus "the market for DNA sequencers will be absolutely 
huge," he predicts.

New applications for DNA-sequencing technology, most notably 
in the clinical diagnostic arena, will also expand the 
market for sequencers, bringing new technologies and lower-
priced instruments to commercialization, say many industry 
observers.

Alternative approaches--such as capillary gel 
electrophoresis, hybridization, and time-of-flight mass 
spectrometry--may bear fruit before the end of the decade. 
But until then, the current technique of using slabs of 
polyacrylamide gel to separate DNA fragments will remain the 
method of choice. And, at least for now, the Applied 
Biosystems technology is predominant.

Applied Biosystems claims to have about 85 percent of the 
market in automated DNA sequencers in the United States, 
leading Steve Lombardi, product manager for the AB 373 DNA 
sequencer, to boast, "We own the market." One of the main 
reasons for the company's market dominance is that it was 
the first to come out with a sequencer, introducing the AB 
373 in June 1986. Another reason is throughput. With its 
unique four-dye technology, Applied Biosystems sequencers 
read all four nucleotides in a single lane. Other systems 
require four parallel sequencing reactions for a single DNA 
strand. This multiplexing approach quadruples Applied 
Biosystems' output over competing manufacturers, according 
to the company.

Applied Biosystems, as well as Molecular Dynamics, also 
sells automated robotic systems that perform the pre-
separation reaction chemistry developed by Sanger, which is 
still the basis for DNA-sequencing technology. "Our goal is 
to automate the molecular biology lab and all the different 
applications in that lab," says Lombardi. "We don't just 
sell sequencers anymore. We sell genetic analyzers." In 
addition to DNA sequencing, these systems can be used to 
perform DNA fingerprinting, mutation screening, linkage 
mapping, and microsatellite analysis.

Sequencing The Sanger Way
The chemistry used to prepare samples for the currently 
available automated sequencers is based on the tried-and-
true method developed in the 1970s (F. Sanger, Proceedings 
of the National Academy of Sciences, 74:5463-7, 1977). In 
this reaction, DNA is fragmented with restriction enzymes 
into single-stranded lengths that readily pass through gels, 
with the preferred length about 500 bases. The single-
stranded fragment is then mixed with DNA polymerase, and 
with free nucleotides. The DNA polymerase runs along the 
strand, "repairing" it by building a complementary strand. 
If left alone, the reaction would end when the entire double 
strand was completed. However, this would provide no 
information on the sequences within the strand.

The trick used in the Sanger method is to force DNA 
polymerase to occasionally terminate the reaction at base 
number 1, then base number 2, number 3, and so on, resulting 
in sequential DNA strands up to 500 base pairs in length. To 
do this, a small amount of aberrant nucleotides, called 
dideoxynucleotides, is mixed in with the normal 
deoxynucleotides. These aberrant nucleotides lack the usual 
free 3*-OH, which is needed to continue the polymerization 
reaction. Whenever the DNA polymerase picks up an aberrant 
nucleotide and incorporates it into the complementary 
strand, the reaction halts. In the end, the test tube is 
filled with a series of fragments ranging from one to 500 
bases in length.

This is the point at which the manufacturers' technologies 
diverge. AB utilizes four dyes, each of which is specific to 
a particular dideoxynucleotide. One dye would react only 
with dideoxyguanosine, another would react only with 
dideoxyadenosine, and so on, so that each base fluoresces at 
a characteristic wavelength, allowing all four bases to be 
read in the same lane of the gel.

In the next step, the fragments are loaded manually onto a 
DNA sequencer gel, which separates the fragments into 
discrete bands that differ in length by one base. These 
fragments will then migrate down the gel at a rate 
proportionate to their length, with the shortest passing 
through the most quickly. The length is thus determined by 
its time of migration, and the base is determined by which 
of the four wavelengths it fluoresces at.

The other manufacturers use a single-dye approach. At the 
chain-termination step, the DNA fragment is put into four 
separate reaction tubes, each one having only one of the 
four possible aberrant nucleotides. The four separate 
reactions are then loaded into four separate lanes on the 
gel, with each lane corresponding to a different nucleotide. 
The lower throughput obtained on these systems is simply a 
consequence of needing four separate lanes, instead of just 
one, to run one DNA strand.

