Astronaut Marsha Ivins (STS-98) with weightless long hair. . Credit: NASA

The American space agency NASA is going through a mid-life crisis. Its future is at stake, and whatever directions are chosen they will be controversial. While NASA isn’t the be-all end-all of world space efforts, it is arguably the biggest, most visible, and iconic of the world’s space agencies. So the discussion about NASA is also a discussion about the world’s approach to space.

One of the hottest discussions is an old one: What should be the role of humans in space? Put another way: Is it better to use electronics and mechanics (probes and robots), or live human beings to explore space? In the Congress of the United States, some of the most famous living astronauts have lined up to give impassioned speeches on one side or another. (They are mostly in favor of human exploration; no surprise.)

There is an expression that is currently heavily overused in the U.S. that goes: “…overlooking the elephant in the room.” For the argument about humans in space, let’s alter the expression just a little: “…overlooking the weightless elephant in the room.” There are at least a couple of problems concerning humans living in space for more than a very limited time (a few months): One is the problem of radiation, especially high radiation from solar storms. The other problem is free-fall and microgravity. Let’s talk free-fall and gravity here.

It’s often said that astronauts in orbit, for example in the International Space Station, are in ‘zero gravity.’ This is a misconception. The astronauts float around inside the space station not for lack of gravity. The gravity of the station is only about 6% less than that of the surface of the Earth. They float because the station is in continuous free fall, where its orbital motion is in balance with the force of gravity. Microgravity, where gravity still exists but is very small relative to the surface of Earth, is encountered much further out in space; where so far only the astronauts to the Moon have experienced it.

It’s been known since the very earliest space programs that for human beings neither free-fall nor microgravity is a healthy combination. All living things from Earth are adapted to gravity. Our body structures, cell functions, molecular configuration, and organic chemical reactions are all the product of incorporating the effects of gravity. To remove the effect of gravity in any substantial way is to create an all encompassing alien environment. Very little about living things functions quite normally in microgravity or free fall. For one thing, there is no ‘up’ or ‘down’, so blood systems, lymph systems, and the fluid systems within cell tissue that usually rely on directionality (for example, the complex system used to return blood from feet and hands against gravity) suddenly don’t have the expected resistance. Over time they may lose their effectiveness (by atrophy), which is one reason that astronauts who have been in space more than a few days often appear somewhat weak when they first return to Earth.

Some of the problems associated with free fall and microgravity have been known for some time. Bone loss, for example, was recorded whenever humans spent more than a few weeks in orbit. Some of the problems are temporary, such as space adaptation syndrome (SAS), which strikes about 45% of space travelers with various combinations of nausea, headaches, vertigo, and lethargy. Other problems, such as muscle atrophy can be addressed with increased exercise. However, some of the research that has been done is finding areas where the problems are more subtle, and dangerous. They may even be what the Americans call a ‘show stopper.’

One study from the University of New South Wales (Australia) used a NASA rotating wall vessel (a spinning container) to simulate free fall. They exposed human embryonic stem cells to this environment for varying periods of time and observed the changes. Seventy percent of the proteins that were produced in the free fall cells are not found in those that grow in normal gravity. In short, the protein manufacturing chemistry of the stem cell was radically altered. More proteins were manufactured that negatively regulate bone density, and less anti-oxidant proteins, which protect the DNA, were created. As the lead researcher, Dr. Brendan Burns put it:

“A lot of work has been done on microgravity at a systemic level, such as the effects on the immune system. No-one has really looked at the effect of microgravity at a cellular level and we think that is a huge gap.

“What we’ve found is a range of different proteins that are potentially important for astronaut health were more or less predominant in terms of different gravity.”

[Source: University of New South Wales]

Another recent study led by immunologist Ty Lebsack at the University of Arizona (Tucson, USA) has studied mice sent into orbit to observe that weightless orbiting changes the activity of genes that control immune and stress response, perhaps leading to more sickness.

The researchers focused their attention on the thymus gland of four healthy mice that spent 13 days in orbit (as compared to similar mice kept on the ground as a control group). The thymus gland is the producer and reservoir of T-cells, a key component of the immune system. They found that 970 individual genes changed their expression (up or down) by a factor of 1.5 or greater. The changed genes were primarily those involved with signaling molecules that regulate cell death in response to stress. These results were also checked against mice that were placed in a clinostat (basically, the same device use by the researchers at the University of New South Wales) to simulate free fall; the results were similar – T-cells in the thymus were more likely to die without the stimulus of gravity.

“Previous studies with cell cultures in clinostats showed increased cell death in T-cells when you take away the gravity stimulus,” said Lebsack, “so it was a logical step to test whether we find the same effects in animals exposed to an actual lack of gravity.”

“We observed an overall pattern about the genes whose expression was changed by space flight: All of them are involved, in one way or another, in the development, control and programmed cell death of immune cells.”

[Source: EurekAlert]

Both of these studies point to problems at the molecular level. This should not be surprising. What is surprising is the relative lack of comprehensive studies involving the effects of long term free fall or microgravity on the delicate genetic and molecular processing functions at the cell level. These are problems potentially much more fundamental than temporary illness or even bone loss (although there may be relationships).

I get the sense from much of the literature in this area that research has been done largely within the context of astronauts who spend a relatively brief time in space. Most of the research has been ‘higher level’ observation – for example the SAS symptoms, or the muscle atrophy – mainly because those are the most readily observed problems for this context. What’s missing, with the exception of some work done by the Russians who spent much longer periods in space, are experiments aimed at evaluating the effects of free fall or microgravity over the kinds of time periods that would be involved with serious deep space missions – months or years. In particular, what’s missing are the evaluations at the molecular and chemical pathway level – the very small things that make up the real elephant in the room.