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Borger & Kämmerer, Corona & qPCR, Pseudoscience & Conspiracy Theory Revisited - an Analytical Essay -

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Abstract

Analysis of the pseudoscientific critique of Pieter Borger, Ulrike Kämmerer and allies concerning the qPCR test for SARS-CoV-2 published by V Corman, C Drosten and co-authors in 2020.
Borger & Kämmerer, Corona & qPCR,
Pseudoscience & Conspiracy Theory Revisited
- an Analytical Essay -
by Andreas Beyer
Westfälische Hochschule Gelsenkirchen, Bocholt, Recklinghausen (W-Hs.de), 01.05.2021
Summary
By the end of 2019, a novel corona virus, SARS-CoV-2, was transmitted from animals to
humans in China and quickly spread out from there over the globe. In January 2020, a con-
sortium of scientists – Victor M Corman, Christian Drosten and 22 co-authors published a
qPCR-assay for this virus [1]. In November 2020, a group of corona-critics Pieter Borger,
Ulrike Kämmerer and 20 co-authors launched a text in the internet [2a] containing harsh
criticism of the Corman-Drosten qPCR test for SARS-CoV-2 in surprisingly aggressive diction
[see 2a and 3].
It can be shown that this critique is insubstantial [3]. The text contains quite a few fallacies
and moreover reveals a severe lack of PCR expertise in the Borger-Kämmerer group. Fur-
thermore, they criticise a version of the PCR-test that at the time of publication (Nov. 2020)
already had been obsolete, since the test had been refined already some weeks after its
publication in January 2020. In February 2021 the Borger-Kämmerer group answered [4] to
my analysis, among other aspects criticising the fact that I had ignored their „Addendum“.
Here, my first analysis [3] is reconsidered, taking into account the answer of the Borger-
Kämmerer group [4] – again demonstrating that the critique of Corman-Drosten is not
scientifically founded. Moreover, their „Addendum“ is just as flawed as their „Report“.
The problem with such pseudoscientific publications is their impact: The critique by the
Borger-Kämmerer group though ignored in the professional world for good reason has
been cited thousands of times worldwide outside the scientific realm and turned out to be
very influential especially in conspiracy theory circles.
Meanwhile, science is attacked from all sides – anti-vaccinationists, creationists, climate
change deniers, 9/11 conspiracists to mention only a few. And as in the case addressed here
they begin to link with each other to form networks (1
st
author Borger and one of the co-
authors are leading members of Germany's most important young-earth creationist society).
Unfortunately, there is no scientific forum to analyse such pseudoscientific and fake-science
publications because they are meaningless with regard to their contents. However, to the
public this looks as if science is unable to refute such attacks and/or that scientists are ig-
norant. Hence I strongly suggest to the scientific community to found a peer-reviewed
Journal of Scientific Evidence and/or Sceptic Analysis Journal providing a platform
where such publications – or even better: every peace of bad science – can rigorously
and in-depth be analysed, unmasked and debunked. It is time to offensively argue
against such movements that well have the potential to seriously harm our knowl-
edge- and science-based society.
Moreover I ask all colleagues please to spread this essay so that it may make a
contribution to defence against myths spread by corona-sceptics.
Background
In January 2020, Corman et al. published one of the first test systems (a qPCR) for SARS-
CoV-2 in the journal Eurosurveillance (here referred to as „Corman-Drosten test“ or
„Corman-Drosten paper“ [1]). Within the next months, quite a few publications appeared
introducing other test systems, or improving the Corman-Drosten test, and others comparing
different test systems available at the given time (i.e. Afzal 2020, Jung et al. 2020, Konrad et
al. 2020, Matheeussen et a. 2020, Muenchhoff et al. 2020, Nalla et al. 2020, Pan et al. 2020,
Vogels et al. 2020). In November 2020, a group of people, some of them scientists, pub-
lished in the internet severe accusations (here referred to as „Borger-Kämmerer-text“ [2a])
against the Corman-Drosten paper – thereby attacking the very first version of the qPCR
protocol which at that time already had been updated since months! (Muenchhoff et al. 2020;
Matheeussen et al. 2020). They also submitted that text as a manuscript to Eurosurveillance
combined with a „retraction request“. In January 2021 I published an analysis (here referred
to as „my analysis“ [3]) of the Borger-Kämmerer-text in which I have shown that this text is
pseudoscientific and denialistic
1
– completely in line with the scientific world. Since that time I
am not unexpectedly target for attacks and insults; in February 2021 Borger and allies
have published a harsh answer to my analysis (here referred to as Borger-Kämmerer answer
[4]). I took this as a motive for a summary in the form of an analytical essay [this text]. Mean-
while, Eurosurveillance has rejected the „retraction request“ associated to the Borger-Käm-
merer-text [1] with an explanatory statement [5]
2
. So far, the Borger-Kämmerer manuscript
[2] has not been published by any peer-reviewed journal.
The Corman-Drosten qPCR test [1]
By the end of 2019, in China a novel corona virus was transferred most likely indirectly
from bats to humans (Andersen et al. 2020, Tang et al. 2020, Wang et al. 2020 to mention
only a few). Already in January 2020 first sequence information for this virus was available
(GenBank acc. MN908947, additional four genome sequences were to follow on Jan 12
th
)
and it was clear that it belonged to the beta coronavirus taxon and moreover is a closer rela-
tive of SARS-CoV-1. For this reason it has been named SARS-CoV-2. Moreover, a couple of
cases of death already had to be attributed to this virus (Chen et al. 2020). Some scientists
(primarily responsible were two working groups at the Berlin Charité hospital in Germany)
decided to quickly develop a qPCR test for SARS-CoV-2 to have it available if CoViD-19 (the
disease caused by SARS-CoV-2) would turn out to be a global threat. And it did.
Design of this test was thorough and rigorous. The available genomic sequences of SARS-
CoV-2 were considered as well as some 100 other sequences of (more or less) related as
well as unrelated viruses. However, due to limited sequence information available by that
time, primer design was – though good – not optimal. With plenty of new sequences coming
up and hence robust information on SARS-CoV-2 genome sequence and sequence con-
servation available, this test was further developed and optimised by different researchers
and several commercial companies, more tests were added during 2020 and further surely
will be.