The single-dye approach has advantages, however, explains 
James Nelson, product manager for the Vistra line of 
sequencers from Molecular Dynamics: "Because it's a single-
dye system, it's selected for much less expensive optics and 
laser systems." The Applied Biosystems technology uses a 
fairly complex argon laser, which is designed to produce 
excitation wavelengths matched to the four different dyes. 
As such, its output is not optimized for each individual 
dye's absorption maxima, says Nelson. The single-dye system 
used by Molecular Dynamics allows use of an inexpensive 
helium-neon laser optimized for the company's dye.

The LI-COR system uses a simple infrared (IR) laser, the 
same type of laser used in compact disc players. According 
to Abraham Oommen, an applications scientist at LI-COR, the 
IR laser system is far more sensitive than other detectors, 
allowing less sample to be loaded. Plus, he notes, "most 
biological molecules don't fluoresce in the infrared, so 
background [interference] is negligible." Less interference 
translates to longer read lengths, with LI-COR claiming that 
researchers can routinely read out to 800 bases with "base 
calling," or the identification of the bases, accomplished 
automatically by the computer software. Longer read lengths 
mean that fewer subclones have to be generated, which can be 
a great cost and time advantage for university 
investigators.

But LI-COR does not claim to be competitive with AB when it 
comes to throughput. "Massive sequencing facilities would 
not benefit from our machine," Oommen says. "We get out to 
1,000 bases, but not with thousands of samples. So, if you 
want to process 100 samples a day, go with an Applied 
Biosystems machine."

Falling Prices
As is true of any lab equipment, price is always a powerful 
consideration for researchers considering the purchase of a 
sequencer. The $110,000 price tag for an Applied Biosystems 
machine is something only the most dedicated user or core 
facility can afford. For those on a tighter budget, 
Pharmacia offers a sequencer that lists at $90,000 but can 
usually be discounted into the $75,000 to $80,000 range, 
says Ball. "And that's a significant [reduction] in prices." 
Besides being a laser-excited, single-fluorescent dye system 
with computer-based, automated base calling, the ALF 
sequencer has a thermally jacketed gel plate, allowing 
precise temperature control of the separation process. Also, 
sequencing and data analysis are controlled by a 486 
computer running under an OS/2 operating system. The OS/2 
system was selected because it is truly multi-tasking, 
meaning that data from one run can be manipulated, stored, 
or printed with a completely different application while the 
computer is running the separation and data analysis for the 
current run.

The LI-COR system, which also takes advantage of the 
multitasking capability of OS/2, is significantly less 
expensive than Applied Biosystems' sequencer, however. 
Priced at about $79,000, it has the advantage of longer read 
lengths and higher sensitivity over other systems.

The Applied Biosystems and Molecular Dynamics sequencers run 
on a Macintosh-based system. And, as Molecular Dynamics' 
Nelson points out, "If you look out into the marketplace, 
all the software [for genomic analysis] has been written for 
the Mac. That's not because it's superior. It's just 
history." Apple aggressively marketed its Macintosh systems 
to colleges and universities, and much of the DNA software 
written by professors and students is Mac-based, he says. In 
light of this, Molecular Dynamics' sequencer allows the user 
to easily interface with the extensive repertoire of 
existing Mac-based programs by running on an Apple Quadra 
610. But the real advantage of Molecular Dynamics' Vistra 
system is its comparatively low price, listing at just 
$54,900, half the cost of an AB 373. A robotic system, also 
available from Molecular Dynamics, that can be used for 
automating sequencing and PCR reactions may be added for 
$59,000. Thus, for the price of an AB 373, a lab can get 
both an automated sequencer and reaction system.

Will this competitive price put Applied Biosystems at a 
market disadvantage?

