As has been widely reported, a major bottleneck in addressing the novel coronavirus outbreak in the U.S. is the extremely limited testing capacity. While South Korea has tested over a quarter million people, the U.S. has performed only 33,000 tests to date*, just three times South Korea’s daily testing capacity. Speculations about negligence, incompetence, and deliberate conspiracy have been floating around to explain this discrepancy. In reality, as is almost always the case, the factors impacting the U.S.’s ability to ramp up testing are incredibly complex. Complications include regulatory hurdles at the federal and local levels, shortages of supplies, equipment, and certified personnel, as well as technical challenges associated with the test itself.

Given these challenges, it may surprise you to learn that the coronavirus test is relatively simple, and operationally the same in every country. As a molecular biologist, I have run similar procedures hundreds of times. So with South Korea performing an order of magnitude more tests than the U.S., where did we go wrong? If the test is so simple that it can be performed in any molecular biology lab, why aren’t we routinely testing thousands of people every day? Why aren’t results available for days after testing? Will curbside and at-home testing help?

To detect a virus, we just have to look for its instruction manual.

How does the coronavirus test work?

To answer these questions, let’s first consider the culprit the test aims to detect: the virus itself. Viruses, at their core, are surprisingly simple entities: capsules with machinery to penetrate a cell, containing genetic information with instructions to make more viruses. Once a virus enters a cell, the instructions are read and more viral parts are made and assembled. Newly made viruses have mechanisms to escape their host cells and, in the case of coronavirus, travel further down the respiratory tract, eventually reaching the lung cells. When infected, lung cells can no longer perform their normal jobs, leading to the respiratory symptoms of Covid-19 (the disease caused by the novel coronavirus).

There are a number of ways to detect the presence of a virus in a clinical sample. We can look for an indication that our immune system is reacting to it, or we can look for the virus itself. The latter turns out to be much more straightforward because we have a tried-and-true, easily adaptable method to detect one feature of the virus: the “how to make more virus” instructions that it carries.

These instructions are the virus’ genetic information, similar to our DNA. They are a chain of molecular building blocks — abbreviated as As, Cs, Gs, and U’s — strung together in an order we understand — they are a manual we can open and read, letter by letter. To detect a virus, we just have to look for its instruction manual.

To do so, we use a standard molecular biology technique called polymerase chain reaction, or PCR. PCR allows us to make copies of a small, specific section of DNA — say, a sentence from the instruction manual — as long as we know the first and last word of that sentence. These flanking words are called primers, and as you will see, it is important to choose them wisely. By combining primers with the patient sample and a few other components in a machine that can cycle through a few different temperature settings, we can produce millions of copies of our chosen DNA “sentence” relatively quickly (in 30–45 minutes).

The coronavirus test is relatively simple, and operationally the same in every country.

(To be totally accurate, coronavirus is actually an RNA virus. RNA is similar to DNA, but this method looks a little different in practice and is referred to as RT-PCR. The outcome is the same: Many, many copies of the DNA are made from the viral RNA instructions.)

But wait, which sentence in the instruction manual are we trying to copy…and why? The sentence itself turns out not to matter much, as long as it exists exclusively in the coronavirus’ instruction manual; it must be absent from the genetic code of other common viruses like flu. We make copies not so we can read them, but purely to see they can be made.Think of it this way: A million copies of a document are easier to see than a single sheet of paper. To “see” these copies, we use a fluorescent probe, which only emits light when it binds to DNA — the more DNA copies are made, the more light is emitted from the sample. In a sample from an uninfected individual — where no viral material exists in the first place — no copies will be made, and no light will be emitted. A sample containing viral RNA will get brighter over time. We can track the amount of light emitted by each sample in real time, as shown below.

The tests developed by the Center for Disease Control (CDC) in the U.S., the World Health Organization (WHO), and in-house at labs around the U.S., as well as those used in South Korea, all employ this basic strategy: using RT-PCR to detect viral RNA.

If the test is so simple, why is the U.S. having trouble getting it to work?

The U.S. initially mandated the use of CDC-developed test kits for all coronavirus testing, but labs reportedly had trouble getting them to work. The CDC was criticized for not using test kits developed in Germany, which were successfully detecting coronavirus around the world and were backed by WHO. U.S. labs responded by developing their own tests, and in some cases reporting quicker turnaround of results. This prompts the question: What are the differences between these tests and why do some work better than others?

