Archive for the ‘General Virology’ Category

Purifying TMV: a blast from the archives

16 February, 2017

We have had an in-house method for purifying Tobacco mosaic virus (TMV) and its various relatives ever since I got to Cape Town – and it was propagated by copying and re-copying of what was effectively an abstract for a talk given at our local Experimental Biology Group quarterly meeting in early 1970, published in the South African Medical Journal.

Marc van Regenmortel was Professor of Microbiology at the time, and had a long history of physicochemical and serological work on TMV and strains and mutants of TMV. He also had Barbara von Wechmar, later to become my PhD supervisor, working for him as a Scientific Officer – and together they came up with an ingeniously simple, easy, high-yielding method to purify TMV out of infected tobacco.

So why do we care now? Well, we’re trying to purify some derivatised TMV [details redacted while patent is sought], and Sue Dennis in my lab could only find techniques that involved extraction with chloroform, PEG/salt precipitation x 2, high-speed centrifugation – all of which sounded unnecessarily laborious, given I knew we had a better method.

Trouble is – I cleaned up my office a while back, and seeing as “we’ll never work with TMV again, will we??”, I’d thrown out all of the old practical manuals that included it.

So I go to the old papers I could find online, and they all referred to “von Wechmar and van Regenmortel, 1970”, with no methodological details. And of course, there was no record of this paper anywhere I could find, not even using [obscure Russian language site details redacted].

Then I chanced upon the very bare bones online archive of the SAMJ, married that up with the much snazzier-looking-but-devoid-of-desired pdfs official site to find issue numbers – and there we were! Via some fascinating side trips through a history of the plague in Cape Town, among other things, but finally, a PDF of the original EBG abstract.


In fact, I have a big section of our coldroom with myriad bottles of purified TMV, all at 5 mg/ml concentration or higher, still infectious, and up to 40 years old – all made by this technique.

tmv sedim

So Sue is about to apply it right now, as she conveniently has a freshly mashed extract of N benthamiana ready waiting, and we have PEG and NaCl…we’ll give the charcoal/Celite a miss this time, because it can get a bit messy, but it is THE way to get pigments out of your virus preps – or even nanoparticles, @FrankBioNano & @Lomonossoff_Lab?

From plant virology to vaccinology: a personal journey

15 February, 2017

A couple of years ago now, an Editor of the journal Human Vaccines & Immunotherapeutics contacted me to say they would like to profile me as a vaccinologist. Being of a suspicious nature, I immediately inquired how much this would cost me. The encouraging answer was “Nothing!” – so I jumped straight in.

The end result is as near to a current autobiography as I will probably ever get, so I may as well put it up here. So, if you’re interested in finding out what the connections are between a swimming pool in Zambia, not doing Biochemistry (twice), plant virology and making vaccines – click below!

Fall armyworm – and how viruses could help combat the plague.

15 February, 2017

Kenneth Wilson of the Univ of Lancaster has recently written a blog post on the plagues of African and “Fall” armyworms (aka caterpillars, larvae of moth species in the genus Spodoptera) that are currently chewing their way through southern African maize and other crops. I wrote the following as a comment to his blog.

Nice article – which very ably demonstrates the perils of importing agricultural pests from elsewhere!

I am interested that you wrote:
“There are non-chemical, biological pesticides that could also be effective. These are pesticides derived from natural diseases of insects, such as viruses, fungi and bacteria.”

Some years back (OK, nearly 30) Barbara von Wechmar in the then Microbiology Dept was instrumental in our finding a number of insect viruses that were seriously lethal to aphids and green stinkbugs. These were inadvertent discoveries, which happened three times – twice with different viruses for aphids which we were investigating as wheat/barley pests, and once (with two viruses) for stinkbugs causing problems in passionfruit – and were due to observations that high density lab colonies of the insects in question often developed disease that caused rapid colony death. Barbara went on, after characterisation and publication of the viruses by me and Carolyn Williamson, to show that highly effective insecticides could be made by simply grinding up recently dead insects in some buffered saline, sieving the bits out, and spraying the juice onto plants. This worked for aphids, and was especially effective for stinkbugs.