Lombardi contends that Applied Biosystems has no intention 
of dropping its prices to compete with the newcomer. "As the 
market leader, you don't really like to respond," he 
explains. "We just say that for $110,000, you're going to 
get a well-respected instrument that's going to do the work 
that needs to be done."

Instead of competing head-to-head with Applied Biosystems, 
Molecular Dynamics is focusing on a different market. "The 
AB system has been targeted at core labs and genome 
sequencers with high throughput requirements," says Nelson. 
"We're focusing on a different market niche, where 
throughput is not as much an issue." 

Throughput is relatively immaterial to Lonnie Ingram, a 
professor in the microbiology and cell science department 
at University of Florida, Gainesville, who has a LI-COR 
sequencer in his lab. He confirms that the LI-COR will give 
a longer read length than an Applied Biosystems sequencer, 
and for his lab that's an advantage, since there are fewer 
subclones and less wasteful overlapping of sequences. His 
lab was doing all its sequencing manually before getting an 
automated system. One big advantage of going from a manual 
to an automated  system was getting the radioactive isotopes 
used in manual processes out of the lab--and the radiation 
safety department off his back.

Capillary-Based Sequencing
A number of new sequencing approaches are under active 
development, with some of them possibly coming onto the 
market within the next few years. Chief among these 
technologies is multiple-capillary gel electrophoresis. 
Molecular Dynamics and Beckman Instruments Inc. of 
Fullerton, Calif., are both reportedly working on such 
systems, though neither company's representatives would 
comment on exactly what stage of development it has reached 
nor when the units might become available.

Capillary gel electrophoresis differs from the conventional 
method in that the polyacrylamide, instead of being poured 
out as a slab, is pumped into a 100-micron (internal 
diameter) capillary. This narrow-bore capillary permits the 
use of  a much higher field strength,  allowing separations 
to be completed in about an hour, instead of the usual six 
hours or more. 

With currently available systems, only one capillary can be 
run at a time, so throughput is not very high. Under 
development, though, is a capillary array in which 24, 48, 
or even 96 capillaries can be bundled and run in parallel, 
allowing more sample lanes than a slab gel and a six-fold 
increase in throughput over the current Applied Biosystems 
technology.

One of the drawbacks with such a system is that the price of 
the capillaries does not lend them to disposability. And 
once the polyacrylamide gel is cross-linked it cannot be 
scraped out as is done to recycle conventional gel plates. 
But Barry Karger, a chemist at the Barnett Institute of 
Northeastern University in Boston, says he is close to a 
solution: "What we're pushing pretty hard is replaceable 
matrices for capillaries." In this approach, the linear 
polyacrylamide is not cross-linked and can thus be blown in 
and then blown out of capillaries at the end of each run. In 
a commercial system, the capillary preparation steps could 
even be automated, he says. Better yet, unlike gel slabs, 
which require tedious manual loading of samples, the sample 
loading in a multiple-capillary system can be automated by 
simply dipping the capillaries into sample wells and letting 
the electric field draw in the DNA.

When will a multiple-capillary system be available? Karger 
says that Molecular Dynamics has already debuted a 48-
capillary system at a recent trade show. While the company 
didn't actually demonstrate the separation of DNA samples 
with this system, it showed that it has solved some of the 
design issues, such as how to scan the array of capillaries 
with the laser. Karger thinks it could be as soon as "a year 
or so" before such a system hits the market.

Sequencing On A Chip
Also just over the horizon is the hybridization approach, 
such as the one being developed at Affymetrix Inc. in Santa 
Clara, Calif. According to Robert Lipshutz, a mathematician 
and director of bioinformatics at Affymetrix, the company is 
developing a "DNA chip," which takes advantage of the 
propensity of single-stranded DNA to complex with 
complementary strands of DNA. A set of probes, consisting of 
oligomers from eight to 20 nucleotides in length, can be 
generated that will adhere to the target DNA. In the 
Affymetrix approach, these oligomers are attached to glass 
plates using the process of photolithography, widely used in 
making computer chips and nano-machines.

