Humans, and particularly space agencies, have long dreamed of landing on Mars and transforming science fiction into science fact.
However, governments and space agencies have learnt that achieving this feat is significantly more multifaceted in its complexity than it originally seemed. The significant challenges and setbacks that space agencies have faced in building space shuttles that can enter Mars’ atmosphere and land safely on the planet’s surface are only the tip of the iceberg.
One of the main issues facing space agencies as they prepare for longer and deeper space missions is tackling the adverse effects of long-term weightless on astronauts’ health.
Major concerns include the slowing of cardiovascular system functions, changes to the immune system and the deterioration of the skeleton, as well as the unknown impact of deep space radiation on the human body.
The necessity of just-in-time medicines
To support preparations for deep space missions like Mars, the US National Aeronautics and Space Administration (NASA) has tasked the Baylor College of Medicine-based Translational Research Institute for Space Health (TRISH) with finding “new approaches and new technologies for the challenges of deep space missions,” TRISH scientist and assistant professor at Baylor College of Medicine’s Centre for Space Medicine Dr Emmanuel Urquieta explains.
TRISH’s primary role is to select and fund early-stage, novel solutions for NASA’s high priority concerns regarding human health. One of these priorities is so-called just-in-time medications, which Urquieta describes as the capability to manufacture “medications from scratch and in real -time” on-board space missions.
Two of these on-demand medications projects recently received two-year funding from TRISH. The first is from the Massachusetts Institute of Technology (MIT) and creates just-in-time medications from gastric resident microbial systems, the second from the University of California, Davis (UC Davis) involves genetically modifying and growing lettuces to produce associated drugs.
Most commercially available medicines have shelf lives of two years or less. Urquieta explains that this is not currently an issue for astronauts residing in low orbit on or near to the International Space Station (ISS) because the ISS is kept fully stocked with medicines through monthly resupplies from earth.
However, this short shelf life poses a challenge for “deep space missions, such as the mission to Mars, [which] is going to be a three year mission, [where] you will need to take all the food, medications and water for the entire mission, because there is nowhere to stop to resupply,” he said.
Even if the shelf life of medications could be extended to more than three years, storage, mass and power limitations mean it is not possible for the spacecraft to carry a whole pharmacy of prescription and over-the-counter medications that the astronauts might need for three years, as well as provide sufficient refrigeration storage. Urquieta notes that NASA has a list of 100 conditions that could arise in deep space ranging from nail delamination to cardiac arrest.
As a result there is a need to move to develop the capacity to manufacture therapeutics on demand during a long, deep space mission. So if a medical condition arises then the astronauts can self-sufficiently and easily produce pharma products for administration within 24 hours.
The mother machine : manufacturing drugs within the stomach
One of the TRISH-funded just-in-time medicines projects is led by MIT’s David H Koch Institute professor Robert Langer and involves a gastric resident device called the “mother machine”.
This non-bulky drug delivery device is ingested by the astronauts in the same manner as an oral drug, it then resides in their stomach for a specific period and gradually releases the drug it manufactures into their body.
Langer’s proof of concept will involve using bacterium, such as E. Coli, which Urquieta explains “is currently used to manufacture insulin and other biologics”, to produce three medications – caffeine, melatonin and acetaminophen – within the device. These are all over-the-counter medications and are used to treat conditions such as headaches and other minor pains, as well as sleep disorders. It is hoped that this device’s capacity would be expanded to a broader range of conditions in the future.
This resident device has been designed by Langer to protect oral drugs from the harsh environment of the stomach and intestines, and to be broken down safely and passed through the patient’s digestive tract once the drug has been released.
After the two-years of funding have elapsed, Urquieta states TRISH hopes Langer’s device will be ready to move into testing and clinical trial stages to ensure it is “safe for human consumption”.
‘Grow your own’ drugs: lettuce-based genetically modified approaches
The second is a synthetic biology project led by UC Davis’ Karen McDonald based around genetically modifying ordinary lettuce so they can produce certain medications. This builds upon McDonald’s lab at the university, which looks into how to harness plants as biopharma factories.
Astronauts would grow the lettuce on the spacecraft, like is currently done on the ISS, meaning they will be “harvesting, smelling [and eating] fresh foods”, allowing them access to some of the comforts of the space station or earth and distracting them from the isolation of being on a space shuttle for three years; Urquieta believes this will bring an additional benefit linked to astronauts’ mental health.
The general concept is that if you need a medicine, the next time you grow a lettuce, you will grow it from seeds containing one of three genes – granulocyte-colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GMCSF) and parathyroid hormone (PTH) – and the lettuce will produce the medications you need. Urquieta notes that it is currently unclear how the drug will be extracted from the lettuce, it could be from eating it or through a different route.
GCSF and GMCSF would particularly useful in space as they increase the number of blood cells in the patients; on earth GCSF-based drugs are used to increase the number of certain blood cells before chemotherapy or a stem cell transplant, while GMCSF-based drugs are used after chemotherapy or transplants to support white blood cell recovery.
Therefore, drugs created from these genes could be useful in preventing the slowing of the CV system and changes in the immune system that occur from long-term weightlessness.
Value of just-in-time medicines on earth
It is important that the money being invested in innovations for protecting human health in space also have applications back on Earth. With regard to just-in-time medications, Urquieta states they could be transformative for “populations that are very isolated” from healthcare providers or pharmacies, such as in developing countries. They also have a defence industry application, as they provide the “potential to make medication in real time in the [battle] field”.
Langer is already studying whether a version of his resident device could replace inconvenient, long term regimes of multiple doses of drugs, which ultimately lead to high levels of non-adherence, especially where there is limited access to medical facilities.
He is focusing on malaria and tuberculosis (TB) currently; patients must undergo a two-week treatment regimen to be cured of malaria and six-month course of daily antibiotics for TB. However, he believes these “ultra-long-lasting oral systems…could have an effect on all kinds of diseases, such as Alzheimer’s or mental health disorders.”