Cann’s Principles of Molecular Virology, 7th Edition – revised by Ed Rybicki

3 November, 2022

In August 2019, Kattie Washington of Elsevier’s Cambridge MA office wrote to me to inform me that Alan J Cann had declined to develop the 7th Edition of his long-running franchise, and had suggested that I revise it instead. This was most unexpected and a signal honour, as I was of the opinion since the 1st Edition (in 1993) that this was the first Virology textbook that organised things they way I had in my lectures since the early 1980s – that is, he described viruses and how they work in a comparative way, from first encountering a host cell, through replication and expression, to exiting the cell – and I had avidly subscribed to subsequent editions and recommended it to my Virology classes.

I was getting along quite well by early 2020, and I see Elsevier had even put up a pre-order page promising publication by June 2021: this of course did not happen, for a number of reasons – chief among which were that The Good Wife and I were running the Virology Africa Conference in February 2020 in Cape Town, that the COVID-19 pandemic was declared shortly thereafter, and that I unexpectedly became Head of our Molecular and Cell Biology Department in mid-2020. Accordingly, I ended up during a hard lockdown in South Africa not only trying to remotely manage a biggish Department, but also trying to convert 40+ undergraduate lectures into narrated Powerpoint AND video AND PDF presentations to fulfill my teaching obligations, that I had stupidly not minimised when I became HoD.

Oh, I battled on when I had time, but that was in short supply until I thankfully reached the end of my sentence – pardon, HoD tenure – in December 2021, at which point I dived back in.

It turns out that adapting a textbook, however much you liked it, is no trivial thing. I had to marry Alan’s well-established vision with my own equally well-established thinking about teaching Virology, and update what was by then a 6 year-old book – in the middle of a pandemic that was and still is rewriting our understanding of viruses and immunology to a pretty significant extent. Thanks to COVID, and to my weakness for Ebola and other viruses that kill people in messy ways, I added a new Chapter on Panics & Pandemics:

New pathogenic viruses are being discovered all the time, and changes in human activities result in the re-emergence of known viruses, or the emergence of new or previously unrecognized diseases. Most of the viruses of concern are either arboviruses – transmitted by arthropods, in which they also multiply – or are derived from zoonotic infections, entering the human population from direct or indirect contact with wild animals. The potential of certain groups of viruses such as arbo-, hanta-, influenza A, filo-, paramyxo- and coronaviruses to cause serious and unexpected outbreaks of disease is explored, together with the potential of viruses to be used as bioweapons.

I also got halfway through another new Chapter on Viruses in Biotechnology, sparked by all of the frantic vaccine development for SARS-CoV-2, but reluctantly decided that it was stretching the revision out just a bit too far, so I culled it – until the next Edition.

Right now, I have finished all the proofreading, and Elsevier published the book on February 24th 2023.

I like this as a cover: SARS-CoV-2 against the background of a cell in which the virus is replicating, from Russell Kightley Media.

Links to buy the book:

Elsevier’s home site

Amazon Kindle site

So thanks, Andreas Schiermeyer, for pre-ordering a copy AND providing some names for Chapter 1; thanks Mart Krupovic for critting Chapter 3 and providing some Figures; thanks Aris Katzourakis for Figures and thanks Guru Alan J Cann for passing on the baton!

Twitter, where art thou?

5 April, 2022

A strange thing happened to me at the end of February: I got banned from Twitter FOR LIFE*. (see update at end)

Yes, for LIFE: @edrybicki, my handle for 12+ years and which has 4000-odd followers, is no more.

How, you ask? After all, I’m not a malignant orange narcissist, or someone guilty of war crimes, or someone who peddles lies about vaccines or diseases, or threatens violence to all and sundry.

Except, according to Twitter Central, I AM that last thing.

Some context here: my long-time Twitter and social media friend Ian Mackay put up the next in a long series of cat pictures that he takes in his garden, while walking his cats – all dressed up in their little harnesses. This is it:

mackay cat

To which I replied, in the spirit of things,

“@MackayIM Come near me with that feckin’ lead and I rip your face…”

It was a bit of a surprise later that I discovered I couldn’t tweet anything – and when I reloaded Twitter on my browser to fix it, I get this message:

So I submit an appeal, with the facts of the case, and get this:


After investigating your appeal, we have determined that your account posted content that was threatening and/or promoting violence in violation of the Twitter Terms of Service. Accordingly, your account has been suspended and will not be restored.

I looked up why, and got this:

Specifically, for:

“Violating our rules against posting violent threats. You may not threaten violence against an individual or a group of people.”

I submitted ANOTHER appeal, with the facts as shown, and got this:


We’re reviewing your appeal. 

We’ll respond as soon as possible, and we appreciate your patience while we review your account. 



And…nothing. I have tried to submit appeals again twice, and get exactly the same responses, meaning there are NO humans in the loop AT ALL.

Let me reiterate: this was in response to a picture of a CAT wearing a harness and standing on its hind legs, looking aggressive. This was in NO way a threat of violence against anyone, or demonstrating aggression. It was harmless, in Ian’s (@mackayim) own words in an email supporting my previous appeal:

Re: Case# 0255238514: Appealing an account suspension – @edrybicki    [ ref:_00DA0K0A8._5

Please Twitter support, this was friendly banter and the mimicry of a cat!

This was not violent or in any way intending harm to me as the recipient.

Could you revoke this block? There is no harm done here.

Still nothing.

I have pointed out that ” I am a well-respected Twitter user who uses his account to inform the lay public and students about viruses, and in fact directly for teaching University-level undergraduates and informing people about vaccines”, and that I have never – in more than 12 years – threatened anyone with anything. Moreover, I have even extolled the virtues of using Twitter and other social media for teaching purposes – see here – and firmly believe in this, and am now unable to do it.


I am now in a situation where I have to get the 5-odd essential articles I used to pick up on every day second-hand, via emails from sympathetic tweeps or from my students. I also cannot engage in idle banter with the MANY folk I used to interact with, and I seriously miss it. I am also getting messages via platforms as diverse as LinkedIn, ResearchGate and Facebook asking me what happened to @edrybicki – and I can only say “ask Twitter”.

So please do that, won’t you, if you see this?

Thank you.

* And what do you know: thanks to a vigorous campaign by Ian Mackay and Larry Lynam, and MANY people who read this post and tagged Twitter Support – I got my account back! No apologies, and in fact, they demanded I delete my “humorous” tweet, but @edrybicki is back!! Thanks, all!! B-)

Insertion of SARS-CoV-2 sequences into human cell genomes

13 May, 2021

Updated 31/05/2021 – see end.

RE-updated 10/06/2021 – see end

A group of researchers who claimed in a preprint a while ago that they could show integration of SARS-CoV-2 genomic sequences into the genome of cultured human cells has now doubled down, with a Proc Natl Acad Sci paper (!!) further claiming proof of ability to insert in cultured cells, and of proof of insertion in patient tissue.

