Medical Breakthroughs Set to be Fast-Tracked by Innovative New Health Agency
In 2007, Matthew Might's son, Bertrand, was born with a life-threatening disease that was so rare, doctors couldn't diagnose it. Might, a computer scientist and biologist, eventually realized, "Oh my gosh, he's the only patient in the world with this disease right now." To find effective treatments, new methodologies would need to be developed. But there was no process or playbook for doing that.
Might took it upon himself, along with a team of specialists, to try to find a cure. "What Bertrand really taught me was the visceral sense of urgency when there's suffering, and how to act on that," he said.
He calls it "the agency of urgency"—and patients with more common diseases, such as cancer and Alzheimer's, often feel that same need to take matters into their own hands, as they find their hopes for new treatments running up against bureaucratic systems designed to advance in small, steady steps, not leaps and bounds. "We all hope for a cure," said Florence "Pippy" Rogers, a 65-year-old volunteer with Georgia's chapter of the Alzheimer's Association. She lost her mother to the disease and, these days, worries about herself and her four siblings. "We need to keep accelerating research."
We have a fresh example of what can be achieved by fast-tracking discoveries in healthcare: Covid-19 vaccines.
President Biden has pushed for cancer moonshots since the disease took the life of his son, Beau, in 2015. His administration has now requested $6.5 billion to start a new agency in 2022, called the Advanced Research Projects Agency for Health, or ARPA-H, within the National Institutes of Health. It's based on DARPA, the Department of Defense agency known for hatching world-changing technologies such as drones, GPS and ARPANET, which became the internet.
We have a fresh example of what can be achieved by fast-tracking discoveries in healthcare: Covid-19 vaccines. "Operation Warp Speed was using ARPA-like principles," said Might. "It showed that in a moment of crisis, institutions like NIH can think in an ARPA-like way. So now the question is, why don't we do that all the time?"
But applying the DARPA model to health involves several challenging decisions. I asked experts what could be the hardest question facing advocates of ARPA-H: which health problems it should seek to address. "All the wonderful choices lead to the problem of which ones to choose and prioritize," said Sudip Parikh, CEO of the American Association for the Advancement of Science and executive publisher of the Science family of journals. "There is no objectively right answer."
The Agency of Urgency
ARPA-H will borrow at least three critical ingredients from DARPA: goal-oriented project managers, many from industry; aggressive public-private partnerships; and collaboration among fields that don't always interact. The DARPA concept has been applied to other purposes, including energy and homeland security, with promising results. "We're learning that 'ARPA-ism' is a franchisable model," said Might, a former principal investigator on DARPA projects.
The federal government already pours billions of dollars into advancing research on life-threatening diseases, with much of it channeled through the National Institutes of Health. But the purpose of ARPA-H "isn't just the usual suspects that NIH would fund," said David Walt, a Harvard biochemist, an innovator in gene sequencing and former chair of DARPA's Defense Science Research Council. Whereas some NIH-funded studies aim to gradually improve our understanding of diseases, ARPA-H projects will give full focus to real-world applications; they'll use essential findings from NIH research as starting points, drawing from them to rapidly engineer new technologies that could save lives.
And, ultimately, billions in healthcare costs, if ARPA-H lives up to its predecessor's track record; DARPA's breakthroughs have been economic game-changers, while its fail-fast approach—quickly pulling the plug on projects that aren't panning out—helps to avoid sunken costs. ARPA-H could fuel activities similar to the human genome project, which used existing research to map the base pairs that make up DNA, opening new doors for the biotech industry, sparking economic growth and creating hundreds of thousands of new jobs.
Despite a nearly $4 trillion health economy, "we aren't innovating when it comes to technological capabilities for health," said Liz Feld, president of the Suzanne Wright Foundation for pancreatic cancer.
Individual Diseases Ripe for Innovation
Although the need for innovation is clear, which diseases ARPA-H should tackle is less apparent. One important consideration when choosing health priorities could be "how many people suffer from a disease," said Nancy Kass, a professor of bioethics and public health at Johns Hopkins.
