StemCell Therapy

Editors Note: The Atlantic is making vital coverage of the coronavirus available to all readers. Find the collection here.

Michael Mina is a professor of epidemiology at Harvard, where he studies the diagnostic testing of infectious diseases. He has watched, with disgust and disbelief, as the United States has struggled for months to obtain enough tests to fight the coronavirus. In January, he assured a newspaper reporter that he had absolute faith in the ability of the Centers for Disease Control and Prevention to contain the virus. By early March, that conviction was in crisis. The incompetence has really exceeded what anyone would expect, he told The New York Times. His astonishment has only intensified since.

Many Americans may understand that testing has failed in this countrythat it has been inadequate, in one form or another, since February. What they may not understand is that it is failing, now. In each of the past two weeks, and for the first time since the pandemic began, the country performed fewer COVID-19 tests than it did in the week prior. The system is deteriorating.

Testing is a non-optional problem. Tests permit us to do the most basic task in disease control: Identify the sick, and separate them from the well. When tests are abundant, they can dispel the fear of contagion that has quieted public life. The only thing that makes a difference in the economy is public health, and the only thing that makes a difference in public health is testing, Simon Johnson, the former chief economist of the International Monetary Fund, told us. Optimistic timelines suggest that vaccines wont be widely available, in the hundreds of millions of doses, until May or June. There will be a transition period in which doctors and health-care workers are vaccinated, but teachers, letter carriers, and police officers are not. We will need better testing then. But we need it now, too.

Read: How the pandemic defeated America

Why has testing failed so completely? By the end of March, Mina had identified a culprit: Theres little ability for a central command unit to pool all the resources from around the country, he said at a Harvard event. We have no way to centralize things in this country short of declaring martial law. It took several more months for him to find a solution to this problem, which is to circumvent it altogether. In the past several weeks, he has become an evangelist for a total revolution in how the U.S. controls the pandemic. Instead of restructuring daily life around the American way of testing, he argues, the country should build testing into the American way of life.

The wand that will accomplish this feat is a thin paper strip, no longer than a finger. It is a coronavirus test. Mina says that the U.S. should mass-produce these inexpensive and relatively insensitive testsunlike other methods, they require only a saliva samplein quantities of tens of millions a day. These tests, which can deliver a result in 15 minutes or less, should then become a ubiquitous part of daily life. Before anyone enters a school or an office, a movie theater or a Walmart, they must take one of these tests. Test negative, and you may enter the public space. Test positive, and you are sent home. In other words: Mina wants to test nearly everyone, nearly every day.

The tests Mina describes already exist: They are sitting in the office of e25 Bio, a small start-up in Cambridge, Massachusetts; half a dozen other companies are working on similar products. But implementing his vision will require changing how we think about tests. These new tests are much less sensitive than the ones we run today, which means that regulations must be relaxed before they can be sold or used. Their closest analogue is rapid dengue-virus tests, used in India, which are manufactured in a quantity of 100 million a year. Mina envisions nearly as many rapid COVID-19 tests being manufactured a day. Only the federal government, acting as customer and controller, can accomplish such a feat.

If it is an audacious plan, it has an audacious payoff. Mina claims that his plan could bring the virus to heel in the U.S. within three weeks. (Other epidemiologists arent as sure it would workat least without serious downsides.) His plan, while costly, is one of the few commensurate in scale to the pandemic: Even if it costs billions of dollars to realize, the U.S. is already losing billions of dollars to the virus every day. More Americans are dying of the coronavirus every month, on average, than died in the deadliest month of World War II. Donald Trump has said that the U.S. is fighting a war against an invisible enemy; Mina simply asks that the country adopt a wartime economy.

George Packer: We are living in a failed state

We have been covering coronavirus testing since March. For most of that time, the story has been one of failure after failure. But in the past few weeks, something has changed. After months without federal leadership, a loose confederation of scientists, economists, doctors, financiers, philanthropists, and public-health officials has assembled to fill in that gap. They have reexamined every piece of the testing system and developed a new set of tactics to address the months-long testing shortage. Minas plan is the most aggressive of these ideas; other groupssuch as the new nonprofit Testing for America, founded by private-sector experts who helped the White House in the springhave advanced their own plans. Taken together, they compose a box of tools that could allow the country to fix its ramshackle house.