The authors were investigating their hypothesis that inserted fragments of viral genomes that were not infectious, were responsible for the phenomenon of prolonged positive PCR tests in patients who had completely recovered from COVID-19, and who did not shed infectious virions. They investigated this by transfecting HEK293 cells with human LINE1 transposable element-encoding plasmids, then infecting them with SARS-CoV-2. The addition of LINE1 was “To increase the likelihood of detecting rare integration events“. They isolated DNA from cells 2 days post-infection, and did PCR amplification of the N gene from gel-purified “large fragment DNA” that they claim was successful. While they claim this as proof of reverse transcription and integration of the SARS2 N gene into genomic DNA, they went further and subjected extracted cell DNA to Nanopore long-read sequencing. This resulted in their finding evidence of integration of 63 instances of the whole or part of the genomic 3′-terminal N gene in a variety of chromosomal locations, flanked by host DNA sequences in 2 cases and on one side in 61, with a 20 bp direct repeat with “a consensus recognition sequence of the LINE1 endonuclease” in the two whole sequence instances. There appeared to be preferential insertion into exon-associated sites. The integrated DNA was mainly from the 3′ end of the SARS2 genome.

Figure by Ed Rybicki, copyright 2021

Repeating this analysis with SARS2-infected HEK293T and Calu3 cells that had not been transfected with LINE1 DNA gave 7 integrations, again characteristic of a LINE1-type mechanism, and again preferentially associated with exons.

Another claim they make is that integrated sequences can be expressed. They tested this by looking at published RNA-seq data for SARS2-infected cells and organoids from a variety of human tissues, and “found” a number (0.004 – 0.14% of all SARS2-specific reads) of “chimaeric reads”, or virus-human gene fusions in RNA. The abundance of these reads, correlated with the level (=concentration?) of viral RNAs, and most mapped to the SARS2 N gene – which makes the most abundant mRNAs. An important observation was the following:

“Single-cell analysis of patient lung bronchoalveolar lavage fluid (BALF) cells from patients with severe COVID … showed that up to 40% of all viral reads were derived from the negative-strand SARS-CoV-2 RNA …. Fractions of negative-strand RNA in tissues from some patients were orders of magnitude higher than those in acutely infected cells or organoids”,

because they go on to say (after admitting that they showed no chimaeric sequences in patient BALF samples), that:

“in some patient-derived tissues, where the total number of SARS-CoV-2 sequence-positive cells may be small, a large fraction of the viral transcripts could have been transcribed from SARS-CoV-2 sequences integrated into the host genome”.

Yes. Well. Ummmm…no. Seriously, no. Aside from the objections that others have raised – such as the fact that the way they analysed other data as well as their own undue notice of what could very well all be artefactual chimaeras – they do not appear to have a very deep understanding of how ssRNA+ viruses replicate, or that there may be circumstances – such as in dead or dying cells, or bits of cells resulting from processes such as apoptosis – where there is NOT a superabundance of ssRNA+ compared to RNA-. For example, in the “acutely infected cells” – presumably in culture – virus is replicating vigorously, and there could be expected to be a lot of progeny immature virions in addition to the double-membrane-enveloped replication complexes, which is where the RNA- is, engaged in making more ssRNA+. In quiescent, dying or dead cells, on the other hand, one would imagine all the assembling virions had budded, that replication would probably have stopped due to depletion of resources – and that only the replication centres, safe and protected from RNAses by their vesicle membranes, would be left. These might also form stable exosome-like structures, which would be a good thing to look for. Moreover, replication complexes are largely dsRNA – that is, essentially equal amounts of + and – strand RNA, which would account for their observations with no integration of viral RNA being required.

However, my objections are mainly directed at the model system they used in the first instance. The use of cultured cells in the first instance, and transfection of them with LINE1 elements for over-expression of RT in the second, is pretty much guaranteed to “force” outcomes that are highly unusual in natural infections. This is akin to saying “See, if I force-feed mice with 100x the recommended dose of X in the presence of known mutagens, it causes cancer!!” It is a TOTALLY artificial situation, done in a transformed human cell line, that has VERY little relevance to the real world. 

Of course, they also did the experiment in two cell lines without LINE1 transfection – and found a lower number of integrations. There is ALWAYS a chance (albeit very small) that a nucleic acid – RNA or DNA – could be integrated into a somatic cell, via illegitimate recombination or LINE1 element-mediated insertion. HOWEVER: integration of a random piece of SARS2 genome would almost certainly do nothing in that cell; moreover, even if the whole genome inserted, the cell would be killed by T-cells the same way an infected cell is – and they did not find very much more than N or partial N genes integrated, which is a tiny fraction of the relatively huge genome. It could be that the virus 3′ end has some unusual properties – it is an origin of replication for the virus genome, after all – that favour mRNAs deriving from it interacting with LINE1 transposition machinery, and being (occasionally) integrated.

While they had a hypothesis that integrated sequences were responsible for positive PCR tests long after “recovery” from infection, their evidence does not support this because they have not shown that all of the sequences targetted by PCR primers are present in the genomes of patients, or even of cells in their experiments. Presence of a product for just one viral gene does not constitute a positive diagnosis. Moreover, there is evidence for SARS2 reactivation months after initial infection, which could be explained far more easily by viral persistence in immune privileged sites, such as has also been demonstrated for Ebola virus disease. This persistence, or even the survival of dsRNA forms of the genome or even of fragments of it in dormant replication centres, would be a far more likely reason for persistence of PCR positivity.

However, and this is the important point I wanted to make, the ONLY way an insertion from SARS2 (or anything else) could cause any sort of a problem is if that insertion results in runaway malignant transformation (a lot more unlikely than the insertion event itself), or if it inserts into germline cells (egg, sperm precursors) AND is passed on to progeny. There, the probabilities start getting very, very small indeed.

So: a fuss about nothing, is what this “result” is. I bet you they could have showed the same for ANY RNA under the same set of conditions – and it would still mean nothing. You are a LOT more likely to have bits of nucleic acid from lettuce or tomatoes insert into gut cells, given you eat them FAR more often, and in quantities FAR greater than you are exposed to from a virus – and has anyone ever reported a problem with those?


So don’t worry about this much-hyped “discovery”.

Added 31/05/2021:

Aaaaaaaand…here’s someone who disliked the paper enough to refute it thoroughly, by experiment, no less! Nathan Smits et al. used nanopore long-read sequencing to show they could find NO proof of SARS2 sequences flanked by human DNA, in a context where they COULD find integrated single genomes of HBV, and multiple LINE insertions.

Human genome integration of SARS-CoV-2 contradicted by long-read sequencing


A recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep (>50x) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find any evidence of the virus existing as DNA. By examining ONT data from separate HEK293T cultivars, we resolved the complete sequences of 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events in vivo are highly unlikely to drive later oncogenesis or explain post-recovery detection of the virus.

Added 09-06-2021

…and then someone else actually went and found SARS2 RNA in degraded lung tissue!

