Eight Big Medical and Science Trends to Watch in 2021
The world as we know it has forever changed. With a greater focus on science and technology than before, experts in the biotech and life sciences spaces are grappling with what comes next as SARS-CoV-2, the coronavirus that causes the COVID-19 illness, has spread and mutated across the world.
Even with vaccines being distributed, so much still remains unknown.
Jared Auclair, Technical Supervisor for the Northeastern University's Life Science Testing Center in Burlington, Massachusetts, guides a COVID testing lab that cranks out thousands of coronavirus test results per day. His lab is also focused on monitoring the quality of new cell and gene therapy products coming to the market.
Here are trends Auclair and other experts are watching in 2021.
Better Diagnostic Testing for COVID
Expect improvements in COVID diagnostic testing and the ability to test at home.
There are currently three types of coronavirus tests. The molecular test—also known as the RT-PCR test, detects the virus's genetic material, and is highly accurate, but it can take days to receive results. There are also antibody tests, done through a blood draw, designed to test whether you've had COVID in the past. Finally, there's the quick antigen test that isn't as accurate as the PCR test, but can identify if people are going to infect others.
Last month, Lucira Health secured the U.S. FDA Emergency Use Authorization for the first prescription molecular diagnostic test for COVID-19 that can be performed at home. On December 15th, the Ellume Covid-19 Home Test received authorization as the first over-the-counter COVID-19 diagnostic antigen test that can be done at home without a prescription. The test uses a nasal swab that is connected to a smartphone app and returns results in 15-20 minutes. Similarly, the BinaxNOW COVID-19 Ag Card Home Test received authorization on Dec. 16 for its 15-minute antigen test that can be used within the first seven days of onset of COIVD-19 symptoms.
Home testing has the possibility to impact the pandemic pretty drastically, Auclair says, but there are other considerations: the type and timing of test that is administered, how expensive is the test (and if it is financially feasible for the general public) and the ability of a home test taker to accurately administer the test.
"The vaccine roll-out will not eliminate the need for testing until late 2021 or early 2022."
Ideally, everyone would frequently get tested, but that would mean the cost of a single home test—which is expected to be around $30 or more—would need to be much cheaper, more in the $5 range.
Auclair expects "innovations in the diagnostic space to explode" with the need for more accurate, inexpensive, quicker COVID tests. Auclair foresees innovations to be at first focused on COVID point-of-care testing, but he expects improvements within diagnostic testing for other types of viruses and diseases too.
"We still need more testing to get the pandemic under control, likely over the next 12 months," Auclair says. "The vaccine roll-out will not eliminate the need for testing until late 2021 or early 2022."
Rise of mRNA-based Vaccines and Therapies
A year ago, vaccines weren't being talked about like they are today.
"But clearly vaccines are the talk of the town," Auclair says. "The reason we got a vaccine so fast was there was so much money thrown at it."
A vaccine can take more than 10 years to fully develop, according to the World Economic Forum. Prior to the new COVID vaccines, which were remarkably developed and tested in under a year, the fastest vaccine ever made was for mumps -- and it took four years.
"Normally you have to produce a protein. This is typically done in eggs. It takes forever," says Catherine Dulac, a neuroscientist and developmental biologist at Harvard University who won the 2021 Breakthrough Prize in Life Sciences. "But an mRNA vaccine just enabled [us] to skip all sorts of steps [compared with burdensome conventional manufacturing] and go directly to a product that can be injected into people."
Non-traditional medicines based on genetic research are in their infancy. With mRNA-based vaccines hitting the market for the first time, look for more vaccines to be developed for whatever viruses we don't currently have vaccines for, like dengue virus and Ebola, Auclair says.
"There's a whole bunch of things that could be explored now that haven't been thought about in the past," Auclair says. "It could really be a game changer."
Vaccine Innovation over the last 140 years.
Max Roser/Our World in Data (Creative Commons license)
Advancements in Cell and Gene Therapies
CRISPR, a type of gene editing, is going to be huge in 2021, especially after the Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna in October for pioneering the technology.