I note that similar phenomena have been seen for a number of insects, including the spruce budworm in North America, and by Don Hendry and others in South Africa for Nudaurelia capensis, the Pine Emperor moth. In the latter case, the larvae can become literal sacs of virus, and bursting of dead caterpillars leaves viruses everywhere in the environment.

It might be a good “boer maak n’plan” type of approach for folk to gather a bucket of these things, feed ’em leaves for a while, see if they start to die – then mulch them in some half-strength (=0.075M) saline and make a spray out of it.

It couldn’t hurt, might help, and would be a pretty good biology lesson B-)

Seriously: you can find insect viruses everywhere you look, and crowding is a really good way of spreading and bringing out otherwise inapparent virus infections, just as it is with humans – with the difference being that insect viruses can reach REALLY high titres in their hosts, and are pretty stable as they are often spread by contact of live larvae with dried juices from dead ones.


John C. Cunningham, Basil M. Arif and Jean Percy. THE STATUS OF VIRUSES FOR SPRUCE BUDWORM POPULATION REGULATION. File Report No. 7 January 1981, Forest Pest Management Institute, Canadian Forestry Service

EP Rybicki and MB von Wechmar. Characterisation of an Aphid-Transmitted Virus Disease of Small Grains. Isolation and Partial Characterisation of Three Viruses. J Phytopathology 103, Issue 4 April 1982 Pages 306–322

Cheryl T. Walter, Michele Tomasicchio, Valerie Hodgson, Donald A. Hendry, Martin P. Hill and Rosemary A. Dorrington.  Characterization of a succession of small insect viruses in a wild South African population of Nudaurelia cytherea capensis (Lepidoptera: Saturniidae). South African Journal of Science 104, March/April 2008

C. WILLIAMSON, E. P. RYBICKI, G. G. F. KASDORF  AND M. B. VON WECHMAR. Characterization of a New Picorna-like Virus Isolated from Aphids. J. gen. Virol. (1988), 69, 787-795

Williamson C, von Wechmar MB. Two novel viruses associated with severe disease symptoms of the green stinkbug Nezara viridula. J Gen Virol. 1992 Sep;73 ( Pt 9):2467-71.


“New Virus Breaks The Rules Of Infection”! No – no, it doesn’t

31 August, 2016

I was prompted to this post by the breathless and much-hyped response to the discovery – the repeated discovery should I say; there was an earlier one that gets glossed over – of a multicomponent flavirus-like virus, this time in mosquitoes.

The actual report was published here: it is a well-done study, describing

“…a genetically distinct, segmented virus isolated from mosquitoes that also exhibits homology to viruses in the familyFlaviviridae and that appears to be multicomponent …, with each genome segment separately packaged into virions”

The authors say

“Although multicomponent genomes are relatively common among RNA viruses that infect plants and fungi, this method of genome organization has not previously been seen in animal viruses [my emphasis]

…which is why there’s all the hype, of course: claiming the virus “…breaks the rules of infection” is simply incorrect, because it is in fact related to very well characterised single-component ssRNA+ viruses of arthropods and mammals – flaviviruses – and infects its mosquito host exactly as these do, except with its genome in separate particles. Which makes it similar to quite a few plant viruses, several of which are, incidentally, probably evolutionarily related to viruses infecting insects – but more later.

Thus, a claim like “…a new study published Thursday is making researchers rethink how some viruses could infect animals” is simply hype.  But it is a sort of hype familiar to plant virologists, who after all showed that multicomponent viruses (=viruses with multipartite genomes packaged in separate particles) existed over 50 years ago – and who also showed that gene silencing was a factor in plant resistance to viruses long before their better-funded animal-researching colleagues got in on the act, but that is another story.

The way in which multicomponency was discovered with plant viruses is interesting: it relied on the fact that plants can respond with local lesions – qualitatively the same as plaques in bacterial or animal cell lawns – to mechanical infection, and that this can be used an an accurate assay of virus titre, as for phages or animal viruses (see here).  It became evident, though, that certain plant viruses produced significantly steeper lesion vs dilution curves than were expected from “one-hit” kinetics, where infection with a single virus particle sufficed to cause a lesion.