The answer is relatively simple: Each test chose a different “sentence” to copy from the viral RNA. Effectively, this changes the primers (first and last word of the sentence), the fluorescent probe (corresponding to some word in the middle), and the “positive control” (a tube of DNA containing the “sentence” that is used to make sure the test is working properly). In fact, the CDC’s test kits are really just this: a few tubes containing the three components above.

Most molecular biology labs can develop such a test in a week or two, but those who have done so have come against another major hurdle: FDA regulations.

Choosing primers for any PCR experiment turns out to be tricky and sometimes unpredictable. Primers are just short pieces of DNA themselves, and some DNA has a tendency to fold in on itself, creating a “hairpin” structure which inhibits PCR. (This is a bit like the matching letters in a palindrome finding one another). These “palindrome” primers can produce a false negative — an infected patient whose sample appears to lack the virus. Alternatively, the primers can work just fine to make copies of coronavirus RNA, but might also be capable of copying some part of human DNA. Because patient samples (most often nasal swabs) contain both viral particles and human cells, these primers can produce a false positive — an uninfected individual testing positive for the virus. Other potential sources of RT-PCR failure are temperature issues, low primer or sample concentration, and contamination, among others.

Whether the CDC’s primers were inferior to others’ has been debated, but U.S. labs have another critical reason to develop their own tests: The CDC’s test kits are in short supply. In principle, most molecular biology labs can develop such a test in a week or two, but those who have done so have come against another major hurdle: FDA regulations barring them from testing patient samples and returning results.

Federal regulations complicate in-house testing

Before we get into the weeds here, it is important to remind ourselves why FDA regulations exist: to protect the consumer — us — from being given incorrect medical information. Typically, there is regulatory oversight both of the laboratories where clinical tests are performed and of the tests themselves (though as this article points out, prior to this outbreak, FDA oversight of clinical tests under the current administration has been alarmingly slim).

In response to this outbreak, the FDA initially mandated use of the CDC’s tests exclusively, but loosened restrictions when it became clear that the need severely outpaced the CDC’s supply. Currently, CLIA-certified labs (those already certified to perform clinical testing) are permitted to develop and use their own tests, but must submit an Emergency Use Authorization application, which involves careful (and time-consuming) validation of in-house tests and sample collection procedures. Labs with extensive experience and infrastructure to perform viral PCR assays of clinical samples, but whose primary focus has historically been research rather than clinical diagnostics, must obtain CLIA certification as well. This added requirement temporarily prevented at least one well-equipped lab which played a central role in uncovering the extent of Seattle’s outbreak from doing further testing.

It is a complicated matter that pits individual consumer protections against the country’s immediate need to ramp up testing quickly in the face of a public health emergency. Stringent and time-consuming FDA requirements are preventing academic and clinical labs around the country, with capacity and willingness to develop and deploy testing within their communities, from being able to do so.

Though a path to certification exists, it is neither quick nor painless, and in a crisis that grows exponentially worse every day, where widespread testing has proven effective in curbing transmission, it is crucial that the federal government do everything in its power to allow willing labs to pick up the slack where it has ultimately failed: being prepared to mobilize quickly in the event of a public health crisis — a job that was formerly held by the pandemic preparedness team which Trump disbanded in 2018.

Massive supply shortages require creative solutions

Labs that manage to get proper certification to run clinical testing face another hurdle: a massive shortage of supplies. Patient samples are most commonly collected as nasal swabs, and before RT-PCR, viral RNA must be separated from mucous, human cells, and other debris. Commercially available RNA extraction kits are by far the quickest and safest way to process many samples at once, but unsurprisingly, demand has quickly outpaced supply, forcing testing labs to seek donations locally via social media.

PCR machines are another major bottleneck, as well as trained individuals needed to run them at capacity. Although some researchers argue that FDA restrictions should be lifted to allow all academic labs to fire up their idle PCR machines and start testing immediately, even they recognize this would substantially increase the rate of erroneous results, leading us into uncharted and unpredictable territory. It seems more prudent for the FDA to move quickly to certify a set of well-equipped labs, which can train volunteer scientists to perform approved in-house tests at scale. On the West Coast, it’s already all hands on deck. Both the University of Washington’s School of Medicine and UC Berkeley’s Innovative Genomics Institute are training willing academic researchers, graduate students, and postdocs to perform coronavirus testing.

