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Claimed micro-encephaly 'conspiracy theories' are rooted in science
Article awaiting publication on or before 9th March
How do you know when you have published something important? By the number of Shares, Likes and Tweets? By how many people tell you what a wonderful article you have authored? Or by the volume of vitriolic attack you suffer?
If the latter, then two recent articles on The Ecologist must have been very important indeed. Though, to be honest, they did pretty well on the social media side too. These are first, my own article titled 'Pandora's box: how GM mosquitos could have caused Brazil's microcephaly disaster', and second, the article by Claire Robinson of GMWatch titled 'Argentine and Brazilian doctors suspect mosquito insecticide as cause of microcephaly'.
The articles have been attacked in the Guardian, by the Washington Post food correspondent, in the New York Times, Grist, in New Scientist's Feedback column (twice), and doubtless other publications I have missed. The British environmental journalist George Monbiot has also tweeted against them and denounced them in correspondence.
The criticisms are severalfold but most accuse The Ecologist of peddling "conspiracy theories". In fact, none of these articles has suggested any conspiracy. It now seems that any idea that departs from the canonical mainstream is, by assertion if nothing else, described by that now portmanteau epithet.
Many of the critics also appear blissfully ignorant of what it is they are criticising, as Robinson points out in her subsequent article 'Zika, microcephaly, and pesticides: half-truths, hysteria, and vested interests'. Numerous critics appear utterly ignorant even of the difference between the Zika virus and the microcephapy which it is suspected to cause.
But some of the criticisms do have a genuine scientific basis - and it these, as opposed to the merely ignorant and stupid, that I propose to consider here.
DNA versus RNA
My article on Zika and Oxitec's transgenic mosquitos raises the possibility - stating it only as a possiblity, not asserting it as fact - that the transposons ('jumping DNA' sequences) used in the mosquitos could have transferred into the genetic material of the Zika virus, so introducing its capacity to cause the birth defects.
The idea is of course speculative. A reader who took the trouble of analysing different versions of the entire Zika virus also established pretty conclusively that what was proposed did not, in fact take place. But I did not, as New Scientist's Feedback page suggested, feel "chastised" as a consequence. The nature of scientific progress is that hypotheses are advanced, and some are falsified.
There is no shame in proposing an idea that turns out to be wrong, provided the idea is scientifically grounded. On the contrary, it is most useful to do so as in the process, the search for the truth is narrowed down and focused.
Feedback also stated that the 'piggyBac' transposon is "made of double-stranded DNA rather than single-stranded RNA like the virus, meaning the proposed combination would have made for a Nobel prizeworthy discovery." A similar claim was made in the Guardian by Mark Lynas: "the mosquitoes couldn't inadvertently insert additional DNA into the Zika virus genome, because Zika has no DNA - it's an RNA virus. That's a different type of molecule."
But it ain't necessarily so. As Kenneth Stedman pointed out in his 2015 paper: "genetic exchange across viral kingdoms, for instance between nonretroviral RNA viruses or ssDNA viruses and host genomes or between RNA and DNA viruses, was previously thought to be practically nonexistent. However, there is now growing evidence for both RNA and ssDNA viruses recombining with host dsDNA genomes and, more surprisingly, RNA virus genes recombining with ssDNA virus genomes."
So there is no 'hard barrier' of the kind proposed by Lynas and Feedback. There is, rather, a high degree of mutability between DNA and RNA genetic material, including double stranded DNA and single stranded RNA. And this genetic material can transfer between viruses and the genetic material of their hosts. Sadly for Stedman, I do not believe that he won a Nobel prize for his discovery.
Where's the transposase?
Another objection made is that the transposons are effectively contained within the mosquito genome due to the lack of the appropriate transposase enzyme needed for it to transfer. But once again, examination of the literature shows that the real situation is very diferent.
As Rubin et al show, the 'mariner' transposons they studied "are apparently horizontally transmitted among diverse eukaryotes and can also transpose in vitro in the absence of added cofactors." Rubin's team also created 'minitransposons' flanked by antiobiotic markers and found that "these elements can efficiently transpose after expression of transposase from an appropriate bacterial promoter."
