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Follow the money

The COVID-19 pandemic hit the world in early 2020 and the world hit back. With cash.

According to Devex, an independent media platform specializing in global development based in Washington, D.C., as of June 27, 2020, investments totaling U.S.$291.2 billion were made globally through 1,489 program announcements and 1,204 grants. This money didn’t go to health care research though: 86 percent of funding announcements had an economic link to their objectives, with just 1.3 percent clearly linked to health objectives and 0.8 percent for vaccines and treatments.

Yet health care research into the virus proceeded, and within nine months, two vaccines were ready to go. Research and development like that needs investment.

“Understanding who has been doing what is challenging, since there are no complete databases on global research and development. Some sources are proprietary, and in many cases, funding is non-transparent,” says Bhaven Sampat, an associate professor in the Department of Health Policy and Management at Columbia University. “However, the data we can piece together reveal a consistent picture of public-sector support for downstream research, development and production.”

Sampat’s research found the largest funding response came from the U.S. government, with roughly U.S.$15 billion of the U.S.$4 trillion allocated to the COVID-19 response given to R&D for vaccines and treatments. A worldwide rush of research on treatments and vaccines had begun, and as the world’s largest funder of biomedical research, the National Institutes of Health (NIH), took steps to coordinate the efforts of public and private

researchers globally, to focus on promising candidates and avoid duplicate research.

“Other global actors also contributed funding for therapies and vaccines,” Sampat says. “The European Union has provided financing from the European Investment Bank, member states such as France and Germany have provided research funding, and while data is unavailable from China and Russia, both appear to have made substantial investments in R&D and are responsible for seven of the fourteen vaccines in Phase 3 trials.”

PHILANTHROPY TO THE RESCUE

Philanthropic actors have also had a huge part in the response. Not only did philanthropies donate money to vaccine and treatment development but they also played a coordinating role, helping to facilitate the global scale-up. “In Latin America, the Carlos Slim Foundation supported at-risk manufacturing of the Oxford/AstraZeneca vaccine in Argentina and Mexico,” Sampat says.

At-risk contracts are advance market commitments: They are promises to purchase the product, enabling manufacturers to raise the financing to build the facilities and workforces necessary for emergency production. In vaccine manufacturing, there’s a regulatory aspect too. The Oxford/AstraZeneca vaccine was still awaiting approval, meaning the manufacturers would be turning out doses without knowing whether they’d pass regulatory scrutiny. Risky business.

RAPID RESPONSE?

“The COVID-19 pandemic tested the NIH’s ability to fund critical research to answer research questions that significantly affect public health and require urgent scientific clarity,” Tinglong Dai, professor of operations management and business analytics at John Hopkins University, says. Dai’s research focuses on the health care ecosystem and health care operations management. Dai looked into the funding awarded by the NIH for COVID-19 research, finding just 2 percent of the NIH-funded projects had anything to do with COVID-19 research in 2020.

“In 2020, COVID-19 research accounted for 5.3 percent of the annual NIH budget of $41.7 billion,” Dai says. “In the first three months of the global pandemic, a total of six grants were awarded for COVID-19 research, with the NIH spending a total of 0.1 percent of its annual budget on COVID-19 research in this time. By the end of 2020, that total had risen to 5.3 percent.”

Dai and his fellow researchers found that infrastructure and education accounted for 55.9 percent of NIH COVID-19 funding, yet many of the major clinical questions surrounding transmission were left unanswered, creating challenges for evidence-based policymaking. This may have influenced the public response to COVID-19 measures such as mask mandates and social distancing. The researchers also pointed out that the lack of rapid clinical research funding to understand COVID-19 transmission may have contributed to the politicization of the virus.

“Some of the most basic questions that were being asked of medical professionals in early 2020, such as how it spreads and whether masks protect individuals, went unanswered,” Dai says. “In the absence of evidence-based answers, political opinions filled that vacuum. As the largest research-funding arm of the federal government, the NIH has a responsibility to fund research that can address misinformation with evidence. A resilient health care system in times of crisis should be able to pivot funding toward specific grants answering critical gaps in knowledge.”

Dai says he believes the NIH should develop mechanisms to rapidly award funding to addressing scientific unknowns associated with sudden, large-scale health emergencies: “Supporting sound clinical research aimed at developing evidence-based recommendations is important for public policy and promotes public trust in the medical profession during a pandemic.”

