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                          THE SCIENTIST


VOLUME 8, No:24                              DECEMBER 12, 1994
(Copyright, The Scientist, Inc.)

===============================================================
Articles published in THE SCIENTIST reflect the views of their 
authors and not the official views of the publication,         
its editorial staff, or its ownership.                         
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THE SCIENTIST 
(Page numbers correspond to printed edition of 
THE SCIENTIST)

FOR SEARCHING PURPOSES:  
AU   = author
TI   = title of article
TY   = type
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------------------------------------------------------------
TI :                      CONTENTS
TY : NEWS
PG : 3 
============================================================

                              NEWS

DATABASE DISPUTE: The terms of access to a new database
of complementary DNA sequences--specifically, the
exclusion of commercial users--has one drug maker so
incensed that it has sponsored a competing database
that it says will place these cDNAs completely in the
public domain  
PG   : 1

FUTURE SHOCK: The major surprise in the predictions of
scientists, sociologists, and architects researching
and planning the laboratory of the future may be
that--rather than a concentration on fantastic new
technologies or equipment--the emphasis will be on
promoting the interdisciplinary collaboration and
well-being of investigators  
PG   : 1

DUAL CHALLENGES: Tough economic times in the
pharmaceutical industry are presenting its researchers
with two major problems heading into 1995, observers
say. Recent layoffs and R&D downsizing present a bleak
employment picture, and those scientists who survive
are increasingly under pressure to develop novel
therapeutics  
PG   : 1

FAMILY AFFAIR: For one new member, the announcement of
the latest inductees into the Institute of Medicine
holds extra-special meaning. She is the third member of
her family to be so honored  
PG   : 3

SCIENCE-POLICY FEST: The symposium honoring astronomer
and space scientist Carl Sagan's 60th birthday was as
much a forum on national and international
science-policy issues as a testimonial to the career of
the celebrated science figure  
PG   : 4

                             OPINION

FINDING A WAY: Much as the Heisenberg Uncertainty
Principle revealed the difficulty of forecasting the
position and momentum of subatomic particles,
scientists and research administrators are struggling
to find direction amid the intersection of societal
goals, politics, and the scientific merits of the
national research enterprise, asserts Argonne National
Laboratory chief Alan Schriesheim  
PG   : 12

COMMENTARY: One of the most disturbing trends in
research funding, says University of Texas Health
Science Center professor Naomi Kraus, is the alarming
decrease in the number of young scientists being
funded, reflecting the science establishment's low
tolerance for controversy--and, therefore, for original
thought and innovation  
PG   : 13

                            RESEARCH

REFINING ITS MISSION: The National Institute of General
Medical Sciences recently reorganized--in order,
according to institute officials, to become more
efficient in its support of basic biomedical research
and training and to promote interdisciplinary work  
PG   : 14

HOT PAPERS: Medical geneticists Harry Orr and Huda
Zoghbi describe their search for an unstable
trinucleotide repeat; plant biologist Daniel Cosgrove
reports on the extension of plant-cell walls  
PG   : 15

                       TOOLS & TECHNOLOGY

UPWARD MAbILITY: Though the popularity of monoclonal
antibodies has ebbed and flowed dramatically over the
past two decades, MAbs have nonetheless become a staple
of cell biology, and numerous suppliers have emerged to
facilitate researchers' access to them  
PG   : 16


                           PROFESSION

DAZZLING DISCOURSE: In making a successful scientific
presentation, preparation as well as respect for and
consideration of one's audience is key, according to
cell biologist Robert Anholt, author of Dazzle 'Em With
Style, excerpted here  
PG   : 22

BEATRICE MINTZ, a researcher at the Fox Chase Cancer
Center, has received the John Scott Award from the city
of Philadelphia  
PG   : 23

                           SHORT TAKES

NOTEBOOK       PG  : 4

CARTOON        PG  : 4

LETTERS        PG  : 13

NEW PRODUCTS   PG  : 19


(The Scientist, Vol:8, #24, p.3, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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

------------------------------------------------------
TI   :The Lab Of The Future: Movable Walls, 'Office     
      Pods,' And Well-Being 

AU   : KAREN YOUNG KREEGER

TY   : NEWS

PG   : 1

It is early morning in the year 2024. A cell biologist
at a major university climbs the massive, open stairway
of her research facility, heading for her "office pod,"
one of several clustered in a wing of the building.
Donning her lab coat, mug of coffee in hand, she sets
off toward the skybridge that connects the offices to
the laboratory suites that dominate the other side of
the facility.

Along the way, she bumps into an old friend and current
colleague, a radiologist with whom she shared an
early-morning physics class in her undergraduate days;
he is now a nuclear science professor at the school.
Reliving old times and casually discussing their
disparate research, they settle in a nearby alcove, one
of several "interaction spaces" that dot the
architecture of the building.

An off-hand remark by her friend implants the germ of
an idea that might crystallize a theory she is
developing. Invigorated by the new concept, she rushes
off to her lab. As she gazes out the floor-to-ceiling
window overlooking the campus, she contemplates a quick
reconfiguration of her lab, moving the walls to
accommodate an armada of workbenches, instruments, and
other equipment she will wheel in to test her newfound
notions. What she doesn't know, of course, is that 
this  chance  encounter  will  garner  her the 2060
Nobel Prize in physiology or medicine, its $19 million
cash prize, and the adulation of millions of her
colleagues worldwide. . . .

Scientists, sociologists, and architects planning and
researching the lab of the future have come up with
predictions that some might find quite surprising.

They believe that, rather than concentrating on
facilitating space-age technologies, undreamed-of
equipment and instrumentation, and wondrous new
organisms and materials, lab designers in the next
century will place a heavy emphasis on less-fantastic
considerations, such as fostering interdisciplinary
communication, creating highly adaptable and
cost-efficient facilities, and alleviating the sense of
isolation that has long been the lot of the researcher.
A June 1993 workshop sponsored by the New York Academy
of Sciences (NYAS) examined some of these issues. In a
subsequent report distributed in October by the 
academy, "Research Facilities of the Future," (S.
Stark, ed., Annals of the New York Academy of Sciences,
Vol. 735, 1994), the participants summarized their
views on the factors they see dominating the research
centers of the 21st century:

"The lab will continue to be the heart of the
scientific workplace, requiring more adaptability, more
user autonomy, and tighter control over the
environment. . . . Because labs are where scientists
live as much as where they work . . . more concessions
to user comfort will be demanded [as well as] a
reduction of barriers between disciplines."

Although he did not take part in the workshop, Tom
Gieryn, an associate professor of sociology at Indiana
University in Bloomington, says that his research into
the sociology of the architecture of university-based
biomedical and biotech labs jibes with many of the
conclusions drawn in the report, especially the need to
relieve the isolation reinforced by today's lab design.

"I think that there was a sense in the minds of
architects until fairly recently that science is a very
secluded activity, one where you had to have a little
cubbyhole to get away," Gieryn asserts. "That's true,
that's what scientists have their offices for; but much
more important is the space where there are a lot of
people at work." 

The report notes that the primary inhabitants of these
new labs will probably be academic scientists, although
as industrial-academic collaborations continue to grow,
logistical and sociological dynamics of these
facilities will also be affected. 

Some of the planners' theories are grounded in
steel-and-stone realities of today. They point to
several recently constructed facilities that have
already incorporated some of these principles in their
design.

Prompting--and challenging--the work of these theorists
is the universality of the lab as the primary
scientific workplace and the issues it engenders for
its inhabitants. According to Rodney W. Nichols, chief
executive officer of the academy and former executive
vice president at Rockefeller University, this common
bond prompted the workshop. "We wanted to sponsor
activities that, in the long run, would be of greater
interest to a broader cross-section of the academy's
community," he says. "A conference like this covers
everyone in science."

The purpose of the workshop was "to stimulate debate"
among the research-facility designers and scientists in
industry, government, and academia who attended, he
adds.

Two years ago, Nichols recalls, Stanley Stark, a
partner and director of research facility design at
Haines Lundberg Waehler, an architectural firm in New
York, approached the academy to develop the workshop.
Stark, an architect and urban designer who has been
involved in building research facilities for more than
25 years, explains, "With the millennium approaching,
that's what led me to think about what might be
happening" in lab design.

Fostering Collaboration
Facility design that promotes interaction among diverse
investigators was the basis of much of the discussion
at the workshop, say its organizers. This same theme
also permeates Gieryn's sociological research, which
has included dozens of interviews with life scientists.
Gieryn comments that to determine what scientists want
in an ideal work environment, it is "key" to understand
how buildings can facilitate "unexpected, unpatterned"
interactions.

"The trick is how to design a building so that people
are going to run  into  colleagues  that  they wouldn't
be expecting to run into," he observes. "That's
apparently very important for cultivating the
collaborative thinking that science requires."

For example, he points out, the concept of promoting
unplanned encounters as a design element "works
beautifully" at the life sciences-oriented Thomas
Laboratory of Princeton University. In this facility,
bulges in the hallways--referred to by architects as
"interaction spaces"--are essentially open lounges,
with tables, chairs, and blackboards for informal
discussions. 

Two scientists who spoke at the workshop--Nathaniel
Heintz, a Howard Hughes Medical Institute investigator
at Rockefeller, and Samuel J. Williamson, a professor
in the department of physics and the Center for Neural
Science at New York University--said that other public
spaces, such as stairways, could be used more
effectively to enhance communication among colleagues.

"Instead of hiding the center stairway, make it a focal
point by opening it to view," proposed Williamson. He
noted: "If hotels draw tourists by such a display,
would it not provide a similar sense of fun and
dynamism to professionals in [a science] building?"
Stark concurs: "Stairways will have to become much
bigger and inviting places. Right now stairway design
is [essentially] governed by life-safety codes."

Form And Function
In addressing issues of the comfort and well-being of
future scientists, designers are examining features as
seemingly mundane as adding windows. A common plea from
scientists at the workshop, as well as the researchers
Indiana's Gieryn has spoken with, is for facilities to
have "a view of the outside, so you do not feel like a
lab animal when you are trying to do your experiments,"
as Heintz put it in the report.

"Let's face it, a room without a window is just a bad
place to do science," maintains Gieryn. He says that
all of the buildings that he has studied--places that
have been designed from 1985 on--have emphasized
natural light as part of their design.

"I suspect that most scientists, if forced into a
choice of having a window in their lab or in their
office, would choose to have a window in their lab,"
Gieryn contends. The reason for this, at least in
mo-lecular biology, he says, is that although
scientists "might be dealing with some fundamental
properties of life," the day-to-day tasks can be
"tedious and repetitious." Having "the ability to look
out a window to see what the weather is like and to
feel that the day is changing with the passing light"
is important to lab researchers, he adds.

Another innovative idea discussed at the workshop is
what Stark calls the "lab as a shell" concept. A lab is
a "raw, utility-rich, but otherwise bare space . . .
capable of accommodating many different layout
alternatives, which can either be built in, rolled in,
or plugged in very quickly," wrote Stark in the
workshop report. Movable walls and workbenches on
wheels are examples of likely contents of the shell
lab.

Stark says this flexibility has much appeal to
scientists because they see it as "a quick way to
readapt" to changing research proj-ects. But, other
experts ask, is it cost-effective?

"You can't really see a lab as an empty space," because
a large percentage of the total cost to build a
facility goes for the delivery of services--the
plumbing and heating, for example, Gieryn reasons.

"You can't really just sort of stop those and stub them
at the walls and pretend like you have a cavern that
you then can outfit," he asserts.

Stark says he thinks if research- facility designers
are careful in their planning, shell labs could be
cost-effective. He adds that some industrial labs,
which have to move quickly between a basic research
function and a development function, are one example of
how shell labs might work well. 

"You roll it [equipment] in and roll it out and just
make adjustments to the finishes, but the systems must
be designed to be validatable," Stark describes,
referring to the fact that, especially in industrial
labs, there must be a mechanism to constantly verify
air and water quality and other such factors.

'Entrepreneurial Seedbed'
NYAS CEO Nichols predicts that universities--funded by
individual states and such private philanthropies as
the Chevy Chase, Md.-based Howard Hughes Medical
Institute and the Pew Charitable Trust in
Philadelphia--will probably continue to be the primary
constructors of scientific laboratories.

On the other hand, industry, after a boom of building
labs in the 1980s, has been thinning out
research-and-development activities, he says. The bulk
of private-sector expansion, he remarks, will most
likely continue with small start-up companies. 

Because government funds are drying up, forcing
university-based researchers to foster more
collaborations with industry, Stark calls academia the
"seedbed for entrepreneurial companies." In this vein,
Heintz forecasted in the report that scientists may
increasingly want to maintain proximity to these 
companies in order to retain some control over the
development of their research findings. As a result of
this, he wrote, "small-scale mixed research and
development facilities accessible to the universities"
may spring up, and these new ways to collaborate "may
lead to [universities'] having a very active role in
these small [business] ventures."

State Of The Art
According to Stark and other experts in facility
design, some lab buildings constructed in the last five
to eight years--Princeton's Thomas Lab; the Schering
Plough Research Institute Drug Discovery Facility,
Kenilworth, N.J.; and the Glaxo Research Center in
Research Triangle Park, N.C., for example--do
incorporate some of the design elements discussed at
the academy's meeting.

Another lab that "makes significant gestures toward the
future," according to Stark, is the Beckman Institute
for Advanced Science and Technology, located at the
University of Illinois, Urbana-Champaign.

"In general, one's discipline of origin plays a minor
role in the [administrative] groupings" at the
institute, says William Greenough, a neuroscientist at
Beckman. "Instead of grouping people because their
Ph.D.'s are in, say, physiology or cell biology, we
group them by functional interests." 

Greenough's group, which studies how the nervous system
processes and stores information, includes researchers
in analytical chemistry, biochemistry, cell and
molecular biology, physiology, psychology, physics, and
electrical engineering. "If you think about how that
maps to a typical college campus, these people would be
blocks from each other in different buildings,"
Greenough remarks.

Echoing Gieryn and others, Greenough, who participated
in the planning of the institute, stresses that part of
the goal in designing the Beckman facility was to
"create a building that really emphasized
interactions--getting people to-gether."

For example, he says that faculty and postdoctoral
offices are arranged in "pods"--a grouping of offices
instead of a more traditional lab-office pairing. The
effect, he says, is that "you have faculty bumping into
each other in the halls all the time." 

Much like the hallway interaction spaces at Princeton's
Thomas lab, Greenough says that open areas--equipped
with tables, chairs, and wipeboards--on bridges that
connect the office wing to the lab wing of the building
are used for impromptu discussions of research ideas.
"They're used all the time," says Greenough. "The
culture here is when people are starting to work on
something," they go to the meeting areas to work out
the details. "Sometimes it's fun to walk past the
boards filled with writing and guess what people were
talking about."

(The Scientist, Vol:8, #24, p.1, December 12, 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  : Pharmaceutical Companies Stress Innovative        
      Research For Success

AU  : NEERAJA SANKARAN

TY  : NEWS

PG  : 1

As 1995 approaches, changing economic forces in the
pharmaceutical industry are presenting its scientists
with tough challenges, both professional and
scientific, according to researchers, company
officials, and other observers.

Financial setbacks and shifting business dynamics, such
as mergers and takeovers, have caused companies to
drastically downsize their work force in recent years,
they say, with more cuts anticipated. "There were some
40,000 layoffs through the entire industry in the last
two to 21/2 years, and the industry will become leaner
still in the years to come," predicts Robert Ruffolo,
Jr., vice president and director of pharmacological
sciences departments at Philadelphia-based SmithKline
Beecham Laboratories.

For scientists surviving the carnage, observers
maintain, the pressure is on to focus on novel ideas
and to increase efficiency in discovering and producing
new drugs. "Innovation has to be part of everybody's
job description," stresses Mary Graves, director of
biotechnology of Hoffmann-La Roche Inc., Nutley, N.J.

"We can't afford to do 'me-too' drugs any more,"
Ruffolo agrees, referring to times when companies
worked on improving and refining existing drugs to make
them most efficient. "In order for a company to invest
research dollars into development," he explains, it
"has to be a 'pioneer' drug the first to be able to
bind to a novel target molecule." 

But so long as the focus is on novelty, many say, there
is still plenty of opportunity for research within the
industry. According to Michael Steinmetz, vice
president of preclinical research and development for
Hoffmann-La Roche, "Biotechnological innovations now
allow us to understand mechanisms of disease, so that
things are very different from 20 years ago, when we
used blind approaches and random screening procedures
for drug discovery."