The government has also done more in the past month to stimulate the creation of new kinds of tests than it has done in any period of the pandemic so far. The National Institutes of Health has awarded $248 million in grants to companies so that they can scale up alternate forms of COVID-19 testing as quickly as possible. The Centers for Medicare and Medicaid has begun to support the nascent testing market as well. This investment is belated and too meagerby comparison, the government has spent more than $8 billion on vaccine developmentbut it is significant.

If the new proposals make anything clear, its that it is in our power to have an abundance of tests within monthsand to return life to normal, or something close to it, even before a vaccine is found. There is a way out of the pandemic.

Today, if you go to the doctor with a dry cough and fever, and get swabbed for COVID-19, you will probably receive a test that was not designed for an out-of-control pandemic. Its called a reverse-transcription polymerase chain reaction test, or PCR, test, and it is one of the miracles of medicine. The PCR technique has allowed us to probe the genomes of the Earth: Its invention, in 1983, cleared the way for the Human Genome Project, the early diagnosis of certain cancers, and the study of ancient DNA. It works, in essence, like a zoom-and-enhance feature on a computer: Using a specific mix of chemicals, called reagents, and a special machine, called a thermal cycler, the PCR process duplicates a certain strand of genetic material hundreds of millions of times.

When used to test for COVID-19, the PCR technique looks for a specific sequence of nucleotides that is unique to the coronavirus, a snippet of RNA that exists nowhere else. Whenever the PCR machineas designed and sold, for instance, by the multinational firm Rocheencounters that strand, it makes a copy of both that sequence and a fluorescent dye. If, after multiplying both the strand and the dye hundreds of millions of times, the Roche machine detects a certain amount of the dye, its software interprets the specimen as a positive. To have a confirmed case of COVID-19 is to have a PCR machine detect the dye in a sample and report it to a technician. Tested time and time again, the PCR technique performs stunningly well: The best-in-class PCR tests can reliably detect, in just a few hours, as few as 100 copies of viral RNA in a milliliter of spit or snot.

The PCR test has anchored the American response to the pandemic. In CDC guidelines written by a council of state epidemiologists, a positive PCR result is the only way to confirm a case of COVID-19. And the Food and Drug Administration, which regulates all COVID-19 tests used in the U.S., judges every other type of test against PCR. Of the more than 62 million COVID-19 tests conducted in the U.S. since March, the overwhelming majority have been PCR.

Read: Theres one big reason the U.S. economy cant reopen

However, a small but growing pile of clinical evidenceand a sky-scraping stack of real-world accountshas revealed glaring issues with PCR tests. From a public-health perspective, the most important questions that a test can answer are: Is this person infected and contagious now? and If hes not contagious, might he be soon? But these are not questions that even a positive PCR result can address. And especially as theyre conducted in the U.S. today, PCR tests do not tell us what we need to know to stop the virus.

Imagine that, at this instant, you are exposed to and infected with the coronavirus. You now have COVID-19it is day zerobut it is impossible for you or anyone else to know it. In the following days, the virus will silently propagate in your body, hijacking your cells and making millions of copies of itself. Around day three of your infection, there might be enough of the virus in your nasal passages and saliva that a sample of either would test positive via PCR. Soon, your respiratory system will be so crowded with the virus that you will become contagious, spraying the virus into the air whenever you talk or yell. But you likely will not think yourself sick until around day five, when you start to develop symptoms, such as a fever, dry cough, or lost sense of smell. For the next few days, you will be at your most infectious.

And here is the first problem with PCR. To cut off a chain of transmission, public-health workers have to move faster than the virus. If they can test you earlyaround day three of your infection, for instanceand get a result back in a day or two, they may be able to isolate you before you infect too many people.

But right now, the U.S. is not delivering PCR results anywhere close to that fast. Brett Giroir, the federal coronavirus-testing czar, admitted to Congress last month that even a three-day turnaround time is not a benchmark we can achieve today. As an outbreak raged in Arizona this summer, some PCR results took 14 days or more to come back. Thats worse than uselessI would not call that a test, Johnson, the economist, told usbecause most bouts of COVID-19 last 14 days or fewer. The majority of all U.S. tests are completely garbage, wasted, Bill Gates, who has helped fund COVID-19 testing, recently said.

After your symptoms start around day five, you might remain symptomatic for several days to several months. But some recent studies suggest that by day 14 or sonine days after your symptoms beganyou are no longer infectious, even if you are still symptomatic. By then, there is no longer live virus in your upper respiratory system. But because millions of dead virus particles line your mouth and nasal cavity, and because they contain strands of intact RNA, and because the PCR technique is very sensitive, you will still test positive on a PCR test. For weeks, in fact, you may test positive via PCR, even after your symptoms abate.

