DNA, RNA, RT-PCR, Testing Methods, Supply Chains… and Politics

What is Reverse Transcription Polymerase Chain Reaction?

Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase chain reaction (PCR). It is primarily used to measure the amount of a specific RNA. This is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR). Combined RT-PCR and qPCR are routinely used for analysis of gene expression and quantification of viral RNA in research and clinical settings.

Blah Blooh Bleeh Blah. Right?

Well, this is the test that will tell us if a person has got the corona virus or not. So listen up!

The corona virus is in the form of RNA:

Coronaviruses, so named because they look like halos (known as coronas) when viewed under the electron microscope, are a large family of RNA viruses. The typical generic coronavirus genome is a single strand of RNA, 32 kilobases long, and is the largest known RNA virus genome. Coronaviruses have the highest known frequency of recombination of any positive-strand RNA virus, promiscuously combining genetic information from different sources when a host is infected with multiple coronaviruses. In other words, these viruses mutate and change at a high rate, which can create havoc for both diagnostic detection as well as therapy (and vaccine) regimens.

But as best as I can tell, detecting the corona virus becomes pretty difficult unless it turns into DNA, which can be done by a process called Reverse Transcription.

With the newly formed DNA, replicate it – have it reproduce a lot, basically. That’s where PCR comes in. And with that (and a fluroscent dye that is added to make detection easier) you have a sample that you can check for the presence of the corona virus.

The first, PCR, or polymerase chain reaction, is a DNA amplification technique that is routinely used in the lab to turn tiny amounts of DNA into large enough quantities that they can be analyzed. Invented in the 1980s by Kary Mullis, the Nobel Prize-winning technique uses cycles of heating and cooling to make millions of copies of a very small amount of DNA. When combined with a fluorescent dye that glows in the presence of DNA, PCR can actually tell scientists how much DNA there is. That’s useful for detecting when a pathogen is present, either circulating in a host’s body or left behind on surfaces.

But if scientists want to detect a virus like SARS-CoV-2, they first have to turn its genome, which is made of single-stranded RNA, into DNA. They do that with a handy enzyme called reverse-transcriptase. Combine the two techniques and you’ve got RT-PCR.

So, here’s how it works, best as I can tell:

Coronavirus Detection Steps


That article I linked to from Wired has a more detailed explanation, including more detailed answers about the “how”, if you are interested. Please do read it fully!

Now, which kit to use to extract RNA from a snot sample, which dye to use, which PCR machine to use – all of these and more are variables. Think of it like a recipe – different steps, different ingredients, different cooking methods. Except, because this is so much more important than a recipe, the FDA wags a finger and establishes protocol.

That protocol doesn’t just tell you the steps, but it also tells you whether you are authorized to run the test at all or not. And that was, uh, problematic.

For consistency’s sake, the FDA opted to limit its initial emergency approval to just the CDC test, to ensure accurate surveillance across state, county, and city health departments. “The testing strategy the government picked was very limited. Even if the tests had worked, they wouldn’t have had that much capacity for a while,” says Joshua Sharfstein, a health policy researcher at Johns Hopkins School of Public Health and the coauthor of a recent journal article on how this testing system has gone awry. “They basically were saying, we’re going to use a test not only developed by CDC, but CDC has to wrap it up and send it to the lab, and it’s just going to be state labs doing it.”

The effect was that the nation’s labs could only run tests using the CDC’s kits. They couldn’t order their own primers and probes, even if they were identical to the ones inside the CDC kits. And when the CDC’s kits turned out to be flawed, there was no plan B.

By the way, if you want a full list of the various protocols that are listed by the WHO, they can be found here.