The Washington, D.C.-based Pharmaceutical Research and
Manufacturers of America (PhRMA), an industry trade
group, reports that about 10 percent of the total cuts
in the industry are in research and development. 

Furthermore, PhRMA records show, the industry
experienced the slowest rate of growth in R&D
expenditure in 22 years. What this means, Steinmetz
explains, is that "researchers are vulnerable" to
layoffs within a company, and that as a whole the
research departments will have to "learn to live with
less funds."

One way the pharmaceutical industry appears to be
coping with financial troubles is by moving toward
consolidation, several observers note. An example is
the recent buyout of Palo Alto-based Syntex Corp. by
Hoffmann-La Roche's parent company, the Roche Holding
Company of Basel, Switzerland. Another Basel company,
Ciba-Geigy Ltd., just initiated a $2.1 billion
investment into Chiron Corp., a biotech company in
Emeryville, Calif.

"The advantage in consolidations both alliances and
buyouts_is that it helps broaden the base of
innovation," Steinmetz explains. "We have better access
to the latest technologies in many different fields."
Researchers, however, are feeling the brunt of the
downside to these mergers, he says. "Such alliances can
initiate another round of head-count reduction," he
acknowledges, "so as to reduce duplications."

"It's like merging a basketball team you can only have
12 men," remarks Richard Stevenson, assistant to the
director of preclinical research and development at
Hoffmann-LaRoche. "Therefore only the best get taken."

"In a way, the large drug companies today are where the
big oil companies were at 15 years ago," notes an
academic researcher working with a major drug firm,
speaking on condition of anonymity.

"Rather than go out and dig wells themselves, it was
cheaper to buy the smaller companies who had already
struck oil," he elaborates, drawing a parallel to the
current trend on the part of large pharmaceutical
companies to invest in or take over smaller,
biotechnology-based start-up firms.
"No company is big enough to be completely
self-sufficient," Ruffolo explains, "and we are
increasingly going to the outside for new ideas. We
need to make sure we are scanning the horizon
thoroughly so that we can jump on an idea no matter
where it occurs.

"Science in the research community is advancing at such
a rapid pace that it's critical to keep abreast of
what's happening," and collaborations with smaller
firms are one way to stay current, he says.

Graves does not agree entirely with the oil-company
analogy. While she concurs that "no one turns a blind
eye to outside opportunities," she emphasizes that
"most of these collaborations  come about for the
licensing of one particular product," with the larger
company providing the financial backing for carrying an
idea through development to production.

"We will go and use [small] biotechnology companies,"
Graves says, "not to replace our own research programs,
but rather where we have gaps in a therapeutic
pipeline, or to strengthen what we already have."

"It is important to realize that there is a lot of
innovative work going on in-house, as well," Steinmetz
points out. Despite a layoff of 5,000 employees
worldwide and the recent termination of the Roche
Institute of Molecular Biology in Nutley, Hoffmann-La
Roche officials claim, the company is maintaining its
commitment to research. In October, Hoffmann-La Roche
opened its new Multidisciplinary Science Building, a
$100 million facility, at its Nutley location.

Eye On Innovation
New research ideas still abound, drug industry
researchers maintain. "There will always be a need for
an innovative new medicine," Graves stresses. "We have
to focus on important diseases that have unmet medical
needs."

For example, Ruffolo notes, "the race is on [throughout
the drug industry] to find LTD4 antagonists." LTD4 is
one of a class of molecules called leukotrienes that
are released as part of an allergic reaction during an
asthmatic attack. An antagonist, he explains, would
counteract the molecule and may thus be developed as a
drug to treat asthma.

Other promising avenues of investigation, he
enumerates, include the search for insulin
sensitizers_"drugs for treating type 2 diabetes, which
poses a major health problem," and serotonin
antagonists. "Serotonin seems to be involved in many
brain disorders," and by studying it as a potential
target molecule, researchers may be able to identify
targets for conditions like Alzheimer's disease.

At the Nutley location, investigations into therapies
for inflammation, autoimmune diseases, cancer, and
metabolic disorders are currently under way. "From the
research perspective there are exciting times ahead,"
Graves says. "We have new tools and technologies for
making significant discoveries."

Ruffolo advises graduate students interested in
entering the industry to focus on the molecular aspects
of disease. "We now have the means to look into the
workings of complex diseases and identify new targets
at the molecular level," he points out.

As the U.S. increasingly focuses on health-care issues,
Steinmetz predicts, the current strained circumstances
should abate. "As soon as people realize that the
pharmaceutical industry is contributing to an overall
cost-cutting in health care by  keeping more people out
of hospitals, they'll be willing to spend more money on
research," he anticipates. "It's not going to happen
now immediately but we should see some change over the
next five to 10 years."


(The Scientist, Vol:8, #24, p.1, December 12, 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  : PHARMACEUTICAL INDUSTRY JOB STATISTICS

TY  : NEWS

PG  : 11

The Pharmaceutical Research and Manufacturers of
America (PhRMA), a trade association of research-based
pharmaceutical companies, reports an almost 15 percent
reduction in the overall work force in the past two to
three years, with current employment totaling 266,000.

               Job Cuts, by year--1990-94

1990                          0
1991                      2,700
1992                      5,950
1993                     24,850
1994                     12,880

Total                    46,380

              Job Cuts, by company--1993-94

                     1993

May               Ciba-Geigy Corp.             600
July              Marion Merrell Dow Inc.    1,850
                  Merck & Co. Inc.           2,100
                  Syntex Corp.                 700
August            Johnson & Johnson          3,300
September         Bristol-Myers Squibb Co.   1,500
October           Eli Lilly and Co.          4,000
                  Pfizer Inc.                4,000
                  Upjohn Co.                 1,500
                  American Cyanimid Co.      2,500
                  (Lederle)
November          Warner-Lambert Co.         2,800

                     1994

January           Bristol-Myers Squibb Co.      3,500
                  DuPont Merck                    800
                   Pharmaceutical Co.   
April             Ciba Geigy Corp.                450
June              Rhone-Poulenc Rorer Inc .       200
July              American Home Products Corp.  2,300
October           Carter-Wallace Inc.             630
                  Hoffmann-La Roche Inc.        5,000

Source:  Pharmaceutical Research and Manufacturers of
America (PhRMA)

(The Scientist, Vol:8, #24, p.11, December 12, 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  :  Limited Access To cDNA Database Has Drug         
       Manufacturer Up In Arms

Incensed that the terms exclude industrialscientists,
Merckannounces sponsorship of competing project

AU   : FRANKLIN HOKE

TY   : NEWS

PG   : 1

A powerful new, privately held database of human
complementary DNA (cDNA) sequences has become available
to researchers eager to test its capabilities to
rapidly identify new genes. The proposed terms of
access to the database, however, exclude pharmaceutical
and other industry-affiliated scientists, angering some
companies, including drug giant Merck and Co. Inc.
The conditions have prompted the Whitehouse Station,
N.J.-based firm to sponsor another, largely duplicative
project that will deposit data into a publicly
accessible database. 

Other terms of access have raised concerns among
potential noncommercial users of the database developed
by J. Craig Venter, president of The Institute of
Genomic Research (TIGR), Gaithersburg, Md., a nonprofit
research institute. These include the right to preview
papers on resulting discoveries and to retain control
of patents.

The database, two years in development, currently
consists of about 150,000 expressed sequence tags, or
ESTs, which are partial sequences of human cDNA
obtained from various tissues. Because many genes are
expressed in multiple tissues, the data represent about
35,000 unique human genes, more than a third of the
estimated 100,000 human genes. TIGR has a contract
worth about $100 million with biotech firm Human Genome
Sciences Inc. (HGS), Rockville, Md., for patent options
on its discoveries; in turn, Philadelphia-based
SmithKline Beecham has agreed to pay HGS about $125
million for development rights to the discoveries.

Merck claims its objection to the terms is based purely
in science. "We see human genes [sequences] as being
essential research tools for all of drug research in
the future," says Alan R. Williamson, vice president
for research strategy worldwide at Merck. "And we've
taken the position that research tools should be shared
amongst everyone who wants to make an impact on drug
research or any therapeutic application to benefit
mankind. They should not be proprietary. We could have
taken a private position on this [new data], too, but
we decided to take a public position."

The competing sequencing project being backed by Merck
will be conducted at Washington University School of
Medicine in St. Louis. The aim of the effort, expected
to take roughly 18 months, is to sequence about 200,000
cDNA segments, with the results deposited immediately
into GenBank, a publicly accessible database of
sequences managed by the National Center for
Biotechnology Information at the National Library of
Medicine in Bethesda, Md.

Venter predicts the protests will lessen over time. He
notes that the Howard Hughes Medical Institute has
agreed to the terms, as have a number of universities.
"As people look at it closely, the issues go away, and
the initial emotional responses from the publicity
that's been generated by Merck and others totally
vanishes, because all the data's available to academic
scientists anywhere in the world," Venter says. "Over
half the data has no strings attached to it at all,
except that somebody be at a not-for-profit institution
and that they cite the database when they publish their
data."

University technology-transfer officers say that the
terms for use of the database by academic scientists
are comparable to those of companies providing
proprietary re-search materials. Genetics investigators
with no plans to commercialize their research can use
the database without restriction, and those who have
used it praise its power and do not anticipate any
limitations on their work.

One point of contention underlying the picture of
dueling databases is a sharp difference of opinion as
to the intellectual-property value of the sequences
that constitute Venter's database.

The National Institutes of Health attempted to patent,
and thereby control all future uses of, Venter's ESTs
several years ago, when he was an intramural researcher
at the agency. The move was widely criticized at the
time because no basic biological knowledge of the
genes' functions accompanied the partial sequences. 

Some critics charged that such patents, if allowed,
would have foreclosed future research. Venter, however,
claimed that placing the partial sequences into the
public domain would have rendered full genes developed
from them unpatentable, removing the incentive to work
on them (R. Eisner, The Scientist, Dec. 9, 1991, page
1). After an initial rejection of the patent filings,
NIH chose not to pursue appeals. 

"It's only the added biology that makes the DNA
sequences of any value at all as far as intellectual
property goes," Williamson contends.

Misguided Expectations?
Many scientists expected that Venter's database, when
completed, would be made publicly available because he
developed the EST technology in 1991 while he was a
government researcher or because TIGR is a nonprofit
organization. Venter acknowledges that because of the
contractual ties established among TIGR, HGS, and
Smith-Kline Beecham, the database is being made
available with restrictions to protect and capitalize
on its value as intellectual property.

"I think that everyone assumed that you only needed to
do this once, that it was being done by HGS and
TIGR--and particularly by TIGR, which was a
non-profit-making institution--and that it would be
made [publicly] available," says Williamson. "The
academic community backed off from generating this sort
of data, because they were under the impression that
this would all be made public. Once we realized that
wasn't going to be the situation, then the need for
this sort of database became apparent to us, and we
decided to commission the production of it."

According to Williamson, "many academics have said they
wanted to do this sort of thing, but they couldn't get
funded to do it because they were told it's being
done."

Officials at the National Center for Human Genome
Research (NCHGR) at NIH confirm that, because of
statements made by Venter early in his development of
the database at TIGR, they expected the data to be
publicly available and did not finance what they
thought would be redundant work.

"There was the anticipation on our part and the part of
people who are advising us that that information would
come into the public domain," recounts Mark Guyer,
assistant director for program coordination at NCHGR.
"And I think Craig would argue that he's putting it
into the public domain now and is fulfilling those
statements. So, the idea from our advisers was: This is
being done, the information is going to get out, and
therefore there's no point in the federal project
duplicating it."

Widespread expectations that the database would be made
public, Guyer adds, probably were "not entirely
consistent with what a private organization has to do
to protect its own interests. That is, in part, where
the current disagreements are based."

"People can accept a certain amount of trade-secret
mentality from a traditional company," says Joyce
Brinton, director of the office for technology and
trademark licensing at Harvard University, "But this
company isn't a traditional company, so maybe people
aren't as willing to accept the idea that they would
act like a company."

In defending his institute's contractual relationship
with HGS, Venter draws a parallel between his situation
and that of some of the scientists who now hope to
access his database.

"What I needed to do to get the funding was: I signed
away rights to commercialize discoveries made by myself
and my colleagues at the institute," Venter observes.
"Now, because of drops in federal funding, more and
more scientists are having to do that on a smaller
scale at their universities. To get funding from a
pharmaceutical company, they sign away all their rights
to commercialize [discoveries]."

Assigning Values
A question confronting university technology-transfer
officers and academic scientists is whether the
information in the database is worth what TIGR and HGS
are asking: a piece of any patents that may result. The
issue becomes one of assessing relative intellectual
contributions and recalls the debate over whether ESTs
are tools or patentable discoveries.

"It comes down to this question of how much should a
provider of something get in return for it," says
Brinton. "Do we--and I don't know the answer--have a
distorted picture of the relative values of what our
scientists would be doing vs. the [value of the]
information that we got from HGS in the first place?"
The agreement that HGS is asking institutions and their
investigators to sign to use the database is typical,
Brinton says, of so-called material-transfer agreements
involving the exchange of proprietary biological
reagents between companies and academic re-searchers. 

"But usually information has been treated in a
different way than [materials], and there is a general
view among people in the academic community that
information should be shared," she points out.

On balance, Brinton expects that arrangements will be
possible allowing Harvard researchers access to
Venter's cDNA sequences. The information, which is the
main product of TIGR and HGS, does have value, she
notes, and "a company does have obligations to its
investors. It can't give away its seed corn."

While the monetary worth of the database is still to be
determined, the experiences of several scientists who
have had the opportunity to search for genes using it
suggest that its research value may be significant.

"There was a yeast gene that we knew the amino acid
sequence of, that was involved in a biochemical pathway
of purely aca-demic interest," recalls Phillip A.
Sharp, chairman of the biology department at
Massachusetts Institute of Technology and a 1993 Nobel
Prize winner in physiology or medicine. "And it was
very laborious to think about getting the human
counterpart. But by taking the amino acid sequence and
looking directly in the cDNA database, we were able to
find a human cDNA that encoded a related amino acid
sequence, and, therefore, the equivalent protein, which
we could not get by nucleic acid homology. We then just
got the cDNA and cloned out the gene. So, it's going to
be useful, there's no question."

"The database provides a very efficient way to identify
those genes for which you might be looking because you
already know the sequence of some related gene or some
gene with a similar function," says Bert Vogelstein, a
professor of oncology at Johns Hopkins University. 

"Sometimes the classical approach to identifying a gene
can be very difficult. It can take a long time,
sometimes months, sometimes even longer, or sometimes
it may not work at all. But if the gene has already
been cloned and is in the database, it's a matter of,
literally, a few seconds to find that gene."

Vogelstein adds that, for his purposes, there were no
problems with terms of access to the database.

TIGR and HGS officials are confident that, as
researchers become more familiar with the database and
the terms of access, they will come to see the
conditions as fair ones. William Haseltine, chairman
and chief executive officer of HGS, notes that for most
scientists who use the database for research purposes
only, there is no cost. They are, however, obliged to
show their scientific papers to HGS at least 30 days
before publication for an assessment of patentability. 

Only when a discovery is deemed to be patentable and to
have commercial potential does HGS seek to exercise its
patent option, according to Haseltine, meaning that the
company will be the sole developer of commercial
products based on the discovery. The patent itself,
Haseltine notes, is the property of the university, and
the company and the school must still negotiate
specific terms for development. If they cannot agree
within six months, nor within a three-month extension
period, the rights remain with the university.

"If [a discovery] has commercial value, we've given
them something of value, and we'd like something back,"
Haseltine says. "And that's reasonable. You don't give
people the fruits of your labor for free. You just
don't do it."


Mapping Out Concerns
Officers in TIGR and HGS note that access to the
database is essentially unencumbered for most basic
researchers. For those involved in mapping projects,
however, rather than hunts for single genes, this may
not be the case. Mapping requires the use of many
sequences, and, concerned about losing control of their
data, TIGR and HGS have placed restrictions on how maps
derived from the human cDNA database may present
information.

"The people who want to construct a map have said that
they want all of the data that goes into that map
freely available," Haseltine explains. "Our position is
we're willing to make the data available in bulk for
the mapping community, provided that the points on the
map get referred to the database, and the sequences go
back to the database."

