Written by Helena Windsor

 

 

In his open letter to Sajid Javid and Grant Schapps, published here on July 9th , Anthony Webber made a number of derogatory claims about the use of PCR tests to detect SARS Cov-2, the virus that causes Covid-19. Very few ordinary members of the public, journalists, or even political commentators are likely to be familiar with the PCR test, let alone have actually carried out these tests in a laboratory. So just what is a ‘PCR Test’?

It is nearly seventy years since James Watson and Francis Crick worked out the structure of DNA from Rosalind Franklin’s X-ray diffraction photographs. Read Watson’s book, The Double Helix, about the events leading up to it, if you haven’t already. Spoiler alert, he fluffs his maths and is called out by Franklin. And a trigger warning for younger readers, 1950s attitudes to women, especially clever women in science, are appalling.

DNA consists of four nucleotides, or bases, adenine, thymine, guanine and cytosine, with a sugar and phosphate backbone. When adenine bonds to thymine and cytosine to guanine on another strand they form the familiar helical structure of double-stranded DNA. So here is the secret dance of life – a single strand of DNA is the template for the second strand; an enzyme, called DNA polymerase adds extra bases according to the code of the base pairs – adenine to thymine and cytosine to guanine. The dance carries on, in each and every cell, as the codes embedded in that nucleic acid genome generate a multitude of different Messenger RNA strands, the templates used by ribosomes to make proteins.

Watson and Crick had liberated the genie from the bottle; scientific work with DNA expanded and expanded. In 1983, Kary Mullis, a chemist working for Cetus Corporation in California, had a light bulb moment whilst driving to his country cabin with his girlfriend. Could he tag for replication a desired DNA sequence and copy it using DNA polymerase? This would allow rapid amplification of a small stretch of DNA via repeated heating and cooling cycles. When double stranded DNA is heated, the strands separate, Mullis’ idea was to introduce targeted, short complementary sections to anneal, or bind to the separated strands during cooling, then extend the sequence with the polymerase enzyme.

In 1986, a colleague at Cetus, Randall Saiki, working on the new technique, used the enzyme from Themophilus aquaticus (Taq) a bacterium found in hot springs. Taq polymerase is heat resistant and only needs to be added to the reaction once. This modification revolutionized biochemistry, molecular biology, genetics, medicine, and forensics, giving scientists the ability to amplify DNA of a specific sequence, starting from a few simple chemicals and some temperature changes. Mullis was awarded the Nobel Prize in chemistry in 1993.

Claims that Mullis has said that PCR – the Polymerase Chain Reaction, should not be used for detection of infectious disease, or infectious viruses, have circulated widely, along with a comment that he once made about HIV, “If they could find this virus in you at all, with PCR, if you do it well, you can find almost anything in anybody.”  The latter remark has been widely abused to suggest PCR testing for Covid is fake. Well, yes, with the right primers for whatever gene or disease agent you are seeking, his statement is true, without them, you won’t. We can’t ask Mullis sadly, as he died in early 2019, but one thing we can be sure of, he would have known by then that PCR was the detection method of choice in clinical and veterinary diagnostic laboratories worldwide. This is particularly true for virus infections. Whereas bacteria can be visualised with special stains using a light microscope and many grow up in a day or two, viruses must be grown in cell cultures and need an electron microscope to be seen.

When Zhang Yongzhen, a Chinese virologist and professor at Fudan University, sequenced and published the genome of SARS CoV-2, the virus that causes Covid-19, in early January 2020, it was inevitable that PCR would become the dominant method for detection. Once the genome sequence was known, a specific PCR test could be developed and shared around the world far more quickly than alternative methods. The lateral flow and laboratory run equivalent tests, need the laboratory-based generation of antibodies to the target, which are then usually tagged to something that gives a colour when the two bind (those red lines on your LFT).

A conventional PCR requires the sample to be sent to a lab for processing, for this reason, I personally believe that more rapid, point of use or care tests should supersede PCR for Covid testing.