That perspective could justify cancer as a top objective. Cancer and heart disease have long been the two major killers in the U.S. Leonidas Platanias, professor of oncology at Northwestern and director of its cancer center, noted that we've already made significant progress on heart disease. "Anti-cholesterol drugs really have a wide impact," he said. "I don't want to compare one disease to another, but I think cancer may be the most challenging. We need even bigger breakthroughs." He wondered whether ARPA-H should be linked to the part of NIH dedicated to cancer, the National Cancer Institute, "to take maximum advantage of what happens" there.
Previous cancer moonshots have laid a foundation for success. And this sort of disease-by-disease approach makes sense in a way. "We know that concentrating on some diseases has led to treatments," said Parikh. "Think of spinal muscular atrophy or cystic fibrosis. Now, imagine if immune therapies were discovered ten years earlier."
But many advocates think ARPA-H should choose projects that don't revolve around any one disease. "It absolutely has to be disease agnostic," said Feld, president of the pancreatic cancer foundation. "We cannot reach ARPA-H's potential if it's subject to the advocacy of individual patient groups who think their disease is worse than the guy's disease next to them. That's not the way the DARPA model works." Platanias agreed that ARPA-H should "pick the highest concepts and developments that have the best chance" of success.
Finding Connections Between Diseases
Kass, the Hopkins bioethicist, believes that ARPA-H should walk a balance, with some projects focusing on specific diseases and others aspiring to solutions with broader applications, spanning multiple diseases. Being impartial, some have noted, might involve looking at the total "life years" saved by a health innovation; the more diseases addressed by a given breakthrough, the more years of healthy living it may confer. The social and economic value should increase as well.
For multiple payoffs, ARPA-H could concentrate on rare diseases, which can yield important insights for many other diseases, said Might. Every case of cancer and Alzheimer's is, in a way, its own rare disease. Cancer is a genetic disease, like his son Bertrand's rare disorder, and mutations vary widely across cancer patients. "It's safe to say that no two people have ever actually had the same cancer," said Might. In theory, solutions for rare diseases could help us understand how to individualize treatments for more common diseases.
Many experts I talked with support another priority for ARPA-H with implications for multiple diseases: therapies that slow down the aging process. "Aging is the greatest risk factor for every major disease that NIH is studying," said Matt Kaeberlein, a bio-gerontologist at the University of Washington. Yet, "half of one percent of the NIH budget goes to researching the biology of aging. An ARPA-H sized budget would push the field forward at a pace that's hard to imagine."
Might agreed. "It could take ARPA-H to get past the weird stigmas around aging-related research. It could have a tremendous impact on the field."
For example, ARPA-H could try to use mRNA technology to express proteins that affect biological aging, said Kaeberlein. It's an engineering project well-suited to the DARPA model. So is harnessing machine learning to identify biomarkers that assess how fast people are aging. Biological aging clocks, if validated, could quickly reveal whether proposed therapies for aging are working or not. "I think there's huge value in that," said Kaeberlein.
By delivering breakthroughs in computation, ARPA-H could improve diagnostics for many different diseases. That could include improving biowearables for continuously monitoring blood pressure—a hypothetical mentioned in the White House's concept paper on ARPA-H—and advanced imaging technologies. "The high cost of medical imaging is a leading reason why our healthcare costs are the highest in the world," said Feld. "There's no detection test for ALS. No brain detection for Alzheimer's. Innovations in detection technology would save on cost and human suffering."
Some biotech companies may be skeptical about the financial rewards of accelerating such technologies. But ARPA-H could fund public-private partnerships to "de-risk" biotech's involvement—an incentive that harkens back to the advance purchase contracts that companies got during Covid. (Some groups have suggested that ARPA-H could provide advance purchase agreements.)
Parikh is less bullish on creating diagnostics through ARPA-H. Like DARPA, Biden's health agency will enjoy some independence from federal oversight; it may even be located hundreds of miles from DC. That freedom affords some breathing room for innovation, but it could also make it tougher to ensure that algorithms fully consider diverse populations. "That part I really would like the government more involved in," Parikh said.
Might thinks ARPA-H should also explore innovations in clinical trials, which many patients and medical communities view as grindingly slow and requiring too many participants. "We can approve drugs for very tiny patient populations, even at the level of the individual," he said, while emphasizing the need for safety. But Platanias thinks the FDA has become much more flexible in recent years. In the cancer field, at least, "You now see faster approvals for more drugs. Having [more] shortcuts on clinical trial approvals is not necessarily a good idea."