Haseltine points out that a sequence is more than a
point on a map. It is also an enabling technology,
particularly for genetic medicine.

Richard K. Wilson, a research associate professor at
Washington University who will be directing the
Merck-backed cDNA-sequencing project along with
genetics department chairman Robert Waterston, cites as 
one of the strengths of his project the fact that the
entire body of his results will be available to
mappers.

For these scientists, Wilson says, "our effort is not
redundant, because we're going to provide a lot of
sequences very quickly. These [sequences] are just
going straight to GenBank from our labs, and there is
absolutely no restriction on anything in GenBank."



(The Scientist, Vol:8, #24, p.1, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
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U.S.A.

NXT:   
------------------------------------------------------
TI  :  For One Newly Elected IoM Member, The Honor Is   
       All In The Family
AU  :  NEERAJA SANKARAN

TY  :  NEWS

PG  :  3

For more than two decades, election to membership in
the prestigious Institute of Medicine (IoM) has been a
source of pride for the honorees and their families.
But for the family of one of the 50 recently announced
members of the institute, the occasion carried an
extra- special meaning.

Margaret A. Hamburg, health commissioner of the New
York City Department of Health, became the third member
of her family to be elected to IoM. Her parents,
psychiatrists David A. Hamburg, currently president of
the New York-based Carnegie Corporation, and Beatrix A.
Hamburg, who now serves as the president of the William
T. Grant Foundation, were elected to the institute in
1971 and 1979, respectively. 

Margaret Hamburg recalls that at the October annual
meeting, at which she and the other new members--32 men
and 18 women in all--were announced, "there was a sense
of real enthusiasm and fun that the
father-mother-daughter constellation had been formed."

"It's a real distinction in the medical profession,"
adds Hamburg, who at 39 is one of the youngest people
to ever be elected to IoM. She and the other new
members will be formally inducted into the institute
during its October 1995 annual meeting.

IoM was chartered in 1970 by the National Academy of
Sciences (NAS) to address issues of health and delivery
of health services to society. Described by a longtime
member--Mary Ellen Avery, a professor of pediatrics at
Harvard Medical School--as "the medical arm of NAS,"
IoM conducts studies at the request of the United
States government and issues reports on a wide array of
policy issues related to health and medicine. Other
than sharing similar operating procedures, the two
organizations run independently. There is some overlap
in the two memberships, although induction into one
does not guarantee the other; Avery, for instance, has
been an IoM member since 1981 and served as a member of
the governing council from 1987 to 1993, but was not
elected to the academy until earlier this year.

New institute members are chosen by an electoral
process within its active membership, which according
to the charter cannot exceed 600 people and currently
stands at 493. New honorees are obliged to volunteer
their time to serve on various IoM committees engaged
in various studies. Individuals aged 66 or over are
transferred to the roster of senior members, who cannot
vote or hold office, but serve in an advisory capacity.

With this year's additions, including five individuals
elected directly to senior membership, IoM has a total
of 536 senior members in addition to 38 foreign
associates, who also do not have voting rights.

Both of the elder Hamburgs are now senior members. At
the time of her election, Beatrix Hamburg held an
appointment as an associate professor of psychiatry at
Stanford University School of Medicine. At the time of
his induction, David Hamburg, who went on to serve as
IoM president from 1975 to 1980, was chairman of the
department of psychiatry at Stanford.

While NAS advises the federal government in matters of
science and technology policy, Avery notes, "it covers
all of science, and physicians have a very small piece
of the action." As medicine and health care began to
play a bigger role in society, she adds, it became
apparent that these issues "had a dimension that was
not strictly science, but social and humanistic." The
input of professionals involved in the social,
behavioral, legal, and administrative aspects of health
issues is important for setting policy, she points out.
This realization led to the establishment of IoM.

Diverse Membership
IoM's charter provides for a broad-based membership
from within the medical community--including practicing
physicians, re-searchers, nurses, and public health
officials--and also mandates that at least one-quarter
of the total active membership be drawn from outside
the health professions. New inductee Amitai Etzioni,
founder and director of the Center for Policy Research
in Washington, D.C., and University Professor at George
Washington University, is one such example. 

"I look forward to interacting with colleagues from
'real' science and medicine," says Etzioni, a
sociologist who maintains a special interest in issues
of medical and health ethics. He is well known as the
author of the book Genetic Fix (New York, Macmillan
Publishing, 1973) in which he raised several questions
on the ethics of genetic engineering.

Over the years, Avery points out, IoM has conducted
investigations and prepared reports on crucial issues
in health policy. In the 1980s, it was "the first to
issue a study on the seriousness of AIDS," she notes.
Two reports--AIDS and Behavior: An Integrated Approach,
focusing on various behavioral and mental-health
aspects of HIV infection; and Growing Up Tobacco Free:
Preventing Nicotine Addiction in Children and
Youths--were released earlier this year, and a third,
entitled Weighing the Options: Criteria for Evaluating
Weight Management Programs, was released only last
week. Current projects being conducted by the institute
include an assessment of HIV transmission through blood
products and an evaluation of ways to bolster dental
education in the U.S.

As most new members have not yet attended any of the
institute's meetings, many say it is too soon to know
which of the specific committees and projects they will
choose to work on. Instead, they identified the areas
they would like to be involved in. For instance, Anne
B. Young, a physician and professor of neurology at
Harvard Medical School who specializes in such
neurodegenerative disorders as Alzheimer's,
Huntington's, and Parkinson's diseases, expresses her
concern with "how to deal with the increasing numbers
of people afflicted with dementing disorders." In
addition, she says, "I am interested in evaluating the
criteria for applying new predictive genetic tests to
populations at risk for various neurologic diseases."

One of the few inductees to have attended last
October's IoM meeting, Shu Chien, a professor of
bioengineering at the University of California, San
Diego, says, "I was very impressed with the timeliness
of the topics--[such as] the health aspects of
violence--and the discussions were very informative."

Chien says that his tenure as president of the
Federation of American Societies for Experimental
Biology (FASEB) in 1992-93 involved him in health
research and education, and he hopes to be involved in
these areas at IoM. 

"I still don't know what I will be involved with,
though I would like to contribute to as many [projects]
as possible. I am very honored to have been elected,"
he says.

With a diverse academic background that includes
medical training in Taiwan, a Ph.D. in physiology, and
considerable exposure to physics and engineering
through his work in bioengineering, Chien maintains
multiple research interests, including studies of blood
flow, such hematological disorders as atherosclerosis
and ischemia,  and tissue engineering.


(The Scientist, Vol:8, #24, p.3, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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

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U.S.A.

NXT:   

-------------------------------------------------------
TI  : LIST OF NEW IOM MEMBERS

TY  : NEWS

PG  : 10


Nancy E. Adler, professor of medical psychology and
director, Health Psychology Program, University of
California, San Francisco

Dyanne D. Affonso, dean and professor, Nell Hodgson
Woodruff School of Nursing, Emory University, Atlanta

Huda Akil, Gardner C. Quarton Professor of
Neurosciences, department of psychiatry; research
scientist, Mental Health Research Institute;  director,
neuroscience program, University of Michigan, Ann Arbor

Bobby R. Alford, executive vice president, dean of
medicine, and distinguished service professor, Baylor
College of Medicine, Houston

Stephen J. Benkovic, professor of chemistry,
Pennsylvania State University, University Park

Paul C. Brucker, president, Thomas Jefferson
University, Philadelphia

Patricia A. Buffler, dean and professor of
epidemiology, School of Public Health, University of
California, Berkeley

Ann W. Burgessvan, Ameringen Professor of Nursing,
University of Pennsylvania, Philadelphia

Anthony Cerami, president, Picower Institute for
Medical Research, Manhasset, N.Y.

Shu Chien, professor and chairman, department of
bioengineering, University of California, San Diego

Paul D. Cleary, professor, departments of health-care
policy and social medicine, Harvard Medical School,
Boston 

Jordan J. Cohen, president, Association of American
Medical Colleges, Washington, D.C.

Molly Joel Coye, senior vice president for community
care, Good Samaritan Health System, San Jose, Calif.

Mickey S. Eisenberg, director, Emergency Medicine
Service and section head, division of general internal
medicine, University of Washington Medical Center,
Seattle

Amitai Etzioni, director, Center for Policy Research,
Washington, D.C.; university professor, George
Washington University, Washington, D.C.

Ruth R. Faden, senior research scholar, Kennedy
Institute of Ethics, Georgetown University, Washington,
D.C.; professor and director, Program in Law, Ethics,
and Health, Johns Hopkins School of Hygiene and Public
Health, Baltimore

Thomas B. Fitzpatrick, Wiggleworth Professor of
Dermatology, Emeritus, Massachusetts General Hospital

Elaine V. Fuchs, investigator, Howard Hughes Medical
Institute Research Laboratories; Amgen Professor of
Molecular Genetics and Cell Biology, University of
Chicago

Patricia Goldman-Rakic, professor of neuroscience,
section of neurobiology, and joint appointment,
department of psychology, Yale University School of
Medicine, New Haven, Conn.

Ann M. Graybiel, professor of neuroanatomy,
Massachusetts Institute of  Technology, Cambridge

Margaret A. Hamburg, health commissioner, New York City
Department of Health

Peter M. Howley, George Fabyan Professor and chairman,
department of pathology, Harvard Medical School

Dean T. Jamison, professor of public health and of
education, Graduate School of Education; professor,
School of Public Health; director, Center for Pacific
Rim Studies, University of California, Los Angeles

Michael M. Kaback, professor, pediatrics and
reproductive medicine; and chief, division of medical
genetics, department of pediatrics, School of Medicine,
University of California, San Diego

Janet C. King, professor of nutrition, University of
California, Berkeley
Mary-Claire King, professor of genetics, department of
molecular and cell biology; professor of epidemiology,
School of Public Health, University of California,
Berkeley

Peter O. Kohler, president, Oregon Health Sciences
University, Portland

Robert J. Lefkowitz investigator, Howard Hughes Medical
Institute Research Laboratories; James B. Duke
Professor of Medicine, Duke University Medical Center,
Durham, N.C.

David E. Longnecker,Dripps Professor and chairman,
department of anesthesia, University of Pennsylvania
Medical Center

Clement J. McDonald, Distinguished Professor of
Medicine, Indiana University School of Medicine; chief,
Computer Science Research Group; codirector,
Regenstrief Institute for Health Care; associate
administrator, Wishard Memorial Hospital, Indianapolis

James J. Mongan, dean, Kansas City School of Medicine,
University of Missouri; executive director, Truman
Medical Center, Kansas City, Mo.

Joseph E. Murray, professor of surgery, emeritus,
Harvard Medical School; chief (plastic surgery),
emeritus, Brigham and WomenUs Hospital and Children's
Hospital Medical Center, Boston

Hans Neurath, professor emeritus, department of
biochemistry, University of Washington School of
Medicine, Seattle

Jane S. Norbeck, dean and professor, School of Nursing,
University of California, San Francisco

Kenneth Olden, director, National Institute of
Environmental Health Sciences, Research Triangle Park,
N.C.

Theodore L. Phillips, professor and chairman,
department of radiation oncology, University of
California, San Francisco

Irwin H. Rosenburg, Jean Mayer Professor of Nutrition
and Medicine and director, USDA Human Nutrition
Research Center on Aging, Tufts University, Boston 

Allen D. Roses, Jefferson-Pilot Professor of
Neurobiology and Neurology and chief, division of
neurology, department of medicine, Duke University
Medical Center

F. Sherwood Rowland, Donald Bren Professor of
Chemistry, University of California, Irvine

Joe Leigh Simpson, Ernst W. Bertner Chairman,
department of obstetrics and gynecology; professor,
department of molecular and  human genetics, Baylor
College of Medicine


Jerome F. Strauss III, Luigi Mastroianni Jr. Professor;
director, Center for Research on WomenUs Health and
Reproduction; associate chairman, department of
obstetrics and gynecology, University of Pennsylvania
School of Medicine

Richard W. Tsien, George D. Smith Professor, department
of molecular and cellular physiology, Stanford
University School of Medicine, Stanford, Calif.

Ming T. Tsuang, Stanley Cobb Professor of Psychiatry,
Harvard Medical School; superintendent and head,
Harvard department of psychiatry at Massachusetts
Mental Health Center, Boston

Stanley J. Watson, associate director and research
scientist, Mental Health Research Institute; associate
chairman for research and Theophile Raphael Professor
of Neurosciences, department of psychiatry, University
of Michigan, Ann Arbor

Alice S. Whittemore, professor of epidemiology and
biostatistics, department of health research and
policy, Stanford University School of Medicine

Jean D. Wilson, Charles Cameron Sprague Distinguished
Chair in Biomedical Science; chief, division of
endocrinology and metabolism, department of internal
medicine, University of Texas Southwestern Medical
School, Dallas

Flossie Wong-Staal, Florence Seeley Riford Professor of
AIDS Research and professor of medicine and biology,
University of California, San Diego

Tadataka Yamada, John G. Searle Professor and chairman,
department of internal medicine, University of Michigan

Anne B. Young, Julieanne Dorn Professor of Neurology,
Harvard Medical School; chief, Neurology Service,
Massachusetts General Hospital, Boston

Gordon H. DeFriese, professor of social medicine,
epidemiology, and health policy and administration;
director, Cecil G. Sheps Center for Health Services
Research, University of North Carolina, Chapel Hill

Paul Nutting, director, Ambulatory Sentinel Practice
Network, Denver

John A. Oates Jr., professor of medicine and
pharmacology; Thomas F. Frist, Sr. Professor and
chairman, department of medicine, Vanderbilt University
School of Medicine, Nashville

Richard L. Simmons, George Vance Foster Professor of
Surgery and chairman, department of surgery, University
of Pittsburgh; associate dean for clinical affairs,
School of Medicine; associate vice president for
clinical affairs, University of Pittsburgh Medical
Center

Gerald N. Wogan, Underwood-Prescott Professor and
director of toxicology, Whitaker College of Health
Sciences and Technology, Massachusetts Institute of
Technology

William J. Hadlow, former research veterinarian, Rocky
Mountain Labs (NIAID), Hamilton, Mont.


(The Scientist, Vol:8, #24, p.10, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
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NXT:   

------------------------------------------------------
TI  : Sagan Symposium Spans Galaxy Of Science

AU  : BARTON REPPERT

TY  : NEWS

PG  : 4

As one might imagine, the topics discussed at a
symposium honoring Cornell University astronomer and
space scientist Carl Sagan's 60th birthday ran the
intergalactic gamut, even venturing into
extraterrestrial intelligence.

But the two-day event on the Ithaca, N.Y., campus in
October was, at times, as much a forum on national and
international policy--especially space policy--as a
testimonial to the career of the celebrated science
figure, with Sagan himself a major contributor to the
eclectic dialogue.

National Aeronautics and Space Administration associate
administrator Wesley T. Huntress, Jr. declared that "we
need to complete a full reconnaissance of the solar
system, and begin an era of surface mapping" while also
striving to detect and study planets around other
stars.

Roald Z. Sagdeev, former chief of the Soviet Union's
leading space institute, urged substantially increased
U.S.-Russian cooperation in space exploration, while
arms-control expert Georgi Arbatov of the Russian
Academy of Sciences contended that the "major enemy" of
both countries is now the proliferation of nuclear
weapons.

Other talks were equally wide-ranging in scope: current
proj-ects and problems of the U.S. space program, the
search for extraterrestrial intelligence (SETI),
studies on the origin of life, future "terraforming" of
Mars so that it might sustain living habitation, the
need for better science education, improving reporting
on science in the news media, and the increasingly
important role of scientists in public-policy debates. 

The occasion drew some 350 scientists, engineers,
social thinkers, government officials, diplomats, and
other invited guests from across the U.S. as well as
Russia and five other countries.

Cornell president Frank H.T. Rhodes told a banquet
audience at the conclusion of the symposium: "It takes
two days and 25 speakers to merely outline Carl's work.
It shows the astonishing breadth, from astronomy and
public policy to education, of his interests."

Sagan, David Duncan Professor of Astronomy and Space
Sciences and director of the Laboratory for Planetary
Studies at Cornell, has played a leading role in the
Mariner, Viking, Voyager, and Galileo planetary
expeditions. He is known for his research on the
massive greenhouse effect on Venus, windblown dust as
an explanation for the seasonal changes on Mars,
organic aerosols on Titan, the origin of life, and the
possible long-term consequences of nuclear war.

