Removing gravity allows researchers to do experiments they could never duplicate on the ground
6 min
Medical research in space is leading to advances that could help patients on Earth.
Several technologies developed for space exploration have afterward contributed to medical products. Infrared thermometers, for example, stem from infrared sensors created to remotely measure the temperature of distant stars and planets.
But increasingly, scientists aim to perform research in space specifically for human health. Interest in conducting medical research in space has grown as researchers recognise possibilities enabled by microgravity, in which objects appear to be weightless, aboard the International Space Station, or ISS, which orbits the Earth about 250 miles from its surface.
Removing gravity’s influence alters biological systems, enabling experiments that can’t be done on the ground. Researchers are sending materials into space to study treatments for cancer, heart disease, neurological disorders, blindness and other conditions.
Such investigations extend beyond civilian medicine. With preparations under way for long-term missions to the moon, and eventually to Mars, scientists are advancing technologies to help astronauts endure extended space travel and confront illnesses and medical emergencies.
Several factors complicate space-based research. The cost of transporting materials, for one, as well as preparations needed to convert experiments conducted on Earth into ones that can be run on the ISS, which is itself a complicated partnership of five space agencies from 15 countries. The station has been occupied continuously since November 2000.
Space studies’ potential to discover cures and create tools that make healthcare more accessible justify the expense and complexity, some scientists say.
“Everything we do onboard has potential applications for healthcare on Earth,” says Dr. Dave Williams, who conducted neuroscience research on space shuttle Columbia, and is now chief executive of Leap Biosystems, a developer of medical devices for virtual clinical care in space and on Earth.
Space travel itself, for example, is known to cause bone and muscle loss, immune suppression, central nervous system changes and other effects. Detrimental as these effects are, they are of particular interest to scientists.
For the most part, health concerns astronauts develop in space resolve when they return, says Dr. Christopher Austin, former director of the National Center for Advancing Translational Sciences and now CEO of biotechnology startup Vesalius Therapeutics. Studying how this reversal occurs could provide insight on turning back the clock on disorders of ageing on Earth, he adds.
Exposure to microgravity seems to replicate the effects of aging at the cellular level, says Michael Roberts, chief scientific officer of the U.S. National Laboratory on the ISS. As a result, investigators in months can glean insights from studies that might require years of research on Earth.
“What happens in space is akin to accelerated ageing,” says Arun Sharma, assistant professor at the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center, who says his experience with space research includes sending stem-cell-derived heart cells to the ISS. “We can study these aging processes in a faster way in microgravity.”
Meantime, companies including drugmaker Merck and biotechnology concerns Axonis Therapeutics and LambdaVision aim to capitalise on microgravity to improve existing treatments or optimize experimental ones.
Merck has been conducting experiments aboard the ISS to determine whether it can come up with a crystalline form of an anticancer drug in its portfolio, Keytruda. The drug, which treats several cancers, generated $20.9 billion in sales in 2022. Patients receive it in 30-minute intravenous infusions. Its active ingredient, pembrolizumab, a large molecule known as a monoclonal antibody, isn’t highly soluble, so developing a high-concentration liquid formulation that can be given through a simple injection is difficult, says Paul Reichert, a Merck Research Laboratories scientist.
One solution is to produce it in crystallised form, a routine process for small-molecule drugs taken as pills. But making an optimal crystalline suspension is challenging for large-molecule, antibody drugs, Reichert says.
So Merck decided to attempt it in space. In 2017 it sent pembrolizumab to the ISS to see whether crystals would form better in space. Without gravity, molecules move more slowly and forces including convection currents are limited. Crystals produced on the ISS were smaller and more uniform than Earth counterparts, Reichert says.
On the ground, Merck identified techniques to mimic these effects and enable high-quality crystals. Now it is conducting long-term stability research to enable a Keytruda formulation that is injectable and, unlike today’s version, stable at room temperature. That would make it more accessible in areas with limited refrigeration.
Such studies will take years, but could lead to a lower-cost version of Keytruda that is easier to administer and cheaper to transport, Reichert says.
“That would be a game-changer for biologics drug delivery,” he adds.
Sometimes space research yields surprising results.
Biotech startup Angiex sought to better understand how an experimental cancer drug interacted with normal cells lining blood vessels, known as endothelial cells, says Paul Jaminet, co-founder, president and chief operating officer. The problem was these cells, when cultured on Earth, typically die quickly unless they are cultured with growth factors and changed to a proliferative state similar to that of endothelial cells in tumours. As a result, there is no good cell-culture model for the normal endothelial cells in which Angiex’s drugs are expected to have their toxicity, he says.