Although the NIH response may have been sluggish, venture capitalists were quick off the mark.

READY, SET, GRANT!

Official advice from the NIH suggests that grant planning should begin nine months in advance of the deadline for the grant. That’s inefficient at the best of times, but needing to pre-empt a crisis no one saw coming makes it a disastrous way to award funding.

Fast Grants is an aptly named response to this funding issue, set up by Patrick Collinson, CEO of Stripe, and Tyler Cowen, economist at George Mason University. On April 7, 2020, Fast Grants launched a call for grant applications, offering a decision within 48 hours. It was immediately swamped, granting its entire budget of U.S.$12 million in less than a week.

The eligibility criteria were simple: Applicants must be a principal investigator at an academic institution, already working on a project that could help with the COVID-19 pandemic within the next six months, and in need of additional funding to complete the project.

In that first week, Fast Grants awarded more than 130 grants, offering the money “as fast as your university can receive it.” Fast Grants promised it would take less than 30 minutes to apply, and a decision would be made within two days, with Cowen making the final decisions to distribute the money. It was immediately obvious that there were thousands of projects just waiting for a final injection of cash, and the venture capitalists behind Fast Grants put up more money for a second call on July 12, 2020.

Applications are now paused “due to receipt of a very large number of qualified submissions,” according to the Fast Grants website. As of 2022, Fast Grants has awarded more than USD$40 million to Covid-19 research that can be finished within six months.

FAST RESULTS

Receiving the money may be super speedy compared with traditional funding avenues, but Fast Grants wanted super speedy results in return. “Most existing funding bodies focus on supporting longer-term work,” the Fast Grants website reads. “Given COVID-19’s human costs, speed is of paramount importance.”

Following successful applications, many projects were completed and contributed significantly to the global pandemic response: Wataru Akahata at Kyoto University and Erec Stebbins at the German Cancer Research Center worked on developing vaccines; Carolyn Bertozzi at Stanford University identified predictive biomarkers for COVID-19 disease progression; Steven Marc Friedman at University of Toronto investigated saliva as a test for SARS-CoV-2; and Alain Townsend at Oxford University looked into antibodies to the virus’ spike protein.

IMAGE: Harry S. Truman Library and Museum
The National Defense Research Committee

Formed: June 27, 1940 Read more›››

Dissolved: June 28, 1941

Role: Coordinate, supervise and conduct scientific research.

Achievements: Provided $6.5 million to scientific research.‹‹‹ Read less

Collinson and Cowen were inspired by a similar funding mechanism dating back to the days of World War II.

The National Defense Research Committee (NDRC) was an organization created in 1940 to “coordinate, supervise, and conduct scientific research on the problems underlying the development, production, and use of mechanisms and devices of warfare” in the United States. In its 12 months of activity, it funded the research into some of the most important technology used during World War II, including radar and the atomic bomb. Although it became the Office of Scientific Research and Development in 1941 and was eventually terminated in 1947, in its one year of existence, the NDRC provided USD$6.5 million to scientific research. And it granted this money quickly.

“Within a week, the NDRC could review the project,” reads the memoir of Vannevar Bush, leader of the project in 1940. “The next day, the director could authorize, the business office could send out a letter of intent, and the actual work could start.”

Although radar and sonar received the bulk of the NDRC attention, arguably its most important project eventually became the Manhattan Project, the full-scale effort to produce nuclear weapons. No longer beholden to the US military for funds, the project ran full steam ahead with NDRC funds.

In a global conflict, time was of the essence. In a global pandemic, it’s the same story. Time mattered in the early days of the Second World War.  Days mattered.

THE NEED FOR SPEED

Days mattered in the early days of the pandemic, too: Getting money to researchers was literally a matter of life or death.

Researchers at Columbia University suggest that had the U.S. begun social distancing just one week earlier, the country could have prevented 36,000 deaths through early May 2020.

“In major metropolitan areas, we found significant reductions in transmission when social distancing and other control measures were implemented,” Jeffrey Shaman, epidemiologist at Columbia University, writes in a paper published in 2020. “Our simulations indicate that had these same control measures been implemented just one to two weeks earlier, a substantial number of cases and deaths could have been avoided. Such dramatic reductions in morbidity and mortality due to more timely deployment of control measures highlights the critical need for an aggressive, early response to the COVID-19 pandemic.”

