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Sunday, June 12, 2011

A Case for Biological Research in Space

Chapter 6K

A Case for Biological Research in Space

The first general concern about biological experiments in space is that the quality of the research has not been very high. Now, I must admit that there is a clear sense in which this charge is correct: Space biology has not produced any research that would qualify as extremely important. The aim of such research has been to gather the preliminary information that can then serve as the inspiration for hypotheses or as the ground for the testing of ideas. Since, except for the clinical research done for the safety of astronauts, most space biology has taken a back seat to other science, it is not surprising that the information obtained is generally inconclusive and sketchy.

Let me illustrate the nature of the problem by discussing the study of mammalian development. Ideally we would want to determine the role of gravity by observing whether any of the important stages in development is affected in microgravity. The first thing we have to do is look, then. We must look at copulation, fertilization, initial cleavages, embryonic and fetal stages, and postnatal maturation. Many of these are, of course, divided into several distinct and important stages. But we have never been able to observe mammalian copulation, let alone postnatal maturation.[1] The flights open to the biologists have been too short for that.

The situation is better, but not all that much better, with other animals or plants. Fertilized eggs of fish have flown in space.[2] These eggs have hatched successfully, whereas frog eggs have not produced tadpoles. And plants have been made to produce seeds.[3] Unfortunately yields have been low and chromosomal abnormalities common. But some of these results could be accounted for by the stress of flight itself (e.g., the accelerations of take-off and re-entry) or by shortcomings of the life-support systems that make up their artificial space environments. In addition to all that, specimens have normally been examined some time after their return to Earth, when gravity has begun to reverse the effects of its absence. We need to go from seed to seed and from egg to egg -- in space. And we need to do this several times over, so that we can isolate and control factors that belong to the inconveniences of spaceflight other than microgravity. But these multi-generational studies would take months, if not years. And then we also need trained biologists to monitor and examine the specimens in space, where the effects we want to discover take place. Living things must be handled delicately and skillfully if they are to bare their secrets. In more recent flights, the reproductive systems of rats have been damaged, with the ovaries shutting down in females and the testes in males shrinking.

The difference between what needs to be done and what has been available makes space biology appear primitive. To a critic, the space biologist's collections of data may resemble the wasteland of empirical social science. Or as someone might say, it is just Baconian science -- without theoretical direction, and thus without theoretical interest.

The critic burdens them with a Catch 22, space biologists feel. To show how their field may be significant they must carry out enough investigations so they can begin to ask fruitful questions. But critics object to those investigations on the grounds that space biology has not yet been shown to be significant.

It may be useful to compare the situation of space biology to that of atomic physics at the beginning of the 20th century and to that of particle physics during the 1960s: Physicists would accelerate particles, crash them against targets, and analyze the debris created in the collision (in atomic physics the aim was to determine the structure of atoms by the deflections of the electrons that crashed against them, in particle physics to discover particles and determine their properties). There is a sense in which the particle and atomic physicists were just "fishing," as the space biologists are now accused of doing.

Critics will no doubt rush to argue that there is a big difference. That difference is presumably is that they were fishing in fundamental waters. Whatever they found would have the most significant consequences. But that is easy to say in hindsight. The proliferation of particles in the 1960s led many to think that further searches -- and extremely expensive searches at that -- would amount to just looking around without any theoretical purpose of note, a Baconian end to a century of exciting physics. As for Rutherford and the other atomic physicists of the turn of the previous century, they were fishing in domains that most other physicists would not even agree were real, let alone significant.[4]

Hindsight is, of course, a wonderful sense. Today we can see that all those particle surveys in the 1960s allowed physicists to classify the particles into families--a classification not unlike that of the chemical table of elements -- and then to propose new theories about the structure of matter. Thus the quark hypothesis and a new era of physics were born.

In both cases, however, it took great vision to see the promise of the research. Some important physicists did think that Rutherford was onto something. They held the notion that fundamental aspects of nature might be explained by discovering how matter was put together at the most elementary level. Many decades later, after discovering so many elementary particles, physicists generally thought that the problem was how to make sense of the array. And thus what might have looked as hack work from a point of view, from another it seemed as the preliminary taxonomy essential for the physics of the future.

My point is precisely that space biology should be given the chance to carry out that preliminary taxonomy, even if it looks like hack work to some critics. The warrant for doing so is the same as in the two cases from the history of physics: the theoretical pay-off comes from testing matter well beyond the range that we have examined previously.

