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Launching medical research

A generation of drugs called monoclonal antibodies, also known as MABs, is altering the landscape of disease treatment by selectively targeting disease-causing agents and kick-starting immune cells. Using space-like conditions for further research may reveal ways to make drugs more targeted, concentrated and easier to administer.

MABs make up about one-third of protein-based therapeutics and are most often used to treat cancer and inflammation. They are widely regarded for their ability to target the specific protein of a pathogen and stop it from invading more cells. This means the therapy is tailored to the patient’s disease. The problem, however, is that patients need to get these drugs in large quantities over extended periods of time.

Proteins are too small to study under a microscope, so growing them into crystals lets researchers get a better understanding of their 3D constitution. Their makeup reveals how each protein works and how it contributes to disease scenarios. Once we understand this, drugs can be developed that mesh with the protein and fight the disease.

As well as being an important category of therapeutics, proteins are themselves drug targets. Drug companies need high-resolution protein structures to design suitable drugs.
This is where microgravity comes in.
Earth’s gravity can inhibit the growth and quality of crystals by affecting how the molecules position themselves on the exterior of the crystal. This makes space or a space-like environment ideal for this type of research.

AN INVOLVED PROCESS

David Sheehan, professor of biochemistry at Khalifa University, has been working on a method of crystalizing proteins for 12 years. His proteins are awaiting the arrival of vacuum chambers that mimic microgravity in a collaboration with Sean Shan Min Swei of the Department of Aerospace Engineering.

While turning proteins into crystals might seem like a cool magic trick, the process is quite involved. And many of the victories in successful crystallization can be attributed to time, patience and a lot of luck.

CAPTION: Crystals of protein furin grown on earth

Sheehan says initially, the protein is purified or separated from anything that might inhibit crystallization, like fatty materials from cells. The pH level is maintained for an optimum growth environment, and salt might be added to increase the ionic strength — or concentration — of the solution.

Other precipitants like polyethylene glycol or organic solvents, which decrease the protein solubility, are added. Then, the conditions are manipulated in a variety of ways, such as adjusting the temperature or exposure to gravity.

“The chemical additives and pH combined make up a condition. Most proteins only give crystals in a small number of conditions, so it is necessary to screen thousands of conditions to find the small number that will yield usable crystals,” Sheehan tells KUST Review.

And then it’s a waiting game — crystals might form in a week, a year or not at all.

Sheehan says researchers spend most of their time watching and hoping for a crystal, but most won’t see it: “When and if a crystal appears, then you’ve got a project.”

In his case, the crystals responded well to the addition of nanoparticles. While most of these types of experiments might typically result in one or two crystals from thousands, Sheehan’s team grew 15 crystals out of a panel of 16 proteins studied.

“We found one formulation that worked better than the others. So, then we used that nanoparticle with about 200 conditions,” he tells KUST Review.

This is unheard of, he says. And he knew they were on to something significant.

JOURNEY TO MICROGRAVITY

The project has a long history.

Sheehan grew his first nanoparticle-doped protein crystal over a decade ago, the result of an idea that had been brewing, a fridge full of available proteins, a student looking for a project and a friend with access to a synchrotron, a machine that uses electricity to create intense X-ray beams to study matter’s chemical and structural properties.

The student experimented with two nanoparticles, different from the ones used on the recent project: “The crystals grew very quickly and in the presence of a nanoparticle, they were larger, they grew faster, and they really grew. And that worked with both nanoparticles,” he says.

The stars (or crystals rather) aligned, and Sheehan and his student were soon transporting proteins to Dublin to a crystallographer friend who agreed to take them to the Paris synchrotron.

A synchrotron is about the size of a football field and is an ideal way to determine the three-dimensional atomic structure of a protein. It generates very intense X-ray beams that pass through a protein crystal and are scattered by the protein’s electrons.

