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


                          THE SCIENTIST


VOLUME 8, No:18                                  SEPTEMBER 19, 1994
(Copyright, The Scientist, Inc.)

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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
PG   : 3
                            NEWS

TRIALS AND ERRORS: The financial pressure put on by recent 
high-profile clinical trial failures of several 
biotechnology drug candidates has created a situation in 
which some biotechs are cutting corners to bring their 
products to market--ironically, dooming them to continued 
rejection by the Food and Drug Administration   
PG   : 1

HELPING HAND: Biotechnology companies increasingly are 
turning to independent contract research organizations to 
take their drug candidates through the long, exhaustive 
process of regulatory approval   
PG   : 1

ODD APPLICATIONS: As the mission of the Department of 
Energy's national labs shifts from military and nuclear 
research to civilian technology, multidisciplinary 
collaborations with industry, academia, and other government 
agencies are yielding some unexpected and sometimes 
extraordinary projects   
PG   : 1

LINUS PAULING REMEMBERED: Friends, colleagues, and even his 
sometime adversaries are recalling Linus Pauling--who died 
last month at age 93--as one of the most flamboyant, 
outspoken, and influential figures of this century, within 
science as well as outside it   
PG   : 1

IS ANYBODY LISTENING? A widely distributed consensus 
statement advocating increased United States government 
funding of biomedical research has largely been ignored by 
science policymakers and Congress. Nonetheless, the 
documentUs drafters are taking heart in the diversity and 
prestige of its more than 200 signatories   
PG   : 3

                          OPINION


THE BOOK OF THE FUTURE: It is within the realm of 
possibility, says biochemist Elie A. Shneour, that libraries 
and bookshops as we know them today will fade out of 
widespread use in the future, as the traditional book is 
replaced by teleprinted volumes, ordered via computer and 
printed out in the reader's own living room or study   
PG   : 12

COMMENTARY: A recent effort by French Culture Minister 
Jacques Toubon to require reports on scientific research 
funded by his nation to be published only in French was 
stymied, much to the relief of The Scientist's publisher, 
Eugene Garfield, who over the years has called for 
recognition of English as the "lingua franca" of science   
PG   : 13

                          RESEARCH

DRUGS FROM THE DEPTHS: Marine scientists and colleagues in 
industry, academia, and government are combing the seas in 
search of organisms to produce drugs to fight a variety of 
diseases   
PG   : 14

HOT PAPERS: Geneticist Jean Weissenbach discusses his lab's 
genetic linkage map; geophysicist Steven C. Cande reports on 
his geomagnetic polarity time scale; molecular biologist 
Matti Saraste expands on the crystal structure of SH3   
PG   : 16

CD-ROM JOURNALS: As journal publishing enters the electronic 
age, scientific societies are taking the lead in preparing 
their publications for CD-ROM, providing easy storage and 
interactive capabilities   
PG   : 17

EARLY TO PRESS: With rapid advances of research and the 
traditional pressure to publish or perish, some journals are 
responding to the demand to slash the time it takes to 
publish articles   
PG   : 21

MATHEMATICIANS Jean Bourgain, Pierre-Louis Lions, Jean-
Christophe Yoccoz, and Efim I. Zelmanov have won the 1994 
Fields Medals   
PG   : 22

NOTEBOOK   PG  : 4

CARTOON    PG  : 4

LEADERS OF SCIENCE    PG : 10  

LETTERS    PG  : 13

CD-ROM PUBLICATIONS DIRECTORY   PG : 18

NEW PRODUCTS   PG   : 19

CROSSWORD      PG   : 22


(The Scientist, Vol:8, #18, pg.3, September 19, 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
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The Scientist,
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U.S.A.

                          --------
NXT:

------------------------------------------------------------
TI    :  From Stud-Finding To Badger-Spying,  National  Labs 
         Pursue A Host Of New And Very Different Challenges

Their refdefined mission is leading researchers at DOE labs 
to take on unusual--sometimes bizarre--assignments

AU   :   Karen Young Kreeger

At the Oak Ridge National Laboratory in Tennessee, 
researchers are taking the bang out of old munitions dumps, 
using a special group of TNT-eating microorganisms. 
Meanwhile, on a weapons-test site near Lawrence Livermore 
National Laboratory in Livermore, Calif., a remotely 
operated, minature robot helps biologists study the behavior 
of the American badger.

Scenes like this are becoming more and more common at United 
States Department of Energy (DOE) labs as the facilities 
shift from their traditional focus on weapons development 
and energy investigations to new applications in a wide 
array of disciplines.

They are responding to President Bill Clinton's mandate that 
the labs use their capabilities for more practical, 
economically worthwhile purposes (B. Goodman, The Scientist, 
July 25, 1994, page 1). In so doing, investigators from such 
diverse fields as materials science, computing and 
information management, laser technology, and energy 
research are applying their expertise to solve problems in 
disciplines and industries as varied as biomedicine, 
environmental science, and the automotive industry.

It is not unusual for the projects to take researchers far 
afield from what they've been doing in the past. 
Supercomputing technology, for example, which was developed 
at many labs to facilitate weapons research, is now being 
used at Sandia National Laboratories in Albuquerque, N. 
Mex., by computer scientists working with New York-based 
Citibank Corp. to reduce bank fraud.

And at Brookhaven National Laboratory in New York, 
scientists, along with their colleagues in other DOE and 
university labs, are working to link the many sectors of the 
textile industry--the largest employer in the U.S.--via a 
computer network. 

Collaborations like these have Ropened up new vistasS for 
lab scientists, says Roger Lewis, director of technology 
utilization in the DOE Office of Technology Partnerships in 
Washington, D.C. In LewisUs view, these joint ventures have 
"exploded" since the 1989 passage of the National 
Competitiveness Technology Transfer Act.

Other DOE officials and researchers agree, adding that 
although the labs' involvement in developing "offshoot" or 
cross-disciplinary technologies has been evolving and 
expanding over the last two decades, an explicit emphasis on 
industry collaboration is a comparatively recent 
development.

The 1989 act established the cooperative research and 
development agreement, or CRADA, the purpose of which is to 
foster collaborative research between government labs and 
industry. Specifically, DOE offers private-sector partners 
rights to patents and other intellectual property from the 
joint research. 

DOE currently is engaged in more than 600 CRADAs with more 
than 500 industrial partners. The firms involved run the 
gamut from small, local companies to international 
conglomerates.

For example, Oak Ridge has licensed the microbiological 
technology to convert TNT into a non-toxic form to nearby 
EODT Services, a two-year-old bioremediation company. 
Meanwhile, Los Alamos National Laboratory in New Mexico is 
pooling resources with such giants as Digital Equipment 
Corp., headquartered in Maynard, Mass., and Cray Research 
Inc. of Eagan, Minn., to work in supercomputing.

Scientists at DOE labs and their industry collaborators 
point out that there are many more examples of such swords-
to-plowshares endeavors.

In fact, one lab might even branch out to collaborate with 
the multibillion-dollar entertainment industry. Sandia is 
currently considering working on projects with Walt Disney 
World's Epcot Center. Although officials at both Sandia and 
Epcot refuse to discuss details at this time, a statement 
from Sandia does hint at the nature of potential 
relationships in the future. 

"Walt Disney World and Sandia National Laboratories have a 
common interest in providing an authentic vision of the 
future, enabled by science and technology. . . . We are 
conducting continual explorations about how these common 
interests can be furthered through a showcase opportunity to 
authentically represent the future to the public," said Pace 
VanDevender, director of Sandia's Center for National 
Industrial Alliances, in the statement.

Retooling Radars
One defense-related radar-technology project at Lawrence 
Livermore Laboratory has spawned two industry partnerships 
so far, with about a half-dozen other applications waiting 
in the wings to be developed. "It's a spinoff from the Nova 
laser program here at Livermore,S says electrical engineer 
Tom McEwan of the multipurpose Rpocket radarS he developed. 

The cigarette-pack-sized radar sends out electrical pulses 
at a rate of more than 1 million per second. These bounce 
off an object and echo back to the detector to be 
interpreted on a display screen.

Key advantages of the device, according to McEwan, are its 
low cost and high margin of safety. 

The hand-held radar, he claims, can be made for less than 
$10, and "poses no health hazard at all. The average 
emission level from the unit is a million times lower than a 
cellular phone."

Zircon Inc., a Campbell, Calif.-based producer of electronic 
hand tools, has licensed the technology to develop a stud-
finder for the do-it-yourself home-improvement market. And 
Amerigon Inc. in Burbank, Calif., is developing the device 
as a high-tech car component to warn drivers of objects or 
people behind them, among other automotive uses.

McEwan envisions that the unit could also be used to locate 
earthquake survivors buried beneath fallen debris; in the 
sports and fitness industry; in home security; and in 
biomedicine. 

In the health-care field, he foresees, the device could be 
used as a high-quality stethoscope, as a non-contact patient 
monitor, and for three-dimensional imaging of the human 
body. "I showed this to a couple of M.D.'s, and they just 
flipped," McEwan says. 

Underground Activity
In addition to industry-lab collaborations, many intriguing 
partnerships also arise from in-house research needs at the 
labs. Livermore laser scientist John Christensen, for 
example, is applying his expertise to learn more about the 
nonhuman creatures that inhabit the lab's land. Because of 
programs required by other federal agencies, such as the 
Fish and Wildlife Service, Livermore must monitor how 
certain weapons-research projects affect wildlife living on 
test sites. 

Since most of the 7,000-acre, non-nuclear-explosive test 
site--called Site 300--is desert, many of the areaUs animals 
live in burrows to escape the heat, according to recently 
hired wildlife biologist Jim Woollett. This habit poses a 
problem for monitoring such Site 300 inhabitants as the 
American badger and burrowing owl. Woollett went to 
Christensen with the dilemma. 

"John said, `Tell me exactly what you want.' And he went 
from there. It was marvelous," Woollett recalls.

The result was ChristensenUs design and manufacture of a 
remotely operated robot that Woollett sends on spying 
missions down the holes of Site 300 burrowing animals. The 
device is called the Miniature Optical Lair Explorer, or 
simply MOLE. 

"I kind of like to describe it as an all-terrain vehicle, 
except that instead of having a person on top, it has a 
camera that rotates 360 degrees," says Woollett of the 5 x 
5-inch, tethered robot, which sends images in real time to a 
television monitor on the surface. MOLE runs on treads taken 
from a toy tank; its "headlights" are red, light-emitting 
diodes; and its "brain" is an electronic circuit board 
attached to the camera. 

In addition to the opportunity to learn about the animals, 
he says, the project has given "a new awareness to a large 
scale of people" at the lab that life does exist below the 
test ground's surface. 

Of the MOLE project's potential for changing weapons-testing 
protocols, Woollett declares: "It is something that's 
coming. I think that it is a consideration that has just 
been brought to the surface, so I think that we'll see more 
of it in the future."

Thus far, the animals don't seem to mind the intrusion. 
"With the red light--Lord knows why--they really don't react 
in an aggressive manner. At least they haven't yet," reports 
Woollett.

Leaner, Cleaner Autos
Scientists at most DOE labs are working on another sort of 
vehicle. "The overall goal," says Mark Smith, technical 
group leader for the materials processing group at Pacific 
Northwest Laboratory (PNL) in Richland, Wash., "is to build 
clean, highly efficient vehicles."

Teaming up with researchers at U.S. auto manufacturing 
giants Ford Motor Co., Chrysler Corp., and General Motors 
Corp., DOE lab scientists are working on the supercar of the 
future. Challenged by Clinton's 1993 Partnership for a New 
Generation of Vehicles initiative--with a goal to produce an 
80-mile-per-gallon, environmentally friendly car in the next 
decade--federal and industry investigators are feverishly 
collaborating to meet that objective. 

To do this, DOE labs, other federal agencies, and industry 
partners are developing technologies that will reduce 
vehicle emissions; lighten the heavier components of cars, 
such as the power train; and produce standard and new types 
of cars that will run on alternative fuels. 

PNL, for example, has $6 million in CRADAs with the "Big 
Three" automakers for fiscal year 1994. Specifically, PNL 
researchers are working on such items as light-weight 
aluminum auto parts, a hydrocarbon trap to reduce polluting 
emissions, and laser holographic techniques to examine fuel-
combustion efficiency.

Most of DOE's labs have become increasingly involved in 
other environmental science-related areas in the last 
decade, with department officials describing 

the labs' work in this field as a growth area. 
Bioremediation, alternative energy, and air and water 
pollution monitoring are only a few examples. 

In a three-year, $1.8 million CRADA, for instance, Argonne 
National Laboratory in Illinois is joining forces with 
Advanced Research Development Inc. (ARDI) of Athol, Mass., 
to develop a new type of solar energy material called 
Lumeloid. The material's inventor, Alvin M. Marks, president 
and chief scientist at ARDI, predicts that the material 
could "become a major power source for the world."

Lumeloid is a stretchable, polarizing film embedded with 
molecular diodes--devices for conducting electricity in one 
direction. 

"When we get finished," Marks predicts, "we will have a 
structure which will collect light photon energy and direct 
that energy in one direction."

Researchers on the project envision that consumers will be 
able to buy a roll of Lumeloid--nicknamed "solar-cell-on-a-
roll"--in local hardware stores, place it in a panel and, 
via current-carrying wires, plug appliances directly into 
the sun's energy.

Lumeloid's main advantages, according to Marks, are that 
"it's extremely clean. There's no waste generated, and it's 
easy to make. The [potential] decreased cost per watt is 
dramatic. We figure a cost of about $5 per square meter for 
the film and an output of 500 watts per square meter [of 
film] in bright sunlight." The total investment cost for the 
consumer, he adds, works out to be about 30 to 50 cents per 
peak watt, compared with $1 to $1.50 per watt for coal or 
oil-generated power. Marks and collaborators at Argonne also 
say that with its theoretical  efficiency of 70 percent 
energy conversion, Lumeloid will need to be only about one-
fifth the size of conventional solar cells to get the same 
amount of energy output.

Material Matters
DOE and the biomedical community have been involved in 
collaborative research in a big way for nearly a decade, 
with DOE's substantial support of the Human Genome Project 
as one prime example.

There are, however, dozens of other, less publicized 
innovations in bioscience that have also arisen from DOE 
projects, agency researchers and officials note.

One such effort is taking place at the Lawrence Berkeley 
Laboratory in Berkeley, Calif. A group of materials 
scientists and chemists headed by Deborah Charych has 
developed a biomolecular film to quickly and easily detect 
the flu virus.

One part of the bluish-colored, double-layered film contains 
sialic acid sugars--a type of molecule that all known flu 
strains bind to--and the other part serves as the film's 
backbone. 

When an infected sample is dropped onto the film, the flu 
virus binds to the sialic acid sugars. This binding changes 
the structure of the backbone, causing the film to absorb a 
different wavelength of light. This changes the film's color 
from blue to red, indicating that the sample contains the 
flu virus. The film also has the potential to be used as an 
assay for screening new inhibitor compounds. 

Jon Nagy, a chemist on the team, claims that this method 
offers a more direct, less expensive way to detect viruses 
over such methods as the enzyme-linked immunosorbent assay, 
or ELISA. Charych says that her group is in discussions with 
several biomedical diagnostics companies to develop and 
market the film, but that as yet "no formal deals have been 
established."

For information about interdisciplinary research at DOE 
contact Roger Lewis, DOE, 1000 Independence Ave., S.W., 
Washington, D.C. 20585; (202) 586-5388. Fax: (202) 586-8854. 
E-mail: roger.lewis@mailgw.er.doe.gov.


(The Scientist, Vol:8, #18, pg.1, September 19, 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   :  Clinical Trial Reversals Forcing Biotech Firms To 
        Refine Strategy

Under pressure to reap return on investment, companies are 
seeking ways to ensure success in designing drug tests

AU   :  SUSAN L-J.DICKINSON

TY   :  NEWS

PG   :  1


This past July, Synergen Inc. suspended clinical trials of 
its anti-inflammatory drug candidate, Antril--being tested 
to fight sepsis--for lack of efficacy. Faced with the 
setback to its $100 million-plus investment, the Boulder, 
Colo.-based biotech was forced to lay off more than half its 
work force and shut down two major manufacturing facilities. 
Soon after, the firmUs stock price dropped almost 50 
percent, and today, despite its reputation for solid 
research, industry analysts consider Synergen a prime 
takeover candidate.

Synergen is not the only biotech firm that has suffered from 
such a debacle. In fact, since the beginning of this year, 
seven other such companies have been hammered by highly 
publicized clinical trial failures and seen dramatic drops 
in their stock prices as a result. With many biotechs under 
the gun to prove their com- mercial viability before 
returning to investors for another round of financing, 
industry participants and analysts report that some of  the  
companies  are  cutting corners on the design of clinical 
trials--further undermining their products' chances of 
garnering Food and Drug Administration (FDA) approval.

This Catch-22 situation underscores an urgent dilemma for 
the biotechnology industry, observers say. The competing 
forces of stockholder impatience for profitable products and 
the necessity of conducting exhaustively thorough testing 
(see accompanying story) are making their decisions about 
shepherding compounds to market more crucial than ever. The 
proper way to proceed is the subject of debate and second-
guessing among corporate decision-makers and analysts. What 
is clear, however, is that hundreds of millions of dollars 
and even the future of some companies are riding on their 
decisions.

"I find that biotech CEOs are fairly open to admitting that 
financial pressures are playing a role in how they run their 
companies," says Kenneth B. Lee, Jr., national director of 
New York-based accounting firm Ernst and Young's Life 
Sciences Practice, and coauthor of the company's prestigious 
annual report on the biotechnology industry. "These 
pressures do impact how clinical trials are approached," he 
adds, "and they're probably a negative factor."