The U.S. response wasn’t entirely sedate, however. In May 2020, a program named Operation Warp Speed was initiated to accelerate the development, manufacturing and distribution of COVID-19 vaccines, therapeutics and diagnostics. The program promoted mass production of multiple vaccines and types of vaccine technologies, allowing for faster distribution if clinical trials confirmed one of the vaccines was safe and effective.

The plan anticipated that some of these vaccines would not prove safe or effective, making the program more costly than typical vaccine development, but potentially leading to the availability of a viable vaccine several months earlier than typical timelines.

By January 2021, Operation Warp Speed had put its U.S.$18 billion budget to good use, funding five of 16 SARS-CoV-2 vaccines around the world to Phase 3 clinical trial stage.The US threw money at the problem, and it paid off with the development of the Moderna and Pfizer/BioNTech vaccines.

It’s important to note, however, that the NIH was mandated by Congress to disburse its COVID-19 funds over a nearly five-year time frame. This allows for more planning and longer-term research, while negating the need for a huge change in funding processes.

With other initiatives such as Operation Warp Speed, it could be claimed that the NIH did not need to change the way it awards funding, especially when combined with a perhaps expected injection of billions of dollars in public-private collaborations and investment from the private sector.

WHEN PRIVATE AND PUBLIC PLAY TOGETHER

Although governments around the world struggled to respond to COVID-19, scientists and researchers made the most of expedited resources to tackle the virus.

In only a few weeks, Public-Private Partnerships (PPPs) were formed. These collaborative relationships mostly include governmental agencies and intragovernmental organizations (such as the World Health Organization as public actors, and university and research institutes, commercial pharmaceutical companies and professionals as private actors. Complementary expertise and knowledge is pooled, and the rewards are shared.

“We saw the rapid formation of PPPs to develop new vaccines for the novel coronavirus,” says Vijay Pereira, associate professor of humanities and social sciences at Khalifa University. “The private sector offered the funds and tapped into the knowledge base of partners from academic, public, and private-sector organizations to leverage each other’s strengths towards a common goal.”

In many ways, partnerships between academia and industry make sense: There are many societal problems in need of a technological solution, and industry is willing to pay for these solutions. Researchers with interests in line with public concerns can contribute to solving the problem, and industry can then get these solutions to the public.

To put it bluntly: Industry players spend money to make money and will spend that money on research that can ultimately make them more money. This is great for times of crises like the COVID-19 pandemic and the increasingly extreme climate change — crises that are a central risk to human prosperity and health.

But this leaves researchers looking into less industry-friendly science at a loss. Government funding is harder to get, and there’s no money to be made from the more esoteric scientific questions.

Industry funds applied-solutions-oriented science, not science for science’s sake (the so-called “blue sky” science).

The private sector offered the funds and tapped into the knowledge base of partners from academic, public, and private-sector organizations to leverage each other’s strengths towards a common goal.

– Vijay Pereira, associate professor of humanities and social sciences at Khalifa University

And yet there is value in science for its own sake, for research into questions that don’t have an immediate application. Value that goes beyond the potential much of this science will ultimately have (mRNA vaccine, anyone?). Converting this value from curiosity to cold hard cash is where the problem lies.

Unless you’re a billionaire research scientist, you’ll need external funding for your work. Traditionally, this involves you or your team bidding for funding, writing endless documents about your work and your ideas, with the application review process and administration taking months. If funded, projects are given a time frame: In three to five years, you should have an answer, a result.

Whether your proposal receives funding will rely heavily on whether your purpose and goals closely match the priorities of granting agencies.

The COVID-19 pandemic was the perfect example of science with immediate application being prioritized and a dramatic shift in the way research is funded.

RECOVERING FROM COVID-19

As money and focus were channeled into COVID-19 research over the past few years, it had to come from somewhere. In many cases, projects that would otherwise have been funded had to be overlooked in favor of grappling with an emerging crisis.

The National Institute for Health and Care Research (NIHR) in the United Kingdom funded research into COVID-19 with U.K. Research and Innovation (UKRI), a non-departmental public body sponsored by the Department for Business, Energy and Industrial Strategy; a public body, yes, but one intrinsically linked to the department overseeing business and industry in the United Kingdom. Industry-funded research, if you will.

