With the ongoing Covid-19 situation, there are some questions repeatedly going around:
-"How did China, Korea etc manage to create a test for a completely novel virus so fast?"
-"Why are rest of the world so slow?"
-"What happened in the US with the first test being faulty?"
-"How did China, Korea etc manage to create a test for a completely novel virus so fast?"
-"Why are rest of the world so slow?"
-"What happened in the US with the first test being faulty?"
I am going to try to explain the test here. Buckle up for some #scicomm
To answer these questions, we first need to understand how the test works. It tests whether the genetic material unique to the virus is present in the patient sample.
To answer these questions, we first need to understand how the test works. It tests whether the genetic material unique to the virus is present in the patient sample.
Coronaviruses, of which Covid-19 is just one kind, all contain RNA just like humans carry DNA in each cell. This RNA is a set of letter A,G,C and U, arranged in a unique sequence. Chinese scientists deciphered this unique sequence for Covid-19 in Jan (tinyurl.com/vfqms3h).
Researchers used this to compare against all other sequences known to us to identify bits of the sequence that are unique to the virus but not present in humans. , This is like a signature, which we can search for in patient samples to test whether the patient is infected.
Based on the virus signature sequence, we can manufacture small pieces of DNA called probes. We make 2 probes infact, which read in opposite directions. So, for instance, if the virus sequence is ATGCATGGGGAACC, we make ATGC and CCAA.
(I know this is technically incorrect for you afficianados, but I am simplifying here). Also remember, probes are inexpensive and easy to make.
Now, how we do the search is a multi-step method called RT-PCR (tinyurl.com/r596odq). In the first step, the swab sample is separated into two – one containing all the RNA (human AND viral, and anything else), and the other tube containing everything else.
Then, an enzyme, Reverse Transcriptase (RT) is used to make DNA from the RNA. This is because DNA works better for the next step, Polymerase Chain Reaction (PCR). Now, remember this will have human AND viral DNA at this point.
We now introduce the probes we have made earlier along with a catalyst that can make many copies (>10,000) of the unique signature, even if only handful of viruses were originally present – however, the catalyst *cannot* do its job if there is no DNA from the virus.
We also add a chemical dye at this stage that will glow (emit fluorescent light) when it attaches to a copy of the unique sequence. So, this way, we can measure light as a way to detect the virus.
If you see a sufficient amount of light, you know there is virus. If you don’t get light, you can be confident that there is no virus! And voila, that is how the test works.
Infact, this is a very standard test scientists often do in their work as part of research because of its versatility and applicability – by simply changing the probes, you can modify the test quickly to test for anything you like.
Now back to the questions:
China and Korea were able to create the test so fast precisely because of its versatility. Once the virus sequence was deciphered, they only had to find the unique sequence & design probes. This took <2 days, so they could start testing very quickly
China and Korea were able to create the test so fast precisely because of its versatility. Once the virus sequence was deciphered, they only had to find the unique sequence & design probes. This took <2 days, so they could start testing very quickly
Then, why is it hard to ramp up tests quickly? Because the first step of separating the viral RNA from everything else in the patient swab is done using a product made by a handful of companies. (1/2)
This product, while widely available in countries doing scientific research, is not avl in millions needed for such large scale implementation. The companies are ramping up production, but they will need time to achieve production ~50-100 times higher than they normally do. (2/2)
While this is happening, there are lots of other tests being trialed currently (tinyurl.com/r9m243r), some that can report in as fast as 60 mins. But all that I have seen still depend on separating viral RNA as the first step, and that will remain a bottleneck.
Other ideas are also being worked on, for example
What happened with the CDC in the US? The US decided to create new probes than trust the WHO approved probes. However, this was poorly designed and gave wrong results (ie., light even when there was no virus, likely because the probe was too similar to some part of human DNA).
Bonus for those of you who have read this far: How does the drug remdesivir work and why is it being tried as a treatment for Covid-19? See here for a wonderful thread by @jenheemstra