This warrant is clearly seen in the case of some sciences. Take space astronomy, for example. Once we could detect the entire electromagnetic spectrum by placing our telescopes and other instruments above the atmosphere, we embarked in a new survey of the heavens. It may have seemed that we are just looking around. But we had good reason to suspect that what we would find would be significant, that our ideas would be challenged to the utmost. And that reason was precisely that we knew how limited our range of observation had been until then. [5]

In space biology, unlike space astronomy today, but like space astronomy not long ago, we cannot specify the great scientific rewards that await us. We know, however, that the gravity of the Earth has been a constant throughout the evolution of life. We also know that the more pervasive a constant, the more difficult it is for us to determine its role, if any. That is exactly what happens with gravity. How are we to proceed, then? First of all, we cannot resolve the matter by further standard biological analysis. For in analysis we use the tools of prevailing theory to investigate some phenomena. To discover that role by analysis is therefore practically impossible, since nothing in our previous biology makes gravity a crucial element of the theory. What we need is either an alternative theory in which gravity is assigned a specific role, or else the manipulation of gravity to make present theory fail. We can do both.

These new theoretical and experimental directions are suggested in part by some of the early results of space biology, and in part by emphasizing some relevant aspects of standard theoretical biology. They will permit us to show the mistakes in the two notions that buttressed the general low estimate of the value of space biology. The first notion, we may recall, was that microgravity affects organisms only at the systems level. Investigations then have the main purpose of determining just what systemic effects take place and how they can be corrected. This clinical work has made its practitioners confident that with appropriate compensation (diet, drugs, and exercise) men and women can survive in space for periods of many months, perhaps years.

But even if this is true, it takes away nothing from the promise of space biology proper. If we wish to determine the role of gravity as an all-pervasive factor in individual development and in patterns of evolution, the systems level is actually not a bad place to begin. The human body, for instance, appears fine-tuned for the Earth's gravity. We might have expected to extrapolate our centrifuge studies here on Earth (with gravities above 1g) to the microgravity of space. Thus if we lose body mass under an acceleration of several g's, have it normal at 1 g, then presumably we would gain mass at less than 1 g. But it turns out that we lose mass at less than 1g. (The body mass in question here is intracellular mass and does not include fluids or calcium loss in the bones, which is itself pronounced and very worrisome. Similar reactions take place in microgravity with temperature control and other physiological functions. The explanation of some of these reactions seems to be that the shift in body fluids that comes from changes in gravity affects the communication between cells.)

This fine-tuning of physiology to the Earth's gravity -- which is seldom emphasized if realized at all -- should provide a fruitful theoretical perspective to study the relationships between a variety of internal systems and cycles in the human body. Why are physiological functions maximized at 1 g? This leads to questions about why the body works as it does, questions that would not occur that easily otherwise. A preliminary answer is that gravity is used to harmonize a variety of physiological systems. One way to think about this is that gravity is like the glue that holds such systems together. Once the glue is gone, they do not quite work together. And from their failure we learn what makes them work correctly under terrestrial conditions. Another way to think about it is that those systems change their responses in order to adapt to the new conditions. That may also give us significant clues about their normal modes of interaction with other systems or mechanisms.

This fine-tuning to 1g may become acute in issues of development. In microgravity a human male excretes from 1.5 to 2 liters of body fluids, with pronounced reductions in the levels of sodium and potassium. By contrast a pregnant human female is expected, in 1g, to show an increase of 1.5 to 4 liters over her pregnancy, with a marked retention of sodium. Since the development of the fetus follows a strict sequence in which each event must take place within a critical period, and since the availability and composition of the body fluids is essential to the proper environment in the placenta, we can readily see that disruptions at the system level affect physiological processes at lower levels. At the present time it would be morally impermissible to have pregnant women in space.

The human body is resourceful; it may be able to compensate for the effects of microgravity in a systematic fashion even during a pregnancy. But to determine whether it can, we must resort to experiments on animals.[6] By removing gravity, then, we can observe how the development comes unglued; by "dialing" several degrees of gravity we can refine our examination. The mere fact that many systems function optimally at 1 g provides warrant for designing experiments to determine how the timing and feedback controls of development operate. This, it seems to me, is not a matter of small importance.