Right now, CRISPR isn't completely precise and can cause deletions or rearrangements of DNA.
"It's definitely not there yet, but over the next year it's going to get a lot closer and you're going to have a lot of momentum in this space," Auclair says. "CRISPR is one of the technologies I'm most excited about and 2021 is the year for it."
Gene therapies are typically used on rare genetic diseases. They work by replacing the faulty dysfunctional genes with corrected DNA codes.
"Cell and gene therapies are really where the field is going," Auclair says. "There is so much opportunity....For the first time in our life, in our existence as a species, we may actually be able to cure disease by using [techniques] like gene editing, where you cut in and out of pieces of DNA that caused a disease and put in healthy DNA," Auclair says.
For example, Spinal Muscular Atrophy is a rare genetic disorder that leads to muscle weakness, paralysis and death in children by age two. As of last year, afflicted children can take a gene therapy drug called Zolgensma that targets the missing or nonworking SMN1 gene with a new copy.
Another recent breakthrough uses gene editing for sickle cell disease. Victoria Gray, a mom from Mississippi who was exclusively followed by NPR, was the first person in the United States to be successfully treated for the genetic disorder with the help of CRISPR. She has continued to improve since her landmark treatment on July 2, 2019 and her once-debilitating pain has greatly eased.
"This is really a life-changer for me," she told NPR. "It's magnificent."
"You are going to see bigger leaps in gene therapies."
Look out also for improvements in cell therapies, but on a much lesser scale.
Cell therapies remove immune cells from a person or use cells from a donor. The cells are modified or cultured in lab, multiplied by the millions and then injected back into patients. These include stem cell therapies as well as CAR-T cell therapies, which are typically therapies of last resort and used in cancers like leukemia, Auclair says.
"You are going to see bigger leaps in gene therapies," Auclair says. "It's being heavily researched and we understand more about how to do gene therapies. Cell therapies will lie behind it a bit because they are so much more difficult to work with right now."
More Monoclonal Antibody Therapies
Look for more customized drugs to personalize medicine even more in the biotechnology space.
In 2019, the FDA anticipated receiving more than 200 Investigational New Drug (IND) applications in 2020. But with COVID, the number of INDs skyrocketed to 6,954 applications for the 2020 fiscal year, which ended September 30, 2020, according to the FDA's online tracker. Look for antibody therapies to play a bigger role.
Monoclonal antibodies are lab-grown proteins that mimic or enhance the immune system's response to fight off pathogens, like viruses, and they've been used to treat cancer. Now they are being used to treat patients with COVID-19.
President Donald Trump received a monoclonal antibody cocktail, called REGEN-COV2, which later received FDA emergency use authorization.
A newer type of monoclonal antibody therapy is Antibody-Drug Conjugates, also called ADCs. It's something we're going to be hearing a lot about in 2021, Auclair says.
"Antibody-Drug Conjugates is a monoclonal antibody with a chemical, we consider it a chemical warhead on it," Auclair says. "The monoclonal antibody binds to a specific antigen in your body or protein and delivers a chemical to that location and kills the infected cell."
Moving Beyond Male-Centric Lab Testing
Scientific testing for biology has, until recently, focused on testing males. Dulac, a Howard Hughes Medical Investigator and professor of molecular and cellular biology at Harvard University, challenged that idea to find brain circuitry behind sex-specific behaviors.
"For the longest time, until now, all the model systems in biology, are male," Dulac says. "The idea is if you do testing on males, you don't need to do testing on females."
Clinical models are done in male animals, as well as fundamental research. Because biological research is always done on male models, Dulac says the outcomes and understanding in biology is geared towards understanding male biology.
"All the drugs currently on the market and diagnoses of diseases are biased towards the understanding of male biology," Dulac says. "The diagnostics of diseases is way weaker in women than men."
That means the treatment isn't necessarily as good for women as men, she says, including what is known and understood about pain medication.
"So pain medication doesn't work well in women," Dulac says. "It works way better in men. It's true for almost all diseases that I know. Why? because you have a science that is dominated by males."
