COVID Variants Are Like “a Thief Changing Clothes” – and Our Camera System Barely Exists
Whether it's "natural selection" as Darwin called it, or it's "mutating" as the X-Men called it, living organisms change over time, developing thumbs or more efficient protein spikes, depending on the organism and the demands of its environment. The coronavirus that causes COVID-19, SARS-CoV-2, is not an exception, and now, after the virus has infected millions of people around the globe for more than a year, scientists are beginning to see those changes.
The notorious variants that have popped up include B.1.1.7, sometimes called the UK variant, as well as P.1 and B.1.351, which seem to have emerged in Brazil and South Africa respectively. As vaccinations are picking up pace, officials are warning that now
is not the time to become complacent or relax restrictions because the variants aren't well understood.
Some appear to be more transmissible, and deadlier, while others can evade the immune system's defenses better than earlier versions of the virus, potentially undermining the effectiveness of vaccines to some degree. Genomic surveillance, the process of sequencing the genetic code of the virus widely to observe changes and patterns, is a critical way that scientists can keep track of its evolution and work to understand how the variants might affect humans.
"It's like a thief changing clothes"
It's important to note that viruses mutate all the time. If there were funding and personnel to sequence the genome of every sample of the virus, scientists would see thousands of mutations. Not every variant deserves our attention. The vast majority of mutations are not important at all, but recognizing those that are is a crucial tool in getting and staying ahead of the virus. The work of sequencing, analyzing, observing patterns, and using public health tools as necessary is complicated and confusing to those without years of specialized training.
Jeremy Kamil, associate professor of microbiology and immunology at LSU Health Shreveport, in Louisiana, says that the variants developing are like a thief changing clothes. The thief goes in your house, steals your stuff, then leaves and puts on a different shirt and a wig, in the hopes you won't recognize them. Genomic surveillance catches the "thief" even in those different clothes.
One of the tricky things about variants is recognizing the point at which they move from interesting, to concerning at a local level, to dangerous in a larger context.
Understanding variants, both the uninteresting ones and the potentially concerning ones, gives public health officials and researchers at different levels a useful set of tools. Locally, knowing which variants are circulating in the community helps leaders know whether mask mandates and similar measures should be implemented or discontinued, or whether businesses and schools can open relatively safely.
There's more to it than observing new variants
Analysis is complex, particularly when it comes to understanding which variants are of concern. "So the question is always if a mutation becomes common, is that a random occurrence?" says Phoebe Lostroh, associate professor of molecular biology at Colorado College. "Or is the variant the result of some kind of selection because the mutation changes some property about the virus that makes it reproduce more quickly than variants of the virus that don't have that mutation? For a virus, [mutations can affect outcomes like] how much it replicates inside a person's body, how much somebody breathes it out, whether the particles that somebody might breathe in get smaller and can lead to greater transmission."
Along with all of those factors, accurate and useful genomic surveillance requires an understanding of where variants are occurring, how they are related, and an examination of why they might be prevalent.
For example, if a potentially worrisome variant appears in a community and begins to spread very quickly, it's not time to raise a public health alarm until several important questions have been answered, such as whether the variant is spreading due to specific events, or if it's happening because the mutation has allowed the virus to infect people more efficiently. Kamil offered a hypothetical scenario to explain: Imagine that a member of a community became infected and the virus mutated. That person went to church and three more people were infected, but one of them went to a karaoke bar and while singing infected 100 other people. Examining the conditions under which the virus has spread is, therefore, an essential part of untangling whether a mutation itself made the virus more transmissible or if an infected person's behaviors contributed to a local outbreak.
One of the tricky things about variants is recognizing the point at which they move from interesting, to concerning at a local level, to dangerous in a larger context. Genomic sequencing can help with that, but only when it's coordinated. When the same mutation occurs frequently, but is localized to one region, it's a concern, but when the same mutation happens in different places at the same time, it's much more likely that the "virus is learning that's a good mutation," explains Kamil.
The process is called convergent evolution, and it was a fascinating topic long before COVID. Just as your heritage can be traced through DNA, so can that of viruses, and when separate lineages develop similar traits it's almost like scientists can see evolution happening in real time. A mutation to SARS-CoV-2 that happens in more than one place at once is a mutation that makes it easier in some way for the virus to survive and that is when it may become alarming. The widespread, documented variants P.1 and B.1.351 are examples of convergence because they share some of the same virulent mutations despite having developed thousands of miles apart.
