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.

Justifying the expense

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.”

Anticancer drug

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.

Surprising results

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.

Restoring sight

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.

The new iPhone models unveiled last week are missing a proprietary silicon chip that Apple had spent several years and billions of dollars trying to develop in time for the rollout.

The 2018 marching orders from Apple Chief Executive Tim Cook to design and build a modem chip—a part that connects iPhones to wireless carriers—led to the hiring of thousands of engineers. The goal was to sever Apple’s grudging dependence on Qualcomm, a longtime chip supplier that dominates the modem market.

The obstacles to finishing the chip were largely of Apple’s own making, according to former company engineers and executives familiar with the project.

Apple had planned to have its modem chip ready to use in the new iPhone models. But tests late last year found the chip was too slow and prone to overheating. Its circuit board was so big it would take up half an iPhone, making it unusable.

Investors had counted on Apple saving money with an in-house chip to help compensate for weak demand in the larger smartphone market. Apple—which hasn’t publicly acknowledged its modem project, much less its shortcomings—is estimated to have paid more than $7.2 billion to Qualcomm last year for the chips.

Engineering teams working on Apple’s modem chip have been slowed by technical challenges, poor communication and managers split over the wisdom of trying to design the chips rather than buy them, these people said. Teams were siloed in separate groups across the U.S. and abroad without a global leader. Some managers discouraged the airing of bad news from engineers about delays or setbacks, leading to unrealistic goals and blown deadlines.

“Just because Apple builds the best silicon on the planet, it’s ridiculous to think that they could also build a modem,” said former Apple wireless director Jaydeep Ranade, who left the company in 2018, the year the project began.

There were two reasons for the push, said former Apple executives and engineers familiar with the matter: Apple believed it could replicate the success of the microprocessor chips it designed for iPhones. Adoption of those chips fattened profit margins and improved performance for billions of devices. Second, Apple wanted to sever ties with Qualcomm, which it had accused in a 2017 lawsuit of overcharging for its patent royalties.

The companies settled the suit in 2019, and Apple, facing the expiration of its previous Qualcomm agreement, announced a deal last week to continue buying the company’s modem chips through 2026. Apple isn’t expected to produce a comparable chip until late 2025, people familiar with the matter said. There could be further delays, these people said, but the company believes it will eventually succeed.

Apple found that designing a microprocessor, essentially a tiny computer to run software, was easy by comparison. Modem chips, which transmit and receive wireless data, must comply with strict connectivity standards to serve wireless carriers around the world.

“These delays indicate Apple didn’t anticipate the complexity of the effort,” said Serge Willenegger, a former longtime Qualcomm executive who left the company in 2018 and doesn’t know the current state of the Apple chip. “Cellular is a monster.”

Apple’s push to build more of the various semiconductors used in its products stretches back more than a decade. In 2010, the company began using its own processing chips in iPhones and iPads. The chips helped Apple outperform many of its Android rivals, which relied on chips from Qualcomm, Taiwan-based MediaTek and other makers.

The company in 2020 began replacing processor chips from Intel, used for years in Mac computers, with a proprietary chip that allowed its laptops to run faster and generate less heat, improvements that helped boost flagging Mac sales. The Apple chip also saved the company an estimated $75 to $150 on every computer.

Credit for the success of Apple processor chips brought praise and increased authority to Johny Srouji, the company’s chip leader. “After shipping the first iPhone, we decided that the best way to deliver the best experience to our customers is to own and develop and design our silicon in-house,” Srouji said this year at Technion-Israel Institute of Technology, his alma mater.

Split screen

Apple code-named its modem chip project Sinope, after the nymph in Greek mythology who outsmarted Zeus. It began taking shape in 2018, following the directive of Cook, Srouji, and others for Apple to build its own wireless components, said Chris Deaver, a former Apple human-resources executive and co-founder of BraveCore consultants.

By then, Apple’s relationship with Qualcomm had turned ugly. The companies bickered and swapped accusations of lying, theft and monopolistic practices.

Rubén Caballero, Apple’s longtime head of wireless, supported the Intel chip partnership at the time, while Srouji, senior vice president of hardware technologies, backed the pursuit of a company-built chip, said people involved in the project. Caballero left Apple in 2019.

Many members of Caballero’s team who were versed in wireless chip design were placed under Srouji. Other employees engaged in complementary wireless work, such as antenna design, were split off into the hardware engineering group. One of the top project managers on Srouji’s team had no background in wireless technology, said people who worked on the project.

Apple, which had been poaching engineering talent from Qualcomm for years, stepped up those efforts in March 2019. The company announced a new engineering hub in San Diego, Qualcomm’s hometown, and planned to add around 1,200 local jobs. That summer, Apple announced the acquisition of Intel’s wireless team and a portfolio of wireless patents.

Srouji flew to Munich to greet Apple’s newly acquired Intel wireless employees in December 2019. He told a gathering that the modem-chip project would be a game changer for Apple, the next step in the company’s evolution, said people who watched the meeting. He said the chip would distinguish Apple devices, as Apple’s processors had done.

