A string of the code that comprises a DNA molecule, pictured at Miraikan, the National Museum of Emerging Science and Innovation in Japan.
News about COVID-19 continues to relentlessly dominate as Omicron surges around the globe. Yet somehow, during the pandemic’s exhausting twists and turns, progress in other areas of health and biotech has marched on.
In some cases, these innovations have occurred despite a broad reallocation of resources to address the COVID crisis. For other breakthroughs, COVID served as the forcing function, pushing scientists and medical providers to rethink key aspects of healthcare, including how cancer, Alzheimer’s and other diseases are studied, diagnosed and treated. Regardless of why they happened, many of these advances didn’t make the headlines of major media outlets, even when they represented turning points in overcoming our toughest health challenges.
If it bleeds, it leads—and many disturbing stories, such as COVID surges, deserve top billing. Too often, though, mainstream media’s parallel strategy seems to be: if it innovates, it fades to the background. But our breakthroughs are just as critical to understanding the state of the world as our setbacks. I asked six pragmatic yet forward-thinking experts on health and biotech for their perspectives on the most important, but under-appreciated, breakthrough of 2021.
Their descriptions, below, were lightly edited by Leaps.org for style and format.
New Alzheimer's Therapies
Mary Carrillo, Chief Science Officer at the Alzheimer’s Association
Alzheimer's Association
One of the biggest health stories of 2021 was the FDA’s accelerated approval of aducanumab, the first drug that treats the underlying biology of Alzheimer’s, not just the symptoms. But, Alzheimer’s is a complex disease and will likely need multiple treatment strategies that target various aspects of the disease. It’s been exciting to see many of these types of therapies advance in 2021.
Following the FDA action in June, we saw renewed excitement in this class of disease-modifying drugs that target beta-amyloid, a protein that accumulates in the brain and leads to brain cell death. This class includes drugs from Eli Lilly (donanemab), Eisai (lecanemab) and Roche (gantenerumab), all of which received Breakthrough Designation by the FDA in 2021, advancing the drugs more quickly through the approval process.
We’ve also seen treatments advance that target other hallmarks of Alzheimer’s this year. We heard topline results from a phase 2 trial of semorinemab, a drug that targets tau tangles, a toxic protein that destroys neurons in the Alzheimer’s brain. Plus, strategies targeting neuroinflammation, protecting brain cells, and reducing vascular contributions to dementia – all funded through the Alzheimer's Association Part the Cloud program – advanced into clinical trials.
The future of Alzheimer’s treatment will likely be combination therapy, including drug therapies and healthy lifestyle changes, similar to how we treat heart disease. Washington University announced they will be testing a combination of both anti-amyloid and anti-tau drugs in a first-of-its-kind clinical trial, with funding from the Alzheimer’s Association.
AlphaFold
Olivier Elemento, Director of the Caryl and Israel Englander Institute for Precision Medicine at Cornell University
Cornell University
AlphaFold is an artificial intelligence system designed by Google’s DeepMind that opens the door to understanding the three-dimensional structures and functions of proteins, the building blocks that make up almost half of our bodies' dry weight. In 2021, Google made AlphaFold available for free and since then, researchers have used it to drive greater understanding of how proteins interact. This is a foundational event in the field of biotech.
It’s going to take time for the benefits from AlphaFold to transpire, but once we know the 3-D structures of proteins that cause various diseases, it will be much easier to design new drugs that can bind to these proteins and change their activity. Prior to AlphaFold, scientists had identified the 3-D structure of just 17 percent of about 20,000 proteins in the body, partly because mapping the structures was extremely difficult and expensive. Thanks to AlphaFold, we’ve now jumped to knowing – with at least some degree of certainty – the protein structures of 98.5 percent of the proteome.
For example, kinases are a class of proteins that modify other proteins and are often aberrantly active in cancer due to DNA mutations. Some of the earliest targeted therapies for cancer were ones that block kinases but, before AlphaFold, we had only a premature understanding of a few hundred kinases. We can now determine the structures of all 1,500 kinases. This opens up a universe of drug targets we didn’t have before.