Will drive-thru & at-home testing help?

First, let’s clear up some confusion here. When it comes to coronavirus testing, “drive-thru” and “at-home” do not describe the test itself, which requires training and specialized equipment. These terms refer instead to how and where nasal swabs are collected. Though these strategies may not substantially increase the speed of testing, there may be immense public health benefits to performing sample collection via mail or a drive-thru point. Why? Because those who fear they are ill need not travel to a clinic, risking infecting others while there or in transit. Plans to implement at-home sample collection are already in progress, and drive-thru testing is already available for UW Medicine patients and staff. But regulatory hurdles exist in this domain as well. To process at-home tests, labs must provide substantial evidence that these samples are reliable relative to those collected by trained individuals, further hampering labs’ ability to quickly roll out these operations.

Where do we go from here?

The challenges outlined here all converge around one conclusion: The U.S. was completely unprepared for a public health emergency of this scale. South Korea revamped its emergency preparedness plans after the MERS outbreak of 2015, recognizing that early detection and isolation were effective to mitigate an outbreak, and putting resources and procedures into place which could be mobilized quickly.

Hopefully, the U.S. government learns from this catastrophe and diverts more resources toward emergency preparedness in the future. In the meantime, scientists are heroically doing what they can to pick up the slack, and it should be the government’s immediate priority to simplify and accelerate regulatory procedures to permit qualified and well-equipped labs to scale up testing. To paraphrase Trevor Bedford, a virologist and leading voice reporting on the virus’s predicted prevalence and expected trajectory, increasing testing capacity is crucial to reduce rates of transmission and get the coronavirus outbreak under control in the U.S.

As a scientist, I feel proud and encouraged by the quick and selfless responses of fellow scientists to extend testing, communicate important information to the public, and begin developing and testing vaccines at record speed. Ultimately, we are all in this together.

Last New Year’s Day—a mere three months ago—few could have imagined that by this date the United States would be in the deathgrip of a pandemic and on the brink of a prolonged economic recession. The nation’s sudden envelopment into this two-fold crisis has left politicians and policy-makers scrambling just to make sense of events, let alone to make the life-and-death decisions that fall to them. Given the sheer scale and complexity of the crisis, it is not surprising that public officials should struggle to find answers. At a minimum, however, they need to ask the right questions, especially about what they do not know, which is a great deal more than most would care to admit.

In recent days, a few public officials, including President Trump, have suggested that the current efforts to mitigate the impact of the coronavirus outbreak—social distancing and public closures—should be curtailed earlier than public health experts, including the president’s own advisors, think is prudent. It is clear that the virtual lockdown of the country is causing vast economic damage. It is also true that recessions and economic hardship have life-and-death consequences, often resulting in higher rates of suicide, domestic violence and substance abuse.

We do not know, for example, whether the official number of deaths in the United States will be 10,000, 80,000 or more.

It is understandable, then, that people are asking whether the coronavirus mitigation measures are doing more harm than good. These discussions usually take the form of comparing an unknown data point (i.e., the number of avoidable deaths Covid-19 will cause) against another unknown data point, which is assumed to be worse (i.e., a second Great Depression), or against a known, unarguable good (i.e., economic growth).

As for the first unknown, the number of avoidable deaths, we do know something—namely, that there will be many such deaths and each involves a profound human tragedy. We also know that the epidemiological models have large confidence intervals, meaning that the actual number of avoidable deaths is projected to fall within a very large range. We do not know, for example, whether the official number of deaths in the United States will be 10,000, 80,000 or more.

The reason the confidence intervals are so large is because we have terribly insufficient data, due in large part to the inadequate availability of testing. The federal government has badly bungled its response. The effects of ongoing, systematic underinvestment in the nation’s public health infrastructure were made worse by a president who spent the first weeks of this impending crisis behaving as though the number of cases would remain low. Mr. Trump downplayed the threat, and a federal bureaucracy unaccustomed to using its own power (including marshaling and coordinating private-sector forces) failed to efficiently address problems that affect the common good.

It is impossible to make good prudential decisions about completely unknown risks.

If U.S. officials had prepared for the coronavirus landfall by building up effective testing capacity, the nation would have been better able to enter into the required calculus. Perhaps the United States would have been able to mount a response similar to that of South Korea—isolating and contact-tracing known infected individuals instead of quarantining the whole population. This would permit public officials to accurately compare a more narrowly modeled epidemiological risk against the economic risk. As of now, we do not know enough to make that comparison.