This is best shown by a plot like the one below, modified from REF Matthews’ Virology, 3rd Edn, attributed to Lous van Vloten-Doting from 1968.  This shows the curves obtained from accurate and painstaking local lesion assays with the single-component Tobacco necrosis virus (TNV), and the multicomponent Alfalfa mosaic virus (AMV): both are ssRNA+ and have isometric particles, but TNV has a single-component genome, and AMV a tripartite genome packaged in 3 particles.


The insect virus investigators did much the same thing:

“We used a similar approach to assay the nature of segment packaging for GCXV using cell culture plaques instead of leaf lesions. The dose-response curve for GCXV differed significantly from expectations for a single-component virus (i.e., the number of plaques decreased more quickly than expected with dilution of the inoculant)…we used our dose-response curve to estimate the presence of 3.27 ± 0.37 distinct GCXV particles required for plaque formation”

…but with the addition of rapid sequencing techniques not available in 1968, to show that indeed, the different segments were 5 distinct pieces of ssRNA, 3 mono- and 2 tricistronic (=3 ORFs), with the 2 largest monocistronic pieces being similar to flavivirus NSPs and the 3 smallest not encoding anything similar to sequences in the databases.  Four RNAs were essential for infectivity, while the smallest appeared dispensable.  Particles formed during infection of cultured cells were enveloped and 30-35 nm in diameter, considerably smaller than flavivirus virions.

This is a very interesting finding, although not unique: similar viruses were previously found in ticks in 2014, when the authors claimed that:

“To our knowledge, JMTV is the first example of a segmented RNA virus with a genome derived in part from unsegmented [flavi]viral ancestors

They were also wrong: there are a number of viruses for which this could have been said years ago, like the picornavirus superfamily-related comoviruses of plants. These have two-component genomes which both encode polyproteins, one with non-structural and the other with structural ORFs.  In fact, an evolutionary precursor to such viruses could be the more closely picornavirus-related dicistroviruses of insects, which have a classic picornavirus precursor polyprotein ORF split into two, with the structural protein ORF at the 3′ end and the regulatory or non-structural polyprotein at the 5′ end.

I got into this because it irked me mildly that such a fuss was being made of a second group of animal-infecting multicomponent ssRNA viruses, when the multicomponent plant virus precedent and history was VERY well established – but then got more interested when speculation started about what advantage multicomponency could confer on a virus.

I have thought for years that people discussing this generally have it backwards: it’s not that having a divided genome in separate particles offers advantage(s), it’s that it is not a DISadvantage in some circumstances – and particularly where there is no selection against the state.

A reason that multicomponency HAS been seen quite frequently with plant viruses could be that mechanically-transmitted viruses can reach VERY high concentrations in infected plants, and even obligately vector-transmitted viruses (eg: the bicomponent ssDNA begomoviruses, multicomponent ssDNA nanoviruses) reach quite high concentrations in the phloem tissue to and from which they are transmitted, compared to viruses in vertebrates.

This is also true for viruses of arthropods compared to vertebrate viruses: dicistroviruses in aphids can reach concentrations that are comparable to those of viruses like TMV in plants, to the point that aphids inject enough virus into plants that our lab originally mistook Rhopalosiphum padi virus for a plant virus. Moreover, plant virus virions often aggregate into quasi-crystalline arrays which can be hard to separate and which are even visible inside insect vectors, thus virtually guaranteeing that >1 virion will be present in any inoculum, even if significantly diluted.

This is most definitely NOT the case for vertebrate viruses, even where the same virus infects both an arthropod and a vertebrate host: the titre in the latter is guaranteed to be orders of magnitude lower, largely due to a more sophisticated immune system keeping viraemia in check. Thus, high inoculum concentrations relative to vertebrate viruses, and a tendency to aggregate, mean there is no DISadvantage inherent in multicomponency.

Having said this, there may be advantages to having a multicomponent genome: one such is presented in a recent article by Sicard et al. (2013), (thanks, @LauringLab and @DiagnosticChick!) in a study of the ssDNA nanovirus Faba bean necrotic stunt virus (FBNSV), which has an 8-component genome of ~1 kb/segment, encapsidated in 8 virions. They proposed:

“…that the differential control of gene/segment copy number may represent an unforeseen benefit for multipartite viruses, which may compensate for the extra costs induced by the low-frequency segments”

Thus, multicomponent viruses may achieve the sorts of gene dosage control only possible in viruses with larger genomes, by virtue of having multiple genome components rather than control elements which add genomic bulk.