Additional progress has been made this year toward potentially using AlphaFold to develop blockers of certain protein receptors that contribute to psychiatric illnesses and other neurological diseases. And in July, scientists used AlphaFold to map the dimensions of a bacterial protein that may be key to countering antibiotic resistance. Another discovery in May could be essential to finding treatments for COVID-19. Ongoing research is using AlphaFold principles to create entirely new proteins from scratch that could have therapeutic uses. The AlphaFold revolution is just beginning.
Virtual First Care
Jennifer Goldsack, CEO of Digital Medicine Society
Digital Medicine Society
Imagine a new paradigm of healthcare defined by how good we are at keeping people healthy and out of the clinic, not how good we are at offering services to a sick person at the clinic. That is the promise of virtual-first care, or V1C, what I consider to be the greatest, and most underappreciated, advance that occurred in medicine this year.
V1C is defined as medical care accessed through digital interactions where possible, guided by a clinician, and integrated into a person’s everyday life. This type of care includes spit kits mailed for laboratory tests and replacing in-person exams with biometric sensors. It’s built around the patient, not the clinic, and provides us with the opportunity to fundamentally reimagine what good healthcare looks like.
V1C flew under the radar in 2021, eclipsed by the ongoing debate about the value of telehealth more broadly as we emerge from the pandemic. However, the growth in the number of specialty and primary care virtual-first providers has been matched only by the number of national health plans offering virtual-first plans. Our own virtual-first community, IMPACT, has tripled in size, mirroring the rapid growth of the field driven by patient demand for care on their terms.
V1C differs from the ‘bolt on’ approach of video visits as an add-on to traditional visit-based, episodic care. V1C takes a much more holistic approach; it allows individuals to initiate care at any time in any place, recognizing that healthcare needs extend beyond 9-5. It matches the care setting with each individual’s clinical needs and personal preferences, advancing a thorough, evidence-based, safe practice while protecting privacy and recognizing that patients’ expectations have changed following the pandemic. V1C puts the promise of digital health into practice. This is the blueprint for what good healthcare looks like in the digital era.
Digital Clinical Trials
Craig Lipset, Founder of Clinical Innovation Partners and former Head of Clinical Innovation at Pfizer
Craig Lipset
In 2021, a number of digital- and data-enabled approaches have sustained decentralized clinical trials around the world for many different disease types. Pharma companies and clinical researchers are enthusiastic about this development for good reason. Throughout the pandemic, these decentralized trials have allowed patients to continue in studies with a reduced need for site visits, without compromising their safety or data quality.
Risk-based monitoring was deployed using data and thoughtful algorithms to identify quality and safety issues without relying entirely on human monitors visiting research sites. Some trials used digital measures to ensure high quality data on target health outcomes that could be captured in ways that made the participants’ physical location irrelevant. More than three-quarters of research organizations, such as pharma and biotech, have accelerated their decentralized clinical trial strategies. Before COVID-19, 72 percent of trial sites “rarely or never” used telemedicine for trial participants; during COVID, 64 percent “sometimes, often or always” do.
While the research community does appreciate the tremendous hope and promise brought by these innovations, perhaps what has been under-appreciated is the culture shift toward thoughtful risk-taking and a willingness to embrace and adopt clinical trial innovations. These solutions existed before COVID, but the pandemic shifted the perception of risks versus benefits involved in these trials. If there is one breakthrough that is perhaps under-appreciated in life sciences clinical research today, it’s the power of this new culture of willingness and receptivity to outlast the pandemic. Perhaps the greatest loss to the research ecosystem would be if we lose the momentum with recent trial innovations and must wait for another global pandemic in order to see it again.
Designing Biology
Sudip Parikh, CEO of the American Association for the Advancement of Science and Executive Publisher of the Science family of journals
American Association for the Advancement of Science
As our understanding of basic biology has grown, we are fast approaching an era where it will be possible to design and direct biological machinery to create treatments, medicine, and materials. 2021 saw many breakthroughs in this area, three of which are listed below.