Analysts agree that these are tight times for biotechnology, 
an industry in which many companies have less than two 
years' cash on hand, according to Ernst and Young. The 
Medical Technology Stock Newsletter, published in Berkeley, 
Calif., recently reported that the Amex Biotech Index 
dropped nearly 50 percent during the first half of the year. 
And continuing failures in clinical trials have turned up 
the heat.

Companies are trying a variety of strategies to face the 
challenge. Some are hiring contract research organizations 
to run clinical trials (see story on page 1); others are 
finding corporate partners to share the cost, risk, and 
potential reward of late-stage development. And some, 
evidently, are designing clinical trials that they hope will 
hasten the day that their product will be on pharmacy 
shelves.

Nothing illegal or dishonest is occurring, experts are quick 
to reassure, and FDA regulations are in no way being 
compromised. Rather, it is in the design of the trials 
themselves--for example, how many extra patients to enroll 
to allow for natural attrition, or which indication to 
pursue approval for first--that some firms are trying to 
take shortcuts and, ironically, dooming their compounds to 
scientific failure.

"Small, undercapitalized companies are doing this to save 
time and money," notes David Holveck, president and CEO of 
Centocor Inc., a biotech firm in Malvern, Pa. "There is no 
question about it."

One way biotechs are trying to shave dollars and months from 
a project is by enrolling fewer patients in a study. Before 
a clinical trial begins, the company and FDA must agree on 
the parameters and design of the test: what clinical factors 
will be evaluated, and what percentage of patients showing a 
certain outcome will be considered statistically meaningful. 
But for a variety of reasons--ambiguous diagnosis, 
complicating symptoms, or death, for instance--some patients 
will always drop out of a study, so extra patients must be 
enrolled from the beginning.

"You must empower the study with sufficient numbers if you 
hope to be able to  answer the statistical question at the 
end," says Frank Martin, vice president and chief scientific 
officer for Liposome Technology Inc. in Menlo Park, Calif. 
He maintains that such a deficiency hurt Berkeley-based Xoma 
Corp.'s Phase III trial of the sepsis compound E5 last year.

Biotechs are also trying to speed development time by 
enrolling patients from more sites, which would shorten the 
amount of time it takes to accrue a certain number of 
patients, and by designing hybrid Phase II/Phase III 
studies, rather than conducting them sequentially, according 
to Holveck.

"Any time you compromise on numbers because of cost or time 
you are endangering your study," he warns. "You inject a 
higher degree of variable elements and heighten the risk 
that the trial will fail."

Large drug companies will often conduct a number of Phase II 
studies to best determine which subpopulation of patients 
and what clinical endpoints to target, thus enabling them to 
design the full-scale Phase III trial with much less risk, 
Holveck says.

Martin agrees, noting that a large company like Merck and 
Co. Inc., for instance, "would never consider skimping on 
the size of a trial, because [such a move] is fraught with 
danger. But this is where Wall Street enters into the 
equation. Wall Street doesn't want to wait for more people, 
because in this game, time is money."

Clinical drug development has always been an arduous 
venture. Statistics from the Pharmaceutical Manufacturers 
Association show that it takes, on average, 12 years for a 
compound to move from preclinical testing through the three 
phases of FDA-regulated clinical trials, costing an average 
$359 million along the way. Moreover, the association 
estimates that for every 5,000 compounds originally 
evaluated in the laboratory, only one approved drug will 
result. 

Failure of a clinical trial can carry a big price tag. When 
Synergen stopped the Phase III trial of Antril, the $100 
million the company had invested in the drug was exclusive 
of manufacturing costs, which included construction of what 
the firm billed at the time as "the largest pharmaceutical 
protein manufacturing plant in the world."

The Antril failure forced Synergen to terminate 375 jobs--60 
percent of its work force--and close down both its 
manufacturing plant and its Japan office. Synergen's stock 
plummeted 49 percent the day of the restructuring 
announcement.

At the time Synergen was not criticized for the design of 
the Antril trialsQsufficient numbers of patients were 
enrolled, and the company was performing the trials in a 
targeted subpopulation of patients who appeared to most 
benefit from the drug. But some industry watchers suggest 
that the company should have pursued Antril's effectiveness 
in rheumatoid arthritis first, before tackling the complex 
and ill-understood syndrome of sepsis. 

"Companies are going after targets that are less understood 
in terms of basic pathophysiology, because those indications 
offer a higher potential payoff," observes Herbert Loveless, 
vice president for clinical development at Tanox Biosystems 
in Houston.

Indeed, sepsis is responsible for an estimated 100,000 
deaths in U.S. hospitals each year, and generates more than 
$10 billion a year in U.S. hospital bills--so it represents 
a lucrative target for the first company to get a 
therapeutic approved for use against it.

"What has been missing," Loveless adds, "is a lot of the 
fundamental risk-assessment analysis. That is why a lot of 
people have lost a lot of money. If you pursue a smaller 
indication first, it gives you credentials--the company 
gains an approval, the experience of going through the 
approval process, and a revenue stream," notes Lee. "It's 
not a grand-slam home run, but it is a solid approach to 
building a business."

Another factor exacerbating the financial losses of trial 
failures is that many small companies, such as Synergen, are 
developing expensive infrastructure--regulatory departments; 
clinical-trial design groups; manufacturing, marketing, and 
production operations--to support a single lead compound.

"For Synergen it wasn't so much the failure per se," says 
John Groom, president and CEO of San Carlos, Calif.-based 
Athena Neurosciences Inc. "It was the accompanying 
developments built on the assumption that Antril would 
succeed. If they had waited to do all of the rest until 
after they had Phase III approval, then they would not have 
been burning $20 million per quarter."  

But developing these capabilities in sequence rather than 
simultaneously, according to Robert Thompson, executive vice 
president for research and clinical affairs at Synergen, 
would have added two years of development to the time  
between  Antril's  approval and when the drug reached 
patients. This would not only have delayed income, he points 
out, but also "would have been an unconscionable position 
for us [in treating] a life-threatening disease."

Some observers maintain that negative results are inherent 
in the process. "It's the nature of drug development: You 
get bad news before good news," says James McCamant, editor 
of the Medical Technology Stock Newsletter. "It's just that 
the industry is still young. It hasn't developed a history 
of successes along with the failures yet, so people 
overreact."

"Everyone knows that only one in 10 candidates make it from 
preclinical testing to a new drug application," acknowledges 
John Steuart, chief financial officer of Alafi Capital Co., 
an Emeryville, Calif.-based investment firm. "The problem is 
that naive investors are losing a lot of money because they 
overpaid for the stock.

And many industry insiders say the concerns of anxious 
investors on the outside do play a role in scientific 
decisions, especially when the high-cost stages of advanced 
clinical trials are reached.

"Science and business interests can be in conflict as I 
weigh whether to go forward with a project," Athena 
Neurosciences' Groom acknowledges. Clinical trial design 
requires a CEO to juggle several factors, including cost, 
potential market, and scientific potential, he says. The 
balance between these factors can shift in a tight economic 
environment.

"There is no question that pressure from Wall Street enters 
into decisions on when to file for approval of a compound, 
or what calculated risks to take [in the design of a 
trial]," Martin points out. "I've seen it personally. In a 
meeting to set the time line for a trial, for example, the 
medical person will lay out the time frame in a best-case 
scenario."

Companies are learning, however, that measures that offer 
savings may also increase the risk that a compound will not 
pass testing.

"Rushing [clinical trials] is very shortsighted," says Larry 
Kurz, vice president of communications for Emeryville-based 
Chiron Corp. "It's almost suicidal."

Susan L-J Dickinson is a freelance writer based in Philadelphia.


(The Scientist, Vol:8, #18, pg.1, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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                          --------
NXT:

------------------------------------------------------------
TI   :  Contract Research Organizations Help Guide Compounds 
        To Approval

AU   :  Franklin Hoke

TY   :  NEWS

PG   :  1

These days, many biotechnology and pharmaceutical firms 
facing the daunting road to market with a new drug are 
opting to get help from contract research organizations, or 
CROs. These service companies specialize in providing all or 
part of the necessary clinical trials; they also manage 
regulatory reviews. And their participation in the drug-
development process is growing dramatically as the number of 
candidate compounds coming through the so-called research 
pipeline climbs. 

"Many biotech companies don't have the capabilities to do 
this kind of drug development," says Sara Creagh, an 
executive vice president with Quintiles Transnational Corp., 
the parent company of Quintiles Inc., a fast-growing CRO. 
Both are headquartered in Research Triangle Park, N.C. "Many 
times, even pharmaceutical companies don't have those 
capabilities, but little biotech companies--the new ones, 
the emerging ones--certainly don't."

As the growing use of CROs enhances the commercial prospects 
for organizations, it is improving the career outlook for 
many individuals, as well, since--for scientists with 
Ph.D.'s in fields such as immunology, pharmacology, 
biochemistry, and physiology who also have clinical 
experience--the expansion of these companies represents a 
burgeoning area of new job opportunities.

Fueling growth in the CRO sector is the enormous 
productivity of basic researchers at biotechnology and 
pharmaceutical companies, which has led to a steadily 
growing number of candidate drugs. It is the hoped-for 
result--a fully developed, profitable product--that is 
crucial to keeping the company afloat and its discovery-
oriented scientists at their benches in the future.

"That's key," says David Stump, senior director of clinical 
research at Genentech Inc., based in South San Francisco, 
Calif. "It's the business weUre in. If you're not developing 
drugs, all the elegant research in the world won't take you 
anywhere."

He adds: "We're using biotechnology to produce breakthrough 
products. In order to clearly show that we have a 
breakthrough product, we have to show that it does something 
important in patients with disease. And the whole process 
has to work, from discovery to development to marketing."

While recognizing the need to develop their innovative 
compounds in order to survive, many biotechs, especially 
smaller companies, may be reluctant to hire the staff 
necessary to plan and manage the full-scale safety and 
efficacy trials regulators demand.

"They don't want to throw their money into building the 
infrastructure to develop their drugs," says CRO executive 
Creagh. "They want to create the drug, and then let the 
clinical development happen somewhere else. [CROs] let them 
put their resources into what they do best. A simple way to 
look at it is that they focus on the R in R&D, and we do the 
D."

Among the leading CROs, in addition to Quintiles, are G.H. 
Besselaar Associates, Princeton, N.J.; IBAH Inc., Blue Bell, 
Pa.; PAREXEL International Corp., Waltham, Mass.; and 
Pharmaco LSR in Austin, Texas. Besselaar, the oldest and 
best established of the CROs, moved from small-scale 
consultancy status to being a full-fledged CRO in the mid-
1970s, according to CRO executives. The others grew 
substantially in the mid- to late 1980s and the beginning of 
this decade.

In 1993, pharmaceutical and biotechnology firms spent about 
$25.6 billion on R&D, according to one industry estimate, of 
which approximately $17 billion went to clinical drug 
development. Of this amount, CROs claimed about $3.5 
billion. Current annual growth rates at several leading CROs 
are estimated at between 20 and 30 percent by company 
officials.

In addition to sparing the sponsoring company much of the 
work of drug development, CROs bring other advantages. 
Through specialization, they often possess clinical 
expertise the sponsor may not, which they are able to 
translate into streamlined protocol designs, efficient data 
collection and analysis, and complete regulatory-submissions 
packages, thereby shortening the overall time needed for 
development. With the average time needed to bring a new 
drug through the development process to market in the United 
States currently estimated at more than eight years--and 
with a drug's patent protection at a mere 17 years--this 
time saving can be critical. 

Moreover, industry observers point out, the pharmaceutical 
market today is international, requiring that sophisticated 
trials be designed that will be able to satisfy regulators 
in, say, Japan, Australia, North America, and Europe 
simultaneously.

"There was a time five years ago when you'd do one 
development in Europe and you'd do one in the U.S.," notes 
Helen Davies, an M.D. who heads the clinical operations 
group at Quintiles. "Now, you do one drug development for a 
regulatory-submission package across the world."

Providing Flexibility
The larger CROs can conduct full-scale clinical trials from 
start to finish if asked to do so--designing the trials, 
recruiting investigators, managing data collection and 
analysis, and dealing with regulators--but this is not the 
only working model. The sponsoring company may want to plan 
and direct the entire campaign, using the CRO only for 
logistical support. Or the hiring company may need help with 
only one aspect of the process, perhaps the regulatory 
review phase or the more complex Phase IV trials.

"The client doesn't say, `Here's a vial of white powder; 
call us when the drug's approved,' " says Jeffrey Lazar, an 
M.D. with a Ph.D. in pharmacology who is executive vice 
president at Pharmaco LSR.

"It virtually never works like that now, although things are 
changing. A company may have a very rich pipeline, with more 
compounds than it can deal with. Its senior scientists are 
managing the development, but what they need are field 
extensions. So, they come to us for trial monitors or 
project managers."

Genentech, for example, uses CROs in this way, seeking 
outside help with development while retaining ultimate 
control of the process.

RWe use CROs for the tactical side of this much more than 
for the strategic side," says Genentech's Stump. "We believe 
strongly that our clinical scientists and our internal 
regulatory staff should take the lead in designing the 
trials, plotting out the developmental strategy for which 
trials will be done, when they'll be done, and where they'll 
be done. We'll then use a CRO as a tactical extension of us, 
for doing the work.

"We have to have ownership of the strategy behind the 
process," he adds. "We've invested a lot into every product 
by the time it ever comes to clinical trial, so, we take a 
very active role."

"We use [CROs] because we don't have the resources at a 
given moment to carry out our functions," says Richard 
Devlin, an immunologist and director of clinical research 
operations at Genetics Institute, based in Cambridge, Mass., 
"either because we have so many other projects--that's 
typically the case--or because we don't want to staff up for 
a project only to then have personnel on board that we might 
not need for some other project."

Expanding Opportunities
The need in the biotechnology and pharmaceutical industries 
for clinical researchers to design and manage trials and to 
shepherd regulatory submissions is expected to grow 
vigorously in the coming decade and beyond. At the same 
time, many of these companies have gone through recent 
cycles of downsizing, mergers, and layoffs, trimming their 
clinical personnel sharply in some cases. CROs are growing 
sharply in response to these moves, as is their own need to 
add new scientific and medical staff.

"It's certainly a growing area," Quintiles' Davies says. 
"The Ph.D.'s tend to go into our medical and regulatory 
groups where they work on strategic-development plans and 
writing of final reports. And then we have a large 
statistical-analysis group."

Biological scientists with statistical training are 
especially in demand at the CROs, because of these 
researchers' crucial role  in interpreting clinical data.

"Biostatisticians have a very important role in drug  
development, and we  have a large biostatistics department," 
says Pharmaco LSR's Lazar. "Although  all of us would like 
to think that a drug either works or it doesn't--it lowers 
blood pressure or it doesn't--life is, unfortunately, not 
that black-and-white."

THE FDA APPROVAL PROCESS
Typically, after the discovery of a new compound and 
preclinical laboratory and animal studies to show its safety 
and biological activity, a company will file what is called 
an investigational new drug (IND) application with the Food 
and Drug Administration (FDA). Unless FDA raises objections, 
Phase I human clinical trials can begin 30 days later. In 
these trials, small numbers of healthy volunteers, usually 
fewer than 100, help to assess basic safety and dosage 
levels. In Phase II trials, groups of 100 to 300 volunteers-
-often with different illnesses or conditions--are given the 
new drug to determine target diseases and generate early 
data on effectiveness, safety, and dose-response curves. 

Phase III trials may involve thousands of volunteers, some 
healthy and some with the target disease or condition, in 
double-blind and placebo-controlled studies to establish 
clinical evidence of efficacy and safety. If all goes well, 
a new drug application (NDA) to FDA follows. Even if the 
drug is approved for use at this stage, Phase IV trials may 
yet be required to assess the drug's ongoing performance in 
actual patient populations.

--Franklin Hoke

(The Scientist, Vol:8, #18, pg.1, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

------------------------------------------------------------
TI   :  Scientists Remember The Outspoken, Linus Pauling

AU   :  Neeraja Sankaran

TY   :  NEWS

PG   :  1

Admirers and antagonists alike are remembering Linus 
Pauling--who died on August 19 at the age of 93--as one of 
the most flamboyant, outspoken, and influential figures of 
this century, within science as well as outside it.

The two-time Nobel laureate, winner of prizes in chemistry 
in 1954 and peace in 1962, passed away at his home in Big 
Sur, Calif. He succumbed to prostate cancer, which he had 
been battling for about a year.

"He was, in my judgment at least, the greatest and most 
original scientist--especially in chemistry--in the 20th 
century," says Norman Davidson, a professor, emeritus, of 
biology and chemistry at the California Institute of 
Technology, Pasadena, where Pauling had spent the bulk of 
his career from 1922 to 1963. A longtime friend and 
colleague of Pauling's, Davidson recalls the days when he 
was a junior member of Caltech's faculty and teaching 
assistant to Pauling for a beginner-level chemistry course.

"I remember going to him before a lecture, and his 
announcing that he had just come up with an interpretation 
for the seemingly anomalous structure of hydrogen fluoride--
`sitting with my feet above my head for convenience'--and 
showing it to me," he remembers. According to Davidson, this 
sort of constant mental activity was typical of Pauling.

Indeed, Pauling remained scientifically active throughout 
his life, treading a winding path that took him through many 
corridors of science from the early days of his experimental 
work on molecular structure of silicates and other minerals 
in the 1920s; through his Nobel-winning work in the early 
1930s, when he applied the concepts of quantum theory and 
resonance to describe the nature of chemical bonds; on to 
the chemistry of a host of biological molecules, notably 
hemoglobin, antibodies, proteins, and DNA; and finally, his 
much-publicized and controversial interest in the beneficial 
effects of vitamin C. 

The author of many papers in these various fields, Pauling 
continued to publish scientific papers on his ideas until 
very recently. His latest publications appeared in widely-
circulated, peer-reviewed journals: Proceedings of the 
National Academy of Sciences (91:897-99, 1994); and Science 
(91:983, 1994).