However, even variants that are emerging in different places at the same time don't present the kind of threat SARS-CoV-2 did in 2019. "This is nature," says Kamil. "It just means that this virus will not easily be driven to extinction or complete elimination by vaccines." Although a person who has already had COVID-19 can be reinfected with a variant, "it is almost always much milder disease" than the original infection, Kamil adds. Rather than causing full-fledged disease, variants have the potiental to "penetrate herd immunity, spreading relatively quietly among people who have developed natural immunity or been vaccinated, until the virus finds someone who has no immunity yet, and that person would be at risk of hospitalization-grade severe disease or death."
Surveillance and predictions
According to Lostroh, genomic surveillance can help scientists predict what's going to happen. "With the British strain, for instance, that's more transmissible, you can measure how fast it's doubling in the population and you can sort of tell whether we should take more measures against this mutation. Should we shut things down a little longer because that mutation is present in the population? That could be really useful if you did enough sampling in the population that you knew where it was," says Lostroh. If, for example, the more transmissible strain was present in 50 percent of cases, but in another county or state it was barely present, it would allow for rolling lockdowns instead of sweeping measures.
Variants are also extremely important when it comes to the development, manufacture, and distribution of vaccines. "You're also looking at medical countermeasures, such as whether your vaccine is still effective, or if your antiviral needs to be updated," says Lane Warmbrod, a senior analyst and research associate at Johns Hopkins Center for Health Security.
Properly funded and extensive genomic surveillance could eventually help control endemic diseases, too, like the seasonal flu, or other common respiratory infections. Kamil says he envisions a future in which genomic surveillance allows for prediction of sickness just as the weather is predicted today. "It's a 51 for infection today at the San Francisco Airport. There's been detection of some respiratory viruses," he says, offering an example. He says that if you're a vulnerable person, if you're immune-suppressed for some reason, you may want to wear a mask based on the sickness report.
The U.S. has the ability, but lacks standards
The benefits of widespread genomic surveillance are clear, and the United States certainly has the necessary technology, equipment, and personnel to carry it out. But, it's not happening at the speed and extent it needs to for the country to gain the benefits.
"The numbers are improving," said Kamil. "We're probably still at less than half a percent of all the samples that have been taken have been sequenced since the beginning of the pandemic."
Although there's no consensus on how many sequences is ideal for a robust surveillance program, modeling performed by the company Illumina suggests about 5 percent of positive tests should be sequenced. The reasons the U.S. has lagged in implementing a sequencing program are complex and varied, but solvable.
Perhaps the most important element that is currently missing is leadership. In order to conduct an effective genomic surveillance program, there need to be standards. The Johns Hopkins Center for Health Security recently published a paper with recommendations as to what kinds of elements need to be standardized in order to make the best use of sequencing technology and analysis.
"Along with which bioinformatic pipelines you're going to use to do the analyses, which sequencing strategy protocol are you going to use, what's your sampling strategy going to be, how is the data is going to be reported, what data gets reported," says Warmbrod. Currently, there's no guidance from the CDC on any of those things. So, while scientists can collect and report information, they may be collecting and reporting different information that isn't comparable, making it less useful for public health measures and vaccine updates.
Globally, one of the most important tools in making the information from genomic surveillance useful is GISAID, a platform designed for scientists to share -- and, importantly, to be credited for -- their data regarding genetic sequences of influenza. Originally, it was launched as a database of bird flu sequences, but has evolved to become an essential tool used by the WHO to make flu vaccine virus recommendations each year. Scientists who share their credentials have free access to the database, and anyone who uses information from the database must credit the scientist who uploaded that information.
Safety, logistics, and funding matter
Scientists at university labs and other small organizations have been uploading sequences to GISAID almost from the beginning of the pandemic, but their funding is generally limited, and there are no standards regarding information collection or reporting. Private, for-profit labs haven't had motivation to set up sequencing programs, although many of them have the logistical capabilities and funding to do so. Public health departments are understaffed, underfunded, and overwhelmed.
University labs may also be limited by safety concerns. The SARS-CoV-2 virus is dangerous, and there's a question of how samples should be transported to labs for sequencing.