1
For here, this definition may be sufficient: https://en.wikipedia.org/wiki/Pseudoscience
For denialism see Diethelm & McKee (2009)
2
Documents in the historical line of the Corman-Drosten paper, the critique by the Borger-Kämmerer team and
the subsequent discussion are referred to by numbers [1] to [5]. All other citations are given by first author
name and year of publication.
The Borger-Kämmerer-Text [2a]
The Borger-Kämmerer text [2a] lists ten allegedly severe flaws in the Corman-Drosten paper
[1]. They published their text on different sites in the internet and also submitted it to Euro-
surveillance who meanwhile have rejected it [5]. I will list the points addressed by Borger-
Kämmerer and allies, thereby also referring to their answer [4]. Different aspects of the
Borger-Kämmerer text will be addressed below, sorted by subject area.
Test Design of the Corman-Drosten qPCR [1]
A couple of points in [2a and b] refer to the test design. The points made by the Borger-
Kämmerer group are given in Italics (verbatim citation from [2]).
There exists no specified reason to use these extremely high concentrations of
primers in this protocol. The described concentrations lead to increased nonspecific
bindings and PCR product amplifications, making the test unsuitable as a specific
diagnostic tool to identify the SARS-CoV-2 virus.
PCR-Primers are used at a standard concentration between 0.5 and 1 µM (final conc.), for
multiplex-PCR one will usually take less, say, 0.2 to 1 µM and 0.1 to 0.4 µM for probes. How-
ever, this is no fixed rule and surely no law of nature – it is a rule of thumb. There are cases
in the literature of substantially higher concentrations used in validated TaqMan qPCR sys-
tems (Pan et al. 2020, to mention just a single example). Everyone who has ever constructed
and established a PCR assay knows: Appropriate primer concentrations, annealing temper-
ature, additives like DMSO, FA, glycerine have to be tested. It is a misunderstanding to
interpret the published rules and the empirical formulas available in the internet as being
strict in a mathematical sense.
Six unspecified wobbly positions will introduce an enormous variability in the real
world laboratory implementations of this test […] making the test unsuitable as a
specific diagnostic tool to identify the SARS-CoV-2 virus.
These unspecified positions should have been designed unequivocally.
It is hard to answer to such an argument in a sober and polite manner because it is too much
off-topic and shows, that the Border-Kämmerer team is lacking any deeper understanding in
contemporary PCR technology. First, the appropriate term is degenerate positions rather
than „wobbly positions“ (wobbling occurs in the ribosome during translation). Second, there is
some severe misunderstanding concerning the nature of such positions: They are more or
less dictated by the facts (namely by sequence conservation) rather than „designed“. Creat-
ing a PCR assay, the first step always is sequence analysis and in the case of a virus detec-
tion PCR it is multiple sequence alignment and identification of conserved regions. Primers
then are designed matching such conserved sequence segments. In many cases, however,
nature is not „friendly“ enough to provide us with a completely defined consensus sequence
of sufficient length and then you have to accept degenerate positions which no more can
be „designed unequivocally”. This is not a mistake, this is an approved tool in PCR. I
have employed such degenerate primers in my PhD thesis in the 1990ies (!), right now I use
degenerate primers in a sewage water project to amplify microbial 16S rDNA segments. In
other words, the principle of degenerate primers is 3 decades old (Kwok et al. 1994,
Linhard & Shamir 2005, 2007, Najafabadi 2018 to mention only a few), but all the members
of the Borger-Kämmerer alliance seemingly do not know it. Third the degeneracy of the
Corman-Drosten primers [1] lies well under 100 variations and hence is low. Much higher
degree of primer degeneration by orders of magnitude can be employed in PCR. The
predication that degenerate primers do not allow a specific PCR process is neither supported
by scientific record nor by experience and hence just a claim.
A difference of 10° C with respect to the annealing temperature Tm for primer pair1
(RdRp_SARSr_F and RdRp_SARSr_R) also makes the test unsuitable as a specific
diagnostic tool to identify the SARS-CoV-2 virus.
This argument, too, refers to primer design and the answer is more or less the same: Primers
of equal length, well-balanced GC/AT ratio, equal Tm are desirable. Again sequence context
and conservation dictate what is feasible. Again only practical testing will show which design
will work and which one will not. The Corman-Drosten qPCR system has been thoroughly
and rigorously tested (see [1]) and this is what counts. In contrast to this it is embarrassing
that the Borger-Kämmerer team brings up such claims without having performed a single
experiment by their own. By the way, the correct term to use here would have been be
melting temperature (which is a feature of an oligonucleotide) and not „annealing tempera-
ture” (which is a parameter to be chosen)... This again demonstrates the lack of expertise in
the Borger-Kämmerer group.
The PCR products have not been validated at the molecular level. This fact makes
the protocol useless as a specific diagnostic tool to identify the SARS-CoV-2 virus.
Validation of PCR products should be performed by either running the PCR product
in a 1% agarose-EtBr gel together with a size indicator (DNA ruler or DNA ladder) so
that the size of the product can be estimated. (...) The fact that these PCR products
have not been validated at molecular level is another striking error of the protocol,
Of course – and in contrary to the claims of the Borger-Kämmerer group [2a] – PCR products
have been analysed by gel electrophoresis (AGE)! This is always the standard procedure
and even not worth mentioningyou also won't mention that you run you gels by electro-
phoresis in an electrophoresis chamber, this is self-evident.
Only PCR fragments with sufficiently clear and well-defined appearance in AGE will further
be considered a the basis of a a TaqMan qPCR system to be designed. If everything looks
fine and if the three-oligonucleotide qPCR system works well, sequencing of the product
indeed may be conducted but is unnecessary.
The PCR test contains neither a unique positive control to evaluate its specificity for
SARS-CoV-2 nor a negative control to exclude the presence of other coronaviruses,
making the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2
virus.
