Anti-radiation Biological Countermeasures: Amifostine

Amifostine (image rights: Ganfyd-licence user Mlj)

Amifostine (image rights: Ganfyd-licence user Mlj)

Whenever human spaceflight comes up, inevitably someone mentions radiation. Personally, I think the radiation risk is WAY overblown. “Compound conservatism” is rampant, I believe, and gets worse as time goes on and people keep recycling the same sources, adding some safety factor each time. (see here for a slightly longer explanation) Being extra conservative with radiation risk assessment eventually can cause an estimate for the tolerable risk that’s completely detached from reality, leaving very little budget left to deal with the other, much bigger risks if there’s even any money left to do the mission at all!

If we followed EVERYONE’s conservative advice for radiation risk, we’d be asking astronauts to fly in a giant sphere of polyethylene with no windows, hardly any room, and no EVAs ever (no “one small step” moment because of the risk of radiation, let alone a colony). We certainly wouldn’t be flying to ISS as we are now.

That aside, we can look at what IS a reasonably feasible and low-mass approach to dealing with radiation. Instead of the usual water or polyethylene or regolith shielding or magnetic shielding, I will look at a somewhat over-looked option: biological countermeasures. Radiation is, of course, often used to treat cancer. As such, there is a sizable body of work and several possible treatments that limit the toxicity of radiation to normal (non-cancerous) cells (thus allowing a higher dose to be used against cancerous cells, which are protected less). The most studied drug is, I believe, Amifostine. “Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues.” (Cakmak et al)

While most such studies look at the ability of Amifostine to protect healthy cells from cell death and other damaging effects of radiation (such as damage that may lead to neurodegeneration), which seems to be effective (according to Cakmak and friends), what is most relevant to us in this discussion is the effect on a specific type of radiation-induced toxicity: carcinogenesis. People have suggested that stopping cell death may actually increase tumor-related toxicity (I see their argument, but it is much more likely that, due to Amifostine’s free radical scavenging, the total damage to the DNA is reduced) but is that actually true? No. No it’s not:

Paunesku et al:

Amifostine protected against specific non-tumor pathological complications (67% of the non-tumor toxicities induced by gamma irradiation, 31% of the neutron induced specific toxicities), as well as specific tumors (56% of the tumor toxicities induced by gamma irradiation, 25% of the neutron induced tumors). Amifostine also reduced the total number of toxicities per animal for both genders in the gamma ray exposed mice and in males in the neutron exposed mice.

(note: neutrons have a high quality factor, sort of like GCRs)

However, there is the argument that long-term use of a radioprotectant is not very effective, since it could reduce the body’s natural defense mechanisms.

As an aside, these very natural defense mechanisms are exactly why I think the threat posed by long-term chronic low doses of radiation is actually quite low… The body adapts to the constant radiation by increasing its natural repair/scavenging mechanisms… But with a short, very large acute dose, the body does not have time to adapt and its repair mechanisms are over-whelmed. It is these large acute doses that the general risk of cancer is actually based off. I find that extrapolating down from acute doses is incredibly unrealistic (on the ultra-pessimistic side). Aside over.

So, it may be that Amifostine and similar drugs are really most effective against acute doses of radiation. You might want to inject a little Amifostine when you learn a flare is on its way (once you get inside your radiation shelter). BUT I am not entirely convinced that there’s no benefit at all to Amifostine for chronic low-dose radiation. Even so, this whole field has tremendous potential. Imagine, you can potentially reduce the tumor toxicity of a really bad solar flare event by 25% with just a few grams of extra mass! And that’s on top of the benefit you might get from shielding and fast transit. One a per-mass basis, biological countermeasures are essentially unbeatable. This is why I think that if we’re going to spend any resources on solving the radiation problem, it probably should be to maximize whatever benefit we can get from drugs like Amifostine and, say, finding out if we can maximize our bodies’ built-in repair mechanisms through, say, targeted gene therapy. There are examples of extreme radiation tolerance and gene repair in nature that put even some rad-hard electronics to shame, so the ultimate potential (on the physics side) of biological countermeasures is pretty high as well. Biology may be a lot messier and frustratingly complex, but the potential gains make this path toward radiation mitigation worth it. Once developed, a drug or treatment would be very cheap, while shielding your transit craft with tens of tons of polyethylene or something will always be fairly expensive (even with space mining) or at least cumbersome.

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8 Responses to Anti-radiation Biological Countermeasures: Amifostine

  1. Chris Stelter says:

    An interesting article:
    http://journal.frontiersin.org/article/10.3389/fonc.2014.00381/full

    Gene therapy is an interesting approach.