Persistence of SARS-CoV-2 RNA in lung tissue after mild COVID-19

On Dec 1, 2020, we reported a successful case of double-lung transplantation from a SARS-CoV-2 seropositive donor 105 days after the onset of mild COVID-19.1 Although repeated quantitative (q)RT-PCR analyses of donor nasopharyngeal swabs were negative, this technique detected RNA of the SARS-CoV-2 N gene (delta Ct 35) from a biopsy of the right lung taken during organ procurement. Viral culture of this biopsy was negative and donor-to-recipient transmission did not occur. Complementary orthogonal methods were needed to corroborate and interpret the qRT-PCR results.Therefore, we did ultrasensitive single-molecule fluorescence RNA in-situ hybridisation with RNAscope technology on formalin-fixed paraffin-embedded sections of the same lung biopsy (appendix p 1), and compared the results with those of a lung biopsy from a deceased patient with acute COVID-19 (figure A and Bappendix p 2). We stained 14 slides of the donor lung biopsy, each containing one 5 μm section, as follows: five slides with a probe for the N gene; five slides with a probe for the S gene; and four slides with probes for N and S. A probe for the basigin gene, which has been proposed to encode an alternative host recipient for SARS-CoV-2, served as a positive control on the ten slides stained for N or S only.2 We identified characteristic RNAscope puncta in three out of nine slides for the N probe, and in six out of nine slides for the S probe (figure C and D). These puncta appeared to be located in clumps of sloughed-off material, and no cells or cell nuclei could be discerned in this debris-like tissue. [my emphasis]

Antibody-dependent enhancement in coronaviruses

11 April, 2020

This is a condensation / concatenation of a series of 13 tweets put up recently by someone who tweets as “The Immunologist” with the handle @eclecticbiotech. I was impressed enough by it that I thought it deserved to be all in one piece – and he agreed. He also declined any more accreditation, saying only “No credit necessary. This thread is entirely due to the important work carried out by fellow scientists”.

A thread on antibody-dependent enhancement (ADE) in coronaviruses from The Immunologist.

While developing vaccines, treating patients with convalescent plasma, and considering immunity passports, we must first understand the complex role of antibodies in SARS, MERS and COVID19.

Rabbits infected with MERS develop antibody responses but are not protected upon rechallenge and worsened pulmonary pathology observed. Passive transfer of infected rabbit serum to naïve rabbits not protective and enhances lung inflammation.

Analysis of 9 healthcare workers infected with MERS found most severe cases had highest anti-spike antibody titres. Three asymptomatic patients and one patient with mild disease had no detectable antibody response on the basis of ELISA and IFA.

Macaques vaccinated with MVA encoding full-length SARS-COV spike protein have worsened lung pathology upon rechallenge. Transferring purified anti-spike IgG into naïve macaques results in all recipients developing acute diffuse alveolar damage.

SARS-COV ADE is strongly mediated by anti-spike antibodies rather than anti-nucleocapsid antibodies. Diluted sera containing anti-spike IgG can increase in vitro infectivity.

Serum containing anti-spike antibodies enables spike-pseudotyped lentiviral particles to infect human macrophages (which do not express ACE2). Could this similarly allow SARSCoV2 to enter cell types outside the natural tropism?

Antibodies targeting the receptor-binding domain (RBD) of the spike protein can cross-neutralize both human and palm civet SARS coronaviruses. Could cross-neutralizing antibodies from previous common cold coronaviruses provide ADE to SARSCoV2?

Clinical data from SARS shows early seroconversion associated with more severe disease and higher mortality (also correlated with advanced age). 32/347 patients (9.2%) had no detectable antibodies.

A very thorough paper demonstrating immunization with various SARS coronavirus vaccine constructs results in pulmonary immunopathology after challenge with SARS-COV virus. Consistent findings in multiple animal models

In COVID19, anti-spike antibodies higher in elderly/middle-aged patients than young patients. 10/175 (5.7%) of patients have no detectable anti-spike antibodies. Anti-spike antibody titres positively correlate with CRP, an inflammatory biomarker.

Similarly, anti-spike IgG positively correlated with age in COVID19. Interesting how the relationship between age and antibody titres is more linear in females. Additionally, anti-spike IgG positively correlated with inflammatory marker LDH

Questions to consider:

Why do some COVID19 patients not make detectable antibody responses? Do these patients have a more potent CD8+ T-cell (CTL) response? Does cross-reactivity of anti-spike antibodies from previous coronavirus exposure increase risk of severe disease?

Are antibodies produced by SARSCOV2 infection protective from reinfection? If so, how durable is this protection and how long will it last? Do anti-spike antibodies provide ADE and worsen pulmonary immunopathology in COVID19 comparable to SARS and MERS in vivo models?

Sage questions indeed – and ones that anyone developing vaccines to SARS2 should take seriously.

Answers to questions can be directed to TI on Twitter, or put up here for relaying. Enjoy!

Plant-made vaccines and reagents for SARS-CoV-2 in South Africa

4 April, 2020

Plant-Made Vaccines and Therapeutics

I have published a number of reviews on plant-made vaccines (see below), and our Biopharming Research Unit (affectionately known as “The BRU”) has been very active in this research area for nearly twenty years now. The theme running through all our publications is always “Plants are a cheaper, faster, safer and more scalable means of producing pharmaceutically-relevant proteins than any of the conventional expression systems…” Since 2003 we have published 50-odd articles on plant-made recombinant proteins, including human and animal vaccine proteins and enzymes, so we have used this justification a lot.

Which begs the question, why isn’t Big Pharma using plant plant production, then?

After all, it’s been 30-odd years since the first “molecular farming” product was made, and many proofs of principle and several of efficacy of therapeutics and vaccines have been obtained, yet the pharmaceutical world has just two products that have been licenced or emergency licenced for use in humans. The first is Elelyso from Pfizer, better known in molecular farming circles as glucocerebrosidase developed by Protalix, which is an enzyme replacement therapeutic for persons suffering from Gaucher disease. This is not strictly speaking a plant product, though, as it is made in transgenic suspension cultured carrot cells, in 800 litre plastic bags.

The other is ZMapp, which is a cocktail of three “humanised” monoclonal antibodies (mAbs) which bind to Ebola virus, made by transient expression in Nicotiana benthamiana plants, and which were used in people as a post-infection therapy in the West African Ebola disease outbreak from 2014-2016.

If you consider that the first products to receive regulatory body approval – both in 2006 – were a mAb to hepatitis B virus surface antigen (HBsAg) that was used in purification by a Cuban company of the protein from yeast culture lysates, and tobacco suspension culture-produced Newcastle disease virus vaccine made for Dow AgroSciences that was never marketed, there has been effectively no market breakout at all for plant-made pharmaceuticals (PMPs).

Why is this? Why is it that a technology that can produce biomass containing product-of-interest between 100 and 1000 times more cheaply than mammalian CHO cells, or 10 – 100-fold cheaper than yeast or bacterial cultures, and be scaled from lab to industrial levels of production quicker than any other system, still languishing in the biotech industry doldrums?