Cofounder and president of the 100,000-member,
Pasadena, Calif.-based Planetary Society, the world's
largest space-interest group, Sagan is the author,
coauthor, or editor of more than 20 books. Among his
best-known titles are The Dragons of Eden (New York,
Random House, 1977), Broca's Brain (Random House,
1979), and the novel Contact (New York, Simon and
Schuster, 1985), which is currently being made into a
movie starring Jodie Foster. His newest book, Pale Blue
Dot: A Vision of the Human Future in Space, is to be
released this month (see accompanying story).

Sagan's television series "Cosmos" has won Emmy and
Peabody awards, and became the most widely watched
series in the history of American public television.
The companion book, also called Cosmos, was on the New
York Times bestseller list for 70 weeks and became the
best-selling science book ever published in the English
language.

Although plaudits for Sagan himself were abundant, most
of the speakers at the symposium eventually turned
their attention to his favorite subject--space. 
Huntress told the attendees that "for many on this
planet, Carl is the personification of science--and in
particular space science and space exploration. He's
reached millions of people with his articles, his
television appearances, and his books."

The NASA official added: "Carl realized long ago that
scientists have a responsibility to participate in
society. They cannot stay safely in their labs and
offices any longer, divorced from the rest of the
world. Carl recognized early, more than most, that
science can continue to prosper only if the public can
participate in its excitement--and that scientific
discoveries have value only if they are shared."

Surveying the field of space exploration, Huntress said
that, in addition to further probes studying the solar
system, "it's time to expand the purview of planetary
science, and detect and classify planets around other
stars, what their atmospheres are like, and whether
they are inhabited or whether they are habitable. We
also need to complete a map of the universe along the
entire electromagnetic spectrum."

O.B. Toon, a space scientist at NASA's Ames Research
Center, Moffett Field, Calif., hypothesized that in the
future it might be possible to utilize carbon,
nitrogen, and oxygen in the soil of Mars to
"rehabilitate" portions of that planet so they could
sustain human or at least plant life. However, he
cautioned, "terraforming Mars would be a massive
project."

Elsewhere in the universe, Toon added, "the most
exciting development of the next few decades" would be
the discovery of "habitable zones," offering conditions
amenable to life, in solar systems around other stars.

A Mission To Mars?
Sagdeev, former head of Moscow's Institute of Space
Research, and now director of the East-West Center for
Space Science at the University of Maryland, College
Park, reviewed the sometimes-checkered history of
Soviet lunar and planetary missions. He noted that in
1988, Sagan went to Russia to discuss the possibility
of a joint manned flight to Mars, but that then-Soviet
leader Mikhail S. Gorbachev failed to persuade
President Ronald Reagan on the merits of such a
project.

Looking ahead, Sagdeev said, a possibility remains for
a robotic mission to Mars in 1998. The Russians, he
noted, also are considering an unmanned mission to
Venus; a robotic lunar landing; a mission to return
samples from Phobos, a moon of Mars; and perhaps
reviving efforts toward a joint U.S.-Russian manned
mission to Mars.

At a news conference during the symposium, Sagan
confirmed about Mars exploration that "there are, in
fact, 25 robotic missions that are either in the works
or in the serious planning stage, between 1996 and
2005. This involves the United States, Russia, the
European Space Agency, Germany, Italy, Japan, a
consortium of smaller nations including Austria, and
England. It's very clear that, at least as far as
robotic exploration goes, we are on the threshold of an
extremely exciting time in the exploration of Mars."
However, a manned mission to Mars, he speculated, is
unlikely: "That's much more expensive, much more
difficult. It's premature to do that."

Frank Drake of the University of California, Santa
Cruz, described past efforts in the SETI program. Now,
he said, "there is a great deal of evidence that
planets like our own are abundant. It suggests modes of
life are abundant in the Milky Way."

Drake, director of the SETI Institute, pointed out that
today, using radio telescopes such as the one at the
Cornell-operated Arecibo Observatory in Puerto Rico,
"SETI is capable of detecting signals anywhere in the
universe."

Arbatov, former director of Moscow's Institute of the
USA and Canada, who served as a senior adviser to
Soviet leaders, told the audience that in the wake of
the Cold War "there is the need for a real revolution"
in international relations, in order to overcome the
"militarized mentality" of past decades.

With the end of the communist system and the breakup of
the Soviet Union, he said, "we deprived you of an
enemy. We deprived ourselves of an enemy. Never had the
powers spent as much on military power as during the
nuclear era, and we were not ready. Because we don't
have the United States as an enemy and you don't have
us, our major enemy is the proliferation of nuclear
weapons. All other nations will ask, why shouldn't we?
This is the most important thing that has to be taken
into account now."

How the U.S. will stand up to challenges, especially
scientific ones, is a cause for concern to Sagan.
Commenting about the overall performance of the
Clinton-Gore administration in the science and
technology area, Sagan told reporters at the news
conference, "There's no question that the vice
president is the most scientifically literate and, in a
way, gifted president or vice president in many, many
years.

"But on the other hand, the political muscle of this
administration is somewhat dubious. So their ability to
carry out well-conceived programs is not certain. It's
very striking how little they've been able to do on the
environment, despite the clear dedication of the vice
president."

Other speakers at the symposium included Edward C.
Stone, director of NASA's Jet Propulsion Laboratory in
Pasadena, Calif.; Richard P. Turco of the University of
California, Los Angeles, coauthor with Sagan of a
controversial study on the "nuclear winter" likely to
follow a nuclear war (Science, 222:1283-92, 1983);
William G. Aldridge, executive director of the National
Science Teachers Association; Richard Garwin, a senior
scientist with IBM Corp. of Armonk, N.Y.; Frank Press,
White House science adviser during the Carter
administration and former president of the National
Academy of Sciences; and Walter Anderson, editor of
Parade magazine.


Barton Reppert is a freelance science writer based in
Gaithersburg, Md.

(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

------------------------------------------------------
TI  :  THE LATEST FROM SAGAN

AU  :  BARTON REPPERT

TY  :  NEWS

PG  :  4

Carl Sagan's latest book, Pale Blue Dot: A Vision of
the Human Future in Space (to be released this month by
Random House), serves as a sequel to his 1980
bestseller, Cosmos. Following are a few excerpts:

On Humanity's Place in the Universe: "The Earth is a
very small stage in a vast cosmic arena. . . . It has
been said that astronomy is a humbling and
character-building experience. There is perhaps no
better demonstration of the folly of human conceits
than this distant image of our tiny world [as viewed
from the Voyager 1 spacecraft, while heading out of 
the  solar  system].  To  me,  it  underscores  our 
responsibility to deal more kindly with one another,
and to preserve and cherish the pale blue dot, the only
home we've ever known."

On Future Settlements on Other Worlds: "Surface or
underground habitats on asteroids or the Moon seem
technically feasible by the middle- to late 21st
century. Many resources could be supplied from the
world itself. Because the gravity is so low,
human-powered flight would be easy."

On Settling Mars: "If we wanted to set up housekeeping
on Mars, it's easy to see that, in principle at least,
we could do it. There's abundant sunlight. There's
plentiful water in the rocks and in underground and
polar ice. The atmosphere is mostly carbon dioxide.
There's a great deal of organic matter on nearby
Phobos, which could be plowed out and delivered to Mars
below. . . .  It seems likely that in self-contained
habitats--perhaps domed enclosures--we could grow
crops, manufacture oxygen from water, recycle wastes."

On the Search for Extraterrestrial Intelligence (SETI)
Project: "SETI is one of those search programs
irritating to those who want well-defined cost/benefit
ratios. Whether ETI can be found, how long it would
take to find it, and what it would cost to do so are
all unknown. The benefits might be enormous, but we
can't really be sure of that either. It would of course
be foolish to spend a major fraction of the national
treasure on such ventures, but I wonder if
civilizations cannot be calibrated by whether they pay
some attention to trying to solve the great problems."

On Seeking Future Security in Space: "Since, in the
long run, every planetary society will be endangered by
impacts from space, every surviving civilization is
obliged to become spacefaring--not because of
exploratory or romantic zeal, but for the most
practical reason imaginable: staying alive. . . .  A
cataclysmic impact on one world would likely leave all
the others untouched. The more of us beyond the Earth,
the greater the diversity of worlds we inhabit, the
more varied the planetary engineering, the greater the
range of societal standards and values--then the safer
the human species will be."

--B.R.


(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   


                        NOTEBOOK

------------------------------------------------------
TI  : Take This Grant And . . .

TY  : NEWS (NOTEBOOK)

PG  : 4

Molecular biologist John Fagan made nationwide
headlines the week before Thanksgiving when he said
thanks--but no thanks--to the National Institutes of
Health, returning a grant of nearly $614,000. Fagan, a
professor of molecular biology at Maharishi
International University (MIU) in Fairfield, Iowa,
returned the grant--for research on two genes that are
blueprints for cytochromes P450, involved in carcinogen
and toxin metabolism--to protest genetic engineering, a
field he believes is progressing too rapidly and
without consideration of its harmful implications.
Fagan, who got his Ph.D. from Cornell University in
1977 and was a research fellow at NIH before he joined
MIU in 1991, brought a measure of respect to the
institution,  the site of 1994 Ig Nobel Prize-winning
research concluding that meditators caused a decrease
in violent crime in Washington, D.C. Losing the funding
is "a big hit" for the school, acknowledges Fagan, who
is redirecting his work toward cancer prevention and
hopes to obtain future NIH grants. Jerome Green,
director of NIH's Division of Research Grants, says
Fagan's ability to obtain subsequent funding "depends
on how far afield he goes" from areas in which he has
demonstrated "competence and experience."


(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
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NXT:   

------------------------------------------------------
TI  : A Year On The Hill

TY  : NEWS (NOTEBOOK)

PG  : 4

Applications are currently being solicited for the
1995-96 congressional Office of Technology Assessment
(OTA) Congressional Fellowship Program, in which
scientists take a year off to advise Congress in its
deliberations of science and technology issues
affecting public policy. Salaries range from $35,000 to
$70,000. Applications must be submitted by February 1.
The fellowship is expected to begin in September. For
information, contact Morris K. Udall Fellowships,
Personnel Office, Office of Technology Assessment, 600
Pennsylvania Ave., S.E., Washington, D.C. 20003.


(The Scientist, Vol:8, #24, p. , December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

-------------------------------------------------------
TI  : The Verdict

TY  : NEWS (NOTEBOOK)

PG  : 4

In a long-anticipated report made public on November
25, the Office of Research Integrity (ORI) concluded
that Thereza Imanishi-Kari, who was a researcher in
David Baltimore's Massachusetts Institute of Technology
laboratory in 1986, committed scientific misconduct
when she "fabricated and falsified" data published in
Cell, 45:247-59, 1986, as well as data appearing in a
letter of correction to the paper, published in Cell,
57:515-6, 1989, and in two National Institutes of
Health grant applications. The report, which found
Imanishi-Kari, now at Tufts University, guilty of 19
charges of misconduct, was made available to her in
September; on November 23, she requested a hearing on
the findings. If ORI's conclusions are sustained,
Imanishi-Kari would be prohibited from receiving
federal grant or contract money or participating in
cooperative agreements for 10 years. She did not return
telephone calls from The Scientist seeking comment.


(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

---------------------------------------------------
TI  : Interview With Several Bats

TY  : NEWS (NOTEBOOK)

PG  : 4

The mythical image of the bat might conjure visions of
Bela Lugosi, or, more to the moment, Tom Cruise, as
vampires seem to be making a comeback on the silver
screen. In fact, say the Penn State University authors
of a study of the nesting habits of "house" bats, the
more appropriate image might be a star of a
do-it-yourself home-repair show. For example, according
to Lisa Williams, a graduate research assistant who led
the investigation for Pennsylvania's Wild Resource
Conservation Fund, female big brown bats, which use
attics to communally raise their young, appear to
assess external aspects of a house--such as age,
height, home style, accessibility, and roofing
material--in selecting roosting sites. The study is
important for those who want to coax the creatures from
their attic or even attract the mammals to their
homestead, a tactic that Williams, who coauthored the
study with Penn State associate professor of wildlife
resources Margaret Brittingham, encourages. The
investigators designed a box that would precisely mimic
the height, decor, and ambience--such as widely
fluctuating temperatures--of the attics bats find so
attractive. The boxes are hung from trees or attached
to the buildings themselves. 


(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)
              ================================


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NXT:   

------------------------------------------------------
TI  : And No Tan Lines!

TY  : NEWS (NOTEBOOK)

PG  : 4

Researchers at Boston University School of Medicine
(BUSM) have developed a method to get a permanent jump
on the tanning season without messy, orange-tinted
"sunless tanning" products. The team, led by BUSM
dermatology department chairwoman Barbara A. Gilchrest,
developed a topical preparation that causes an increase
in melanin pigment production and a darkening of the
skin color identical to that resulting from exposure to
ultraviolet light. The preparation's secret ingredient:
small DNA fragments, especially thymidine
dinucleotides--ask for them by name.


(The Scientist, Vol:8, #24, p.4, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

                     OPINION

------------------------------------------------------
TI  : U.S. Science Confronts A New Uncertainty          
      Principle

AU  : ALAN SCHRIESHEM

TY  : OPINION

PG  : 12

Sixty-seven years ago, German physicist Werner
Heisenberg informed us that we cannot determine with
any degree of accuracy both the position and the
momentum of a subatomic particle. This is the famous
Heisenberg Uncertainty Principle of quantum mechanics.

This principle revolutionized high-energy physics,
taught us to think in relativistic rather than absolute
terms, and has guided subsequent generations of
research scientists.

Heisenberg, of course, received the 1932 Nobel Prize
for his trouble.

Today, science in the United States faces a new
uncertainty principle. This principle says that we
cannot forecast with much accuracy the position, the
momentum, or the probable intersection of society's
goals, the nation's political agenda, and the
scientific merits of our national research enterprise.

Like Heisenberg's postulation, this new uncertainty
principle is revolutionizing the management and the
direction of America's labs, is teaching us to think in
relativistic rather than absolute terms, and is
guiding--and sometimes vexing--modern generations of
research laboratory directors, including this one.

There is an important difference, however. Our reward
for planning the labs' future in accord with this new
uncertainty principle will not be a Nobel Prize.
Instead, our reward will be our survival in the 21st
century as vital and essential American institutions.

Conflicting Agendas
Once, the vagaries of scientific research were
acceptable in America because political, scientific,
and social agendas largely coincided: We wanted
national security in the face of threats from a large
and well-defined enemy, we were destined to grow, and
we needed energy to do it. These agendas no longer
coincide.

Interplay and occasional conflict among the objectives
of science, government, and society are relatively new
additions to the environment within which the nation's
research labs function. 

The divergence of political, social, and scientific
agendas happened slowly. It was, perhaps, the chemists
who came up against it first--in the environmental
firestorm erupting from the pages of Rachel Carson's
Silent Spring (Boston, Houghton Mifflin, 1962) and the
anger of Love Canal. The energy labs got a wake-up call
from the OPEC oil embargo, smog warnings, Three Mile
Island, Chernobyl, oil-soaked shore birds, and the
so-called ozone hole. Our colleagues in high-energy
physics encountered it somewhat more recently, in the
scuttling of the superconducting supercollider (SSC).

But the biggest single impetus to change in American
research came when the Cold War collapsed in the rubble
of the Berlin Wall. Suddenly, America no longer faced a
well-armed, technologically sophisticated enemy capable
of destroying us with just 30 minutes' warning. Defense
research needs, projections, and budgets dropped
precipitously, and are still falling.

Major new challenges moved to the forefront in
post-Cold War America, and the national scientific and
technological establishment began to feel the pain and
promise of a fundamental transformation. Nowadays,
industry increasingly is seeking out opportunities to
team with other R&D performers--including former
competitors--in the development of new technologies. 

There is growing political pressure for all public
investments to be tied more closely to national
needs--as those needs are perceived by the Washington
political establishment.

Scientific latitude was greater in the past because we
could presume continued national consensus on exactly
what the needs were. That's no longer so. The startling
results of the November elections are the latest in a
series of reminders that the definition of "national
needs" today is a moving target. Here's the core of the
whole "New Uncertainty Principle": Science must not
only determine what today's definition is, but also
project--some might say divine--what the definition
will be tomorrow and plan accordingly. Assuming we do
that, and to further compound a complex situation, we
must craft our course to recognize tomorrow's
definition while not falling afoul of today's.