As geneticist Mae Wan Ho wrote of these findings in 2001, "The experiment shows that the transposon can be stripped down to the bare minimum of the flanking repeats, and it can still jump into genomes. The reason, as mentioned earlier, is that the transposase function can be supplied by a 'helper' transposon. Such helper transposons are ubiquitous. So, it would seem obvious that integrated transposon vectors may easily jump out again, to another site in the same genome, or to the genome of unrelated species."
She then goes on to discuss the piggyBac transposon - as employed by Oxitec: "There are already signs of that in the transposon, piggyBac, used in the GM bollworms to be released by the USDA this summer. The piggyBac transposon was discovered in cell cultures of the moth Trichopulsia, the cabbage looper, where it caused high rates of mutations in the baculovirus infecting the cells by jumping into its genes." (References in MWH article.)
She adds that the transposon "was later found to be active in a wide range of species, including the fruitfly Drosophila, the mosquito transmitting yellow fever, Aedes aegypti, the medfly, Ceratitis capitata, and the original host, the cabbage looper. The piggyBac vector gave high frequencies of transpositions, 37 times higher than mariner and nearly four times higher than Hirmar."
A further 2010 paper by Aziz et al, titled 'Transposases are the most abundant, most ubiquitous genes in nature' emphasises these points. "Genes, like organisms, struggle for existence, and the most successful genes persist and widely disseminate in nature. ...
"Here, we analyzed 10 million protein-encoding genes and gene tags in sequenced bacterial, archaeal, eukaryotic and viral genomes and metagenomes, and our analysis demonstrates that genes encoding transposases are the most prevalent genes in nature. ...
"Their mobile nature not only promotes dissemination of transposable elements within and between genomes but also leads to mutations and rearrangements that can accelerate biological diversification and - consequently - evolution. By securing their own replication and dissemination, transposases guarantee to thrive so long as nucleic acid-based life forms exist."
There is, therefore, nothing for me to feel 'chastised' about as a result of the suggestion that I advanced. The specific sequence of steps I outlined on this occasion appears not to have taken place in the case of Oxitec's GM mosquitos and the Zika virus, however there is no hard barrier to similar events having taken place, or taking place in future.
Indeed there is a considerable body of science that demonstrates the mutability and transferability of genetic material in the broad manner that I set out. There are very good reasons to be extremely precautionary about taking similar risks in the future.
If anyone should be feeling truly chastised in all this is above all Mark Lynas for his astonishing combination of scientific ignorance and gratuitous insult aimed at Mae Wan Ho. Here are his words:
"Tickell quoted an 'expert', Dr Mae Wan Ho, fresh with a new theory. Dr Ho proposed that the DNA sequence used in genetically engineering Oxitec's mosquitoes might somehow have jumped into the Zika virus and caused it to mutate into a more pathogenic form. Sounds plausible? The article seems impressively technical, quoting Dr Ho waxing lyrical on 'integrated transposon vectors' and other sciencey-sounding language.
"The Ecologist failed to note Dr Ho's real credentials, however. She is a decades-long anti-GMO activist who today divides her time between pushing anti-vaccine misinformation about MMR, bizarre ideas about about mobile phones causing cancer, and pseudo-scientific woo about homeopathy and 'holistic' Chinese medicine.
"Plus she made an elementary mistake: the mosquitoes couldn't inadvertently insert additional DNA into the Zika virus genome, because Zika has no DNA - it's an RNA virus. That's a different type of molecule, Dr Ho. Moreover, the DNA sequence in question is 8400 bases long, almost as long as the entire Zika virus genome. Dr Ho's purported mechanism is a biological impossibility and the Ecologist story is science fiction."
The Emperor of 'science' has no clothes
So here is is Lynas accusing Mae Wan Ho of being a complete phoney whose discourse is riddled with elementary scientific errors. Only in fact, as we saw above, her statements are all based on peer-reviewed scienctific publications. Lynas has not cited even a single scientific reference he can hide behind.