In this application, a 1.28 x 1.28 cm region of a glass 
surface is chemically prepared so that linker molecules, 
terminated with a photolabile compound, are attached. Next, 
using a photolithographic mask, a stripe of light is beamed 
across a quarter of the plate's width, thus removing the 
photolabile compounds in that area. Then, adenosine, for 
instance, can be covalently bound to the glass through the 
linker molecule. The free end of the nucleotide is capped 
with a photolabile group to prevent any further reaction 
until it is next exposed to light.

The process is repeated until there are four stripes: one 
with adenosine (A), one with guanosine (G), one with 
cytosine (C), and one with thymine (T). Afterward, the mask 
is turned 90 degrees to form a cross hatch of stripes with 
A, G, C, and T attached to the first set of nucleotides so 
that all 16 possible nucleotide dimers are formed. Using 
successively finer stripes of light, the oligomers can be 
built up to a chain with a length up to 20 nucleotides, 
which are attached to the glass plate at known positions, 
says Lipshutz. "We can make a high-density chip with over 
65,000 probes in 30 to 60 steps, taking about 10 minutes per 
step." And the company can make 16 identical DNA chips at 
the same time.

Fluorescently labeled DNA strands can then be washed over 
the DNA chip, whereupon the DNA will hybridize with the 
complementary sequences in the probes. The fluorescence is 
determined by reading the chip with a confocal microscope 
linked to an automated image scanner. For sequencing, this 
approach could be extremely rapid, but there is still the 
"ambiguity problem" to overcome, explains Lipshutz. That is, 
DNA occasionally will form mismatches when complexing with 
the oligomers.

Affymetrix is currently working out how to detect and deal 
with these mismatches. "It's still a ways off until people 
can do de novo sequencing," he says. But high-speed genome 
sequencing is not the company's first goal. Affymetrix would 
like to see the DNA chips applied to the rapid determination 
of mutations in HIV, for example. When the virus is 
challenged with a drug like AZT, which targets the reverse 
transcriptase (RT) enzyme, the virus develops resistance via 
mutations in the RT gene. What the DNA chip could provide is 
information on when that mutation has taken place so that an 
alternative drug regimen can begin. Lipshutz says the 
company hopes to commercialize the DNA chip technology by 
1996.

Clinical Diagnostics
The fastest-growing application for traditional DNA 
sequencing today is  in clinical diagnostics. Take, for 
example, the well-known oncogene p53--mutations of this gene 
play a role in a growing list of cancers. The p53 gene 
consists of 11 exons, and it encodes for a 53,000-dalton 
phosphoprotein that regulates cell proliferation.

What's been found, says Pharmacia's Ball, is that there are 
dozens of different mutations that the p53 gene can undergo. 
For researchers to discriminate among these mutations, the 
p53 gene from a patient's tumor is sequenced to see whether 
it is an aggressive type or one that is more treatable.

Another application is in diagnosing retinoblastoma (RB), a 
rare inherited eye tumor that can cause blindness but, if 
detected early, can be eradicated with laser surgery. To 
date, more than 300 mutations of the RB gene have been 
documented. The Eye Research Institute of Canada, affiliated 
with the Hospital for Sick Children in Toronto, is using a 
Pharmacia system to rapidly identify members of families 
that carry a mutation of the RB gene. This allows the 
researchers to exclude the unaffecte

Despite the promise of newly emerging capillary- and chip-
based technologies, users shouldn't expect that conventional 
sequencing will vanish any time soon, says Pharmacia staff 
scientist Anthony Murray. "I don't think the slab is dead," 
he asserts. Detectors capable of reading narrower lanes will 
allow higher lane densities to be read on conventional gel 
systems, which will extend the life span of the existing 
technology. "I think in the near term, the gel approach is 
going to be pretty hard to displace," he says.      


Scott Veggeberg is a freelance science writer based in 
Swarthmore, Pa.