CAPTION: https://kustreview.com/wp-content/uploads/2025/04/Launching-medical-research-intext-2.jpg

The crystal is rotated and a second scatter pattern is obtained. From these scatter patterns an atomic level structure can be calculated, Sheehan says.

FOCUS ON PROTEINS

But why are we so focused on proteins? Why not other molecules?

Proteins are the worker bees of a cell. They play an essential role in most biological systems and are responsible for most cellular functions. They are responsible for the shape, the interior design, production, cleanup, general upkeep and communication of cells. This makes them of great interest for targeted drug development, Sheehan says.

There are more than 130 protein-based therapeutics on the market, and the next step is to make them even better.

Current drugs for diseases like cancer, for example, require patients to take them for lengthy periods. Patients might sit in a clinic, hooked up to an IV for hours at a time, to ensure they get the right concentration of treatment. These treatments can go on for months or years. Imagine if patients could receive a simple injection in a doctor’s office.

“When and if a crystal appears, then you’ve got a project.”

– David Sheehan, professor of biochemistry at Khalifa University

And this type of drug development is dependent on research like that of Sheehan and his team.

Furin, for example, is a potential antiviral drug target for treating COVID-19.

Aside from the contributions to science, fighting disease and improving patient care, it could also mean a commercial venture.

“This could be very big,” Sheehan says. “I can see two options for commercialization, one of which is to market this as a crystallization screen and the other a start-up offering this as a service to pharmaceutical companies, biopharma and scientists around the world who have proteins they want to structure.”

With the team’s current success rate of more than 90 percent, it’s promising.

Sheehan and his researcher Salma Sultana Syed have patented their screen in the USA, UAE and Europe. They are exploring creating a start-up to be called ProScreenix. after incorporating a vast number of additional proteins into their research and changing up the nanoparticles using their current screen. This will create a more difficult problem, but test the method against a more robust array of challenges and hopefully improve the success rate. If you can’t take your proteins to space, bring space to your proteins.

Success is also dependent on microgravity, so Sheehan’s team will use space-simulation chambers that mimic these conditions, offering faster crystallization time and higher quality crystals.

The team is also hoping to acquire a robot that will help increase the number of conditions from 160 to approximately 1,000 and increase the number they can test daily. “At this point, when you get to that stage, you’re in the zone of talking about having a center for excellence,” Sheehan says.

Now they just need the right investors.

According to Allied Market Research, the protein therapeutics global market value is expected to reach U.S.$566.6 billion by 2030, up from U.S.$283.64 billion in 2020.

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Weightless wellness

Astronaut health care — prior to, during and post mission — has historically been served by specialized medical doctors called “flight surgeons.” While the name suggests surgeries are taking place in the air, it is rather misleading. But with longer space missions on the horizon, flight surgeons may soon be aptly named.

The role of flight surgeons, or aerospace medicine specialists, is varied but they are primarily responsible for the care of crews whether they are flying in space or in the air.

The current protocol is to stabilize the patient and send him or her back to Earth for medical intervention. That won’t work for a seven-month journey from Mars, so is it time for flight surgeons to up their game with actual surgery?

LISTEN TO THE DEEP DIVE

But what could go wrong? Doing surgery. In space. In microgravity.

The problem: There is little knowledge and even less experience. To date, there have been only minor procedures in space. But there is a lot of research focused on medical obstacles to deep-space, moon and Mars missions to come.

PREVENTING BLOOD LOSS

IMAGE: Freepik
What happens to the human body in space?

On Earth, we spend our days walking from room to room, home to car, car to office, running around the office, exercising and running errands. Every single step includes flexion and extension at the hip, knee, and ankle, involving 200 muscles. Read more›››

Strong muscles contribute to bone density health. The stronger a muscle is, the more it pulls on the bones it’s attached to, making them stronger.

This also means the weaker the muscles, the weaker the bones. So imagine if you were just floating about your day and not using any of the muscles or joints your body was designed for. What might happen to those muscles? And those bones?