And here is PCRs second problem: By this point in your illness, a positive PCR test does not mean what you might expect. It does not mean that you are infectious, nor does it necessarily mean that there is live SARS-CoV-2 virus in your body. It does not make sense to trace any contacts youve had in the past five days, because you did not infect them. Nor does it make sense for you to stay home from work. But our countrys public-health infrastructure cannot easily distinguish between a day-two positive and a day-35 positive.

The final issue with PCR tests is simple: There arent enough of them. The U.S. now runs more than 700,000 COVID-19 tests a day. On its own terms, this is a stupendous leap, a nearly 800-fold increase since early March. But we may be maxing out the worlds PCR capacity; supply chains are straining and snapping. For months, it has been difficult for labs to get the expensive chemical reagents that allow for RNA duplication. Earlier this summer, there was a global run on the tips of pipettesthe disposable plastic basters used to move liquid between vials. Sometimes the bottleneck is PCR machines themselves: As infections surged in Arizona last month, and people lined up to be tested, the number of tests far exceeded the machines capacity to run them.

When tests dwindle, the entire medical system suffers. In Arizona, many doctors offices were short-staffed at the peak of the outbreak, because any doctor exposed to the virus needed to test negative before returning to work, and the system simply couldnt handle the volume of tests. Weve had people out seven to 10 days waiting for a negative result, Catherine Gioannetti, the medical director of health and safety for Arizona Community Physicians, told us. Its essentially a broken system, because we dont have results in a timely fashion.

If labs dont have the capacity to turn around doctors tests, which are often fast-tracked, they definitely do not have the capacity to test contagious people who are wholly asymptomatic. These silent spreaders may remain infectious for weeks but never develop any symptoms. They are the viruss secret power, one testing executive told us, and they account for 20 to 40 percent of all infections. Some evidence suggests that they may be more infectious than symptomatic people, carrying higher viral loads for longer.

The challenge is clear: We need an enormous number of tests. As some have argued since the spring, the American population at largeand not just feverish, coughing peoplehas to be screened. Lets say, for instance, that you wanted to test everyone in the U.S. once a week. Thats 45 million tests a day. How can we get there?

In the immediate future, the only way to increase testing is to squeeze more tests out of the existing PCR system. Our best bet to do so fast is through a technique called pooling, which could get a few hundred thousand more tests out of the system every day.

Pooling is straightforward: Instead of testing each sample individually, laboratories combine some samples, then test that pooled sample as one. The technique was invented by Robert Dorfman, a Harvard statistician, to test American soldiers for syphilis during World War II. Today it is commonly used by public-health labs to test for HIV. It works as follows: A lab technician mixes 50 HIV samples together, then tests this pool. If the result is negative, then none of the patients has HIVand the researcher has evaluated 50 samples with the same materials it takes to run one test.

But if the pooled sample is positive, a new phase starts. The technician pools the same specimens again, this time into smaller groups of 10, and retests them. When one of these smaller pools is positive, she tests each individual sample in it. By the end of the process, she has tested 50 people for HIV, but used only a dozen or so tests. This approach saves her hundreds of tests over the course of a day.

Pooling is a great first step to maximizing our test supply, Jon Kolstad, an economist at UC Berkeley, told us. This is in part because regulators and public-health officials are already familiar with it. The FDA has told Quest Diagnostics, LabCorp, and BioReference, three major commercial laboratories, that they can start pooling a handful of coronavirus samples at a time. In some parts of New England that havent seen much of the virus, pooling could triple or even quadruple the number of tests available, a team at the University of Nebraska has found.

But pooling is only a stopgap. It works best for diseases that are relatively rare, such as HIV and syphilis. If a disease is too common, then the work of poolingthe laborious mixing and remixing of samplesis more work than its worth. (About twice as many Americans have been infected with the coronavirus as have contracted HIV since 1981.) In Arizona and some southern states burning with COVID-19, traditional pooling would not be worth the effort, the same Nebraska team found.

Kolstad and Johnson, the MIT economist, are experimenting with ways to increase the efficiency of pooling. By grouping samples more deliberately, they can create larger pools of people with similar risks. A group of office workers might be at lower risk than a group of meatpackers who work close together, and even within a meatpacking plant, workers on one side of the plant might be at greater risk than those on the other. And because pooling saves money, companies and colleges and schools could run more tests. This would create a virtuous cycle. Each day, a person has a certain chance of being infected that varies with the prevalence of the disease in a community. Test every day, and there is simply less time between tests in which a person could have been infected. This makes it possible to build larger pools of people who are likely negative.