What is already apparent is that the principles of
total quality management increasingly are being applied
throughout industry and government, including at
research institutions. And the traditional boundaries
between federal R&D agencies are getting fuzzier, as
the nation seeks to provide multiagency, coordinated
approaches to satisfying national needs. "Progress at
any cost" is out. Fiscal accountability, environmental
responsibility, and cost efficiency are in. And, in a
trend likely to continue, research under way or
projected is far more likely than in the past to have a
strong thrust toward marketplace applications.

Environmental protection, long a goal of some research,
is rapidly becoming a precondition for all research.
International competitiveness and job creation are only
slightly below in the pecking order.

>From Push To Pull
We now find corporations with global competitive
interests deeply involved in cooperative R&D agreements
with national laboratories. At Argonne, we already work
with DuPont Co. of Wilmington, Del.; Midland,
Mich.-based Dow Chemical Co.; Amoco Corp. of Chicago;
IBM Corp. in Armonk, N.Y.; New York-based Exxon Corp.;
and many other companies. We are collaborating on
profit-oriented projects aimed at producing
higher-quality fiber, stronger materials, more
effective pharmaceuticals, faster computers, safer
herbicides, and lower-cost gasoline. We are fully
engaged in technology transfer and have even helped
create spin-off companies.

Ten years ago, these activities would have been
exceptional. Today, they represent a major research
management trend at the national laboratories. We
increasingly serve as a common ground to integrate
skills, capabilities, technologies, facilities, and
research organizations--including partners from
throughout the laboratory system, other federal
agencies, industry, academia, and other nations. 
Clearly, we are moving from a technology-push
philosophy to a market-pull philosophy.

New Paradigms
Increasingly, we find that proposed research must be
shown to benefit social goals and political objectives
as well as to advance science and technology. Whether
we call that "kitchen-table impact," "sustainable
development," or some other term, it is the new
reality. What also makes it the new uncertainty is the
fluid nature of societal goals and the political
agenda--not to mention the inherent uncertainties of
venturing beyond the state of the art.

This new paradigm does hold promise for the nation,
particularly in the short term. But it is not without
its pitfalls, especially for those of us engaged in
basic research, for which the industrial, economic, and
environmental pay-offs are unspecified and largely
unpredictable and, for the average citizen, can be so
obscure as to be nonexistent.

Eminent marine biologist Eugenie Clark wrote in 1969
(The Lady and the Sharks, New York, Harper and Row,
Chapter 1): "Not many appreciate the ultimate power and
potential usefulness of basic knowledge accumulated by
obscure, unseen investigators who, in a lifetime of
intensive study, may never see any practical use for
their findings but who go on seeking answers to the
unknown without thought of financial or practical
gain." Her comment is even more apt today, as anyone
involved in the ill-fated SSC will no doubt agree.

Hers is a point we should remember as we strive to
blend scientific potential with political reality,
economics, and environmentalism heading into the 21st
century. We must continue to advance science in a
society where researchers will increasingly be
challenged to justify their work, especially on
economic and environmental grounds. Such concerns, now
largely confined to North America and Europe, will
expand to Asia, Africa, and other areas where they have
not traditionally been a major consideration.

Proposed products and processes will have to be proved
environmentally benign before they receive approval to
proceed. This prior-proof requirement could have one
troublesome effect--shorter-term thinking in the
research community. We may be tempted toward the safer
course of evolving current products rather than the
environmentally and economically riskier path of
developing wholly new products.

Most of the research projects American science
undertakes from now on almost certainly will include a
strong energy context, flavored with an environmental
and job-creation agenda. In fact, the energy imperative
will supplant defense as the main research driver in
the 21st century. World population is expected to
double by mid-century. Global energy demands are
projected to at least quadruple (even with stringent
conservation measures in place). Society's burgeoning
need is apparent.

Walking through a bookstore one recent weekend, I
noticed a copy of Thomas Wolfe's famous work You Can't
Go Home Again. Wolfe wasn't writing about research
laboratories, of course, but he might just as well have
been. For we can't go home again, either. That is, if
"home" means the past--a time when science was apart
from, or "above," society and politics, somehow
entitled to the public's support yet not really
accountable except to future generations.

Management Principles
To come to terms with the new uncertainty principle,
we--like Heisenberg's contemporaries--must change our
perspective and our methods. We must formulate and
adopt new research-management paradigms. Here are four
candidates:

1. The degree to which politics and society will
support scientific research is directly proportional to
perceived return on investment. We research directors
must be able to articulate the return to be derived
from public investments in our work. We must not only
be able to, but also willing to.

2. Pre-challenge political involvement is always more
effective than post-challenge involvement. The research
community must become more engaged in the political
world and with its denizens, preferably before projects
are challenged. We must overcome our community's
traditional disdain for the "soft sciences," such as
politics and sociology, recognizing that ultimately
politics controls the money and support we need to do
our work. The extent to which we avoid the political
process is precisely the extent to which others will
decide our fate.

3. The more the public knows about science and
technology, the more likely it is to support science
and technology. Here is an important issue for the 21st
century--scientific literacy. We scientists have a
clear obligation to increase scientific literacy in
American society. Doing so will help our fellow
citizens cope with what we all know will be an
increasingly technological world. Doing so will also
foster greater understanding of what it is that we do. 

In short, working to improve scientific literacy is not
only the right thing to do, but also the smart thing.

4. Finally, it is wise to remember that, when you are
speaking to an audience of Greeks, communications
efficiency increases markedly if you speak Greek. 

Scientists must do a better job of making our case in
terms that politics and society understand. In
hindsight, arguing for billions of dollars to build the
SSC because it might help us locate the Higgs boson may
go down as a textbook example of speaking Russian to
the Greeks, and then being surprised when the Greeks do
not understand--or do not wish to contribute to the
effort.

At the national laboratories, we see our role in the
21st century as that of a neutral site and a robust
bridge, connecting all the country's research
communities; universities; industries; and federal,
state, and local government agencies in a common
research enterprise geared to the needs of society,
both today and tomorrow.

Precisely because the national labs deal daily with the
New Uncertainty Principle, we may well become the
catalyst that helps our colleagues in the American
research community continue the advance of science and
technology.

Alan Schriesheim is director and CEO of Argonne
National Laboratory in Illinois. This essay is adapted
from remarks he delivered at the General Motors R&D
Center, Detroit, on Nov. 9, 1994.

(The Scientist, Vol:8, #24, p.12, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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U.S.A.

NXT:   

                        COMMENTARY

------------------------------------------------------
TI  : Scientific World's Low Tolerance For Controversy  
      May Be What's Excluding Young Investigators

AU  : NAOMI KRAUS

TY  : OPINION (COMMENTARY)

PG  : 13

The process by which research is supported is under
continuous scrutiny, which is a good thing, because it
means that those responsible for policy-making do care.
It is also the topic utmost on the minds of scientists.
For example, the National Institutes of Health recently
conducted a roundtable discussion on many diverse
aspects of the funding process (FASEB Newsletter,
August/September 1994, page 4). And the congressional
General Accounting Office this year released its
findings on the peer-review system, concluding that it
appears to be working reasonably well (E. Marshall,
Science, 265:86, 1994).

Among scientists, Joachim Messing, in his excellent
commentary (The Scientist, June 27, 1994, page 13),
made the case for supporting many small, rather than a
few large, projects. Some excellent suggestions on
improvements have also been proposed by Jose M.
Musacchio, though he, too, refrains from suggesting
major changes in the peer-review system (FASEB Journal,
8:679-83, 1994).

Of all the information recently brought out on
sponsored research, one fact is truly alarming. This is
the decrease in the number of young scientists who
apply for grants. According to a new report by the
National Research Council (NRC), applications for
National Institutes of Health funding from researchers
under 36 years of age declined about 55 percent between
1985 and 1993 (The Funding of Young Investigators in
the Biological and Biomedical Sciences, Washington,
D.C., National Academy Press, 1994). If this trend
continues, it will lead to the decline, if not the
extinction, of academic research in the United States.

The NRC study found that young investigators' success
rate in obtaining funds "was lower than that of many
age groups--a new and special disadvantage." I want to
propose the thesis that this is hardly a coincidence:
Younger investigators might have a lower success rate
than older and established investigators exactly
because of their ability to approach problems in a new
and original viewpoint--the very qualities that form
the basis of progress in science.

When I started to observe the scientific scene, about
30 years ago, controversy was viewed as an integral
part of progress, a process in which ideas and facts
are sorted out and paradigms are shaped. For several
years I regularly anticipated the discussions between
Peter Mitchell, who presented arguments for the
chemiosmotic mechanism of oxidative phosphorylation,
and his opponents, who vigorously argued against it, at
various meetings of the Federation of American
Societies for Experimental Biology. Those arguments
were exciting. The atmosphere was electrifying, and I
felt that I was part of an endeavor that was not only
stimulating but also open, in which the best arguments
and facts eventually would win.

I no longer feel this way. Controversy is no longer
viewed as the warf and woof of the fabric of science.
On the contrary, it seems to be perceived by the powers
that be as a potential source of embarrassment, which
might create problems for the public image of science.
As reported in a recent article on grantsmanship (A.S.
Moffat, Science, 265:1921, 1994): "The most challenging
part of developing a research proposal . . . is to find
a balance between something sure and something new." 

However, the message being sent to conveyors of the new
is that not only should their work have the assurance
that its support does not involve risks--namely, it
will result in X number of publications--but also that
it should be in line with, rather than challenge,
existing views. Young investigators (and some nave,
incorrigible, old investigators) might not have learned
the importance of staying in the "mainstream"--which
might contribute to their lower success rate.

However, the way young scientists fare is the way the
future of science fares. In order to arrest this trend
of decline in successful young applicants, either they
should be taken out of the present peer-review system
and their applications considered under a specifically
designated new category, or the powers that be need to
reevaluate the type of research that is funded. The
current emphasis on "mainstream" thinking, along with
discouragement of dissent and innovation, ultimately
stifles--if not entirely paralyzes--progress in
science.

Naomi Kraus is a professor in the department of
physiology and cell biology at the University of Texas
Health Science Center, Houston.


(The Scientist, Vol:8, #24, p.13, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   
                          LETTERS

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

AU  : JOSE M. MUSACCHIO

TY  : OPINION (LETTERS)

PG  : 13

Hugh Stamper's letter (The Scientist, Oct. 17, 1994,
page 13) concerning my commentary "Triage At NIH: A
Smoke Screen Concealing The Real Problems Facing
American Science" (The Scientist, Sept. 5, 1994, page
13) contains some interesting news, but also some
unsubstantiated statements. I was glad to learn that
the National Institute of Mental Health (NIMH) has
changed the triage procedures regarding communication
with the applicants, who now will receive the unedited
comments from each reviewer. We discussed a preliminary
triage model in the NIMH Initial Review Groups (IRG)
chairpersons' meeting of Dec. 6, 1993. The model
(attachment 3, NIH memorandum No. OER 88-5) indicated
that the principal investigators whose applications
were deemed noncompetitive (NC) were going to receive
only an abbreviated summary statement. The model
attached contained about 220 words, and its brevity was
considered to be an advantage and a selling point for
the reviewers.

It is good to know that the plans were changed, and
that the applicants will receive the reviewers' full
comments. The bad news is that the change will impose
an even higher burden on the study-section members, who
now must write their reviews in an objective editorial
style, suitable for consumption by deeply disappointed
applicants. In the good old days, reviewers who do not
write well, like me, relied on the editorial abilities
and good judgment of the scientific-review
administrators. It is obvious that to write the
critiques in final form will require more time and
effort, no matter what Stamper says. However, this
problem has been neglected, perhaps because reviewers
are not paid for their writing time. Despite the
reviewers' increase in work, applicants whose proposals
are deemed NC will not receive a summary of the IRG
discussions. This can hardly be considered an advantage
for the applicants, but at least the load of the
scientific-review administrators will be drastically
reduced. They certainly deserve a break.

I was surprised that Stamper got involved with such a
small issue, but I was glad to know that triage was
reinvented with a better flavor. I am also pleased with
his silence on more important issues, because it may
indicate that he agrees with my views in "American
science in crisis: The need to revise NIH funding
policy" (FASEB Journal, 8:679-83, 1994).

Finally, and contrary to Stamper's opinion, I think
that I do understand that the issue of triage can be
logically separated from the current crisis in
biomedical research funding. What I do not understand
is the excessive time and effort spent in discussing,
advertising, and implementing superfluous changes,
instead of concentrating on drastically revising the
NIH funding policy, as I proposed.

Jose M. Musacchio
Department of Pharmacology
New York UniversityMedical Center
550 First Ave.
New York, N.Y. 10016


(The Scientist, Vol:8, #24, p.13, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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NXT:   

-------------------------------------------------------
TI  : 'One-Party' Science

AU  :  PAUL EVANS

TY  :  OPINION (LETTERS)

PG  :  13


I was supportive of J. Philippe Rushton until he
attacked those he believes to be "politically correct"
("'One-Party' Science Poses Threat To Scientists'
Intellectual Freedom," The Scientist, Oct. 3, 1994,
page 13). Rushton needs to learn that some people are
earnestly sensitive to the issues he is studying and
are concerned about the implications of the misuse of
this scientific information. He should not label all
who disagree with his form of "one-party science" as
politically correct.

The arts and the sciences are under attack by those who
do not understand them. His threatened "I'm a victim"
stance does nothing to help his case and makes this
black scientist question his motives.

As a member of the American Association for the
Advancement of Science, I am pleased that the
association actually has the courage to have a dialogue
on the ethical issues that are of concern to all good
scientists, and Rushton as well. He would do well to
get off of his soap box and listen.

Paul Evans
P.O. Box 1830
Boston, Mass. 02205

(The Scientist, Vol:8, #24, p.13, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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NXT:   

                         RESEARCH

-----------------------------------------------------
TI  : Changing Scientific Times Drive NIGMS Research    
      Agenda

AU  : KAREN YOUNG KREEGER

TY  : RESEARCH

PG  : 14

>From the early days of research in molecular
biology--the discovery of restriction enzymes, which
paved the way for recombinant technology, for
example--to pharmacologist Alfred G. Gilman's 1994
Nobel Prize-winning investigations of G proteins,
scientists funded by the National Institute of General
Medical Sciences (NIGMS) have been advancing the life
sciences. In fact, more than half of the National
Institutes of Health-supported Nobel Prize winners have
received grants from NIGMS.

Today the institute--which supports extramural
investigators almost exclusively--funds basic research
in such areas as cell biology, genetics, and
biochemistry aimed at finding out how systems work,
usually before the implications for specific diseases
are known.

Last October, NIGMS reorganized its administrative
structure with the purpose, according to an institute
statement, of becoming more efficient in its support of
basic biomedical research and training and to reflect
the increasingly interdisciplinary nature of science. 

Specifically, four program branches--cellular and
molecular basis of disease; genetics; biophysics and
physiological sciences; and pharmacology and biorelated
chemistry--have been reorganized into three divisions:

y cell biology and biophysics;
y genetics and developmental biology; and
y pharmacology, physiology, and biological chemistry.

Two other NIGMS programs have also become divisions:
minority opportunities in research and extramural
activities. Cost-cutting measures, as part of the
Clinton administration's efforts to decrease the
federal work force--particularly middle management--was
a secondary, but not a deciding, factor shaping the
reorganization, institute officials maintain. They
point out that no one at the institute has lost his or
her job as a result of the restructuring; however, they
say, NIGMS is meeting its goal of reducing employee
numbers by not filling some open positions.

"Part of the immediate incentive was the requirement to
streamline as with all other parts of the federal
government," explains Marvin Cassman, acting director
of NIGMS. "You just can't ignore that. In addition, the
[old] programs have been in place for a long time, 10
years for some and 20 for others." He says that "it was
time to reconsider how we grouped our research
portfolio" to reflect the way science has grown and the
different directions in which it has developed. He adds
that Ruth Kirschstein, NIGMS director from 1974 to 1993
and currently deputy director of NIH, was instrumental
in focusing the institute's research and training
programs.

W. Sue Shafer, associate director for extramural
activities, says that some NIGMS-funded scientists were
concerned that certain areas of science would no longer
"have a home at NIGMS." But because the institute
solicited broadly for comment from its scientific
constituents during the review phase of the
reorganization proposal, she maintains, groups such as
professional societies that were especially concerned
did have input into the restructuring, thereby
dissipating their apprehension.