By contrast, as Wikipedia records, "Ho received a Ph. D. in Biochemistry in 1967 from Hong Kong University, was Postdoctoral Fellow in Biochemical Genetics, University of California, San Diego, from 1968 to 1972, Senior Research Fellow in Queen Elizabeth College, Lecturer in Genetics (from 1976) and Reader in Biology (from 1985) in the Open University, and since retiring in June 2000 Visiting Professor of Biophysics in Catania University, Sicily."
And what of Lynas's scientific credentials? His website informs us that he is a "a member of the advisory board of the science advocacy group Sense About Science, and campaigns on behalf of various pro-science causes." He also has numerous institutional affiliations, with for example Cornell and Oxford Universities.
But in terms of actual science, we are faced with a big black hole. He has a degree from Edinburgh University in ... History & Politics. Has he even got an A-level in a science subject? He's not letting on. And yet he has the impudence to attack real, distinguished scientists as 'sciencey' conspiracy theorists!
What can be said of him is that adherence to mainstream narratives of science, technology and the role of corporations in society have enormously endeared him to powers-that-be - in academia, mainstream media, the Gates Foundation, and governmental circles.
His ever-reliable propoundments in favour of GMOs, nuclear power and other abominations - all couched as being somehow 'scientific' are just what his worldly sponsors want to hear. And the fact that his scientific credentials are absolutely zero is a topic easily circumvented by pliant journalists.
Special qualities of flaviviruses
However there is one place where Lynas could have scored a hit, if only he was half as expert in science as he likes to believe he is. It so happens
There are a quite small, but not insignificant, number of examples of partial genomes of RNA and single-stranded DNA viruses that have been incorporated into cellular DNA genomes and even fewer examples of a gene from a purely RNA virus which appears to have been acquired by an ssDNA virus (which we originally discovered, see Diemer and Stedman, 2012). However, there are NO examples of the inverse, that is to say purely RNA viruses or ssDNA viruses picking up genes from host genomes. This is not from want of trying, there have been extensive sequencing efforts on purely RNA viruses, including Zika, and none of these viruses have been found to contain cellular genes.
There are 2 reasons for the unidirectionality, purely RNA viruses, such as the flaviviruses, of which Zika is a member, have RNA genomes that make copies of their genome from RNA, there is no DNA intermediate and they use a special virus-specific RNA polymerase to do this. The second is that most ssRNA viruses (and flaviviruses in particular) are very constrained in terms of how much RNA they can hold, so they are extremely unlikely to pick up any "extra" genes without causing the virus to be non-viable. On the other hand, cellular genomes are not under such constraints and can acquire RNA and ssDNA virus genes by fascinating mechanisms (some of which are outlined in my Annual Reviews of Virology paper).
As such, the hypothesis that the GM mosquitos may be implicated in the microcephaly cannot be ruled out at this stage. First, the self-killing effect of the transposon in the mosquitos is suppressed in the presence of the antibiotic tetracycline, widely used in intensive livestock farming and on humans, providing a mechanism for the transposons to survive and mutate in wild Aedes aegyptii populations.
Second, the transposon (in whole or in part) may therefore have inserted itself into other viruses and bacteria that inhabit the mosquitoes. It may also be mutagenic on such organisms, and on the mosquitoes themselves. Third, as Mae Wan Ho suggested to me, "the 'killing gene product' from the transgenic mosquito may have been transferred into pregnant women, thereby causing microcephaly."
To draw attention to the potential dangers is not, as one well-known critic has suggested, either "irresponsible" or "the equivalent of shouting fire in a crowded theatre." The science strongly suggests the need for for more research into these possibilities, and for considerable caution over additional releases of Oxitec's transgenic mosquitos either as a response to the microcephaly outbreak or for other purposes.
And the article is most definitely not, as Feedback went on to claim in a subsequent note (27/02/16), "roundly debunked". However this second item mainly concerns another article published on The Ecologist by Claire Robinson of GMWatch, which sets out another possible cause of the microcephaly, namely the contamination of drinking water with insecticides added to water storage tanks.