(The Scientist, Vol:8, #20, pg.17, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : SUPPLIERS OF DNA SEQUENCERS, SYSTEMS, AND SOFTWARE

TY   :  TOOLS & TECHNOLOGY

PG   : 21

American Bioanalytical Inc.
Natick, MA
Circle No. 101 on Reader Service Card

Amersham Corp.
Arlington Heights, IL
Circle No. 102 on Reader Service Card

Applied Biosystems
Division of Perkin-Elmer
Foster City, CA
Circle No. 103 on Reader Service Card

Beckman Instruments Inc.
Fullerton, CA
Circle No. 104 on Reader Service Card

Biomed Instruments Inc.
Fullerton, CA
Circle No. 105 on Reader Service Card

Biomedical Research & 
Development Labs Inc.
Gaithersburg, MD
Circle No. 106 on Reader Service Card

Bio-Rad Laboratories
Life Science Group
Hercules, CA
Circle No. 107 on Reader Service Card

Boehringer Mannheim Corp.
Indianapolis, IN
Circle No. 108 on Reader Service Card

C.B.S. Scientific Co.
Del Mar, CA
Circle No. 109 on Reader Service Card

DNA ProScan Inc.
Nashville, TN
Circle No. 110 on Reader Service Card

DNASTAR Inc.
Madison, WI
Circle No. 111 on Reader Service Card

EG&G Berthold
Nashua, NH
Circle No. 112 on Reader Service Card


Fisher Scientific 
Pittsburgh, PA
Circle No. 113 on Reader Service Card

Hoefer Scientific Instruments
San Francisco, CA
Circle No. 114 on Reader Service Card

Inotech Biosystems
Lansing, MI
Circle No. 115 on Reader Service Card

Integra BioSciences Inc.
Woburn, MA
Circle No. 116 on Reader Service Card

IntellliGenetics Inc.
Mountain View, CA
Circle No. 117 on Reader Service Card

Intermountain Scientific Corp.
Kaysville, UT
Circle No. 118 on Reader Service Card

Jordan Scientific Co. Inc.
Bloomington, IN
Circle No. 119 on Reader Service Card

Laboratory & Research 
Products
New Haven, CT
Circle No. 120 on Reader Service Card

Li-Cor Inc.
Lincoln, NE
Circle No. 121 on Reader Service Card

Life Technologies Inc.
Gaithersburg, MD
Circle No. 122 on Reader Service Card

Marsh Biomedical Products Inc.
Rochester, NY
Circle No. 123 on Reader Service Card

Midwest Scientific
St. Louis, MO
Circle No. 124 on Reader Service Card

Molecular Biology Resources Inc.
Milwaukee, WI 
Circle No. 125 on Reader Service Card

Molecular Dynamics
Sunnyvale, CA
Circle No. 126 on Reader Service Card

National Biosciences Inc.
Plymouth, MN
Circle No. 127 on Reader Service Card

Owl Scientific
Woburn, MA
Circle No. 128 on Reader Service Card

Perkin-Elmer
Norwalk, CT
Circle No. 129 on Reader Service Card
Pharmacia Biotech Inc.

Piscataway, NJ
Circle No. 130 on Reader Service Card

Promega Corp.
Madison, WI
Circle No. 131 on Reader Service Card

Scanalytics
Billerica, MA
Circle No. 132 on Reader Service Card

Stratagene
La Jolla, CA
Circle No. 133 on Reader Service Card

Textco Inc.
West Lebanon, NH
Circle No. 134 on Reader Service Card

Time Logic Inc.
Moorpark, CA
Circle No. 135 on Reader Service Card

UVP Inc.
Upland, CA
Circle No. 136 on Reader Service Card

Zymark Corp.
Hopkinton, MA
Circle No. 137 on Reader Service Card


(The Scientist, Vol:8, #20, pg.21, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   :  NEW PRODUCTS

TY   :  TOOLS & TECHNOLOGY

PG   :  22


Hamamatsu Introduces Low-Light CCD Camera

The C4880 dual-mode, cooled charge coupled device (CCD) 
camera is designed for use in measurements requiring low 
light and high dynamic range as well as in photometry and 
precision still-image acquisition. It has a sensitivity of 
10 lx to 10-7 lx and a resolution of 1 million pixels (1,000 
x 1,018 pixels). The C4880 offers both fast- and precision-
scan modes. It has an analog-to-digital conversion rate of 
up to 10 MHz per pixel. Its digital output of up to 16 bits 
is compatible with most frame-grabber and display hardware 
on the market. The camera  may  also  be  
controlled  by  computer through its RS-232C serial 
interface.
Hamamatsu Corp., Bridgewater, NJ                    
Circle No. 138 on Reader Service Card