Another possible advantage that I recall being touted by plant virological luminaries is the ease of reassortment compared to recombination: this is exemplified by the reo- and orthomyxoviruses, albeit in vertebrates, where they are constrained by having to have all genome components in the same capsid to guarantee infectivity.

I think Vincent Racaniello is correct in the breathless article I quoted in opening, where he is quoted as saying

“There’s so much we don’t know about viruses…We should always expect the unexpected.”

Absolutely. And I think it’s a safe bet that a LOT more multicomponent viruses will be found in arthropods – and even in some vertebrates, to which they will have been transmitted by arthropods. Because that’s the link between many of these viruses: an evolutionary history that involves plants and arthropods, or arthropods and other animals, at an early stage of life on land. Because that’s all there was for advanced eukaryotes, early on: primitive vascular plants, insects that preyed on them and on each other, and protists.

So: will smallpox come back to kill us, from the melting permafrost??

17 August, 2016
Variola virus, the agent of smallpox.  Image courtesy Russell Kightley Media.

Variola virus, the agent of smallpox. Image courtesy Russell Kightley Media.

There has been a lot of tweeting today about how Smallpox Will Come Back From The Grave And Kill Us All: see here, here and here for lurid examples.

This is alarmism at its insidious best: shouting out a headline, based on flimsy evidence, that says “We’re all going to die!” or similar nonsense.

Really: this IS nonsense.  Some corpses were found in the permafrost in Siberia, that MAY have had smallpox-like lesions on them, and from some of which which smallpox virus DNA could be recovered – presumably by PCR.

This does NOT constitute a threat of live virus being present, or escaping from the corpses even if it WERE there.  I have railed on about this sort of thing before, and I am as unconvinced now as I was then, albeit with SOME reservation about the possibility for smallpox.

"Pithovirus sibericum", from Jean-Michel Claverie and Chantal Abergel

“Pithovirus sibericum”, from Jean-Michel Claverie and Chantal Abergel

I can believe you could get live anthrax: those spores are incredibly tough, and can last for many years in soil, let alone in ice. I could also believe that one could find live megaviruses – the so-called pitho- and molliviruses – in permafrost, because their putative hosts are unicellular protozoans and because they are also seriously stable.

But smallpox? The virus is probably not as stable as the megaviruses mentioned; it relies for infection on its structure, which has membranes integral to it – AND it infects people, who, when they die, don’t cool down very quickly, and whose cells release all sorts of nasty enzymes (lipases, proteases) as they die. Which could be expected to chew up most things, including poxviruses.

Oh, sure, poxviruses CAN survive for years at a pinch – in the form of dried secretions or scabs, which, because they are dehydrated and full of protein, tend to stabilise virus particles. This is how the old variolators and vaccinators (literally: people who used variola or “vaccine” to vaccinate against smallpox) used to preserve their inocula, when they weren’t using fresh material.

Melting tundra is not like that, I will note: bodies with intact virions in them will thaw and rot all over again, and that rotting will reduce what little virus there may be even further.

So I am not a believer in Death From The Permafrost!

And nor should you be.  But it might not hurt for someone qualified to test whether or not there IS live virus in frozen samples, by culturing an extract?

The Internet Journal of Comprehensive Virology

15 July, 2016


See Home Page for details

New developments in a South African HIV vaccine trial

7 June, 2016
HIV life cycle - Russell Kightley Media

HIV life cycle – Russell Kightley Media

Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap 

A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 109 PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4+ T-cell and CD8+ T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4+ T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4+ T-cell responses to HIV-1 envelope. (This study has been registered at under registration no. NCT00574600 and NCT01423825.)

This is a pretty big deal – because it reports an extension of a wholly South African-originated vaccine trial, that consisted of a DNA prime with a subtype C gp150 gene and an artificial Gag-RT-Tat-Nef polyprotein gene, followed by a rMVA boost, that was as immunogenic as anything else trialled around the same time.