Rybicki, 2009: Drug Discov Today. 2009 Jan;14(1-2):16-24. doi: 10.1016/j.drudis.2008.10.002

Granted, biomass production is only the upstream part of pharmaceutical production; the downstream purification / refinement / vialling and packaging costs for plant-made products will be the same as for conventionally-made versions, and these are typically much higher than biomass production costs. My own back-of-the-envelope calculations, done at a conference I attended where these costs were broken down by an industry expert, came out with plant-made finished product in a vial being 32% cheaper than the conventional equivalent. Given the large markup on finished product, this “advantage” is in itself not sufficient motivation for Big Pharma to change the means of production, given their typically enormous investments in stainless steel and other infrastructure.

And yet…doubling production capacity for any given product by a single Big Pharma supplier using conventional cell culture technology would entail spending the same amount again to get more stainless steel – which is typically multiples of at least US$100 million – as well as spending an inordinately long time getting the new plant certified. Also, even making a new product from scratch using existing infrastructure would involve heroic cleaning and rejigging of tanks and feed pipes and other paraphernalia used for biomass production, recertifications and the like, which could take months.  With plant-based manufacture, on the other hand, doubling production capacity means using double the number of cheaply-grown plants, possibly doubling the volume of Agrobacterium tumefaciens suspension to dunk them into, and then having enough space to put them under lights for 5-7 days or so, all with the same downstream processing capacity.

Then, there is the speed of scalability, which is unmatched for plant-made proteins. Consider this: given a ready supply of plants, it is theoretically possible for a molecular farming industrial facility to scale plant production of any given protein from lab bench scale – say a few milligrams/batch –  to industrial scale (kilograms per batch), in as long a time it takes to culture the few hundred litres of Agrobacterium you would need for infiltration. Keeping a large reserve of plants is cheap; commercial greenhouses could do this very cheaply – meaning biomass is effectively instantly available to whatever volume required. Culturing Agrobacterium to scale would also literally take a couple of days, meaning infiltrating and incubation for target molecule synthesis could take just a few days from obtaining a gene. Scaling a new line of stably transfected CHO cells from a flask up to 30 000 litres, on the other hand…this takes many cell doublings, with the attendant problems of maintaining both genetic integrity and sterility, and is far more expensive and takes longer.

Plant-Made COVID-19 / SARS-CoV-2 Vaccines

In fact, in 2012 as part of the DARPA “Blue “Angel” challenge, Medicago Inc. of Quebec in their new North Carolina facility, managed to make 10 million doses of H1N1 influenza virus vaccine as virus-like particles (VLPs), vialled and labelled, within a month of being given the sequence of the virus. If one considers that seasonal influenza vaccines take at least six months to make by egg culture, even with accelerated clinical testing and certification, this is a truly impressive improvement on current technology, and probably the quickest development of an influenza virus vaccine ever*. The company has since advanced to making and testing a quadrivalent seasonal influenza vaccine candidate through Phase III clinical trial, for imminent commercial release, was awarded “Best New Vaccine Technology/Platform” prize at the World Vaccine Congress in 2019 – and on March 12th 2020 announced they had made a viable vaccine candidate against COVID-19. They did this in just 20 days after receiving (presumably) the S envelope glycoprotein gene, and moreover made VLPs using their proprietary technology: VLPs are better immunogens than soluble subunit proteins, as they are much better at stimulating both antibody and cellular immune responses.

Virus-like particles made the same way Medicago will probably make SARS-CoV-2 VLPs – from this paper:

They are not alone in this space: just two weeks later, British American Tobacco (BAT) gained a lot of media attention when they also announced a candidate plant-made vaccine against SARS-CoV-2. While many hailed the repurposing of tobacco by a cigarette-manufacturing company as being an unexpected and good thing, it was really the BAT subsidiary RJ Reynolds’ recent purchase of Kentucky BioProcessing Inc, itself a spinout of one of the pioneering molecular farming companies (Large Scale Biology Inc., now sadly defunct) and the firm that had produced the largest amounts of the anti-Ebola ZMapp mAbs, that allowed them to take the credit. History aside, KBP announced they had “cloned a portion of COVID-19’s genetic sequence to create an antigen, which induce an immune response in the body” – which almost certainly means the S glycoprotein, or a portion of it – and that they could potentially make 3 million doses a week.

These announcements are the most important in the molecular farming space – although there have been others, such as by my long-time friend George Lomonossoff in the UK –  and the vaccine candidates are almost certainly going to be cheaper and quicker to make than conventionally manufactured subunit-based equivalents like the Coalition for Epidemic Preparedness Innovations (CEPI)-sponsored University of Queensland product announced recently. Indeed, a local “futurist” – Pieter Geldenhuys, interviewed by Moneyweb on 29th March – said, of the news that Medicago had developed a vaccine:

“Once one of the multitude of medical research teams have developed an effective vaccine for the strain prevalent in South Africa, it will take several months, or even years, before enough vaccines could be produced to fill the global need. This is where tobacco plants come in”

Geldenhuys’s advice for various governments around the world is clear. Keep your ear on the ground and start reaching out to companies like these. Once initial tests show success, consider building your own tobacco cultivation plants to ensure that you can reproduce the vaccine at speed.

A very recent article in the Wall Street Journal also soberly assesses the prospects of plant-made vaccines against SARS2 – with some help from some molecular farmers we may know B-)

Molecular Farming Manufacturing Possibilities in South Africa

Our group in the BRU, our recent spinout partners* Cape Bio Pharms, and a group at the SA Council for Scientific and Industrial Research (CSIR) are the three premier molecular farming research and development teams in South Africa. We have jointly made a host of candidate vaccines, virus-derived reagents for use in molecular biology labs and in diagnostics, and mAbs for use as reagents and potentially as therapeutics. Presently, Cape Bio Pharms and possibly the CSIR represent the only pilot-scale manufacturing facilities in South Africa for plant-made biologics, despite initiatives over years involving us and the CSIR and various government departments. A symposium in Franschhoek in the Western Cape Province in November 2017, hosted by the BRU and by iBio Inc of Bryan Texas, pitched a plan to assembled invited delegates for public/private partnership to construct a facility in this country to make pharmaceutical products using molecular farming technology. In announcing it, we said the following:

iBio’s plant growth facility, October 2018

“The conference brings together leaders from public agencies, academic institutions, parastatals, private companies, regulators and private capital to map out concrete steps to establish the plant-based manufacturing platform in South Africa. The Department of Science and Technology (DST) leads a broad science and technology innovation effort including of advanced health care products to create socio-economic opportunities.   The Technology Innovation Agency (TIA) is an active funder of human and animal health care initiatives in South Africa.     The Industrial Development Corporation (IDC) is a primary developer of manufacturing capacity and has important initiatives in biotechnology. Other participating agencies include the Council for Scientific and Industrial Research (CSIR), with its own molecular farming pipeline, and the Department of Trade and Industry (DTI).

