Analysis of 1998 ASCB Report on NASA Life Science Research

Editor’s note: This was first published on NASA Watch in 1998.

The following was sent to NASA Watch by a prominent NASA space life scientist who had complained to the ASCB about the gross errors in their report and asking for the scientific references used by the ASCB in deliberating their scientific postion. The following was provided by Tim Leshan of the ASCB in response:

Date: Wed, 15 Jul 1998 16:13:35 -0400

From: Tim Leshan [TLESHAN@ASCB.ORG]

To:

Subject: Re: NASA Life Science Report

This is by no means an exhaustive list of the items the ASCB
committee reviewed but these are some of the materials the ASCB
Committee used in drafting their report. It should also be noted that
this diverse group of people came to this committee with their own
expertise regarding NASA’s life sciences program which they relied upon
as well. As for the specific reference for each statement made, I have
forwarded your comments to Don Brown the Chair of the committee for his
input given that he is the primary author of the report. I hope this
helps.

1. The FY’99 FASEB Consensus Conference report.

2. Last years FY’98 FASEB Consensus Conference report on NASA.

3. The 1996 speech given by Dan Goldin at the ASCB Annual meeting.

4. NASA’s FY’99 budget proposal and background budget materials.

5. Testimony by Dr. Arnal E. Nicogossian on NASA Microgravity Sciences,
Feb 25, 1998.

6. A Report on NASA Gravitation Biology and Ecology Section by Dave
Capco.

7. A Science article regarding the FY’99 NASA budget, VOL 279 page 977.

8. A letter from Joan Vernikos, Ph.D., Director of Life Sciences
Division at NASA outlining some areas of improvement over the last year.

9. A Washington Fax article regarding a recent House Science Committee
hearing on the Space Station, Feb 12, 1998.

10. An article from the Washington Post about NASA and Dan Goldin, Feb.
10, 1998.

11. A Nature article regarding the space station, Vol 391 page 721.

12. Materials sent from NASA regarding the Neurolab mission.

13. Several items from the NASA Office of Life and Microgravity Sciences
Web page.

I do not see a single technical or scientific paper mentioned either from general or peer-reviewed journal! To put out a report alledging to be the considered scientific opinion not only of the authors – but also of this society – based upon such generic source material is grossly irresponsible. ASCB should be ashamed to have their name affiliated with this “report”!

Yet this group passes judgements on space mission scientific return, space vehicle design and crew operations, NASA’s Earth Observing System, Neurolab and its neurovestibular research, the origin of life, life in extreme environments, drug development, microgravity crystallography, and human space physiology – areas where the team seems to have no obvious, personal expertise. Only one of them seems to have hand-on knowledge with space research – and it is apparently confined to research done within a Shuttle middeck locker.

They also pass judgement on NASA Management responsibilities but can’t even get a simple little fact straight i.e.,. that the protein crystallography work they so despise is actually managed by NASA’s Microgravity Science and Applications Division – not NASA’s Life Sciences Division.

If a group of scientists as ill-suited as this group was to its task were to be assembled to review the areas within which these 7 individuals worked on a day to day basis, and then produced a terse, superficial treatment with threatening recommendations, and announced it Capitol Hill, they’d be howling in protest – with ample justification.

When Congress fails to obtain credible scientific and technical expertise when making decisions, the taxpayers and the country’s research base suffer. However, when scientists themselves produce superficial pronouncements such as the ASCB “report” and deliver it to Congress, they undermine the credibility of all scientific expertise – everywhere.

One final word to NASA: I certainly hope something public will result from NASA on this wholly unsubstantiated smear on life and microgravity science research in space. It is about time NASA spent real effort to portray the actual results of its research to Congress, professional societies, the press, industry, and the general public. All too often NASA does as little as possible in this regard, often in unconnected, rarely promoted, and hard-to-find locations.

I expect to get angry notes from NASA telling me that they do these things. All I can say folks is whatever you are doing, it ain’t working.

Contact: Tim Leshan 301-530-7153, 301-530-7139 (fax),
tleshan@ascb.org

July 9, 1998

ASCB Urges NASA to Concentrate on

Ground, Not Space, Research

Bethesda, MD- A Blue Ribbon Committee of the American Society
for Cell Biology has issued a review of NASA’s life sciences program.
The Committee was appointed by ASCB President Elizabeth Blackburn
of the University of California, San Francisco and its recommendations
were passed unanimously by the Society’s governing Council.