And development of which was shut down for political reasons in 2009, but that is old news….
This new development, where a subtype C gp140 (soluble form of Env) was given with MF59 adjuvant to trial participants 2 years after the initial vaccinations, showed that recall responses were strong – in both cellular and humoral arms of the immune system. Moreover, neutralising Ab were elicited.
This is a very promising development in the saga of HIV vaccinology, and it is to be hoped that further trials will be funded.
And both my sister-in-law and my wife are involved B-) What can I say, we’re a virological family!

AIDS: 35 years old this month

6 June, 2016
HIV particle.  Russell Kightley Media

HIV particle. Russell Kightley Media

I was alerted via Twitter this morning to the fact that the CDC’s Morbidity and Mortality Weekly report that reported the first recognition of the syndrome we now know as AIDS, was published on 5th of June 1981.  It appears – sadly – that their archive only goes back to 1982: there’s a missed chance to expose some history, CDC?!

Thirty five years: I was a novice lecturer, just starting out; the Web was still science fiction; HIV and its relatives were still undiscovered – but they had already started to spread out of Africa, after smouldering away in the tropical forests of Gabon and the Congos for decades.

I started an information web page on HIV/AIDS back in 2000 or so, largely in response to the ridiculousness of Thabo Mbeki’s pronouncements on the virus and the disease: thanks to tectonic shifts in the UCT Web policy, these disappeared – but thanks to the invaluable Wayback Machine, can still be found.  If you want a slice of history, and to see how bad I am at designing web pages, go take a look. Still MOSTLY valid, although many of the links are now dead – sic transit the web content, unfortunately!

And here we are in 2016: I’m now an elderly academic, the Honours student who alerted me to the fact the the “GRIDS” syndrome virus may have been identified in 1983 is now a senior Professor and distinguished HIV researcher – there’s a whole career there, Carolyn! – and HIV/AIDS is still with us. And unfortunately, Thabo Mbeki is still being wilfully if not malevolently ignorant, and I am still feeling it necessary to crap on him.

At least the pandemic appears to have peaked in terms of incidence, and ARVs are increasingly good and employed widely; however, we still don’t have a decent vaccine, and people are still being infected. This pandemic will last out my career – but hopefully not those of some of the people I have trained.

New Approaches to Vaccines for Human and Veterinary Tropical Diseases. Or maybe sophisticated safari science?

27 May, 2016

The Keystone Symposia organisation held a meeting entitled “New Approaches to Vaccines for Human and Veterinary Tropical Diseases” in Cape Town this week (May 22-26, 2016).  A summary of the meeting was given as:

Human and livestock vaccines can contribute to improved human welfare and income generation by maintaining human health and meeting the demand for meat, milk and fish in developing countries. All of these factors contribute to the growing importance of improving food safety, availability and nutritional security. An important component of this Keystone Symposia meeting will be to stimulate crosstalk between the human and veterinary vaccine communities by highlighting cross-cutting technical advances and new science and knowledge from laboratory and field research. The meeting will also provide a rare opportunity for scientists from the Northern and Southern hemispheres to interact and pool resources and knowledge in the common fight against tropical diseases.”

It succeeded admirably in a couple of these goals: there were delegates there from 31 African countries, as well as many Europeans, Brits and Americans; the juxtaposition of veterinary and medical talks on similar themes created an excited buzz among folk who hadn’t been exposed to the “other”; there was a wealth of dazzling new tech on display in talks, and intriguing insights into how similar – and sometimes, how different – human and animal responses to vaccines were.  It was obvious that approaches used to develop malaria vaccines could benefit animal vaccinology, and indeed, Vish Nene and colleagues from ILRI in Kenya are following some of the same approaches in their work with the East Coast fever disease organism in cattle.

But, there were a couple of buts.  An important one for me was that while there were many Africans there, they were not much exposed in talks, apart from several South Africans. While amazing results were displayed from deep sequencing of antibody gene repertoires of humans and animals and how these developed with affinity maturation; while grand predictions were made as to how bioinformatics and molecular design would revolutionise vaccinology – this was more of the same kind of thing we have got used to in HIV vaccine meetings over nearly twenty years, where Big Science is always going to provide a solution, but never quite gets to it. Why was there no mention of ZMapp antibody therapy for Ebola, when this (OK, I’m biased) was the single most exciting thing to come out of the Ebola outbreak and the international response to it?