As Apple filled the project’s ranks with Intel engineers and others hired from Qualcomm, company executives set a goal to have the modem chip ready for fall 2023. It soon became apparent to many of the wireless experts on the project that meeting the goal was impossible.

Apple found that employing the brute force of thousands of engineers, a strategy successful for designing the computer brain of its smartphones and laptops, wasn’t enough to quickly produce a superior modem chip.

Tall order

Modem chips are trickier to make than processing chips because they must work seamlessly with 5G wireless networks, as well as the 2G, 3G and 4G networks used in countries around the world, each with its own technological quirks. Apple microprocessors run software programs designed solely for its iPhones and laptops.

Apple executives who didn’t have experience with wireless chips set tight timelines that weren’t realistic, former project engineers said. Teams had to build prototype versions of the chips and certify they would work with the many wireless carriers worldwide, a time-consuming job.

Executives better understood the challenge after Apple tested its prototypes late last year. The results weren’t good, according to people familiar with the tests. The chips were essentially three years behind Qualcomm’s best modem chip. Using them threatened to make iPhone wireless speeds slower than its competitors.

The company scratched plans to use the chips in Apple’s 2023 models, and the planned rollout was moved to 2024. Eventually, Apple executives realised the company wouldn’t meet that goal either. Apple instead opened negotiations with Qualcomm to continue supplying the modem chips. Apple’s licensing deal with Qualcomm expires in April 2025, though it can be extended for another two years.

Apple has the cash and the desire to keep pursuing its modem chip, according to people involved with the project.

“Apple isn’t going to give up,” said Edward Snyder, a managing director of Charter Equity Research and a wireless industry expert. “They hate Qualcomm’s living guts.”

On Wednesday, Federal Reserve officials surprised markets by signalling interest rates won’t fall as much as previously planned.

The tweak might be more important than it looks. In their projections and commentary, some officials hint that rates might be higher not just for longer, but forever. In more technical terms, the so-called neutral rate, which keeps inflation and unemployment stable over time, has risen.

This matters to any investor, business or household whose plans depend on interest rates over a decade or longer. It could explain why long-term Treasury yields have risen sharply in the past few months, and why stocks are struggling.

The neutral rate isn’t literally forever, but that captures the general idea. In the long run neutral is a function of very slow moving forces: demographics, the global demand for capital, the level of government debt and investors’ assessments of inflation and growth risks.

The neutral rate can’t be observed, only inferred by how the economy responds to particular levels of interest rates. If current rates aren’t slowing demand or inflation, then neutral must be higher and monetary policy isn’t tight.

Indeed, on Wednesday, Fed Chair Jerome Powell allowed that one reason the economy and labor market remain resilient despite rates between 5.25% and 5.5% is that neutral has risen, though he added: “We don’t know that.”

Before the 2007-09 recession and financial crisis, economists thought the neutral rate was around 4% to 4.5%. After subtracting 2% inflation, the real neutral rate was 2% to 2.5%. In the subsequent decade, the Fed kept interest rates near zero, yet growth remained sluggish and inflation below 2%. Estimates of neutral began to drop. Fed officials’ median estimate of the longer-run fed-funds rate—their proxy for neutral—fell from 4% in 2013 to 2.5% in 2019, or 0.5% in real terms.

As of Wednesday, the median estimate was still 2.5%. But five of 18 Fed officials put it at 3% or higher, compared with just three officials in June and two last December.

In 2026, officials project the economy growing at its long-term rate of 1.8%, unemployment at its long-run natural level of 4%, and inflation at its 2% target. Those conditions would normally be consistent with interest rates at neutral. As it happens, officials think the fed-funds rate will end the year at 2.9%—another hint they think neutral has risen.

There are plenty of reasons for a higher neutral. After the global financial crisis, businesses, households and banks were paying down debt instead of borrowing, reducing demand for savings while holding down growth and inflation. As the crisis faded, so did the downward pressure on interest rates.

Another is government red ink: Federal debt held by the public now stands at 95% of gross domestic product, up from 80% at the start of 2020, and federal deficits are now 6% of GDP and projected to keep rising, from under 5% before the pandemic. To get investors to hold so much more debt probably requires paying them more. The Fed bought bonds after the financial crisis and again during the pandemic to push down long-term interest rates. It is now shedding those bond holdings.

Inflation should not, by itself, affect the real neutral rate. However, before the pandemic the Fed’s principal concern was that inflation would persist below 2%, a situation that makes it difficult to stimulate spending and can lead to deflation, and that is why it kept rates near zero from 2008 to 2015. In the future it will worry more that inflation persists above 2%, and err on the side of higher rates with little appetite for returning to zero.

Other factors are still pressing down on neutral, such as an aging world population, which reduces demand for homes and capital goods to equip workers.

So neutral has probably risen since 2019, but not to its pre-2008 level. Indeed, futures markets peg rates a decade from now at around 3.75%.

Of course, this is all just a forecast. If inflation comes down painlessly in the next year, if growth slows abruptly, or if Treasury yields drop, then estimates of neutral will also come down. For now, the evidence suggests the public should get used to higher rates as far as the eye can see.