With so many options on the table, ARPA-H needs to show the public a clear framework for measuring the value of potential projects. Kass warned that well-resourced advocates could skew the agency's priorities. They've affected health outcomes before, she noted; fundraising may partly explain larger increases in life expectancy for cystic fibrosis than sickle cell anemia. Engaging diverse communities is a must for ARPA-H. So are partnerships to get the agency's outputs to people who need them. "Research is half the equation," said Kass. "If we don't ensure implementation and access, who cares." The White House concept paper on ARPA-H made a similar point.
As Congress works on authorizing ARPA-H this year, Might is doing what he can to ensure better access to innovation on a patient-by-patient basis. Last year, his son, Bertrand, passed away suddenly from his disorder. He was 12. But Might's sense of urgency has persisted, as he directs the Precision Medicine Institute at the University of Alabama-Birmingham. That urgency "can be carried into an agency like ARPA-H," he said. "It guides what I do as I apply for funding, because I'm trying to build the infrastructure that other parents need. So they don't have to build it from scratch like I did."
COVID-19 prompted numerous companies to reconsider their approach to the future of work. Many leaders felt reluctant about maintaining hybrid and remote work options after vaccines became widely available. Yet the emergence of dangerous COVID variants such as Omicron has shown the folly of this mindset.
To mitigate the risks of new variants and other public health threats, as well as to satisfy the desires of a large majority of employees who express a strong desire in multiple surveys for a flexible hybrid or fully remote schedule, leaders are increasingly accepting that hybrid and remote options represent the future of work. No wonder that a February 2022 survey by the Federal Reserve Bank of Richmond showed that more and more firms are offering hybrid and fully-remote work options. The firms expect to have more remote workers next year and more geographically-distributed workers.
Although hybrid and remote work mitigates public health risks, it poses another set of health concerns relevant to employee wellbeing, due to the threat of proximity bias. This term refers to the negative impact on work culture from the prospect of inequality among office-centric, hybrid, and fully remote employees.
The difference in time spent in the office leads to concerns ranging from decreased career mobility for those who spend less facetime with their supervisor to resentment building up against the staff who have the most flexibility in where to work. In fact, a January 2022 survey by the company Slack of over 10,000 knowledge workers and their leaders shows that proximity bias is the top concern – expressed by 41% of executives - about hybrid and remote work.
To address this problem requires using best practices based on cognitive science for creating a culture of “Excellence From Anywhere.” This solution is based on guidance that I developed for leaders at 17 pioneering organizations for a company culture fit for the future of work.
Protect from proximity bias via the "Excellence From Anywhere" strategy
So why haven’t firms addressed the obvious problem of proximity bias? Any reasonable external observer could predict the issues arising from differences of time spent in the office.
Unfortunately, leaders often fail to see the clear threat in front of their nose. You might have heard of black swans: low-probability, high-impact threats. Well, the opposite kind of threats are called gray rhinos: obvious dangers that we fail to see because of our mental blindspots. The scientific name for these blindspots is cognitive biases, which cause leaders to resist best practices in transitioning to a hybrid-first model.
The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
Leaders can address this by focusing on a shared culture of “Excellence From Anywhere.” This term refers to a flexible organizational culture that takes into account the nature of an employee's work and promotes evaluating employees based on task completion, allowing remote work whenever possible.
Addressing Resentments Due to Proximity Bias
The “Excellence From Anywhere” strategy addresses concerns about treatment of remote workers by focusing on deliverables, regardless of where you work. Doing so also involves adopting best practices for hybrid and remote collaboration and innovation.
By valuing deliverables, collaboration, and innovation through a focus on a shared work culture of “Excellence From Anywhere,” you can instill in your employees a focus on deliverables. The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
This work culture addresses concerns about fairness by reframing the conversation to focus on accomplishing shared goals, rather than the method of doing so. After all, no one wants their colleagues to have to commute out of spite.
This technique appeals to the tribal aspect of our brains. We are evolutionarily adapted to living in small tribal groups of 50-150 people. Spending different amounts of time in the office splits apart the work tribe into different tribes. However, cultivating a shared focus on business outcomes helps mitigate such divisions and create a greater sense of unity, alleviating frustrations and resentments. Doing so helps improve employee emotional wellbeing and facilitates good collaboration.