I hate to be cynical, but seriously: is there one single vaccine in advanced human trial right now that is a result of intelligent molecular design? Has ANYTHING that has been designed from crystallographic evidence or from cryoEM data actually proven useful in animals or people?  Has dissection of the anti-HIV antibody response development actually, really, taught us anything useful about how we should develop vaccines? Even if South Africans were involved?

I told you I was cynical – and my cynicism was reinforced by a couple of displays of “My Ebola vaccine is better than YOUR Ebola vaccine!”, by folk who shall remain nameless – when it was obvious that both ChAdOx and rVSV vaccines have their merits.

Mind you, the tale of how Ebola vaccines were deployed so rapidly, and how what could have been a 15+ year saga was compressed to less than a year for the rVSV-ZEBOV and ChAdOx vaccines was truly inspirational. It is indeed an object lesson in how to respond to an emerging disease that big companies and philanthropic organisations were able to make many thousand doses of different vaccine candidates in just a few months, and that these could be deployed in human “trials” – actually, genuine deployment in ring vaccination for the VSV candidate – almost immediately.  Adrian Hill of Oxford asked the question, albeit outside the meeting at a seminar in our Institute: if this was possible for an Ebola outbreak, why isn’t it possible for everything else?  Why can’t we do it for Zika virus, and for MERS-CoV too?

If there is a Big Lesson to come out of this meeting, why can’t it be – Let’s Make Vaccines Faster!

Oh, there were big plusses too.  There were fascinating parallels to be drawn in the approaches to developing vaccines for malaria and TB and animal parasitic infections; some of the fancier techniques discussed for human vaccines could obviously find applications in veterinary vaccinology; there were even suggestions for vaccine candidates for animals that were drawn from homologous genes in human and animal apicomplexans (=malaria-like organisms).

I was especially impressed by Dean Everett‘s talk, from the Malawi-Liverpool-Wellcome Trust Clinical Research Programme in Malawi, on “Developing Appropriate Vaccines through Bioinformatics in Africa”: they were actually working in under-developed Africa, on pressing local problems, and making significant inroads into the problems.

And yet, and yet: I have railed elsewhere about the J Craig Venter Institute’s grandstanding over their “synthetic” organisms; while the talk here by Sanjay Vashee on “Synthetic Bacterial and Viral Backbones as Antigen Delivery Vehicle” went some way to redeeming my negative impression of the use of this sort of work, I am still left with the impression that there are considerably easier ways of doing what they claim to be able to. Mind you, one of my colleagues was very impressed with the possibility of making Herpesmids (=infectious, engineerable whole genome clones) in yeast, and would love to do it with their poxvirus collection – so maybe I am a touch TOO too cynical.

I also felt that the final address, by Chris Wilson of the Bill & Melinda Gates Foundation, on: “Cross-Disciplinary Science to Accelerate the Discovery of Vaccines for Global, Zoonotic and Emerging Infectious Diseases” exemplified some of the problems inherent in trying to marry up developed and developing world science, especially in vaccinology.  Part of the talk was great: he gave the best description I’ve yet heard of why it could be feasible to inoculate Aedes spp. with Wolbachia, and why it could significantly impact transmission of flavi- and other viruses.  His description of gene drive technology for wiping out selected mosquito populations was also succinct, and masterly – and appropriate for a developing world audience. Then he got on to how dissection of antibody maturation pathways and flavivirus E protein design could provide paths to good vaccines, and the cynicism kicked in again.

We don’t need either technology to get to vaccines for HIV or for flaviviruses that we can test in the near future, and which could have very significant impacts on millions of people.

Really: we don’t. Extant HIV vaccine candidates are almost certainly better than the RV144 Thai trial vaccine components, and they had an efficacy of 60% in the first year. We already have YFV and dengue and JEV live vaccines – why don’t we use one or several of them in combination with an engineered YFV vaccine to protect against ALL epidemic flaviviruses?  Given the Ebola example, we could deploy vaccines for HIV and for flaviviruses in a year or less, and they would have an impact that would tide us over while fancier products were being made. Seriously: we are always waiting for the next best thing; let’s just apply what we know and what we have NOW to make an impact – instead of, like theoretical physicists, perpetually considering the problem of the spherical horse instead of just going out and riding one.