At the same time, the NIHR is embedded in the U.K.’s National Health Service, meaning the research findings it funded were quickly provided to the NHS doctors and nurses to prevent and treat COVID-19.

“Under NIHR’s restart framework, urgent public-health research into COVID-19 continues to be our number one priority,” the NIHR website reads. “We do, however, recognize the importance of also investing in longer-term research.”

Part of this longer-term research is an investigation into the lessons learned during the pandemic on managing the recovery of research into other conditions.

“While the pandemic inevitably reduced the amount of research we have been able to do into other conditions, we have worked hard to maintain a diverse and active portfolio,” the NIHR website reads.

While research into other conditions continued, it was severely affected by a reduction in capacity and accompanying NHS services.

In December 2020, Cancer Research U.K. announced cuts of £45 million to its research budget. CRUK is responsible for roughly half of publicly funded research into cancer in the U.K. The Canadian Cancer Society predicted that the pandemic would cost them CA$100 million in lost donations during the ongoing financial year, which amounts to more than half their budget.

The American Cancer Society saw a decrease in revenue of around U.S.$200 million. The Association of Medical Research Charities predicts that it will take more than four years for spending in the sector to return to pre-pandemic levels, and a decade to rebuild lost capacity and capability.

While the NIH may have been slow to pivot toward funding COVID-19 related projects, it did not cut funding for cancer research, meaning NIH-funded research into other (equally critical) health care issues was able to continue during the pandemic. After all, it’s not like other diseases or health care problems disappeared with the arrival of COVID-19.

Unfortunately, much research into those problems was halted, not necessarily due to a lack of funding, but safety concerns. The vice-chancellor of Cambridge University instructed “unless it is related to COVID-19, all research undertaken on university premises will need to be paused.” Clinical trials around the world were also forced to stop as it was simply unsafe for patients to visit hospitals unless absolutely necessary, and medical staff were needed elsewhere to support care for COVID-19 patients. All this adds up to serious delays in finding treatments for other serious illnesses. How these projects will recover from the pandemic remains to be seen.

Short-term measures are bound to have a long-lasting impact on the research world. As funding decreased for non-COVID-19-related projects, recruitment had to stall, meaning there are quality researchers out there with no jobs. Lab closures mean projects can’t be completed by their deadlines, with grant money running out and PIs unable to pay their lab members. Not to mention the long-term economic downturn as a result of the pandemic means science funding could face longer-term impacts and cuts. The cancer charities seeing fewer donations is a direct result of a weakened economy.

Many of the world’s largest research funders did adapt their funding policies in response to the pandemic but these changes can’t have saved every project.

THE FUTURE OF FUNDING

The COVID-19 pandemic put a spotlight on health care research and its pathways for funding. It’s clear that research in academia would benefit from significant restructuring to deal with global challenges that require fast solutions.

“Our findings revealed critical flaws in the funding of critical public health research in the United States,” says Dai, the Johns Hopkins University professor who looked into COVID-19 funding. “Research responsiveness — that is, an infrastructure that allows for rapid and near-real-time learning in terms of clinical practice, public health measures and management principles — is a critical dimension of health care resilience.

“While, in the future, research infrastructure should be rapidly expandable and facilitated during times of crisis to better understand the impact and solutions, non-crisis-related research should not be halted, but supplemented by crisis-related research to minimize disruptions in other health care and public-health priorities. Additionally, surveillance of novel threats should be funded before an issue even arises, so we can be better prepared in the event of a new crisis.”

Research responsiveness — that is, an infrastructure that allows for rapid and near-real-time learning in terms of clinical practice, public health measures and management principles — is a critical dimension of health care resilience.

– Tinglong Dai

“The COVID-19 innovation system represents a departure from business as usual,” says Columbia’s Sampat. “Considering the remarkable progress to date, especially on vaccine development, this raises the question of whether this model is useful only for crisis times, or whether biomedical innovation policy in ‘normal’ times might productively incorporate some elements of the COVID-19 model as well.”

In the wake of the pandemic, we can all reflect on what we got right and what we got wrong. It’s clear that getting funding to scientists in a matter of days helped enormously in dealing with a global health threat, but the volume of applications for such grants proved how much science there is out there in need of just a final boost of investment.

A need for quick answers to some of the most pressing questions highlighted the burdensome process of applying for grants and accessing funding. The pandemic not only paused projects, but impacted researcher careers, especially those in the early stages, and now there may not be roles to return to.