According to NASA, lengthy stays in space can lead to muscle atrophy (loss) — a condition that astronauts aim to avoid with intensive strength-training sessions during missions on the International Space Station. Astronauts on a mission from five to 11 days can lose up to 20 percent of their body’s muscle mass. Short-term missions don’t have much impact on bone-density loss but longer missions do — and the effects are really noticeable upon return to Earth.

The normal weight bearing on the skeletal system on Earth can be a shock to weakened bones and would put them at higher risk of breakage and for osteoporosis. This risk factor continues to be an obstacle for long-term space stays for astronauts, with a monthly average of 1 to 2 percent bone mineral density loss. The World Health Organization says that an osteoporosis diagnosis is based on a 25 percent deficit on the average bone density of a 30-year-old. And osteoporosis is not reversible.

The International Space Station orbits the Earth at 400 kilometers from sea level and can be reached in anywhere from four hours to several days. NASA estimates a journey to Mars will take approximately seven months. This means by the time astronauts reach Mars, they could experience a 20 percent mineral loss.

But flight surgeons counter this with rigorous cardiovascular exercise and resistance training up to two hours daily. And after a six-month stay on the International Space Station, astronauts return with minimal loss.

Dr. Sergi Vaquer Araujo of the European Space Agency says the hydraulic resistance machines to maintain muscle mass and strength enable the astronauts to walk very quickly after their return to Earth.

“They all lose bone, but the amount is always within a very big safety margin that would classify as a normal human bone mineral density,” Vaquer Araujo tells KUST Review.

“All in all, what I’m trying to say is that if you look at the commonalities on how to treat those three things, bone, muscle and heart and vessels, they all benefit from exercise, our main drug, and we treat it as a drug.

“So that means what we’re doing in space works for six months, the one-year mission (on the Russian and American side) showed that, yes, it (effects of time in microgravity) is more pronounced, but still within manageable ranges.”‹‹‹ Read less

Innovations are underway to prevent blood or other fluids escaping the surgical site in microgravity conditions.

A surgical fluid management system developed by the astrosurgical team at University of Louisville in the United States was tested in 2021 aboard a Virgin Galactic flight. The technology, funded by NASA’s program to prepare for long missions, is basically a dome that fits over the surgical site to contain fluid. It is fitted with specific points where surgical instruments can be inserted without fluid escaping.

The fully automated test included injecting a blood-like fluid into the dome and manipulating the pressure within it to control bleeding. But the technology is multi-faceted and included tests of its irrigation abilities, suction and ability to vacate fluids from the dome. The dome keeps fluid in but also protects the surgical site from contaminants.

George Pantalos, head of the University of Louisville’s astrosurgery team, said the device operated as expected. “There was a little bit of variation in how things worked compared to gravity on Earth, but they weren’t showstoppers by any means.”

The team is also working on ways to allow non-surgeons to perform emergency surgeries as well as a space-saving 3D printer that will print recyclable surgical tools.

SURGICAL ROBOTS

Another potential path to success: robotic surgeries.

Remotely operated surgical robot MIRA (Miniature In-Vivo Robotic Assistant), created by Virtual Incisions’ Shane Farritor, will make a jaunt to the International Space Station for testing in 2024.

The tiny MIRA robot will conduct small surgical-type functions inside a small compartment with simulated materials.

Robotic surgeries contain the internal organs and bodily fluids while reducing contamination. They also offer less invasive procedures with quicker recovery time, which means lower risk of infection – especially important considering microgravity’s damaging effects on the human immune system.

MICROGRAVITY AND WOUNDS

Microgravity also appears to have an effect on wound healing. Current research indicates slowed cellular growth and decrease in collagen fibers. A 2022 paper published in Nature suggests that time spent in space leads to a reduction in red blood cell count in astronauts — a condition known as anemia. Oxygen-rich red blood cells are instrumental in building tissue for wound healing.