Starting up these systems would require clearing logistical and regulatory hurdlesa positive coronavirus sample is a low-level biohazard, and the FDA regulates it as such. Dina Greene, who directs lab testing for Kaiser Permanente in Washington State, says that contamination problems are already difficult for labs to manage, and would be more so if labs have to manually mix together samples.

Kolstad has been thinking through this problem. His team is experimenting with a different technique, which one might call intermediate pooling. Instead of having labs make pools on the back end, Kolstad proposes deploying trained nurses in mobile pooling labs in retrofitted vans. It would work well for nursing homes, he says: The nurses might arrive at a certain time every day, test every employee, pool the samples in the van, and then drop them off at a nearby clinical lab. (Because the FDA regulates pooling in clinical labs more strictly than in this type of surveillance testing, it may also be easier to obtain FDA approval for this plan.) Kolstad and his team are trying out this technique with a network of nursing homes in the Boston area, and delivering the pooled tests to a nearly complete, fully automated COVID-19 testing facility run by Gingko Bioworks, a $4 billion start-up in Cambridge that is pitching another method to scale up U.S. testing, one that could vastly increase the pace of processing.

Since its founding in 2009, Ginkgo Bioworks has specialized in synthesizing new kinds of bacteria for use in industrial processes. Its engineers spin new forms of DNA using genetic-sequencing machines made by Illumina, a large and publicly traded biotechnology company. But in the spring, as viral testing buckled, Ginkgos engineers realized that their Illumina machines could be put to another use: Instead of creating genes, they could identify existing onesand do so much faster than a PCR machine can.

Unlike PCR machines, which can analyze at most hundreds of individual samples per run, sequencing machines can read thousands of samples simultaneously. A high-end PCR machine, operated by a round-the-clock staff, can run up to 1,000 samples a day; a single Illumina machine can read more than 3,000 samples in half that time. Ginkgo has sharpened that advantage by building its fully automated factory in Boston, centered on Illumina machines, which it says could test about 250,000 samples a day. It aims to open the facility by mid-October; in two months more, another three could go up and Ginkgo could be testing 1 million samples each day.

The company has designed its supply chain to withstand high demand. It has rejected some reagents, for instance, because it doesnt trust that there will be enough of them; it uses saliva samples, not swabbed nose or throat samples, because it does not think there are enough swabs in the world to meet demand. The genetic-sequencing supply chain is already built for such scale because other automated factoriesdoing noninvasive neonatal testing, for examplealready use Illumina machines.

Both Ginkgo and an Illumina-backed start-up, Helix, have received NIH grants to rapidly scale up their testing. If the technique receives FDA approval, as many expect, the two companies could as much as triple the countrys testing capacity. In three months, I think we could be at between 1 and 3 million additional tests per day in this country, without any problem at all, John Stuelpnagel, a bioscience entrepreneur and one of the founders of Illumina, told us.

The approach has its challenges. Any samples must be shipped to one of Ginkgos or Helixs centralized testing locations, which imposes a huge logistical obstacle to scaling up. The incumbent testing companiesQuest and LabCorphave achieved dominance because of their ability to collect samples from places where theyre tested. But in Ginkgos full vision, 1 million tests will cover far more than 1 million people.

The key to this approach is front-end pooling. Imagine that every day, when kids arrive in their classroom, they briefly remove their mask and spit into a bag. (It is a perfect plan for second graders.) The bag would then be shipped to the nearest Ginkgo factory, which could test the pooled sample and deliver a single result for the classroom by the next morning. If you pool together one classroom, and test that classroom together, then if you get a positive, you can send the whole classroom home, Blythe Adamson, an economist and epidemiologist at the nonprofit Testing for America, told us. For children, it protects their privacywe dont know which student tested positive.

Front-end pooling could also drive costs down, partly by saving on materials. Do 10 people spit in one bag? Thats one-tenth the cost, Jason Kelly, Ginkgos chief executive, told us. Its logistically simpler, because one bag shows up, not 10, so theres 10 times less unboxing, 10 times less robotic movement. The challenge, he said, is chiefly one of industrial design, not molecular biology: There is no FDA-approved device, at present, that will let 10 kids safely spit into one vial. We should have federally backed development and fast regulatory approval for that kind of device, Kelly said.

