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."
Netscape co-founder-turned-venture capitalist billionaire investor Marc Andreessen once posited that software was eating the world. He was right, and the takeover of software resulted in many things. One of them is data. Lots and lots and lots of data. In the previous two years, humanity created more data than it did during its entire existence combined, and the amount will only increase. Think about it: The hundreds of 50KB emails you write a day, the dozens of 10MB photos, the minute-long, 350MB 4K video you shoot on your iPhone X add up to vast quantities of information. All that information needs to be stored. And that's becoming an issue as data volume outpaces storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible.
"There won't be enough silicon to store all the data we need. It's unlikely that we can make flash memory smaller. We have reached the physical limits," Victor Zhirnov, chief scientist at the Semiconductor Research Corporation, says. "We are facing a crisis that's comparable to the oil crisis in the 1970s. By 2050, we're going to need to store 10 to the 30 bits, compared to 10 to the 23 bits in 2016." That amount of storage space is equivalent to each of the world's seven billion people owning almost six trillion -- that's 10 to the 12th power -- iPhone Xs with 256GB storage space.
The race is on to find another medium capable of storing massive amounts of information in as small a space as possible. Zhirnov and other scientists are looking at the human body, looking to DNA. "Nature has nailed it," Luis Ceze, a professor in the Department of Computer Science and Engineering at the University of Washington, says. "DNA is a molecular storage medium that is remarkable. It's incredibly dense, many, many thousands of times denser than the densest technology that we have today. And DNA is remarkably general. Any information you can map in bits you can store in DNA." It's so dense -- able to store a theoretical maximum of 215 petabytes (215 million gigabytes) in a single gram -- that all the data ever produced could be stored in the back of a tractor trailer truck.
Writing DNA can be an energy-efficient process, too. Consider how the human body is constantly writing and rewriting DNA, and does so on a couple thousand calories a day. And all it needs for storage is a cool, dark place, a significant energy savings when compared to server farms that require huge amounts of energy to run and even more energy to cool.
Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
Researchers first succeeded in encoding data onto DNA in 2012, when Harvard University geneticists George Church and Sri Kosuri wrote a 52,000-word book on A, C, G, and T base pairs. Their method only produced 1.28 petabytes per gram of DNA, however, a volume exceeded the next year when a group encoded all 154 Shakespeare sonnets and a 26-second clip of Martin Luther King's "I Have A Dream" speech. In 2017, Columbia University researchers Yaniv Erlich and Dina Zielinski made the process 60 percent more efficient.
The limiting factor today is cost. Erlich said the work his team did cost $7,000 to encode and decode two megabytes of data. To become useful in a widespread way, the price per megabyte needs to plummet. Even advocates concede this point. "Of course it is expensive," Zhirnov says. "But look how much magnetic storage cost in the 1980s. What you store today in your iPhone for virtually nothing would cost many millions of dollars in 1982." There's reason to think the price will continue to fall. Genome readers are improving, getting cheaper, faster, and smaller, and genome sequencing becomes cheaper every year, too. Picture it: tiny specks of inert DNA made from silicon or another material, stored in cool, dark, dry areas, preserved for all time.
"It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
Plus, DNA has another advantage over more traditional forms of storage: It's very easy to reproduce. "If you want a second copy of a hard disk drive, you need components for a disk drive, hook both drives up to a computer, and copy. That's a pain," Nick Goldman, a researcher at the European Bioinformatics Institute, says. "DNA, once you have that first sample, it's a process that is absolutely routine in thousands of laboratories around the world to multiply that using polymerase chain reaction [which uses temperature changes or other processes]. It just takes a few minutes to double a sample. A few more minutes, you double it again. Very quickly, you have thousands or millions of new copies."
This ability to duplicate quickly and easily is a positive trait. But, of course, there's also the potential for danger. Does encoding on DNA, the very basis for life, present ethical issues? Could it get out of control and fundamentally alter life as we know it?
The chance is there, but it's remote. The first reason is that storage could be done with only two base pairs, which would serve as replacements for the 0 and 1 digits that make up all digital data. While doing so would decrease the possible density of the storage, it would virtually eliminate the risk that the sequences would be compatible with life.