Larger, for-profit organizations often have the tools and distribution capabilities to safely collect and sequence samples, but there hasn't been a profit motive. Genomic sequencing is less expensive now than ever before, but even at $100 per sample, the cost adds up -- not to mention the cost of employing a scientist with the proper credentials to analyze the sequence.
The path forward
The recently passed COVID-19 relief bill does have some funding to address genomic sequencing. Specifically, the American Rescue Plan Act includes $1.75 billion in funding for the Centers for Disease Control and Prevention's Advanced Molecular Detection (AMD) program. In an interview last month, CDC Director Rochelle Walensky said that the additional funding will be "a dial. And we're going to need to dial it up." AMD has already announced a collaboration called the Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance (SPHERES) Initiative that will bring together scientists from public health, academic, clinical, and non-profit laboratories across the country with the goal of accelerating sequencing.
Such a collaboration is a step toward following the recommendations in the paper Warmbrod coauthored. Building capacity now, creating a network of labs, and standardizing procedures will mean improved health in the future. "I want to be optimistic," she says. "The good news is there are a lot of passionate, smart, capable people who are continuing to work with government and work with different stakeholders." She cautions, however, that without a national strategy we won't succeed.
"If we maximize the potential and create that framework now, we can also use it for endemic diseases," she says. "It's a very helpful system for more than COVID if we're smart in how we plan it."
Scientists turn pee into power in Uganda
At the edge of a dirt road flanked by trees and green mountains outside the town of Kisoro, Uganda, sits the concrete building that houses Sesame Girls School, where girls aged 11 to 19 can live, learn and, at least for a while, safely use a toilet. In many developing regions, toileting at night is especially dangerous for children. Without electrical power for lighting, kids may fall into the deep pits of the latrines through broken or unsteady floorboards. Girls are sometimes assaulted by men who hide in the dark.
For the Sesame School girls, though, bright LED lights, connected to tiny gadgets, chased the fears away. They got to use new, clean toilets lit by the power of their own pee. Some girls even used the light provided by the latrines to study.
Urine, whether animal or human, is more than waste. It’s a cheap and abundant resource. Each day across the globe, 8.1 billion humans make 4 billion gallons of pee. Cows, pigs, deer, elephants and other animals add more. By spending money to get rid of it, we waste a renewable resource that can serve more than one purpose. Microorganisms that feed on nutrients in urine can be used in a microbial fuel cell that generates electricity – or "pee power," as the Sesame girls called it.
Plus, urine contains water, phosphorus, potassium and nitrogen, the key ingredients plants need to grow and survive. Human urine could replace about 25 percent of current nitrogen and phosphorous fertilizers worldwide and could save water for gardens and crops. The average U.S. resident flushes a toilet bowl containing only pee and paper about six to seven times a day, which adds up to about 3,500 gallons of water down per year. Plus cows in the U.S. produce 231 gallons of the stuff each year.
Pee power
A conventional fuel cell uses chemical reactions to produce energy, as electrons move from one electrode to another to power a lightbulb or phone. Ioannis Ieropoulos, a professor and chair of Environmental Engineering at the University of Southampton in England, realized the same type of reaction could be used to make a fuel from microbes in pee.
Bacterial species like Shewanella oneidensis and Pseudomonas aeruginosa can consume carbon and other nutrients in urine and pop out electrons as a result of their digestion. In a microbial fuel cell, one electrode is covered in microbes, immersed in urine and kept away from oxygen. Another electrode is in contact with oxygen. When the microbes feed on nutrients, they produce the electrons that flow through the circuit from one electrod to another to combine with oxygen on the other side. As long as the microbes have fresh pee to chomp on, electrons keep flowing. And after the microbes are done with the pee, it can be used as fertilizer.
These microbes are easily found in wastewater treatment plants, ponds, lakes, rivers or soil. Keeping them alive is the easy part, says Ieropoulos. Once the cells start producing stable power, his group sequences the microbes and keeps using them.
Like many promising technologies, scaling these devices for mass consumption won’t be easy, says Kevin Orner, a civil engineering professor at West Virginia University. But it’s moving in the right direction. Ieropoulos’s device has shrunk from the size of about three packs of cards to a large glue stick. It looks and works much like a AAA battery and produce about the same power. By itself, the device can barely power a light bulb, but when stacked together, they can do much more—just like photovoltaic cells in solar panels. His lab has produced 1760 fuel cells stacked together, and with manufacturing support, there’s no theoretical ceiling, he says.
Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofit into urban wastewater utilities.
This image shows how the pee-powered system works. Pee feeds bacteria in the stack of fuel cells (1), which give off electrons (2) stored in parallel cylindrical cells (3). These cells are connected to a voltage regulator (4), which smooths out the electrical signal to ensure consistent power to the LED strips lighting the toilet.
Courtesy Ioannis Ieropoulos
Key to the long-term success of any urine reclamation effort, says Orner, is avoiding what he calls “parachute engineering”—when well-meaning scientists solve a problem with novel tech and then abandon it. “The way around that is to have either the need come from the community or to have an organization in a community that is committed to seeing a project operate and maintained,” he says.
Success with urine reclamation also depends on the economy. “If energy prices are low, it may not make sense to recover energy,” says Orner. “But right now, fertilizer prices worldwide are generally pretty high, so it may make sense to recover fertilizer and nutrients.” There are obstacles, too, such as few incentives for builders to incorporate urine recycling into new construction. And any hiccups like leaks or waste seepage will cost builders money and reputation. Right now, Orner says, the risks are just too high.
Despite the challenges, Ieropoulos envisions a future in which urine is passed through microbial fuel cells at wastewater treatment plants, retrofitted septic tanks, and building basements, and is then delivered to businesses to use as agricultural fertilizers. Although pure urine produces the most power, Ieropoulos’s devices also work with the mixed liquids of the wastewater treatment plants, so they can be retrofitted into urban wastewater utilities where they can make electricity from the effluent. And unlike solar cells, which are a common target of theft in some areas, nobody wants to steal a bunch of pee.
When Ieropoulos’s team returned to wrap up their pilot project 18 months later, the school’s director begged them to leave the fuel cells in place—because they made a major difference in students’ lives. “We replaced it with a substantial photovoltaic panel,” says Ieropoulos, They couldn’t leave the units forever, he explained, because of intellectual property reasons—their funders worried about theft of both the technology and the idea. But the photovoltaic replacement could be stolen, too, leaving the girls in the dark.
The story repeated itself at another school, in Nairobi, Kenya, as well as in an informal settlement in Durban, South Africa. Each time, Ieropoulos vowed to return. Though the pandemic has delayed his promise, he is resolute about continuing his work—it is a moral and legal obligation. “We've made a commitment to ourselves and to the pupils,” he says. “That's why we need to go back.”
Urine as fertilizer
Modern day industrial systems perpetuate the broken cycle of nutrients. When plants grow, they use up nutrients the soil. We eat the plans and excrete some of the nutrients we pass them into rivers and oceans. As a result, farmers must keep fertilizing the fields while our waste keeps fertilizing the waterways, where the algae, overfertilized with nitrogen, phosphorous and other nutrients grows out of control, sucking up oxygen that other marine species need to live. Few global communities remain untouched by the related challenges this broken chain create: insufficient clean water, food, and energy, and too much human and animal waste.
The Rich Earth Institute in Vermont runs a community-wide urine nutrient recovery program, which collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms.
One solution to this broken cycle is reclaiming urine and returning it back to the land. The Rich Earth Institute in Vermont is one of several organizations around the world working to divert and save urine for agricultural use. “The urine produced by an adult in one day contains enough fertilizer to grow all the wheat in one loaf of bread,” states their website.
Notably, while urine is not entirely sterile, it tends to harbor fewer pathogens than feces. That’s largely because urine has less organic matter and therefore less food for pathogens to feed on, but also because the urinary tract and the bladder have built-in antimicrobial defenses that kill many germs. In fact, the Rich Earth Institute says it’s safe to put your own urine onto crops grown for home consumption. Nonetheless, you’ll want to dilute it first because pee usually has too much nitrogen and can cause “fertilizer burn” if applied straight without dilution. Other projects to turn urine into fertilizer are in progress in Niger, South Africa, Kenya, Ethiopia, Sweden, Switzerland, The Netherlands, Australia, and France.
Eleven years ago, the Institute started a program that collects urine from homes and businesses, transports it for processing, and then supplies it as fertilizer to local farms. By 2021, the program included 180 donors producing over 12,000 gallons of urine each year. This urine is helping to fertilize hay fields at four partnering farms. Orner, the West Virginia professor, sees it as a success story. “They've shown how you can do this right--implementing it at a community level scale."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.