Here I simply recommend reading the methods section of the Corman-Drosten paper [1]. The
authors have tested a great variety of samples and specimens. SARS-CoV strain Frankfurt 1
explicitly was suggested as positive control. As negative controls quite a few specimens may
serve (e.g. other respiratory viruses and / or other coronaviruses mentioned in [1]), all of
them appear in the Corman-Drosten paper [1]. After all it is self-evident and needs no men-
tioning that genuine SARS-CoV-2 genomic RNA is to be used as positive control as soon as
it becomes available
3
. So, criticising the lack of positive controls in November 2020, when the
Borger-Kämmerer text was launched, was last year's snow because at that time plenty of
authentic material was available for this purpose. So why should this item even be men-
tioned?
Concerning „other corona viruses“ the only sarbecovirus circulating in mankind to date is
SARS-CoV-2. Other betacoronaviruses, such as HKU1, OC43, and MERS-CoV have been
included in the validation program as well as two alphacoronaviruses causing common cold,
all of them not members of the sarbeco taxon SARS-CoV-1 and -2 belong to. So this qPCR
system can well discriminate between SARS-CoV-2 and other viruses.
The Borger-Kämmerer „Addendum”
The Borger-Kämmerer group has provided an „Addendum” to their text [2b] in which they list
references to strengthen their claims. In their answer [4] they rebuke me for having ignored
this „Addendum”. Well, (a) in their „Report” there is no direct and explicit cross reference
from the listed arguments to the „Addendum”, so the argumentation of the „Report” stands for
its own (as it should anyway). (b) So one might well ask why the Borger-Kämmerer alliance
has neither included the information given in the „Addendum” in the main text and not even
have cross referenced to it? (c) Very generally applies: If someone claims to have con-
structed a time machine or a perpetual motion machine, no „Addendum” is needed to debunk
such claims. And the copious flaws in the Borger-Kämmerer „Report” [see 3 and this text]
speak for themselves. So I took notice of the „Addendum” but saw no reason to address it.
Well, ok, what's about this „Addendum”? To get to the point: The Borger-Kämmerer group
cites peer-reviewed literature in order to substantiate their claims [2b]. However, in doing so,
they either cite irrelevant or mistaken facts or they address points which already had been
obsolete. Let's keep in mind: The Corman-Drosten paper [1] represents „version 1.0” of the
test relying on limited sequence information. This test version had been upgraded already
five months before publication of the Borger-Kämmerer text (Matheeussen et al. 2020,
Muenchhoff et al. 2020). The Borger-Kämmerer text at best is criticising last year's snow.
Even Christian Drosten himself was participating in test optimisation and primer re-design
(Muenchhoff et al 2020, Matheeussen et al. 2020) - why do Borger-Kämmerer ignore this
fact? - This is a really interesting question and it raises concern on their seriousness.
This is how analytics work, this is how science works: Systems are planned, designed and
subsequently they are continuously refined and optimised. Metaphorically speaking it does
not make any sense to blame physicians or diagnosticians from year 2000 for their „primitive
methods” – here with the only difference that in the case of SARS-CoV-2 / CoViD-19 scien-
tific development was faster than ever before in history of mankind. The Borger-Kämmerer
alliance, however, even cite Muenchhoff et al. (2020) as document in support for wrongdoing
and misconduct of the Corman-Drosten group. This is breathtaking and leaves me speech-
less.
In the pages below I will analyse a couple of fallacies and wrong conclusions to demonstrate
that the „Addendum” is not better in its quality than the „Report”.
3
... since April 2020 latest, see
https://ec.europa.eu/jrc/en/news/new-control-material-developed-jrc-scientists-help-prevent-coronavirus-test-failures
Addendum Fig. 4
In the Muenchhoff et al. publication Christian Drosten does not properly disclose his COIs
and affiliations (Figure 4). As in the Corman-Drosten paper, his affiliation as Director of
Virology at Labor Berlin is not listed, a laboratory which operates commercially within the
PCR-testing realm. [5]
Figure 4: Christian Drosten fails to list his affiliations properly: He is Director of Virology
at Labor Berlin, a commercially oriented company which offers PCR-testing.
(verbatim citation from [2b])
Well, Drosten indeed is one of the directors of Labor Berlin
4
and he may also be a member of
a country club or a church parish or may be not. This study was a multicentre scientific study
in which the German Center for Infection Research, Partner Site Munich and Associated
Partner Site Charité, Berlin and Associated Partner Site Frankfurt, Germany played the cen-
tral role as can easily be seen by the fact that 15 out of 22 authors (including Drosten) have
their affiliations right there. And indeed Drosten also is a director at Charité. Both participated
in this study. Neither Labor Berlin did participate nor Drosten's parish or country club, so they
should not be mentioned. To blame Drosten here for having given a wrong affiliation is in
very neutral wording – inept.
It is just the other way round, many of the Borger-Kämmerer group fail to give their correct af-
filiations and keep silent in conflicting interests. Senior author Kämmerer calls herself expert
in virology though she isn't. She is collaborating with "Stiftung Corona-Ausschuss" and Dr.
Wordag, in other words, she is closely linked to corona conspiracy organisations
5
. This is
conflicting interest! Borger does not mention that he is a member of the young-earth creation-
ist society „Wort und Wissen” („Word and Knowledge”). It is his full-time job to produce
pseudoscientific creationistic PR material. Instead he calls himself „Research Associate”
4
Charité - Universitätsmedizin Berlin and Vivantes Netzwerk für Gesundheit GmbH are the mother companies
of Labor Berlin. Of note, both Charité and Vivantes are companies of the State of Berlin: thus Labor Berlin
is also part of the public sector.
5
see https://www.youtube.com/watch?v=Ymer59vTrSA
which is at least fraudulent misrepresentation: At „Wort und Wissen” there is no lab, there is
no research group. All they do is screening the literature to collect arguments (by quote
mining and cherry pickingsee below) which they can employ against evolution in their PR
material. This, too, is conflicting interest. Henrik Ullrich, by the way, is their chairman, which
he also fails to disclose.
