The ESA Life Sciences Programme

Introduction

Results obtained in space life sciences over the past decade have had a remarkable influence on the current thinking on the role gravity plays at all levels of life, from the organisation of a single cell to the nature of gravity-driven responses in more highly developed organisms including man. Experiments in space have invalidated quite a number of established theories about the mechanics of dynamic behaviour in certain animal and plant systems. They have generated new insights and new questions.

Based on the results obtained worldwide from microgravity and relevant ground-based research, including 10 years of European contributions, the ESA Microgravity Advisory Committee (MAC) undertook a status review with the help of the expertise available within ESA's life-science and materials/fluid-science working groups.

As a result, ESA obtained a recommendation from MAC as to how to proceed with respect to focusing on selected areas of research, which were considered to hold promise of tangible results that could justify the effort involved.

The MAC proposed to vigorously exploit Europe's current scientific strength in space life sciences by concentrating the programme on the most promising research areas with outstanding expertise in Europe. As exciting and novel ideas are emerging continuously, indicating the potential for development and the stimulus for innovative ideas in this field, the programme will not be restricted to existing knowledge, but remain open to new ideas at any time. It is intended in this way to form the foundation for sound future development.

Life Sciences: Results of previous experiments

Human physiology
One of the most important findings to date has been the remarkable tolerance of higher organisms to microgravity, even for extended periods of time. The "backbone " of this tolerance is, however, built into the compensatory mechanisms providing an equilibrium of all systems.

Nevertheless, it quickly became apparent that profound changes are induced in the human body once it is deprived of the ever-present gravity stimulus. There are effects that occur within minutes, such as disorientation with respect to the environment, or rapid displacements of body fluids from the lower part to the thorax and head. With longer exposure to microgravity, profound diminution of muscle mass and strength occurs, together with loss of bone minerals and degradation of its structure. The long-term effects of space radiation on the human body, on the other hand, are still totally unknown.

Biology
The past decade of space biology has demonstrated that gravity plays an important role in a variety of biological processes. Such a role could be expected in all those systems that were known, from ground-based gravitational biology, to be adept at perceiving gravity, such as the root tips in plants and the vestibular systems in animals. It could also be expected that weight-carrying structures like the mammalian skeleton, which are dynamic and adapt to changes in the loading environment, would be influenced by gravity. What could not be anticipated was the lower limit of biological dimension at which a changing gravity vector would still have an impact. There is now compelling evidence that this is at the sub-cellular level, in the sub-micrometre-sized world, where the force of gravity is almost negligible if compared with the forces governing molecular interactions. Apparently, there are conditions in which the weightless environment influences the cellular machinery fundamentally. Other results achieved are noted in Section Research focus for Space Biology.

Programmatic Background

Human Physiology
ESA's early support to a human physiology research programme culminated in the provision of 'Anthrorack', a laboratory supporting integrated research into cardiopulmonary and endocrine systems in the human body on a largely non-invasive basis. The programme concentrated almost exclusively on the fundamental science, thereby contributing to:

• expansion of knowledge in ground-based research with concept-breaking progress in terms of current theories;

• applications in the field of diagnostics and therapeutics for medicine;

• potential for system-level insights leading to new discoveries.

More recently, ESA has undertaken two very successful missions to the Russian space station MIR, where a broad programme of human-physiology research has been performed. Cardiopulmonary, endocrine, musculo-skeletal as well as radiation effects were the main research topics, as well as a general investigation into the question of metabolism, energy turnover, as also related to the countermeasures programme. During 1996, the Life and Microgravity Sciences Spacelab (LMS) mission was successfully flown with an ESA facility, the Torque Velocity Dynamometer (TVD), for research into muscle physiology.

Biology
Numerous biological experiment facilities have been developed over the past years by ESA, including Biorack, Biobox and Biopan, enabling biological experiments to be executed on a diversity of carriers such as the US Space Shuttle, Russian retrievable satellites and sounding rockets. As a result, a broad range of flight durations have been offered.

The space-biology programme concentrates on fundamental science in the area of gravitational biology (in general terms: what happens to living organisms in the absence of gravity). This has:

• contributed strongly to existing ground-based research, because of the unique elimination of gravity effects, and
• holds promise for new discoveries on fundamental aspects of the cellular activities.

In addition radiation biology, exobiology and chemical evolution have been addressed.

Research focus for Human Physiology

The following major topics have been recommended as focii in future research. The recommendations are based primarily on previous results published in refereed journals of high repute, and which hold the promise of yielding the expected progress in the field concerned.