Angiex’s team hypothesised that culturing them in microgravity would be a solution, sending endothelial cells to the ISS in 2018. The cells did grow in space, but as they adapted to microgravity, they took on unusual characteristics that may not have a counterpart on Earth, Jaminet says.
The findings may advance understanding of how microgravity affects astronauts, he says. “In science, unexpected results are very precious,” he adds.
But since it appears the cells cultured in microgravity don’t resemble normal endothelial cells, and acquired a novel pathological state not previously seen, it isn’t yet clear if these cells are useful for drug-development purposes. Further work, he says, will be needed to understand this novel state and see if it is useful for understanding diseases on Earth.
“When you put cells into a completely new system, you’re going to get intended results and unintended results,” says Dr. Serena Auñón-Chancellor, an astronaut who worked on the Angiex research on the ISS, and a clinical associate professor of medicine for the LSU Health Sciences Center in Baton Rouge.
Axonis in August had good luck with a project to coax two kinds of human brain cells, neurons and astrocytes, to unite into a three-dimensional model of the brain in microgravity. It used the model to test a gene therapy designed to restore neural connections damaged by neurodegenerative diseases or spinal-cord injury.
The experiment provided evidence that Axonis’s gene therapy travels to its intended target, neurons, and avoids astrocytes, says co-founder and Chief Scientific Officer Shane Hegarty. In labs on Earth, neurons and astrocytes would form a carpet-like, two-dimensional layer. This doesn’t fully represent the brain’s complexity and is less useful for advancing the gene therapy, Hegarty adds.
The implications of this research are that scientists could use patients’ own cells to create models of their disease in space to speed their search for treatments, he says.
“For any drug-development effort, you need a good model first,” Hegarty says.
One long-term research program on the ISS is LambdaVision’s effort to restore vision to people blinded by diseases of the retina, the light-sensitive tissue at the back of the eye.
LambdaVision has flown eight payloads to the ISS since 2016, says Chief Scientific Officer Jordan Greco, adding that the company has found that its artificial retina seems to come together better in microgravity.
Microgravity enables more ordered and even packing of protein molecules onto the scaffold, CEO Nicole Wagner says. If its artificial retina, expected to enter clinical trials in about three years, earns regulatory approval, LambdaVision will manufacture it on the ISS or a commercial space station, she says.
Considering the demand for vision-restoration therapy, reimbursement from insurers should be sufficient to justify this expense, Wagner says. “With artificial retinas, there’s a clear unmet need,” she says.
To convert its lab process into one viable for the ISS, LambdaVision teamed with space-biotech company Space Tango to condense the process into a device that looks like a metal shoebox. The automated system contains proteins, polymers and solutions to assemble the artificial retina layers, and cameras that let researchers monitor and control the process from the ground, Wagner says.
Also using Space Tango is Encapsulate, a biotech with grant funding to launch into space biochips containing micro tumours made from patient cancer cells. The chips could predict an individual’s response to drugs, helping oncologists tailor treatment, Encapsulate co-founder and CEO Armin Rad says.
When adapting scientists’ projects for space “we have to take the human out of it and stuff it all into a box,” Space Tango Chief Strategy Officer Alain Berinstain says. Biotechs also express interest in the automated system for ground use, which was unexpected, he says. “It’s turned into a new business opportunity for us,” he adds.
The National Aeronautics and Space Administration plans a crewed mission to the lunar surface in 2025 and eventually a mission to Mars. Astronauts will require medications for the trip, and they can’t pack every drug they might need, says Phil Williams, a professor of biophysics in the School of Pharmacy at the University of Nottingham.
Medications degrade faster in space because of high radiation levels, says Williams, who is working with NASA researcher Lynn Rothschild on an astropharmacy, a briefcase-like system enabling astronauts to produce medications on demand.
In one version under study, cellular machinery that certain microbes use to make proteins would be combined with genetic sequences that code for specific biological medicines, Williams says. This could be paired with a production system to express the therapeutic protein and DNA-synthesis technology, he adds.
The notion of an astropharmacy extends to other extreme environments. If the technology proves effective in space it could also be used in hard-to-reach locations on Earth, he says.
“If we can make the drug for the astronaut, then we can make it for anybody,” Williams says.
