Space motion sickness and alien microbes: learning from astronauts
Andrew Haynes investigates the drugs used by astronauts and the potential of space orbit for research leading to new medicines and medical techniques
Astronaut in space
And so this is Christmas. If the night sky is clear on Christmas Eve, you may hope for a glimpse of Santa’s sleigh or the Star of Bethlehem. But if you look up shortly after sunset, you may spot a slow-moving, bright white dot crossing the sky. This is almost certainly the International Space Station (ISS), which orbits the earth some 400km above us, housing a crew condemned to spend the festive season away from their loved ones.
But what, you may ask, does the ISS have to do with pharmacy? Quite a lot, in fact, since the consumption of drugs by astronauts and the use of space orbit for drug research have both increased our knowledge of drugs and their manufacture.
Astronauts blasting off into space take with them a range of medicines to combat the illnesses they are most likely to encounter during their odyssey. As “Didapper” has reported (PJ, 18 July 2009, p80), when Apollo 11 first took man to the moon in 1969, it carried a medical kit containing antibiotics, antinauseants, stimulants, painkillers, decongestants, antidiarrhoeals and hypnotics.
All these are still taken into space, but the most frequently used are antinauseants, since most astronauts suffer from space motion sickness (SMS) during the first few days. In the US, the National Aeronautics and Space Administration developed an antinauseant formulation containing hyoscine 0.4mg and dexamfetamine 5mg. The “dex” was intended to counteract any drowsiness induced by hyoscine, but it does not help with other side effects such as dry mouth, blurred vision and photosensitivity. The combination is known as ScopeDex — a contraction of scopolamine (the US name for hyoscine) and dexamfetamine. More than 40 years on, ScopeDex is still used, even though it has been shown that rather than aid adaptation to microgravity it merely delays it, so astronauts can develop SMS when they stop taking it. The main alternative is promethazine, which, unlike hyoscine, does not seem to delay adaptation and may even hasten it.
Because drug side effects might impair performance, key crew members such as commanders, pilots and flight engineers are not allowed prelaunch antinauseants. But mission specialists often take a preflight dose of promethazine 25mg or 50mg, either on its own or with dexamfetamine. (Promethazine has also been used as an intramuscular injection or suppository to treat SMS symptoms during space flight.)
Alternative antinauseants such as dimenhydrinate and metoclopramide do not work as well as promethazine. Their variable success may, in part, be due to physiological changes that affect drug absorption and metabolism during space flight. For example, the weightlessness of gastric contents in space may reduce the movement of drugs out of the stomach, and microgravity may affect hepatic metabolism and renal excretion rates.
As well as nausea, astronauts risk dizziness and loss of balance caused by changes in gravity. By studying how these changes affect the brain, the inner ear, the senses and blood pressure, NASA hopes to develop treatments that can be used both in space and on earth to correct balance disorders. In
the meantime, NASA relies on midodrine to help astronauts cope with dizziness. This drug is normally indicated for symptomatic orthostatic hypotension and is widely used to help wean patients off intravenous vasopressive drugs. (It has also been suggested as a treatment for chronic fatigue syndrome.)
Astronauts also use modafinil to cope with fatigue and to optimise their performance. On earth, modafinil is used as a wakefulness-promoting drug to treat narcolepsy, shift work sleep disorder and daytime sleepiness associated with obstructive sleep apnoea. In space, astronauts use it as a psychostimulant when sleep is not an option. It is said to improve memory, brighten mood and enhance wakefulness, attention capacity and vigilance.
Also included in modern space travellers’ medical kits are tranquillisers for use if an astronaut gets the heebie-jeebies. Should a crew member become suicidal or psychotic, his companions are recommended to bind his wrists and ankles with duct tape, strap him down and administer a tranquilliser.
Other drugs are taken into space to counteract the longer-term side effects of microgravity. One of the more detrimental is the loss of bone m ass. As a means of slowing this effect, NASA is studying the use of bisphosphonates, such as zoledronate, which is normally used to prevent secondary bone tumours in cancer patients. Astronauts also take supplementary calcium and vitamin D to help maintain bone mass.
Back down to earth
Once back on earth, astronauts have to go through a rigorous quarantine procedure that involves the use of a range of disinfectants to kill off any virulent alien micro-organisms they may have brought back with them. And those returning from extended spells in space must go through a rehabilitation process because of microgravity’s adverse effects — not just bone demineralisation but also muscle atrophy, impaired co-ordination, cardiovascular deconditioning, altered hormone levels, orthostatic intolerance and even hallucinations. As Kevin Fong, co-director of the space medicine centre at University College London, has said: “Space really screws you up.”
Returning astronauts may need an immediate transfusion of normal saline to boost their blood pressure. They may also need help with walking and balance for at least a few days. And because up to 1 per cent of bone density is lost for every month spent in space, an astronaut returning from a long mission may take several years to recover from bone mass loss.
Research is being carried out to minimise the adverse effects of microgravity on astronauts. And it is widely expected that this will also lead to better treatments for some medical conditions on earth, particularly those suffered by bed-bound patients who, like astronauts, may develop osteoporosis, muscle wasting and orthostatic intolerance.