John Perkins, president of the Rockville, Md.-based
American Society for Pharmacology and Experimental
Therapeutics (ASPET), concurs with Shafer's assessment,
noting that ASPET officials were involved in an
external review of the reorganization and pronouncing
ASPET "comfortable" with the scheme.

"We're still funding the same constellation of
projects. What we hope is that the new organization
will stimulate new interactions and perhaps new
connections between areas of research that we support,"
stresses Cassman. One area that is new is an initiative
to fund projects that contain risky or unorthodox ideas
and methods (see accompanying story).

Getting Inside The Cell
James Cassatt, division director of cell biology and
biophysics, says this division "brings together the
cellular aspects of biomedicine--how the cell is
organized and how things happen within the cell--with
those programs where people are trying to explain these
same things but in molecular terms." He adds that the
division's programs also dovetail with initiatives that
look at "the detailed three-dimensional structures of
many of the molecules that are involved" in cellular
processes.

Among many "exciting" areas of research in the
division, Cassatt cites projects elucidating the
three-dimensional structure of such mo-lecular motors
as the muscle protein actin; studying the proteins
embedded in cellular membranes; and determining the
structure of various G proteins and nucleic
acid-binding proteins.

In biophysics, Cassatt remarks, "we're supporting a lot
in the area of protein folding. If you're working for a
biotech company and you make a protein, you have to
make sure it folds properly.  

"Recently it's been discovered that there are helper
molecules called chaperonins that help in the folding
process. Ultimately what one would like to do is to
look at an [amino acid] sequence and deduce from that
sequence the structure of the folded protein. Nature,
of course, does this very well and the information is
there, we just don't know how to interpret it
completely."

Cellular Processes
Judith Greenberg, director of the genetics and
developmental biology division, comments that "one of
the extremely hot areas" of research in her division
has focused on cell-cycle regulation. Scientists in
this field, she explains, study what causes cells to
divide, what stops cells from dividing, and how cells
proceed through the process of replicating DNA to
undergoing mitosis.

"In the last several years, cell-cycle regulation has
really been taking off in a big way," she elaborates.
"There have been a lot of discoveries in what appear to
be disparate areas of research that have all been
coming together and causing just an explosion of
information. A lot of this feeds into cancer research,
also." 

She mentions that the study of cell-cycle regulation is
also important to determining what genes regulate very
early development in embryos. "It will have an impact,
I think, on understanding birth defects," Greenberg
predicts.

Another "explosive" research topic, she reports, is
"the whole area of homologous recombination, better
known these days as gene targeting." This basically
entails coming up with a way of substituting one gene
for a very similar one in a cell, which is useful in
creating transgenic mice, among other applications.

"A big breakthrough a number of years ago was the
ability to get a specific piece of DNA into the right
location on a chromosome. These cells are put back into
a mouse, so you can create a mouse that is lacking a
specific gene or one that has a gene that's in some way
been modified from the norm." She says two NIGMS
grantees originated some of those gene-targeting
technologies, which eventually led to the development
of the mouse model for cystic fibrosis.

"Another area that we have just been moving into is
transcriptional regulation--what turns a gene on and
makes it active," adds Greenberg. "This [field of
study] has now moved beyond what I would consider
genetics into structural biology. What's happening is
that scientists refine certain protein-DNA
interactions, such as transcription factors, in the
genetics program. This work then moves over into the
realm of structural biology as people start to look at
[molecules involved in transcription] with X-ray
crystallography and NMR [nuclear magnetic resonance
imaging]." 

Molecular Keys
Michael Rogers, acting director of the newly formed
pharmacology, physiology, and biological chemistry
division, says that research in his section covers a
number of areas, including molecular pharmacology; the
molecular basis of the action of anesthetics; and
understanding the pathogenesis of septic shock and the
molecular basis of wound healing in burn victims.

Specifically, he notes that biochemistry-related
projects that fall under the aegis of this new division
"look at basic problems of how proteins are handled in
the body--how they actually carry out their catalytic
function."

This division also has a large program in synthetic
chemistry, which is primarily directed towards drug
synthesis, namely learning how to produce drugs that
come in only one chemical configuration. "You can have
drugs that are the same [substance], but exist in
different configurations [isomers], sort of like your
two hands, which are the same, but they don't fit on
top of each other," Rogers explains. "Working out ways
to prepare just one molecule is very important right
now to the drug industry."

Rogers likens this scientific conundrum to finding the
right molecular key to fight diseases: "Sometimes those
drugs--the right-handed key vs. the left-handed
key--might have very different effects on the body. But
most chemical reactions will produce both the
right-handed and the left-handed forms, and most drugs
on the market today are an equal mix of both forms. 

Sometimes one of those is the active drug and sometimes
the one that's inactive may be involved in some of the
[drug's] side effects. So there's been a push to
develop new medicines that only have one of the
isomers," so as to minimize the harmful side effects.

For more information on NIGMS programs, contact W. Sue
Shafer, associate director for extramural activities,
National Institute for General Medical
Sciences/National Institutes of Health, 45 Center Dr.,
MSC 6200, Natcher Building, Room 2AN-32C, Bethesda, Md.
20892-6200;   (301) 594-4499. Fax: (301) 480-1852.
E-mail: wst@cu.nih.gov.


(The Scientist, Vol:8, #24, p.14, December 12, 1994)  
(Copyright, The Scientist, Inc.)
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NXT:   

-------------------------------------------------------
TI  : HIGH RISK, HIGH PAYOFF

AU  : KAREN YOUNG KREEGER

TY  : RESEARCH

PG  : 14

In a Nov. 7, 1994, letter, Marvin Cassman, acting
director of the National Institute of General Medical
Sciences (NIGMS), informed NIGMS grantees that the
institute is "making special efforts" to fund
applications that contain risky or unorthodox ideas or
methods. Specifically, these would be applications that
contain ideas that challenge current dogma; include
experimental approaches that have inherent or
unavoidable elements of risk; propose experimental
models that are not fully developed or whose utility is
not adequately shown; and/or are lacking data to
establish the feasibility of the proposed ideas.

"A lot of people in the field don't seem to know that
about a year ago the institute and our council
recommended that we take 5 percent of our competing
research dollars and set it aside to support 'risky'
research," Cassman says. These types of grants are
typically funded for two years for a total of $120,000
in direct costs.

"These are applications that would have gone through
the normal peer-review process, not a separate [call
for proposals]," and would likely have been denied, he
explains. "These would be applications where the [study
section] said: 'This is really a terrific proposal. It
has exciting possibilities. But the preliminary
experiments aren't done yet. But we're not sure that
it's going to work. But the investigator hasn't had
much experience in this area.'

"It's all of these 'buts' that are so damaging in peer
review. We're looking for applications where the
reviewers themselves said: 'If it works, it's
potentially very important.' And it's those [proposals]
that we're taking a flyer on."

"We're trying to subtly influence [grant applicants']
behavior," maintains W. Sue Shafer, associate director
for extramural activities. "We want scientists in the
field to be a little less conservative and put some of
their riskier ideas that they feel would really have a
high payoff into their applications. We're not asking
for any special treatment in the review process,
although DRG [NIH's Division of Research Grants] is
encouraging reviewers to note--regardless of how they
are scoring the applications--where they think there is
something that is risky but if it panned out would be
very important."

Judith Greenberg, director of the genetics and
developmental biology division, adds: "In my own view,
investigators are so conditioned by the system that
they need to submit a safe application. Even though
they have novel ideas, they often keep them to
themselves." 

In the long run, however, for the progress of science,
these applications need to be funded, she asserts: "You
never know what's going to turn up [in conducting
science]. It could be a bomb, but on the other hand,
the payoff could be enormous. If it turns out to be
correct it could really result in a whole paradigm
shift."

Greenberg maintains that NIGMS is actively driving to
change at least part of its funding strategy because
"although scientific research is in the midst of an era
of tight budgets, [researchers] still need to push
science."

--K.Y.K.

(The Scientist, Vol:8, #24, p.14, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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NXT:                          

                           HOT PAPERS

------------------------------------------------------
TI  : MEDICAL GENETICS

TY  : RESEARCH (HOT PAPERS)

PG  : 15

H.T. Orr, M. Chung, S. Banfi, T.J. Kwiatkowski, Jr., A.
Servadio, A.L. Beaudet, A.E. McCall, L.A. Duvick,
L.P.W. Ranum, H.Y. Zoghbi, "Expansion of an unstable
trinucleotide CAG repeat in spinocerebellar ataxia type
1," Nature Genetics, 4:221-26, 1993. (Cited in 114
publications through October 1994)

The subject of this paper, the genetic basis of the
neurodegenerative disease spinocerebellar ataxia type 1
(SCA1), has been the focus of an ongoing collaboration
between the laboratories of Harry Orr at the University
of Minnesota, Minneapolis, and Huda Zoghbi at Baylor
College of Medicine in Houston. 

"It demonstrates that the DNA mutation that causes SCA1
is the expansion of an unstable trinucleotide--CAG, in
this case--repeat in the coding region of the gene for
a protein called ataxin 1," explains Orr, who is a
professor of laboratory medicine and pathology and a
member of the Institute of Human Genetics at Minnesota.

"A normal genome can have anywhere from six to 39
repeats of the CAG unit. When the trinucleotide is
transmitted from parent to child, it can grow in
length, and this expansion causes the disease." 

Zoghbi, a professor of molecular and human genetics,
pediatrics, and neurology at Baylor, notes that "SCA1
was the fifth disease to be correlated with a
trinucleotide-repeat expansion, which confirmed the
theory that unstable repeats may represent a common
mutational mechanism. We may have, in fact, discovered
a unifying mechanism for late-onset neurodegenerative
diseases." Other disorders associated with CAG repeats
include Huntington's disease, spino-bulbar muscular
dystrophy, and Machado-Joseph disease.

While the reason for the association of this mutation
with nervous-system disorders is not known, Zoghbi
speculates that it may be partially due to the
inability of nerve cells to regenerate: "The appearance
of the expanded repeat unit in the genes may be causing
an accumulation of a faulty gene product, for instance,
which could eventually result in the death of a nerve
cell." Currently, her laboratory is working on defining
the function of the normal ataxin 1 protein, which is
defective in SCA1, and on determining the nature of the
disruption caused by the mutation. 

"We hope that by finding out the mechanism we will have
a greater ability to treat this group of diseases,"
adds Orr, whose current line of research involves
modeling SCA1 in transgenic mice, to "understand how
the disease develops."

Both Orr and Zoghbi point out other reasons for the
widespread interest in their paper. "It was the first
to show the correlation of the size of expansion with
severity and age of onset of the disease," comments
Zoghbi. 

"We can more closely predict the age of onset by the
number of repeats for SCA1 than in the case for
Huntington's [disease], for instance," says Orr.
"However, because of ethical concerns [regarding
genetic testing] and since we do not yet fully
understand all the factors involved in determining age
of onset, no information regarding age is given based
on the SCA1 repeat number."

The research detailed in the paper is also unique in
that it was the first time investigators used a focused
strategy to find an unstable repeat, according to
Zoghbi. Since then, other investigators (R. Koide et
al., Nature Genetics, 6:9-13, 1994; S. Nagafuchi et
al., Nature Genetics, 6:14-18, 1994; Y. Kawaguchi et
al., Nature Genetics, 8:221-27, 1994) have used a
similar targeted approach to detect mutations in other
neurodegenerative diseases.


(The Scientist, Vol:8, #24, p.15, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

------------------------------------------------------
TI  : PLANT BIOLOGY

TY  : RESEARCH (HOT PAPERS)

PG  : 14

S. McQueen-Mason, D.M. Durachko, D.J. Cosgrove, "Two
endogenous proteins that induce cell wall extension in
plants," Plant Cell, 4:1425-33, 1992. (Cited in 21
publications through October 1994)

Daniel Cosgrove, a professor of biology at Pennsylvania
State University, University Park, says that this paper
breaks new ground in that it gives the first insights
into "the biochemical basis of one of the key processes
in plant-cell growth; namely, the extension of the cell
walls.

"We identified proteins that make cell walls grow in
surface area," he adds.

Plant-cell walls are composed of large units of
polysaccharides (such as cellulose fibers), held
together by hydrogen bonds, with different proteins
embedded in this matrix.

The newly discovered proteins, explains Cosgrove, "act
on the polysaccharide component of the cell wall to
cause slippage between units so as to enable extension.
"For more than 50 years, people had hypothesized the
presence of such 'wall loosening' proteins, but they
had remained elusive until now. Our lab identified the
first of this class of proteins."

The discovery of these proteins--now referred to as
expansins--and the elucidation of their mode of
activity in a subsequent paper (S. McQueen-Mason, D.
Cosgrove, Proceedings of the National Academy of
Sciences, 91:6574-8, 1994) have caused considerable
excitement among the community of scientists interested
in cell growth.

Based on the finding that these proteins acted on
hydrogen bonds between polysaccharide units, these
scientists are able to better explain how plant cells
grow in volume and surface area up to 10 times   their  
original   size   without  disrupting  the   integrity 
of the cell wall (L. Taiz, PNAS, 91:7397-89,  1994; 
S.C.  Fry, Current  Biology,  4:815-17, 1994).

"The fact that a protein acts in a nondegradative
fashion on pure cellulose, for instance, caught many
people's fancy," Cosgrove observes.

Since expansins act on the polysaccharide without
disrupting the backbone, many re-searchers  are 
speculating  as  to the potential uses of these
proteins in the recycling of paper, he adds.


(The Scientist, Vol:8, #24, p.15, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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NXT:   


                  TOOLS  &  TECHNOLOGY

-------------------------------------------------------
TI  :  Monoclonal Antibodies Find Utility In Cell       
       Biology

AU  :  RICKI LEWIS

TY  :   TOOLS & TECHNOLOGY

PG  :   16


In its short lifetime, monoclonal antibody (MAb)
technology has experienced more ups and downs than a
yo-yo. As this brilliant invention has evolved into a
difficult technology, numerous suppliers have emerged
to facilitate researchers' access to the new
antibodies. Today, MAbs are partners in such
cell-biology staples as fluorescence microscopy, flow
cytometry, and affinity chromatography. Investigators
use these antibodies to track cells as they communicate
and interact, respond to various stresses, turn
cancerous, and die. 

But, just as antibodies are finding increasing utility
in cell biology, a new Food and Drug Administration
classification for those products with clinical utility
may affect researchers' access to the important
technology (see accompanying story).

Monoclonal History
MAbs were born in 1975, when Georges Kohler and Cesar
Milstein at the Medical Research Council Laboratories
in Cambridge, England, fused two types of cells to form
a hybridoma. Part antibody-secreting B cell, part
myeloma cell, a hybridoma combines the talents of each
constituent, continuously releasing a single type of
antibody when cultured in ascites fluid in a mouse's
abdomen. This secretion of a monoclonal (single-type)
antibody is in contrast to the response of an animal's
challenged immune system, which is termed polyclonal
because several types of antibodies are produced
against a single type of foreign antigen, each zeroing
in on a different portion of the target.

Hybridoma technology, the research community thought,
would finally provide a way to isolate and at the same
time mass-produce a single antibody type, harnessing
its exquisite specificity. But capturing that quality
did not come easily.

"When Kohler and Milstein made the first hybridoma,
everyone started making them. But by the mid-1980s,
hybridoma technology fell out of favor," says Krishna
Balakrishnan, vice president of research and
development at Richmond, Calif.-based Berkeley Antibody
Company (BAbCO). Researchers found it exceedingly
difficult to create hybridomas, select a youthful one,
and culture it successfully enough to provide ample
antibodies, he explains.

But as MAb research nears its 20th anniversary, it is
experiencing a resurgence. "In the early 1990s,
hybridomas came back into fashion because many people
realized that there are a lot of specialized
applications that only a MAb can do," notes
Balakrishnan, referring to MAbs that zero in on
chemical groups small enough to be specific to one
molecule.

Finding A Niche
Many researchers agree that nurturing a hybridoma to
secrete a desired antibody is technically challenging.
First, the animal providing the B-cell part of the
hybridoma must be immunized against the appropriate
antigen, then B cells isolated and fused with myeloma
cells to provide them unlimited cell division, or
immortality. Next is the onerous task of selecting
hybridomas whose antibodies suit researchers' needs.
Obstacles are everywhere in the long process--cells
won't fuse, hybridomas die or won't propagate. 