Addendum Fig. 5
The Borger-Kämmerer group shows this picture to argue for sloppy primer design in the Cor-
man-Drosten test [1]. The respective primer, so the message, forms self-dimers and hence is
inoperative. The technical background behind is this:
If primers are capable of hybridising with each other they may form primer dimers which will
be amplified, in this way (a) quickly reducing the pool of available, intact primer molecules
and (b) producing artificial primer dimer products. In the internet quite a few analysis tools
are available to analyse self-complementarity and the scheme on the right shows such a
result. Ok ... so is this primer unsuitable?
First, the left picture is completely unrealistic and fanciful. Melting temperature of the five
paired bases is below 20°C – not to mention the CpC dinucleodide... So only an evanescent
portion of the molecules is paired in this way, the equilibrium is far away from this state. A
greater portion – albeit still minute amounts at the annealing temperature defined in the PCR
protocol may hybridise as shown on the right side. Does this render the primer useless?
No, for a simple reason: Both 3' ends are A-C mismatches and such are elongated by
TaqPol with extremely low efficacy. In short: This primer surely will produce no primer dimer,
at least not more frequent than any other well designed primer, too.
This effect is the basis of one of the oldest types of diagnostic PCR tests, namely ARMS-
PCR (Newton et al. 1989). As in standard PCR two primers are used, one of which ends
exactly at the SNP position. As a consequence, in the no-match case one primer binds per-
fectly and the other one with all its positions except for the 3' nucleotide. This is sufficient to
prevent formation of an amplicon! Almost all mismatches dramatically reduce amplification
efficiency (Huang et al. 1992, Rejali et al. 2018), only G-T mismatches are extended effi-
ciently (by the way tested by myself: Beyer & Varsanyi 1997). Hence this primer with the
terminal A-C mismatch will produce primer dimers on extremely low level – if at all.
Here, a general problem of the Borger-Kämmerer alliance becomes obvious: It is not enough
and it is not science to put some sequence data into some analysis software and enjoy
the output. One has to understand and interpret the output and this requires well-funded
theoretical knowledge and practical skills obviously not available in the Borger-Kämmerer
alliance.
Addendum Fig. 5
While most labs run these tests in different wells (1-plex), it is certainly risky
practice to have primer dimers between 1-plexes, especially when factoring in that
liquid handling of millions of tests can create numerous contaminations. Such
primer contaminations are not just a theoretical risk but are in fact reported in the
peer-reviewed literature referred to below.
(verbatim citation from [2b])
Well, you shouldn't cook your tea with vinegar. You shouldn't put together pure glycerine and
nitrating acid. You shouldn't confuse a beaker with herbicide with your beer mug. You
shouldn't pour water into your laptop. You shouldn't assign samples to the wrong patients.
And shouldn't mix up or contaminate primers with each other. It's a simple principle: garbage-
in, garbage-out! in such a case, the best design won't help. For such problems, all analyt-
ical laboratories have implemented quality management systems.
No, it is very difficult to comment on this nonsense in sober and placid wording. Interestingly
and by the way: The Borger-Kämmerer group here reference to "peer-reviewed literature"
without citing it. Honi soit qui mal y pense...
Addendum Fig.7: From Jung et al (2000)
Here the Borger-Kämmerer group concludes [verbatim citation from 2b]:
The RdRp PCR from the Corman et al. publication produces less false positive
amplification than the US and China CDC N1 and N PCR, however it still produces
a very problematic amplification of “water only” which is a clear no-go for a PCR
reaction intended for diagnostic use.
The misunderstanding lies here in the fact that the Borger-Kämmerer group mixes up the
production of primer dimers at the end of a PCR process with the generation of a (TaqMan
qPCR-) fluorescence signal. Furthermore one has to distinguish production of signal due to
contamination (which unfortunately happens sometimes: That's the reason why negative
controls are all-important!) with signal produced by the system itself in late cycles. Moreover
the Borger-Kämmerer group here admits – hear, hear ! – that the Corman-Drosten system is
more specific than two other systems tested. Well ... no further comment.
Addendum Fig.11: From Konrad et al. (2000) (Figure 2):
commented by Borger-Kämmerer group (verbatim citation from [2b]):
Konrad et al. report similar problems with false positive (FP) signals at high Ct.
They report 61% FPs with their first test system. They improve upon this by
changing their PCR master mix but still achieve a 5.1% FP rate with the
improvement.
In contrary to the suggestions of the Borger-Kämmerer alliance, the picture shows how such
a test works and how it has to be interpreted. In this case and in this experimental setting,
the qPCR is specific until about cycle 30 as shown by the positive controls. The other curves
demonstrate that at higher Ct values the test is no more reliable (as easily can be seen by
the shape of the amplification curves).
The Borger-Kämmerer group writes:
There are several significant homologies but none that have both primer and
probes in close proximity. While these off-target homologies are not cata-
strophic for assay performance, they do demonstrate the lack of in silico
analysis done prior to publication and they may play a role in the in-vitro
synthesis of more diverse 3 prime ends of primers during the cold (55C)
reverse transcription step of RT-qPCR.
Addendum Fig.29: (a homology BLAST search performed by the Borger-Kämmerer group)
This is again a puzzling argument which is hard to follow.
- As Borger-Kämmerer admit, a single primer match in our genome even if perfect!
does not compromise the assay at all. So why discussing it?
- How Borger-Kämmerer get to the idea the primers had not been blasted by the Corman-
Drosten consortium remains obscure.
- Reverse transcription occurs prior to qPCR, priming is usually achieved with short ran-
dom oligomers to avoid a bias in cDNA distribution. Here, a one-step or a two-step proto-
col can be applied. Two step: The PCR primers and probes are to be added later when
an aliquot of the generated cDNA is put into the qPCR sample... which means that the
qPCR oligonucleotides are not present in the reverse transcription step. One step: Here
indeed all primers are present and one could think mispriming of genomic DNA could
happen. However, all steps for cDNA synthesis are performed well below melting temper-
ature of DNA. So gDNA remains double stranded and mispriming does not happen.