AzarGen Biotechnologies is a private South African biotechnology company will be part of the private sector representation. AzarGen, primarily funded by the IDC, has worked with iBio for the last three years to develop biotherapeutics that include surfactin for infant respiratory distress syndrome and a biobetter rituximab monoclonal antibody for the treatment of non-Hodgkin’s lymphoma and certain autoimmune diseases. The BioVac Institute and Onderstepoort Biologicals, manufacturers of human and animal vaccine products respectively, will also present. ENSafrica will speak to Intellectual Asset Management and Cape Venture Partners will overview the private capital opportunities in South Africa. Technology Innovation Group, a US based consulting group, will talk about the structure of successful public/private partnerships.”

While the idea of a full-scale facility similar to iBio’s – costed at around USD30 million/R450 million – did not appeal to funders present, the idea of a cGMP-certified pilot manufacturing facility costing USD10 million – R150 million at the time – constructed using iBio’s expertise and assistance, found more favour. In fact, various entities promised to survey interested parties to establish the need and feasibility of internally funding it.

To the best of my knowledge, nothing along the lines of a survey has happened to date. Since then, and in the absence of any apparent interest from what were DST, DTI, IDC, TIA and others, iBio has gone on in 2019 to announce a partnership with Azargen in the area of rituximab biosimilar production, and as of a few days ago, as a contract manufacturing organisation, is offering their services in making COVID/SARS2 reagents at industrial scale in plants. Cape Bio Pharms has also established itself as a reagent manufacturer independently of any outside associations, with only local investment and a THRIP grant from Dept of Trade and Industry (DTI). I note that a previous proposal from some years ago involving the CSIR and Kentucky BioProcessing for establishment of an even cheaper pilot facility, also fell flat. For comparison, I will point out that the cost of just the revamping of Onderstepoort Biological Products’ (OBP, SA’s premier veterinary vaccine manufacturer) facility to be able to achieve cGMP certification is estimated to be ~R500 million.

SARS2/COVID Vaccines and Reagents for South Africa

Very early on in the present pandemic, Dr Mani Margolin of both the BRU and the Vaccine Research Group (VRG) of Prof Anna-Lise Williamson ordered a synthetic gene for a soluble version of the SARS-CoV-2 S protein, and has since successfully expressed the protein in both tissue cultured human cells, and in Nicotiana benthamiana plants via transient Agrobacterium-mediated expression. Both expression strategies leveraged technologies for which our research groups have either applied for or been granted patents, and established the very real possibilities of making both a DNA vaccine and a protein subunit vaccine against SARS2. He has gone on to insert the S protein gene into other vaccine vectors in the VRG.

Cape Bio Pharms (CBP)*, acting in parallel, ordered a gene for the “head” portion of the S protein – termed S1 – which they have also successfully expressed in N benthamiana, along with several variants of the protein, and they plan to collaborate with another new biotech company in South Africa to use it to produce mAbs for use as reagents, and potentially as therapeutics.

The CSIR is planning to leverage their established expertise in making mAbs to HIV and rabies in plants to produce a panel of mAbs to SARS2 for the same purposes.

These efforts have already resulted in ad hoc partnerships with other research groups and organisations, with S and S1 protein being supplied to others for use in establishing enzyme immunoassays and other diagnostic tests for serosurveillance and bedside testing, and other genes being shared with us and CBP for expression as reagents. I will note that the efforts that have resulted in the S-derived products are probably the fastest production at scales greater than a few micrograms in this country of any protein-based reagents, and probably the most quickly and cheaply scalable of any reagents. We are presently awaiting news of possible funding for molecular farming projects involving SARS2, albeit in a very rapidIy changing landscape where every day brings new developments – and where the future economic prospects of our country look dire, which may work against us.

Lessons From the Past

We have been here before, though. In 2006 our group received “Emergency Response” 1-year funding for H5N1 vaccine development from the Poliomyelitis Research Foundation (PRF) in SA – a then-handsome amount of R250 000 – which we then parlayed into another PRF 3-year grant, as well funding from the SA Medical Research Council (SAMRC). This quote from a profile published in Human Vaccines & Immunotherapeutics nicely sums up what we did:

As a result of a conference held in Cape Town in 2005, where a WHO influenza expert warned us “When the pandemic comes, you in the developing countries will be on your own”, we applied for extraordinary funding from the PRF in SA to explore the possibility of making a pandemic flu virus vaccine in South Africa. We chose the highly pathogenic avian influenza virus A H5N1 type haemagglutinin (H5 HA) as a target, and James Maclean was again instrumental in designing and successful early testing of plant-made soluble and membrane-bound forms. Further funding from the PRF and the SA MRC allowed proof of principle that we could in fact produce flu virus vaccine candidates in South Africa – both as [plant-made] subunit protein and as DNA vaccines.

In retrospect, while these projects were impossibly ambitious and not a little naïve, we and our co-workers received a crash course in both research vaccinology and the handling of big projects that has been crucial for all our subsequent work. We were also able to establish stable and well-qualified teams of people, with a nucleus of senior scientists who have been around us for up to 15 years. Another very important lesson was that we should patent our discoveries: in my case, this has led to me and my co-workers having the largest patent portfolio at our institution, and the largest molecular biotechnology-related portfolio in Africa – most of them to do with vaccines (14+ patent families). The development of a set of well-tried protocols around expression of novel antigens in a variety of systems has also been invaluable – especially when funding circumstances demanded that we change direction….

The potential importance of molecular farming for human health has been underlined recently with the apparently successful use of plant-produced MAbs (ZMapp) against Ebola virus disease in West Africa, and the proof of large-scale and rapid emergency-response production in plants of potentially pandemic influenza vaccines by Medicago Inc, among others [my emphasis] . We see our future role in exploiting niche opportunities for production of vaccine candidates and reagents for orphan or geographically-limited disease agents that do not attract Big Pharma attention – like CCHFV and RVFV – as well as for emerging animal diseases such as BTV and AHSV and BFDV, where rapid responses and small manufacturing runs may be needed [my emphasis].

Despite the fact that we ambitiously entitled our 2012 flu vaccine paper “Setting up a platform for plant-based influenza virus vaccine production in South Africa“, and our 2013 DNA vaccine paper as “An H5N1 influenza DNA vaccine for South Africa“, nothing happened. Nothing, despite the then Minister of Health Dr Aaron Motsoaledi saying during the influenza H1N1 2009 pandemic, that:

“South Africa has arrived at a situation where we have no option but to start developing our own vaccine capacity, not only for H1N1, but generally,” Motsoaledi told parliament.

“The disturbing feature about today’s world… has been expressed by the minister of health for Cambodia… who noted that the developed world, after producing the vaccine, may want to cover their own population first before thinking about the developing world,” Motsoaledi said.

It’s been nearly 11 years. Nothing has happened still. Despite distributing some 25 million doses of vaccines annually in South Africa, our only human vaccine firm – The Biovac Institute – still makes no virus vaccines. We have licenced our patented technology – for plant-made human papillomavirus vaccines and influenza virus vaccine – outside the country, for the lack of any interest locally.

This really should change. Maybe we have an opportunity now.

*= potential conflicts of interest due to partnerships.