But even if scientists and researchers choose to use four base pairs, other safeguards are in place that will prevent trouble. According to Ceze, the computer science professor, the snippets of DNA that they write are very short, around 150 nucleotides. This includes the title, the information that's being encoded, and tags to help organize where the snippet should fall in the larger sequence. Furthermore, they generally avoid repeated letters, which dramatically reduces the chance that a protein could be synthesized from the snippet.
"In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
Inevitably, some DNA will get spilt. "But it's so unlikely that anything that gets created for storage would have a biological interpretation that could interfere with the mechanisms going on in a living organism that it doesn't worry me in the slightest," Goldman says. "We're not of concern for the people who are worried about the ethical issues of synthetic DNA. They are much more concerned about people deliberately engineering anthrax. In the future, we'll know enough about someone from a sample of their DNA that we could make a specific poison. That's the danger, not those of us who want to encode DNA for storage."
In the end, the reality of and risks surrounding encoding on DNA are the same as any scientific advancement: It's another system that is vulnerable to people with bad intentions but not one that is inherently unethical.
"Every human action has some ethical implications," Zhirnov says. "I can use a hammer to build a house or I can use it to harm another person. I don't see why DNA is in any way more or less ethical."
If that house can store all the knowledge in human history, it's worth learning how to build it.
Editor's Note: In response to readers' comments that silicon is one of the earth's most abundant materials, we reached back out to our source, Dr. Victor Zhirnov. He stands by his statement about a coming shortage of silicon, citing this research. The silicon oxide found in beach sand is unsuitable for semiconductors, he says, because the cost of purifying it would be prohibitive. For use in circuit-making, silicon must be refined to a purity of 99.9999999 percent. So the process begins by mining for pure quartz, which can only be found in relatively few places around the world.
"Dust thou art, and unto dust shalt thou return." Whoever wrote that famous line probably didn't realize that dust actually contains a secret weapon.
"We have developed the capability to turn dust into data that can be used to trace problems in the supply chain."
Far from being a collection of mere inanimate particles, dust is now recognized as a powerful tool filled with living sensors. Studying those sensors can reveal an object's location history, which can help brands fight unethical manufacturing.
"We have developed the capability to turn dust into data that can be used to trace problems in the supply chain," explains Jessica Green, the CEO of Phylagen, a San-Francisco-based company that she co-founded in 2014.
So how does the technology work?
Dust gathers everywhere—on our bodies, on objects—and that dust contains microbes like bacteria and viruses. Just as we humans have our own unique microbiomes, research has shown that physical locations have their own identifiable patterns of microbes as well. Visiting a place means you may pick up its microbial fingerprint in the dust that settles on you. The DNA of those microbes can later be sequenced in a lab and matched back to the place of origin.
"Your environment is constantly imprinted on you and vice versa," says Justin Gallivan, the director of the Biotechnology Office at DARPA, the research and defense arm of the Pentagon, which is funding Phylagen. "If we have a microbial map of the world," he posits, "can we infer an object's transit history?"
So far, Phylagen has shown that it's possible to identify where a ship came from based on the unique microbial populations it picked up at different naval ports. In another experiment, the sampling technology allowed researchers to determine where a person had walked within 1 kilometer in San Francisco, because of the microbes picked up by their shoes.
Data scientist Roxana Hickey, left, and CEO Jessica Green of Phylagen.
One application of this technology is to help companies that make products abroad. Such companies are very interested in determining exactly where their products are coming from, especially if foreign subcontractors are involved.
"In retail and apparel, often the facilities performing the subcontracting are not up to the same code that the brands require their suppliers to be, so there could be poor working conditions," says Roxana Hickey, a data scientist at Phylagen. "A supplier might use a subcontractor to save on the bottom line, but unethical practices are very damaging to the brand."
Before this technology was developed, brands sometimes faced a challenge figuring out what was going on in their supply chain. But now a product can be tested upon arrival in the States; its microbial signature can theoretically be analyzed and matched against a reference database to help determine if its DNA pattern matches that of the place where the product was purported to have been made.
Phylagen declined to elaborate further about how their process works, such as how they are building a database of reference samples, and how consistent a microbial population remains across a given location.
As the technology grows more robust, though, one could imagine numerous other applications, like in police work and forensics. But today, Phylagen is solely focused on helping commercial entities bring greater transparency to their operations so they can root out unauthorized subcontracting.
Then those unethical suppliers can – shall we say – bite the dust.