These process failures have left Americans to debate ethical tradeoffs for which we lack the information to make good prudential decisions. It is impossible to make good prudential decisions about completely unknown risks, and it is a catastrophic failure of imagination and moral responsibility to act as if we are unable to learn what we need to know to make a better decision.

Making decisions such as these necessarily involves risk assessments and weighing different possible outcomes. But such decision-making must not descend into a strict arithmetical calculation that values human life as merely one material good among many. The inherent worth and dignity of human life are immeasurable.

We know there are many people who know more than the rest of us. We should listen to them. Experts can be overrated and can surely make mistakes, but in a public health emergency, prudence dictates both following their advice and doing what is possible to improve the data they are using to provide it.

And their nearly unanimous advice is clear: As Dr. Anthony Fauci told CNN on March 26: “When the numbers are going up, that’s no time to pull back. That’s when you have to hunker down and mitigate, mitigate, mitigate—get the people taken care of, that’s what you have to concentrate on.”

The Factors that Led to the Great Depression of the 1930s Had a Lot in Common with Today’s Economy, but That Depression Was Very Different.

The coronavirus or COVID19 has affected all aspects of our lives and most notably has affected the stock market. While the stock market is not always an indicator of overall economic health for an one way or the other, it’s the canary in the coal mine that reflects important economic factors.

What is worth watching is the effect COVID19 has on all factors affecting the economy, not only in the U.S. but globally. Certain impacts lead to a recession, and if those impacts are long-term, economies fall into what is described as a depression.

What is a Depression?

The term “economic depression” does not have a formal definition. Traditionally, it has been described as an extended and severe recession. Not surprisingly, recessions and depressions are never announced immediately.

It’s not until some key factors continue in a certain way over a period of time that economists reluctantly declare that a recession is occurring, and much later surrender to the realities of a depression.

What is a Recession?

Unlike a depression, a recession has a formal definition: “Two consecutive quarters of shrinking GDP.”

GDP stands for gross domestic product. It represents everything we produce over a specific period. Coming out of 2019, U.S. GDP growth stood at 2.3% in the last quarter. In the first quarter of 2020, it’s currently running at 1.6%. If the second quarter of 2020 sees a reduction from 1.6% by the end of the quarter, it will fit the formal definition of a recession.

However, most economists will wait until the end of the third quarter of 2020 before they even think to declare a recession, while ignoring that a third quarter of falling GDP is the sign of a depression.

The Unemployment Factor

In addition to a consistent decline in GDP is a rise in unemployment. While job numbers have been rising as of late, the effect of COVID19 on numerous industries has already become apparent.

• Professional sports venues across all sports have shut down their seasons and the jobs that accompany them in both stadiums and other peripheral suppliers.
• Retailers are either closing or reducing their hours, particularly in clothing and general merchandise.
• Restaurants and bars are closed in many parts of the U.S. for an unknown period of time.
• Theaters, gyms, and other spaces and places where large groups of people gather in close contact are closing.
• Cruise ship companies and many vacation resorts have shut down or closed for an unknown period of time.
• Airlines have seen a dramatic falloff of up to 50% and will all be bankrupt by the end of May if nothing changes.
• Tourist destinations in the U.S. are either closing or seeing a rapid decline.

As a result, 18% of U.S. workers have already lost jobs or hours since the impact of coronavirus hit about a week ago. 

As businesses and locations that combine large numbers of people for any length of time continue to close or reduce hours, the impact on employees for all of those businesses will grow. Some stopgap measures have been implemented by the federal government to cover loss of employment but for now that only averages two weeks.

What happens if the closures continue? The obvious answer is growing unemployment which was one of the primary causes of the Great Depression of the 1930s.

In a press conference on March 16th, President Trump stated that social distancing and the effects of COVID19 could extend well into the summer. He also stated that there is a possibility of a recession. That’s longer than two weeks for anyone receiving brief unemployment benefits.

What Happened in the 1930s?

Most people are unaware that the Great Depression actually consisted of two severe recessions. One lasted from 1929 to 1934 and the second lasted from 1937 to 1939. A variety of factors caused the recessions of the 1930s including poor government policies related to management of the money supply, banking, interest rates, and taxes.