Solving the facetime concerns of proximity bias
But what about facetime with the boss? To address this problem necessitates shifting from the traditional, high-stakes, large-scale quarterly or even annual performance evaluations to much more frequent weekly or biweekly, low-stakes, brief performance evaluation through one-on-one in-person or videoconference check-ins.
Supervisees agree with their supervisor on three to five weekly or biweekly performance goals. Then, 72 hours before their check-in meeting, they send a brief report, under a page, to their boss of how they did on these goals, what challenges they faced and how they overcame them, a quantitative self-evaluation, and proposed goals for next week. Twenty-four hours before the meeting, the supervisor responds in a paragraph-long response with their initial impressions of the report.
It’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
At the one-on-one, the supervisor reinforces positive aspects of performance and coaches the supervisee on how to solve challenges better, agrees or revises the goals for next time, and affirms or revises the performance evaluation. That performance evaluation gets fed into a constant performance and promotion review system, which can replace or complement a more thorough annual evaluation.
This type of brief and frequent performance evaluation meeting ensures that the employee’s work is integrated with efforts by the supervisor’s other employees, thereby ensuring more unity in achieving business outcomes. It also mitigates concerns about facetime, since all get at least some personalized attention from their team leader. But more importantly, it addresses the underlying concerns about career mobility by giving all staff a clear indication of where they stand at all times. After all, it’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
Such best practices help integrate employees into a work culture fit for the future of work while fostering good relationships with managers. Research shows supervisor-supervisee relationships are the most critical ones for employee wellbeing, engagement, and retention.
Conclusion
You don’t have to be the CEO to implement these techniques. Lower-level leaders of small rank-and-file teams can implement these shifts within their own teams, adapting their culture and performance evaluations. And if you are a staff member rather than a leader, send this article to your supervisor and other employees at your company: start a conversation about the benefits of addressing proximity bias using such research-based best practices.
When the COVID-19 pandemic began invading the world in late 2019, Peter Hotez and Maria Elena Bottazzi set out to create a low-cost vaccine that would help inoculate populations in low- and middle-income countries. The scientists, with their prior experience of developing inexpensive vaccines for the world’s poor, had anticipated that the global rollout of Covid-19 jabs would be marked with several inequities. They wanted to create a patent-free vaccine to bridge this gap, but the U.S. government did not seem impressed, forcing the researchers to turn to private philanthropies for funds.
Hotez and Bottazzi, both scientists at the Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine, raised about $9 million in private funds. Meanwhile, the U.S. government’s contribution stood at $400,000.
“That was a very tough time early on in the pandemic, you know, trying to do the work and raise the money for it at the same time,” says Hotez, who was nominated in February for a Nobel Peace Prize with Bottazzi for their COVID-19 vaccine. He adds that at the beginning of the pandemic, governments emphasized speed, innovation and rapidly immunizing populations in North America and Europe with little consideration for poorer countries. “We knew this [vaccine] was going to be the answer to global vaccine inequality, but I just wish the policymakers had felt the same,” says Hotez.
Over the past two years, the world has witnessed 488 million COVID-19 infections and over 61 million deaths. Over 11 billion vaccine doses have been administered worldwide; however, the global rollout of COVID-19 vaccines is marked with alarming socio-economic inequities. For instance, 72 percent of the population in high-income countries has received at least one dose of the vaccine, whereas the number stands at 15 percent in low-income countries.
This inequity is worsening vulnerabilities across the world, says Lawrence Young, a virologist and co-lead of the Warwick Health Global Research Priority at the UK-based University of Warwick. “As long as the virus continues to spread and replicate, particularly in populations who are under-vaccinated, it will throw up new variants and these will remain a continual threat even to those countries with high rates of vaccination,” says Young, “Therefore, it is in all our interests to ensure that vaccines are distributed equitably across the world.”
“When your house is on fire, you don't call the patent attorney,” says Hotez. “We wanted to be the fire department.”