The Society recognizes the importance of land based research
in such areas of interest to NASA as plant biology, cell and developmental
biology of the vestibular system, environmental sciences, and
evolutionary biology including investigations into the origins
of life. However, the report is sharply critical of many ongoing
and proposed NASA space-based research on these topics. The report
underscores the greater standard of scientific interest that should
be satisfied to justify the exorbitant and difficult-to-control
nature of research in space.

Specifically, the Society calls for the abandonment of the
space-based crystallography program, claiming that "no serious
contributions to knowledge of protein structure or to drug discovery
or design have yet been made in space." The report explains
"the International Space Station should mainly be a platform
to study astronaut physiology and most basic research relating
to how plants develop, how gravity is detected by living systems,
or how life originates and evolves should be ground-based."

The Blue Ribbon Committee was chaired by former ASCB President,
Donald Brown, of the Carnegie Institution of Washington and included
Ursula Goodenough of Washington University, Steven Harrison of
Harvard University, Anthony Mahowald of the University of Chicago,
Elliot Meyerowitz of California Institute of Technology, Christopher
Somerville of Stanford University and the Carnegie Institution,
and Andrew Staehelin of the University of Colorado.

The ASCB will participate in a press conference with Representative
Tim Roemer (D-IN) regarding this report and the International
Space Station on July 15 at the Capitol.

Report on NASA Life Sciences Research
to the ASCB Council

"… we have decided that what we are going to do is
not build engineering temples in search of science…"
–Daniel Goldin at the December 1996 ASCB meeting.

NASA’s program in the life sciences is devoted to two general
missions. The first is to determine the effects of prolonged exposure
to the space environment — weightlessness, confinement, and cosmic
radiation — on astronaut health. This mission falls outside the
purview of both the committee and the ASCB and will not be considered
further.

The second mission is to explore the micro gravity environment
as an experimental variable, studying its effects on living systems
and on such biotechnological processes as protein crystallization
and drug design. The committee has reviewed the planned NASA research
investment in these areas and concludes that most of it is driven
by the need to make use of the engineering temple called the International
Space Station (ISS).

In the paragraphs below we describe our concerns about space-based
life science research. The ISS should mainly be a platform to
study astronaut physiology. We then describe ground-based research
opportunities in the basic life sciences that we hope NASA will
pursue in its quest to understand how plants develop, how gravity
is detected by living systems, how life originates and evolves,
and how ecosystems are maintained and perturbed.

Space-Based Research

The Problems with Space-based Research

It is difficult to exaggerate the complexities and cost of
carrying out biological research in space. The launch itself,
the special equipment needed for an experiment in space that would
be simple and cheap on earth, the use of space crews as technicians,
their inability to trouble-shoot a failed experiment, the long
lag between an interesting observation and its follow-up, all
make research carried out in space orders of magnitude more costly,
difficult, and inefficient than that carried out on earth. These
facts will make the ISS the most expensive and inflexible research
laboratory ever built. Given these difficulties, biological and
technological experiments on the ISS should be characterized by
their path breaking importance.

Choosing Space-based Basic Biological Research Projects

NASA has already documented, in its shuttle and station experiments
over the past decades, that several invertebrate organisms (flies
and worms) can traverse their life cycles in the absence of gravity
without adverse effect, as can plants and amphibians. This means
that the fundamental processes of earth life: regulation of gene
expression, signal transduction, and cellular differentiation,
do not depend on the perception of gravity.

Considering these findings, and the extreme difficulty and
expense of carrying out life science research in space, the committee
strongly recommends two stringent reviews for any further cellular,
molecular, or developmental experiments proposed for space. The
first review should compare the particular subject with land-based
projects and ask whether a space environment is essential for
the success of the experiment. The second review should address
the merit of the specific proposal. Thus, not only should the
project be meritorious, but the extraordinary use of space facilities
must be justified.