Antibodies may be produced in too low a yield, may bind
to their targets with poor affinity, or may bind to
target regions (epitopes) that different molecules have
in common, drastically reducing specificity and making
cross-reactivity possible.

These technological hurdles have opened a wide niche
for dozens of companies that MAbs have overcome these
obstacles and nurture for researchers. Such vendors
offer extensive lists of monoclonal and polyclonal
antibodies, partial antibodies, and antibodies
conjugated to various marker molecules.

Firms that grow hybridomas and scale up production of
desired antibodies report that such contract services
are extremely popular. "Lately we have been providing
mostly customized products. Some people want special
forms of antibodies, such as without preservatives or
with a certain conjugate, or just a FAb fragment [the
portion of an antibody that binds antigen]," says Bret
G. Wien, president of Research Diagnostics Inc. in
Flanders, N.J.

Richard Plante, associate scientist at the Robert Wood
Johnson Pharmaceutical Research Institute in Don Mills,
Ontario, works in drug discovery and doesn't have time
to create monoclonals. "We work with the glucocorticoid
receptor, for which there is no good clone available,"
he explains. A colleague had been supplying MAbs, but
the hybridoma died. "So Affinity BioReagents [Inc. of
Neshanic Station, N.J.] has been a good source of the
antibodies I'm interested in."

Sharon Devereaux, a research scientist at Abbott
Laboratories Inc. in Abbott Park, Ill., is another
satisfied hybridoma customer. BAbCO grew her MAbs.
"They were very cooperative, everything was documented
well, and they gave timely results and feedback," she
says.

Backbone Of Biological Research
MAbs are powerful tools in cell, molecular, and
developmental biology. They have helped researchers
dissect the complex pathways of signal transduction,
cell adhesion, the stress response, carcinogenesis, and
cell death. In short, MAbs reveal life at the
biochemical level. And investigators are finding that
their small, individual glimpses into the lives of
cells are connected, through signaling pathways. "The
whole cell biology area has taken off, and signal
transduction is at the core of that. A lot of the
signal-transduction work is antibody-related," comments
Wesley Russ, immunodetection product manager and senior
scientist in research and development at Life
Technologies in Gaithersburg, Md.

Geneticists are using small MAbs to identify proteins.
"We're finding more and more molecular biologists
working with recombinant DNA turning to monoclonals as
tools to isolate molecules. For example, a researcher
with a partial gene sequence reconstructs the
corresponding peptide, then uses a monoclonal to fish
out the gene product," notes BAbCO's Balakrishnan. "You
couldn't do that with polyclonal antibodies--you need a
highly specific signal."

Researchers can use generic antibodies to obtain gene
products via an approach called epitope tagging. To do
this, a scientist attaches a synthetic oligonucleotide
encoding six to 10 amino acids to a fragment of the
gene of interest. The oligonucleotide specifies a
"peptide tag," an extra bit of protein attached to the
gene's product. BAbCO supplies MAbs that are attracted
to such tags. "Then you express the gene product as a
fusion protein, and use the universal antibody to
detect the fusion protein. The epitope tag antibody
purifies the gene product from a mixture," Balakrishnan
explains. "It is very powerful because of its universal
use."

An antibody's specificity allows developmental
biologists to isolate and highlight individual steps of
differentiation. This is the case for anti-agrin MAbs,
a product of StressGen Biotechnologies Corp. of
Victoria, British Columbia in Canada.

Agrin is a protein found in the basal lamina (the
connective tissue boundary between tissues) that, early
in development, stimulates receptors for the
neurotransmitter acetylcholine to cluster at the tip of
a muscle fiber--a prelude to formation of a
neuromuscular junction. "Agrin is released into the
space [between a nerve and muscle cell] and it clusters
the receptors to increase the signal. We offer a group
of five monoclonals to different regions [epitopes] of
agrin," notes Henry Rodriguez, director of StressGen's 
biochemical division. The anti-agrin antibodies became
available last month.

Many companies offering MAbs also supply polyclonal
antibodies, which, when purified by affinity
chromatography, are specific enough for many research
needs. "Affinity-purified peptide polyclonals have
specificities similar to those of monoclonals, with the
advantage of multiple clones to the same epitope, which
provides higher affinity. A lot of people are going
this way, because it's easier than going through the
process of screening for monoclonals," according to
James Stiehr, president of Affinity BioReagents.

Big sellers are polyclonal antibodies to nitric-oxide
synthase, the enzyme that catalyzes formation of nitric
oxide, a messenger molecule that takes part in
vasodilation, neurotransmission, and cytotoxicity.

Antibodies In Biotech
Monoclonal antibodies are key components of several
biotechnologies. They are conjugated to other molecules
so that they can be detected, such as to a fluorescent
dye for fluorescence microscopy, or to an
electron-dense marker for electron microscopy. Antibody
bound to an inert matrix forms an affinity column, with
the antibody pulling out its target molecule from an
extract passed over the column. An antibody's signal
can be amplified by binding it (at a region other than
the antigen binding site) to a second antibody, which
is in turn bound to a label.

In another popular approach, an antibody is bound to
the vitamin biotin, which then binds a labeled form of
the bacterial protein streptavidin. Labeled MAbs are
also used in Western blots to detect peptides or
proteins separated on a polyacrylamide gel by
electrophoresis.

In an enzyme-linked immuno-sorbent assay (ELISA), a
primary antibody binds to its target antigen as well as
to a secondary antibody. The secondary antibody is
bound to an enzyme, such as alkaline phosphatase, that
catalyzes a reaction whose products are easily
detectable. Because one enzyme molecule is used over
and over, catalyzing thousands of reactions, a single
primary antibody, via its linkage to a single enzyme,
gives off a very powerful signal.

Jaspreet Sidhu, a senior fellow in the Department of
Environmental Health at the University of Washington,
Seattle, is evaluating a new ELISA kit for Life
Technologies. "We're field-testing an ELISA to measure
levels of the second-messenger cyclic AMP [cAMP],
looking at stimulation of intracellular cAMP in various
cells, such as human smooth muscle and rat
hepatocytes," he reports.

Fluorescently labeled MAbs are also used in flow
cytometry, a method of separating cells or their
components in a device called a fluorescence-activated
cell sorter. In the technique, up to four groups of
cells are labeled with MAbs coupled to different
fluorescent dyes. The cells are propelled through a
stream of water. A vibrating crystal breaks the stream
into droplets, which pass through a laser that excites
the dyes linked to the MAbs marking cells. The cell
sorter, programmed to recognize specific combinations
of dyes, emits pulses of electricity that deflect
droplets carrying different types of marked cells into
separate fractions.

Life Technologies offers several MAbs specific for
cluster-of-differentiation (CD) cell-surface antigens,
con- jugated to fluorochromes for use in flow
cytometry. "A fluorochrome-labeled antibody recognizes
an epitope on a cell, such as CD4 marked with
fluorescein," explains the company's Wesley Russ. "A
certain percentage of cells will be selected because
they have that protein exposed. Then add an antibody to
something else on the cell surface, labeled with
phytoerythrin, such as CD8, and then get the percentage
of cells marked with CD4 and CD8. Add a third antibody,
and get additional information." 

Specific Applications: 
Cancer: Antibodies can be used to follow the many ways
that cancer cells depart from normalcy. Directed by
expressed oncogenes or dampened tumor-suppressor genes,
cancer cell surfaces and shapes grow more fluid, and
the cells secrete biochemicals that enable them to
invade and travel through healthy tissue. Antibodies
that target any biochemical implicated in
carcinogenesis or metastasis are valuable tools for
basic research as well as in the clinic, as the basis
of diagnostic tests and for evaluating response to
therapy. Such antibody targets include variants of
normal molecules, altered patterns of cell-surface
antigens, or normal proteins in abnormal places. 

Consider cathepsins. Inside a cell, these enzymes are
confined to lysosome sacs, where they degrade old
proteins. But invading tumor cells release cathepsins
instead, and they chew through the basal lamina. As a
result, the cancer grows and spreads. 

Calbiochem-Novabiochem International Inc. of La Jolla,
Calif., offers polyclonal antibodies to cathepsins,
enabling researchers to detect the leading edge of a
tumor.

Monoclonal antibodies--from Minneapolis-based R&D
Systems Inc.--to a cell-surface glycoprotein called
CD44 are also being used to probe carcinogenesis.
Because CD44 pokes out onto the cell's surface, extends
through the cell membrane, and has a tail portion
emerging on the membrane's inner face, it probably
plays a major role in signal transduction--and
disrupted relay of messages into a cell can lead to
cancer.

The link between CD44 and cancer is that certain types
of cancer cells have characteristic combinations of
CD44 variants--but there's only one CD44 gene. The
variants arise from expression of different exons
(protein-encoding sequences) of the gene. R&D Systems'
MAbs to CD44 correspond to portions of the protein that
different subsets of exons encode, allowing users to
further follow this glycoprotein's role in
carcinogenesis.

Multidrug Resistance: At Immunotech Inc. in Westbrook,
Maine, the cancer focus is on multidrug resistance
(MDR). On a cellular level, MDR is an adaptive response
to protect the cell from toxins--such as the botanical
biochemicals that are the bases of many cancer drugs.
The MDR response derives from a transmembrane protein
called permeability-glycoprotein, or P-gp, which pumps
drugs out of the cell. Immunotech sells a MAb that is
specific for a portion of P-gp that protrudes from the
surfaces of cancer cells resistant to the commonly used
chemotherapeutic drug adriamycin. "If a patient's cells
have the MDR marker, this indicates that response to
adriamycin will not be great," says product manager
Linda Diou, adding that the monoclonal is for research
use only.

Steroid hormones such as estrogen diffuse into a cell,
then bind to receptors. The hormone-receptor complex
then binds to DNA, activating certain genes whose
action produces the hormone-associated effects. MAbs to
estrogen receptors are very useful in studying breast
cancer.

Affinity BioReagents markets a monoclonal that targets
a nuclear steroid receptor called the anti-retinoid x
receptor  b, or RxRb. This receptor binds to other
steroid receptors as well as to DNA. "The RxRb antibody
is licensed from NIH. It forms heterodimers with other
steroid receptors to differentially control gene
expression in different tissues," says Affinity
president Stiehr. The antibody can be used to show
which genes the RxRb receptor binds to in different
cell types.

Apoptosis: Cell death is at the forefront of cell
biology research. Two general mechanisms are
recognized. In necrosis, a passive process, the cell
membrane deteriorates. In apoptosis, an active process,
a specific sequence of events culminates in the cell
synthesizing endonucleases that cut its own DNA into
recognizably sized chunks.

Apoptosis is important in the programmed cell death
that forms the embryo; in establishing T- and B-cell
populations in the immune system; and in the  normal
degradation of worn-out tissue. In pathology, apoptosis
is linked to graft-versus-host disease, viral
hepatitis, and cancer.

PanVera Corp. of Madison, Wis., offers a MAb, called
anti-Fas, that induces apoptosis in vitro. "Certain
cell lines have the Fas antigen. The anti-Fas antibody
binds to the antigen on the cell surface, and
cross-links other proteins. This disturbs the membrane,
which leads to downstream events," according to Alex
Vodenlich, technical services manager. The
cross-linking occurs because the antibody is a
pentamer, he adds. PanVera distributes antibodies
developed at two Japanese companies, TaKaRa Shuzo Co.
Ltd. in Kyoto and Medical and Biological Laboratories
Co. Ltd. in Otsu, Shiga.

Cellular Stress Response: Heat shock proteins are part
of a larger group of stress proteins, which increase in
abundance in response to viral infection, cancer, toxic
exposure, ischemia, or oxidation, in addition to heat.
"Stress proteins interact in many different systems.
They are ubiquitous and conserved from one species to
another, which leads people to speculate that they are
essential for life," says James Stiehr of Affinity
BioReagents, which recently added anti-stress protein
antibodies to its product line.

Interest in heat-shock proteins has mushroomed in
recent years because they have been identified as
molecular chaperones. They assist protein synthesis by
controlling transcription factors and protein kinases,
then folding peptides as they form and escorting the
maturing proteins along the secretory network.

The long list of antibodies so many companies offer may
taper off, but MAbs continue to meet their potential as
envisioned in 1975, to provide highly specific tools
with which to dissect events within and between cells.
Ricki Lewis, author of several college biology
textbooks, is a freelance science writer based in
Scotia, N.Y.


(The Scientist, Vol:8, #24, p.16, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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NXT:   

------------------------------------------------------
TI  : REGULATORY ROADBLOCK

AU  : RICKI LEWIS

TY  : TOOLS & TECHNOLOGY

PG  : 16

As cell biology and clinical medicine increasingly
overlap, antibody suppliers are finding themselves in
what many people in the field fear may turn into a
regulatory hell. On October 21, antibody-industry
representatives met with several pathology
organizations and Food and Drug Administration (FDA)
officials for the "Hematological and Pathological
Devices Panel Meeting," at which the convened panel
recommended that antibody-based products that
pathologists might use be regulated as class II medical
devices. Many such products have not been regulated by
FDA because they are used for research purposes only,
but that is changing as more and more antibodies find
clinical utility.

Class II designation requires the manufacturer to
provide various "special controls" (such as
postmarketing surveillance and restricting use to in
vitro applications) and to file a premarket
notification, commonly known as a 510(k).

The pathologists, wishing to avoid a more restrictive
class III designation but still desiring assurance of
consistent safety and efficacy, pushed for class II
status. But a recently formed coalition of antibody
suppliers, the Joint Council of Immunohistochemistry
Manufacturers, argued for less-restrictive class I
status.

The recommendation, if approved by the FDA commissioner
following a review period, may have drastic effects on
the research community, especially concerning
availability of products with markets too small to
justify the cost of complying with regulations. Delores
Graham, manager of regulatory affairs at antibody
supplier Dako Corp. in Carpinteria, Calif., and
cochairwoman of the joint council, said at the October
21 meeting: "In considering the costs of getting an
antibody cleared through the 510(k) process [$23,000 to
$40,000], we have estimated that only 10 percent of the
300 antibodies determined to be clinically useful would
have the sales to justify submission. When we evaluated
our product line, 60 percent of the products fell below
a liberal sales cutoff of $10,000 for submission
consideration, and 20 products below this cutoff could
be found on the pathologists' list of clinically useful
products."

Some antibody manufacturers fear that they may
eventually be required to keep track of which
researchers are using a particular product for basic
research and which for diagnosis, says James Stiehr of
Affinity BioReagents Inc., Neshanic Station, N.J. This
will raise costs even more. However, Carolyn Jones,
director of technology regulatory affairs at the Health
Industry Manufacturers Association in Washington, D.C.,
does not feel that the new classification will stifle
researchers' access to antibodies. Instead, she
predicts, the industry will fragment somewhat, with
product lines shrinking as only the larger firms remain
able to afford to market low-demand research antibodies
with clinical applications.

FDA regulation could be in place sometime in 1995, just
as monoclonal antibody technology celebrates its
20-year anniversary. Concludes Stiehr: "This new
classification will have a fairly major impact on the
industry."

--R.L.

