The curse of the PCR method - comments on the COVID-19 criticism by Dr. Wolfgang Wodarg, MD

We would like to make some comments on the COVID-19 criticism, as also uttered by Dr. Wolfgang Wodarg, MD, cf.

• Wolfgang Wodarg, „Die Panikmacher - Die Medien schüren zum Coronavirus die Angst.“, Rubikon News, 14. März 2020, https://www.rubikon.news/artikel/die-panikmacher

[Translation]
“The panic makers - The media stir up fear of the corona virus”

Note: Dr. Wodarg 's website ( www.wodarg.com ) contains further detailed information and is partly available in English. From there the following link,

• John P.A. Ioannidis, “A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data”, Stat News, March 17, 2020, https://www.statnews.com/2020/03/17/a-fiasco-in-the-making-as-the-coronavirus-pandemic-takes-hold-we-are-making-decisions-without-reliable-data/

To better understand what Dr. Wodarg is saying one should know the peculiarities of the PCR method. Dr. Wodarg’s arguments go further and, based on his years of expertise, include important epidemiological aspects. We only refer to the PCR aspect.

Dr. Wodarg was heavily attacked for criticizing measures of the German government. Wrongly, because these are valid arguments that reasonable people would have checked before(!) making a decision. There is no reason to discredit these arguments later, because it was believed that a discussion was not necessary and that the measures taken by politicians are now too drastic for further criticism.

It concerns our core criticism of current biomedicine: large parts of biomedicine live on assumptions that are sometimes not even plausible. Consensus on a presumption regularly replaces scientific evidence in biomedicine.

Attacks of this type, such as those against Dr. Wodarg, are well known from other topics, e.g. the US opioid crisis and the glyphosate discussion. They are always driven by the desire not to allow for a scientific discourse on convenient (and usually profitable) assumptions. The attack on the person replaces the argument and at the same time deters others. Due to the dependency on reviewers for their own research proposals, hardly anyone in the ongoing research business can afford to represent controversial positions contrary to a consensus presumption.

The suppression of criticism violates any scientific standard and is never in the patient's interest.

The peculiarity of the PCR method is that it can only find what one is looking for. This is different than e.g. the light microscope, which amplifies everything that reflects light at the same time! PCR searches with so-called primers. There are always 2 of them, one forward primer and one reverse primer. These are 20-40 bases long DNA single chains, so quite short. (If you are looking for RNA, it must first be translated into DNA in the sample. The resulting cDNA is then analyzed with PCR).

At room temperature, DNA consists of a double strand that is not very reactive (outside the cell). DNA is doubled using the enzyme DNA polymerase (the P in PCR). The cell does this during cell division. You then have 2 double strands.

Here is the PCR cycle: increasing the temperature divides the double strand into 2 single strands. Now the primers can dock on in their complementary positions. Namely the forward primer on one strand and the reverse primer on the (complementary) other strand. On a (very) short piece, one now has a double strand consisting of a single strand of the sample and a primer. This step determines the specificity of PCR. Do the primers dock or not?

The sample is now cooled and the DNA polymerase now extends these short pieces along the respective single strand by incorporating base molecules from the medium. You then have 2 complete double strands again. Now you can repeat the step (cycle), i.e. increase the temperature again to divide the double strand, allow primer to dock, cool and extend primer along the single strands, etc., to generate 4 DNA double strands, 8, 16, etc. (this CR in PCR - chain reaction).

PCR is ultra-sensitive, i.e. it can detect absurdly low levels of DNA. On the other hand, it is only moderately specific in that PCR amplifies everything to which the primers can dock. That is the curse of the PCR method.

On the one hand, the sample purity plays a role. Is the DNA to be examined sufficiently purified or are there any residues of other DNA? These residues can also come from neighboring species, in other words from other virus strains that have not been sufficiently removed in the sample preparation. On the other hand, the base sequence of the primers does not determine the docking of the primers alone, although this is an essential factor, but the electronic structure of the primers.

A so-called gold standard is also required, i.e. a method independent of PCR to demonstrate that PCR amplifies the right thing. These are usually serological tests, but they are difficult to apply for viruses because viruses are sometimes difficult to cultivate and isolate. For this reason, in the past few years, also due to the lack of alternatives, PCR has been declared its own gold standard. That is extremely questionable.

However, PCR is not so unspecific that it can amplify any DNA strands, but there must be a sufficient match with the primers. If you look into the same sample with other primers, another DNA strand is (if sufficiently matching) amplified.

Most of the time, one tries to avoid these problems by using several different primer pairs, which are supposed to dock at different locations of the DNA to be examined. It becomes difficult if there are pathogenic and harmless viruses in a sample, which may have similar gene sequences. Were the primers sufficiently specific or did the harmless viruses cross-react with the primers for the (presumably) dangerous viruses?

Often only guess helps here. If you ask the manufacturers, you usually get the statement that the primers bought are very, very specific.

Concerning cross-reactions it should also be noted that such reactions are usually excluded on the basis of the laboratory samples that have just been used to develop the test. This is based on the very far-reaching assumption that the virome in the rest of the world looks exactly the same as in the laboratory. That is a very questionable.