"Mere" systemic effects can have profound repercussions. A clever probing of them can reveal much not only about development but also about the operation of many physiological functions, including their coordination. This possible gain in knowledge may extend to the cellular level, in spite of the experiments on cells mentioned earlier. The cells of complex organisms are parts of cellular systems, for example, of specialized tissue. The role cells play in those systems largely affects how the structural elements of cells operate. Those structural elements (called cytoskeletal) are responsible for communication among cells, transportation of plasmas, and maintenance of the cells' compartments. Changes in the environment of the cell lead to cellular changes in shape, in ability to move, and in internal metabolism (i.e., polarity, secretion, hormone regulation, membrane flow, and energy balance).[7] Changes that take place at the systems level in the organism, such as body fluid shifts, are bound to affect several cellular systems, change the cellular environment, and thus affect the cells themselves.

The experiments that indicated that gravity was irrelevant at the cellular level were performed in cell cultures; they did not examine cells that formed part of the complex wholes that are the cells' normal environments. It is not surprising, then, that such experiments could not expose the indirect action of gravity that starts at the systems level of the organism and works its way down into the realm of the small.

Since genes contain the “language of life,” and since organisms are presumably the books written in that language, we tend to think that significance in biology goes from the small to the big. But we have just seen that much of the small depends on the big, since the function of the small depends on the larger whole to which it belongs (and that whole often depends on an even larger one of which it is a part, and so on). It is true, however, that genes are in some sense supposed to be independent of the organism's environment: Theory demands that genetic variation not be coupled to the mechanism of selection (i.e. that the environment cannot have a hand in inducing the variations that are compatible with it, otherwise it would be possible to inherit acquired characteristics). Nonetheless, even if this demand is strictly interpreted,[8] many molecular processes may still be open to the influence from above I have just discussed.

It is also true that, in many areas of biology, real and fundamental progress is achieved when a strong connection can finally be made to the genotype of the organism in question; that is, when we can finally explain how the genes give rise to the mechanism or function in question. Be that as it may, it is misleading to think of genes as the blueprint of some sort of archetype that the organism will grow into, barring acts of God and other misfortunes. Given a certain genotype -- and the right circumstances at many different stages of development – a certain individual organism will likely be the outcome. But at many critical junctures within those stages of development, things could go slightly differently. The outcome would be a different organism.

The important point for our issue is that at those critical junctures, genes and the various structures to which they give rise take advantage of many environmental constants in order to keep their appointed rounds. Nature does not create everything anew and at once. It takes advantage of what is already there; it builds on the structures it finds in place; it develops not by reaching for an ideal but by a process best described as jury-rigging.

My suggestion is, of course, that the fine-tuning of several physiological functions for 1 g indicates that gravity is one of those constants that provide the context in which the language of life comes to make sense. Without it, aspects of the human genotype would be expressed very differently, if they could be expressed at all. If my suggestion is correct, the manipulation of gravity could return a theoretical profit to the study of genetics in space.

The reason becomes clearer if we emphasize some of the points already made. It is not easy to discover genes and then ask what they do. Often the question goes from the top down: given a certain function or structure, how do genes contribute to bring it about? This indicates that we need knowledge of all the other levels in order to guide genetics. Moreover, it is not necessary that all the alignments and states of equilibrium that many physiological systems reach be encoded in any one set of genes. Some genes may have been selected for because they lead to the construction of an organ or function that finds accommodation with earlier organs or functions. And the genes that lead to those earlier organs or functions are now preserved because the new arrangements are advantageous to the organism as a whole.

The point is this: Even if we knew what genes brought about the newer organ or function, and even if we knew all the steps in the construction, we still would not understand that aspect of physiology. For those genes and those steps make biological sense only against the background of the existence of those other organs or functions. And all these together make sense only in the context of whatever constants a form of life has come to take for granted. Thus, for example, the pattern of a net of nerves may not be encoded in the genes. The only "instruction" may be for the nerves to keep growing in search of a particular chemical attractor, but since the tissue in which they grow does not permit easy penetration, the nerves have to work their way around. (See Figure 10) The result is a very specific kind of net, although nowhere in the genotype could we find the "blueprint" for such a net.[9]

The moral of this story is that knowledge of one level – even if it is "fundamental" – is very limited without knowledge of the other levels. But this more complete knowledge can be gathered only to the extent that we grasp the context in which genes find ultimate expression. And that requires the manipulation of constants in order to determine their role.[10]

I have already suggested some reasons why gravity is one of those relevant constants. It may turn out, of course, that the actual threshold for the proper functioning of physiological and developmental is less than 1g; that as soon as a gravity vector (direction and intensity of gravity) is detected, things will work normally or almost normally. Determining that threshold is one of the important initial tasks of biology in space (that subdivision of the field is called "gravitational biology"), a task that finds no counterpart in doing centrifuge studies on the Earth.[11]

But there are other ways in which genetic studies can be done advantageously in space. In a recent experiment samples of salmonella bacteria flew in the Space Shuttle while control samples under identical conditions, except for the presence of gravity, remained on the ground. The space-traveling salmonella became much more virulent because certain genes changed their level of activity in microgravity – genes crucial to the control of a protein called Hfq, which allows bacteria to adapt to changing conditions[12]. This finding, worthwhile in itself, may also help us understand some causes of increased virulence of such bacteria on Earth.

