Uncontrolled spread, p.30
Uncontrolled Spread, page 30
The CDC’s assertion of intellectual property rights over the COVID tests would be more understandable if the agency had allowed commercial manufacturers also to compete to develop tests. But the CDC exerted tight control over the access to the viral samples that test makers needed and didn’t allow labs to go forward with their own tests without first getting permission from the agency. If labs were eventually given permission to develop tests, they would be required to follow the CDC’s protocols. Through these regulatory measures, the CDC basically owned the entire market, essentially preventing manufacturers from developing their own inventions. Anyone who wanted to make a lab test for COVID had to follow the CDC’s test design, but to use that blueprint, they had to first secure a license to the agency’s intellectual property.
During COVID, critics said that the CDC paid inordinate attention to its intellectual property in the agreements it negotiated with manufacturers. Companies seeking to make the test kits described extended negotiations with the CDC that stretched for weeks as the agency made sure that the contracts protected its inventions. Some test makers balked at the provisions. In other cases, companies tried to maneuver around the CDC’s intellectual property claims, by modifying tests to avoid infringing the CDC’s claimed designs. The FDA told the CDC on February 20 that the commercial manufacturers were telling regulators that companies couldn’t deploy the CDC test because of “IP limitations.” Following up on this, the FDA pressed the CDC simply to license its design to manufacturers that could mass produce testing kits that could be commercially distributed.
In one episode, in an attempt to protect its intellectual property, the CDC balked at providing its quality-control procedures to New York State so the state’s labs could start using the protocol to validate the tests they had developed. The FDA provided the procedures to New York anyway, without notifying the CDC that they had been shared. On another occasion, the CDC asked the FDA to change the authorization for the CDC’s tests to make sure that the regulatory documents contained language that would protect the CDC’s inventions and allow the agency to collect royalties on its diagnostics. The CDC wouldn’t fully relent on some of its most burdensome intellectual property claims, particularly those governing the process for validating the reliability of tests, until March.
These practices should be revisited. They don’t serve an identifiable policy goal, especially in the setting of a public health emergency, where speed to testing is paramount. The CDC isn’t pressing its patent claims to make sure that the resulting tests are more accessible, nor is the agency asserting property claims to make the tests more affordable to patients. It’s largely just guarding its turf.
Part of the agency’s posture reflected its belief that in the past it had been burned when it fashioned innovations, only to see private companies profiting off its inventions. An episode that stood out in the minds of some CDC officials occurred in the early 1980s, when the CDC and drug maker Chiron entered into a research collaboration aimed at developing a test for hepatitis C, but then several years later, Chiron received exclusive rights to the test and a lucrative commercial monopoly.43 After academic scientists criticized the CDC for letting Chiron get the monopoly over the test, the agency challenged Chiron’s patent and proposed an agreement that would have assigned the CDC a half interest in the patents and a ten-year royalty of 3 percent of net sales. Chiron declined to go along and, following a protracted legal fight, ultimately prevailed, agreeing in 1990 to a much smaller concession to the CDC and to Dr. Daniel W. Bradley, who had spent twenty-three years at the CDC and whose research to isolate and clone the hepatitis C virus, the CDC argued, was central to the development of the test. Under the settlement, Chiron agreed to pay Bradley $67,500 a year for five years “in recognition of his contributions to the field” of hepatitis C research.44 Shortly before the five years ran out, in 1994, Bradley (who had since left the CDC for a job at the WHO) filed suit against Chiron, claiming, once again, that Chiron had used his research and then shut him out of a patent resulting from the discovery. Bradley would lose on appeal. The experience with Chiron left some bitterness at the CDC that, along with some similar episodes, made the agency more aggressive in trying to assert intellectual property rights over its work.45 That indignation carried through into its work on other pathogens, including SARS-1, when the CDC asserted ownership of the SARS-1 virus and its entire genetic content after CDC researchers had helped map the pathogen’s genome. Rather than try to profit from the patents on SARS-1, the CDC said its aim was to prevent other companies and researchers from monopolizing the field the way Chiron had with hepatitis C.46
Part of the challenge to America’s efforts to rapidly field a test in a crisis is that the CDC can effectively maintain a monopoly on the development and design of tests through its control over the access to viral samples and the power to determine which labs and companies are authorized to manufacture a test and start screening for a new pathogen. This creates the potential for a conflict of interest if the CDC can compel commercial manufacturers to forgo their own development work through the agency’s control over test creation and then require commercial manufacturers to pay royalties to the CDC for the right to use the agency’s test design—and submit to the CDC’s commercial terms.
At the very least, the terms that the CDC seeks should be standardized and settled in advance with a handful of manufacturers who are then prepositioned to take a warm handoff from the agency in the event of a crisis. This would ensure that the transition from the CDC to commercial manufacturers happens smoothly and quickly in a crisis. In such a framework, the commercial test kit makers would function largely as contract manufacturers to the CDC. During COVID, some manufacturers that might have been able to copy the CDC’s test design, and produce kits in large quantities, instead initially sat on the sidelines, worried that they would infringe the CDC’s intellectual property claims, fail to secure access to its assays, or be unable to reach commercial terms with the agency.