The Ginkgo sequencing approach and front-end pooling have never been tried before, because they make sense only in a pandemic. Only at the scale of tens of thousands of tests do Ginkgo tests start to cost less than PCR, Adamson said. But at that scale, their cost drops quickly in comparisonpossibly down to $20, Stuelpnagel said, if not $10, compared with more than $100 for a PCR test.

Youd never do [any of this] for HIV, Kelly said. Its only in a pandemic you go, Oh my God, were undertesting by a factor of 10.

But what if testing needs to scale up not 10 times, but 20, or 50, or 100 times? Thats where another type of testan antigen testcomes in.

At the same time that Ginkgo and other next-gen sequencing tests should come online, antigen tests will be scaling up. Unlike a PCR or a Ginkgo-style test, an antigen test does not identify any of the viruss genetic material. Instead, it looks for an antigen, a slightly redundant name for any chemical thats recognized by the test. Antigen tests arent as sensitive as genetic tests, but what they sacrifice in accuracy, they make up in speed, cost, and convenience. Most important, an antigen test can be conducted quickly at a point of care location, such as a doctors office, nursing home, or hospital.

Two of the most anticipated such tests are already on the market. Manufactured by two companies, Quidel and Becton, Dickinson and Company, they look for an antigen called nucleocapsid, which is plentiful in the SARS-CoV-2 virus. The companies say they will be making a combined 14 million tests a month by the end of September; for comparison, the U.S. completed 23 million total tests in July. This scale alone will make this type of test an important factor in fall testing. Hospitals and doctors told us they are eager to get their hands on antigen tests, in part because theyre worried about dealing with COVID-19 during the coming flu season. In years past, if a patient had a cough and a runny nose in December, she would likely be diagnosed with the flu, even if she tested negative on a rapid flu test. But now we cant presume [patients] have the flu, because they might have COVID-19, says Natasha Bhuyan, the West Coast medical director for One Medical, a chain of primary-care clinics. An antigen test seems to offer a way out of this dilemma.

The tests cost less than half as much as standard PCR tests, and they dont need to be sent away to a lab. They can deliver a result in 15 minutes. But this approach has downsides. While the tests work well enough, successfully identifying most people with high viral loads, they have sometimes delivered false positives. Last week, Ohio Governor Mike DeWine tested positive on the Quidel test, leading him to cancel a meeting with President Trump. But later that day, he tested negative, three times, when analyzed by PCR.

And while these tests will be useful, they have their own supply-chain drawbacks. Both companies tests can be interpreted only with a proprietary reader, and while many clinics and offices already have these readers on hand, neither company is prepared to mass-produce them at the same scale as the tests. (Quidel now makes 2,000 of its readers a month, but is aiming to scale to 7,000 a month by September, a spokesperson told us.) Because both tests look for nucleocapsid, which exists only inside the coronavirus, they need a way to sever the viruss outer membrane. This requires more reagents. For many technicians, these drawbacks arent worth the benefits. Most people who are real lab experts are steering away from all that stuff because they cant justify it, Greene, the Kaiser lab director, said.

The readers are a particular sticking point for Michael Mina, the Harvard epidemiologist. He calls the BD and Quidel systems Nespresso tests, because, just as a Nespresso pod can transform into coffee only through a Nespresso brewer, they can deliver results only when their readers are at hand. What I want is the instant coffee of tests, he told us. What if there was an antigen test that could be made in huge numbers and didnt require a specialized reader? What if it worked more like a pregnancy testa procedure you can do at home, and not only at a doctors office?

Such tests existand have existed since Apriland they are made by e25 Bio, a 12-person company in Cambridge. An e25 test is a paper strip, a few inches long and less than an inch wide. It needs only some spit, a saline solution, and a small cupand it can deliver a result in 15 minutes. Like a pregnancy test, the strip has a faint line across its lower third. If you expose the strip to a sample and it fills in with color, then the test is positive. It does not require a machine, a reagent, or a doctor to work.

Its unusual quality is that it does not look for the same antigen as other tests. Instead of identifying nucleocapsid, the e25 test is keyed to something on the outside of the virus. It reacts to the presence of the coronaviruss distinctive spike protein, the structure on the viruss skin that allows it to hook onto and enter human cells. I think were the only company in North America that has developed a spike antigen test, Bobby Brooke Herrera, e25s co-founder and chief executive, told us.