Besides this, even mispriming of gDNA at single sites would be irrelevant – see above
(ARMS PCR). This again shows the lack of PCR knowledge in the Borger-Kämmerer al-
liance.
There would be a lot more to say concerning the „Addendum“ but it would literally require a
whole book to deal with all these errors, mistakes, and their way of arguing. The examples
dealt with here are sufficient to show that the „Addendum“ is not better than the „Report“.
Let us keep in mind the phrasing of the Borger-Kämmerer alliance: The Corman-Drosten test
is „flawd”, „useless”, contains „numerous technical and scientific errors”, lacks „accurate test
validation”, is „confusing for users”. I could find such expressions in none of the cited papers.
In contrary: It has been shown several times that the Corman-Drosten qPCR works (e.g.
Afzal 2020; Matheeussen et al. 2020; Nalla et al. 2020; Vogels et al. 2020).
Yes and once again: This test [1] was version 1.0 and not optimal. Genuine positive control
RNA had not been available at that time. Cutoff-Ct-values could not be defined since at that
time no standardised sample processing protocol had been established. But no one uttered
such claims. I only can recommend reading the cited literature to see where the citations
made by the Borger-Kämmerer group are out of context.
To set an important point: The question is not if the Borger-Kämmerer alliance has mis-
interpreted facts and literature on purpose. I do not know what they believe but this question
is completely irrelevant. The only intention of this essay as well as of my first analysis [3] is to
expatiate on the facts.
And one last point: How can it be, that the fulltext of the Corman-Drosten paper has been
read roughly 400.000 times and cited (in scientific journals) more than 1.400 times by the
end of March 2021
6
but no scientist has realised these severe flaws and errors making the
test unsuitable“? How can it be it requires a group of laypeople to unmask the useless Cor-
man-Drosten test? How can it be that this futile qPCR was the starting point for further de-
velopment and its follow-up versions are meanwhile used worldwide? The Borger-Kämmerer
alliance claims that the flawed and unspecific [Corman-Drosten] test“ produces lots of false
positives which leads to significant overestimation of incidence rates. Well, though the
(updated) version of the Corman-Drosten test is employed worldwide, there are quite a few
countries (like USA and China) using different tests. Surprisingly, those countries also have
been experiencing their corona pandemic as well. How come? How can that be?
Communication and Conveyance
The test design in the Corman-Drosten paper is so vague and flawed that one can
go in dozens of different directions; nothing is standardized and there is no SOP.
This highly questions the scientific validity of the test and makes it unsuitable as a
specific diagnostic tool to identify the SARS-CoV-2 virus. (verbatim citation from [2])
Behind this statement, there is some deep misunderstanding concerning setup, validation,
and implementation of a test system. In the first step, a test system is designed and sub-
sequently simply tested for functioning. Then, validation takes place by determining robust-
ness, specificity and sensitivity with respect to relevant parameters (here: other viruses that
may well be present in the respiration tract).
A Standard Operation Procedure (SOP), however, always applies to the given laboratory,
three-dimensionality and technical devices. Quite a few parameters, e.g. threshold, are de-
pendent on the qPCR machine and cannot be defined a priori. For this reason, a validated
test system always has to be established in the course of implementation in a given lab /
working group (and this may be time-consuming!). Some of my graduating students have
spent their complete bachelor project / thesis with such projects in laboratory medicine labs.
Only after this last step an SOP can be written. Hence it does not make any sense to rebuke
Corman-Drosten [1] for a missing SOP.
The Borger-Kämmerer alliance fortifies their accusations against my argumentation (brand-
ing it ad hominem attack”, pseudo-argument”, twice utter nonsense verbatim citation
6
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2020.25.3.2000045#metrics_content
from [4]). Their justification: A diagnostic test has to be optimised, established and certified
before it is sold. I only can recommend to the Borger-Kämmerer alliance reading the Cor-
man-Drosten paper [1] and take note of the fact that the Corman-Drosten team has provided
a SARS-CoV-2 qPCR test version 1.0. They don't sell kits. Finally establishing a test lays
always in the realm of the user. It is completely naive to think that the boss of an analysis lab
will put the Corman-Drosten paper [1] on the desk of a technical assistant who then orders
the components (of course from Corman & Drosten!) to afterwards run the test. Procedures
and everyday business in an analysis lab are different. As mentioned, tests have to be estab-
lished and this happens always under supervision of a skilled scientist. And afterwards,
primers, chemistry, and premixes usually are purchased from the usual supplier-of-trust.
Being the Borger-Kämmerer alliance I would be cautious with my word choice.
Six unspecified wobbly positions will introduce an enormous variability in the real
world laboratory implementations of this test; the confusing nonspecific description in
the Corman-Drosten paper is not suitable as a Standard Operational Protocol mak-
ing the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
This high number of variants not only is unusual, but it also is highly confusing for
laboratories.
Here, it is again hard to keep a polite tone, since this is again completely mistaken. As
already pointed out, primers with degenerate positions are a standard tool in PCR (see
above). And every expert in the field knows the IUPAC one-letter-code for nucleic bases as
we all know the ABC. There's nothing to confuse users.
Diagnosis
A severe error is the omission of a Ct value at which a sample is considered positive
and negative. This Ct value is also not found in follow-up submissions making the
test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
I am not completely sure what the Borger-Kämmerer group is criticising here. Is it that thresh-
old 't' has not been defined? This parameter is suggested by the software and confirmed or
changed by user. Or is it threshold-cycle 'Ct'? Ct values are not defined, they are determined
as a result of the qPCR process. Or is it a cutoff-Ct-value? This depends on the dilution and
the inoculum. And still another question is the interpretation of measured values.