    …also, we’re making substantial progress in improving cancer survival rates using immunotherapy, reprogrammed T-cells, and the like.

  2. DougSpace says:

    The choices are not limited to the well understood protection of tens of tonnes of polyethylene versus the poorly understood protection of biological countermeasures. Another option is to have the crew spend their sedentary time positioned such that the mission’s provisions (e.g. food and water) are also providing radiation protection. Think of it as hanging out in the pantry. Then, when you need to stretch your legs and move around, you leave that protection, hang out in the neighboring inflatable module but you limit your time there in order to keep within your radiation budget.

  3. Chris Stelter says:

    BTW, given modern models of GCR dose on the surface of Mars (after traveling through the atmosphere) when you include neutrons bouncing back and neutron activation, aluminum does zero good and even makes things slightly worse. Better off in a spacesuit than under a few inches of aluminum on the surface of Mars.

    Polyethylene is still useful, though.

    But big pet peeve: graphs in these papers always end at 0km altitude, which is dumb. EDL constraints alone would probably force a surface mission to land at well below 0km altitude, and as I keep saying, Hellas Planatia is -7km, down to below -8km.

  4. gbaikie says:

    –Whenever human spaceflight comes up, inevitably someone mentions radiation. Personally, I think the radiation risk is WAY overblown. —

    I would say in a way it’s overblown, but I also would say best way to get to Mars is by using a Nuclear Orion- ie exploding nukes in Earth’s atmosphere to provide rocket thrust.
    And the risk of radiation this causes is overblown. But I don’t recommend launching Nuclear Orion from the Earth surface. But in terms using Nuclear Orion from the moon, Mars, Venus, or Mercury, would be possible [politically].

    The radiation problem regarding getting to Mars, can be solved by getting crew to Mars in shorter travel times. And it shorter travel times can be done by chemical rockets [rather than Nuclear Orions, other kinds of nuclear propulsion, Ion, or something like VASIMR]. In terms of Mars settlements [vs Mars exploration] perhaps
    non chemical rockets can be used. Ie, whenever there is are more than 1000 people living on Mars, the Martian could use Nuclear Orions or whatever.

    With hohmann transfer one has shorter travel times to the inner planets as compared
    to travel times from Earth to Mars. It’s 5 months to Venus and about 4 months to Mercury distance, as compared to 8.5 months to Mars from Earth.
    Venus though longer distance to Mars in term of closest approach distance has shorter orbital distance in terms of hohmann transfer, and even shorter orbital distance from Mercury to Mars. Or Venus to Mars is about 7.2 months vs Earth to Mars of 8.5 months.
    If you doing a hohmann transfer from Venus [or Mercury] to Mars, one’s orbital speed at Mars distance is slower than compared to doing an hohmann from Earth to Mars. This important to remember because people tend to think that the faster one goes from Earth to Mars translates to higher velocity difference at Mars distance- which is true if doing something like a hohmann transfer from Earth to Mars.

    Or a Venus to Mars hohmann transfer has to cross Earth’s orbital distance, and by doing a non hohmann transfer from Earth can get one to same orbit as a Venus to Mars transfer orbit, and if one did this, one arrives at Mars distance parallel to Mars at a lower orbital speed [and one get to Mars [from Earth to Mars] faster than than the 7.2 months of Venus to Mars hohmann. And if you don’t interact with the planet Mars the return trajectory, returns you to Venus distance in 7.2 months [and also crosses at earth distance in shorter time period than the 7.2 months- about 4.5 months.
    Now one can do trajectories similar to hohmann transfer from Earth to Mars which can get you to Mars orbit in about 7 months rather than 8.5 months- hohmann + conic patched trajectories, And same applies if going from Venus to Mars- or you can do a transfer similar to true hohmann transfer, which arrives from Venus to Mars in 4 to 5 months, rather than the 7.2 months travel time a simple hohmann transfer.
    Other than getting to Mars faster, these patched conic maneuvers alter the return leg of the orbit- or you are change the orbit [it doesn’t return to Earth distance {or venus distance} the rocket burn is raising the Perihelion distance from the sun.
    So if doing a Earth to Mars hohmann + patched conic, and after you do this maneuver and also don’t interact with Mars gravity then the return leg would end up between Earth and Mars distance. And if instead if one were doing a Venus to Mars hohmann + patched conic, one end up between Venus and Earth.
    So it’s possible if one were a Venusian, to leave Venus and do a mars hohmann + patched conic, miss planet Mars and end up in a Earth to Mars hohmann transfer orbit. Of course if wanted to interact with the gravity of Earth, one needs to arrive at same time as the arrival for a given trajectory.
    And one can also do this, starting from Earth, but it’s not a hohmann transfer from Earth to Mars- it only ends up being one, once one has done the patched conic maneuver near Mars distance.
    Since it’s not hohmann transfer from Earth to Mars it is not an efficient use of delta-v, but it gets to Mars much faster than any hohmann transfer from Earth to Mars.