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4 min
U.S. investors’ enthusiasm over Japanese stocks at this time last year turned out to be misplaced, but the market is again on the list of potential ways to diversify. Corporate shake-ups, hints of inflation after years of declining prices, and a trade battle could work in its favor.
Japanese stocks started 2024 off strong, but an unexpected interest-rate increase in August by the Bank of Japan triggered a sharp decline that the market has spent the rest of the year clawing back. Weakness in the yen has cut into returns in dollar terms. The iShares MSCI Japan ETF , which isn’t hedged, barely returned 7% last year, compared with 30% for the WisdomTree Japan Hedged Equity Fund .
The market is relatively cheap, trading at 15 times forward earnings, about where it was a decade ago, and events on the horizon could give it a boost. Masakazu Takeda, who runs the Hennessy Japan fund, expects earnings growth of mid-single digits—2% after inflation and an additional 2% to 3% as companies return more to shareholders through dividends and buybacks.
“We can easily get 10% plus returns if there’s no exogenous risks,” Takeda told Barron’s in December.
The first couple months of the year could be volatile as investors assess potential spoilers, such as whether the new Trump administration limits its tariff battle to China or goes wider, which would hurt Japan’s export-dependent market. The size of the wage increases labor unions secure in spring negotiations is another risk.
But beyond the headlines, fund managers and strategists see potential positive factors. First, 2024 will likely turn out to have been a record year for corporate earnings because some companies have benefited from rising prices and increasing demand, as well as better capital allocation.
In a note to clients, BofA strategist Masashi Akutsu said the market may again focus on a shift in corporate behavior that has begun to take place in recent years. For years, corporate culture has been resistant to change but recent developments—a battle over Seven & i Holdings that pits the founding family and investors against a bid from Canada’s Alimentation Couche-Tard , and Honda and Nissan ’s merger are examples—have been a wake-up call for Japanese companies to pursue overhauls. He expects a pickup in share buybacks as companies begin to think about shareholder returns more.
A record number of companies have also delisted, often through management buyouts, in another indication that corporate behavior is changing in favor of shareholders.
“Japan is attracting a lot of activist interest in a lot of different guises, says Donald Farquharson, head of the Japanese equities team for Baillie Gifford. “While shareholder proposals are usually unsuccessful, they do start in motion a process behind the scenes about the capital structure.”
For years, money-losing businesses were left alone in large corporations, but the recent spate of activism and focus on shareholder returns has pushed companies to jettison such divisions or take measures to improve them.
That isn‘t to say it is going to be an easy year. A more protectionist world could be problematic for sentiment.
But Japan’s approach could become a model for others in this new world. “Japan has spent the last 30 to 40 years investing in business overseas, with the automotive industry, for example, manufacturing a lot of the cars in the geographies it sells in,” Farquharson said. “That’s true of a lot of what Japan is selling overseas.”
Trade volatility that hits Japanese stocks broadly could offer opportunities. Concerns about tariffs could drag down companies such as Tokio Marine Holdings, which gets half its earnings by selling insurance in the U.S., but wouldn’t be affected by duties. Similarly, Shin-Etsu Chemicals , a silicon wafer behemoth that sells critical materials, including to the chip industry, is another potential winner, Takeda says.
If other companies follow the lead of Japanese exporters and set up shop in the markets they sell in, Japanese automation makers like Nidec and Keyence might benefit as a way to control costs in countries where wages are higher, Farquharson says.
And as Japanese workers get real wage growth and settle into living in an economy no longer in a deflationary rut, companies focused on domestic consumers such as Rakuten Group should benefit. The internet company offers retail and travel, both of which should benefit, but also is home to an online banking and investment platform.
Rakuten’s enterprise value—its market capitalization plus debt—is still less than its annual sales, in part because the company had been investing heavily in its mobile network. But that division is about to hit break even, Farquharson says.
A stock that stands to benefit from consumer spending and the waves or tourists the weak yen is attracting is Orix , a conglomerate whose businesses include an international airport serving Osaka. The company’s aircraft-leasing business also benefits from the production snags and supply-chain disruptions at Airbus and Boeing , Takeda says.
An added benefit: Its financial businesses stand to get a boost as the Bank of Japan slowly normalizes interest rates. The stock trades at about nine times earnings and about par for book value, while paying a 4% dividend yield.
Corrections & Amplifications: The past year is expected to turn out to have been a record one for corporate earnings in Japan. An earlier version of this article incorrectly gave the time frame as the 12 months through March. Separately, Masashi Akutsu is a strategist at BofA. An earlier version incorrectly identified his employer as UBS.