This has several advantages. It means, first, that the e25 test does not have to rupture the virus, which is why it doesnt need reagents. And it means, second, that the e25 test is actually looking for something more relevant than the viruss genetic material. The spike protein is the coronaviruss most important structureit plays a large part in determining the viruss infectiousness, and its what both antibodies and many vaccine prototypes targetand its presence is a good proxy for the health of the virus generally. Weve developed our test to detect live viruses, or, in other words, spike protein, Herrera said.

Working with two manufacturers, e25 thinks that it could make 4 million tests a month as soon as it receives FDA approval. Within six weeks of approval, it could make 20 million to 40 million tests a month. In short, e25 could single-handedly add as many as 1.2 million tests a day to the national total.

But FDA approval has not yet arrived, because the FDA compares every test to PCR, and no antigen test, however advanced, can stand up to the accuracy and sensitivity of the PCR technique. The FDA, early on in the outbreak, said we had to follow a rubric of 80 percent sensitivity compared to PCR. How they got that number, Im uncertain, but my best guess is it came from influenza epidemics in the past, Herrera said.

This requirement has made antigen tests worse, Herrera argues, because it causes manufacturers to prioritize sensitivity at the cost of speed or convenience. Its why other antigen tests use readers, or centrifuges, or look for nucleocapsid, he contends. By slightly weakening those guidelines, to 60 or 70 percent sensitivity, the FDA could let cheaper at-home tests come to market. The models that e25 uses show that even an at-home test that caught 50 percent of positives and 90 percent of negatives could detect outbreaks and reduce COVID-19 transmission.

Recall the coronaviruss infection clockhow, from day zero of an infection to day five, the amount of the virus in your system exponentially increases; how it begins to ebb with the onset of symptoms; how, by day 14 or so, the PCR test is likely detecting only the refuse RNA of dead virus. While antigen tests need the equivalent of 100,000 viral strands per milliliter, a typical PCR test can detect a positive from as little as 1,000 strands per milliliter. There is only about a day at the beginning of an infection when the two tests would give different resultswhen there are more than 1,000 viral strands per milliliter of your saliva or snot but fewer than 100,000, according to Dan Larremore, a mathematician at the University of Colorado at Boulder. During that periodapproximately day two or day three of an infectionantigen tests are truly inferior to PCR tests.

Yet the opposite is true as COVID-19 fades: There are potentially weeks at the end of an infection when there is enough viral RNA to clear the threshold for a positive PCR test but not enough to set off an antigen test. During that period, antigen tests, such as e25s, outperform PCR tests, Mina argues, because they identify only people who are still contagious. So why, he asks, are they judged against PCR testsand kept off the marketfor failing to find the virus when there is no intact virus to find?

Antigen tests are not better than PCR tests in every instance. When someone at a hospital presents with severe COVID-19-like symptoms, for example, health-care workers cannot risk a false negative: They will need a PCR test. Some experts worry that at-home tests will have a much lower accuracy rate than advertised. Laboratory tests are conducted by professionals on machines they are familiar with, but amateurs will conduct at-home tests, which risks introducing errors not captured by official ratings or even imagined by regulators. At a national scale, this could mean that someone might have COVID-19, fail to realize it, and infect other people. Whats concerning is the salami slicing of sensitivity. A percent here, a percent there, and pretty soon youre talking real people, Alex Greninger, a laboratory-medicine professor at the University of Washington, told us. Jennifer Nuzzo, an epidemiologist at the Johns Hopkins Center for Health Security, told us that its not yet clear whether people who receive a positive result on an at-home test will report that information to health authorities and choose to self-isolate.

But given that they are cheaper than PCR tests, have a faster turnaround time, and can be conducted at home, these paper tests do seem different, in a useful way. In some cases, they answer a more helpful question than PCR tests. There is good evidence to infer that a high viral load, which is what antigen tests detect, is correlated with infectiousness. The more virus in your body, the more contagious you are.

In that light, paper antigen tests arent SARS-CoV-2 tests at all, not like PCR tests are. They are rapid, cheap COVID-19 contagiousness tests. That shift in thinking, Mina argues, should undergird a shift in our national strategy.