Reviews on Molecular Farming

1: Dennis SJ, Meyers AE, Hitzeroth II, Rybicki EP. African Horse Sickness: A Review of Current Understanding and Vaccine Development. Viruses. 2019 Sep 11;11(9). pii: E844. doi: 10.3390/v11090844. Review. PubMed PMID: 31514299; PubMed Central PMCID: PMC6783979.

2: Rybicki EP. Plant molecular farming of virus-like nanoparticles as vaccines and reagents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020 Mar;12(2):e1587. doi: 10.1002/wnan.1587. Epub 2019 Sep 5. Review. PubMed PMID: 31486296.

3: Chapman R, Rybicki EP. Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation. Vaccines (Basel). 2019 Jun 13;7(2). pii: E50. doi: 10.3390/vaccines7020050. Review. PubMed PMID: 31200559; PubMed Central  PMCID: PMC6632145.

4: Margolin E, Chapman R, Williamson AL, Rybicki EP, Meyers AE. Production of complex viral glycoproteins in plants as vaccine immunogens. Plant Biotechnol J.  2018 Jun 11. doi: 10.1111/pbi.12963. [Epub ahead of print] Review. PubMed PMID: 29890031; PubMed Central PMCID: PMC6097131.

5: Chabeda A, Yanez RJR, Lamprecht R, Meyers AE, Rybicki EP, Hitzeroth II. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Res. 2018 Jun;5:46-58. doi: 10.1016/j.pvr.2017.12.006. Epub 2017 Dec 19. Review. PubMed PMID: 29277575; PubMed Central PMCID: PMC5887015.

6: Rybicki EP. Plant-made vaccines and reagents for the One Health initiative. Hum Vaccin Immunother. 2017 Dec 2;13(12):2912-2917. doi: 10.1080/21645515.2017.1356497. Epub 2017 Aug 28. Review. PubMed PMID: 28846485; PubMed Central PMCID: PMC5718809.

7: Williamson AL, Rybicki EP. Justification for the inclusion of Gag in HIV vaccine candidates. Expert Rev Vaccines. 2016 May;15(5):585-98. doi: 10.1586/14760584.2016.1129904. Epub 2015 Dec 28. Review. PubMed PMID: 26645951.

8: Rybicki EP. Plant-based vaccines against viruses. Virol J. 2014 Dec 3;11:205.  doi: 10.1186/s12985-014-0205-0. Review. PubMed PMID: 25465382; PubMed Central PMCID: PMC4264547.

10: Scotti N, Rybicki EP. Virus-like particles produced in plants as potential vaccines. Expert Rev Vaccines. 2013 Feb;12(2):211-24. doi: 10.1586/erv.12.147. Review. PubMed PMID: 23414411.

11: Thuenemann EC, Lenzi P, Love AJ, Taliansky M, Bécares M, Zuñiga S, Enjuanes L, Zahmanova GG, Minkov IN, Matić S, Noris E, Meyers A, Hattingh A, Rybicki EP, Kiselev OI, Ravin NV, Eldarov MA, Skryabin KG, Lomonossoff GP. The use of transient expression systems for the rapid production of virus-like particles in  plants. Curr Pharm Des. 2013;19(31):5564-73. Review. PubMed PMID: 23394559.

12: Rybicki EP, Hitzeroth II, Meyers A, Dus Santos MJ, Wigdorovitz A. Developing  country applications of molecular farming: case studies in South Africa and Argentina. Curr Pharm Des. 2013;19(31):5612-21. Review. PubMed PMID: 23394557.

14: Lotter-Stark HC, Rybicki EP, Chikwamba RK. Plant made anti-HIV microbicides–a field of opportunity. Biotechnol Adv. 2012 Nov-Dec;30(6):1614-26. doi: 10.1016/j.biotechadv.2012.06.002. Epub 2012 Jun 28. Review. PubMed PMID: 22750509.

15: Rybicki EP, Martin DP. Virus-derived ssDNA vectors for the expression of foreign proteins in plants. Curr Top Microbiol Immunol. 2014;375:19-45. doi: 10.1007/82_2011_185. Review. PubMed PMID: 22038412.

16: Rybicki EP, Chikwamba R, Koch M, Rhodes JI, Groenewald JH. Plant-made therapeutics: an emerging platform in South Africa. Biotechnol Adv. 2012 Mar-Apr;30(2):449-59. doi: 10.1016/j.biotechadv.2011.07.014. Epub 2011 Aug 3. Review. PubMed PMID: 21839824.

17: Rybicki EP, Williamson AL, Meyers A, Hitzeroth II. Vaccine farming in Cape Town. Hum Vaccin. 2011 Mar;7(3):339-48. Epub 2011 Mar 1. Review. PubMed PMID: 21358269.

18: Giorgi C, Franconi R, Rybicki EP. Human papillomavirus vaccines in plants. Expert Rev Vaccines. 2010 Aug;9(8):913-24. doi: 10.1586/erv.10.84. Review. PubMed PMID: 20673013.

19: Rybicki EP. Plant-made vaccines for humans and animals. Plant Biotechnol J. 2010 Jun;8(5):620-37. doi: 10.1111/j.1467-7652.2010.00507.x. Epub 2010 Mar 11. Review. PubMed PMID: 20233333.

20: Pereira R, Hitzeroth II, Rybicki EP. Insights into the role and function of L2, the minor capsid protein of papillomaviruses. Arch Virol. 2009;154(2):187-97. doi: 10.1007/s00705-009-0310-3. Epub 2009 Jan 25. Review. PubMed PMID: 19169853.

Endlessly revisiting a bad idea

10 December, 2019

I see, in my travels through TwitterSpace (thanks @evelienadri!) that the ICTV is mulling a major rework of virus taxonomy – and that they’re wanting, among other things, to

  1. have a binomial nomenclature system, like cellular organisms
  2. work some Latin into it.

A downloadable paper on this is provided here.

Now as a sometime Study Group Chair (two different groups of plant viruses; Bromoviridae and Geminiviridae), member of a third (Potyviridae) and longtime member of (since 1987) and contributor to the ICTV, I am frankly aghast that we are revisiting territory that we left behind more than fifty years ago. It was recognised then that viruses are not like cell-based organisms, and that we had a chance to get away from the straitjacket of Latinate binomials imposed on us several hundred years ago. And now – we are to return to binomials, and to Latin, yet??

No! Please, no! The idea has exercised me and some others sufficiently to cause a bit of a Twitter storm:

The problems with virus taxonomy and nomenclature, such as they are, are largely the making of folk who ignore established and customary rules, and establish names like “Marseillevirus”: what is this? The name gives absolutely no idea; neither does “mimivirus”, which I still think was named after someone’s dog.

Bean golden mosaic begomovirus, on the other hand, very aptly describes the type member of the genus Begomovirus, as does Panicum streak mastrevirus – both geminiviruses (family Geminiviridae) in good standing. Plant virologists seem to have been the most law-abiding of ICTV members, and it was from their ranks that the idea of using generic names as identifiers first came from, as in the usage shown above.