Inspirational Insights

"He had good instincts about what was fundamentally 
important in biology," says Norman Horowitz, an emeritus 
professor of biology at Caltech. "He emphasized that the 
nature of the hydrogen bond made it important in biological 
molecules like proteins and DNA."

Pauling's contributions to the flourishing field of 
molecular biology are acknowledged by luminaries in that 
field. "He brought very deep insights into explaining 
biological systems in chemical terms," says Francis Crick, 
currently a distinguished research professor at the 
Kieckhefer Center of Theoretical Biology at the Salk 
Institute of Biological Studies in La Jolla, Calif. Crick, 
who along with James Watson and Maurice H.F. Wilkins won the 
1962 Nobel Prize in physiology or medicine for determining 
the "double helix" structure of DNA, says that Pauling--who 
also worked on the problem but provided an incorrect model--
was a very important influence. 

"He understood the importance of modeling based on 
crystallographic data--each by itself provided only half the 
data you wanted for a structure," says Crick. "Linus put 
incomplete data together to show that sometimes, but not 
always, you could predict the right structure. He got the a-
helix and b-sheet [of proteins] right; he was wrong about g 
proteins and DNA."

In any case, Crick adds: "He showed us how to solve the 
problem."

Horowitz credits Pauling with being the first person to show 
that the gene actually controlled the structure of the 
protein, through his work on the chemistry of hemoglobin in 
sickle cell anemia patients. "Until then, we knew that the 
disease was inherited, and that a gene had to be present for 
a protein," he says. "But until Pauling showed the sickle 
cell hemoglobin was different from the normal, we had no 
idea that the gene actually controlled the structure of the 
protein."

"Pauling may not have been the first to think about or study 
a problem," says John D. Roberts, a chemistry professor at 
Caltech, "but he brought new insights which made all the 
difference in arriving at the final results."

Former associates at Caltech, where Pauling served as 
division chairman for chemistry, also remember him as a 
brilliant administrator. 

"He was important in a political way--in the sense that he 
was responsible in getting a lot of notable scientists to 
come to Caltech," Horowitz recalls. Horowitz moved to the 
Pasadena school from Stanford University when Pauling 
arranged for his supervisor, George Beadle--a 1958 Nobelist 
in physiology or medicine--to be appointed to the biology 
division in 1946. Max Delbrck, who was a winner of the Nobel 
Prize in physiology or medicine in 1969, also came to 
Caltech because of Pauling, says Horowitz.

Pauling himself left Caltech in 1963, owing to tension with 
the school's officials regarding his enthusiastic 
involvement in the peace movement. He vocally promoted 
pacifism in the late 1940s through the 1950s. He signed many 
peace appeals, including the famous Mainau Declaration in 
1955, which called for an end to all war and was endorsed by 
more than 50 Nobel laureates. Pauling campaigned against the 
atmospheric testing of nuclear weapons, to which end he 
wrote and circulated the Scientists' Bomb-Test Appeal. This 
document was signed by more than 12,000 scientists worldwide 
and personally presented by Pauling to the United Nations in 
1958; for his efforts he was awarded the peace prize in 
1962. However, he received very little support for his 
activities from Caltech, where administrators demanded that 
he resign his 22-year chairmanship of the chemistry division 
in 1958. The reason they cited was that his involvement in 
these activities took him from his duties in the department.

"I think it was disgraceful the way Caltech treated him 
then," says Crick, adding that he didn't learn about the 
details of the resignation and Pauling's departure from the 
school until many years later, at one of Pauling's birthday 
celebrations.

After leaving Caltech in 1963, Pauling spent a few years 
each at the Center for the Study of Democratic Institutions 
in Santa Barbara, Calif.; the University of California, San 
Diego; and Stanford University before establishing in 1973 
the Linus Pauling Institute (LPI) of Science and Medicine, a 
publicly funded, nonprofit research organization in Palo 
Alto, Calif. 

Pauling set up the institute chiefly to further research on 
vitamin C, a topic that had begun to excite his interest 
during his tenure at Stanford. He became convinced of the 
beneficial effects of very high doses of this dietary 
supplement and, at different times in the course of the next 
15 to 20 years, promoted it as a cure for colds, cancer, and 
heart disease.

The institute, like its outspoken founder, has found itself 
embroiled in some controversial incidents over the years: In 
1978, its cofounder and president Arthur Robinson was fired 
over controversies regarding data on the instituteUs anti-
cancer research, which led to prolonged lawsuits until 1983. 
In 1993, Mathias Rath, who came to LPI as the first director 
of cardiovascular research in 1990, filed a lawsuit against 
the institute to clarify the intellectual property of his 
discoveries on the connections between vitamin C and heart 
disease. The case is still in litigation.

Although Pauling continued in his conviction in the value of 
vitamin C, and had been taking it in large doses since the 
1970s, the scientific community remains equivocal on the 
subject of its effectiveness, with some researchers 
rejecting Pauling's claims outright.

"Linus deserved his Nobel Prize in chemistry, he deserved 
his peace prize, but was completely deluded as to the uses 
of vitamin C," says Victor Herbert, a professor of medicine 
at the Mount Sinai School of Medicine in New York City, and 
director of the hematology and nutrition research lab at the 
Bronx Veterans Affairs Medical Center. "We have shown that 
vitamin C supplements are lethal to people with iron 
overload disease, and can actually cause certain cancers," 
he adds. Herbert's findings are summarized in a recent 
editorial titled "The antioxidant supplement myth" (American 
Journal of Clinical Nutrition, 60:157-8, 1994).

"Linus and I were actually good friends until the late 
1960s," Herbert says.

"We worked together during the peace movement. We got along 
because we were both very outspoken. But then he got 
delusional about vitamin C."

Crick attests to Pauling's outspokenness, as well, pointing 
out the scientist's willingness to speculate on a myriad of 
different scientific problems: "Sometimes he was wrong, 
sometimes he was right. But he was never afraid to stick his 
neck out."


(The Scientist, Vol:8, #18, pg.1, September 19, 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:

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TI   : Consensus Statement' Fails To Capture Attention In 
       Washington, D.C.

AU   : Barbara Spector

TY   : NEWS

PG   : 3

A "consensus statement" advocating increased United States 
government funding for biomedical research--endorsed by more 
than 230 institutions, associations, and companies and 
distributed widely last May--has generally been accepted in 
polite silence by lawmakers in Washington, D.C. The chairman 
of the forum at which the document was drafted says he is 
disappointed by the lack of attention given it by 
legislators and the media.

At the same time, he and other framers of the statement say 
they are gratified that so many diverse and prestigious 
organizations have put their support behind the effort.

"I guess I had hoped that more congressional offices and 
more parts of the [Clinton] administration would have taken 
note of the breadth of the constituents that had thought it 
important to prepare a statement," says Leon Rosenberg, 
president of the Bristol-Myers Squibb Pharmaceutical 
Research Institute in Princeton, N.J. Rosenberg chaired the 
March 9 meeting sponsored by Research!America, an 
Alexandria, Va.-based research-advocacy organization, at 
which the declaration was conceived.

The document begins with the assertion that "too many 
Americans are suffering and dying needlessly because, as a 
nation, we don't invest enough in medical research." It 
concludes with recommendations, including calls to 
"incorporate the promotion of medical research as an 
integral element of health-care reform" and "encourage, do 
not obstruct, the discovery and development of innovative 
and effective pharmaceuticals . . . by private industry." 
(For the full text, see The Scientist, May 30, 1994, page 
12.)

Research!America president Mary Woolley estimates that the 
consensus statement was distributed to 2,000 individuals; it 
was hand-delivered to every member of Congress. The 
lawmakers, however, have not been quoting from the text in 
major speeches or using it in other publicity-generating 
ways. Moreover, despite the influential science and business 
constituencies represented among its signatories, the 
document has not inspired any new legislation.

Dave Kohn, an aide to Rep. John Porter (R-Ill.), says that  
his boss is in accord with the document's tenets: "John 
Porter agrees with Research!America that biomedical research 
is an important aspect [of health care] and deserves to have 
very strong support." But Porter has planned no action on 
the statement, according to Kohn. "He received it, he 
generally agreed with its emphasis, but he hasn't responded 
in any particular way or used it in any particular way."

The statement also has not made a splash in journalistic 
circles. While articles about it have appeared in The 
Scientist (B. Spector, May 30, 1994, page 1) and Wash-ington 
Fax--Life Science (June 13, 1994), most news organizations 
have ignored it. (A search of the Lexis-Nexis database for 
reports on the declaration turned up blank.)

William T. Golden, former cochairman of the Carnegie 
Commission on Science, Technology, and Government who served 
as special consultant on scientific activities to President 
Harry Truman, speculates that many do not view the statement 
as revolutionary because it was issued by parties that stand 
to gain from implementation of its recommendations. "All 
these organizations will benefit from greater funding for 
scientific research. If the Association of Methodist 
Ministers sent such a document, they'd get attention for 
it," he says, citing a hypothetical, fictional nonscientific 
organization. "Congressmen are used to lobbyists and 
institutions looking for funding. It's hardly news--it's~ 
`dog bites man.' "

Bruce L.R. Smith, a science-policy analyst at the 
Washington, D.C.-based Brookings Institution, says decision-
makers may be ignoring the document because of deficiencies 
in its approach. "It doesn't deserve any attention," he 
says. Compared with the physical sciences, "the life 
sciences have been just booming in research support. [The 
signatories] assume they've been singled out for problems 
when theyUre the ones that have been spared." The authors of 
the text, Smith says, are "trying to make a case for 
continued support at a time when there's going to have to be 
some downsizing."

But Rosenberg doubts that policymakers are disregarding the 
statement because they object to it. "I would find it hard 
to believe that anyone would take umbrage with the way the 
statement was framed," he maintains. "Great effort was made 
to be statesmanlike, to be positive, to be brief, to be 
constructive."

Observers also speculate that the lack of response may just 
boil down to bad timing. "Congress is so totally enveloped 
with health-care reform that anything not related is pushed 
[down on the list of priorities]," says Susanne A. Stoiber, 
director of the Public Health ServiceUs Office of Health 
Care Reform.

"Research is just not something that is at the center of 
attention. [Legislators] are focused on big regulatory 
issues [and on reform details like an] employer mandate. 
Research has been sort of tagging along in all this, in what 
I think is a fairly successful way."

Wide Distribution
In addition to congressional representatives, the statement 
was given to key figures at the National Institutes of 
Health, the National Science Foundation, and other agencies. 
Several responded with letters to Research!America president 
Woolley.

William R. Harlan, associate director for disease prevention 
at NIH, wrote that the statement "is an important manifesto 
that responds to the changing health care scene and the 
challenges faced by health research."

Harlan says he intends to use the statement to respond to 
"people [who] call me from time to time and want background 
information [on] who supports a particular viewpoint. I 
would pull it out and quote from it [but] I wouldn't send 
people copies; it's not my part to do that. I wouldn't be 
circulating it widely or saying, `This is the direction we 
want to go.' "

Ira C. Magaziner, senior adviser for policy development to 
the president, in a letter to Woolley, wrote: "You expressed 
concern about health research under the President's health 
care reform proposal. This is an issue that the 
Administration considered carefully while formulating the 
President's proposal." Magaziner's letter does not refer to 
the document.

"It was disappointing that the only response from the White 
House failed to even mention the statement," says Rosenberg. 
"As a passionate advocate of biomedical research, I wanted 
the president of the United States to personally notice that 
effort."

But Woolley notes that "Science in the National Interest," a 
White House report on U.S. science policy issued in August 
(B. Reppert, The Scientist, Aug. 22, 1994, page 1), 
parallels key issues in the statement. Specifically, she 
points to the three "strategic goals" in "Science in the 
National Interest," which she finds reflected in the Re-
search!America document: economic growth and job creation; 
government that is responsive to citizens' needs; and world 
leadership in science, math, and engineering. "The 
biomedical research community is tracking very closely to 
the administration," she says.

Some of the points made in the statement are likewise 
reflected in the Harkin-Hatfield Fund for Medical Research 
amendment to the health-care reform bill (No. S2357) 
introduced by Sen. George Mitchell (D-Maine). The amendment, 
originally proposed last spring by Sens. Tom Harkin (D-Iowa) 
and Mark O. Hatfield (R-Ore.), would set aside 1 percent of 
all monthly health insurance premiums for medical research 
above the NIH appropriation.

The statement--which "emphasizes the need to encourage 
investment [in biomedical research] in the public and 
private sector'--notes Samuel C. Silverstein, president of 
the Federation of American Societies for Experimental 
Biology and a member of the group that drafted the document, 
is "absolutely congruent with Harkin-Hatfield."

Silverstein, John C. Dalton Professor and chairman of the 
department of physiology and cellular biophysics at Columbia 
University, acknowledges that "Harkin and Hatfield proposed 
that idea long before" the Research!America text was 
written, and had received broad support in Congress prior to 
distribution of the statement. Yet he believes that the 
consensus document nonetheless should have received more 
attention from legislators. "It's the broadest consensus on 
anything to do with biomedical research ever achieved in 
this country," he says. "I don't know why it didn't do 
better."

On the other hand, Carl Feldbaum, president of the 
Washington, D.C.-based Biotech-nology Industry Organization 
(BIO), which endorsed the document, says, "I don't have 
regrets; I didn't anticipate that it would be widely noted 
much outside our community. It's a pure policy statement; I 
don't believe it was ever intended as a press release."

Names Added
A signficant cause for optimism, say framers of the 
statement, is the growing list of organizations that have 
endorsed it. Names continue to be added, even though 
Research!America says it has stopped soliciting sign-ons. 
"In some sense, that means [the statement] has taken on a 
life of its own: by word of mouth, hand to hand, 
organization to organization, institution to institution," 
Rosenberg says.

"It's  become  the thing to do now  for  organizations--when 
200-plus organizations have signed, who wants to be off  the 
list?"

Research!America has circulated to signatories and potential 
en-dorsers a "Consensus Statement Action Packet," including 
a list of "ideas on how to maximize the impact." The group 
suggests that associations mention it in their newsletters, 
write to legislators about it, and contribute op-ed pieces 
on the subject to local newspapers, among other activities. 
As a result, the statement has been publicized in several 
organizationsU internal publications and at conferences.

"We created this statement to give our members and those who 
are our partners lucid, clear messages to use as they make 
the case for research in health-care reform," explains 
Woolley. "I get good feedback; people are glad it's out 
there."

"It's got legs to it," BIO's Feldbaum says of the statement. 
"It's got a long half-life. We can point to it again as wide 
and deep support [for biomedical research] in next year's 
budget." He adds that he would like to see "a new consensus 
to implement the statement in the form of real 
appropriations."

Research!America president Woolley says no further action is 
planned at the moment: "I think we have done closest to the 
maximum we're going to with the consensus statement." But, 
she adds, "We're certainly open to new ideas." For example, 
"as [`Science in the National Interest'] moves more to an 
action phase, if there's a way for the consensus statement 
to tie in to that process, we'll certainly do so, but these 
things are going to have to evolve."

Rodney W. Nichols, chief executive officer of the New York 
Academy of Sciences and a member of the steering committee 
for Research!America's Fall Outreach Campaign for New York, 
New Jersey, and Connecticut, says the act of signing the 
statement in itself constitutes a role in the health-care 
reform process. "It doesn't matter that there aren't any 
pyrotechnics; those signers will be more engaged in the 
debate about what the country wants [and thus] confronted 
with all the other forces in the debate. These participants, 
even in the act of signing on, are involved."


(The Scientist, Vol:8, #18, pg.3, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

WE WELCOME YOUR OPINION.  IF YOU WOULD LIKE TO COMMENT  
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The Scientist,
3600 Market Street, Suite 450, Philadelphia,  PA 19104
U.S.A.

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                          NOTEBOOK

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TI   :  BACK TO BASICS

TY   :  NEWS (NOTEBOOK)

PG   :  4


Back To Basics
In AIDS   Although last month's 10th International 
Conference on AIDS in Yokohama, Japan, yielded little in the 
way of good news concerning progress to date in efforts to 
combat the pandemic, some researchers were able to leave the 
meeting with the hope that future gatherings will be less 
gloomy. William E. Paul, head of the National Institutes of 
Health's Office of AIDS Research, announced a measure to 
encourage innovative approaches to basic AIDS research with 
federal funds gained by cutting current financial support of 
unpromising clinical trials of AIDS-related vaccines and 
drugs. The move was welcomed by, among others, Bernard N. 
Fields, chairman of the department of microbiology and 
molecular genetics at Harvard Medical School in Boston, who 
recently called for just such a realignment of funding 
priorities (Nature, 369:95-6, May 12, 1994). Fields says 
that the research reassessment represents a realistic 
acknowledgment of the difficulties impeding current 
investigations into HIV pathology, adding that researchers 
should not be discouraged by their lack of progress so far. 
"It's really an expectations issue," he says. "If you view 
the problem as simple, then you're going to be disappointed 
when you havenUt solved it. If, on the other hand, you 
define it in all its glory and complexity, then you can say 
realistically, `Where do we need to go next on the path to 
solving this?' It's just that the time frame for a problem 
with this many unknowns was a little too optimistic."


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   :  A NEW TWIST

TY   :  NEWS (NOTEBOOK)

PG   :  4

A New Twist
The unusual muscle arrangement of a Papua New Guinea 
lizardUs tail may revolutionize robotic design, say 
researchers. Kevin C. Zippel, a senior biology major at 
Cornell University in Ithaca, N.Y., studied the biomechanics 
of the Solomon Islands skink's tail for his senior honors 
thesis in comparative anatomy. He says the way the muscles 
are arranged is rare in the animal world and undocumented in 
animal tails, describing the muscles as looking "like stacks 
of snow-cones." In nature, the skinkUs grasping tail winds 
around branches like a corkscrew, allowing one part of the 
tail to be rigid while other parts are flexible. It can also 
twist and turn in every direction. The natural design of the 
skink's tail could be applied to retooling robotic 
appendages--which are currently able to move only back and 
forth, up and down, and sometimes rotate--say Zippel and his 
adviser, John E.A. Bertram, a professor of anatomy at 
Cornell. 