Space anemia was originally thought to be caused by initial exposure to microgravity resulting from bodily fluids shifting upward. Further research, however, shows that the anemia is present during and after exposure. This also should be considered for surgical aftercare on long-term missions.

These are only a handful of challenges.

Then there is the matter of who is going to perform such surgeries. Currently medical officers on board spacecraft aren’t doctors — they are flight crew with 60 hours of medical training. Flight surgeons monitoring the health of astronauts currently do so from the ground.

Flight surgeons for astronauts aren’t typically astronauts themselves or surgeons for that matter. If flight surgery is in your path, however, you are in for a bit of a long haul. On top of a four-year degree, four years of medical school and three years of residency, it will be another two years of specializing in space medicine to reach the final frontier, says NASA flight surgeon Rick Sheuring in an interview with the University of Strathclyde in Glasgow, Scotland.

That’s a 13-year journey, plus astronaut training. But it could just land you on the cutting edge of space-medicine development.

THE CURE

Though many of these developments are in process, Dr. Sergi Vaquer Araujo, intensive care medicine specialist and leader of the European Space Agency’s space medicine team, says there will be limits to what can be done. This means astronauts will have to accept that there are health issues that simply can’t be properly addressed in space.

But some conditions can be anticipated and prepared for.

Vaquer Araujo’s team works closely with NASA to prepare a kit that will address as many likely emergent scenarios as possible. Not necessarily open-cavity surgeries, but treating illnesses and performing procedures, such as suturing small wounds or extracting teeth, that have been performed on the International Space Station.

“Imagine a micrometeorite penetrates the vehicle and penetrates the chest of an astronaut, for instance, and then not having the tools to manage that. That would be a pity, and the person dies because I didn’t have the tools,” Vaquer Araujo says.

What tools to take to space can be a high-stakes guessing game.

“That’s a very frustrating thing, but one has to be also realistic, and if you cannot have everything you need to assess the chances of that happening and if the chances are low, you need to take a gamble,” he tells KUST Review.

IMAGE: Abjad Design

He says astronauts are well aware of the risks, but as a doctor, there are still ethical concerns with sending people on a mission without every possible means to maintain their health and safety.

The European Space Agency and NASA have different approaches to how they build their medical kits, but they are complementary. The organizations continue to work to combine them.

The philosophy goes something like this: It’s not what happens, it’s what the body needs to solve the problem.

“For example, if I’m bleeding, what I need is to stop the bleeding and administer fluids. But if I have septic shock, meaning I have a completely uncontrolled infection, I also need fluid and I will also need the same tools for both things to know the status,” he says.

“What this all means is when you’re in a critical medical situation and conditions escalate to a failure of a system, those failures are diagnosed with almost the same tools. So, our approach is to try to find all those commonalities and build our kit, so at least we have something to treat those commonalities. So, you do not think whether this could be a micrometeorite that penetrates the chest — you just know that if you have insufficient lung function, you will need oxygen,” Vaquer Araujo says.

OTHER THINGS TO CONSIDER

He is encouraged by the fact that the ESA’s kit and NASA’s are in line up to 90 percent now. They also agree that at this stage, major surgery in space is not feasible. And the challenges of microgravity are not necessarily the major concerns.

For complicated open surgeries, a full operating room is imperative, which means more space in space is required.

But this space would also require an amount of flammable oxygen that would put the entire crew at risk.

Also to consider are the sterilization capabilities, which Vaquer Araujo believes is the biggest concern.

You also need the skill of an actual surgeon on board, but what if that surgeon is the patient? And what type of medical doctor do you put on board as the surgeon? What if you place an internal medicine doctor in the field and there is a trauma issue? And that ”surgeon” spends the two years prior to the mission training as an astronaut but not treating patients — what risks does two years away from practicing pose?

The list of questions is unending. The cure, it seems, is time, innovation and a lot of money.