The understanding of the human microbiome is growing as is our ability to modify it. One example is the movement toward the notion of the “bug as the drug.” In June, scientists at the Brigham and Women’s Hospital published a paper showing that they had genetically engineered yeast – using CRISPR/Cas9 – to sense and treat inflammation in the body to relieve symptoms of irritable bowel syndrome in mice. This approach could potentially be used to address issues with your microbiome to treat other chronic conditions.
Another way in which we saw the application of basic biology discoveries to real world problems in 2021 is through groundbreaking research on synthetic biology. Several institutions and companies are pursuing this path. Ginkgo Bioworks, valued at $15 billion, already claims to engineer cells with assembly-line efficiency. Imagine the possibilities of programming cells and tissue to perform chemistry for the manufacturing process, inspired by the way your body does chemistry. That could mean cleaner, more controllable, and affordable ways to manufacture food, therapeutics, and other materials in a factory-like setting.
A final example: consider the possibility of leveraging the mechanics of your own body to deliver proteins as treatments, vaccines, and more. In 2021, several scientists accelerated research to apply the mRNA technology underlying COVID-19 vaccines to make and replace proteins that, when they’re missing or don’t work, cause rare conditions such as cystic fibrosis and multiple sclerosis.
These applications of basic biology to solve real world problems are exciting on their own, but their convergence with incredible advances in computing, materials, and drug delivery hold the promise of game-changing progress in health care and beyond.
Brain Biomarkers
David R. Walt, Professor of Biologically Inspired Engineering, Harvard Medical School, Brigham and Women’s Hospital, Wyss Institute at Harvard University
David Walt
2021 brought the first real hope for identifying biomarkers that can predict neurodegenerative disease. Multiple biomarkers (which are measurable indicators of the presence or severity of disease) were identified that can diagnose disease and that correlate with disease progression. Some of these biomarkers were detected in cerebrospinal fluid (CSF) but others were measured directly in blood by examining precursors of protein fibers.
The blood-brain barrier prevents many biomolecules from both exiting and entering the brain, so it has been a longstanding challenge to detect and identify biomarkers that signal changes in brain chemistry due to neurodegenerative disease. With the advent of omics-based approaches (an emerging field that encompasses genomics, epigenomics, transcriptomics, proteomics, and metabolomics), coupled with new ultrasensitive analytical methods, researchers are beginning to identify informative brain biomarkers. Such biomarkers portend our ability to detect earlier stages of disease when therapeutic intervention could be effective at halting progression.
In addition, these biomarkers should enable drug developers to monitor the efficacy of candidate drugs in the blood of participants enrolled in clinical trials aimed at slowing neurodegeneration. These biomarkers begin to move us away from relying on cognitive performance indicators and imaging—methods that do not directly measure the underlying biology of neurodegenerative disease. The identity of these biomarkers may also provide researchers with clues about the causes of neurodegenerative disease, which can serve as new targets for drug intervention.
Doctors worry that fungal pathogens may cause the next pandemic.
Although C. auris typically doesn’t sicken healthy people, it afflicts immunocompromised hospital patients and may cause severe infections that can lead to sepsis, a life-threatening condition in which the overwhelmed immune system begins to attack the body’s own organs. Between 30 and 60 percent of patients who contract a C. auris infection die from it, according to the CDC. People who are undergoing stem cell transplants, have catheters or have taken antifungal or antibiotic medicines are at highest risk. “We’re coming to a perfect storm of increasing resistance rates, increasing numbers of immunosuppressed patients worldwide and a bug that is adapting to higher temperatures as the climate changes,” says Prabhavathi Fernandes, chair of the National BioDefense Science Board.
Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures.
Although medical professionals aren’t concerned at this point about C. auris evolving to affect healthy people, they worry that its presence in hospitals can turn routine surgeries into life-threatening calamities. “It’s coming,” says Fernandes. “It’s just a matter of time.”