Now what could possibly be wrong with yellow fever flavivirus, or its relative hepatitis C hepacivirus? Very descriptive of exactly which virus you mean, rather than calling them flavivirus YF35 or hepacivirus H1, or some such gobbledegook.

I realise that virology has a problem with the enormous number of sequences that appear to be whole virus genomes, that no-one knows what to do with. The answer is that a sequence is NOT a virus, until it is shown to be one – at which point it can get a name, based on its phylogenetic relationships.

Jumbling up names that have been in common usage for many years is going to be resisted; having a taxonomic scheme that reverses the order by which virologists have known things, more so. Why bother?? What is so wrong with our present naming system, that we have to so drastically change it – and moreover, have species names that may be completely different to the common names of actual viruses?

I see no good reason to get in line with the rest of biology: viruses are, after all, the most numerous lifeforms on the planet; cramming them into an archaic straitjacket devised for organism with legs or leaves, and grudgingly extended to microbes, is simply retrograde.

So let’s not do it. Please?!

Influenza and History of Discovery of Viruses ebooks

14 November, 2019

I discover to my annoyance that the Apple Store changed the access URLs to my two ebooks without informing me – so I am re-advertising them here. Who knows, I may get more sales!

Influenza is available in the US Store via this link; Discovery of Viruses via this one. Please buy: you’ll be funding my impending retirement!

A new vaccine hope for African horse sickness, from an unlikely source

22 November, 2018


A new vaccine hope for African horse sickness, from an unlikely source



Researchers at the University of Cape Town’s ​Biopharming Research Institute (BRU)​ have created a promising new vaccine candidate to help prevent the devastating effects of African Horse Sickness (AHS). And they’re producing it in tobacco plants.

“We’ve got a vaccine candidate that’s extremely immunogenic,” says Prof Ed Rybicki, Director of the BRU. “It also produces neutralising antibodies when administered to healthy horses.” That means that the vaccine works really well in initial tests, but needs to be tested against an actual outbreak of AHS before it can be sold. BRU recently published these results in the respected Veterinary Research​ journal.

The need for an effective AHS vaccine is pressing. The disease is a devastating one, particularly in Africa, with up to 90% of infected horses dying in some outbreaks. The current commercial vaccine is known as a live-attenuated vaccine, and while it remains effective, it carries some risks. According to Prof Alan Guthrie, Director of the ​Equine Research Centre​ at the University of Pretoria and a former collaborator on this project, live vaccines can and occasionally do cause outbreaks of their own.

“There are two problems with a live-attenuated virus vaccine – reassortment of the genome and reversion to virulence,” he says. “Both can lead to outbreaks, which is what happened in the Cape in three different AHS outbreaks over the last 15 years – in 2004, 2011, and 2014.”

This is why other parts of the world don’t use the currently-available vaccine, says Guthrie. And this is a looming threat, as a changing climate allows the midge that carries the virus to spread to new parts of Europe and the United Kingdom.

According to ​Sue Dennis, PhD candidate and lead author on this study, the BRU’s plant-produced vaccine doesn’t carry any of these risks, which makes it suitable for use around the world.

“We’ve used tobacco plants to produce four different virus proteins that automatically assemble to form a virus-like particle (VLP). It looks the same as the virus, just without any genetic material; so it cannot replicate or infect horses with the disease.”

This VLP is the vaccine – when injected into an animal, the immune system produces antibodies to the virus that will fend off the real thing and protect the animal from disease. Dennis says that initial results look very promising, but there is more work to be done.

“When we tested the plant-produced vaccine in healthy horses, we saw an immune response at the same level as the live vaccine,” she says. When first testing vaccines in live animals, the most important thing is to show that the animal’s health is not affected, and that the immune system produces neutralising antibodies – the best indication that the vaccine will work against the live virus. On both counts, the BRU study has been a success.

“The presence of neutralising antibodies is a strong indication that horses will be protected from the virus,” she says. “But to confirm that the vaccine offers complete protection, we need what’s called a live challenge.”

In addition, the VLPs produced by Dennis and colleagues represent just one strain of AHSV; they are currently working on producing vaccines against the other strains.

This success builds on more than 10 years of work at the BRU producing VLPs and other proteins in tobacco plants. In particular, years of work on bluetongue virus, which is related to AHS virus, has contributed to this breakthrough.

The next step is to test the protective power of the vaccine in horses against a challenge with live, virulent AHSV (the so-called live challenge), to see whether this promising vaccine candidate can stand up against the live virus. If it does as well as the current live-attenuated vaccine, BRU researchers believe they will be well on their way to a new global AHS vaccine.

This research was funded in part by the ​Technology Innovation Agency​, and related intellectual property has been protected through UCT’s ​Department of Research, Contracts and Innovation​, who receive a rebate from the DST National IP Management Office (NIPMO) to support patenting.


About BRU

The Biopharming Research Unit​ (BRU, Department of Molecular and Cell Biology at ​UCT) ​ makes recombinant proteins in plants for use as diagnostics or vaccines for human and animal diseases. The Unit comprises research groups led by Professor Ed Rybicki, Associate Professor Inga Hitzeroth and Dr Ann Meyers, and boasts the largest portfolio of biotechnology patents at UCT, as well as the largest molecular biotechnology portfolio in South Africa. ​


About UCT

The University of Cape Town (UCT) is the leading research-intensive university in South Africa and on the African continent, with a tradition of academic excellence that is respected worldwide. ​


About RCI

Research Contracts and Innovation (RC&I) acts as the liaison between UCT’s research community and the private sector with regards to intellectual property protection, commercialisation and business development activities. ​


For media enquiries, please contact Dr Ann Meyers on 021 650 5712 | ann.meyers To read the full paper, go to ​​.


Press release written and distributed for the Biopharming Research Unit by ​ScienceLink​.


Teaching Virology With Social Media

12 July, 2018

I have had a Web presence since we first had access to the Web, here at the University of Cape Town, back in 1994: a few of us had discovered this new and shiny thing, and asked our IT Services if UCT had a server – to be told “Yes, but you can’t use it”. We – my colleague Vernon Coyne and I – quickly disabused them of this notion, and got unfettered access to what was then a very primitive Webiverse. Imagine: we were still using FTP and Gopher to move stuff around on the internet at the time; we also had to compose our self-taught HTML using Windows Notepad, for browsers like Cello that didn’t support graphics!

I pretty quickly got the notion that one could teach Virology via the Web, and set up teaching pages from 1995 or so that survived until UCT’s Big Clean Up a few years ago, which basically killed the whole legacy Web environment for us. Delightfully primitive they were, at first: I blogged about this here two years ago, noting that the ONLY record of all that work was via the Wayback server, that has an admirable if slightly spotty set of historical links to material that does not survive anywhere else.