Cancel the Space-based Crystallography Program

NASA has had an extensive program aimed at improving protein
crystals by growing them under micro gravity conditions. Gravity
can influence protein crystal growth through convection in the
supersaturated solution from which the crystals grow, and through
positioning of the crystal within the volume of growth solution.
Neither are major, limiting factors in solving important problems.
Biochemical purity and stability are in all cases the most crucial
parameters for obtaining good crystals of proteins and protein
complexes. These parameters are harder to control in space than
in a conventional laboratory. No serious contributions to knowledge
of protein structure or to drug discovery or design have yet been
made in space. Thus, there is no justification for a NASA protein
crystallization program, and this committee strongly recommends
that no further funds be spent on crystallization of proteins
in space.

Ground-Based Research

Plant Biology

Previous space flights have shown that growth and reproduction
of plants are not fundamentally affected by micro gravity. Most
questions concerning the gravitational effects on plants can be
better investigated on earth using a mutant analysis to identify
the signaling and response pathways. The most rapid advances in
plant sensory biology are coming from genetic experiments with
model systems such as Arabidopsis, and with robust research support,
plant gravitropism systems could be well understood within a few
years without the use of micro gravity. One tangible outcome of
understanding these mechanisms might be the design of a surrogate
signaling system that would permit the development of genetically
modified plants that behave in a micro gravity environment the
way they do on earth. At the stage when such plants can be designed
rationally, their predicted response to micro gravity will need
to be confirmed on the ISS or on shuttle flights.

A second area in plant research of importance to NASA is learning
to control plant growth in space (space horticulture) since, should
long-term space missions ever be attempted, astronauts will have
to grow their own food. There are two elements necessary to this
research. One is learning to make sealed plant growth systems
with maximal use of recycling and minimal use of energy, and optimizing
plant growth within them. The other is to learn more about the
fundamental mechanisms of plant growth, development, and environmental
response (not only to gravity, but also to light, water, gases
such as ethylene that the plant produces, etc.) so that problems
with plant growth in space can be anticipated and solved, and
so the plants themselves can be optimized by genetics for growth
in space.

Plants that can provide for human needs during space exploration
can be designed by genetic modifications in laboratories on earth.
In order to do this we need a deep understanding of the molecular
mechanisms that control plant growth and development. The outcome
would not only be plants that could be used in space but also
redesigned plants beneficial for earth life thus generating the
kinds of useful "spin-offs" that NASA hopes for from
its programs. As with the proposed approach to gravity (above),
once new plants are developed on land, their growth, development,
and their potential utility to humans in a space environment will
need to be confirmed in ISS-based experiments.

The support for basic plant biology in the US is truly inadequate
and is patched together from several agencies. NASA could make
a major contribution to human welfare and to the eventual use
of plants in interplanetary missions by investing long term support
in earth-based basic plant science.

Cell and Developmental Biology of the Vestibular System

Particular organs in animals have evolved to detect and monitor
gravity, notably the vestibular system and its evolutionary antecedents.
Investigations of these systems in the context of astronaut health
are obviously important for long term manned space flights. The
current Neurolab flight is concentrating on the development of
these organs in micro gravity, but these space-based experiments
are surely premature. Important discoveries on the development
and function of these systems can best be achieved using the powerful
approach of molecular genetics with model organisms such as zebra
fish and mice. This involves finding mutants that are defective
in vestibular function, cloning and analyzing the expression of
the affected genes and the defective organs, identifying suppresser
genes, and so on. Only when this land-based research has characterized
the system fully can efficient space-based experiments be designed.

Evolutionary Biology

A major impetus for the exploration of the solar system is
to search for evidence of (previous) life on other planets, and
critical parameters for conducting that search can be established
by learning how life evolved on Earth: its origins, its constraints
and accelerating factors, its patterns, its occurrence in extreme
environments. The tools of molecular cell biology are now in place
to tackle these problems, and the results are certain to be fascinating.
NASA’s new "Astrobiology" program is now gearing up
for this initiative, and the committee urges NASA to direct major
resources to this program in future years by providing stable,
long-term support of peer-reviewed research projects.