An emerging global threat
“Fungi are found in the environment,” explains Fernandes, so Candida spores can easily wind up on people’s skin. In hospitals, they can be transferred from contact with healthcare workers or contaminated surfaces. Most Candida species aren’t well-adapted to our body temperatures so they aren’t a threat. C. auris, however, thrives at human body temperatures. It can enter the body during medical treatments that break the skin—and cause an infection. Overall, fungal infections cost some $48 billion in the U.S. each year. And infection rates are increasing because, in an ironic twist, advanced medical therapies are enabling severely ill patients to live longer and, therefore, be exposed to this pathogen.
The first-ever case of a C. auris infection was reported in Japan in 2009, although an analysis of Candida samples dated the earliest strain to a 1996 sample from South Korea. Since then, five separate varieties – called clades, which are similar to strains among bacteria – developed independently in different geographies: South Asia, East Asia, South Africa, South America and, recently, Iran. So far, C. auris infections have been reported in 35 countries.
In the U.S., the first infection was reported in 2016, and the CDC started tracking it nationally two years later. During that time, 5,654 cases have been reported to the CDC, which only tracks U.S. data.
What’s more notable than the number of cases is their rate of increase. In 2016, new cases increased by 175 percent and, on average, they have approximately doubled every year. From 2016 through 2022, the number of infections jumped from 63 to 2,377, a roughly 37-fold increase.
“This reminds me of what we saw with epidemics from 2013 through 2020… with Ebola, Zika and the COVID-19 pandemic,” says Robin Robinson, CEO of Spriovas and founding director of the Biomedical Advanced Research and Development Authority (BARDA), which is part of the U.S. Department of Health and Human Services. These epidemics started with a hockey stick trajectory, Robinson says—a gradual growth leading to a sharp spike, just like the shape of a hockey stick.
Another challenge is that right now medics don’t have rapid diagnostic tests for fungal infections. Currently, patients are often misdiagnosed because C. auris resembles several other easily treated fungi. Or they are diagnosed long after the infection begins and is harder to treat.
The problem is that existing diagnostics tests can only identify C. auris once it reaches the bloodstream. Yet, because this pathogen infects bodily tissues first, it should be possible to catch it much earlier before it becomes life-threatening. “We have to diagnose it before it reaches the bloodstream,” Walsh says.
The most alarming fact is that some Candida infections no longer respond to standard therapeutics.
“We need to focus on rapid diagnostic tests that do not rely on a positive blood culture,” says John Sperzel, president and CEO of T2 Biosystems, a company specializing in diagnostics solutions. Blood cultures typically take two to three days for the concentration of Candida to become large enough to detect. The company’s novel test detects about 90 percent of Candida species within three to five hours—thanks to its ability to spot minute quantities of the pathogen in blood samples instead of waiting for them to incubate and proliferate.
Unlike other Candida species C. auris thrives at human body temperatures
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Tackling the resistance challenge
The most alarming fact is that some Candida infections no longer respond to standard therapeutics. The number of cases that stopped responding to echinocandin, the first-line therapy for most Candida infections, tripled in 2020, according to a study by the CDC.
Now, each of the first four clades shows varying levels of resistance to all three commonly prescribed classes of antifungal medications, such as azoles, echinocandins, and polyenes. For example, 97 percent of infections from C. auris Clade I are resistant to fluconazole, 54 percent to voriconazole and 30 percent of amphotericin. Nearly half are resistant to multiple antifungal drugs. Even with Clade II fungi, which has the least resistance of all the clades, 11 to 14 percent have become resistant to fluconazole.
Anti-fungal therapies typically target specific chemical compounds present on fungi’s cell membranes, but not on human cells—otherwise the medicine would cause damage to our own tissues. Fluconazole and other azole antifungals target a compound called ergosterol, preventing the fungal cells from replicating. Over the years, however, C. auris evolved to resist it, so existing fungal medications don’t work as well anymore.
A newer class of drugs called echinocandins targets a different part of the fungal cell. “The echinocandins – like caspofungin – inhibit (a part of the fungi) involved in making glucan, which is an essential component of the fungal cell wall and is not found in human cells,” Fernandes says. New antifungal treatments are needed, she adds, but there are only a few magic bullets that will hit just the fungus and not the human cells.