                           -----

ScanalyticsU RFLPscan Package For Protein, DNA Analysis
Version 2.0 of RFLPscan is a Windows-based software package 
for performing genetic analyses derived from DNA restriction 
fragment patterns, DNA fingerprints, protein typing 
patterns, and other identity-profiling gel images. It is 
able to analyze images obtained from film densitometers, 
flatbed scanners, CCD video cameras, storage phosphor 
devices, and radiometric detectors. The software offers 
comprehensive databasing capabilities that permit the 
comparison of lane profile data from gels as well as 
pairwise and simultaneous matching of individuals.
Scanalytics, Billerica, MA                                          
Circle No. 139 on Reader Service Card

                           -----

ImageSpace Software Available As Stand-Alone Product
ImageSpace 3.1 software was previously available only as a 
part of Molecular DynamicsU CLSM systems. The confocal 
package offers an integrated environment for rendering, 
processing, analysis, and display of confocal images, using 
an intuitive graphical user interface. Running on a Silicon 
Graphics workstation, ImageSpace software allows 
investigators to perform quantitative image analysis on 
three-dimensional data. Advanced analytical capabilities 
include automated object counting, seeding, and segmention; 
the program features tools for quantitative co-localization 
studies. The different 3-D analysis and 3-D visualization 
tools can be combined.
Molecular Dynamics, Sunnyvale, CA   
Circle No. 140 on Reader Service Card

                           -----

Gilson Announces Robotic Liquid Handler
The 215 Liquid Handler is an XYZ coordinate system robot that 
automates various manual liquid-handling procedures and sample-
preparation protocols. It has the capability to pierce thick tube 
septa to reduce the risk of exposure to potentially hazardous or 
infectious samples. Non-piercing probes for open-tube sampling 
are also available. The system is fully programmable and performs 
with a positional accuracy of 1 0.5 mm in the X and Y axes. It 
features a built-in dilutor for autodilution tasks, a large 
selection of syringe sizes, 15 standard and thermostatic racks, 
and several tube options.
Gilson Inc., Middleton, WI                                         
Circle No. 141 on Reader Service Card

                           -----

New Electroporation System From BTX
The Electro Cell Manipulator (ECM) 600 for electroporation 
of prokaryotic and eukaryotic cells features two voltage 
ranges (2.5 kV/500 V), an additive capacitor bank, and 
resistance timing, and makes possible instantaneous 
monitoring within a single unit. It is equipped with 
internal monitoring that measures true peak voltage and 
pulse length. The system includes a safety stand, cuvette 
rack, and a package of 50 sterile, disposable cuvettes in 1 
mm, 2 mm, or 4 mm gap sizes.
BTX Inc., San Diego, CA                                           
Circle No. 142 on Reader Service Card

                           -----


Storage And Reaction Tubes
Offered For PCR Applications
HotStart 100 storage and reaction tubes are 0.5 ml thin-wall 
polymerase chain reaction (PCR) tubes with a wax bead 
preadhered on the interior surface. The wax forms a uniform 
convective vapor barrier, which is said to reduce mispriming 
and primer oligomerization. The convective barrier also 
allows for separation of reaction components until the 
annealing temperature of the PCR reaction has been reached. 
The wax barrier seals the PCR product or prealiquotted 
master mixes for long-term storage in a lab freezer or 
standard refrigerator.
Molecular Bio-Products Inc., San Diego, CA
Circle No. 143 on Reader Service Card