(The Scientist, Vol:8, #24, p.16, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
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NXT:   
                       NEW PRODUCTS

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

TY  :  TOOLS & TECHNOLOGY
PG  :  19

PRO Scientific Introduces Laboratory Homogenizer
The PRO250 is a hand-held or post-mounted homogenizer
reportedly capable of processing sample volumes as
small as 0.03 ml. The unit features a 3/4 -horsepower
motor and built-in variable speed control up to 30,000
rpm. It is capable of homogenizing with the full line
of PRO quick-connect generators, safety-sealed
chambers, and ST series assemblies.
PRO Scientific Inc., Monroe, CT

Circle No. 100 on Reader Service Card
 


New Water Objective Available From Zeiss

The C-Apochromat 40X/1.2 water objective for
high-resolution imaging of specimens in aqueous media
is designed to eliminate refractive index mismatch and
the effects of temperature changes on image quality. It
reportedly minimizes spherical aberration in the
imaging of live tissue or cells.
Carl Zeiss Inc., 
Microscope Division,
Thornwood, NY

Circle No. 102 onReader Service Card



Worthington Releases New Cardiomyocyte Isolation System

The Worthington Neonatal Cardiomyocyte Isolation
System, a new kit utilizing purified enzyme
preparations, contains all the necessary materials for
five separate tissue dissociations of up to 12 hearts
each. Separate vials each contain Hank's Balanced Salt
Solution (HBSS), Purified Trypsin, Soybean Trypsin
Inhibitor, Purified Collagenase, and Leibovitz L-15
powdered media. Also included are five Falcon Cell
Strainers, a phenol red color card for checking pH, and
a protocol.
Worthington Biochemical Corp.,
Freehold, NJ

Circle No. 103 on Reader Service Card



Bio Image Announces Band Analysis Software For Gel
Scanning

Whole Band Analysis Software, for use with Bio Image's
gel scanner systems, automatically reads gels or films,
detects lanes and bands, quantifies the amount of
material present, corrects for smiling, and determines
fragment sizes. The results can be compared using the
Whole Band Matcher, a data-management application for
creating and searching customized databases.
Bio Image,
Ann Arbor, MI

Circle No. 104 on Reader Service Card



Activated Cultureware For Cell Growth

ProNectin F Activated Cultureware provides
anchorage-dependent cells with a culture surface said
to be immediately able to support receptor-mediated
cell adhesion and spreading, initiating cell growth. 
The RGD cell attachment ligand of fibronectin is
presented directly on the culture surface in the form
of ProNectin F, a genetically engineered
cell-attachment factor. The product is sterile, stable,
and ready-to-use in dish and multiwell plate formats.
Protein Polymer Technologies Inc., San Diego, CA

Circle No. 101 on Reader Service Card



(The Scientist, Vol:8, #24, p.19, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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

                       PROFESSION

------------------------------------------------------
TI  : A Successful Presentation Can Enhance A           
      Scientific Career

AU  : ROBERT R.H. ANHOLT

TY  : PROFESSION

PG  : 22

Editor's Note: "For many of us, giving a scientific
presentation can be stressful," writes Duke University
Medical Center molecular neurobiologist and cell
biologist Robert R.H. Anholt in his book Dazzle 'Em
With Style (New York, W.H. Freeman and Co., 1994), a
guide to presenting an effective talk. "Yet," he adds,
"the ability to deliver a polished oral presentation in
front of an audience of peers is an essential skill
that is indispensable for a successful scientific
career. . . . The skill of presenting an engaging and
well-structured seminar often determines our
professional reputation and future success--especially
when the seminar is part of a job interview." Anholt
teaches an annual seminar course in which students are
required to prepare and deliver lectures to fellow
students and faculty members. An excerpt from the book
follows.

A scientific presentation should always be prepared
with the audience in mind. To blindly offer a showcase
of your own accomplishments, reflecting only your
interests, is a sure recipe for miscommunication and
results in a poor performance from the perspective of
the audience.

Communication is the key. Look upon your presentation
as a dialogue with the audience, not a monologue. Be
sensitive to the needs and interests of your audience,
and reflect on the questions: What do they expect to
learn from my presentation? How can my presentation be
useful to them? A presentation prepared with these
questions in mind is more likely to succeed with the
audience than a presentation intended from the outset
solely to impress the listeners by glorifying the
speaker's self-perceived accomplishments.

Try to find out beforehand who might be in attendance
during the presentation. Often it is possible to give
credit to a specific member of the audience during the
talk. Always greatly appreciated are statements such as
"After we learned about the elegant experiments of Dr.
Smith [in the audience], we decided to . . ." or "Since
the approach developed by Dr. Jones worked so well in
her system, we adopted a similar strategy," or "Our
results agree closely with previous observations by Dr.
Doe, who showed . . ." I once heard a speaker present
data on calcium influx in synaptic terminals; he was
unfamiliar with the most recent publications of one of
the pioneers of his field, who happened to be in the
audience! Such embarrassing in-stances can do
irreparable damage to an otherwise excellent 
presentation and are entirely preventable. Invited
speakers should always browse through a departmental
brochure and try to learn a little about the
organization and history of the host institution before
arriving on the scene.

Structure Your Material
After having obtained as much information as possible
about the audience and its interests, the next step in
preparing the presentation is outlining the talk. A
presentation is usually preceded by a brief
introduction by the host and followed by a discussion
period. Normally, there is a predetermined time
allotted for the entire event. It is crucial for the
speaker to stay within the boundaries of this time.

Like hikers who go into the wilderness with a food
supply just sufficient for the intended duration of the
trip, people who attend a seminar anticipate the
predetermined period and come equipped with an amount
of listener energy just sufficient to cover this
period. As soon as the speaker goes over time, the
audience becomes impatient and restless. As a result,
the speaker will be forced to rush through the most
important part of the presentation, namely the
conclusion and take-home message. When the presentation
is part of the symposium, the chairperson and
subsequent speakers will be greatly irritated if a
speaker exceeds the allotted time, since this
interferes with the next speaker and delays the entire
symposium.

It is also essential to leave enough time for
questions. This provides a precious opportunity for the
speaker to engage in a direct discussion with the
audience, which is essential when you are trying to
communicate information effectively. If a 60-minute
presentation is scheduled, prepare a 45- to 50-minute
talk. This will leave ample time for the introduction
and to answer questions at the end. A good rule of
thumb is to keep the presentation at a length that is
75 percent to 80 percent of the allotted time.

In designing the presentation, remember the interests
and expectations of the audience and put the
presentation into context accordingly. Using the same
set of data, for example, you can often shift the focus
of a presentation from molecular aspects to cellular or
behavioral aspects or from the nature and generation of
a stimulus to the response of the target tissue. A
strong presentation on the effects of bronchodilators
delivered via inhalation as aerosols would not be
structured identically for a group of physiologists
interested in the effects of the drug on pulmonary
function and for an audience of biomedical engineers
concerned mainly with the design of the inhaler and its
mechanism of drug delivery.

If it is important to design your presentation
according to the interests of the audience, it is
essential to make the audience aware of your focus from
the very outset. Suspense and mystery are excellent
tools for playwrights and movie directors, but they are
the nemesis of scientific presentations. To communicate
scientific information effectively and maintain the
attention of your audience, adhere to the old rule:
"Tell 'em what you're gonna tell 'em, then tell 'em,
then tell 'em what you've told 'em."

An outline on the blackboard goes a long way toward
keeping the audience aware of the central line of
thought of the presentation. A verbal description that
outlines the seminar early in the talk also guarantees
that the speaker and the audience march to the beat of
the same drummer--and in the same direction. Such a
statement establishes a line of thought that enables
the audience to comfortably make an organized mental
inventory of the information that is about to follow
and to apportion their total listener energy in
installments that correspond to the announced segments
of the presentation.

Each presentation consists of three segments. (1) The
introduction provides the background and perspective
necessary to appreciate the remainder of the
presentation. (2) The body of the presentation, usually
the largest section, conveys new information to the
audience; this section can often be divided into
distinct, interrelated subsections. (3) The conclusion
summarizes the presentation and should provide the
audience with a clear take-home message. When preparing
a structure for your presentation, divide the allotted
time and assign a defined number of minutes to each
section of the presentation--for instance, 10 minutes
for the introduction, 30 minutes for the main body of
the presentation, and five minutes to summarize and
conclude.

In many cases, the arrangement of slides or
transparencies will help structure your presentation by
providing landmarks along which the lecture can be
organized. A good rule of thumb is to allot
approximately two minutes of presentation per slide,
making 20 to 25 slides a good number to aim for when
preparing a 45-minute presentation.

A single sheet of paper with titles or key words that
identify each slide and perhaps a few small reminder
notes can provide a convenient "cheat sheet" to which
you can refer during your presentation. Alternatively,
you can prepare a sheet that contains photocopies of
all your slides in the correct sequence. A
well-prepared abstract, an organized set of well-chosen
slides, a concise "cheat sheet," and an outline to put
on the board should all help keep you on track during
your seminar.

Know Your Stuff
It happens often, especially in cases of novice
speakers, that unjustified self-confidence leads to the
belief that eloquence and style will make up for lack
of knowledge, incomplete understanding, or absence of
crucial data. A false sense of intellectual superiority
to the audience, instilled by the assumption that no
one else knows more about the topic than the speaker,
frequently leads to the illusion that he or she will be
able to "wing it" yet give the impression of being on
solid ground. More often than not the speaker discovers
too late that the audience consists of highly
intelligent and insightful individuals. It takes only
one knowledgeable listener to expose a lack of
knowledge or data that the speaker has tried to hide
behind a cloak of superficial information.

Long before the question period, it will become evident
even to a lay audience whether the speaker has a
thorough understanding and a broad, solid command of
the field. Nothing is more embarrassing to a
professional than to be caught unprepared to discuss
recent literature or details of important, albeit
peripheral, aspects of the field. Nothing is more
disappointing to an expectant audience than a speaker
who, having no data or only a limited amount, spends
most of the time talking about planned but not yet
performed experiments. If you have no data for a
scheduled research seminar, choose another topic for
which solid data are available or simply decline to
speak. The decision not to speak is sometimes more
beneficial to a person's reputation than a lecture
devoid of data.

Finally, knowledge and data alone are not sufficient.
Critical examination of the information is
indispensable. This is perhaps one of the most
difficult tasks: to stand back and critically look upon
your own work. Yet those who are able to do that can
prevent or anticipate embarrassing questions.
Furthermore, a critical, careful presentation during
which you demonstrate familiarity with pitfalls of
experimental design and ongoing controversies in the
literature, as well as understanding the limitations of
the data presented and their statistical reliability,
further instills confidence that you are truly an
authority in the field.

Rehearse
No matter how experienced a speaker is, it is always a
good idea to rehearse a presentation. Often, the same
presentation can be given on a number of occasions, but
not without adaptation. "Canned" seminars pose the
danger of providing a product not optimally tuned in to
the audience.

Substantial time for preparation of the presentation
should be allowed prior to the scheduled date. Frantic
last-minute preparations can result in acceptable
performances but seldom in memorable ones. A scientific
presentation is an expression of creativity, and
creation takes time. I usually start thinking about
scheduled presentations weeks, sometimes months, in
advance. I draw up a rough outline early on and then
brood and daydream, letting the presentation go around
in my mind, letting the concepts mature at their own
slow pace, like a fine wine in the cellar of a French
chateau. Rehearsing the presentation and going through
the slides, rearranging them until I am fully satisfied
with their final order, is--in my experience--best done
in the evening right before retiring.

A rehearsal in front of an honest and perceptive
colleague is invaluable. This person should preferably
be someone who could fit in as a member of the
prospective audience and who does not feel inhibited
about giving frank and critical feedback, with regard
to both the presentation's scientific content and the
delivery. For such a rehearsal to be useful, honesty
must prevail over politeness. Inexperienced speakers
can benefit from rehearsing their presentations with a
tape deck or cassette recorder. Listening to your own
voice can be very revealing and may help turn a dull,
monotonous account into an exciting story. A video
recorder can also be helpful.

Prepare--Then Relax
You have familiarized yourself with the composition and
interests of your audience. You are armed with solid
data, well-rounded knowledge, and a thoroughly
organized presentation. You can do nothing more than
confidently and quietly await the moment of truth.
Relaxation is now essential. I have seen more seminars
fail because of the self-destructive nervousness of the
speaker than for any other cause.

I always advise my students to have fun the night
before their scheduled presentations, to avoid any
further rehearsals or preparations, and to engage in
activities that take their minds completely off the
upcoming presentation.

Robert R.H. Anholt is a molecular neurobiologist and
cell biologist at Duke University Medical Center in
Durham, N.C. 

(The Scientist, Vol:8, #24, p.22, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


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ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE  
FOLLOWING ADDRESSES:

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U.S.A.

NXT:   

                       PEOPLE

------------------------------------------------------
TI  : City Of Philadelphia's John Scott Award Honors    
      Cancer Researcher For 'Crazy Ideas'

AU  : NEERAJA SANKARAN

TY  : PROFESSION (PEOPLE)

PG  : 23

Beatrice Mintz, a senior member of the Institute for
Cancer Research at the Fox Chase Cancer Center in
Philadelphia, was presented with the John Scott Award
during a reception on November 18 at the American
Philosophical Society in Philadelphia.

The prize was set up in the early 1800s by John Scott,
a Scottish druggist, who entrusted the administration
of the award--originally $20 and an inscribed copper
medal--to the city of Philadelphia. Scott's intention
was to reward people for their useful inventions that
contributed in a significant way to the "comfort,
welfare, and happiness" of mankind. Early awards went
to inventors of such items as a knitting machine and
door lock. Notable winners through this century have
included Thomas Edison, Jonas Salk, the Wright
brothers, and Kary Mullis.

"This award is a paeon in praise of crazy ideas,"
Mintz, who was honored for her novel and creative
research in the fields of developmental biology and
cancer research, remarked at the ceremony.

Her first "crazy idea," she says, was to attempt to
fuse embryos of mice having different genotypes into a
single mass during the very early stages of
development, and eventually produce mice that shared
characteristics from both originating embryos. One of
her early published works detailing the techniques
involved, which appeared in a book she contributed to
(Methods in Mammalian Embryology, J. Daniel, Jr., ed.,
San Francisco, W.H. Freeman, 1971, pages 186-214) has
been cited in almost 150 publications, according to the
Institute for Scientific Information in Philadelphia.
Nowadays, Mintz says, the techniques are so standard
that "most people forget to cite the source."

Mintz is also well-known for her experimental research
in the 1970s that led to the concept of cancers arising
from defects in cell differentiation and development
(B. Mintz, K. Illmensee, "Normal genetically mosaic
mice produced from malignant teratocarcinoma cells,"
Proceedings of the National Academy of Sciences,
72:3585-89, 1975). At 73, she is still actively doing
research, her most recent target being malignant
melanomas. 

Mintz received her Ph.D. in 1946 in developmental
biology from the University of Iowa.

Before coming to the Fox Chase Cancer Center in 1960,
she served for several years on the faculty of the
University of Chicago. She has been a member of the
National Academy of Sciences since 1973 and of the
American Philosophical Society since 1982.

--Neeraja Sankaran


(The Scientist, Vol:8, #24, p.23, December 12, 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  :  Tennessee Professor Is The First Veterinarian To 
       Receive Award Relating Smoking And Health

AU  :  BARBARA SPECTOR

TY  :  PROFESSION (PEOPLE)

PG  :  23

Hildegard Schuller, a professor of pathology at the
University of Tennessee College of Veterinary Medicine
in Knoxville, has become the first woman and the only
veterinarian to receive the Alton Ochsner Award
Relating Smoking and Health. The nine-year-old award,
presented October 31 at the annual meeting of the
American College of Chest Physicians in New Orleans,
honors outstanding research into the mechanisms of
smoking-related lung cancer. It carries a cash prize of
$15,000 funded by Marion Merrell Dow Inc. of Kansas
City, Mo., and is named for the first physician to
recognize that cigarette smoking is a major cause of
lung cancer.

Schuller, 48, points out that her work involves human
lung cancer cell lines in vitro, not animals. "Most
people think that because I'm a veterinarian, I do all
of my research on animals," she notes. "But anyone who
has a background in biological sciences could do this
type of research."

Her award-winning work focuses on nitrosamines,
cancer-inducing chemicals found in cigarette smoke as
well as beverages, foods, and cosmetics. She determined
that these chemicals bind to specific lung-cell
receptors that trigger the progression of cancer.
Her most startling finding was that "nicotine itself is
involved in the stimulation of cells involved in
cancer." This went against the conventional wisdom that
nicotine is not a carcinogen.

"I had great difficulty over the last five years [in
getting] this work published and funded," Schuller
recalls, adding that the research did not gain credence
until Italian and Canadian teams came out with similar
findings. Schuller's paper reporting these results
(H.M. Schuller, "Cell type specific, receptor-mediated
modulation of growth kinetics in human lung cancer cell
lines by nicotine and tobacco-related nitrosamines,"
Biochemical Pharmacology, 38:3439-42, 1989) has been
cited in 17 subsequent articles.

A native of Germany, Schuller received her veterinary
degree in 1971 from Justus Liebig University in
Geissen, Germany, and her Ph.D. in pathology in 1972
from the College of Veterinary Medicine in Hannover,
Germany. Prior to joining Tennessee's veterinary
college faculty in 1985, she was on the staff of the
National Cancer Institute.

--Barbara Spector


(The Scientist, Vol:8, #24, p.23, December 12, 1994)  
(Copyright, The Scientist, Inc.)

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