The vaccine developed by Hotez and Bottazzi recently received emergency use authorisation in India, which plans to manufacture 100 million doses every month. Dubbed ‘Corbevax’ by its Indian maker, Biological E Limited, the vaccine is now being administered in India to children aged 12-14. The patent-free arrangement means that other low- and middle-income countries could also produce and distribute the vaccine locally.
“When your house is on fire, you don't call the patent attorney, you call the fire department,” says Hotez, commenting on the intellectual property rights waiver. “We wanted to be the fire department.”
The Inequity
Vaccine equity simply means that all people, irrespective of their location, should have equal access to vaccines. However, data suggests that the global COVID-19 vaccine rollout has favoured those in richer countries. For instance, high-income countries like the UAE, Portugal, Chile, Singapore, Australia, Malta, Hong Kong and Canada have partially vaccinated over 85 percent of their populations. This percentage in poorer countries, meanwhile, is abysmally low – 2.1 percent in Yemen, 4.6 in South Sudan, 5 in Cameroon, 9.9 in Burkina Faso, 10 in Nigeria, 12 in Somalia, 12 in Congo, 13 in Afghanistan and 21 in Ethiopia.
In late 2019, scientists Peter Hotez and Maria Elena Bottazzi set out to create a low-cost vaccine that would help inoculate populations in low- and middle-income countries. In February, they were nominated for a Nobel Peace Prize.
Texas Children's Hospital
The COVID-19 vaccination coverage is particularly low in African countries, and according to Shabir Madhi, a vaccinologist at the University of the Witwatersrand, Johannesburg and co-director of African Local Initiative for Vaccinology Expertise, vaccine access and inequity remains a challenge in Africa. Madhi adds that a lack of vaccine access has affected the pandemic’s trajectory on the continent, but a majority of its people have now developed immunity through natural infection. “This has come at a high cost of loss of lives,” he says.
COVID-19 vaccines mean a significant financial burden for poorer countries, which spend an average of $41 per capita annually on health, while the average cost of every COVID-19 vaccine dose ranges between $2 and $40 in addition to a distribution cost of $3.70 per person for two doses. In December last year, the World Health Organisation (WHO) set a goal of immunizing 70 percent of the population of all countries by mid-2022. This, however, means that low-income countries would have to increase their health expenditure by an average of 56.6 percent to cover the cost, as opposed to 0.8 per cent in high-income countries.
Reflecting on the factors that have driven global inequity in COVID-19 vaccine distribution, Andrea Taylor, assistant director of programs at the Duke Global Health Innovation Center, says that wealthy nations took the risk of investing heavily in the development and scaling up of COVID-19 vaccines – at a time when there was little evidence to show that vaccines would work. This reserved a place for these nations at the front of the queue when doses started rolling off production lines. Lower-income countries, meanwhile, could not afford such investments.
“Now, however, global supply is not the issue,” says Taylor. “We are making plenty of doses to meet global need. The main problem is infrastructure to get the vaccine where it is most needed in a predictable and timely way and to ensure that countries have all the support they need to store, transport, and use the vaccine once it is received.”
Taufique Joarder, vice-chairperson of Bangladesh's Public Health Foundation, sees the need for more trials and data before Corbevax is made available to the general population.
In addition to global inequities in vaccination coverage, there are inequities within nations. Taufique Joarder, vice-chairperson of Bangladesh’s Public Health Foundation, points to the situation in his country, where vaccination coverage in rural and economically disadvantaged communities has suffered owing to weak vaccine-promotion initiatives and the difficulty many people face in registering online for jabs.
Joarder also cites the example of the COVID-19 immunization drive for children aged 12 years and above. “[Children] are given the Pfizer vaccine, which requires an ultralow temperature for storage. This is almost impossible to administer in many parts of the country, especially the rural areas. So, a large proportion of the children are being left out of vaccination,” says Joarder, adding that Corbevax, which is cheaper and requires regular temperature refrigeration “can be an excellent alternative to Pfizer for vaccinating rural children.”
Corbevax vs. mRNA Vaccines
As opposed to most other COVID-19 vaccines, which use the new Messenger RNA (mRNA) vaccine technology, Corbevax is an “old school” vaccine, says Hotez. The vaccine is made through microbial fermentation in yeast, similar to the process used to produce the recombinant hepatitis B vaccine, which has been administered to children in several countries for decades. Hence, says Hotez, the technology to produce Corbevax at large scales is already in place in countries like Vietnam, Bangladesh, India, Indonesia, Brazil, Argentina, among many others.