Feedback states: "Pyriproxyfen, an insecticide that inhibits the growth of mosquito larvae, has been added to water tanks in Brazil since 2014. There is no evidence to suggest it causes birth defects - and plenty to demonstrate that it doesn't, having been thoroughly tested in animals - but that didn't stop The Ecologist republishing the claims."
In the course of editing the article for publication, I in fact added words to precisely this effect: "The chemical has a relatively low risk profile as shown by its WHO listing (http://www.who.int/whopes/quality/en/pyriproxyfen_eval_specs_WHO_jul2006.pdf), with low acute toxicity. Tests carried out in a variety of animals by Sumitomo found that it was not a teratogen (did not cause birth defects) in the mammals it was tested on."
But as I also noted, "this cannot be taken as a completely reliable indicator of its effects in humans - especially in the face of opposing evidence." We know that, for example, thalidomide was tested on rats and received the 'all clear'. As Robert Brent wrote in 1964 (http://www.sciencedirect.com/science/article/pii/S0022347664806260), "Thalidomide was administered to pregnant rats by various routes without significantly interfering with embryonic development. ... Until drug testing becomes somewhat more sophisticated, our most reliable method of protecting the public from all the harmful effects of drugs is through strict clinical surveillance programs."
So we have to ask: what 'strict clinical surveillance programs' have been undertaken by its manufacturer, Sumitomo, or Brazilian public health officials who have knowingly and deliberately exposed pregnant women to pyriproxyfen? As far as I am aware, the answer is: none whatsoever. If they had, after all, they would have been able to respond to the huge public concern in Brazil over this issue, which has led the state of Rio Grande do Sul to ban this use of pyriproxyfen. As it is, Sumitomo has released no more than bland assurances (http://sumivector.com/news/sumitomo-chemical%E2%80%99s-response-to-recent-articles-pertaining-to-pyriproxyfen-in-the-brazilian) which refer only to animal studies.
It should be noted that pyriproxyfen works as a growth inhibitor of mosquito larvae, altering the development process from larva to pupa to adult, thus generating malformations in developing mosquitoes and killing or disabling them. Even though the pathway it targets is not found in mammals, the idea that it may be pharmacologically active in developing human embryos is somewhat short of extraordinary - and has certainly not been disproved. The 'strict clinical surveillance programs' that surely should have been carried out before exposing mass populations to the chemical, including pregnant women, appear never to have been instituted.
There has nonetheless been a substantial backlash against this cautiously worded article. It is notable that considerable commercial interests are at stake here. If pyriproxyfen is deployed as a global 'solution' to Aedes aegyptii and the diseases it carries, Zika and Dengue fever, there billions of pounds, dollars or euros to be made. Conversely, if it is proven that pyriproxyfen, or any of the other insecticides deployed in the 'fight against Zika', are teratogenic in humans and responsible for the microencephaly, manufacturers and governments could be held liable for billions of pounds, dollars or euros in compensation claims. Similar considerations attach to Oxitec's transgenic mosquitos.
This leaves me wondering why journalists like George Monbiot (https://twitter.com/georgemonbiot/status/695264851485130752) and Mark Lynas (http://www.marklynas.org/2016/02/another-day-another-zika-conspiracy-theory/) are deploying their valuable time to attack The Ecologist for promulgating "absurd conspiracy theories and other such nonsense" when the suggestions made are, in fact, entirely reasonable and scientifically grounded. All the more so as The Ecologist has, in fact, never suggested any 'conspiracy' whatsoever in this context.
And surely there is a much bigger story here for investigative journalists to follow: that of huge biotech and chemicals companies, working with governments, deliberately exposing entire populations to agents whose oft-claimed safety is considerably less certain than claimed, and which might be responsible for a major public health disaster whose actual causes, as even WHO admits (http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika/en/), remain unproven to this day.
Oliver Tickell, 25/02/16.
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