Although some in the scientific community challenge that females are not interesting or too complicated with their hormonal variations, Dulac says that's simply not true.
"There's absolutely no reason to decide 50% of life forms are interesting and the other 50% are not interesting. What about looking at both?" says Dulac, who was awarded the $3 million Breakthrough Prize in Life Sciences in September for connecting specific neural mechanisms to male and female parenting behaviors.
Disease Research on Single Cells
To better understand how diseases manifest in the body's cell and tissues, many researchers are looking at single-cell biology. Cells are the most fundamental building blocks of life. Much still needs to be learned.
"A remarkable development this year is the massive use of analysis of gene expression and chromosomal regulation at the single-cell level," Dulac says.
Much is focused on the Human Cell Atlas (HCA), a global initiative to map all cells in healthy humans and to better identify which genes associated with diseases are active in a person's body. Most estimates put the number of cells around 30 trillion.
Dulac points to work being conducted by the Cell Census Network (BICCN) Brain Initiative, an initiative by the National Institutes of Health to come up with an atlas of cell types in mouse, human and non-human primate brains, and the Chan Zuckerberg Initiative's funding of single-cell biology projects, including those focused on single-cell analysis of inflammation.
"Our body and our brain are made of a large number of cell types," Dulac says. "The ability to explore and identify differences in gene expression and regulation in massively multiplex ways by analyzing millions of cells is extraordinarily important."
Converting Plastics into Food
Yep, you heard it right, plastics may eventually be turned into food. The Defense Advanced Research Projects Agency, better known as DARPA, is funding a project—formally titled "Production of Macronutrients from Thermally Oxo-Degraded Wastes"—and asking researchers how to do this.
"When I first heard about this challenge, I thought it was absolutely absurd," says Dr. Robert Brown, director of the Bioeconomy Institute at Iowa State University and the project's principal investigator, who is working with other research partners at the University of Delaware, Sandia National Laboratories, and the American Institute of Chemical Engineering (AIChE)/RAPID Institute.
But then Brown realized plastics will slowly start oxidizing—taking in oxygen—and microorganisms can then consume it. The oxidation process at room temperature is extremely slow, however, which makes plastics essentially not biodegradable, Brown says.
That changes when heat is applied at brick pizza oven-like temperatures around 900-degrees Fahrenheit. The high temperatures get compounds to oxidize rapidly. Plastics are synthetic polymers made from petroleum—large molecules formed by linking many molecules together in a chain. Heated, these polymers will melt and crack into smaller molecules, causing them to vaporize in a process called devolatilization. Air is then used to cause oxidation in plastics and produce oxygenated compounds—fatty acids and alcohols—that microorganisms will eat and grow into single-cell proteins that can be used as an ingredient or substitute in protein-rich foods.
"The caveat is the microorganisms must be food-safe, something that we can consume," Brown says. "Like supplemental or nutritional yeast, like we use to brew beer and to make bread or is used in Australia to make Vegemite."
What do the microorganisms look like? For any home beer brewers, it's the "gunky looking stuff you'd find at the bottom after the fermentation process," Brown says. "That's cellular biomass. Like corn grown in the field, yeast or other microorganisms like bacteria can be harvested as macro-nutrients."
Brown says DARPA's ReSource program has challenged all the project researchers to find ways for microorganisms to consume any plastics found in the waste stream coming out of a military expeditionary force, including all the packaging of food and supplies. Then the researchers aim to remake the plastic waste into products soldiers can use, including food. The project is in the first of three phases.
"We are talking about polyethylene, polypropylene, like PET plastics used in water bottles and converting that into macronutrients that are food," says Brown.
Renewed Focus on Climate Change
The Union of Concerned Scientists say carbon dioxide levels are higher today than any point in at least 800,000 years.
"Climate science is so important for all of humankind. It is critical because the quality of life of humans on the planet depends on it."
Look for technology to help locate large-scale emitters of carbon dioxide, including sensors on satellites and artificial intelligence to optimize energy usage, especially in data centers.