                           -----


Bio-Rad Unveils Vertical Electrophoresis Cell
PROTEAN II xi cells perform a variety of separations, 
including SDS-PAGE, native, preparative, gradient, and high-
resolution nucleic acid agarose electrophoresis. In 
addition, with the two-dimensional electrophoresis 
technique, they are able to separate in both the first and 
second dimension. The cells enable users to run one, two, or 
four slab gels, or up to 16 IEF tube gels simultaneously. 
They are available in 1 cm or 2 cm gel lengths with a 
selection of combs and spacers.
Bio-Rad Laboratories, Hercules, CA                       
Circle No. 144 on Reader Service Card

                           -----

Double-Stranded, Site-Directed Mutagenesis Kit
The Chameleon kit is designed for single- and multiple-base 
substitution, insertion, and deletion mutations in virtually any 
double-stranded plasmid. Its site-elimination mutagenesis 
procedure introduces a new mutnS host strain, XLmutS, which is 
EndAQ. The endA mutation removes an endonuclease that degrades 
miniprep DNA. The kit can be used with almost any plasmid 
template containing a unique, nonessential restriction site and 
does not require CsCl-purified DNA.
Stratagene, La Jolla, CA                                            
Circle No. 145 on Reader Service Card

                           -----
WhatmanUs SMART Colorimeter
The SMART Colorimeter and SMART Reagents offer menu-driven 
operation for analysts measuring a variety of water-quality 
parameters. The SMART Colorimeter uses a tungsten lamp to 
deliver  colorimetric analysis of absorbance readings from 1 
to 2A and %T readings from 0 to 100 percent. In the 
laboratory or field, the alphabetical test selection plus 39 
prepackaged reagents are designed to reduce analysis time 
and save on reagent time and preparation.
Whatman LabSales Inc., Hillsboro, OR                    
Circle No. 146 on Reader Service Card

                           -----
Mettler-Toledo's Volumetric Evaluation Printer Debuts
The LC-PVolume is a compact printer designed for evaluating 
the performance of volumetric equipment by means of 
gravimetric analysis. The single-balance system, based on 
guidelines from the National Committee for Clinical 
Laboratory Standards, automatically performs complex 
calculations and prints them in a user-defined report. 
Features of the system include storage of 60 programs, 
password protection, alphanumeric input, and a verification 
report for International Standards Organization and Good 
Laboratory Practices requirements.

Mettler-Toledo Inc., Hightstown, NJ
Circle #147

                           -----


MathWorks Releases MATLAB Update For Windows

A new feature of MATLAB version 4.2c for Windows is the 
MATLAB Notebook, which integrates the softwareUs Technical 
Computing Environment with Microsoft Word 6.0. The Notebook 
Suite also provides an intuitive front-end for MATLAB 
through a dynamic link with Microsoft Word 6.0. This enables 
users to incorporate MATLAB graphics and commands directly 
into reports via a word-processing application interface; 
make changes in one portion of the document or any 
underlying data; and recalculate graphic and data results 
throughout the entire document.
MathWorks Inc., Natick, MA                                   
Circle No. 148 on Reader Service Card

                           -----

(The Scientist, Vol:8, #20, pg.22, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

                           PEOPLE

------------------------------------------------------------
TI   : Penn State Researcher Chosen To Receive American 
       Chemical Society's Bader Award

AU   : NEERAJA SANKARAN

TY   : PROFESSION (PEOPLE)

PG   : 24

Stephen J. Benkovic, a professor of chemistry at the 
Pennsylvania State University at University Park, has been 
named as the winner of the American Chemical Society's 1995 
Alfred Bader Award in Bioinorganic and Bioorganic Chemistry. 
He will receive the award at ACS's national meeting next 
spring in Anaheim, Calif.

Benkovic's research over the years has focused on 
understanding how enzymes catalyze chemical reactions. "My 
early work involved looking at the mechanisms of organic 
reactions of small molecules that mimic biological 
processes, and extrapolate that information to how an enzyme 
might work," he explains.

During his years as a graduate student at Cornell 
University, Ithaca, N.Y.--where he received a doctorate in 
1963--and a postdoctoral fellow at the University of 
California, Santa Barbara, he coauthored a two-volume set of 
books defining the subject of bioorganic chemistry along 
with his research supervisor, Thomas Bruice (Bioorganic 
Mechanisms, Vols. I and II, New York, Benjamin, 1966).

