Commentary: A More Perfect Astronaut

With new techniques in genetic experimentation, can biologists make hardier space dwellers?

Even when one is inside a climate-controlled spacecraft, sheltered from the deadly vacuum outside, space is a hostile setting. Terrestrial organisms venturing off the planet face a number of threats, chief among them cosmic radiation and the near absence of gravity. In space, medaka fish become disoriented, turning continuous somersaults as they swim. Rats cease to use their hind limbs effectively. For humans, problems include the wasting of postural muscles, the demineralization of bone, and the often disquieting sensation of being upside down.

These well-documented physiological changes seem tolerable for short stays in Earth orbit. But what happens to a species after reproducing in space for many generations? On a space station, colonies that have no precedent for living without gravity will change in fundamental ways. Responding to any new environment involves not only visible changes, like shivering in reaction to cold, but also changes in the pattern of gene expression—the way genes turn on and off—in body tissues.

From the human genome project, we have learned that about 35,000 genes encode a human being. What most people don’t know is that only a fraction of these genes are actually turned on or expressed in any given cell. The genes that are turned on in brain cells, for example, are different from those active in muscle or kidney cells. Gene expression can also reflect the response of the cell to the environment. Start jogging or experience the muscle wasting of space, and gene expression in the affected muscles will change.

New “gene chip” technology can reveal changes in thousands of genes at once, and is revolutionizing understanding of the mechanisms of gene expression. The same technology will prove a powerful technique for studying how organisms react to being on the International Space Station.

Some of the genetic response will be immediate, as is experienced when a person on Earth begins jogging. But for long-duration space colonies, a second, slower force will come into play—natural selection. It’s fun to speculate (which is all we can do right now) on what kinds of traits might turn out to be adaptive for species living off-Earth for multiple generations.

Very simple genetic changes can result in major rearrangements of an organism’s body plan. Animals are made of modular units, like appendages or eyes, controlled by master genes through which entire body parts can be duplicated, removed, modified, or shifted in location. Minimal changes in a single critical gene can therefore produce large changes in an animal’s appearance. Over the course of evolution, alterations in master genes have transformed a limb into a wing and a starfish’s tube feet into a lobster’s claw. The near absence of gravity on the space station will likely exert selection pressure on these control genes. If we envision the creatures that might evolve over very long periods, it wouldn’t be surprising if hind limbs diminished to vestigial stubs and forelimbs gained adhesive properties. Who needs Velcro when your hands are sticky?

We can look to certain oddball organisms on Earth for clues as to what kinds of genes might be helpful to species in space. A species of bacterium called Deinococcus radiodurans can withstand 3,000 times as much radiation as people can. In humans, high radiation levels damage cells by breaking long, continuous strands of DNA. Radiation causes similar damage to D. radiodurans, but within hours the DNA is correctly reassembled. For every other known life-form, any attempt at DNA reassembly would be so fraught with errors that the organism would die. But D. radiodurans has somehow solved this problem, and its genome—the complete set of its DNA—may be a treasure chest of genes that could protect other organisms facing high radiation levels.

How could these genes be put to practical use? Fortunately, the interrelatedness of all species allows the same genes to function identically even in highly unrelated species. In a process called lateral gene transfer, many genes have jumped species over the course of evolution. In fact, tucked into our own human genome are a number of genes that appear to have jumped in from bacteria.

In addition to physical traits, social relationships among animals can have a genetic component. Some male mice, for example, tend to be deadbeat dads, with little interest in caring for their young. Researchers recently have shown that if you take from a prairie vole a gene for something called the arginine vasopressin receptor and transfer it into a mouse, you can produce male mice that, like the voles, stick more closely by their offspring. A simple genetic change leads to a profoundly altered behavior. Could such knowledge be useful for humans, many of whom have trouble spending long periods in isolation, whether in Antarctica or on a three-year trip to Mars?

The bad news for experimentalists is that evolutionary change, even in fast-reproducing species, takes time. How can we study long-term adaptation to space without waiting decades? The answer lies in understanding the deep and profound basis of the evolution. First and foremost, evolution is based on genetic diversity. In humans, the actual DNA sequences, or strings of letters we call the genetic code, differ slightly from individual to individual. These small differences are thought to contribute to, among other things, variations in susceptibility to illnesses such as Alzheimer’s disease, diabetes, and cancer. This is true for other species as well. If 100 rats are placed on the space station, minor differences in their genomes may contribute (along with many other factors, from cage design to nutrition) to their reproductive success. The space station will, for the first time, allow us to watch living organisms adapt to space over generations, and to see which ones do better and which do worse.

Which organisms will make the best test subjects? To watch evolution in action, we need species with short reproductive periods, such as yeast. It also will be useful to study creatures whose genome is known. The list of species whose genome has already been crudely mapped include the fruit fly, a small worm called Caenorhabditis elegans, the wild mustard weed, numerous single-cell organisms, human beings, and soon the mouse and zebra fish. And because sequencing the entire genome of any organism is no longer a formidable task, we shouldn’t limit ourselves to the few species most often studied by biologists. For NASA’s purposes, it might make sense to sequence other organisms that hold the potential of becoming well adapted to space. For example, certain fish create an electric field around them, which they use to detect the presence of intruders. Knowing whether a visitor has entered the field requires a memory of what was previously in the field. And locating the disturbance caused by the intruder requires a set of coordinates related to the orientation of the creature’s body. Will this mechanism work just as well when gravitational orientation is lost? Experiments to test questions like this could yield profound insights into how weightlessness affects both the genetic and physiological bases of spatial learning and memory.

The ability of engineers to build vehicles and space stations that can safely house humans and other species in Earth orbit, or on a voyage to Mars, opens a new biological niche into which life can radiate. With advanced techniques in genetic research arriving at the same time that a sophisticated laboratory is being assembled in Earth orbit, the tools are finally in hand to explore this subject in earnest. The collected genomes of all species, with their staggering diversity, plus the much larger set of synthetic genomes certain to be created from this raw material, hold the potential to create life-forms capable of surviving, even thriving, in the hostile environment of space. The scientific and ethical implications of this will affect not only future astronauts, but the destiny of life on Earth.

 Kenneth Kosik is a Professor of Neurology and Neuroscience at the Harvard Medical School, and a senior neurologist at Brigham and Women's Hospital in Boston.  He was a principal investigator for the STS-90 Neurolab space shuttle mission in 1998.

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