Environmental Sciences

Environmental sciences, crucial to future well-being of the
planet, needs the kind of robust support that NASA could provide.
TheEarth Observing System (EOS) program and its data-gathering
capacities is a worthwhile NASA program because it provides information
about our planet on a scale that we could never obtain any other
way. This satellite system allows for relatively high resolution
imaging of the surface of the earth in many wavelengths. Much
of global ecology research is based on its use, but a great deal
of the accumulated data remains unanalyzed and represents a rich
resource for future research programs.

Conclusions

We strongly recommend that the ASCB Council communicate its
concern about the cost and ineffectiveness of NASA’s space-based
life sciences research which should be restricted to the most
select and carefully chosen experiments. Areas of research such
as protein crystallization, drug design, and basic animal and
plant cell and developmental biology can not be used to justify
a space mission.

NASA should develop its support of ground-based research in
several key underfunded areas that are relevant to the agency’s
long-term goals and important to national well being.

Respectfully submitted,

Donald D. Brown, Chairperson

Ursula W. Goodenough

Steven C. Harrison

Anthony P. Mahowald

Elliot M. Meyerowitz

Christopher R. Somerville

Andrew L. Staehelin

Originally published on NASA WAtch 15 July 1998

By Keith Cowing, Editor, NASA Watch

kcowing@reston.com

Let’s take a look at the topics covered by this “report”

• Space-Based Research: The Problems with Space-based Research
  
• Choosing Space-based Basic Biological Research Projects
  
• Cancel the Space-based Crystallography Program
  
• Ground-Based Research: Plant Biology
  
• Cell and Developmental Biology of the Vestibular System
  
• Evolutionary Biology
  
• Environmental Sciences – The earth Observing System (EOS)
  

Now, let’s look at the list of authors of this report, and their expertise, as presented on their home institution’s websites:

“The Blue Ribbon Committee was chaired by:

former ASCB President, Donald Brown, of the Carnegie Institution of Washington

“Metamorphosis, role of hormones in development, gene regulation; D.Sc.,

University of Chicago; Staff member and director emeritus, Carnegie Institution of Washington, Department of Embryology

• a renowned developmental biologist, he was one of the first to isolate genes; he developed an early model of gene control using the frog Xenopus

• currently focuses on the role of hormones in development, especially in metamorphosis; his work on thyroxine may some day have medical benefits

• received the 1996 E.B. Wilson Award from the American Society for Cell Biology”
  

Ursula Goodenough, Washington University, email: goodenough@wustlb.wustl.edu

Research Interests: “The mating-type (mt) locus of the unicellular green alga
Chlamydomonas reinhardtii exists as two apparent alleles
(mt ⁺ and mt ^–) and controls the
various life-cycle transitions of the organism, including
gametogenesis. The locus proves to cover ~800 kb of recombinational
suppression, and includes a central ~200 kb domain which is highly
non-homologous between mt ⁺ and
mt^–. We have cloned the entire locus from both
mating types and are now analyzing its constituent genes and the
control of their expression during the life cycle. Genes identified
to date include fusl, which encodes a mt
⁺-specific sexual adhesin; mid, which encodes a
product necessary for the mt ^– gametogenesis
program; and ezy-1, involved in the uniparental inheritance of
chloroplast DNA. These genes are undergoing rapid evolution in
conjunction with speciation.”

Stephen Harrison, Harvard University, email: schadmin@xtal0.harvard.edu

“We use X-ray crystallography and allied physico-chemical tools to understand the structures of large macromolecular
assemblies and the principles of molecular recognition that these assemblies reveal.

(1) The structure of polyomavirus has led us to an examination of the role of the interactions of the virus with its
oligosaccharide receptors. The strength and specificity of these interactions have important consequences for viral
pathogenesis. Likewise, the structure of the envelope glycoprotein from a flavivirus has significant implications for viral
attachment and entry and for vaccine design. The structures of rotavirus single-shelled particles and of reovirus cores are
major technical challenges in modern crystallography.

(2) Interactions among multiple regulatory proteins are an essential aspect of gene regulation by transcriptional enhancers
and promoters. A goal of our structural studies is to visualize examples of such multi-component control by crystallizing
the appropriate assemblies of proteins and DNA.”