Going forward, we need a hot base of industrial testing capacity. This is what South Korea did. Its government offered contracts to its manufacturers to get them to focus on COVID before cases even arrived. It also guaranteed its test manufacturers a return on their investment, so there were economic incentives in place at the very outset. The equipment needed for deploying hundreds of new testing sites and running samples was already in place.
In the US, we turned to our commercial labs and test kit manufacturers late and didn’t coordinate their efforts in any meaningful way. The result was hundreds of different labs and manufacturers entering the market, often with custom-made solutions that couldn’t be deployed widely because they would work only on specific instruments or only in certain labs.
This disorganized approach used up unnecessary supplies on tests that could never achieve sufficient scale to provide a meaningful volume of screening. It diverted the resources of regulators who should have focused their efforts on a more curated set of manufacturers capable of producing tests that could be used in the largest number of labs and on the greatest number of patients. Ultimately, once commercial manufacturers were able to get into this market in late March and April 2020, the scattershot nature of the early development efforts meant that we had fewer accessible tests than if that development work had been more carefully orchestrated.
A pandemic strategy should include a plan for leveraging the expertise and capacity of a defined set of labs and test kit manufacturers. They should be contracted with in advance, and their help should be enlisted early in a crisis, to ensure that the needed testing is in place if an outbreak unexpectedly turns into an epidemic. These partners should be given the resources they need (such as viral samples) to develop kits that can be run on the largest possible installed base of testing instruments. The CDC should have these commercial firms on standby, with some dedicated resources that are financed in advance and ready to be ramped up when needed.
We also need a mechanism to buy test kits in advance of an epidemic, and not wait until a new pathogen becomes widespread. The federal government needs to be willing to start stockpiling these kits when a new virus first surfaces, so we’ll have them if an epidemic erupts.
In the US, very little money was allocated to diagnostics, even once Operation Warp Speed got under way. Early on, BARDA made some individual investments in certain tests. However, many of these were novel, point-of-care diagnostics and at-home tests that would be needed later to solve specific needs. Most of the US government funding would be focused on vaccines.47 Meanwhile, the US manufacturers capable of designing tests for COVID were reluctant to jump into this market. The FDA’s professional staff had been working with commercial manufacturers and labs starting in January, but there was no leadership from HHS or from the FDA commissioner to encourage these developers into the market. Secretary Azar looked to the CDC to solve the testing shortage problem. During January and February 2020, the HHS leadership was mostly preoccupied with the travel restrictions and repatriating Americans from other nations. The commercial manufacturers and labs, in turn, were frozen by a belief that the CDC had this covered and would soon flood the market with its own kits. The industry’s difficult experience trying to market tests for Zika skewed their response to COVID. When the Zika outbreak emerged, device makers had pivoted quickly into the production of new tests only to get financially burned when the threat dissipated, and the government wouldn’t reimburse some labs and manufacturers for the tests that they had produced and performed.48
To get the manufacturers and commercial labs into the market early, senior officials needed to guarantee the purchase and payment for their tests. We needed to anticipate the threat, and the officials at HHS needed to create a market where one didn’t yet exist. However, nobody predicted how quickly the epidemic would explode, how much spread was already under way, and how much testing we would need. Even if these needs had been anticipated, there was no natural home for mounting such a testing response. South Korea reformed its CDC after MERS and gave it responsibility for creating a testing market in a crisis. In the US, HHS turned to the CDC, and the CDC didn’t have the policy orientation, operational experience, or industrial expertise to pull off an effort on this scale. As a consequence, we never had enough testing to keep up with the initial spread, and we lost control of the pandemic at its very outset. It made the need for safe and effective therapeutics and vaccines even more urgent.
Chapter 15
Evidence Is Hard to Collect in a Crisis
He had a low-grade fever. Then some muscle aches. However, at first it wasn’t so bad. Not bad enough to keep him from traveling. He got on a commercial airplane from Saudi Arabia, where he was working as a healthcare provider, bound for Chicago, and then took a seventy-minute bus ride before arriving at his home in Indiana. Three days later, his nagging symptoms abruptly worsened: he grew short of breath and developed a high fever. He was evaluated at a local hospital, where a chest X-ray showed a right-lower-lobe pneumonia, and a CAT scan would show that the infection had progressed to both of his lungs. As his condition deteriorated, he was admitted to the Community Hospital in Munster, Indiana.
These events took place at the end of April 2014. The man admitted to the hospital was America’s first known case of a novel coronavirus known as Middle East Respiratory Syndrome, or MERS. During the course of his trip through the healthcare system, fifty-three healthcare workers were in contact with him before his diagnosis emerged. Probably hundreds of others were exposed to the virus during his journey from Saudi Arabia.1
A few days after the Indiana man was admitted to the hospital, a second case of MERS emerged in America, another healthcare provider who worked in Saudi Arabia and had similarly traveled by a commercial airline from the kingdom via London, Boston, and Atlanta, to his final destination in Orlando. He had first started to feel sick on the flight, but it wasn’t until a few days later, on May 9, that he visited a local emergency room and was admitted.2 The Florida Department of Health confirmed his diagnosis on May 12.3
Once again, hundreds of people had been exposed along his route.