Other technologies focus on alleviating the root cause of climate change: emissions of heat-trapping gasses that mainly come from burning fossil fuels.
Direct air carbon capture, an emerging effort to capture carbon dioxide directly from ambient air, could play a role.
The technology is in the early stages of development and still highly uncertain, says Peter Frumhoff, director of science and policy at Union of Concerned Scientists. "There are a lot of questions about how to do that at sufficiently low costs...and how to scale it up so you can get carbon dioxide stored in the right way," he says, and it can be very energy intensive.
One of the oldest solutions is planting new forests, or restoring old ones, which can help convert carbon dioxide into oxygen through photosynthesis. Hence the Trillion Trees Initiative launched by the World Economic Forum. Trees are only part of the solution, because planting trees isn't enough on its own, Frumhoff says. That's especially true, since 2020 was the year that human-made, artificial stuff now outweighs all life on earth.
More research is also going into artificial photosynthesis for solar fuels. The U.S. Department of Energy awarded $100 million in 2020 to two entities that are conducting research. Look also for improvements in battery storage capacity to help electric vehicles, as well as back-up power sources for solar and wind power, Frumhoff says.
Another method to combat climate change is solar geoengineering, also called solar radiation management, which reflects sunlight back to space. The idea stems from a volcanic eruption in 1991 that released a tremendous amount of sulfate aerosol particles into the stratosphere, reflecting the sunlight away from Earth. The planet cooled by a half degree for nearly a year, Frumhoff says. However, he acknowledges, "there's a lot of things we don't know about the potential impacts and risks" involved in this controversial approach.
Whatever the approach, scientific solutions to climate change are attracting renewed attention. Under President Trump, the White House Office of Science and Technology Policy didn't have an acting director for almost two years. Expect that to change when President-elect Joe Biden takes office.
"Climate science is so important for all of humankind," Dulac says. "It is critical because the quality of life of humans on the planet depends on it."
Scientists are making machines, wearable and implantable, to act as kidneys
Like all those whose kidneys have failed, Scott Burton’s life revolves around dialysis. For nearly two decades, Burton has been hooked up (or, since 2020, has hooked himself up at home) to a dialysis machine that performs the job his kidneys normally would. The process is arduous, time-consuming, and expensive. Except for a brief window before his body rejected a kidney transplant, Burton has depended on machines to take the place of his kidneys since he was 12-years-old. His whole life, the 39-year-old says, revolves around dialysis.
“Whenever I try to plan anything, I also have to plan my dialysis,” says Burton says, who works as a freelance videographer and editor. “It’s a full-time job in itself.”
Many of those on dialysis are in line for a kidney transplant that would allow them to trade thrice-weekly dialysis and strict dietary limits for a lifetime of immunosuppressants. Burton’s previous transplant means that his body will likely reject another donated kidney unless it matches perfectly—something he’s not counting on. It’s why he’s enthusiastic about the development of artificial kidneys, small wearable or implantable devices that would do the job of a healthy kidney while giving users like Burton more flexibility for traveling, working, and more.
Still, the devices aren’t ready for testing in humans—yet. But recent advancements in engineering mean that the first preclinical trials for an artificial kidney could happen soon, according to Jonathan Himmelfarb, a nephrologist at the University of Washington.
“It would liberate people with kidney failure,” Himmelfarb says.
An engineering marvel
Compared to the heart or the brain, the kidney doesn’t get as much respect from the medical profession, but its job is far more complex. “It does hundreds of different things,” says UCLA’s Ira Kurtz.
Kurtz would know. He’s worked as a nephrologist for 37 years, devoting his career to helping those with kidney disease. While his colleagues in cardiology and endocrinology have seen major advances in the development of artificial hearts and insulin pumps, little has changed for patients on hemodialysis. The machines remain bulky and require large volumes of a liquid called dialysate to remove toxins from a patient’s blood, along with gallons of purified water. A kidney transplant is the next best thing to someone’s own, functioning organ, but with over 600,000 Americans on dialysis and only about 100,000 kidney transplants each year, most of those in kidney failure are stuck on dialysis.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. Each of the 45 different cell types in the kidney do something different.