And that should have been one of the Big Lessons, and we missed it. Instead, there was an element of Safari Science, which is what we in Africa call the kind of endeavour which involves people from the global North flying in to sort out our problems – and leaving with our organisms and disease samples.

Which we could do ourselves, given funding. And that’s another lesson for the folk that do Big Science funding….


Thabo Mbeki rides again. Let’s knock him off his horse, then!

7 March, 2016

Sixteen years ago, two colleagues and I wrote a letter to Nature expressing our concern about our then-President Thabo Mbeki’s denialist views on HIV and AIDS – views he then tried to push into national policy, and which almost certainly were highly influential in delaying the rollout of ARVs in South Africa.  I was also active for several years in the media and in public lectures in trying to negate some of the damage he was causing – and I was very relieved when he took a back seat eventually, and then effectively vanished from the public stage.

However, in an unwelcome development as of this week, it appears that Mr Mbeki has finally, in his ongoing quest to rewrite history, addressed the elephant in the room: his views on HIV/AIDS.

To say this “letter” is self-serving would be to pay it a compliment.  Indeed, he himself has this to say concerning the awful “Castro Hlongwane, Cats, Geese, Caravans, Foot and Mouth and Statistics…” that he almost certainly was the main author of, back there in 2002:

“Thirteen (13) years later today I would stand by everything said in this excerpt and still ask that the questions posed should be answered by those who have the scientific capacity to do so!”

So in other words, he still holds with much of the rubbish he wrote then.  Right – well, so will I revisit something I helped write, back in 2000, after reading that Mbeki had written to Bill Clinton to dispute conventional ideas on HIV/AIDS.

Nature 405: 273, 2000

AIDS dissidents aren’t victims – but the people their ideas kill will be

Sir – As South African scientists working in the field of HIV/AIDS vaccine research, we are extremely concerned about the letter president Thabo Mbeki recently sent other heads of state (Nature 404, 911; 2000). As an individual Mr Mbeki is entitled to his point of view, but as our head of state we feel he risks binding our country to an untenable position.

We would like Mr Mbeki and others to consider how the mass of South Africans would react if he were to give a sympathetic ear to unrepentant proponents of apartheid. His willingness to be influenced by people with no credibility causes as much anguish to those of us working to combat HIV/AIDS.

The simple facts, as shown by a huge volume of scientific and medical research, are that HIV causes AIDS; that in Africa (as in other developing regions) the disease is mainly spread heterosexually; and that AIDS kills poor people in disproportionate numbers. We most emphatically do not need to revisit the debate on the causation of AIDS. What we do urgently need is to educate, train and medicate, to save lives.”

This is germane, because Mbeki has the gall to go back to his Castro Hlongwane crap at the end of his latest letter, and say:

“Beneath the heartening facts about decreased mortality and increasing life expectancy, and many other undoubted health advances, lie unacceptable disparities in wealth. The gaps between rich and poor, between one population group and another, between ages and between sexes, are widening. For most people in the world today every step of life, from infancy to old age, is taken under the twin shadows of poverty and inequity, and under the double burden of suffering and disease.”

“Castro Hlongwane…” says: “Given that our minds on this matter (of HIV and AIDS) have become thoroughly clogged by the information communicated by the omnipotent apparatus, a miracle will have to be achieved to get all our people to use their brains, rather than perish on emotional responses based on greatly heightened levels of fear.”

Really, Thabo??  You’re going to harp on about poverty, again?  Oh, and the “omnipotent apparatus” that is Western Pharma, and of course US capitalism?

Please do us a favour, Comrade: go back to your pipe, and your old friends Johnny and Jack, and stop trying to justify the indefensible.  And I will close with something I wrote for the Mail & Guardian on March 1st back in 2002:

“It does not seem to matter what happens in our country; it does not matter how many people try to engage the slippery python that is the president’s policy and thinking on HIV/Aids; it does not seem to matter how many people die of Aids, and how many babies are needlessly born with HIV – there remains the stubbornness and wilful failure to comprehend that is leading us into disaster. Mr Mbeki, you make an idiot of yourself, and fools of us all for putting up with your views. Leave health policy alone, or resign. Please.

Ed Rybicki, Pinelands”

I see no reason to change my views either, Comrade.