A fixed value for a positive-negative decision cannot be defined under the given conditions: It
depends strongly on the aliquot of the sample given into the test as well as the preparation
method and sample dilution. In a qPCR assay, always a dilution series of a (positive) sample
of defined concentration is co-processed serving as calibration series. Only comparison of
determined values to this „ruler“ allows reliable determination of copy numbers. Since at the
time of the Corman-Drosten paper [1] no standard protocol for sampling / swab tests had
been established, such a cutoff-Ct value could not be defined by the authors, it has to be
established by the user.
This qPCR test is a detection assay for SARS-CoV-2 and not a diagnostic test. No one
claimed (and the Corman-Drosten paper neither did) to have a fully developed test system
for diagnosis at hand – without genuine positive control, without a standardised sample
preparation protocol and without all the sequence information to come up the following
months.
To criticise this point is a so-called straw man: Disprove something that never has been as-
serted. Please just read the Corma-Drosten paper [1] ... The Corman-Drosten test was
nothing more and nothing less than an important first step on a long way.
In the opinion of the Borger-Kämmerer group, 35 cycles, as proposed by Corman-Drosten
paper [1] are too much:
The number of amplification cycles (less than 35; preferably 25-30 cycles) (...) In
case of virus detection, >35 cycles only detects signals which do not correlate with
infectious virus (...) Above a Ct of 35 cycles, rapidly increasing numbers of false
positives must be expected.
This is another severe misunderstanding of the Borger-Kämmerer group concerning qPCR –
nowadays such tests exclusively are online tests: Data is obtained in real time and inter-
preted in comparison to the Ct-values produced by the calibration series (see above). It does
not matter if you run your qPCR another 100 cycles or not. When I had to determine the copy
number of expression cassettes in production cell lines I ran my qPCR over 40 cycles. So I
could easily see from which point on unspecific signal is generated.
The test cannot discriminate between the whole virus and viral fragments. Therefore,
the test cannot be used as a diagnostic for intact (infectious) viruses, making the test
unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus and make
inferences about the presence of an infection.
This is one more deep misconception with regard to the scope of the test, especially the
difference between (molecular) analysis and (medical) diagnosis. This criticism comprises
several errors:
1. A molecular test in this case a qPCR test for SARS-CoV-2 does exactly one thing: It
detects the presence of a given species – fragment! of nucleic acids, in the case of
pPCR additionally including quantification. It is no diagnosis for a distinct disease.
Corman-Dorsten [1] published a test for SARS-CoV-2 and never have claimed to have a
diagnostic test for CoViD-19. So, this is a straw man argument again.
2. Not a single virus test in this word except complete sequencing of the respective com-
plete viral genome – can discriminate between intact viral genomes and fragments. So
why do Borger-Kämmerer [2a] call for this feature here? When detection of defined target
sites in a genome always is regarded as sufficient, why should this be insufficient in
exactly the case of SARS-CoV-2?
3. Besides this, the discrimination between functional and non-functional / fragmented viral
genome copies is completely unnecessary. Fragmented viral copies are neither produced
by our cells nor grow on mucous membranes, nor are beamed into patient's throat like in
Star Trek. Every viral genome copy – irrespective if intact or defective in any way – is pro-
duced by a host cell that has been infected by a functional virion. Hence it is indicating an
infection. Period.
4. If successful infection by a virus causes acute disease is a different question that is never
addressed by detection of pathogen itself. Nevertheless, still a significant portion of per-
sons with silent infection (i.e. clinically unapparent course) still can transmit the infection to
other people. For this reason, in the context of pandemic management it makes really
sense to identify infected people irrespective of disease state.
All this is basic knowledge in infectiology, epidemiology, and diagnostics which raises serious
questions concerning the expertise of the Borger-Kämmerer group.
Alleged Malpractice of Corman, Drosten and co-authors
Most likely, the Corman-Drosten paper was not peer-reviewed making the test
unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
Indeed a review process usually takes weeks or even months. To be honest, this is not due
to necessity but rather a result of … well … priority choice of quite a few colleagues. One can
go through a paper thoroughly within a few hours. It may take a couple of days if reviewers
pose further inquiry. If everything is prepared in the forefront of reviewing even this can be
managed within one day. Here in this case, the complete test design was made available to
the reviewers on a WHO-site more than one week before filing the final manuscript
7
. It is im-
proper that the Borger-Kämmerer group even does not consider alternative explanations but
keep quiet on them.
The Figure below (Fig. Addendum 27 by W.Aukema) shows an analysis of time spans
needed for reviewing by Eurosurveillance. The analysis has been conducted by Wouter
Aukema
8
, who is a corona sceptic and hence will certainly not manipulate and brighten data
for Eurosurveillance's advantage.
Addendum Fig. 27 Time span for review processes at Eurosurveillance (by Wouter Aukema
2020)
This analysis clearly shows two things:
1.: The rapidity of the Corman-Drosten paper [1] review process is extraordinary.
2.: This rapidity does not lie out-of-range, because some other publications also needed only
a few days. Obviously, it is possible – more than ever, if like in this case data had been
available to the reviewers beforehand.
7
the complete protocol had been available to reviewers on Jan. 14th 2020!
8
https://www.xing.com/profile/Wouter_Aukema
[…] the fact that two of the authors of the Corman-Drosten paper (Christian Drosten
and Chantal Reusken) are members of the editorial board of Eurosurveillance.
So what? For this case, well-defined rules exist. It is use in virtually every journal that mem-
bers of the editorial board may publish in their journal. In such cases the respective persons
strictly are excluded from review process. There is nothing more to say about this.
We find severe conflicts of interest for at least four authors […] A conflict of interest
was added on July 29 2020 (Olfert Landt is CEO of TIB-Molbiol; Marco Kaiser is
senior researcher at GenExpress and serves as scientific advisor for TIB-Molbiol),
that was not declared in the original version (and still is missing in the PubMed
version); TIB-Molbiol is the company which was „the first” to produce PCR kits (Light
Mix) based on the protocol published in the Corman-Drosten manuscript, and
according to their own words, they distributed these PCR-test kits before the
publication was even submitted [20]; further, Victor Corman & Christian Drosten
failed to mention their second affiliation: the commercial test laboratory „Labor
Berlin”. Both are responsible for the virus diagnostics there [21] and the company
operates in the realm of real time PCR-testing.