“Applying the COVID-19 model beyond the pandemic would mean more public funding for late-stage research, clinical trials, development and manufacturing,” Sampat says. “The pandemic has demonstrated that effective biomedical research policy does not end with drug and vaccine development alone.”

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Making this the last pandemic

There are a lot of people, Bill Gates included, who could have said “I told you so” at the start of the COVID-19 pandemic. In 2015, Gates warned a pandemic could happen and that the world was unprepared.

In How to Prevent the Next Pandemic, published seven years later, two years into a pandemic, Gates says, “Outbreaks are inevitable, but pandemics are optional.” At first glance, this seems optimistic, if not impossible: In a world this interconnected and interdependent, how can we reasonably and ethically contain outbreaks?

But the experts agree with Gates.

The World Health Organization’s Independent Panel for Pandemic Preparedness and Response says the COVID-19 pandemic was a sign of how vulnerable our world is:

“Our careful scrutiny of the evidence has revealed failures and gaps in international and national responses that must be corrected,” the panel writes in a 2021 report. “Current institutions, public and private, failed to protect people from a devastating pandemic. Without change, they will not prevent a future one. That is why the panel is recommending a fundamental transformation to a new system of complete pandemic preparedness. If we fail to take this goal seriously, we will condemn the world to successive catastrophes.”

Current institutions, public and private, failed to protect people from a devastating pandemic. Without change, they will not prevent a future one.

– WHO’s Independent Panel for Pandemic Preparedness and Response

“No one wants to live through this again ¬— and we don’t have to,” Gates writes. “If we make key investments that benefit everyone, COVID-19 could be the last pandemic ever.”

These key investments? Make and deliver better tools, including vaccines; improve disease monitoring; and strengthen health systems. Gates also advocates for a cross-disciplinary Global Epidemic Response and Mobilization (GERM) team that could contain outbreaks with speed and efficiency.

Some of these investments are already in the making: wastewater monitoring could keep an eye on infections in a community; mRNA vaccine technology has proved its efficacy; telehealth and health wearables changed the way we interact with health-care systems.

Others need more work. Gates calls for data to be available in real time, but data-protection laws and systems lag, and ethical concerns should not be ignored. Plus, changes need to be implemented worldwide, not just in countries that can afford it.

Gates’ calls for monitoring and responding to outbreaks are admirable, but a global coordinated effort is not realistic right now. Pandemics cross borders; they need countries to work together. They need collective investment and effective communication strategies. The COVID-19 pandemic proved some places are not ready, for socioeconomic and political reasons.

Dr. Eeshani Kandpal, senior economist in the Development Research Group of the World Bank, says pandemic-preparedness efforts should focus on the relationship between health inequity and broader social and economic vulnerability.

“The COVID-19 pandemic demonstrates that pandemic preparedness planning cannot be divorced from the fight against inequality,” Dr. Kandpal writes in a 2022 editorial for the British Medical Journal. “Addressing these dual challenges will require investment and political will. Gaps in countries’ capacity to finance health were large before the pandemic and have further widened in its wake, creating a fault line that threatens health security for all. Centering health equity in pandemic preparedness planning is not just the right thing to do, but also the smart thing.”

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History of the mRNA vaccine

Nearly every function in the human body is carried out by proteins. Cells are constantly manufacturing them using single-strand messenger RNA, which is made from a DNA template. Each strand of mRNA holds the information on how to make one type of protein. The cell reads the mRNA, follows the instructions and makes a protein.

mRNA is a recipe book for the body’s cells. The idea? Make precise edits to the recipe, inject people with it, sit back and watch the body make all the proteins you need.

 IMAGE: Anas Al Bounni-KUST Review

Viruses come in different shapes and sizes. Some are DNA viruses, which contain DNA that integrates with the host DNA in certain cells, using that cell’s replication mechanism to multiply. These viruses can activate cancer genes in the host — the human papillomavirus (HPV) is known to cause cervical cancer, for example.

RNA viruses carry RNA and do not integrate that RNA into a host’s DNA. Instead, the RNA is directed to the host ribosomes in cells, with the ribosomes replicating the virus. These viruses do not interact with host DNA.