Mina wants to coat the country in COVID-19 contagiousness tests. To understand the scale of his vision, start with the closest American analogue, the ubiquitous, paper-based, inexpensive at-home pregnancy test. Americans use 20 million of those each year. This is not sufficient for Minas plan. Ideally, were making way more than 20 million [paper tests] a day, Mina said. Entering a grocery store? Take a test first. Getting on a flight? Theres a test station at the gate. Going to work? Free coffee is provided with your mandatory test. He began pitching the idea as a moonshot in July, but it quickly took hold. By the end of the month, Howard Bauchner, the editor in chief of The Journal of the American Medical Association, gushed on a podcast that ubiquitous tests were the best way we can get back to a semblance of working society.

The idea has gained other advocates. Last month, a panel of experts convened by the Rockefeller Foundation called for the U.S. to do 3.5 million rapid antigen tests a day, or 25 million a weekfive times more than the number of PCR tests they recommended. The researchers compiled a list of 12 rapid tests in development, including e25s, and called for an aggressive government-led effort to support them. (The Rockefeller Foundation has also provided funding to the COVID Tracking Project at The Atlantic.) These sort of tests are on the horizon, but getting them into the hands of everyone who needs themschools, employers, health providers, public essential workers, vulnerable communitieswill require the muscle that only the federal government can provide, the experts wrote.

The muscle, specifically, of a wartime economy. The experts called for the White House to invoke the Defense Production Act, a Truman-era law that allows the federal government to compel companies to mass-produce goods in moments of national crisis. (Manufacturers are compensated for their effort at a fair price.) Only naked federal authority could push production fast enough to make enough tests in time to curb the virus, they wrote.

Herrera, the e25 executive, has been waiting for months for the government to invoke such power. There is essentially no resource constraint on the raw materials that make up antigen tests, but there is a profound limit to available productive capacity. Being able to manufacture these products, Herrera said, is where the bottleneck lies. And after it has the tests, Herrera believes, the company will need help sending them where theyre most needed. If testing companies are to save the world, they need federal support to do it.

And here is the tragedyand the promiseof Minas moonshot: To fix testing, the federal government must do exactly what it has declined to do so far. Why is testing still a problem? Partly because the CDC and the FDA bickered in February and delayed by weeks the initial rollout of COVID-19 tests. Partly because infections continued to grow in the spring and summer, further boosting the number of tests needed to track the virus. But those reasons alone still do not explain the fundamental issue: Why has the U.S. never, not since the pandemic began, had enough tests?

The answer is because the Trump administration has addressed the lack of testing as if it is a nuisance, not a national-security threat. In March and April, the White House encouraged as many different PCR companies to sell COVID-19 tests as possible, declining to endorse any one option. While this idea allowed for competition in theory, it was a nightmare in practice. It effectively forced major labs to invest in several different types of PCR machines at the same time, and to be ready to switch among them as needed, lest a reagent run short. Today, the government cannot use the Defense Production Act to remedy the shortage of PCR machines or reagentsbecause the private labs running the tests are too invested in too many different machines.

Because of its trust in PCR, and its assumption that the pandemic would quickly abate, the administration also failed to encourage companies with alternative testing technologies to develop their products. Many companies that could have started work in April waited on the sidelines, because it wasnt clear whether investing in COVID-19 testing would make sense, Sri Kosaraju, a member of the Testing for America governing council and a former director at JP Morgan, told us.

The Trump administration hoped that the free market would right this imbalance. But firms had no incentive to invest in testing, or assurance that their investments would pay off. Consider the high costs of building an automated testing factory, as Ginkgo is doing, said Stuelpnagel, the Illumina co-founder. A company would typically amortize the costs of that investment over three to five years. But that calculation breaks down in the pandemic. Theres no way that were doing high-throughput COVID testing five years from now. And I hope theres not COVID testing being done three years from now that would require this scale of lab, he said. Companies arent built to deal with that level of uncertainty, or to serve a market that would dramatically shrink, or disappear altogether, if their product did its job. Even if the experimentation would benefit the public, it doesnt make sense for individual businesses to take on those risks.

So nothing happenedfor months. Only in the past few weeks has the federal government begun to address these concerns. The NIH grants awarded to Ginkgo, Helix, Quidel, and others were aimed, in part, at providing capital that would let businesses scale up quickly. And the Centers for Medicare and Medicaid has started to ensure that demand will exist for an experimental test: It has promised to buy Quidel or BD tests for every nursing home in the country.