"Over the years my work evolved to the study of the enzymes 
themselves," adds Benkovic, who now does research on a 
variety of enzymes and catalytic antibodies, and recently 
reported an antibody that catalyzes peptide synthesis. (R. 
Hirschmann et al., Science, 265:234-7, 1994).

Benkovic, 56, conducted his undergraduate studies in both 
literature and chemistry at Lehigh University, Bethlehem, 
Pa., before going on to Cornell.

The chemist, who has been at Penn State since 1967, serves 
as Evan Pugh Professor and holds the Eberly Family Chair in 
the chemistry department there. He was elected to the 
National Academy of Sciences in 1985.

--Neeraja Sankaran

(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : Illinois Congressman Honored For Devotion To 
       Biomedical Research

AU   : NEERAJA SANKARAN

TY   : PROFESSION (PEOPLE)

PG   : 24

The American Association of Immunologists presented Rep. 
John Porter (R-Ill.) with a Public Service Award during a 
special ceremony held at the United States Capitol on 
September 20. Porter is the first recipient of an award that 
the 6,000-member, Bethesda, Md.-based scientific society 
established to recognize individuals from the lay community 
who have demonstrated the im-portance of basic biomedical 
research to the public.

The congressman was honored for promoting the importance of 
the National Institutes of Health and its research on 
Capitol Hill. As a member of the House Appropriations 
Committee, and the ranking Republican on the committee's 
Labor, Health and Human Services subcommittee--which funds 
NIH research--Porter has made basic biomedical research a 
priority. Last year, he played a leading role in ensuring 
that the 1994 budget supported NIH research with a 6 percent 
increase, rather than the 1 percent recommended in President 
Clinton's first budget.

"That level of funding would have proved devastating to 
biomedical research," Porter maintains, adding that the 
budgetary increase to NIH was appropriated without  spending  
additional money.

Porter, 59, received his J.D. degree from the University of 
Michigan Law School in 1961, and practiced law in Evanston, 
Ill., until his election to Congress in 1980. He says that, 
in supporting basic research, "it is very, very important 
that politicians don't put themselves in the position of 
managing science. Our role is to give it the tools for 
advancement."

--Neeraja Sankaran


(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI   : Torrey Botanical Club Elects New President

AU   : NEERAJA SANKARAN

TY   : PROFESSION (PEOPLE)

PG   : 24

The Torrey Botanical Club, one of the oldest professional 
societies in the United States, has elected a new president, 
Steven N. Handel, an associate professor of plant ecology in 
the department of biological sciences at Rutgers University 
in Piscataway, N.J. Handel, who will serve a one-year term 
during the 1995-96 academic year, was installed as 
president-elect last month. Handel succeeds Margaret Basile, 
a botanist who is currently a research associate at the City 
University of New York's Lehman College in the Bronx.

Named after 19th-century botanist John Torrey, the club was 
initially founded in 1866. Current worldwide membership 
stands at about 650. Although it has no official 
headquarters, it holds monthly meetings at the Bronx (N.Y.) 
Botanical Gardens and hosts a symposium at the annual 
meeting of the American Institute of Biological Sciences, a 
Washington, D.C., organization of professional societies.

"One of the things I hope to do as president is to arrange a 
symposium on restoration ecology that gets academics, city 
officials, and public-policy regulators together in one 
place to talk about what can be done in big cities like New 
York," says Handel, 49, who specializes in reproductive 
ecology in plants and the evolution of pollination systems. 
He currently is involved in a project--jointly funded by the 
National Science Foundation and New York City's sanitation 
department--to see how plant ecology can help in restoring 
native vegetation in landfill sites in the New Jersey and 
New York area. 

He is a visiting professor at Macquarie University in 
Sidney, Australia, where he studies pollination in orchids.

--Neeraja Sankaran


(The Scientist, Vol:8, #20, pg.24, October 17, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

garfield@aurora.cis.upenn.edu
71764.2561@compuserve.com

The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

                          --------