Part of the lack of progress in artificial kidney design is the sheer complexity of the kidney’s job. To build an artificial heart, Kurtz says, you basically need to engineer a pump. An artificial pancreas needs to balance blood sugar levels with insulin secretion. While neither of these tasks is simple, they are fairly straightforward. The kidney, on the other hand, does more than get rid of waste products like urea and other toxins. Each of the 45 different cell types in the kidney do something different, helping to regulate electrolytes like sodium, potassium, and phosphorous; maintaining blood pressure and water balance; guiding the body’s hormonal and inflammatory responses; and aiding in the formation of red blood cells.
There's been little progress for patients during Ira Kurtz's 37 years as a nephrologist. Artificial kidneys would change that.
UCLA
Dialysis primarily filters waste, and does so well enough to keep someone alive, but it isn’t a true artificial kidney because it doesn’t perform the kidney’s other jobs, according to Kurtz, such as sensing levels of toxins, wastes, and electrolytes in the blood. Due to the size and water requirements of existing dialysis machines, the equipment isn’t portable. Physicians write a prescription for a certain duration of dialysis and assess how well it’s working with semi-regular blood tests. The process of dialysis itself, however, is conducted blind. Doctors can’t tell how much dialysis a patient needs based on kidney values at the time of treatment, says Meera Harhay, a nephrologist at Drexel University in Philadelphia.
But it’s the impact of dialysis on their day-to-day lives that creates the most problems for patients. Only one-quarter of those on dialysis are able to remain employed (compared to 85% of similar-aged adults), and many report a low quality of life. Having more flexibility in life would make a major different to her patients, Harhay says.
“Almost half their week is taken up by the burden of their treatment. It really eats away at their freedom and their ability to do things that add value to their life,” she says.
Art imitates life
The challenge for artificial kidney designers was how to compress the kidney’s natural functions into a portable, wearable, or implantable device that wouldn’t need constant access to gallons of purified and sterilized water. The other universal challenge they faced was ensuring that any part of the artificial kidney that would come in contact with blood was kept germ-free to prevent infection.
As part of the 2021 KidneyX Prize, a partnership between the U.S. Department of Health and Human Services and the American Society of Nephrology, inventors were challenged to create prototypes for artificial kidneys. Himmelfarb’s team at the University of Washington’s Center for Dialysis Innovation won the prize by focusing on miniaturizing existing technologies to create a portable dialysis machine. The backpack sized AKTIV device (Ambulatory Kidney to Increase Vitality) will recycle dialysate in a closed loop system that removes urea from blood and uses light-based chemical reactions to convert the urea to nitrogen and carbon dioxide, which allows the dialysate to be recirculated.
Himmelfarb says that the AKTIV can be used when at home, work, or traveling, which will give users more flexibility and freedom. “If you had a 30-pound device that you could put in the overhead bins when traveling, you could go visit your grandkids,” he says.
Kurtz’s team at UCLA partnered with the U.S. Kidney Research Corporation and Arkansas University to develop a dialysate-free desktop device (about the size of a small printer) as the first phase of a progression that will he hopes will lead to something small and implantable. Part of the reason for the artificial kidney’s size, Kurtz says, is the number of functions his team are cramming into it. Not only will it filter urea from blood, but it will also use electricity to help regulate electrolyte levels in a process called electrodeionization. Kurtz emphasizes that these additional functions are what makes his design a true artificial kidney instead of just a small dialysis machine.
One version of an artificial kidney.
UCLA
“It doesn't have just a static function. It has a bank of sensors that measure chemicals in the blood and feeds that information back to the device,” Kurtz says.