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
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TI   : ENERGETIC ACTIVITY

TY   : NEWS (NOTEBOOK)

PG   : 4

Energetic Activity
 Using a powerful supercomputer, two scientists are working 
on cracking the code of one of nature's most basic 
processes--photosynthesis. Chi Ho Mak, a chemist at the 
University of Southern California, and physicist Reinhold 
Egger of the University of Freiburg, Germany, used the 
computer to model the energy-conversion process--molecule by 
molecule--of bacterial chlorophyll. Their model relies on 
quantum mechanics to explain the flow of electrons that is 
responsible for converting solar energy to biochemical 
energy in plants and other photosynthetic organisms. Because 
the molecular structure of chlorophyll is so complex, 
applying quantum theory to explain the mechanism of 
photosynthesis is difficult, with calculations taking up to 
one month to run, say the researchers. Mak and Egger say 
that their work will provide insights into making solar 
cells with conversion efficiencies approaching that found in 
bacteria--almost 95 percent.


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   : THAT'S EDUTAINMENT

TY   : NEWS (NOTEBOOK)

PG   : 4


That's Edutainment
Science education and high-tech game playing merge in a new 
multimedia form dubbed "edutainment" by its creators. Hyper-
Quest Inc. in Sarasota, Fla., will release its CD-ROM 
"Astronomica: The Quest for the Edge of the Universe" in 
October. The electronic adventure disk, targeting school-
aged children, combines game features with a dramatic 
exploration of the universe, portrayed in full-color, three-
dimensional, animated graphics. "It involves Sarah, our 
heroine, looking for her professor father, who has shut down 
the Astronomica supercomputer, which contains all the 
secrets of the universe," says Joanie Stewart, a Hyper-Quest 
spokeswoman. Indeed, the fate of the universe may depend on 
Sarah's finding her father--and to help her, players must 
solve puzzles and answer trivia questions aided by mentors 
like Galileo and Einstein. Music and sound effects combine 
with simulated holograms and other sophisticated imagery as 
players visit planetary surfaces and black holes. Central to 
the educational aspects of the CD-ROM is an up-to-date 
astronomy encyclopedia provided on the disk into which 
players can take side trips at any time for accurate 
information about the planets, stars, nebulae, and other 
intergalactic entities they may run across in the course of 
their adventure. For information, call Hyper-Quest at (813) 
365-9800. Fax: (813) 365-8324.


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   :  FULLERENE BONANZA

TY   :  NEWS (NOTEBOOK)

PG   :  4

Fullerene Bonanza
Scientists at the University of California, San Diego's 
Scripps Institution of Oceanography have discovered the 
largest and most widespread collection of natural fullerenes 
on Earth in a massive crater in Sudbury, Ontario. The crater 
was formed 2 billion years ago when an asteroid slammed into 
Earth, which coincides with scientistsU beliefs that natural 
fullerenes--soccerball-shaped molecules of carbon--are 
created as a result of high-energy events, such as lightning 
strikes and in the fiery interior of stars. The Scripps 
researchers believe that the fullerenes were either formed 
from the impact of the asteroid or came from the asteroid 
itself, in which case their discovery would mark the first 
detection of fullerenes on Earth derived from an 
extraterrestrial form of carbon. Analysis of samples from 
the 37-mile-long-by-19-mile-wide crater revealed the 
presence of fullerenes in the range of between 1 and 10 
parts per million, amounts that rival the highest production 
levels of man-made fullerenes, according to the scientists. 
The investigators speculate the reason the molecules lasted 
such a long time--fullerenes are known to degrade quickly at 
fairly low temperatures when exposed to oxygenQis that they 
were embedded in ore deposits at the site.


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   : ON THE FLY

TY   : NEWS (NOTEBOOK)

PG   : 4

On The Fly
Researchers at the University of Wisconsin, Madison, Medical 
School have found two new receptors on the fruit fly cell 
membrane that they say have implications for human health. 
The receptors are docking sites--of sorts--that growth 
factor proteins must enter or attach to before they can 
perform their cellular function. Molecular biologist F. 
Michael Hoffman and colleagues found that the fly receptors 
also attach to human growth factor proteins. The function of 
this group of proteins--called the transforming growth 
factor-b family--is essentially the same across species; 
they instruct undefined cells in a developing embryo to 
become organized. In fruit flies, the result is eyes, wings, 
and legs; in humans, it is bone, tissue, and organs. 
Applying knowledge learned from the simpler fruit fly 
system, Hoffman and colleagues are looking into how the 
proteins can stimulate bone repair of severe fractures and 
affect progressive tooth decay in humans.


(The Scientist, Vol:8, #18, pg.4, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   : CHILLING RESULTS

TY   : NEWS (NOTEBOOK)

PG   : 4

Chilling Results
National Institute of Standards and Technology (NIST) 
physicists have cooled cesium atoms to the coldest 
temperature ever recorded for matter. Using lasers to trap 
the atoms in an optical lattice, scientists chilled the 
cesium to 700 nanokelvins, or 700 billionths of a degree 
above absolute zero. This temperature--zero on the Kelvin 
scale and -273! on the Celsius scale--is the point at which 
atomic thermal motion theoretically ceases. Since the 1970s, 
researchers have been pushing the temperature record lower 
and lower in an effort to improve a variety of applications, 
including atomic time-keeping and lithographic processes 
used in the semiconductor industry. NIST scientists achieved 
this record from a technique borrowed from colleagues at the 
Ecole Normale Superieure in Paris.


(The Scientist, Vol:8, #18, pg.4, September 19, 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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TI   :  The Leaders of Science
        The Readers of The Scientist

PG   :  10


"The Scientist is a cutting-edge, thought-provoking 
publication. It is very important reading." - A.L. Hillman


ALAN L. HILLMAN, director, Center for Health Policy at the 
Leonard Davis Institute of Health Economics and associate 
professor of medicine and health care management, School of 
Medicine and the Wharton School, University of Pennsylvania, 
Philadelphia

An adviser to the White House Task Force on National Health 
Policy Reform, Alan Hillman started his career as a 
physician. He soon grew frustrated with a health care system 
that ignored the broader socioeconomic context of medical 
practice and seemed to encourage waste, such as "prescribing 
MRI's for headaches when no test at all would be 
satisfactory." This led Hillman to pursue an M.B.A. degree 
and closely examine the appropriate allocation of health 
care resources. He now forecasts key trends in health care 
economics as director of the University of Pennsylvania's 
Center for Health Care Policy, a leading academic and policy 
research think tank.

Hillman's goal is to provide decision makers with 
information they can understand and apply. He believes that 
scientists must be able to communicate in two wolrds: that 
of academic scholars as well as that of policymakers, who 
base their decisions on succinct summaries of data. He 
states: "If scientists take the time to translate their 
research into readable and concise material, their work 
would be even more meaningful than it already is."

For Hillman, THE SCIENTIST meets two key requirements for 
effective communication between scientists and policymakers-
-accuracy and readability. He says: "THE SCIENTIST is a 
cutting-edge, thought-provoking publication. It is very 
important reading."


(The Scientist, Vol:8, #18, pg.10, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

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

The Scientist,
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U.S.A.

                          --------
NXT:

                          OPINION 

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TI   : The Teleprinted Book Of The Future: One Researcher's 
       Flight Of Fancy

AU   : Elie A. Shneour

TY   : OPINION

PG   : 12

It would appear that the book as a cultural institution is 
in danger of extinction. Indeed, there are those who assert 
that computer technology has made the library obsolete. But 
while important books may be read by a diminishing minority, 
it is a demanding and significant minority that can be 
disregarded only at great peril.

Now, it is true that the printing, publication, and 
distribution of books are clearly in crisis. While more 
books than ever are being published, Sir Thomas Gresham's 
law telling us that bad money drives out the good applies 
with equal force to books.

It is an irony that, while modern technology has created 
electronic typesetting and printing--which, whenever used, 
have dramatically reduced the cost of book production--the 
intensive labor, paper, distribution, and marketing expen-
ses have, at the same time, risen so steeply as to 
jeopardize the long-term survival of the printed book as a 
major component of modern civilization.

Today, books are published and sold in increasingly large 
editions to amortize their cost and generate income. This 
means that insignificant books endowed with great popular 
interest and demand can be published at a profit, while 
works of substance--with, as a rule, much more limited 
appeal--must be sold at a far higher price to survive in the 
marketplace.

A Risky Business
The inevitable consequence is that individuals and libraries 
are discouraged from buying them. In turn, publishers and 
editors--in the effort to retain their jobs in an 
increasingly volatile industry run mostly by bean-counters--
must think long and hard before backing a meritorious but 
risky manuscript for publication. The classic contemporary 
example that comes to my mind is the definitive biography of 
Harry S Truman by David McCullough, whose raw manuscript, 
before finally finding a publisher and eventually gaining 
considerable popularity, was repeatedly rejected for being 
too long, for being of limited interest, and for tilling 
already well-plowed ground.

But it is not principally trade manuscripts that suffer the 
worst ignominies. Far more important--and their fate, 
therefore, far more lamentable--are works of art, history, 
philosophy, fiction, poetry, science, technology, and 
medicine, the very books that civilized society has a stake 
in encouraging and disseminating. In the last analysis, 
these are the books that encompass the record, the memory, 
and the substance of human civilization.

Coming To The Rescue
The encouraging news, however, is that the technology 
endangering the book as it has existed since Gutenberg is 
also poised to come to its rescue. The printed book has 
attributes of great convenience compared with every other 
existing form of information storage and retrieval--no 
matter how sophisticated--and it is unlikely to be easily 
superseded. It is hard to imagine taking a microfilm reader 
to scan in bed, reading an overhead projection on the cool 
edge of a running brook, or curling up with a computer 
display in front of a crackling wood fire. No matter what 
the ingenuity of man can ultimately afford, the book remains 
a more universally human-oriented, concentrated, and 
comfortable device to convey the written word than anything 
else thus far invented.

How to retain all the ergonomic advantages of the book while 
doing away with its defining economic burdens is the 
question that my imagination addresses here. Although it is 
premature to outline the precise technical details that are 
yet to be developed, my speculative flight of technological 
fancy--or at least an approximation or variation of it--is 
within the realm of possibility for the foreseeable future.

A New Kind Of Browsing
Imagine, if you will, that you are at home and at loose 
ends. There is nothing on television or radio that appeals 
to you. But one of last Sunday's newspaper book reviews 
intrigues you. Of course, this late in the evening, 
libraries and most book shops are closed. If your library or 
shop is by any chance still open, the likelihood of finding 
the desired book--too new to be a best-seller--on its 
shelves would be very slim. And even if you were lucky 
enough to locate a copy, you might want to leaf through it 
first before borrowing or buying it.

Imagine further that, in addition to television, radio, 
computer, and stereo, there is in your living room or study 
a black box--not a huge black box, but sizable enough to 
accommodate my fantasy. It hosts a display screen and, 
positioned below it, a quite capacious rectangular slot. 
Adjacent to the black box is a keyboard very much like the 
one for your computer; and on a shelf above the box is a 
collection of books of different sizes and colors but 
without titles. A visitor to your study would be surprised 
to see, when taking one of them off the shelf, that all its 
pages are blank. Indeed, these volumes contain no words--for 
their pages are blank visual tapes of a sort, onto which 
temporary typography and graphics will be imprinted and read 
like any ordinary book, then erased after use.

The Process
To imprint a blank book, you will first type a request on 
the black box keyboard. Your request is relayed to one of 
many data banks that collectively access every published 
book on every available subject. Sources include, for 
example, the Library of Congress in Washington, D.C., as 
well as international repositories such as the Bibliothque 
Nationale in Paris, which, incidentally, is today in the 
process of computerizing its treasures. After the request 
for a particular book has been entered, instructions appear 
on the black box screen, requiring that you specify the size 
of the blank volume that you wish to have printed and, if 
desired, the colors you wish to see used in the printing. 
The instructions also inform you of the price you will be 
charged for this service.

Next, you insert the appropriate blank book into the slot in 
the black box, and within a minute or so the book is 
ejected--its formerly blank pages now in proper order and 
filled with text and multicolored illustrations.

For economic as well as technical reasons, the book will not 
be a permanent addition to your library, since after a time-
-perhaps a few weeks--the type will fade and eventually 
disappear. Of course, you can "renew" your copy by 
teleprinting it again if you so desire, with the cost being 
charged to your account. For a permanent edition, you would 
have to purchase the kind of costly book that is available 
today.

A Reasonable Expectation
The implications of such a scenario are staggering. 
Libraries as we know them might be eliminated, becoming 
instead repositories primarily of the most significant and 
enduring works, including major reference volumes. The 
process would eliminate the high investment costs, 
inconvenience, and headaches of lending libraries. It would 
bring to each individual potential access to the total scope 
of the written word on every subject and in every language.

For economic reasons, popular but ephemeral books would 
probably exist solely in this short-lived form, stored 
permanently only in central data banks in digitally 
compressed format. The technology involved might, for 
example, consist of an advanced form of liquid crystal, with 
paper-thin, pixel-sized capacitors retaining electrical 
charges displaying characters for a few weeks.

But, in a fantasy, the details are unimportant. My point is 
that it is possible to conceive of a teleprinting technology 
that could emulate and exceed the scope of today's Internet. 
Sociologist Wilbur Schramm has provided a keen insight on 
the subject: It took some 5 million years for mankind to 
advance from primitive elements of a spoken language to the 
written word. It took 5,000 years to move from the written 
word on stone tablets and parchment to movable-type 
printing. From Gutenberg's Bible to television, less than 
500 years elapsed. Each of these major advances in 
information handling took, on average, one order of 
magnitude less time than the preceding one.

If this pattern continues, it seems reasonable to expect 
teleprinting of books to make its appearance shortly after 
the beginning of the 21st century. 

Elie A. Shneour, a physical biochemist, is chief executive 
and director of research at Biosystems Research Institute, 
San Diego.
E-mail: eshneour@ucsd.edu.


(The Scientist, Vol:8, #18, pg.12, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

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                          --------
NXT:

                         COMMENTARY


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TI   : Multilingual Capability Is Essential In The Global 
       Science Community

AU   : EUGENE GARFIELD

TY   : OPINION (COMMENTARY)

PG   : 13

It was disappointing to learn that linguistic chauvinism has 
reared its head once again in the form of a law proposed 
several months ago by Jacques Toubon, France's Minister of 
Culture. Ostensibly, the measure promoted the purity of the 
French language. Among its sillier provisions, the law 
banned in official communications thousands of words such as 
"weekend" that are in common use throughout France, but are 
not etymologically home-grown.

Not so silly in its implications is the suppressive spirit 
of the law, an irony in a nation so traditionally identified 
with democracy and the "Rights of Man."

Particularly galling (no pun intended) was another of the 
lawUs implications, which--if the statute had remained in 
effect--would require all scientific papers based on 
publicly funded research to be published in French. 
Considering my past involvement with this matter, I was 
pleased when FranceUs Constitutional Council overturned the 
law (which had, in fact, been passed by the French 
legislature) on grounds that it would infringe on individual 
rights.

Toubon's hobbyhorse, if set to rocking, would have been a 
sorry expression of nationalistic fervor likely to be (a) 
unenforceable, (b) an embarrassing revelation of France's 
inability to integrate itself maturely into today's global 
community, and (c) a heavy setback regarding that nation's 
pursuits in the international science community.

Actually, my annoyance with the likes of Toubon goes back 
more than a quarter-century. In the 1960s, when the 
Institute for Scientific Information was launching the 
Science Citation Index and I was explaining the concept to 
researchers around the world, I frequently lectured in 
France. I couldn't help feeling uncomfortable with the 
frowning faces I saw when I mispronounced a word or botched 
an idiomatic expression. In responding to questions, I 
usually relied on a translation provided by an obliging 
French colleague, to make certain I had grasped all of the 
colloquial nuances.

In the 1970s, I perceived a change taking place: Questions 
from my French audiences were increasingly asked in English, 
and my colleagues--still impatient with my fractured French-
-suggested that I present my lectures in English. I 
developed my own hands-across-the-sea device, beginning 
lectures with brief introductions in French, then continuing 
in English. Not only was I understood, but also it became 
apparent that, in France as elsewhere, the common language 
of the international science community had become English, 
as I noted in an essay titled "The English Language: The 
Lingua Franca Of International Science" (The Scientist, May 
15, 1989, page 12).

I've addressed this subject frequently over the years, 
occasionally stirring up a bit of controversy. Seventeen 
years ago, in a two-part Current Contents essay ("Le Nouveau 
Defi Americain," Essays of an Information Scientist, 
Philadelphia, ISI Press, Vol. 3, pages 88-102, 1977-78), I 
reported on the reaction of Michel Debre, former Prime 
Minister of France, to an article I had published the year 
before in the French journal La Recherche. In the article, I 
had suggested that French science--in part owing to 
linguistic nationalism--was too provincial and that its 
researchers should publish in English. Debre claimed that my 
suggestion posed a threat to French tradition "from which 
people could not recover" and warned that "a nationalist 
revolt" might ensue "if we follow Garfield" (La Recherche, 
7:956, 1976).

Well, the passage of time has proved Debre wrong. I took 
great pleasure in the French Academy of Sciences' decision 
to publish not only an English contents page, but also 
extended resumes in its Comptes Rendus; likewise my reaction 
to the routine inclusion of English texts in the journals of 
the Institut Pasteur. The academy, the institute, and French 
publishers such as Gauthier-Villars realize that survival in 
the international science arena is directly linked to their 
publishing in English. (One might only speculate on the 
outcome of the Montaigner-Gallo dispute had Montaigner and 
his colleagues published their important studies in French-
language journals exclusively.)