“So if you want to rapidly develop and produce and empower low- and middle-income countries, this is the technology to do it,” he says.
“Global access to high-quality vaccines will require serious investment in other types of COVID-19 vaccines," says Andrea Taylor.
The COVID-19 vaccines created by Pfizer-BioNTech and Moderna marked the first time that mRNA vaccine technology was approved for use. However, scientists like Young feel that there is “a need to be pragmatic and not seduced by new technologies when older, tried and tested approaches can also be effective.” Taylor, meanwhile, says that although mRNA vaccines have dominated the COVID-19 vaccine market in the U.S., “there is no clear grounding for this preference in the data we have so far.” She adds that there is also growing evidence that the immunity from these shots may not hold up as well over time as that of vaccines using different platforms.
“The mRNA vaccines are well suited to wealthy countries with sufficient ultra-cold storage and transportation infrastructure, but these vaccines are divas and do not travel well in the rest of the world,” says Taylor. “Global access to high-quality vaccines will require serious investment in other types of COVID-19 vaccines, such as the protein subunit platform used by Novavax and Corbevax. These require only standard refrigeration, can be manufactured using existing facilities all over the world, and are easy to transport.”
Joarder adds that Corbevax is cheaper due to the developers’ waived intellectual rights. It could also be used as a booster vaccine in Bangladesh, where only five per cent of the population has currently received booster doses. “If this vaccine is proved effective for heterologous boosting, [meaning] it works well and is well tolerated as a booster with other vaccines that are available in Bangladesh, this can be useful,” says Joarder.
According to Hotez, Corbevax can play several important roles - as a standalone adult or paediatric vaccine, and as a booster for other vaccines. Studies are underway to determine Corbevax’s effectiveness in these regards, he says.
Need for More Data
Biological E conducted two clinical trials involving 3000 subjects in India, and found Corbevax to be “safe and immunogenic,” with 90 percent effectiveness in preventing symptomatic infections from the original strain of COVID-19 and over 80 percent effectiveness against the Delta variant. The vaccine is currently in use in India, and according to Hotez, it’s in the pipeline at different stages in Indonesia, Bangladesh and Botswana.
However, Corbevax is yet to receive emergency use approval from the WHO. Experts such as Joarder see the need for more trials and data before it is made available to the general population. He says that while the WHO’s emergency approval is essential for global scale-up of the vaccine, we need data to determine age-stratified efficacy of the vaccine and whether it can be used for heterologous boosting with other vaccines. “According to the most recent data, the 100 percent circulating variant in Bangladesh is Omicron. We need to know how effective is Corbevax against the Omicron variant,” says Joarder.
Shabir Madhi, a vaccinologist at the University of the Witwatersrand, Johannesburg and co-director of the African Local Initiative for Vaccinology Expertise, says that a majority of people in Africa have now developed immunity through natural infection. “This has come at a high cost of loss of lives."
Shivan Parusnath
Others, meanwhile, believe that availing vaccines to poorer countries is not enough to resolve the inequity. Young, the Warwick virologist, says that the global vaccination rollout has also suffered from a degree of vaccine hesitancy, echoing similar observations by President Biden and Pfizer’s CEO. The problem can be blamed on poor communication about the benefits of vaccination. “The Corbevax vaccine [helps with the issues of] patent protection, vaccine storage and distribution, but governments need to ensure that their people are clearly informed.” Notably, however, some research has found higher vaccine willingness in lower-income countries than in the U.S.
Young also emphasized the importance of establishing local vaccination stations to improve access. For some countries, meanwhile, it may be too late. Speaking about the African continent, Madhi says that Corbevax has arrived following the peak of the crisis and won’t reverse the suffering and death that has transpired because of vaccine hoarding by high-income countries.
“The same goes for all the sudden donations from countries such as France - pretty much of little to no value when the pandemic is at its tail end,” says Madhi. “This, unfortunately, is a repeat of the swine flu pandemic in 2009, when vaccines only became available to Africa after the pandemic had very much subsided.”