Other startups are getting in on the game. Nephria Bio, a spinout from the South Korean-based EOFlow, is working to develop a wearable dialysis device, akin to an insulin pump, that uses miniature cartridges with nanomaterial filters to clean blood (Harhay is a scientific advisor to Nephria). Ian Welsford, Nephria’s co-founder and CTO, says that the device’s design means that it can also be used to treat acute kidney injuries in resource-limited settings. These potentials have garnered interest and investment in artificial kidneys from the U.S. Department of Defense.
For his part, Burton is most interested in an implantable device, as that would give him the most freedom. Even having a regular outpatient procedure to change batteries or filters would be a minor inconvenience to him.
“Being plugged into a machine, that’s not mimicking life,” he says.
This article was first published by Leaps.org on May 5, 2022.
With this new technology, hospitals and pharmacies could make vaccines and medicines onsite
Most modern biopharmaceutical medicines are produced by workhorse cells—typically bacterial but sometimes mammalian. The cells receive the synthesizing instructions on a snippet of a genetic code, which they incorporate into their DNA. The cellular machinery—ribosomes, RNAs, polymerases, and other compounds—read and use these instructions to build the medicinal molecules, which are harvested and administered to patients.
Although a staple of modern pharma, this process is complex and expensive. One must first insert the DNA instructions into the cells, which they may or may not uptake. One then must grow the cells, keeping them alive and well, so that they produce the required therapeutics, which then must be isolated and purified. To make this at scale requires massive bioreactors and big factories from where the drugs are distributed—and may take a while to arrive where they’re needed. “The pandemic showed us that this method is slow and cumbersome,” says Govind Rao, professor of biochemical engineering who directs the Center for Advanced Sensor Technology at the University of Maryland, Baltimore County (UMBC). “We need better methods that can work faster and can work locally where an outbreak is happening.”
Rao and his team of collaborators, which spans multiple research institutions, believe they have a better approach that may change medicine-making worldwide. They suggest forgoing the concept of using living cells as medicine-producers. Instead, they propose breaking the cells and using the remaining cellular gears for assembling the therapeutic compounds. Instead of inserting the DNA into living cells, the team burst them open, and removed their DNA altogether. Yet, the residual molecular machinery of ribosomes, polymerases and other cogwheels still functioned the way it would in a cell. “Now if you drop your DNA drug-making instructions into that soup, this machinery starts making what you need,” Rao explains. “And because you're no longer worrying about living cells, it becomes much simpler and more efficient.” The collaborators detail their cell-free protein synthesis or CFPS method in their recent paper published in preprint BioAxiv.
While CFPS does not use living cells, it still needs the basic building blocks to assemble proteins from—such as amino acids, nucleotides and certain types of enzymes. These are regularly added into this “soup” to keep the molecular factory chugging. “We just mix everything in as a batch and we let it integrate,” says James Robert Swartz, professor of chemical engineering and bioengineering at Stanford University and co-author of the paper. “And we make sure that we provide enough oxygen.” Rao likens the process to making milk from milk powder.
For a variety of reasons—from the field’s general inertia to regulatory approval hurdles—the method hasn’t become mainstream. The pandemic rekindled interest in medicines that can be made quickly and easily, so it drew more attention to the technology.
The idea of a cell-free protein synthesis is older than one might think. Swartz first experimented with it around 1997, when he was a chemical engineer at Genentech. While working on engineering bacteria to make pharmaceuticals, he discovered that there was a limit to what E. coli cells, the workhorse darling of pharma, could do. For example, it couldn’t grow and properly fold some complex proteins. “We tried many genetic engineering approaches, many fermentation, development, and environmental control approaches,” Swartz recalls—to no avail.
“The organism had its own agenda,” he quips. “And because everything was happening within the organism, we just couldn't really change those conditions very easily. Some of them we couldn’t change at all—we didn’t have control.”
It was out of frustration with the defiant bacteria that a new idea took hold. Could the cells be opened instead, so that the protein-forming reactions could be influenced more easily? “Obviously, we’d lose the ability for them to reproduce,” Swartz says. But that also meant that they no longer needed to keep the cells alive and could focus on making the specific reactions happen. “We could take the catalysts, the enzymes, and the more complex catalysts and activate them, make them work together, much as they would in a living cell, but the way we wanted.”