Once inside the body, the cell reads the vaccine mRNA and begins to make harmless spike proteins of its own. From there, the body recognizes them as a foreign threat and launches an immune response, teaching itself to respond to spike proteins. Should the actual coronavirus come knocking, your cells now know what to do.

The main drawback to mRNA vaccines? The mRNA breaks down very easily. It needs to be delivered inside a protective fatty barrier and kept cold.

mRNA vaccines are a groundbreaking way to elicit an immune response and their real impact is just beginning. Their applications don’t stop at COVID-19; we might be able to figure out the recipe for a cancer or HIV vaccine.

mRNA VACCINE HISTORY

1961-mRNA discovered.

1963-Interferon induction by mRNA discovered.

1965-First liposomes produced.

1969-First proteins produced from isolated mRNA in lab.

1971-Liposomes first used for drug delivery.

1974-Liposomes first used for vaccine delivery.

1978-First liposome-wrapped mRNA delivery to cells.

1984-mRNA synthesized in lab.

1989-First time synthetic mRNA in liposomes is delivered to human cells.

1992-mRNA tested as a treatment in rats.

1993-First mRNA vaccines tested for influenza in mice.

1995-mRNA tested as cancer vaccine in mice.

2005-Discovery that modified RNA evades immune detection.

2013-First clinical trial of mRNA vaccine for infectious disease (rabies).

2020-First mRNA-based COVID-19 vaccine approved for emergency use.

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How UAE managed the COVID-19 pandemic

The UAE was quick to turn to wastewater monitoring when the COVID-19 pandemic struck.

“The United Arab Emirates was the first in the region and the fifth worldwide,” Habiba Al Safar, the director of Khalifa University’s Center for Biotechnology, tells KUST Review.

Al Safar and teammates Shadi Hasan and Ahmed Yousef, in partnership with the Ministry of the Interior and Abu Dhabi Department of Energy, established the surveillance pipeline and strategic plan to tackle the pandemic in its earliest days.

It wasn’t an easy task, Al Safar says.

The team worked around the clock to prepare in-house reagents in this country. We had the full support from the government, and that helped the program to keep going non-stop.

– Habiba Al Safar

“We established a scientific committee to discuss the best way to approach this pandemic by introducing an environmental surveillance program in the UAE. And given the full lockdown and the shortage of the supply chain of chemicals, equipment and reagents, we had to come up with a plan with existing equipment and laboratory facilities in the country. We had to build a dedicated laboratory for this program, and we did it in less than four months.”

Supply-chain issues made importing chemicals and consumables from abroad difficult.

“However, the team worked around the clock to prepare in-house reagents in this country,” Al Safar says. “We had the full support from the government, and that helped the program to keep going non-stop,” she adds.

Over the course of the pandemic, the university and government team members in Abu Dhabi helped inform UAE response policy, meeting weekly with top government officials and providing alerts when they spotted incoming waves, variants and disease hotspots.

This project also led the team to publish, with many surveillance programs established around the world using the project’s protocol, Al Safar says.

The wastewater monitoring, which has since been turned over to Ministry of the Interior, gave the government the information it needed for early detection of upcoming waves. This helped it create procedures and manage lockdowns.

“The UAE has managed the pandemic very well,” she says. “All the procedures and precautions that the decision makers were conducting and the massive PCR testing drives were to the benefit of our society and beloved people.” We are very lucky to have a leadership that cares for our well-being.”

Among other benefits from the project: It also provided training to UAE nationals and police officers, Al Safar says. “We didn’t just provide services. We provided training, knowledge, research and discoveries.”

In addition, the team recently filed a patent for a sensor that can detect the COVID-19 virus in wastewater in less than one minute.

In other responses to the pandemic, Khalifa University launched in 2020 a research and development program to rapidly develop knowledge and solutions in the areas of epidemiology; digital tools for virus-spread mitigation and resiliency; and diagnostics and medical devices. Sixteen projects were funded at a total level exceeding AED 10M. These included developing membranes for anti-viral masks; detailed knowledge regarding how the COVID-19 virus transmits between mammals and humans; and a mobile app that captures health data and detects early signs of COVID-19 symptoms.

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Early warning from the sewers

The virus raged around the world, terrifying the populace with its seemingly random strikes.

Most victims showed no signs of the disease or had mild complaints. Just a fever or fatigue, maybe. Others suffered more serious symptoms, with some becoming unable to breathe on their own. A not insignificant number of patients developed long-term disabilities. In extreme cases, people died.