Back to the Wired article:

Another in-demand approach would look for antibodies to the virus in the blood of patients, a so-called serological test. That’d be useful, because in addition to identifying people with Covid-19, it could tell you if someone was once infected but then recovered. “The better your surveillance, the more cases you’re going to catch, but even with perfect surveillance you won’t catch everything,” says Martin Hibberd, an infectious disease researcher at the London School of Hygiene and Tropical Medicine who helped develop one of the first tests for the coronavirus SARS in the early 2000s. “Until we’ve got a full test of this type of assay, we don’t know how many cases we’ve missed.”

A serological test would also probably be cheaper than a PCR-based one, and more suited to automation and high-throughput testing. A researcher in Singapore is testing one now.

Here’s an early paper on the topic, if you are interested.

Serological assays are of critical importance to determine seroprevalence in a given
population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of Coronavirus SARS-Cov-2 antibody titers will also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.

As far as I can tell, this method has not been deployed at all thus far, and that applies to India as well. Here’s a Wikipedia article about the different methods of detecting Covid-19 – it’s about more than that, the first section applies here. Here’s an article from Science about a potential breakthrough.

But whether you use any variant of the RT-PCR or the serological test, given the sheer number of kits required, there is going to be crazy high demandand a massive supply chain problem.

Along with, what else, politics, and bureaucracy:


The Wired article is based on reporting in the US, obviously, but there are important lessons to be learned here for all countries, including India.

Here are some links about where India stands in this regard:


I’ll be updating the blog at a higher frequency for the time being – certainly more than once a day. Also (duh) all posts will be about the coronavirus for the foreseeable future.

If you are receiving these posts by email, and would rather not, please do unsubscribe.

Thanks for reading!


Econ101: Policy Responses to a Pandemic

If you haven’t played it already, go ahead and give this game a try: The Fed Chairman Game. I have a lot of fun playing this game in class, especially with students who have been taught monetary policy. It usually turns out to be the case that they haven’t understood it quite as well as they think the have! (To be clear, that’s the fault of our educational system, not the students.)

But the reason I started with that is because the game always throws up a scenario that mimics a crisis, and asks you what you would do if you were the Chair of the Fed.

In this case, policymakers the world over are now staring at a very real crisis, and they need to be asking themselves: what should we do?


There are two broad answers, of course: monetary policy, and fiscal policy.

The Federal Reserve has cut interest rates to zero, and while it has other tools to stimulate the economy, a crisis like this requires fiscal as well as monetary responses. The legislation passed thus far has been important, but another round of fiscal policy will be required immediately to fully address this crisis.

A robust fiscal response can provide income support to households, ensure broad and continuous access to safety net programs, provide incentives for employers to avoid layoffs, provide loans to small businesses, give liquidity cushions to households and firms, and otherwise stimulate the economy.

That’s a write-up from Brookings. The specifics follow in that article, but the article makes the point that more of the lifting will need to  be done by fiscal, rather than monetary policy. And that is true for a variety of reasons,  which the article does not get into, but long story short – fiscal, more than monetary.

But, ok, fiscal policy of what kind? Should we give money to firms or to workers? Here’s Paul Krugman with his take…

And here’s Alex Tabarrok with his response:

So what’s the correct answer? Well, as we’ve learnt before, and will learn again, macro is hard! In an ideal world, all of the above, but as is manifestly clear, we are not in an ideal world. If we must choose between giving money to firms or to people, to whom should we give it? My opinion? People first, businesses second. This is, of course, a US centric discussion, what’s up with India?


Here’s, to begin with, a round-up from around the world – you can search within it for India’s response thus far.

Calls are getting louder for governments to support people and businesses until the new coronavirus is contained. The only questions are how much money to shovel into the economy, how to go about doing it, and whether it will be enough.

Already, officials from Paris to Washington DC are pulling out the playbook used in Asia for slowing the spread of Covid-19: they’re restricting travel and cracking down on public gatherings. While those measures have the potential to reduce deaths and infections, they will also damage business prospects for many companies and cause a synchronized worldwide disruption.