    This is analogous to dog legged way to get to GEO from a higher inclination than the equator. Or if launching from say KSC, one can do a GTO at 28 inclination and change the inclination when further from Earth gravity, so orbit become at 0 inclination. Or you can do a dog leg, of basically doing suborbital to near equator, and changing the inclination near Earth’s gravity well [but not when traveling at the much higher orbital speed]. The way commonly used is the former, but latter has been used.

    So one can get from Earth to Mars in about 3 months [or less] and yes it requires more delta-v. Any non hohmann uses more delta-v, but hohmann are also the slowest trajectory. Or nothing going to Mars fast will use a hohmann transfer- whether it’s Nuclear Orions, Ions, or whatever rocket you choose.
    What significant is one can use chemical rockets to get to Mars quite fast. Chemical rocket can do hohmann transfers, and say an ion rocket can’t. The high thrust of Nuclear Orion could do hohmann, but not if it wants to get to Mars quickly. If you have to get to Mars within one month, one is forced to use the Nuclear Orion, but 2 to 3 months is doable with chemical- and I would say cheaper than any other way to get there is fast. Cheaper because we have chemical rockets which can do it, now. Cheaper because one lift rocket fuel cheaper. And no matter how you explore Mars [really explore Mars] one will need to lift a lot of chemical rocket fuel from Earth, and sending crew fast to mars is something like increase the total rocket fuel lifted from Earth, by say 10% of total as compared to what one would need to do if going there slower.

    So you just send the crew to Mars quicker and all the other mass needed is sent the slow path of hohmann transfers.

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  6. Jeff Greason says:

    The real problem with galactic cosmic radiation (GCR) for mission planning is that the uncertainties are very large. Oh, we know the dose — but we know very little about the biological effects of GCR. That unfortunately includes whether the radioprotective approach you discuss above or a host of others are as effective, less effective, or more effective with GCR than with the kinds of radiation we can test. That range of uncertainty leaves huge error bars on risk assessment, ranging from “no big deal” to “giant sphere of polyethylene and/or go really fast”

    Personally, I think we can pile paper studies on this until we get tired of it, until we have a facility for exposing mammalian test subjects to long-duration GCR flux. What data we have is the Apollo flights, some sounding rocket tests, and simulated flux on the ground which is high rate/short time rather than real rate/long time. We really need a lab in cislunar space to settle this.

  7. gbaikie says:

    “……We really need a lab in cislunar space to settle this.”
    The real problem with galactic cosmic radiation is we have a NASA bureaucracy exploring Mars. Or at least that is the plan.
    If it was a religious or even a military bureaucracy it might not be a problem in terms of exploration. In private sector [or not a NASA bureaucracy] people climb Everest knowing there is chance of death and injury.
    NASA is part of a US government which restricts radiation exposure and in in a culture
    which has been brainwashed to fear nuclear power plants.
    We have already got a small segment of crazies frightened by mars life contamination- despite lack of evidence of Mars life.
    GCR is largely a political problem which amplified by the fear of radiation, but one should not think that a political problem can hand waved away. It’s a real problem which can not be solved by efforts at rational discussion.
    I give example, there a millions of idiots [including Obama] who imagine CO2 emission is a problem. If CO2 emission was a problem, the only rational thing one could do is use more nuclear power if you think CO2 emission is serious problem, yet only few brave souls will suggest that the effort should be focus on more use of nuclear energy But none of the idiots listen, because they imagine nuclear energy is too dangerous.

    So the only solution is to do everything possible to reduce exposure to GRC and other space radiation and trying to deny the problem will result in delay and failure of NASA exploring Mars or elsewhere.
    So NASA should explore the lunar poles to determine if there is commercially minable water, and then NASA should plan on sending crew to Mars so they get to Mars in less than 3 months.

  8. Oliver Milne says:

    According to Wikipedia: “Common side effects of amifostine include hypocalcemia, diarrhea, nausea, vomiting, sneezing, somnolence, and hiccoughs. Serious side effects include: hypotension (found in 62% of patients), erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis, immune hypersensitivity syndrome, erythroderma, anaphylaxis, and loss of consciousness (rare).” I think I’d rather stick with the polyethylene, myself.

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