Research to fight infections also has been challenged by a lack of government support. That is changing now that BARDA is requesting proposals to develop novel antifungals. “The scope includes C. auris, as well as antifungals following a radiological/nuclear emergency, says BARDA spokesperson Elleen Kane.
The remaining challenge is the number of patients available to participate in clinical trials. Large numbers are needed, but the available patients are quite sick and often die before trials can be completed. Consequently, few biopharmaceutical companies are developing new treatments for C. auris.
ClinicalTrials.gov reports only two drugs in development for invasive C. auris infections—those than can spread throughout the body rather than localize in one particular area, like throat or vaginal infections: ibrexafungerp by Scynexis, Inc., fosmanogepix, by Pfizer.
Scynexis’ ibrexafungerp appears active against C. auris and other emerging, drug-resistant pathogens. The FDA recently approved it as a therapy for vaginal yeast infections and it is undergoing Phase III clinical trials against invasive candidiasis in an attempt to keep the infection from spreading.
“Ibreafungerp is structurally different from other echinocandins,” Fernandes says, because it targets a different part of the fungus. “We’re lucky it has activity against C. auris.”
Pfizer’s fosmanogepix is in Phase II clinical trials for patients with invasive fungal infections caused by multiple Candida species. Results are showing significantly better survival rates for people taking fosmanogepix.
Although C. auris does pose a serious threat to healthcare worldwide, scientists try to stay optimistic—because they recognized the problem early enough, they might have solutions in place before the perfect storm hits. “There is a bit of hope,” says Robinson. “BARDA has finally been able to fund the development of new antifungal agents and, hopefully, this year we can get several new classes of antifungals into development.”
A space elevator would be cheaper and cleaner than using rockets
This is making space accessible to scientists, startups, and tourists who never could have afforded it previously, but the cheapest way to reach orbit might not be a rocket at all — it could be an elevator.
The space elevator
The seeds for a space elevator were first planted by Russian scientist Konstantin Tsiolkovsky in 1895, who, after visiting the 1,000-foot (305 m) Eiffel Tower, published a paper theorizing about the construction of a structure 22,000 miles (35,400 km) high.
This would provide access to geostationary orbit, an altitude where objects appear to remain fixed above Earth’s surface, but Tsiolkovsky conceded that no material could support the weight of such a tower.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit.
In 1959, soon after Sputnik, Russian engineer Yuri N. Artsutanov proposed a way around this issue: instead of building a space elevator from the ground up, start at the top. More specifically, he suggested placing a satellite in geostationary orbit and dropping a tether from it down to Earth’s equator. As the tether descended, the satellite would ascend. Once attached to Earth’s surface, the tether would be kept taut, thanks to a combination of gravitational and centrifugal forces.
We could then send electrically powered “climber” vehicles up and down the tether to deliver payloads to any Earth orbit. According to physicist Bradley Edwards, who researched the concept for NASA about 20 years ago, it’d cost $10 billion and take 15 years to build a space elevator, but once operational, the cost of sending a payload to any Earth orbit could be as low as $100 per pound.
“Once you reduce the cost to almost a Fed-Ex kind of level, it opens the doors to lots of people, lots of countries, and lots of companies to get involved in space,” Edwards told Space.com in 2005.
In addition to the economic advantages, a space elevator would also be cleaner than using rockets — there’d be no burning of fuel, no harmful greenhouse emissions — and the new transport system wouldn’t contribute to the problem of space junk to the same degree that expendable rockets do.
So, why don’t we have one yet?
Tether troubles
Edwards wrote in his report for NASA that all of the technology needed to build a space elevator already existed except the material needed to build the tether, which needs to be light but also strong enough to withstand all the huge forces acting upon it.
The good news, according to the report, was that the perfect material — ultra-strong, ultra-tiny “nanotubes” of carbon — would be available in just two years.