For Jacques Toubon and other Francophiles who still cling to 
their misguided linguistic dreams, I must repeat a challenge 
I made almost 20 years ago:

The French language will not decline because French 
scientists publish in English--as long as French mothers and 
fathers continue to speak French to their children (even if 
they grow up to become scientists). But in order to become 
significant players in the international science arena, 
French scientists cannot refuse to learn English. Neither 
France nor the French language will ever suffer for having 
encouraged the development of a strong cadre of 
internationally recognized multilingual scientists.

Moreover, the need for multilingual capability is not 
limited to the French. The pursuit of familiarity with, if 
not fluency in, languages other than one's own should be 
fundamental in the education of anyone hoping to participate 
effectively in the modern research world. For reasons that 
the French should understand very well, I urge American 
parents to introduce children to other languages as part of 
the cultural development they will need in order to succeed 
and fully enjoy careers in the global economy.


(The Scientist, Vol:8, #18, pg.13, September 19, 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:
                          LETTERS

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TI   : NO COMMON GROUND

AU   : FREDERICK SPERLING

TY   : OPINION (LETTERS)

PG   : 13

No Common Ground
Regarding the news article in the May 30, 1994, issue of The 
Scientist reporting on the perennial animal research debate 
[N. Sankaran, page 3]: Any new panel, at any level, official 
or nonofficial, is doomed to failure, since no common ground 
exists for discussion between researchers and animal rights 
activists. The quote by John McArdle, scientific adviser to 
the Jenkintown, Pa.-based American Anti-Vivisection Society-
-"The ultimate goal is to replace animals with other 
methods, since we believe it is immoral and unethical to use 
animals"--plainly indicates that a rational discussion is 
impossible and agreement with the activists is wishful 
thinking.

I pointed this out at a National Institutes of Health 
conference a few years ago. It is just as true now as it was 
then. That conference degenerated into name-calling and 
personal attacks by the animal rights participants. No 
agreement of any kind was reached.

I personally resent being characterized as immoral and 
unethical by McArdle and his ilk. It might be interesting to 
investigate the sympathies and ties of these moral and 
ethical animal rights advocates with those who perpetrated 
terrorist acts against laboratories. It has been shown time 
and time again that appeasement is ineffective, as any act 
of appeasement with animal rights activists will be.

Frederick Sperling
Professor Emeritus, Pharmacology and Toxicology
Howard University
College of Medicine
5902 Mount Eagle Dr., #407
Alexandria, Va. 22303


(The Scientist, Vol:8, #18, pg.13, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   :  RADIOIMMUNOASSAY

AU   : FREDERICK C. GREENWOOD

TY   : OPINION (LETTERS)

PG   : 13

Radioimmunoassay
With reference to the article by Rebecca Krumm in the May 
16, 1994, issue of The Scientist on radioimmunoassays [page 
17]: A possible quantitative measure of the current use of 
radioimmunoassay (RIA) might be the data prepared by the 
Institute for Scientific Information on the number of 
references, over the years, to "preparation of iodine-131-
labeled human growth hormone of high specific activity."

This was a preliminary report of the method published by 
W.M. Hunter and F.C. Greenwood in Nature, 914:495-6, 1962. 
This report and the full report, published by F.C. 
Greenwood, Hunter, and S. Glover, Biochemical Journal, 
89:114-23, 1963, were both named Citation Classics. In 
Current Contents  No. 26, June 26, 1989, page 16, I tried to 
explain the apparent paradox in an article entitled 
"Longevity of immunochemical methods that work."

I spent much of my scientific life in England looking at 
hormone levels, first in urine and then in blood, and the 
labeling technique developed by Hunter and myself allowed us 
to develop the first growth hormone RIA. But it also allowed 
the beautiful technique of S.A. Berson and R. Yalow [Journal 
of Clinical Investigation, 38:1996, 1959] to come out of the 
closet of the very highly skilled research lab into more 
mundane practice.

I have long since recognized that measuring systemic 
hormones in plasma is but one minor aspect of the endocrine 
system, and my research here in Hawaii, with my wife, 
Gillian D. Bryant-Greenwood, has focused on the even more 
challenging problems of examining autocrine/paracrine 
aspects of endocrinology using a human model system--the 
human fetal membranes.

Nevertheless, I enjoyed very much your article. It has been 
fun to see a Cadillac method metamorphose into a Volkswagen 
Beetle!

Frederick C. Greenwood
Professor of Biochemistry
Director, Pacific Biomedical Research Center
University of Hawaii at Manoa
1993 East-West Rd.
Honolulu, Hawaii 96822


(The Scientist, Vol:8, #18, pg.1, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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NXT:

                          RESEARCH

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TI   :  Researchers Plumb Depths To Fight A Wide Array Of 
        Human Diseases

AU   :  Karen Young Kreeger

TY   :  RESEARCH

PG   :  14

As his boat rocks gently on the Caribbean Sea a few miles 
off the coast of Jamaica, William Fenical dons his scuba 
gear, slips overboard, and disappears into the warm waters. 
Although deep-sea diving is a pleasure for Fenical, taking 
the plunge, in this case, is by no means a recreational 
pursuit.

Fenical is a marine chemist at the Scripps Institution of 
Oceanography in San Diego, and the object of this dive is to 
gather samples from the feathery seaplume, a type of coral. 
Back in his lab at Scripps, Fenical and colleagues will 
extract a substance called pseudopterosin from the soft-
bodied creature. Working with clinicians, physicians, and 
other biomedical researchers, Fenical's industry 
collaborators will soon be conducting clinical trials using 
the compound to find new and better ways to combat 
inflammatory diseases.

Throughout the world, marine scientists and their partners 
in industry, academia, and government are now searching for 
more effective drugs to treat a variety of diseases, 
including AIDS, cancer, and asthma. These international 
research collaborations draw on expertise from numerous 
disciplines: Ecologists, biochemists, oncologists, cell 
biologists, microbiologists, molecular biologists, 
pharmacologists, and clinicians are just some of the 
researchers involved in these efforts.

"Our program represents marine science--the discovery side," 
says Fenical of his part in a multidisciplinary research 
team at Scripps, which is run by the University of 
California, San Diego. "We're the ones that get into the 
water and get the materials and have a big freezer back at 
the lab to store the stuff. We extract, isolate, and 
identify the material. And once we do that, we collaborate."

Compounds have been extracted from marine plants and animals 
for centuries--Pliny the Elder described the toxic 
properties of sea hares in the genus Dolabella more than 
2,000 years ago. Modern interest in drugs from the sea 
resurfaced about four decades ago. But the current wave of 
activity has welled up in the last five to 10 years, 
researchers agree.

"The majority of drugs are discovered in nature, certainly 
historically. Drugs from natural sources have been the 
foundation of the treatment of human disease," says Fenical. 

But "why do we need to discover new drugs from the sea?" he 
asks. Because, say Fenical and others, some organisms that 
cause disease have evolved resistance to currently used 
drugs, and medical science has conquered only a small 
portion of human disorders.

So what does the sea have to offer biomedicine that 
researchers can't get on the land or in a test tube? Fenical 
explains: "Marine animals have evolved two basic mechanisms 
to survive: physical defenses, such as spines and shells; 
and chemical defenses, which you find in soft-bodied animals 
that swim around in the ocean and are completely left 
alone."

"These animals are noxious as hell. So we go to these highly 
chemically defended invertebrates, and for one reason--we 
know they're rich in unusual organic compounds." Fenical 
notes, however, that when his group began its investigations 
they foresaw no direct connection between defense and anti-
disease activity. That they have found this relationship in 
some sea creatures was "just serendipity," adds Fenical.

According to David Newman, a chemist at the Natural Products 
Branch of the Division of Cancer Treatment at the National 
Cancer Institute (NCI), such connections are just what NCI 
scientists are counting on to find treatments for several 
types of cancer as well as AIDS. One of NCI's first 
contracts associated with marine organisms was initiated in 
1985 with the Australian Institute of Marine Sciences to 
collect plants and animals on the Great Barrier Reef.

Two compounds derived from marine animals are currently in 
Phase I and II trials as anti-tumor agents, and others are 
"in the pipeline," says Newman.

A Hot Field
The potential for finding new, efficacious drugs from the 
sea is only one part of the overall surge in the larger 
field of marine biotechnology in the last decade. According 
to Oskar Zaborsky, president of the Institute for 
BioEnviron- mental Information and Studies (IBIS), a 
nonprofit organization located in McLean, Va., there are 
three very active areas in this growing discipline (see 
story on page 15). "One is the drug area--that sort of can't 
be denied--the second is specialty enzymes from marine 
microbes [M.E. Watanabe, The Scientist, May 30, 1994, page 
14]. And the third one is aquaculture."

Interest in marine biotech is "exploding,' says Rita 
Colwell, a marine microbiologist and president of the 
Baltimore-based University of Maryland Biotechnology 
Institute. "I wrote an article published in Science in 1983 
[R.R. Colwell, "Biotechnology in the marine sciences," 
222:19-24], and since then more than 1,000 papers have been 
published on marine natural products and various aspects of 
marine biotechnology. Also since then, funding in the United 
States has grown to about $80 million, if you take into 
account both federal and private industry." Total federal 
funding for marine biotechnology for fiscal year 1993 was 
nearly $50 million.

The Marine Biotechnology Investment Act, which was passed in 
the House of Representatives, is also expected to pass the 
Senate at the close of the current session, according to 
David Attaway, director of the marine biotechnology program 
for the National Sea Grant College Program in the National 
Oceanographic and Atmospheric Administration.

The act authorizes $20 million for each of its first two 
fiscal years and $25 million for each of two subsequent 
fiscal years to fund research in marine biotechnology. "Of 
course," says Attaway, "it's not often that authorized 
amounts reach appropriated amounts. This authorization sets 
the limit; the appropriation sets the amount."

Congress has already increased the budget for the Sea Grant 
Program for fiscal year 1994 by $3.2 million, according to 
Attaway. This amount was earmarked for marine biotechnology 
research. NOAAUs Sea Grant conducted a special call for 
proposals to utilize these funds, receiving 256 grant 
applications requesting a total of $25 million for the first 
year of research. Attaway says that although the proposals 
were top-notch, Sea Grant could fund only 20 of them.

A Broad Approach
One way to find new drugs from any natural source is to 
gather samples and test them broadly on cultures of cells. 
Investigators from all over the world collect samples from 
marine systems--as well as rainforests, deserts, and just 
about every other ecosystem on Earth--and send them to NCI's 
Natural Products Repository in Frederick, Md., which houses 
more than 500,000 samples of plants, marine life, and 
microorganisms. Here they are stored, extracted, and 
screened for activity against a variety of tumor-forming 
cancers--such as breast, colon, and prostate cancer--for 
which there are no effective drugs. Preliminary testing 
against HIV using extracts from seaweeds is also under way.

Kenneth Rinehart, a chemist at the University of Illinois in 
Urbana, is working with NCI on two compounds that may prove 
useful for a number of cancers. Didemnin B, a substance 
extracted from a marine animal called a tunicate and found 
in the western Caribbean Sea, is currently in Phase II 
clinical trials for non-Hodgkin's lymphoma and a type of 
central nervous system tumor. However, this extract--which 
is the marine compound at the most advanced stage of 
development for use as an anti-cancer agent--has remained in 
Phase II for five years because of debilitating side 
effects. 

"I'm on the edge," says Rinehart about the results so far in 
the didemnin B trials, "because patients' responses to it 
varied from complete to partial, with only about 20 percent 
of them showing this response. But people at the NCI were 
very pleased with that. 

"But, I'm not convinced that didemnin B is the best didemnin 
to be using. There is a new one called dehydro-didemnin with 
six times the potency as didemnin B," he says. This new 
tunicate compound is owned by a Spanish pharmaceutical 
company called Pharmarmor. 

ET 743--another compound derived from Caribbean tunicates--
is currently in preclinical trials and is "scheduled for 
Phase I trials after the first of the year," says Rinehart. 
Thus far, ET 743 has not "encountered any serious toxicology 
problems and its activity in vivo looks very good against 
leukemia, melanoma, ovarian sarcoma, and breast and lung 
cancers."

Given these and other drugs that are in various stages of 
testing, Rinehart says he "is very hopeful" that several new 
compounds will be on the market in the coming years. 

Also taking a "shotgun approach" to testing marine compounds 
for new drugs is David Manyak, president and chief executive 
officer of Oceanix Biosciences Corp. in Hanover, Md., a 
biotechnology firm with about 30 employees.

Manyak says his company obtained Novascreen--a receptor-
binding assay--from Baltimore-based Nova Pharmaceutical 
Corp. more than a year ago to  simultaneously screen dozens 
of substances derived from marine organisms.

"We're most interested in screening for compounds to treat 
central nervous system disorders such as epilepsy, 
Parkinson's disease, and Huntington's disease," says Manyak.

He says Oceanix is also interested in screening for anti-
infective agents. To do this, the company has a research 
agreement with the University of Maryland Center of Marine 
Biotechnology (COMB). "We have an exclusive license to 
screen a collection of marine microbes from COMB. So we are 
building up copies of those microbes internally and that 
library numbers 5,000," says Manyak.

"We are screening 40 to 60 receptors at once, so we think 
we'll have a very high probability of finding new drugs in a 
number of categories just because of the breadth of our 
library of microbes and screening activities."

A Narrow Approach
Rather than screen several types of marine organisms for 
potential antidisease activity, Fenical is concentrating his 
efforts on one type of organism, which he hopes can be used 
for a variety of applications. His group's main interest is 
identifying anti-inflammatory agents to treat such diseases 
as arthritis, asthma, and psoriasis.

"When we became committed to investigating inflammatory 
diseases, we realized that we had focused our efforts very 
narrowly," Fenical says. "But that turned out to be a wise 
decision because we were able to bring together sufficient 
expertise to construct a well-informed research program.

"Our goal is to create new drugs which are far superior than 
existing drugs. We obviously don't wish to reinvent the 
wheel."

The substance at the most advanced stage of development in 
the labs of Fenical and colleagues is pseudopterosin, a 
chemical extracted from the seaplume, which he calls a "very 
potent anti-inflammatory."

Pseudopterosin "will be in clinical trials within the next 
few months," he says.

Fenical and his academic colleagues are working with Thomas 
Sharp, executive vice president and director of research and 
development at OsteoArthritis Sciences Inc., a two-year-old 
biotechnology firm with about 35 employees located in 
Cambridge, Mass.

Sharp reports that pseudopterosin will soon be tested as a 
topical anti-inflammatory for dermatitis. "We expect to 
submit an investigational new drug application [to the Food 
and Drug Administration] at year end," he says.

"The exciting thing about this project is that this drug has 
a novel structure and is unrelated to currently available 
drugs to treat dermatitis," Sharp says. "We believe it will 
have fewer side effects than currently available drugs."

Environmental Connections
The collaboration between biomedicine and marine sciences 
does not end at the lab or hospital doorstep. IBIS's 
Zaborsky says that scientists searching for new remedies to 
fight human disease are taking a growing interest in the 
burgeoning field of marine biodiversity and its 
preservation.

The reason for this meeting of seemingly divergent 
disciplines, he says, is "partly the need for new drugs and, 
for myself and others, the shared conviction that there is a 
logical connection between biodiversity and biotechnology, 
which can be positively reinforced. 

"If people have drug-development programs, they can couple 
these with biodiversity programs, so what is found in nature 
can be preserved. What we [IBIS] try to do is look at that 
in combination with the National Cancer Institute and the 
National Institute of Allergy and Infectious Diseases."

For example, Zaborsky recently submitted a proposal--with 
NCI--entitled RInternational Cooperation in Marine 
Biotechnology for Pharmaceutical Development and 
Preservation of Marine Biodiversity" to the State 
Department. The proposal requests funds to set up an 
international framework to link academic, industry, and 
government research in these areas.






(The Scientist, Vol:8, #18, pg.14, September 19, 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   :  MEETING GROUNDS FOR MARINE BIOTECHNOLOGISTS

TY   :  RESEARCH

PG   :  14

For more information on marine natural products and 
pharmaceuticals, contact:

American Society for Microbiology
1325 Massachusetts Ave., N.W.
Washington, D.C. 20005-4171
Phone: (202) 737-3600
Fax: (202) 942-9340

(For the appropriate E-mail address, call the above number.)

Michael Goldberg, Executive Director
David Schlessinger, president


American Society for Molecular Marine Biology and Biotechnology
P.O. Box 51456
Pacific Grove, Calif. 93950
Phone: (408) 655-6214
Fax: (408) 373-1254

E-mail: fh.dap@forsythe.stanford.edu

Dennis A. Powers, president

A three-year-old journal, Molecular Marine Biology and 
Biotechnology (Blackwell Scientific Publications Inc., 
Boston), associated with ASMMBB, is the only United States 
journal that covers basic and applied marine biotech. 
Contact Powers for more information on the journal.


American Society of Pharmacognosy Department of 
 Pharmacognosy School of Pharmacy
University of Mississippi
University, Miss. 38677

Phone and fax: (601) 232-7026

E-mail: pgclark@vm.cc.olemiss.edu

Alice Clark, president

(The Scientist, Vol:8, #18, pg.14, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

                          --------
NXT:

------------------------------------------------------------
TI   : THE MANY FACES OF MARINE BIOTECH

AU   : KAREN YOUNG KREEGER
TY   : RESEARCH

PG   : 15

Marine biotechnology covers a broad range of topics. 
According to a new book on the subject, entitled Marine 
Biotechnology, Volume I: Pharmaceutical and Bioactive 
Natural Products (D.H. Attaway, O.R. Zaborsky, eds., New 
York, Plenum Press, 1993), the discipline is defined simply 
as "the use of marine organisms or their constituents for 
useful purposes in a controlled fashion."

