Approved by the ASCB Council, Spring, 1998

"... 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.

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.

Adopted at the Recommendation of the Ad Hoc Committee on NASA Life Sciences,

Donald D. Brown (Chair)
Ursula W. Goodenough
Stephen C. Harrison
Anthony P. Mahowald
Elliot M. Meyerowitz
Christopher R. Somerville
Andrew L. Staehelin