Indeed, co-authors may have mentioned these affiliations. But there is no necessity. The
Corman-Drosten team does not sell corona test kits. Who ever decides to establish this
qPCR will for sure not change his or her suppliers of trust. To assume economic / commer-
cial benefit for the Corman-Drosten group is more than far-fetched. For such an accusation
you need facts and hard arguments which, however, have never been provided by the
Borger-Kämmerer alliance. Mere demands and hazy assumptions are not sufficient.
In my mind the accusations of malpractice towards the Corman-Drosten team are more than
just dubious and questionable. Here, the burden of proof lies on the Borger-Kämmerer
alliance and they should be very cautious to utter slanderous claims without hard facts. In my
mind such behaviour is neither compatible with scientific, nor with democratic principles.
The Borger-Kämmerer alliance or „what’s the meaning of ad hominem?”
In my analysis [3] I have pointed out that the Borger-Kämmerer alliance consists of laypeople
both with respect to corona as well as to qPCR. There is even only a single virologist in this
group (Prof. em. Ohashi, who worked solely on Epstein-Barr virus). In their answer [4] as well
as on different sits in the internet the Borger-Kämmerer group accuses me of using ad-
hominem arguments.
„Ad hominem argument” means – in defending one’s own point of view – to attack the person
of the opponent rather than his arguments
9
(Copi 1986, Walton 2008, Bowell & Kemp 2010):
„Einstein’s physics is rubbish, he was a Jew”, „Gödel’s incompleteness theorem is nonsense,
he was a paranoiac”. I cannot see where I have used such kind of argument, and the Borger-
Kämmerer alliance does not specify this accusation. Most probably they refer to my charac-
terisation of their members as laypeople without scientific expertise in the relevant fields to
justify this accusation. So what are the facts?
9
See https://www.txstate.edu/philosophy/resources/fallacy-definitions/Ad-Hominem.html and
https://en.wikipedia.org/wiki/Ad_hominem
(1.) The Borger-Kämmerer alliance calls itself INTERNATIONAL CONSORTIUM OF SCIEN-
TISTS IN LIFE SCIENCES (ICSLS) and „researchers”. Please note: Scientists in life sci-
ences and researchers – you will find this self-designation in the Borger-Kämmerer text [2a]
at the very top and in the abstract, respectively. And at the end of [2a] they claim for five
members that they have conducted research. Hence it is well justified to ask if those people
are scientists and if anyone has conducted any research. This it not an argumentum ad
hominem but nothing than simply measuring the Borger-Kämmerer alliance by their own
standards and self-depiction.
In the Borger-Kämmerer alliance you will find 3D-artist (!), nursing and social sciences (!),
manager (!), pharmacologist, toxicologist, biochemist, pharmacologist, environmental
chemist, microbiologist, nutritionist, physicians (pathologist, andrologist, urologist, internist,
cardiologist, radiologist, specialist in laboratory medicine, oncologist, immunologist, general
practitioner (!), neurologist), many of them out of their field since many years [see 3]. Skills
matter, expertise matters. And, yes, it matters that 1
st
author Borger is a professional young-
earth creationist who is paid for producing creationist fake science. It matters that he believes
that he can overthrow evolution theory with his book (Borger 2018). It matters that Kämmerer
calls herself specialist in virology” though she is an expert in oncology and nutrition instead.
She had published two papers on virology in 1995 and 1998. Well, I published a bioinfor-
matic paper in 1997 as sole author (Beyer 1997) – when nowadays bioinformaticians talk in
most cases I even can not spot which topic they are discussing...
So it is surely not a „pamphlet full with ad hominem attacks” [verbatim citation from 4] to call
the Borger-Kämmerer group laypeople with respect to qPCR analysis. Only a handful of
them are scientists and no one in the field of diagnostic PCR. Solely Prof. Ohashi has been
virologist – but with expertise neither in corona diagnostics nor in qPCR.
Indeed it is exactly the other way around: The self-depiction of this group as scientists in life
sciences” is at least false pretences, wrong facts. And when they show up with such fraudu-
lent representations it is inconsistent when they complain of argumentum ad hominem after
they were debunked.
Further fallacies of Borger et al
Besides straw man argument and argumentum ad hominem (see above) more fallacies can
be found in the Borger-Kämmerer text [2a], namely the argumentum ad verecundiam / argu-
ment from authority
10
(Walton 2008) which in some sense is complementary to the argu-
mentum ad hominem: Instead of strengthening an argument with facts the (true or alleged)
merits of its proponents are stressed: „Even the Pope said ...“, „The famous Scientist Prof Dr.
Dr. Dr. Miller-Smith believes ...“. The Borger-Kämmerer group tries to place exactly this argu-
ment when they – unjustifiably – highlight the expertise of their group members. In the nega-
tive sense they tried to use this argument against myself in their answer [4] by pointing out
that my last peer-reviewed publication was in 2004. Hence in their mind [citation from 4] my
ad hominem attacks are not justified by [my] CV“. The severe mistake behind this statement
is this: The truth of an argument is independent from the person presenting it.
10
see https://writingcenter.unc.edu/tips-and-tools/fallacies/
- The arguments of the Borger-Kämmerer alliance are not flawed because they are not
experts in the field. They are flawed because they are wrong, as my analysis [3, this text]
shows, in line with the qualified opinion of the scientific community. Causality goes ex-
actly the other way around – because the Borger-Kämmerer group are incompetent in the
field of qPCR they have produced such a faulty text.
- And my analysis is correct primarily not because I am skilled in PCR and qPCR (as I am
indeed) but simply because the facts are on my side. By the way – since 2004 I have still
been active in R&D but because this mostly happened in an industrial, competitive field it
has never been published. This is a fact Borger knows but ignores. So it is sordid to
blame me for having no publication since almost two decades, especially because Borger
knows I am still active in science. Hence, this is an argumentum ad hominem the Borger-
Kämmerer alliance uses here.