Something that was potentially more valuable though, and which I pioneered at UCT from 1995, was the real-time updating of virological news – started in 1995 with the Ebola Zaire outbreak in Kikwit in the DRC, and commemorated here 20 years on. I was essentially compiling a daily digest of news on the Kikwit outbreak, and later also on others, and also on Marburg, via sources such as ProMed and internet discussion groups. It all started with an essay by my 1994 Honours student, Alison Jacobson, that was one of the first things I put up on the Web. This subsequently ended up being one of the only sources of information on the virus available online for a while, which terrified Alison, and which I commemorated here.

Occurrences_of_Ebola 2

I used this material at the time to inform undergrad students in second-and third-year courses as to what was going on in the moment – and give them cutting-edge material for exam purposes even after my section(s) of their course(s) had finished.

Inevitably things changed and moved on, and I got busy doing other career-related things – then my long-time internet guru Alan Cann introduced me to the concept of regular blogging via WordPress, and slicker news aggregators such as, and Twitter. The site you’re on right now is of course the blog site I set up in 2007 as a teaching blog for Virology, after guesting on his MicrobiologyBytes site a number of times – and I see with some sadness that his site no longer exists. I did things with ViroBlogy like blogging in detail in 2008 on a great paper describing single-round replication of a West Nile virus vaccine candidate – and then asking a detailed question on it in the 3rd year Defence and Disease course exam, despite there being no coverage of it during the course.

I also signed up for Twitter as @edrybicki in 2008 – mainly to tweet about cups of coffee and Marmite-coated biscuits, it would seem, although I see H1N1pdm flu getting to South Africa got a mention.


I then started up Virology News in 2012 on the site, again following The Guru Cann, for disseminating a wider, more general set of news about viruses to a wider audience. Oh, and news about zombies. And sometimes Led Zeppelin too B-)

Virology_News___Scoop_it turned out to be an excellent add-on to my existing sites, as it could be set up to automatically tweet anything I put up in it, or put it up on my WordPress ViroBlogy site. This actually marked the start of a new endeavour to supply up-to-date information to students of virology, as well as interested lay folk, despite the fact that I was not teaching undergrads between 2010 and 2017 because of secondment to a job as Academic Liaison to UCT’s Research Portal Project.

In any case, the blog site and site and being on Twitter kept me current with news in Virology, and were really useful in informing the two ebooks I published in 2015 on  “A Short History of the Discovery of Viruses“ and “Influenza Virus – Introduction to a Killer“, as well as the Introduction to Molecular Virology I am currently writing. The excerpts from those books that I trialled on this site – and tweeted about – have led to high and consistent page accesses from all over the world, as people search for things like “history of virus”.


What this has led up to, as I am now teaching undergraduates again, is the use of my Web-based news and other people’s materials via Twitter to inform students in the various modules I teach about current outbreaks, new discoveries and exciting developments in Virology and One Health. I tell them upfront in my first lecture that I want them to look at @edrybicki, ViroBlogy and Virology News, and that I will regularly be highlighting things of relevance to them. For instance, my daily trawl through Twitter invariably throws up a few papers I want to read, papers I think students should be interested in, and some news on outbreaks or breakthroughs. I then simply hashtag those with the course code, possibly add a comment, and retweet.


The value of this exercise can be seen in the fact that even well after I finished lecturing, students in the MCB2020F course were able to pick up on outbreak information that simply didn’t exist in that 5-lecture window weeks earlier – and give me material back in their final exam answers to the question “Describe one important virus disease outbreak this year and what it affected [3 marks]” that I had not taught them, from as short a time as 5 days previously. Which I commemorated thus, while marking their exam B-)


I did the same thing for a third-year Viromics course, and while I got fewer non-lecture material-based answers, the value of pointing students to alternative material was again confirmed.

viromics edrybicki__MCB3026F_-_Twitter_Search

I shall continue to do this over the next three years of formal lecturing, for the simple reason that it engages students in the productive use of social media – and makes them go out and find information you didn’t have to teach them. You are warned, MCB2020F / 3026F / 3023S / 3024S and 2022S: hashtags, blogs, Scoops…are all waiting for you B-)



1918 Influenza Pandemic Case Fatality Rate

11 April, 2018


Influenza viruses and birds. Russell Kightley Media

Seeing as I have written an ebook on influenza that includes a short history of the 1918 pandemic, I have a rather keen interest in looking up things like case fatality rates, incidences and the like. I have also picked up on a rather worrying discrepancy in oft-quoted figures that just get recirculated without question, in serious and respected publications.

For example, here is one of the opening paragraphs from an influential review from Jeffery Taubenberger and David Morens, from 2006:

“An estimated one third of the world’s population (or ≈500 million persons) were infected and had clinically apparent illnesses during the 1918–1919 influenza pandemic. The disease was exceptionally severe. Case-fatality rates were >2.5%, compared to <0.1% in other influenza pandemics. Total deaths were estimated at ≈50 million and were arguably as high as 100 million.”

This figure of ~2.5% CFR is found in many references, yet it cannot be right: just from data in that paragraph, one could estimate that the CFR must have been between 10 and 20%!

No less a publication than Nature, in their 25th January issue, has an editorial entitled “The Great Flu” – wherein they say the following – and add to the problem:

“One hundred years ago this month, the 1918 influenza virus was just starting to spread. It would become the greatest public-health crisis of the twentieth century, claiming some 50 million to 100 million lives….

There are few data points to go on — flu pandemics happen only three or four times a century — but one risk is certainly higher: 7.6 billion people share the planet in 2018, up from 1.9 billion in 1918….

The case-fatality rate in the 1918 pandemic was around 2.5% (compared with less than 0.1% in other flu pandemics), and a comparable or worse rate in a future pandemic cannot be discounted.”

pig flu

Influenza viruses in pigs. Russell Kightley Media

From their own figures, then, between 50 and 100 million people died, of 1.9 billion alive at the time. This is a death toll of between 2.6 and 5.2% of the WHOLE POPULATION, and is NOT a case fatality rate. If about one-third of the population was affected, then the CFR would be ~7.5 – 15%, which is far higher than the 2.5% quoted.

Here is a more realistic quote, for me at least, from Influenza Virus

“The global mortality rate from the 1918/1919 pandemic is not known, but it is estimated that 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means that 3% to 6% of the entire global population died. Influenza may have killed as many as 25 million in its first 25 weeks. Older estimates say it killed 40–50 million people while current estimates say 50—100 million people worldwide were killed. This pandemic has been described as “the greatest medical holocaust in history” and may have killed more people than the Black Death.”

Wikipedia even seems to have got it right, in their entry on the 1918 pandemic:

“The global mortality rate from the 1918/1919 pandemic is not known, but an estimated 10% to 20% of those who were infected died. With about a third of the world population infected, this case-fatality ratio means 3% to 6% of the entire global population died.

 So, all you virologists out there: please stop quoting that ludicrously low case fatality rate for the 1918 influenza pandemic of 2.5%, and get real! Oh, and let’s stop calling it the “Spanish Flu” too, please: it’s a much a misnomer as “swine flu” is for the 2009 pandemic, or “Aussie Flu” is for the recent and ongoing H3N2 epidemic.