Note 1: The topic of cross-reactions in PCR tests is usually downplayed, since most of the publications come from the manufacturers themselves. It's been like this for 20 years. And it is particularly bad with the PCR protocols recommended by the WHO. The WHO seems to have never heard of the word cross reaction.

Note 2: PCR cannot detect whether viruses are neutralized by antibodies. PCR is also unable to detect whether the viruses are capable of reproduction. Usually, it is only fragments of the viral genome that are amplified by PCR.

Note 3: whether or not something is found with PCR has nothing to do with the question of whether the species in question, to which the DNA (RNA) examined belongs, is the cause of the disease.

Note 4: PCR diagnostics is a billion dollar market.

Now the comments on the COVID-19 criticism by Dr. Wolfgang Wodarg, MD.

1) Selective measurements on the sick and seriously ill

The influence of the roll-out of the new WHO measurement method (= new primers) is currently being measured in the case numbers. This is because most of the measurements are still from sick or critically ill people and the least from healthy or symptom-free people. The SARS-CoV2 attributed death rate is therefore high. New figures from China are well below the value given by the WHO.

2) Search with PCR for SARS-CoV2
Every year there are virus waves with a seasonal peak in winter. Classic corona viruses are involved in 5 - 15% of the cases, vgl.

• Nickbakhsh et al., “Virus–virus interactions impact the population dynamics of influenza and the common cold”, PNAS December 26, 2019 116 (52) 27142-27150, https://www.pnas.org/content/116/52/27142

You can look for these because you know what the PCR primers must look like.

But these viruses also mutate and change. This means that there are slightly different corona viruses every year. On the one hand, one has not searched for SARS-CoV2 PCR primers in the past, because they did not exist. This means that no SARS-CoV2 could be found or assigned to SARS-CoV2 primers.

On the other hand, PCR also leads to cross-reactions between different coronavirus strains, so that one does not know exactly what has been measured and assigned to the PCR primers used at that time.

Nobody knows what the set of all corona viruses looks like. I.e. nobody can say whether SARS-CoV2 has not existed before, because no one searched for it with SARS-CoV2 primers or whether SARS-CoV2 was measured with other (classic) primers due to cross-reactions. It is naive to think that biomedicine knows exactly what is in the cells. It is very far from that.

See also on cross-reactions of coronaviruses,

• Patrick et al., “An Outbreak of Human Coronavirus OC43 Infection and Serological Cross-reactivity with SARS Coronavirus.”, Can J Infect Dis Med Microbiol. 2006 Nov; 17(6):330-6, https://www.ncbi.nlm.nih.gov/pubmed/18382647

This publication also underlines that classic corona viruses can have serious consequences in an older population (i.e. in a nursing home).

3) Zoonotic hypothesis
PCR cannot prove that SARS-CoV2 is new. And the meaning of the genetic distance between two types of virus is completely open. For the zoonotic hypothesis of SARS-CoV2, which is important for an increased pathogenicity (no time for adaptation), there is not the slightest proof, only guesswork.

There is also the question of why >85% of confirmed cases show no or only mild symptoms in case of a new pathogen? This suggests that large parts of the population are adapted to the pathogen, which speaks against a new pathogen.

What protects these people? Antibodies against classic coronaviruses? They cannot have antibodies against the new virus.

The fact that homologous gene sequences were found across the entire planet within a few weeks(!) is also no evidence of zoonosis. On the contrary, if the virus spreads so easily, why aren't the infection numbers much higher? It can be argued that the virus had time to spread. In Wuhan the new primers were only used for measurement first .

4) Cause of symptoms
There are a variety of viral pathogens that can cause mild or severe respiratory diseases, e.g. flu viruses. In all cases, this would have to be verified with PCR, or better not, to exclude it. However, if you only look for SARS-CoV2 with PCR, you will only find that or assign it to SARS-CoV2. It cannot be said whether it is (exclusively) the cause of the respiratory disease. The flu virus continues to exist. You can't tell from the fever or cough what pathogen it was. Molecular diagnosis is difficult. This is also because quantification of the viral load with PCR is very error-prone. The tremendous sensitivity of PCR can amplify even the tiniest amounts, a few viruses per ml. These are amounts that are so small that they cannot be associated with any acute symptom.

Determining the cause of a disease is usually a very complex process that involves an in-depth and controversial discussion before agreeing(!) on what the current state of science is. At least it should be like that. With SARS-CoV2 it took a few weeks. It gives the impression that one has been waiting for years for a second SARS chance.

The mood in biomedicine is like this. Everything that seems dangerous to fatal drives research forward. And research is always good. Can you ever know enough? However, instead of creating knowledge, it is often merely suffices to reach a somewhat contradiction-free consensus. That doesn't bother anyone as long as the research billions and profits flow.

It does not matter that healthy people also carry many different viruses, some with vital tasks (human virome). Nor does it matter that many types of virus and strains are not pathogenic. To differentiate, one simply assumes ultra-specific methods. Dr. Drosten, the SARS (co)discoverer, has benefited disproportionately from these circumstances in the past.

Scientific standards exist for a good reason. And haste doesn't produce quality. Science, and with it politics, is now running behind. There it is easier to discredit valid arguments as fake news.