One problem with long-term space exploration is that some drugs have a shorter shelf-life in space than on earth. The pharmacy at NASA’s Johnson Space Centre (JSC) repacks drugs into special flight-certified containers, which are stored in compact flight kits. But — as all pharmacists know — repackaging can compromise stability. And on a space mission stability may also be affected by environmental factors such as ionising radiation, excessive vibration and multiple gravity conditions, in addition to variations in temperature and humidity.
A JSC investigation compared physical and chemical changes in 35 drug formulations stored in identical drug kits on the ISS and on earth. After 28 months in space, only 31 per cent of the flight kit drugs passed a potency test, compared with 54 per cent of the earthbound controls. Products that were particularly susceptible to rapid degradation in space included antibiotic combinations such as co-trimoxaxole and co-amoxiclav.
The researchers suggest that the accelerated degradation may be due, in part, to the radiation dose the drugs are exposed to, which is 20 times that experienced on earth. If research can determine why degradation is more rapid in space, it could lead to knock-on improvements in drug stability on earth.
Research at microgravity
In the early 1980s, as a junior PJ reporter, I began drafting an article about a proposed continuous flow electrophoresis process that would efficiently separate and purify biological materials on space shuttle flights. It would have been vastly more efficient in space than on earth, although it would never have been cheap. But before I could finish preparing my piece, ground-based processes had advanced so much that the space project was dropped.
Thirty years later, space still seems to offer little prospect for cost-efficient drug manufacture, but it certainly provides opportunities for research projects relevant to drug manufacture. Understanding how things work in microgravity can help improve earthbound processes, and researchers expect to be able to use space-based research to develop purer, stronger and safer forms of drugs for a wide range of diseases.
Space research is already helping medicine on earth through the development of new drug delivery systems. Experiments on the ISS have produced advances in micro-encapsulation — the technique of forming liquid-filled, biodegradable “microballoons” that can deliver drug solutions direct to a tumour, thus avoiding the unpleasant systemic effects of normal chemotherapy. The benefits of these microcapsules as a cancer treatment delivery system have led to the development of earth-based engineering strategies that produce microcapsules of similar quality. Microcapsules have also been produced to treat deep tissue infections and clotting disorders, and to deliver genetically engineered materials for potential gene therapy strategies.
Another valuable benefit of space orbit is that crystals can grow without being distorted by earth’s gravity. Researchers can produce perfect crystals of complex protein molecules and then use X-ray diffraction to determine their precise structure, providing valuable information for pharmacology research.
Microgravity also allows the growth of healthy three-dimensional tissue cultures in a liquid growth medium, mimicking the way tissues are structured in the human body. A spin-off from space research now allows similar cultures to be grown on earth. Researchers on earth were formerly limited to two-dimensional cultures grown on solid mediums because the need to stir a liquid medium to keep it from stagnating caused turbulence that damaged the delicate cells.
While working on a liquid medium bioreactor for use in space orbit, JSC researchers hit on a way to eliminate harmful turbulence in earth gravity by using a cylindrical bioreactor with a rotating wall — a development that is of great benefit to drug research and development.
Unfortunately, as well as allowing tissue cultures to grow more efficiently, microgravity allows pathogenic micro-organisms to grow and reproduce more rapidly. And research on the ISS has shown that they may also become more resistant to antimicrobials. One experiment found that a yeast dosed with voriconazole at a range of concentrations exhibited clear metabolic activity even at four times the minimum inhibitory concentration for earthbound controls.
NASA research aimed at protecting astronauts from virulent and drug-resistant micro-organisms has led to new findings about how pathogens act. As well as helping to safeguard future space travellers, the research is expected to aid the quest for advanced vaccines and better therapies to fight infection on earth.
What about recreational drugs in space? Caffeine seems to be acceptable, but alcohol is generally disapproved of, although it was certainly carried on early US space flights. In 1969, Buzz Aldrin drank communion wine on the moon. Although NASA has now banned alcohol, it is claimed that many US astronauts hit the bottle shortly before take-off.
Although the ISS is apparently alcohol-free, rumour has it that Russia’s Mir space station, which operated from 1986 to 2001, was supplied with copious stocks of cognac and vodka. The reserves of vodka supposedly available on Russian space stations featured in the recent sci-fi movie “Gravity”.
So what is the future of drug research in space? Because research carried out by orbiting astronauts is expensive, researchers investigating the effects of microgravity are instead developing tiny, free-flying satellites that can carry automated mini-laboratories. These dinky sputniks can easily be carried into space on a flight to the ISS and then launched into independent orbit. After carrying out their programmed microgravity experiments, and transmitting the results back to earth, they eventually drop out of orbit to be burnt up in the upper atmosphere.
As mentioned above, since the 1980s space has been seen as an option for drug manufacture processes that are highly efficient in microgravity. But the immense cost of carrying the starting materials into space and retrieving the finished product seems to make this idea a non-starter. Instead, drug companies should, perhaps, focus on using research in microgravity to improve manufacturing techniques on earth.
Research projects that are difficult or impossible in earth’s gravity are already helping to improve our understanding of biological and biochemical processes. This greater knowledge should lead to the development of innovative new drugs as well as sophisticated medical technologies.
Who knows? Space pharmacy may yet be a subject studied by budding pharmacists.
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Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2013.11132035
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