Here’s the FT from two weeks ago about the impending slow down:

Venu Srinivasan, whose company TVS is one of India’s largest makers of motorcycles and scooters, said the business had lost about 10 per cent of production in February owing to a lack of Chinese-made parts for the vehicles’ fuel injection system. He added that TVS has now managed to find a new supplier.

But Mr Srinivasan said he was bracing for India’s recovery to take longer than anticipated. “One would have expected a V-shaped recovery, but instead you have an L shaped recovery,” he said. “It’s been the long haul.”

R Jagannathan in the LiveMint suggests this:

This is how it could be designed. Any unemployed urban youth in the 20-30 age group could be promised 100 days of employment and/or skilling options paid for by the government at a fixed daily rate of ₹300 (or thereabouts, depending on city). At an outlay of ₹30,000 per person annually, the unemployed can be put to work in municipal conservancy services, healthcare support, traffic management, and other duties, with the money also being made available for any skill-acquiring activity chosen by the beneficiary (driver training for Ola-Uber, logistics operations, etc). All companies could be given an opportunity to use the provisions of the Apprentices Act to take on more trainees, with the apprenticeship period subsidized to the limit of ₹30,000 per person in 2020-21. If the pilot works, it could be rolled out as a regular annual scheme for jobs and skills. Skilling works best in an actual jobs environment.


He also mentions making the GST simpler, which the Business Standard agrees with:

Certainly, the rationalisation of GST will also affect government revenues. However, a simpler and more transparent system would allow greater collection and reduce evasion. The government will receive a windfall this year from lower crude oil prices. The moment to move on the structural reform agenda is now. The GST Council has done well to address the inverted duty structure in mobile phones. Further rationalisation will give confidence to the market that the government is serious about reforms. It was promised that GST would remain a work in progress, and that the GST Council would act often to improve it. So far, however, the changes have been marginal and haphazard. A more structured and rational approach, which outlines a quick path to a single rate, would pay dividends for the economy in the longer run. It would also be an effective way to manage the immediate effects of a supply shock such as is being caused by the pandemic.

Also from the Business Standard, a report on the government now considering (not happened yet) relaxing bad loan classification rules for sectors hit by the corona virus. That’s pretty soon going to be every sector!


Assorted Links about the topic – there’s more to read than usual, please note.

Here is Tyler Cowen on mitigating the economic impacts from the coronavirus crisis.

Here’s Bill Dupor, via MR, about the topic:

First, incentivize behavior to align with recognized public health objectives during the outbreak.

Second, avoid concentrating the individual financial burden of the outbreak or the policy response to the outbreak.

Third, implement these fiscal policies as quickly as possible, subject to some efficiency considerations.

Again, via MR, New Zealand’s macro response.

Arnold Kling is running a series on the macro response to the crisis.

Claudia Sahm proposes direct payment to individuals:

This chapter proposes a direct payment to individuals that would
automatically be paid out early in a recession and then continue annually
when the recession is severe. Research shows that stimulus payments that
were broadly disbursed on an ad hoc (or discretionary) basis in the 2001 and
2008–9 recessions raised consumer spending and helped counteract weak
demand. Making the payments automatic by tying their disbursement to
recent changes in the unemployment rate would ensure that the stimulus
reaches the economy as quickly as possible. A rapid, vigorous response to
the next recession in the form of direct payments to individuals would help
limit employment losses and the economic damage from the recession.

Here are the concrete proposals, the entire paper is worth a read:

Automatic lump-sum stimulus payments would be made to individuals
when the three-month average national unemployment rate rises by
at least 0.50 percentage points relative to its low in the previous 12
• The total amount of stimulus payments in the first year is set to
0.7 percent of GDP.
• After the first year, any second (or subsequent) year payments would
depend on the path of the unemployment rate.


Macroeconomics IS HARD!

Economics in the times of COVID-19, there is already a book. I learnt about it from Tim Taylor’s blogpost. I have not read the book, but will soon.

The NYT, two weeks ago, on the scale of the problem facing policymakers.