It may turn out that we can discover how to compensate for most of the systemic disturbances caused by microgravity in an organism over long periods of time. That would be ideal. We must recall that in many instances proper experimentation requires multi-generational studies, and that multi-generational studies may take years. Not only could we benefit from investigating the effects of microgravity on a variety of organisms, but we could do so without risking serious damage to the biologists carrying out those investigations in space.

The experimental and theoretical promise of space biology is thus far greater than we may imagine from glancing at a few reports of the rather pedestrian biological experiments that have been done so far. Two further considerations should give solid anchor to this conclusion. The first is conceptual; the second is historical. H.A. Lowenstam and Lynn Margulis have argued convincingly that the ability by eukaryote cells to modulate their internal concentrations of calcium made possible the appearance of calcareous skeletons.[13] The appearance of such skeletons in turn made possible, over 500 million years ago, the Cambrian Explosion, during which all the major divisions of life became established. The importance of this argument, for our purposes, is that calcium metabolism is one of the first things affected by microgravity.

Calcium ions in solution are essential for many physiological functions, including cell adhesion, muscle contraction, amoeboid cell movement, and -- as it is now acknowledged -- they are also used to transmit information between cells. Not only is the intracellular regulation of calcium essential to the function of eukaryote cells, it is also important in the genesis of tissues and embryos. The regulation of calcium seems to be one of those physiological functions on which nature has built a whole array of other functions. This key evolutionary role apparently began, according to Lowenstam and Margulis, when "prey, forced to escape from more effective predators, developed highly integrated sensory and motor systems that must have involved increased coordination and speed of the muscle system."[14] These two skills depend on muscle contraction. And muscle contraction "responds directly to calcium release."[15]

Since the regulation of calcium may have been very instrumental in the evolution of complex organisms, and since life develops in a jury-rigging fashion, the biological importance of calcium may go far beyond what standard theory assigns to it. Determining that importance is precisely one of the areas where experimentation in space can be of advantage. This consideration thus provides one more reason for thinking that in space biology, too, exposure to new circumstances may lead to the profound transformation of our ideas.

The examination of the role of gravity in living things has paid off from the beginning. It was Darwin himself who first noticed that the tips of growing roots and shoots were used to detect gravity. "We now know," he said, "that it is the tip alone which is acted on, and that this part transmits some influence to adjoining parts, causing the latter to bend."[16] The study of this influence, in a long series of experiments beginning with the publication of Darwin's work in 1880, yielded the separation (1920's) and chemical identification (1930's) of the first hormone known to make plants grow.[17] Space biology proper seeks the opportunity to continue this history.

Nevertheless, even if these considerations are admitted, the question remains whether the large expenditures of space biology are justified when its significance is more of promise than of record. “$50,000 can pay for a decent experiment in standard biology today,” a biologist told me in the 1980s. But for that money we could hardly get a rabbit into orbit, to say nothing of enough rabbits for biologists to supervise multi-generational studies in space. We must notice, however, that this complaint does not deny that space may be beneficial to biology, or that it may be beneficial in important ways. Its aim is rather to make us favor Earth-based investigations -- which we already know are very important -- over the expensive biological experimentation in space.

Space biologists often respond in two ways. First they point out that their budgets have been small as space budgets go (in the 1980s, for example, it was about $30 million a year -- including the monies for exobiology, gravitational biology, and flight experiments -- which was roughly about 3% of the total space science budget, and not much when compared to all the monies spent for biological research on Earth). Their second point is that most of the money for space biology is not going to come from the general funds earmarked for the life sciences. The money is going to come from space exploration funds.

Critics are unlikely to accept these two points. First of all, even if the space biology budget is a pittance, to do the research properly would take far greater amounts. For example, if space biology is used as one of the justifications for building the space station, we would have to think in terms of hundreds of millions of dollars. As for the second point, to say that the two are not really in competition for the same monies is an easy out. For whatever the name of the account, in the long run society pays for both. Why should space biology take so large a share?

