A few years ago, researchers from the University of California asked a question that doctors and their patients with brain tumors couldn’t ignore any longer: What really happens to your brain when you blast it with radiation? They found that its once-bushy neurons looked like your curbside hedges after the township tree surgeons got through them — they were emasculated of their branches and leaves.
Vipan Parihar and Charles L. Limoli are the radiation oncologists behind that study. Last week, they made another important breakthrough, this time in the nationwide effort to select the best candidates for a one-way trip to Mars. It seems that as long as shielding against cosmic rays is still too difficult, and the trip remains slow enough, than patients with brain cancer end up with a win-win: If the radiation is not hot enough, then no biggie — a one-way trip for someone who already, regrettably, has a one-way sentence. If the radiation is just hot enough to zap their tumors, but spare the brain at large, then great, they are cured for the remainder of the trip. And if the radiation is too hot, and melts both tumor and brain, then at least their consciousness will be numbed to the full horror of its dissolution by tiny degree. [John, I'm a little concerned with your definition of win-win here. -Ed]
Few outside the field generally appreciate the full technicality of the modern science of radiation therapy. Fortunately, nearly every spec is eminently meaningful and it is easy to jump right in. For example, one might blindly think the emission energy spectrum and half life of cesium are the predominate factors for choosing it. Not necessarily so. Cesium has a half life of 70 years and biological half life (the clearance time, if you actually consume or inject it) of a couple months. All of the tumor-busting 662 keV gamma rays it supplies are actually from the barium to which it decays by beta emission. For their original studies of the mouse hippocampus, the researchers irradiated the cranium directly with cesium at a dose rate of 2.07 Gy/min, for a total of 1-10 Gy.
Cosmic rays, on the other hand, are a little different from the perhaps several hundred or so therapeutic radioisotopes now at the radiation oncologist’s disposal. Astronauts aboard the ISS don’t receive anywhere near the total galactically sourced cosmic ray bombardment that someone on a trip to Mars would be expected to receive, because they are still within the protective magnetosphere of Earth. As the authors note, there is really no way to escape these energetic remnants of past supernova events. The shielding required — even dense lead — is prohibitive, as would be the amount of power required to generate electromagnetic force fields to deflect charged particles. Even if you only shielded your head, and had no gravity, the inertia alone of any such helmet would be massive.
The charged particles and fully ionized nuclei found in cosmic rays are characterized as high ZE particles (HZEs), where ‘Z’ is atomic number and ‘E’ is energy. To mimic the effects of these elements, the researchers irradiated mice with up to 30 cGy (10−2 Gy) of 16-O or 48-Ti particles. As we mentioned above, the fine branches of neurons were the anatomical targets that were found to be hit the hardest. Even more ominously, the researchers found significant behavioral deficits in the animals upon cognitive testing. As far as the dendrites, it is tough to say what is really happening. Their tiny spines (as seen below) can perhaps best be thought of as igloos or hatcheries for the mitochondrial residents that build them. It’s these same mitochondria that construct all our fine-scale neurocircuitry.
|Credit: Mulholland Lab, people.musc.edu|
These anecdotal bright flashes in the mind may come from cosmic ray stimulation of pigments or whole neurons in the retina itself. They could also come from any number of potential mindful events stimulated by the elaborate fractal path of an errant ray, shredding a brain unwittingly turned into a scintillating cerebral cloud chamber. These secondary radiation events can be even more damaging to our cells then the primary particle or ray. The researcher’s expertly titled paper, What happens to your brain on the way to Mars?, by no means fully answers the potentially game-changing question now laid bare before us. “In space, no one can see your heart become spherical” was the previous little undeniable truth that we needed to add to the growing list of physiological challenges for life amongst the stars. Now we have another.
If we are to fly to Mars, and enjoy our stay, then speed will be of the essence. Recent reports of new powerplants to turn the trip into one of a few weeks rather than years may be just what the doctor ordered. I will admit some skepticism when the authors suggest that there may be drugs to help the seemingly dire situation would-be voyagers must face. Any pharmacologic strategy to scavenge the ‘free-radicals’ generated by radiation seems dicey, because the way free radicals actually seem to work, is that when they are generated locally in mitochondria, they provide an important feedback signal to the electron transport chain that generates energy.
The logic behind this is that if the mitochondria generate ATP at a rate higher than it is needed, the membrane potential (voltage in mitochondria) tends to collapse, and respiration grinds to a halt through inhibitory feedback. ATP accumulation drives membrane potentials to higher levels, making it even harder to pump the protons that help generate that potential. The respiratory complexes therefore gradually back up with excess electrons and leak away free radicals.
As dangerous as free radicals can be when turned loose in the cell, those feedbacks are something useful you don’t really want to block. A drug which blocks radicals across the board would block those artificially generated by cosmic rays as well as those produced naturally in the cell. And radicals are just one way cosmic rays can hit you.