Don Renn, director of exploratory technology at FMC Corp. in 
Rockland, Maine--a company that has been producing products 
from seaweeds for the biomedical research and development 
market for almost three decades--makes two main distinctions 
beyond the book's definition. He explains that marine 
biotech can mean either manipulating plants and animals 
genetically to obtain useful products from them such as in 
some aquaculture ventures; or using products derived from 
marine organisms for high-tech purposes such as gels for 
molecular biological techniques or in pharmaceuticals.

Some institutions even divide their departments along the 
disciplines that encompass marine biotech. According to 
Madilyn Fletcher, director of the Center of Marine 
Biotechnology at the University of Maryland Biotechnology 
Institute in Baltimore, three areas of research cover the 
center's activities: aquaculture and fisheries molecular 
biology and biotechnology; natural products and processes; 
and marine pollution and bioremediation. The natural 
products component includes marine pharmaceuticals, she 
says.

--K.Y.K.


(The Scientist, Vol:8, #18, pg.15, September 19, 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:
                         HOT PAPERS

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

TY   :  RESEARCH (HOT PAPERS)

PG   :  16

J. Weissenbach, G. Gyapay, C. Dib, A. Vignal, J. Morissette, 
P. Millasseau, G. Vaysseix, M. Lathrop, "A second-generation 
linkage map of the human genome," Nature, 359:794-801, 1992.

Jean Weissenbach (Genethon, Evry, France): "In 1991, the 
French Muscular Dystrophy Association and the Center for the 
Study of Human Polymorphisms (CEPH) created Genethon, a 
laboratory whose goal was to provide the scientific 
community with human genome maps that would hasten the 
localization and identification of human disease genes.

"The first version of the Genethon genetic linkage map was 
published in October 1992. Its advantage lies in the fact 
that it is composed of 813 simple tandem repeats 
(microsatellites), notably (CA)n motifs, which are widely 
distributed throughout the human genome. As first shown by 
J.L. Weber and P.E. May (American Journal of Human Genetics, 
44:388-96, 1989), these markers are highly informative in 
that they are highly polymorphic, which means that an 
individual is likely to possess two different alleles for a 
microsatellite at a given locus. Genetic mapping was 
previously based on other kinds of markers, such as 
restriction fragment-length polymorphisms, which are 
frequently biallelic and have limited usefulness in tracing 
inheritance patterns. This map has already been used for 
localization of genes for at least 15 genetic disorders that 
are caused by single-gene defects, such as colorectal 
cancer, glaucoma, and one form of dwarfism.

"We recently published a second version of this map 
consisting of 2,066 markers (G. Gyapay et al., Nature 
Genetics, 7:246-339, 1994) and are working on a third and 
final version, which will contain about 5,000 
microsatellites. Using these maps as tools, the scientific 
community should now be able to rapidly localize any disease 
due to a single defective gene and begin to study disorders 
that result from defects in more than one gene. Markers from 
this linkage map have already been integrated into 
CEPH/Genethon's physical map, which consists of overlapping 
YAC (yeast artificial chromosome) clones that span about 90 
percent of the human genome (D. Cohen, I. Chumakov, J. 
Weissenbach, Nature, 366:698-701, 1993). These maps can now 
be used as starting points for positional cloning 
strategies, which will lead to precise identification of 
guilty genes and, subsequently, to an understanding of their 
function."

(The Scientist, Vol:8, #18, pg.16, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

                          --------
NXT:

------------------------------------------------------------
TI   : MOLECULAR BIOLOGY

TY   : RESEARCH (HOT PAPERS)

PG   : 16

A. Musacchio, M. Noble, R. Pauptit, R. Wierenga, M. Saraste, 
"Crystal structure of a Src-homology 3 (SH3) domain," 
Nature, 359:851-5, 1992.

Matti Saraste (European Molecular Biology Laboratory, 
Heidelberg, Germany): "Many proteins that function in the 
signaling pathways of animal cells or yeast are made up of 
distinct domains. These are common to a number of proteins 
and have structural or functional independence. The SH3 
domain is one such mobile protein module.

"SH3 was discovered by comparing amino acid sequences among 
several different signaling and cytoskeletal proteins. It 
was  called `Src-homology 3,' after Src, the prototype 
protein tyrosine kinase. The SH3 domain is often accompanied 
by the SH2 domain, which is made up of about 100 amino acids 
and recognizes a peptide containing a phosphorylated 
tyrosine in a specific sequence environment. SH2 is a module 
that is used for specific interactions between 
phosphorylated receptors and their downstream partners in 
signal transduction. SH3 seems to be involved in protein-
protein interactions that are intrinsic to the activating 
and inactivating processes of signal transduction and 
cytoskeletal dynamics. However, its specific function is not 
as well characterized as that of SH2.

"These common protein domains often have a small size, 
which--together with their biological importance and ability 
to be expressed in bacteria--has encouraged their study 
among structural biologists. We determined the first SH3 
structure using X-ray crystallography. The work was mostly 
done by two Ph.D. studentsQAndrea Musacchio, in our group, 
and Martin Noble, working with Dr. Rik Wierenga. This report 
was followed by a cascade of homologous structures obtained 
by both X-ray crystallography and nuclear magnetic resonance 
(NMR) spectroscopy. All SH3 domains have the same basic 
core, made up of two orthogonal b-sheets. They vary in their 
surface loops, which have different sizes and conformations.

"In our paper we commented on how the amino acids that are 
evolutionarily conserved within this family come together in 
space to form a smooth platform at one end of the molecule. 
This surface path is particularly rich in aromatic amino 
acids. We postulated that this surface is involved in 
binding another protein, forming the basis for defined 
interactions between some of the signaling molecules. The 
li-gand that binds to the aromatic surface appears to be a 
proline-rich peptide. Multiple adjacent proteins form a 
rigid peptide that places the flanked or terminal amino 
acids in fixed positions in space. These nonproline residues 
may give the specificity to the SH3-binding motifs.

"The molecular details of the SH3-mediated interactions are 
not yet known. But the structural information helps in the 
design of accurate biochemical experiments that can test 
current models and hypotheses."


(The Scientist, Vol:8, #18, pg.16, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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                          --------
NXT:

------------------------------------------------------------
TI   :  GEOPHYSICS

TY   :  RESEARCH (HOT PAPERS)

PG   :  16


S.C. Cande, D.V. Kent, "A new geomagnetic polarity time scale for 
the  late  Cretaceous  and  Cenozoic,"  Journal  of   Geophysical 
Research, 97:3917-51,1992.

Steven C. Cande (Scripps Institution of Oceanography, 
University of California, San Diego): RThe geomagnetic 
polarity time scale is a cornerstone of the geosciences, 
providing the means for precise global correlation and the 
chronological framework for all modern time scales. The 
first geomagnetic polarity time scale that covered the 
entire Cenozoic era was constructed in the early days of the 
plate tectonic revolution in the late 1960s from a few 
carefully selected marine magnetic profiles (J. Heirtzler et 
al., J. Geophys. Res., 73:2119-36, 1968). This time scale 
not only was extremely valuable but also proved to be very 
durable. Although there have been many revisions to the time 
scale since 1968, they involved--for the most part--applying 
new calibration points to the magnetic anomaly spacings 
determined in the original time scale.

"Over the years it became apparent that the original anomaly 
spacings that formed the core of the Cenozoic time scale 
needed to be revised. For example, global studies of 
seafloor spreading rates were finding synchronous spreading 
rate changes in all the oceans. Although such a phenomenon 
might be real, we speculated that it could also reflect 
errors in the time scale. Consequently, we systematically 
reanalyzed marine magnetic profiles from several different 
oceans, and attempted to derive a more accurate set of 
magnetic anomaly spacings--the basic starting point for 
calculating a new time scale. Our analysis included looking 
for evidence of very short polarity reversals, which show up 
as `tiny wiggles' in the magnetic anomaly record. We then 
came up with a carefully selected set of calibration points 
and derived a revised time scale.

"We noted in our paper that with our revised time scale many 
of the previous indications of synchronous spreading rate 
changes have been eliminated. Other geoscientists who use 
our new time scale have since found that it gives more 
reasonable sedimentation rates. Because of this apparent 
improvement in accuracy, the time scale has been widely 
used.

"Recently other researchers have independently derived a 
magnetic polarity time scale for the late Cenozoic from the 
study of high-resolution climate records, assuming that 
their variability is forced by the well-known variations in 
the Earth's orbital parameters. One direction of our future 
research involves reconciling and merging the results of the 
`astronomical' time scale (which is based on high-resolution 
climate records) with our time scale, which is based on 
marine magnetic anomalies."


(The Scientist, Vol:8, #18, pg.16, September 19, 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:

                     TOOLS & TECHNOLOGY

------------------------------------------------------------
TI    : New Journals On CD-ROM Help Scientists To Build  Personal 
Libraries

AU   : Franklin Hoke

TY   : TOOLS & TECHNOLOGY

PG   : 17

Sitting at her computer, a biochemist studies an on-screen 
page from the journal Protein Science, published on CD-ROM 
by the Protein Society of Bethesda, Md. Embedded in the 
article text is a reference to a figure, with a special icon 
in the margin at that point. With a double-click of the 
computer mouse on the icon, a full-color image of a protein 
structure appears. A few additional commands allow the 
molecule to be rotated in space, tumbled in any direction, 
for a different view. Elements of the molecule can be 
selectively highlighted and intramolecular distances 
measured.

The animated, interactive protein image is called a kinemage 
and is an eye-catching example of the new capabilities that 
digital publishing--especially of scientific journals on CD-
ROM--now offers biological researchers. The added features 
extend the existing advantages of CD-ROMs, such as the fact 
that scientists can quickly search their electronic journal 
holdings by title, author, or keywords, which they cannot do 
directly with their print copies. Also, because of the large 
storage capacity of CD-ROMs--about 650 megabytes--
researchers building a personal library of journals on disk 
can save valuable space in their offices or labs. And CD-
ROMs on the shelf rather than in the university library are 
accessible and complete--issues are never missing. 

In just the past few years, the number of scientific 
societies publishing journals in electronic form has jumped 
(see accompanying list). In addition, the sophistication of 
such publications has improved greatly over earlier efforts, 
many of which were little more than basic American Standard 
Code for Information Interchange (ASCII) files, simple 
computer text packages unable to handle equations and 
scientific symbols. Several societies have CD-ROM journal 
projects in development, scheduled to reach members soon. 
Although commercial publishers are interested in 
facilitating electronic publishing, in many cases it is 
scientists and their professional societies who are tkaing 
the lead in developing innovations digital journals.

"I'm a working scientist," says Stephen H. White, a 
professor of physiology and biophysics at the University of 
California, Irvine. White also expends a considerable amount 
of his energies as the electronic publishing coordinator for 
Protein Science. "The only reason I do this is that I'm 
absolutely convinced that, at this early stage [of 
electronic publishing], working scientists have to be 
involved to create products that will really serve us well. 
This electronic medium has to be mroe useful and more 
convenient thatn the print medium. If we make it that way, 
then it will thrive. And if we don't make it that way, it 
will die."

For the most part, the journals are being designed--and 
priced--with the individual bench scientist in mind as the 
user, rather than, say, academic libraries. Most disks, 
usually containing one year's journal issues, are less tan 
$100 for society members. Librarians, in fact, are somewhat 
skeptical of the CD-ROM's staying power as an electronic 
medium, anticipating and preferring journals to be published 
over the linked computer systems of the worldwide Internet, 
according to scientists and society officials.

"Our concern was that this be a useful product to the 
researcher at the bench," says Walter Peter, deputy 
executive director of the American Society for Microbiologoy 
(ASM), Washington, D.C., which provides all 11 of its 
journals on CD-ROM. "We're a membership organization with 
about 40,000 members, and we designed these products for 
them. Not all libraries are entralled with the notion of 
getting subscriptions on CD-ROM. Most of them would prefer 
to have direct line or to continue with print."

In time, scientific journal publishing is expected to 
graduate to the Internet. However, the virtues of journals 
on CD-ROM for individual scientists are likely to sustain 
the disks' viability for some time, according to scientific 
publishers.

"People are talking about CD-ROM as an interim product on 
the way to an Internet interface," observes Charles Muller, 
publishing projects manager, in Woodbury, N.Y., for the 
American Physical Society (APS), which is headquartered in 
College Park, Md. "But CD-ROM is still a very practical way 
for individual subscribers to build a personal library, to 
be able to have many issues of a journal on one disk that 
just sits very neatly on your shelf."

Muller notes that APS is working to develop CD-ROM versions 
of two of its journals--Reviews of Modern Physics and 
Physical Review Letters.

Searching For Standards
One difficulty for the scientific user is that standards 
have not been established for the software programs used to 
search and display the information in electronic journals, 
as well as for the supporting file formats--although a few 
combinations of programs and file formats are beginning to 
emerge as dominant.

"One of the biggest problems we face is that organizations 
that are involved in producing CD-ROMs all seem to want to 
have their own viewer interface," White points out.

"You don't want to install a different search engine on your 
hard drive for each journal that you get on CD-ROM," says 
Victor Bloomfield, a professor of biochemistry at the 
University of Minnesota, St. Paul, and editor of Biophysical 
Journal, published by the Biophysical Society, Bethesda, Md. 
"One wishes that there were some standards."

Bloomfield says that the society is currently participating 
in an experimental CD-ROM publishing project with the 
journal's printing company to assess which combination of 
search and display software will best serve the readers. A 
trial disk containing three months of the journal was sent 
in April to a group of subscribers. According to Carol 
Gross, a research scientist in the biochemistry department 
at Minnesota who has been tallying responses to the disk, 
users want a more attractive and more capable product than 
they received, and the society is now considering 
alternatives.

One combination they are studying would use a search engine 
called WordKeeper, from William Byrd Press, Richmond, Va. 
WordKeeper is based on a product called CD-Answer from 
Dataware Technologies Inc., Cambridge, Mass., and a display 
program entitled Acrobat from Adobe Systems, Mountain View, 
Calif. Acrobat creates its full-color page display from the 
PostScript files used by many desktop publishing systems and 
by many printers to typeset pages.

This is the same combination that ASM will be using for its 
11 journals beginning in January 1995. ASM has provided its 
journals on CD-ROM since January 1993, but using scanned, or 
bit-mapped, images of the printed page for display, which 
contain less information than do the Acrobat files.

"We're going to use Adobe Acrobat files instead of bit-
mapped pages, so that we will have page images on the screen 
with high-resolution graphics in place,S says Peter. "You 
won't have to link to a graphics file when you have a page 
image up. [Acrobat] takes the PostScript files that we use 
now for setting journal pages and emulates pages on the 
screen, which is a great advantage, because it's an all-
electronic pathway for both the printed page and the CD-
ROM."

The American Institute of Physics (AIP), headquartered in 
College Park, Md., also uses Adobe Acrobat for its CD-ROM 
version of the Journal of Vacuum Science and Technology.

A different approach is used to produce Protein Science, 
with its kinemages. The underlying file is created using 
Standard Generalized Markup Language, or SGML. Some 
scientists and librarians involved in electronic publishing 
predict that SGML is likely to develop as the standard file 
format used by journals published over the Internet. Thus, 
they note, the choice of SGML to produce the CD-ROM may be a 
wise step if online publishing is the goal. A browser called 
DynaText, from Electronic Book Technologies Inc. of 
Providence, R.I., is then used to display and navigate the 
journal. Lightbinders Inc., based in San Francisco, produces 
the Protein Science disks.

The same combination is used by the American Society for 
Biochemistry and Molecular Biology (ASBMB), Bethesda, Md., 
to produce its CD-ROM version of the Journal of Biological 
Chemistry. According to Charles C. Hancock, executive 
officer of ASBMB, the result is an inviting display of the 
journal with helpful links between the text and additional 
information or graphics.

"When you look at it on the screen, it looks like something 
that's nicely printed," Hancock says. "It does not look like 
a word processor has been at it. It also has hypertext 
links, so that if you want to see a footnote, thereUs a 
special icon for footnotes--you just double-click on that 
[with the computer mouse] and the footnote comes up. If, in 
the text, you come to a reference--reference 24, for 
instance--it's in a different color than the normal text. 
You double-click on that and it goes immediately to 
reference 24."

APS's Muller notes that the print version of Physical Review 
Letters is already being produced using SGML, so that the 
society will have the option of choosing DynaText as the 
browser for the CD-ROM version, although other choices are 
still possible. Muller says that additional factors might 
support the selection of DynaText.

"[Publishers] can compose the master file for the CD-ROM 
with DynaText software on personal computer workstations," 
he says, "and then just send that master file to a CD 
[production] house. It's touted to be a very good in-house 
system of CD-ROM composition."

The American Chemical Society (ACS) in Washington, D.C., 
uses a proprietary software package called OPTI-WARE, 
licensed from Online Computer Systems in Germantown, Md., 
for the CD-ROM versions of Biochemistry and the Journal of 
the American Chemical Society. This system presents scanned 
images of journal pages, but also provides hypertext links 
to higher-resolution graphics, as well as tables and other 
elements, according to Susan Barclay, assistant editor of 
directories and databases at ACS.

Despite the capabilities of each system used to produce 
scientific journals on CD-ROM, the variance in technology is 
a limiting factor for the field of electronic publishing 
overall, scientists say. When journal publishing moves to 
the Internet, as it is expected to do at some point, the 
issue of setting standards will become even more important.

"If everybody adopted the same standards, we would be able 
to read everybody's journals online," says White. "And 
that's what the electronic library is going to be about. 
Once all journals adopt the same technology, then the true 
electronic library will be a possibility."

Risky Business
One reason CD-ROMs may be a more durable medium than some 
expect is that they are physical objects that can be bought, 
sold, and used in a familiar way. For publishers, important 
questions concerning control over their products must be 
answered before widespread publication via the Internet will 
become possible.