Another fallacy in the argumentation of the Borger-Kämmerer group is the non sequitur fal-
lacy. This means that their conclusions are not supported by the facts they cite which I have
demonstrated for some points in the Borger-Kämmerer „Report” [2a] as well as for the „Ad-
dendum” [2b] (see above). To get to the point: Indeed, the Corman-Drosten qPCR system
„version 1.0” [1] was „immature” which no one denies. However, already „version 2.0” was
fully functional long before the Borger-Kämmerer text was launched (!) – see above. Various
tests have shown the weak points in „version 1,0”, but no one drew the conclusion that it is
completely unsuitable as claimed by the Borger-Kämmerer group. Non sequitur fallacy (to-
gether with cherry picking: see below).
Another critical point is the way the Borger-Kämmerer group utilises scientific literature. They
pick out whatever seemingly supports their argumentation and ignore the rest. And in doing
so citations are sometimes presented out of their context. This is a technique (or rather fal-
lacy) called cherry picking (take what fits, forget the rest) and quote mining (take what seems
to fit, irrespective of context).
Last discrepancy: Though the Borger-Kämmerer group claims there was no peer review [2]
they present
11
an interview with one of the reviewers. Funny.
refutationofandreasbeyer-version{?}
I published my analysis [3] in January 2021; the Borger-Kämmerer alliance responded in
February [4]. Instantly Pieter Borger repeatedly and pushingly urged me (in personal
communication / eMails) to answer. When I finally wanted to get to this work I saw that the
answer had first been exchanged [4b] and then removed. Several requests to the Borger-
Kämmerer alliance to provide me with this „Refutation” were ignored. I am sorry but this is an
embarrassing behaviour I can neither understand nor interpret. It is outside of respectability
and good scientific practise anyway. I ask myself if this was an action to provoke my answer
and then to disclose their „Refutation” only after this text has been published in order to have
the last word... we will see...
Because I could only retrieve a copy of the Borger-Kämmerer group „Refutation” version 1
from an internet archive [4] my answer is most likely incomplete. Whatsoever. Some of the
11
https://cormandrostenreview.com/eurosurveillance-response/
points have already bee addressed above, some more are dealt with now. This is sufficient
to show lacking quality also for this „Refutation”.
Yes, and once again: The original version of the Corman-Drosten qPCR was suboptimal – it
was version 1.0 and that is why it was immediately refined... a fact which the Borger-Käm-
merer group keeps silent about. They criticise a test version which at the time of publication
of their pamphlet (to use their own diction once) already was obsolete. Is that proper, fair and
decent? Is that good scientific practise? Surely not...
Lockdowns are a direct consequence of PCR-tests” (verbatim citation from [4]).
Nope. Lockdowns are ordered by government, neither by scientists, nor by qPCR machines.
And they are ordered mainly as a consequence of the epidemiologic situation. And here,
results of PCR testing are one of quite a few factors. The most important one is the level of
diseased and severely diseased people as well as the R-factor which – by the way is only
little dependent on false positives, since the ratio of putative false positives is constant for a
given test setting. Hence it hardly influences calculation of an R-value. And meanwhile quite
a few different qPCR tests and rapid (strip) tests are available. If the qPCR test was flawed,
meanwhile a severe discrepancy between different test systems should have been detected.
Why did that not happen? And why do countries using their own qPCR tests systems (and
not the Corman-Drosten assay [1]) experience the same (or even more severe) pandemic?
How come?
Up to date Corman et al has not modified or improved his protocol-design
(verbatim
citation from [4]).
@ Borger-Kämmerer alliance: please simply take notice of publications like Muenchhoff et al.
2020 and Matheeussen et al 2020.
„There was no pandemic situation at the given timeframe but an outbreak of
pneumonia in China with 6 deaths in Hubei province, as stated and referenced in our
main review report.”
(...)
„There was no actual need for any hurry in Europe”
(verbatim citation from [4])
The opposite is true. Already at the end of 2019 it had been clear that SARS-CoV-2 is a
close relative of SARS-CoV-1, both belonging to the sarbeco taxon. Already at the end of
2020 quite a few death cases were to be attributed to SARS-CoV-2(Chen et al. 2020). Hence
the apprehension that it might pose a global threat was well justified. And it did. So what are
we talking about here?!? By the way quite a few authors cited by the Borger-Kämmerer
group stress the danger of SARS-CoV-2 and the necessity to have a test system at hand
very early (e.g. Konrad et al. do it repeatedly). Interestingly, the Borger-Kämmerer alliance
keeps silent about this. This is a fallacy (better: technique) called cherry picking and quote
mining. Take what seemingly fits and simply sweep the rest under the carpet.
Likewise, concerning „positive controls” or „internal controls” everything that has to be said
already has been said [1, 3, this text]. Obviously the Borger-Kämmerer group is not willing to
take notice of facts.
Concluding remarks
The Borger-Kämmerer text is pseudoscience, it is full of misconceptions, errors and flaws.
Therefore it is ignored by experts for good reason. The impact it had in public consciousness,
however, is fatal. Borger reported on Twitter more than 30 Million views of his „Report“
(March 2021). Hence I ask all colleagues please to spread this essay for at least a little
bit of counterbalance.
Moreover it is a problem that analyses like this one cannot be published scientifically after
all, also no one would accept a paper entitled „Atoms Truly Exist”, „Yes, Quantum Physics is
Real” or „Indeed, there is Evolution in Nature”. Though there are sceptic journals in many
countries, these are not peer-reviewed and do not fulfil strict and high scientific standards.
So I urgently appeal to the scientific community: Let's found a peer-reviewed Journal
of Scientific Evidence and a Sceptic Analysis Journal providing a platform where bad
science, pseudoscience and conspiracy theories can rigorously and in-depth be ana-
lysed, unmasked and debunked. It is time to offensively argue against such move-
ments that well have the potential to seriously harm our knowledge- and science-
based society.
Thanks to Victor M Corman, Klaas van Dijk and Frank Visser for helpful comments.
References
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