“[S]teel is not strong enough, neither is Kevlar, carbon fiber, spider silk, or any other material other than carbon nanotubes,” wrote Edwards. “Fortunately for us, carbon nanotube research is extremely hot right now, and it is progressing quickly to commercial production.”Unfortunately, he misjudged how hard it would be to synthesize carbon nanotubes — to date, no one has been able to grow one longer than 21 inches (53 cm).
Further research into the material revealed that it tends to fray under extreme stress, too, meaning even if we could manufacture carbon nanotubes at the lengths needed, they’d be at risk of snapping, not only destroying the space elevator, but threatening lives on Earth.
Looking ahead
Carbon nanotubes might have been the early frontrunner as the tether material for space elevators, but there are other options, including graphene, an essentially two-dimensional form of carbon that is already easier to scale up than nanotubes (though still not easy).
Contrary to Edwards’ report, Johns Hopkins University researchers Sean Sun and Dan Popescu say Kevlar fibers could work — we would just need to constantly repair the tether, the same way the human body constantly repairs its tendons.
“Using sensors and artificially intelligent software, it would be possible to model the whole tether mathematically so as to predict when, where, and how the fibers would break,” the researchers wrote in Aeon in 2018.
“When they did, speedy robotic climbers patrolling up and down the tether would replace them, adjusting the rate of maintenance and repair as needed — mimicking the sensitivity of biological processes,” they continued.Astronomers from the University of Cambridge and Columbia University also think Kevlar could work for a space elevator — if we built it from the moon, rather than Earth.
They call their concept the Spaceline, and the idea is that a tether attached to the moon’s surface could extend toward Earth’s geostationary orbit, held taut by the pull of our planet’s gravity. We could then use rockets to deliver payloads — and potentially people — to solar-powered climber robots positioned at the end of this 200,000+ mile long tether. The bots could then travel up the line to the moon’s surface.
This wouldn’t eliminate the need for rockets to get into Earth’s orbit, but it would be a cheaper way to get to the moon. The forces acting on a lunar space elevator wouldn’t be as strong as one extending from Earth’s surface, either, according to the researchers, opening up more options for tether materials.
“[T]he necessary strength of the material is much lower than an Earth-based elevator — and thus it could be built from fibers that are already mass-produced … and relatively affordable,” they wrote in a paper shared on the preprint server arXiv.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one.
Electrically powered climber capsules could go up down the tether to deliver payloads to any Earth orbit.
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Some Chinese researchers, meanwhile, aren’t giving up on the idea of using carbon nanotubes for a space elevator — in 2018, a team from Tsinghua University revealed that they’d developed nanotubes that they say are strong enough for a tether.
The researchers are still working on the issue of scaling up production, but in 2021, state-owned news outlet Xinhua released a video depicting an in-development concept, called “Sky Ladder,” that would consist of space elevators above Earth and the moon.
After riding up the Earth-based space elevator, a capsule would fly to a space station attached to the tether of the moon-based one. If the project could be pulled off — a huge if — China predicts Sky Ladder could cut the cost of sending people and goods to the moon by 96 percent.
The bottom line
In the 120 years since Tsiolkovsky looked at the Eiffel Tower and thought way bigger, tremendous progress has been made developing materials with the properties needed for a space elevator. At this point, it seems likely we could one day have a material that can be manufactured at the scale needed for a tether — but by the time that happens, the need for a space elevator may have evaporated.
Several aerospace companies are making progress with their own reusable rockets, and as those join the market with SpaceX, competition could cause launch prices to fall further.
California startup SpinLaunch, meanwhile, is developing a massive centrifuge to fling payloads into space, where much smaller rockets can propel them into orbit. If the company succeeds (another one of those big ifs), it says the system would slash the amount of fuel needed to reach orbit by 70 percent.
Even if SpinLaunch doesn’t get off the ground, several groups are developing environmentally friendly rocket fuels that produce far fewer (or no) harmful emissions. More work is needed to efficiently scale up their production, but overcoming that hurdle will likely be far easier than building a 22,000-mile (35,400-km) elevator to space.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