Anthony Mahowald of the University of Chicago,
Research

“My laboratory is primarily interested in the genetic control of oogenesis, using Drosophila melanogaster as a model
system. We have completed extensive genetic screens to identify key functions required for establishing the germ line
and for differentiation of the gonad. We are currently concentrating on three sets of genes involved in ovarian
development. First, genetic analysis has identified ovo as the first gene required in stable differentiation of the female
germ line. Second, we have identified a class of genes required for organizing the ovary into ovarioles. Finally, we have
shown that the vitellogenin receptor is a member of the LDL-receptor superfamily. In each system, we have cloned the
relevant genes and have begun both molecular, genetic and biochemical studies related to understanding their function. “

Elliot Meyerowitz of California Institute of Technology, email: meyerow@cco.caltech.edu

“The recent work of my laboratory has concentrated in three areas, the origin of developmental patterns in flowers, the
control of cell division in meristems, and the mechanisms of plant hormone action. In all of this work we use the
convenient laboratory plant Arabidopsis thaliana, which allows the parallel use of classical and of molecular genetics.”

Christopher Somerville of Stanford University and the Carnegie Institution, email: crs@andrew.stanford.edu

“Chris Somerville has served as Director of the Carnegie Institution’s Department of Plant Biology since July 1, 1993.
Professor Somerville was born in Kingston, Ontario. He earned B.Sc., M.Sc., and Ph.D. (genetics) degrees at the
University of Alberta, completing the Ph.D. in 1978. He was a research associate at the University of Illinois,
1978-1981. In 1982, after briefly serving as a faculty member at the University of Alberta, he moved to Michigan State
University where he served as a professor in the Department of Botany and Plant Pathology of the DOE Plant Research
Laboratory.

Chris has been on various advisory panels to U.S. federal agencies concerned with plant biology, including the
Department of Agriculture, National Science Foundation, and National Institutes of Health. He has served on several
editorial committees for leading journals in his field. In 1991 he was elected a Fellow of the Royal Society, London.”

and Andrew Staehelin of the University of Colorado, email: staeheli@spot.Colorado.EDU

“Functional Organization of the Plant Golgi Apparatus: The Golgi apparatus of plant cells is unique in that synthesis, assembly, and packaging of complex polysaccharides are
its principle functions during growth and development; processing of glycoproteins constitutes usually less than 20% of
its synthetic activities. In addition, plant Golgi stacks are retailored in a cell type specific manner to meet the specific
synthetic needs of different types of cells. These and other features have impeded research on the plant Golgi apparatus
in the past. We have recently overcome many of the technical obstacles associated with these features by developing
novel methods for synchronizing tobacco suspension cultured cells, for controlling Golgi function, and for inducing
synchronized Golgi differentiation in vivo. Using these techniques we are now investigating the functional organization
and retailoring mechanisms of the plant Golgi apparatus.

Photosynthetic Membrane Chaperones: The development of O2-evolving photosynthetic organisms had profound evolutionary consequences that still affect life
today. For example, the resulting O2-rich atmosphere has led not only to more efficient respiratory systems, but also to
oxidative stress phenomena that result from damage to critical biomolecules caused by inadvertently formed, highly
reactive oxygen radicals. Chloroplasts have evolved efficient mechanisms for dealing with free radicals, due to the high
rate at which such molecules arise in conjunction with photosynthesis. We are studying an integral membrane protein of
chloroplasts that appears to protect reaction centers from photo- oxidative stress during their assembly and may also
participate in the assembly process without becoming part of the finished complex. We are investigating the functional
domains of this novel type of molecular chaperone, and the effects of over- (under-) expressing it in transgenic plants.”

This group contains 4 plant biologists, 2 geneticist/developmental biologists, and 1 virologist/crystallographer. As such they should be expected to have some knowledge about these areas of ground-based research.

I went to the NASA Office of Life and Microgravity Sciences and Applications (OLMSA) Research Opportunities online database to see if their names showed up as funded investigators. Of this entire panel, one devoted quite specifically to evaluating NASA’s space-based life science and microgravity sciences research, according to the database only one member (Dr. Staehelin) is a funded NASA investigator .

And what references were used in the production of this report? One would think that a thorough review of peer reviewed literature would have been done so as to provide a firm basis for the “scientific” opinions presented within this rpeort.