The MAC recommendation on research priorities and those made by the workshops organised by the International Strategic Planning Working Group are the following:

In the field of Human Physiology:

Musculo-skeletal system: Impairment of muscle structure and function; mechanisms of bone remodelling and decalcification.

• Recommendations from the recently held International Workshop for Muscle Research, support more detailed research in the following sub-disciplines:
  • Muscle structure, contractile properties, metabolic properties and processes, neuro-motor control, and countermeasures.

• Recommendations from the International Workshop for Bone Research, support more detailed research in the following sub-areas:
  • Within the category "assessment": Methods to be used, increased number of locations to be measured, relation to in-flight countermeasures, investigation of changes in tendons, joints, and cartilage in general.

  • Within the category "countermeasures": Investigate the present model and models which could promote recovery.

  • Within the category "mechanisms": Aspects of biochemical and tissue interaction, the mechanical models, as well as general exchange of matter between the compartments in question.

  • Reliable animal models for periods longer than 14 days.

Finally, the mechano-receptor question seems to be central to the current scientific discussion.

Cardiovascular function: Ventricular performance; regulation of blood pressure and volume.

• Recommendations from the recently held International Workshop for Cardiovascular Research, support more detailed research in the following sub-disciplines:
  • Countermeasures to post-flight orthostatic hypotension.

  • Relationship between intrathoracic / intrapleural / pericardial pressure and the cardiac pressures and volumes.

  • Changes in systemic resistance, baroreflexes during orthostasis.

  • Loading conditions on the heart.

  • Cardiac mass related to cardiac function, orthostatic hypotension.

  • Changes in neurohumoral regulation.

  • Neural control mechanisms in regulating response to exercise and temperature.

  • Peripheral blood flow and regional distribution.

Fluid balance and kidney function: Endocrine components; regional interstitial fluid dynamics.

• Recommendations from the recently held International Workshop for Cardiovascular Research, support more detailed research in the following sub-disciplines:

  • Neurohumoral regulation of fluid balance and sodium ion regulation.

  • Gravity and erythropoietin.

  • Fluid and energy balance monitoring.

  • Fluid shift between the different segments and compartments.

  • Fluid volume control and the atmospheric environment.

Respiratory function: Ventilation / perfusion ratios; chest wall mechanics.

• Recommendations from the recently held International Workshop for Cardiovascular Research, support more detailed research in the following sub-disciplines:

  • The role of gravity in lung function.

  • Breathing mechanics.

  • Perfusion / ventilation distribution.

  • Lung-tissue volume, diffusion capacity.

  • Relationship between intrathoracic / intrapleural / pericardial pressure and the cardiac pressures and volumes.

  • Cardiopulmonary interactions.

Sensory-motor function: Otolith organ; multi-sensory integration and neuronal adaptation; space adaptation syndrome.

• Further recommendations will result from the International Workshop for Neurosciences Research, which will meet in April 1997 in Paris.

Hormones and metabolism: Ca++ homeostasis; energy expenditure; stress.

• Recommendations from the recently held International Workshop for Bone Research, support more detailed research in the following sub-disciplines:

  • Neural control mechanisms and the endocrinological expression thereof.

  • Negative Ca++ balance in simulation and 0g.

  • Inter-individual differences in bone loss and recovery.

  • Activity level and bone formation / bone resorption.

  • Exercise type and duration.

  • Role of bone blood flow, fluid shift, and dehydration.

  • Influence of vitamins and light.

Research focus for Space Biology

ESA has identified a list of topics in space biology that serve as research foci:

Regulatory mechanisms and proliferation and differentiation at the cellular level: Particular relevance to osteobiology, neurobiology, immunology, gametogenesis; the role of the cytoskeleton.

• One of the most interesting findings so far is the strong influence weightlessness can have on signal transduction in in vitro cultures of lymphoid, epidermoid and osteogenic cells.

• Immunological dysfunction, problems with wound healing, and the occurrence of bone demineralization during space flight may hence have a base at the cellular level.

• There are frequent observations of gravity influences on cell proliferation, especially in plants and in unicellular organisms, and on the occurrence of chromosomal aberrations.

• Effects are found on meiosis and gametogenesis. There is at present no clue to an understanding of the phenomena observed.

Investigators are encouraged to search the normal channels to obtain the relevant literature for their proposals. In addition, a number of ESA-issued publications provide some accumulated information on space missions and their scientific results, for details see References Section.