Nevertheless the matter is not as simple as that. Space biology does indeed belong to a large space commitment. Because of that, the notion of competition between standard biology and space biology flounders. To see why, imagine what happens to a man who buys an automobile and wants a radio in it. For the amount of money that he will have to spend, he could have gotten several radios far superior to the one that goes into his car. But those radios would not do quite the same job effectively. Similarly, since we are going into space we have an opportunity to investigate life in ways not open to us before. The whole question of doing space biology must then be taken in the context of having a space program, just as the question of having the car radio arises in the context of having a car and not in that of purchasing radios generally. All the while we must keep in mind how promising a radio this is.

[1] From the "Final Report of the Developmental Biology Working Group," p.3. (Not yet published, extended to me as a courtesy of Dr. Emily Holton).

[2] For a brief summary see G.R.Tylor (Note 19), p.103. For a full report see H.W. Scheld et al, "Killifish Development in Zero-G on COSMOS 782," p.179, NASA TM-78525. Unpublished Soviet studies, however, have raised serious doubts, in J.R. Keefe's opinion, "about the ability of normal vertebrate fertilization under spaceflight conditions." ("Gravity is a Drag," p.6. Unpublished).

[3] See the Annals of Botany supplement cited in Note 17. Dr. Holton has made available to me data from Soviet experiments that show very low yields and that suggest that flowering and fertilization may be sensitive to gravity (as indicated, for example, by lost chromosomes in Dwarf Sunflower and broken chromosomes in oats). When cells are studied not in culture but as part of a system, there is a peculiar increase in chromosomal abnormalities in the majority of organisms, including humans. See, for example, L.H. Lockhart, "Cytogenic Studies of Blood (Experiment M111)," Biomedical Results from Skylab, op. cit., p.217. Investigators are much too quick, in my opinion, to explain away such widespread abnormalities as possible effects, exclusively, of flight stresses.

[4] Whether atoms existed at all was a matter of controversy amongst physicists. Ernst Mach, for example, argued that their existence was not a scientific claim. The controversy was settled in 1905 with the publication of Einstein’s work on Brownian motion.

[5] We might ask whether it is fair to have to spell out the warrant for investigating the role of gravity in biology. After all, the history of science is full of cases where investigations that were considered preposterous led to the most profound changes in thought. But we cannot take this easy way out when space biology requires large sums of money and its critics have credentials and influence. The issue must be faced.

[6] Of particular interest would be animals who exhibit a highly differentiated ability to distribute fluids (e.g., Gerbilline rodents). "Final Report of the Developmental Biology Working Group," op. cit., p.6.

[7] Ibid. p.5.

[8] Every system of the organism tries to maintain homeostasis (a relatively stable state of equilibrium) against the next higher level, and the organism as a whole against the environment. Thus the genes benefit from many levels of homeostasis serving as a buffer zone against the environment. Nonetheless it is clear that the general environment sometimes will affect the intracellular environment and thus may conceivably act as an agent of selection against some pieces of DNA and in favor of others (at the molecular level, that is). This is not to say that acquired characteristics can be passed on, since the features of the environment that will favor some traits at the level of the organism are not of a kind with those that would act on pieces of DNA within the cell. That is what happens, for example, when a change in the cellular environment may permit a mutation to survive which will later be considered a defect of the organism vis. a vis. the general environment.

[9] Stent's work on nerves.

[10] I take it that the general point I am defending here is a corollary of the views I expressed in Chapter 8 of my Radical Knowledge: A Philosophical Inquiry into the Nature and Limits of Science, Hackett, 1981. It is also an expansion of Gunther Stent's work on the "meaning" of the genetic code.

[11] In general, centrifuge studies can be extrapolated to space conditions only with the greatest of cautions.

[12] This example is taken from S. Williams, “Bugs in Space.” Science News, 2007, September 29, Vol. 172, p. 197.

[13] H.A. Lowenstam and Lynn Margulis, "Evolutionary Prerequisites for Early Phanerozoic Calcareous Skeletons," BioSystems, 12, 1980, p.27.

[14] Ibid. p. 36.

[15] Ibid. See also, S.J. Roux, ed., The Regulatory Functions of Calcium and the Potential Role of Calcium in Mediating Gravitational Responses in Cells and Tissues, NASA CP-2286,1983.

[16] C. Darwin, assisted by F. Darwin, The Power of Movement in Plants, John Murray, 1880, p.592.

[17] Adapted from the Dedication to Charles Darwin in the Proceedings of the Sixth Annual Meeting of the IUPS Commission on Gravitational Biology, op. cit.

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