The two episodes showed how easily a novel virus can journey across the world and infect people along the way. MERS had first emerged in Jeddah, Saudi Arabia, two years earlier, with a cluster of infections in June 2012. It would continue to spread across Asia, Africa, and Europe before reaching America.4 By December 2015, a report from the WHO identified 1,621 cases in twenty-six countries, with 584 deaths.5
The MERS virus never obtained the ability to spread easily between people; it was largely transmitted through close contact with its animal hosts, usually camels. When human transmission occurred, most of the cases were confined to healthcare settings, where providers would have sustained contact with patients, often without taking adequate precautions to protect themselves.6 But the virus proved to be dangerous, and it should have been a provocation to take the threat of novel coronaviruses more seriously. MERS arrived just a few years after SARS-1 had already sparked a dangerous epidemic, infecting more than eight thousand people and ultimately spreading to twenty-nine countries, killing at least 774 people worldwide. Most of the cases of SARS-1 would occur over an eight-month period in 2002 and 2003, but the virus would linger for another year.7 It was clear that coronaviruses were on the march.
The emergence of SARS-1 changed our conventional understanding of this class of viruses. It showed that novel coronaviruses could emerge, evolve to infect humans, and become lethal killers. MERS underscored these risks. There were ample reservoirs for new and potentially more serious strains. Coronaviruses could be found in bats, whales, pigs, birds, cats, dogs, and mice.8 The SARS-1 epidemic had its origin in a bat virus that had spread first to civets, an animal sold in live food markets that served as the virus’s intermediate host, before spreading from civets to people. For MERS, the intermediary host animals were camels.9 It was now clear that this once benign class of viruses had pandemic potential.
In virology and in nature, it has often been said that what is past is prologue.10 The proven potential for evolutionary change meant that, as a category of viruses, coronaviruses could pose a substantial risk to human beings. A novel and dangerous strain that was already lurking in an animal reservoir could adapt to human biology and emerge into human circulation for the first time.
This is how SARS-1 came about. It was an existing virus that transferred with just minor modifications, from an animal reservoir in bats and then to its eventual arrival in the human population.11 Making matters more ominous, the reservoir of potential coronavirus threats was deep. One research team traveled to twenty different countries to survey animals where the viral species is known to hide. They sequenced the viruses they found and identified about one hundred different clusters of novel coronaviruses, more than 90 percent of them in bats.12 In a single site known as the Shitou Cave, located just outside of Kunming, the capital of Yunnan Province in southwestern China, the researchers found a coronavirus resembling SARS-1 with attributes that more or less proved that it had the ability to infect human cells. It would provide earlier evidence that SARS-like coronaviruses with the potential to hop from bats to humans were circulating in southern China. In 2013, the scientists published their findings in the prominent journal Nature. It should have provided a grave warning to the world.13
Historically, advances in public health preparedness have come as a result of major crises. In the case of infectious disease, these advances often followed an epidemic or the fear of one. A lot of the progress we made in improving pandemic surveillance, for example, grew out of concerns over the H5N1 bird flu. When it came to novel coronaviruses, investments were made after SARS-1 and MERS, but were transient. Once the immediate threat seemed to subside, so did the interest in improving preparedness.
In 2004, the National Institute of Allergy and Infectious Diseases awarded $104.7 million in annual funding for coronavirus-related research. However, that funding fell to $14.9 million by 2010. It climbed after MERS, but declined again after that threat receded, and by 2019 it was $27.7 million.14 The private sector also made investments, but they, too, didn’t get much support. The biotechnology company Regeneron fashioned a therapeutic antibody that could target MERS and might have been turned into an effective drug. The new treatment worked by mimicking the antibodies that our bodies would produce naturally in response to a MERS infection. Regeneron had tested the drug successfully, but it wasn’t advanced into human trials. After the immediate risk of MERS seemed to fade, policymakers lost interest in these countermeasures.
Then there was work to develop a vaccine to MERS, much of it coordinated by the Coalition for Epidemic Preparedness Innovations (CEPI), a global foundation established to finance independent projects aimed at the development of vaccines against emerging infectious diseases. CEPI is run by Richard Hatchett, one of the original architects of the mitigation tactics included in the 2005 pandemic plan set in motion by President Bush. CEPI’s work is focused on the WHO’s “blueprint list of priority diseases,”15 which include coronaviruses. Launched in 2017 with $460 million from the Bill and Melinda Gates Foundation, The Wellcome Trust, and a group of nations, including Norway, Japan, and Germany, CEPI is the closest thing we have to a collective international effort to develop countermeasures to global threats.16 CEPI is one of the few bodies that remained committed to these risks, but many lost interest in CEPI’s coronavirus-focused efforts after the perceived threats from SARS-1 and MERS seemed to recede.17
The traditional planning for pandemics had always envisioned the US developing countermeasures against specific pathogens. When it came to threats that could spring from nature, there was an almost single-minded focus on flu. When it came to pathogens that could be harvested from a lab and deliberately turned into bioterrorist weapons, much of the emphasis was on anthrax and smallpox. These pathogens consumed most of our attention.