In 1998, Swartz joined Stanford, and began perfecting the biochemistry of the cell-free method, identifying the reactions he wanted to foster and stopping those he didn’t want. He managed to make the idea work, but for a variety of reasons—from the field’s general inertia to regulatory approval hurdles—the method hasn’t become mainstream. The pandemic rekindled interest in medicines that can be made quickly and easily, so it drew more attention to the technology. For their BioArxiv paper, the team tested the method by growing a specific antiviral protein called griffithsin.
First identified by Barry O’Keefe at National Cancer Institute over a decade ago, griffithsin is an antiviral known to interfere with many viruses’ ability to enter cells—including HIV, SARS, SARS-CoV-2, MERS and others. Originally isolated from the red algae Griffithsia, it works differently from antibodies and antibody cocktails.
Most antiviral medicines tend to target the specific receptors that viruses use to gain entry to the cells they infect. For example, SARS-CoV-2 uses the infamous spike protein to latch onto the ACE2 receptor of mammalian cells. The antibodies or other antiviral molecules stick to the spike protein, shutting off its ability to cling onto the ACE2 receptors. Unfortunately, the spike proteins mutate very often, so the medicines lose their potency. On the contrary, griffithsin has the ability to cling to the different parts of viral shells called capsids—namely to the molecules of mannose, a type of sugar. That extra stuff, glued all around the capsid like dead weight, makes it impossible for the virus to squeeze into the cell.
“Every time we have a vaccine or an antibody against a specific SARS-CoV-2 strain, that strain then mutates and so you lose efficacy,” Rao explains. “But griffithsin molecules glom onto the viral capsid, so the capsid essentially becomes a sticky mess and can’t enter the cell.” Mannose molecules also don’t mutate as easily as viruses’ receptors, so griffithsin-based antivirals do not have to be constantly updated. And because mannose molecules are found on many viruses’ capsids, it makes griffithsin “a universal neutralizer,” Rao explains.
“When griffithsin was discovered, we recognized that it held a lot of promise as a potential antiviral agent,” O’Keefe says. In 2010, he published a paper about griffithsin efficacy in neutralizing viruses of the corona family—after the first SARS outbreak in the early 2000s, the scientific community was interested in such antivirals. Yet, griffithsin is still not available as an off-the-shelf product. So during the Covid pandemic, the team experimented with synthesizing griffithsin using the cell-free production method. They were able to generate potent griffithsin in less than 24 hours without having to grow living cells.
The antiviral protein isn't the only type of medicine that can be made cell-free. The proteins needed for vaccine production could also be made the same way. “Such portable, on-demand drug manufacturing platforms can produce antiviral proteins within hours, making them ideal for combating future pandemics,” Rao says. “We would be able to stop the pandemic before it spreads.”
Top: Describes the process used in the study. Bottom: Describes how the new medicines and vaccines could be made at the site of a future viral outbreak.
Image courtesy of Rao and team, sourced from An approach to rapid distributed manufacturing of broad spectrumanti-viral griffithsin using cell-free systems to mitigate pandemics.
Rao’s idea is to perfect the technology to the point that any hospital or pharmacy can load up the media containing molecular factories, mix up the required amino acids, nucleotides and enzymes, and harvest the meds within hours. That will allow making medicines onsite and on demand. “That would be a self-contained production unit, so that you could just ship the production wherever the pandemic is breaking out,” says Swartz.
These units and the meds they produce, will, of course, have to undergo rigorous testing. “The biggest hurdles will be validating these against conventional technology,” Rao says. The biotech industry is risk-averse and prefers the familiar methods. But if this approach works, it may go beyond emergency situations and revolutionize the medicine-making paradigm even outside hospitals and pharmacies. Rao hopes that someday the method might become so mainstream that people may be able to buy and operate such reactors at home. “You can imagine a diabetic patient making insulin that way, or some other drugs,” Rao says. It would work not unlike making baby formula from the mere white powder. Just add water—and some oxygen, too.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.