While the planet waited for a vaccine, governments responded by imposing social-distancing rules as the disease hit again and again in seasonal waves. Events were canceled. City pools were closed. Families avoided public parks.

And epidemiologists in the United States monitored the outbreak by surveilling wastewater – including the untreated waste from household drains and toilets – for evidence of the disease at large.

Preserving samples
for posterity

Taking samples from a community’s wastewater can help public-health authorities track and monitor disease practically in real time. But researchers from the University of Basel in Switzerland and Rockefeller University in the United States are suggesting another use for the technology: creating biological time capsules. Read more›››

In a paper in BMC Infectious Diseases, David S. Thaler and Thomas P. Sakmar suggest systematically storing biological material taken from sewage to create an archive of sorts in case today’s viruses become important in the future.

Preserved “before” and “after” samples could also help scientists studying, for example, a pathogen’s arrival in a city or on a cruise ship, the researchers note.

“There is so much great work throughout the world on monitoring wastewaters for immediate information. If only you could ‘go back in time,’ then it might become possible to learn more about the origin and early spread of infections,” Thaler tells KUST Review. “Also it might help (researchers) understand how effective mitigation measures were. The limiting factor right now is to work out simple, inexpensive ways to obtain and store many samples. Historical records help with understanding so many things.”

Other biological repositories and records include living cell and tissue collections, eDNA and material from museums and medical facilities.‹‹‹ Read less

No, we’re not talking about COVID-19. We’re talking about poliovirus, the pathogen that killed or paralyzed about a half-million people a year worldwide during its peak in the 1940s and ’50s. But the same basic wastewater-surveillance techniques epidemiologists used in Midcentury America to track polio outbreaks would prove useful again some 70 years later when the coronavirus pandemic put an unready world into lockdown.

Of course, the techniques have become much more sophisticated since the 1940s, but the basics remain the same: Take small samples of fecal matter from sewer systems, examine the material in a lab and determine what sorts of pathogens have taken root in a community — whether that community is a city, a neighborhood or even a prison.

REAL-TIME SNAPSHOT

Advances — most notably the emergence in the 1990s of polymerase chain reaction (PCR) to amplify sections of DNA from a small sample — have improved the process, enabling public-health authorities to track disease in a way that might prove difficult by other means because of lag time between tests and results or because the disease is frequently under-reported. This could be because the disease is often asymptomatic or has the kind of nonspecific symptoms that patients are unlikely to report until they get serious, such as influenza, gastroenteritis or, yes, polio. Or the patient or doctor may simply choose not to test.

In those cases, testing sewage removes those barriers from the equation and takes an anonymous, nearly real-time snapshot of a community’s health in a way that would be difficult to achieve by individually testing its members.

“You would have to sequence a ton of clinical or nasal swabs to get that level of resolution,” says Smruthi Karthikeyan, a postdoctoral scholar and lead author of a recent study on using genomic surveillance to detect SARS-CoV-2 infections during 10 months of the pandemic at the University of California, San Diego, in an interview with the Journal of the American Medical Association.

It also gives health authorities an early alert when a new disease is taking a foothold in a community, perhaps warning of an incipient need for more hospital beds or other measures.

In fact, this is what happened when a collaboration between researchers from Stanford University, Emory University and Alphabet company Verily analyzed sewage from 41 communities in 10 U.S. states to track a newly emergent monkeypox in 2022.

“We have now detected monkeypox DNA in sewersheds before any cases were reported in those counties,” Bradley White, a senior staff scientist at Verily, tells Time magazine.

DATA WITHOUT BIASES

Another advantage: It doesn’t have the problem of biases often affecting traditional public-health data.

“A major benefit of wastewater monitoring is that it can capture the health markers of anybody who lives or works in a building connected to a centralized sewer system,” says Aparna Keshaviah, an expert in wastewater epidemiology and principal researcher at Mathematica, a U.S.-based organization that uses data, analytics and technology to address social challenges.

“In other words,” she tells KUST Review, “it doesn’t rely on people to have the will or means for a health-care visit to be counted, and so is less biased than traditional public health data.”

The surveillance can also let those same health authorities know when the storm has passed and it’s time to end such restrictions as social distancing, mask regulations and quarantines.