Another factor was poor land management that led to the dust bowl and rampant unemployment across the farm states and foreclosures on homes and farms. To give you a point of reference, from 1929 to 1932, global GDP fell by about 15%. This was much more than the 1% decline during the Great Recession, which started in 2008.

Many policies and laws have been put into place to forestall some of the mistakes of the 1930s including better management of interest rates and the money supply by the Federal Reserve Banks, the creation of the FDIC to insure cash deposits in banks up to $250,000, lower taxes relative to the 1930s, and better land management practices.

All of these changes should forestall a depression, but the depression we may be facing will be more similar to what happened in Japan in the 1980s. It was driven by real estate and credit speculation and the deflation and falling wages that ensued have continued to this day.

The point is that there is no set formula for a recession and the driving factors can come from anywhere, including a pandemic.

A New Definition of Economic Depression

Based on the past patterns leading to recessions and eventual depressions worldwide, two factors have now been identified as indicators of a depression.

1. GDP must shrink by at least 10% (total GDP contraction).
2. The economic downturn must last longer than three years.

Other signals of a recessionary cycle leading to a depression include growing unemployment, foreclosures, falling wages, credit defaults, deflation, and reduced economic activity. And that last point brings us back around to COVID19.

Reduced Economic Activity

COVID19 is causing an abrupt economic shock that some economists think is more unnerving than the 2008 financial crash, which caused the worst downturn since the Great Depression.

Widespread closures and cancelations seem certain to lead to more losses and layoffs, already reflected in a stock market down 28% in less than a month. A manufacturing survey hit its lowest level since 2009 on March 16, a sign of things to come. “This feels much worse than 2008,” according to Harvard economist Jason Furman.

This all gets back to the fundamental feature of a depression: duration of the recession. If the necessary response to COVID19 continues to have the severe impacts currently indicated… a depression is inevitable.

10 Ways to Prepare for this Depression

You can, in fact, take control of the situation at least to some degree. Here are 10 things to do to prepare for an economic depression:

1. Pay off debt starting with credit cards. 

Eventually, you can move on to other debts. There’s no need to pay off your mortgage, but if you have paid all of your debts and want to make some principal payments, you can consider it, but only after you’ve taken the next step.

2. Shore up your emergency fund for at least 6 months of expenses.

In the event you are laid off, this fund can get you through. However, the standard recommendation is for a 6-month emergency fund even in the best of times. If you’re concerned, you can extend that to the time frame you’re most comfortable with.

3. Build your network, both professional and personal.

If you lose your job, your professional network can be the fastest path to new employment. Also, people need to help and support each other in desperate times, so a strong social network is a smart idea.

4. Learn to prepare food at home and how to can and store food. 

If restaurants continue to be closed for any length of time and you don’t know how to cook, now’s the time to learn. It also saves money and keeps you out of public restaurants. The ability to can and preserve foods is also a good skill and a cost saver.

5. Learn to shop wisely. Shop for sales and only buy what you need.

With many retailers closed or closing, shopping may not be the issue it once was but even then, shop wisely. If you need it, buy it. But ask yourself if you really need it.

6. Plant some food. Start a vegetable . Plant vegetables instead of flowers. 

To a large degree, we depend on imports of produce. If for any reason those imports are affected, the cost and availability of produce could increase significantly. Plant a garden and take a second look at those flower beds. You may be better off planting strawberry plants or vegetables rather than zinnias.

7. Learn to live below your means.

Again, only buy it if you need it. Here are five frugal tips that will save you some money.

8. Keep your car in good condition. Especially if it’s paid off.

A new car payment adds to the debt.

9. Buy classic style clothes, not the latest trend.

Now is the time to think functionally not fashionably.

10. Avoid aggressive investments.

The stock market is deceptive and unless you have a strong grasp of investment fundamentals, stay with the safe investments.

Monitor What’s Happening

What has been true about all past recessions and depressions is that economists and governments don’t announce them until they have become woefully obvious. At some point, they are likely to point back to March 2020 as the beginning of the depression.

Don’t allow yourself to be surprised. Consider the 10 steps listed above and keep a close eye on reports related to GDP and unemployment.

The stock market can be a fool’s game and a fool’s indicator of the underlying strengths or weaknesses in an economy. Statistics related to GDP and unemployment paint a more accurate picture. With any luck, the steps being taken worldwide will curb the pandemic.

Recent reports from Hong Kong indicate life is getting back to normal. How their economy or any other economy in the world recovers has yet to be seen.