"The problems of going online--they just haven't solved them 
yet," says Peter. "There's an ease of use [with CD-ROM]. You 
just pop it in like you would a floppy and run it, whenever 
you feel like it, for as long as you like, and you pay for 
it once. I'm not sure what the economic models are going to 
be for journals online."

"This is a frightful concern for publishers," adds Muller. 
"And, as far as I know, nobody has a handle on it. Nobody 
knows how these issues are going to be resolved. When I go 
to conferences now on online publishing, many publishers are 
just shaking in their boots during the whole conference. 
They don't know what technology they should spend their 
money on. And whatever they spend their money on, they're
going to spend a lot of money very quickly."

"There are many, many questions about electronic 
publishing," agrees White. "Certainly, how to make it cost-
effective for publishers is at the top of the list. The 
problem is that nobody has any experience, because it hasn't 
happened before."

"Most of us feel that a few years from now we will be 
[publishing online]," says Bloomfield. "But I don't think we 
feel a great need to rush into it.

"There's a lot of concern about how you get paid for the 
product. We don't expect to make a profit from the product, 
but we do need to earn enough to finance the editorial 
office, peer reviewing, and distribution aspects of it, so 
that we can't just give it away. The CD-ROM is great in 
terms of publishers being able to keep ahold of their 
product."

Still, Bloomfield contends, Internet publishing promises 
such pronounced advantages over CD-ROMs that the questions 
demand answers.

"Science is an interconnected web of communication," he 
says. "And it doesn't do to just search one year of one 
journal [on CD-ROM]. What you really want to be able to do 
is a much broader, interconnected search. That's why the 
Internet seems, in the long run, much more plausible."

"In this world that we're in, the CD-ROM is a transient 
affair," says White. "The Internet is the future. Delivering 
the data directly is the future."


(The Scientist, Vol:8, #18, pg.17, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

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71764.2561@compuserve.com

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

                          --------
NXT:

------------------------------------------------------------
TI   :  SCIENTIFIC JOURNALS ON CD-ROM PROLIFERATE

TY   :  TOOLS & TECHNOLOGY

PG   :  17

The following scientific societies produce journals on CD-
ROM or have active development projects in the works. For 
more information on society memberships or journal 
subscriptions, contact the societies directly at the 
telephone numbers given.

*  American Chemical Society (ACS), Washington, D.C., (202) 
872-4600 (Biochemistry, Journal of the American Chemical 
Society)

*  American Institute of Physics (AIP), College Park, Md., 
(301) 209-3100 (Journal of Vacuum Science and Technology)

*  American Physical Society (APS), College Park, Md., (301) 
209-3200 (Reviews of Modern Physics, in development; 
Physical Review Letters, in development)

*  American Society for Biochemistry and Molecular Biology 
(ASBMB), Bethesda, Md., (301) 530-7145 (Journal of 
Biological Chemistry)

*  American Society for Microbiology (ASM), Washington, 
D.C., (202) 737-3600 (Clinical and Diagnostic Laboratory 
Immunology, Journal of Bacteriology, Journal of Virology, 
Molecular and Cellular Biology, Applied and Environmental 
Microbiology, Journal of Clinical Microbiology, 
Antimicrobial Agents and Chemotherapy, Infection and 
Immunity, Microbiological Reviews, Clinical Microbiology 
Reviews, International Journal of Systematic Bacteriology)

*  Biophysical Society, Bethesda, Md., (301) 530-7114 
(Biophysical Journal, experimental project in progress)

*  Protein Society, Bethesda, Md., (800) 99-AMINO (Protein 
Science)


(The Scientist, Vol:8, #18, pg.17, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

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

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

                          --------
NXT:

------------------------------------------------------------
TI   : SUPPLIERS OF SCIENTIFIC PUBLICATIONS ON CD-ROM

TY   : TOOLS & TECHNOLOGY

PG   : 18


The following publishers provide a variety of publications 
on CD-ROM. For more information, please use the Reader 
Service Card inserted in this issue.

Annual Reviews
Palo Alto, CA
Circle No. 137 on Reader Service Card

Butterworth-Heinemann
Stoneham, MA
Circle No. 138 on Reader Service Card

Chapman & Hall

New York, NY
Circle No. 139 on Reader Service Card

CRC Press
Boca Raton, FL
Circle No. 140 on Reader Service Card

Elsevier Science Publishing
New York, NY
Circle No. 141 on Reader Service Card

Institute for Scientific Information
Philadelphia, PA
Circle No. 142 on Reader Service Card

The Johns Hopkins University PRess
Baltimore, MD
Circle No. 143 on Reader Service Card

Kluwer Academic Publishers
Norwell, MA
Circle No. 144 on Reader Service Card

Lightbinders Inc.
San Francisco, CA
Circle No. 145 on Reader Service Card

J.B. Lippincott
Hagerstown, MD
Circle No. 146 on Reader Service Card

The MIT Press
Cambridge, MA
Circle No. 147 on Reader Service Card

Oxford University Press
Cary, NC
Circle No. 148 on Reader Service Card

Random House
New York, NY
Circle No. 149 on Reader Service Card

Scientific American Medicine
New York, NY
Circle No. 150 on Reader Service Card

VCH Publishers
New York, NY
Circle No. 151 on Reader Service Card


(The Scientist, Vol:8, #18, pg.18, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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

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

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

                          --------
NXT:


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

TY   :   TOOLS & TECHNOLOGY

PG   :   19


Millipore Announces Immobilon Sequencing Membranes
Two new Immobilon membranes, both constructed of a 
polyvinylidene fluoride (PVDF) base, have been developed for 
specific western blotting and sequencing applications. The 
Immobilon-PSQ membrane reportedly has higher binding 
capacity than does standard PVDF, which ensures sample 
retention after microtransfer and subsequent processing. The 
membrane can be used for blotting and direct sequencing of 
small and rare proteins with automated sequencers. The 
Immobilon-CD membrane facilitates sequencing of N-terminally 
blocked proteins blotted to its surface. Its cationically 
derivatized matrix permits reversible immobilization of the 
sample so that blocked protein bands can be digested and 
eluted off the membrane surface for peptide mapping.
Millipore Corp., Bedford, MA
Circle No. 152 on Reader Service Card


Labconco Introduces WaterPro HPLC/UF Hybrid Polishing Station
The WaterPro PS polishing station is designed for diverse 
applications requiring both high-performance liquid 
chromatography-grade and pyrogen-free ultrafiltered water. 
Type I water is dispensed from a cabinet-mounted valve, and 
pyrogen-free water is delivered through a gun mounted on the 
dispensing station. The system uses carbon filtration, 
deionization, organic adsorption, and ultrafiltration water-
purification technologies. The ultrafilter periodically 
flushes itself to maintain total organic carbon values of 
less than 10 parts per billion, and an ultraviolet reactor 
eliminates trace bacteria. Water is produced on demand; 
therefore, no storage tank is used.
Labconco Corp., Kansas City, MO
Circle No. 153 on Reader Service Card


Multi-Channel Syringe Pipettes From Hamilton
These four- and six-channel syringe pipettes are designed to 
transfer DNA samples by microplate row or column to 
sequencing gels, nylon membranes, or another microwell 
plate. These are offered in addition to the company's eight- 
and 12-channel syringe pipettes, so users may now transfer 
samples from 0.2 ul to 10 ul. Needle diameters are available 
for sample loading between 0.2 mm or thicker polyacrylamide 
gel casting plates, and for sample loading between 0.4 mm or 
thicker plates.
Hamilton Co., Reno, NV
Circle No. 154 on Reader Service Card


Jandel Releases Version 1.2 Of SigmaScan/Image Software
Version 1.2 of SigmaScan/Image for Windows measurement 
software includes more than a dozen new features for 
automating measurements from digitized photographs, charts, 
maps, blueprints, electrophoresis gels, microscope 
specimens, and other scientific and technical images. Among 
the new features available on the software upgrade are gray-
level-based floodfill measurements, multiple-image splicing, 
image-annotation enhancements, and the Jandel Application 
Manager. In addition, the package enables users to save 
color and gray-level data for each pixel to and from the 
data worksheet.
Jandel Scientific Software, San Rafael, CA
Circle No. 155 on Reader Service Card


Corning Costar Corp. Unveils New Series Of Microcentrifuges
Researchers can choose from among three Costar 5Centrifuges: 
a fixed speed and two variable-speed models, with or without 
solenoid locking covers. The maximum speed of 10,000 rpm 
(5,600 x g) is suitable for separating DNA from agarose or 
acrylamide gels. Two rotors are supplied: a six-place for 
1.5 and 2.2 ml tubes, and a 12-place for 0.6 ml tubes.
Corning Costar Corp., Cambridge, MA
Circle No. 156 on Reader Service Card


Molecular Probes' New Gram Stain Kit
Molecular Probes' LIVE BacLight Gram Stain Kit, a 
fluorescence-based assay, consists of two stains that, when 
applied to living bacterial cells, allow viable organisms to 
be analyzed quickly, without the need for fixing or washing 
cells. When stained with the two fluorescent dyes in this 
kit, gram-positive cells appear orange-red while gram-
negative cells appear bright yellow-green. The LIVE BacLight 
Gram Stain is sensitive enough to analyze low numbers of 
bacteria in the presence of background material. The 
reagents can also be adapted for use with a fluorometer or a 
fluorescence microplate reader to quantitiate the relative 
proportion of gram-positive and gram-negative bacteria in a 
sample.
Molecular Probes Inc., Eugene, OR
Circle No. 182 on Reader Service Card


Spyglass Slicer For Volumetric Visualization
Spyglass Slicer, a volumetric data-analysis tool for 
Windows/Windows NT, reads a variety of data and image 
formats, including HDF (float and byte), netCDF, and binary 
and ASCII matrices. It also can convert stacks of 2D, HDF, 
binary, and ASCII data files as well as read HDF, Windows 
Bitmap, Targa, and TIFF image files. After the data are 
imported, the software uses ray tracing to render data as 
volumes, slices, or isosurfaces. Full control of alpha 
values makes it possible to make any object or data value 
transparent, translucent, or opaque for advanced volumetric 
rendering.
Spyglass Inc., Savoy, IL
Circle No. 157 on Reader Service Card


National Biosciences Upgrades OLIGO Primer Analysis Software
Version 5.0 of OLIGO Primer Analysis Software for Windows 
assists scientists in selecting the optimal oligonucleotides 
for the polymerase chain reaction (PCR), sequencing, 
hybridizations, and other applications. The new features 
include an oligonucleotide database for importing and 
exporting oligonucleotide sequences and data; a PCR primer 
search function to locate all cross-compatible primers; 
automatic degenerate primer selection from an amino acid 
sequence; hybridization time calculations; automatic 
searching for ligase chain reaction primers; batch searching 
for unique oligos in multiple files; and restriction enzyme 
searches.
National Biosciences Inc., Plymouth, MN
Circle No. 158 on Reader Service Card


Waters Unveils HPLC System 
This high-performance liquid chromatography (HPLC) system 
with mass spectral compound detection capabilities contains 
a mass spectrometry detector in a user-oriented format that 
is designed to be simpler, more compact, and more economical 
than any mass spectrometers adapted for HPLC work. An 
interactive diskette is available that contains information 
on the following:

* system description;
* mass spectrometry;
* photodiode array detection;
* Millennium technology; and
* validation requirements.

Waters, Milford, MA
Circle No. 183 on Reader Service Card


Perkin-Elmer Offers New Buffers For Capillary Electrophoresis
Perkin-Elmer has introduced a selection of pre-made buffer 
solutions for capillary electrophoresis (CE) that are of 
high purity and meet stringent quality specifications. The 
selection of buffer solutions includes sodium phosphate at 
pH 2.5, sodium acetate at pH 4.0, sodium phosphate at pH 
7.0, sodium borate/phosphate at pH 8.0, and sodium 
tetraborate at pH 9.0. The solutions come in 40-millimole 
concentrations, providing dilution flexibility for 
simplified methods development. Also available is a 200-
millimole sodium dodecyl sulfate (SDS) solution for micellar 
electrokinetic capillary chromatography, for analysis of 
small, neutral compounds.
Perkin-Elmer, Norwalk, CT
Circle No. 184 on Reader Service Card


Novocastra Offers p53 Antibodies
Five clones of anti-human p53 antibody in unconjugated, 
biotinylated, and fluorescein-labeled form are available for 
use in immunohistochemistry, flow cytometry, and western 
blots. Also available are monoclonal and polyclonal 
antibodies to the MDM2 protein, reportedly the latest p53 
binding protein to be discovered. Four anti-p53 clones are 
mouse monoclonals, and one is a rabbit polyclonal. Vector 
Laboratories is the exclusive United States distributor for 
Novocastra Laboratories.
Vector Laboratories Inc., Burlingame, CA
Circle No. 159 on Reader Service Card


DAKO Introduces New Conjugated Antibodies
The RPE-Cy5 fluorochrome-conjugated antibodies have been 
specifically optimized for flow cytometric applications, 
producing a sharp peak with an emission wavelength around 
680 nm. The high fluorescence intensity of RPE-Cy5 
conjugated antibodies is said to make them well suited for 
analyzing cell populations with low antigen expression. The 
company also offers CD3, CD4, CD8, CD13, and CD19 conjugated 
with this fluorochrome.
DAKO Corp., Carpinteria, CA
Circle No. 161 on Reader Service Card


Nikon's Water-Immersion Microscope Objective Debuts
The 60x water-immersion microscope objective is designed to 
resolve detail in living specimens at or close to the 
theoretical limit for optical performance at depths as great 
as 200 microns below the cover glass. The highly corrected 
60x CFN Plan Achromat objective has a 1.2 numerical aperture 
and a 220-micron working distance. It has high transmission 
and chromatic correction for wavelengths in the near 
ultraviolet through the red spectrum, useful for confocal, 
fluorescence, and DIC microscopy. The lensU cover glass 
correction collar allows 0.15mm to 0.18 mm thick cover 
glasses to be used with critical correction.
Nikon Inc., Instrument Group, Melville, NY 
Circle No. 162 on Reader Service Card


CAChe Scientific Releases New Line Of Chemistry Software
The company's new WorkSystem computer-aided chemistry 
software has been designed for the Apple Macintosh PowerPC 
desktop computer. The software features a stereoscopic 
three-dimensional graphics display and an intuitive user 
interface. It has a variety of applications for molecular 
modeling; prediction of chemical properties, structure, and 
reactivity; and experiment setup and documentation.
CAChe Scientific Inc.,
Beaverton, OR
Circle No. 163 on Reader Service Card


Spire's MacSpec Software For Mass Spectral Analysis
The software package enables users to extract and analyze 
information from gas chromatography mass spectrometry (GC-
MS) data. With simple drawing tools, users can enter 
structures of up to 64 atoms or groups containing any 
element in the periodic table. Once entered, portions of the 
molecule may be "lassoed" to obtain formula and mass, at 
high or low resolution. Users may then build lists of 
formulas, calculate expected isotope patterns for each, and 
produce a simulated spectrum. Complex patterns with 
overlapping peaks may also be simplified.
Spire Software, Maplewood, NJ
Circle No. 160 on Reader Service Card


PerSeptive Offers Interferon Enzyme Immunoassay Kits
The new TiterZyme human interferon-g (IFN-g) and mouse IFN-g 
sandwich immunoassay kits are available for quantitative 
determination of human and mouse levels in serum or cell-
culture supernatant. The kits feature detachable well 
strips, coated with the specific IFN-g antibody, for 
flexibility and consistency in simultaneous runs. These 
assays have sensitivities of less than 1 pg/ml in buffer and 
serum diluent. Each kit contains stable reagents for 96 
tests, including a procedure with standard curves.
PerSeptive Diagnostics Inc., Cambridge, MA
Circle No. 164 on Reader Service Card


Interleukin ELISA Kit From Genzyme 
The Predicta IL-1b ELISA kit facilitates rapid, sensitive, 
and specific measurement of IL-1b in human serum, plasma, 
and tissue-culture fluid specimens. The assay can measure 
IL-1b in a range from 3 to 256 pg/ml, and no measurable 
interference or cross-reactivity to IL-1 receptor antagonist 
is detected, according to the company. Each kit contains 96 
precoated breakaway wells on a microtiter plate and the 
reagents needed to perform multiple runs.
Genzyme Corp., Cambridge, MA
Circle No. 165 on Reader Service Card


(The Scientist, Vol:8, #18, pg.19, September 19, 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:

                         PROFESSION

------------------------------------------------------------
TI   :  Journals Feel Pressure To Speed The Publishing Process

AU   :  Ricki Lewis

TY   :  PROFESSION

PG   :  21

With the electronic age having arrived, new technology 
shortening the production phase of publishing, and the pace 
of research rapidly accelerating, science journals are being 
pressed to slash the time from receipt of article 
manuscripts to publication. Correspondingly, it seems that 
researchers are becoming less willing to wait several months 
or longer for their papers to get into print.

"Usually it takes about a year from the time you submit a 
paper until it actually comes out, especially if reviewers 
think something is wrong and the paper is bounced around," 
says Charles E. Lessman, a professor of biology at the 
University of Memphis. "It might take a year and a half to 
be published. It is frustrating. Journals should be able to 
do better."

The Race Is On
Despite the prestige of publishing in large-circulation, 
multidisciplinary journals, researchers are responding quite 
enthusiastically to new ventures promising faster 
publication, say editors. "A journal that can print an 
article in one month gives a way to attract top papers, 
particularly in a competitive field. So it is to a journal's 
advantage to be fast," says Monica Bradford, managing editor 
of Science. Bradford reports that at her journal the time 
between submission and publication averages 20 weeks. 
However, she adds, the process may be speeded up for 
articles with public-health implications, those in very 
competitive areas, or those containing "ground-breaking 
information."

The reasons for the quickening pace of publication are both 
old and new. A huge effort such as a genome project, for 
example, can lead to a torrent of papers from a variety of 
research groups. In such "hot" areas, a delay of a few 
months as a manuscript goes back and forth between author 
and editor could mean the difference between being credited 
for discovering a gene or just confirming a competing 
group's discovery of it.

Traditional pressures--which are mounting these days because 
of heightened competition for scarce jobs--contribute to 
scientists' desire to see their work in print as soon as 
possible. Indeed, this is leading to a backlog of 
unpublished manuscripts in journal offices.

"The publish-or-perish phenomenon is still on," says Martha 
Davis, an assistant professor in the department of agronomy 
at the University of Arkansas in Fayetteville. "Especially 
in academia, there is no promotion or tenure if a researcher 
hasn't published so many articles, and that's true in some 
industries, too. Because of this, some scientists report 
partial experiments, so they can publish two articles 
instead of one. That adds a lot of volume," says Davis, who 
is the author of Scientific Papers and Presen-tations: A 
Graduate Student Handbook, scheduled for publication next 
year by San Diego-based Academic Press.

The Route To Rapid Publication
Journal editors are responding to the demand for faster 
publishing in some innovative ways, merging the speed of new 
communications technology with the ability to keep the human 
parts of the process on track. "People want to publish 
quickly--and that's what a good editor is all about, making 
quick work of the review process and mediating between 
reviewers and authors," says Harvey Bialy, a molecular 
biologist who is research editor at Bio/Technology, 
published by Nature Publishing Co. in New York.

Bialy says that by sending manuscripts out for review within 
two days of receipt, getting comments back within two weeks 
(including verification of practical procedures described in 
papers), and then overseeing revisions, he gets most papers 
published within two to four months of acceptance.

But some journals can beat even Bio/Technology's fast 
timetable. Advances in Scientific Research (ASR), which 
debuted in April, promises publication within one month of 
receipt. "The idea of a rapid-publication journal was the 
result of discussions with many of my colleagues throughout 
the years," says David Philips, who is the cofounder, along 
with physicist David Newman, of the La Jolla, Calif.-based, 
for-profit Institute for Advances in Scientific Research, 
which publishes ASR. Philips is a physicist and chemist now 
interested in environmental sciences who has held research 
positions at Stanford University and the University of 
California, San Diego. Newman held a position at the 
University of Michigan.

Philips and Newman say they keep their promise by tapping 
into a network of expert reviewers who work fast, and by 
asking authors to help. "When we receive a manuscript, we do 
a quick internal review, then send it to a number of peer 
reviewers," Philips says. "We ask reviewers if they can read 
and return the paper in 72 hours. If they can't, we thank 
them and find other reviewers. Then we send the comments to 
the author, and there's some back-and-forth a few times. Of 
course, the speed of the whole process also depends upon the 
author."

Lessman, who coauthored a paper with his graduate student 
that was recently published in ASR, confirms that the 
journal works quickly: "They indeed did it in a week. We 
faxed it [the manuscript] in, we had comments back a week 
later, we made changes and resubmitted it. That's the way 
things should be."

Gary Evans, a professor of chemistry at Bemidji State 
University in Minnesota, had a similar experience. "It was 
less than 40 days from submission until I was looking at 
reprints," he says. "Usually, you don't even hear from the 
journal editor in 40 days."

As if the challenge of publishing quickly weren't enough, 
the new journal also has a very wide focus, accepting papers 
in physics, chemistry, biology, environmental sciences, and 
interdisciplinary studies. "To accommodate such a broad 
range of disciplines, we interact with a network of 
scientists who provide editorial and technical support," 
Philips says.

The journal's willingness to accept innovative research 
articles is what attracted Lessman in the first place. His 
coauthor, Angela Ventura, had written up part of her 
master's thesis as a paper. Lessman suggested to Ventura 
that she submit the article to ASR. "This particular work 
was quite different, unusual," he says. "We centrifuged Rana 
pipiens [leopard frog] cells and tried to look at how 
different factors control movement of the nucleus." Because 
this is the type of descriptive science typical of work 
early in the century, Lessman felt it might be too 
unconventional to be accepted by a more established journal.

Publisher Philips reports that he is very pleased with the 
response to two ads and a postcard campaign inviting 
submissions. Exact circulation figures are not yet 
available, he says; the third issue is scheduled for 
publication this month. Several hundred copies are being 
printed, according to Philips; they are being sent to 
libraries and individuals who responded to the ads.

Another fairly new venture is Rapid Communications of 
Oxford, England, a subsidiary of the International Thomson 
Organization. Rapid Communications was founded in 1990 by 
Ivan Klimes, formerly an editor at Elmsford, N.Y.-based 
Pergamon Press. After extensive market research identified 
neuroscience as a field ripe for rapid publication, the 
founder distributed a leaflet in June 1990 announcing the 
creation of NeuroReport, guaranteeing publication of papers 
12 weeks after submission or sooner.

Within days of the announcement, papers began arriving by 
fax, and the pace of submission has increased ever since. 
"NeuroReport is a testimony to the fact that a rapidly 
published journal can be successful," says Kate McKay, who 
until recently was vice president of Rapid Communications of 
America. The company closed its New York office earlier this 
month because it found that it could accomplish its work via 
fax and electronic mail from its office in England.

"We have a high rejection rate because the number of 
submissions is incredible," McKay says. The journal 
receives, on average, five submissions every day. McKay 
credits "word of mouth in the neuroscience community" with 
the high submission rate. "Researchers say, `If you've got 
something hot and want it out quickly, go here,' " she 
explains. Rapid Communications currently publishes 24 
journals in addition to NeuroReport.

As is also true of ASR, the key to Rapid Communications' 
ability to work swiftly is the fax machine. A paper is faxed 
to the relevant journal, where an editor faxes it to 
appropriate reviewers. A reviewer has five days to fax the 
paper back to the journal, which then faxes it to the 
author, who also has five days to respond to the review. 
Authors help by limiting page length, preparing art, and not 
seeing proofs, which stimulates them to submit higher 
quality papers, the editors says. NeuroReport now publishes 
within nine weeks of submission.

So far, finding reviewers who are both expert enough and 
have the time to perform a rapid review has not been a 
problem, say Philips and McKay. "You simply get on the phone 
or the computer and network," Philips explains, "It often 
happens by word of mouth--someone knows someone who knows 
someone who knows someone, and ultimately ou reach someone 
who has both quality and time."

Maintaining Quality
Several editors of mainstream serials interviewed for this 
article do not doubt that it is possible to regularly 
publish an issue's worth of peer-reviewed papers prepared 
within a month of submission. "It probably is feasible, if 
they liberally use fax and E-mail," suggests Charles 
Bertsch, head of the journals department at the American 
Chemical Society (ACS) in Washington, D.C. "It all goes very 
quickly if done right."

But such a peedy process may result in a sacrifice of 
quality, cautions Kevin Davies, editor of Nature Genetics. 
"When a journal guarantees that any paper will be published 
in a certian amount of time from submission, that's 
prejuding the review process," he says. "A journal should 
focus on promising quick processing once a paper is 
accepted."

Fast-tracking is possible at any journal if an editor 
suspects that a paper will sail through the review process, 
as recently happened at Nature Genetics with a paper 
describing the gene that cuases Crouzon syndrome, a defect 
of the face and head bones. The papers received on August 10 
and was published in the September 1 issue. "It was reviewed 
and accepted in five days, revised in five days," Davies 
reports. "We worked overtime, and faxed figures and E-mailed 
like crazy. Another shortcut was that we set the text [in 
type] before the final decision was made, assuming it would 
be accepted." But Davies stresses that this wasn an unusual 
case: "We can make such preparations for exceptional 
papers," Other shortcuts include permitting only vital 
changes in proofs and "sacrificing niceties," such as 
consistency in reference terminology.

"Every journal starting up these days promises more rapid 
publication," says Davies. "For example, Human Molecular 
Genetics, our competitor, began in April 1992, about when 
Nature Genetics did. They made a similar promise of a 
certain number of weeks from submission to publication. They 
have kept to it and are doing well." Ads for this Oxford 
University Press journal claim: "In 1993, Human Molecular 
Genetics had the fastest average receipt to publication time 
of any genetics journal."

Paul Ginsparg, a physicist at Los Alamos National Laboratory 
in New Mexico, provides a service that combines rapid access 
to recent research with interactive capabilities: E-Print 
Archives, which supplies current and archival preprints 
online to 20,000 physicists worldwide. "One of the primarily 
useful things about E-Print Archives is not the rapidity of 
communication, but access to the older papers," he says. 
"People find it much easier to click a button on a screen 
than to go across the street to the library, look through 
journals, and maybe find that the one they want is off to 
the bindery."

A complete online journal, the Online Journal of Current 
Clinical Trials, was started by the American Association for 
the Advancement of Science (AAAS) in collaboration with a 
computer library service in July 1992. However, few 
subscribers signed up for the journal. Rather than undertake 
a huge marketing campaign itself, AAAS recently sold the 
venture to London-based Chapman & Hall, a subsidiary of 
Thomson (J. Kaiser, Science, 265:867, 1994).

Will electronic publishing become too fast for peer review? 
So far, those interviewed for this article seem to think 
that peer review can indeed keep pace. "Electronic 
publishing should have nothing to do with peer review," says 
Bialy. "When everyone is wired in correctly, it will 
accelerate peer review by saving mailing."

Ginsparg thinks that the question is moot because peer 
review, at least in fields like his own, in which the 
readers are experts, isn't even necessary. "I'd rather have 
30 percent more papers to read in one to two weeks of their 
submission than see them six to nine months after submission 
with some small amount of filtering provided by peer 
review," he says.

Although they take longer to be disseminated than online 
services, print science journals are unlikely to be put out 
of business soon, their editors say. They note that there's 
still something to be said for reading a paper journal on 
the train or out by the pool. "In terms of archival and 
reference aspects, people want to have papers in a journal 
that libraries have, and are not out in the electronic 
ether," says Bio/Technology's Bialy.

Ginsparg says there's room in the scientific community for 
both print and online publication: "It's like asking if you 
can make the transition from radio to television; suddenly 
you have an extraordinary new set of possibilities." But 
like radio--which is still alive and well despite television 
and VCRs--print journals, at least for the near future, will 
continue as a primary outlet for the dissemination of 
scientific information.


Ricki Lewis is a freelance science writer based in Scotia, 
N.Y.


(The Scientist, Vol:8, #18, pg.21, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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NXT:

------------------------------------------------------------
TI   :  FOR MORE INFORMATION

TY   :  PROFESSION

PG   :  21

Advances in Scientific Research
4275 Executive Square, Suite 800
La Jolla, Calif.  92037
Phone: (619) 546-2979
Fax: (619) 453-4932
E-mail: ascires@cerf.net
E-Print Archives (Paul Ginsparg)
Los Alamos National Laboratory MSB285
Los Alamos, N.Mex. 87545
Phone: (505) 667-7353
Fax: (505) 667-5585
E-mail: hep-th@xxx.lanl.gov 
(Use the word "help" in "subject" line.)

Rapid Communications of Oxford
The Old Malthouse
Paradise Street
Oxford OX1 1LO
U.K.
Phone: 44 865 790 447
Fax: 44 865 244 012 or 44 865 793 533
E-mail: rapidcom@vax.oxford.ac.uk

Publishers of 25 journals:
Anti-Cancer Drugs
Behavioural Neurology
Behavioural Pharmacology
BioMetals
Blood Coagulation
and Fibrinolysis
Cancer Causes and Control
Chromosome Research
Clinical Autonomic Research
Clinical and Experimental
Metastasis
European Journal of
Cancer Prevention
European Journal of Neurology
Glycosylation and Disease
Imaging
Immunology and Infectious
Diseases
International Clinical
Psychopharmacology
Journal of Orthopaedic
Rheumatology
Mediators of Inflammation
Melanoma Research
NeuroReport
Obesity Surgery
Pharmaceutical Science
Communications
Primary Care Psychiatry
Psychiatric Genetics
Quality of Life Research
World Journal of Microbiology and Biotechnology

(The Scientist, Vol:8, #18, pg.21, September 19, 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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TI   : Russian, Belgian, And Two Frenchmen Rake In Honors As 
       1994 Fields Medalists

AU   : NEERAJA SANKARAN

TY   : PROFESSION (PEOPLE)

PG   : 22

Four mathematicians--Jean Bourgain, a professor at the 
Institute for Advanced Study, Princeton, N.J.; Pierre-Louis 
Lions of the University of Paris-Dauphine in France; Jean-
Christophe Yoccoz, University of Paris-Sud, Orsay, France; 
and Efim I. Zelmanov, a professor at the University of 
Chicago currently on leave from the University of Wisconsin, 
Madison--have been awarded the 1994 Fields Medals.

The medals were presented during the International Congress 
of Mathematicians, held August 3 through 11 in Zurich, 
Switzerland.

The Fields Medals--officially known as the International 
Medals for Outstanding Discoveries in Mathematics--are 
presented every four years to two to four individuals under 
the age of 40 in recognition of both their existing work and 
the promise of future achievements. Unlike the Nobel and 
other big prizes, however, the Fields Medals carry no 
monetary award.

Winners are decided upon by a committee within the 
International Mathematical Union--a professional 
mathematical society of worldwide membership, headquartered 
this year in Rio de Janiero, Brazil--which arranges the 
International Congress. Thirty-four individuals have been 
honored since 1936.

`Triumphant' Work
Zelmanov, 38, was recognized for his work in the area of 
abstract algebra and group theory, specifically for his 
proof of a mathematical conjecture called the restricted 
Burnside problem, named for British mathematician William 
Burnside.

"In 1902, Burnside formulated a conjecture on what makes a 
group finite," explains Zelmanov. "He said that if imposed, 
two restrictions--a [fixed] number of generators and 
periodicity--are enough to make a group finite."

Though this conjecture--known as the Burnside Problem--was 
shown to be false in 1968, Zelmanov states that in a few 
important cases it still holds true. He furnished proofs for 
these special cases, called the restricted Burnside problem 
(E.I. Zelmanov, "A solution of the restricted Burnside 
problem in 2-groups," Mathematics of the USSR-Sbornik, 
72:543-565, 1992).

Zelmanov, who moved to the United States in 1990, did most 
of his work on the problem while a professor at the Academy 
of Sciences of the USSR in Novosibirsk, Siberia, where he 
completed his doctorate in 1980. Zelmanov's colleague 
Jonathan Alperin at the University of Chicago refers to the 
Russian mathematician's achievements as "a real triumph."

Versatility
According to Princeton UniversityUs Charles Feffer-man, 
himself a 1978 Fields medalist, Bourgain, 40, has made "very 
deep contributions" to several areas of mathematics.

Bourgain's particular areas of expertise in mathematics are: 
the geometry of infinite dimensional spaces; harmonic 
analysis, which is the study of complicated vibrations; and 
non-linear wave equations. Educated in his native Belgium 
(Ph.D. from the Free University of Brussels, 1977), Bourgain 
came to the Institute for Advanced Study earlier this year. 
Previously, he held a professorship at the Institut des 
Hautes Etudes Scientifiques in Paris.

According to the Science Citation Index of the Institute for 
Scientific Information, Philadelphia, Lions, 38, has 
published more than 30 original mathematical papers in the 
past four years alone. His versatility is exemplified in the 
wide variety of mathematical topics his papers cover, 
including partial differential equations, numerical 
analysis, and calculations for such scientific methods as 
image processing, fluid mechanics, and the viscosity of 
solutions.

Yoccoz, 37, is the youngest of the medalists this year, and 
like Lions  hails  from  France. His most recent 
publication, a seminal paper on hyperbolic sets entitled 
"Homoclinic tangencies for hyperbolic sets of large 
Hausdorff dimensions," appears in Acta Mathematica (172:91-
136, 1994).

--Neeraja Sankaran


(The Scientist, Vol:8, #18, pg.22, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
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TI   : UC-San Francisco Physiologist Assumes Directorship Of 
       NIH Neurological Institute

AU   : NEERAJA SANKARAN

TY   : PROFESSION (PEOPLE)

PG   : 22

Zach W. Hall, formerly a professor of physiology at the 
University of California, San Francisco, has assumed the 
directorship of the National Institute of Neurological 
Disorders and Stroke (NINDS), in Bethesda, Md. He began in 
his new job September 1.

NINDS is the agency within the National Institutes of Health 
(NIH) for research on brain and nervous-system disorders. As 
director, Hall will be in charge of an annual budget of more 
than $630 million, which goes toward maintaining a staff of 
about 700 scientists and administrators, as well as 
supporting research at various institutions across the 
United States. Coming into the position, he says, he has "no 
set agenda."

"This is a tremendously exciting period for the 
neurosciences," Hall says. "I hope to be able to work 
cooperatively with the other [NIH] agencies to promote both 
extramural and intramural research programs."

A particular challenge for the institute, he says, will be 
in the clinical applications of fundamental neuroscience 
research. 

"Neurologists have always had elegant ways of diagnosing 
various disorders," he says, adding that treatments have not 
emerged at the same pace. "In the coming decade we should be 
able to apply our findings from basic research more 
effectively toward treating neurologic diseases."

Other areas of neurology that Hall sees as making great 
progress are developmental neurobiology and central nervous 
system physiology.

A native of Atlanta, Hall, 56, studied English (B.A. 1958) 
at Yale University, New Haven, Conn., and received a Ph.D. 
in biochemistry from Harvard University, Cambridge, Mass., 
in 1966.

He came to UC-San Francisco's department of physiology in 
1976, and headed  the biomedical sciences graduate program 
there from 1992 until his appointment at NINDS.

--Neeraja Sankaran


(The Scientist, Vol:8, #18, pg.22, September 19, 1994)
(Copyright, The Scientist, Inc.)
  
                         ----------

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