And it works. Many studies have shown that wastewater monitoring provides an accurate view of disease in a community. COVID-era studies also confirmed that the technique was an accurate reflection of the coronavirus’ course in a community.

A Dutch group, for example, began monitoring the sewage from seven cities and an airport in February 2020, detecting the presence of COVID-19 at five sites just about a week after the first case was reported in the country. Meanwhile, Karthikeyan’s work at UC-San Diego found variants of concern up to two weeks before they turned up in clinical tests.

USED AROUND THE WORLD

At least 55 countries worldwide use wastewater monitoring to track COVID-19. In 2020, the United States launched its National Wastewater Surveillance System, working with health systems across the country to track disease and trends. And in 2021, the European Union asked all member states to put in place wastewater monitoring to track COVID-19 and its variants, with the EU’s Environment Commissioner Virginijus Sinkevičius telling EURACTIV.com that the process is a “cost-effective, rapid and reliable complementary tool.”

Another benefit: The testing can immediately assist more than researchers looking to track disease. It can also provide a real-time heads-up to members of the community.

“In communities where the wastewater data are made public in a timely fashion (for example, when public-facing wastewater dashboards are updated weekly with new information on wastewater viral levels), individuals can monitor the data to gauge their risk of exposure to COVID-19 and make more informed decisions about what risks they’re willing to take,” Keshaviah says.

The testing, however, relies on the existence of robust wastewater-treatment and -disposal systems. Most wastewater monitoring, therefore, occurs in more economically advanced nations.

This leaves low- and lower-middle-income countries unable to take full advantage of the public-health benefits. According to Utrecht University’s Edward R. Jones and his team in a paper published in Earth System Science Data, most wastewater isn’t even collected in those countries.

COMMUNICATION IS KEY

Another problem: Information is only as good as the communication network it relies on.

“During this pandemic, many communities launched local or regional wastewater monitoring for the SARS-CoV-2 virus that causes COVID-19. But based on results from a global wastewater survey we recently conducted in partnership with the Rockefeller Foundation and the United Kingdom Health Security Agency, the resulting data have not always been shared in a timely fashion with neighboring communities, let alone with other countries across the globe,” Mathematica’s Keshaviah tells KUST Review.

“In today’s interconnected world, international travel is 56 times more common than it was in 1950, and so one country’s local infectious disease outbreak can quickly become a global pandemic,” she says. “If we’re to have any chance at getting an early warning of the next new health threat before it explodes into another pandemic, we need global leadership to coalesce the many individual wastewater initiatives that now exist into a multi-nodal, unified disease-monitoring network that’s always on and always communicating.”

CAPTION: Khalifa University

Wastewater monitoring can be used for more than detecting disease. It has also been used to detect the use of illicit drugs in a community.

The European Monitoring Centre for Drugs and Drug Addiction used data from studies conducted since 2011 to plot the prevalence of such substances as cocaine, methamphetamines and cannabis in 80 European cities and towns, revealing what it called distinct geographical and temporal patterns.

CONCERNS ABOUT PRIVACY

Surveillance could perhaps do more. And that raises privacy and civil-liberties concerns.

A paper from academics in law and medical programs at Wayne State University and the University of Maryland that was published in the Journal of Law and the Biosciences notes that there are legal and ethical implications to consider, such as governments using evidence of a pathogen in public wastewater to justify additional screenings of certain neighborhoods or impose penalties on those who refuse to cooperate.

Mathematica’s Keshaviah sees a potential for concern that small communities and individuals might be identifiable via wastewater monitoring, but also a solution:
“When wastewater data are collected at centralized wastewater treatment plants that serve many hundreds, thousands or millions of people (which is the most cost-effective way to detect novel threats), there’s little chance that the data could be identifying. However, when monitoring occurs at the neighborhood or facility level, when the threat being monitored is quite rare, or when wastewater data are combined with other data sources, the risk of identifying individuals can increase.

“That said, just as with medical data, wastewater data can be blinded before they’re shared, so that individuals or communities are not stigmatized by the results. The data can be collected at a localized level to inform decision making, but shared in such a way that obscures the precise communities represented by the data, to preserve privacy,” she says.

In the meantime, wastewater monitoring continues to help public-health authorities track disease via the public sewers.

In October 2022, researchers with the U.S. Centers for Disease Control and Prevention and various public-health programs published an article about investigating a potential emerging viral threat in New York City.

They found polio.