But even if those companies succeed in delivering what theyve promised, life will not go back to normal. An extra 1 million tests a day will allow us to ramp up contact-tracing operations and slow down the virus, but they will not change the texture of daily life in the pandemic, especially if there is another resurgence of the virus in the winter. For that, Minas moonshot is required. It will require much more than the $200 million the federal government has invested in testing technology so far, and it will require the full might of the federal government, with its unique ability to coerce manufacturing capacity. But its costs are not astronomical. If every paper test costs $1, as Mina hopes, and every American takes a test once a week, then his plan will cost about $1.5 billion a month. Congress has already authorized at least $7 billion to fix testing that the Trump administration had declined, for months, to spend. And even if Minas plan cost $300 million each day, the annual expense would amount to a fractionabout 3 percentof the more than $3 trillion Congress has already spent dealing with the economic fallout of the pandemic. Yet the plan wouldnt merely mitigate the harm of the pandemic. It could end it. To escape the pandemic in this way, the U.S. must make hundreds of millions of contagiousness teststests that are not perfect, but just good enough.

Mass-producing a cheap thing fast is, as it happens, something the United States is very good at, and something this country has done before. During the Second World War, the U.S. realized that the most effective way of shipping goods to Europe was not to use the fastest ship, but to use cheap Liberty ships, which were easy to mass-produce. The Allies created this model of a ship that was kind of cheap, not as fast as they could make it, and not as good as they could make it, Mark Wilson, a historian at the University of North Carolina at Charlotte, told us. They were building cheapone might say disposableships. They werent very good. But they just wanted to out-volume their opponents.

We must out-volume the virus, and what will matter is not the strength of any one individual ship, but the strength of the system it is part of. When the FDA regulates tests, though, it looks at the sensitivity and specificity of a single testhow well the test identifies illness in an individualnot at how the test is part of a testing regimen meant to protect society. For this reason, Mina proposes that the FDA make room for the CDC or the NIH to oversee the use of contagiousness tests. I think the CDC could potentially create a certification process really simply. They are the public-health agency, and could say, We will evaluate different manufacturers. None of these will be fully regulated by law, but here are the ones you should or should not choose.

Paper tests do have downsides. Testing tens of millions of people each day would be an unprecedented biotechnical intervention in the country, and it might have unpredictable, nasty side effects. Minas plan is being pushed without really thinking through the operational consequences, Nuzzo said on a recent press call. Brett Giroir, the federal testing czar, has worried that a deluge of positive paper tests could lead asymptomatic people to swamp the rest of the medical system. You do not beat the virus by shotgun testing everybody, all the time, he said on the same call. Paper tests are based on an inference about human behavior. For example, if people knew that every paper test would catch only seven or eight infections out of every 10 (compared with PCR, which would catch all 10), would they keep taking them? Would the countrys testing system split in two, delivering PCR tests for the rich and cheap paper tests for the poor? Each way of testing for the virus is not only a technology or a medical device. Each is its own hypothesis about public health, human behavior, and market forces.

So here is what May 2021 could look like: Vaccines are rolling out. You havent gotten your dose yet, but you are no longer social distancing. When your daughter walks into her classroom, she briefly removes her mask and spits into a plastic bag; so do all the other children and the teacher. The bag is then driven across three states and delivered to the nearest Ginkgo processing facility. When you arrive at work, you spit into a plastic cup, then step outside to drink coffee. In 15 minutes, you get a text: You passed your daily screen and may proceed into the office. You still wear your mask at your desk, and you try to avoid common areas, but local infection levels are down in the single digits. That night, you and your family meet your parents at a restaurant, and before you proceed inside, you all take another contagiousness test. Its normal, now, to see the little cups of saliva and saline solution, each holding a strip of color-changing paper, sitting on tables near the entrance of every public place. And before you fall asleep, you get a text message from the school district. Nobody in your daughters class tested positive this morninginstruction can happen in person tomorrow.

There is no technical obstacle to that vision. There is only a dearth of political will. The lack of testing is a motivation problem, Stuelpnagel said. Its going to take a lot of effort, but it should take a lot of effort, and we should be willing to take that effort. Mina is frustrated that the answer is so close, and so doable, but not yet something the government is considering. Lets make the all-star team of people in this field, pay them whatever they need to be paid, put billions of dollars in, and get a working test in a month that could be truly scalable. Take it out of the free-market, capitalistic world and say: This is a national emergencywhich, he said, it is.

More here:
The Plan That Could Give Us Our Lives Back - The Atlantic

This entry was posted on August 16, 2020 at 12:56 am and is filed under Genetic medicine. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |