Posts Tagged ‘contamination’

GMOs: poisons that will kill our children, or harmless foods?

29 October, 2013

I think I hung my colours out long ago in this “controversy”, but let us just be clear:

I DON’T BELIEVE ANY OF THE GMOs CURRENTLY BEING FARMED WORLDWIDE POSE ANY THREAT TO HUMANS OR STOCK ANIMALS AT ALL.  NONE!  NOR DO MOST BIOLOGICAL SCIENTISTS WHO ACTUALLY UNDERSTAND WHAT GENETIC MANIPULATION OF PLANTS ENTAILS.

Is that clear enough?  No ambiguity there?  Good!  Because the people who have taken poor Fair Lady magazine to task recently, mainly on their Facebook page, for daring to publish an article saying the same thing, would have you believe otherwise.  By relentless recycling of discredited animal feeding studies, reiteration of untruths, canards and plain lies, and by personal attacks on anyone expressing an alternate view.

Title page of the article

Title page of the article

I don’t think that Fair Lady will complain if I reproduce the title page, because I think their article is a reasoned, well written and factual exploration of the topic – which is a LOT more than I can say for most of the comments about the article.  Which includes gems like this:

“Oh dear Fairlady Magazine has made a BIG mistake!!!! Writing an article like this could put them out of business. I will never buy a Fairlady Magazine again and neither will any of my family. Stick to fashion Fairlady. Let Farmers Weekly publish an articles on GMO’s!!!! GMO’s are killing people. It’s not an exaggeration. It is proven, published, peer-reviewed fact. How many people do you know with cancer? Can you count on one hand or two. Ask yourself why. Maybe you could ask well-Informed People who are Fully Aware of the Irreversible Damage unleashed by Toxic GMOs on Earth.”

Now the problems that I have with the kinds of attacks on GMOs that are exemplified by these responses, are the following: these are the assertions that

  1. EVERYTHING is Monsanto’s fault
  2. ALL GMOs are toxic / poisonous
  3. There is ample evidence of harm to both animals and humans

All three of these straw men are, of course, rich in taurine excreta.  In the first place, while Monsanto may well have started the ball rolling on a big scale, and owns patents and seed rights on much of the early and simple one-trait GMOs, they do NOT own everything, and are NOT responsible for many of the recent developments still coming down the developmental pipeline – which are considerably more sophisticated than the ubiquitous herbicide-resistant or Bt-producing maize or cotton.  These would include plants resistant to various viruses, bacteria and fungi, plants engineered for higher nutrient / vitamin content (eg: Golden Rice and golden bananas), and drought- and salt-tolerant plants.

As for toxicity, NO GMO can be released if there is convincing evidence of toxicity in animal feeding trials, which HAVE to be conducted for each new “event”, or novel GMO.  I have sat on panels in SA which have assessed applications by seed companies to grow / produce GM crops, and I can tell you that this is a major feature of any application.  Where non-expert people often get confused is the fact that certain crop plants have been engineered to make insect-specific toxins normally produced by the bacterium Bacillus thuringiensis.  These are collectively known as “Bt toxins”, and the ones used as insecticides are specific for narrow ranges of related insects, and most often for lepidopterans – which include moths and butterflies.  Now the larvae of particularly certain species of moths are major agricultural pests, and include agents such as maize stalk borer and the cotton bollworm – and from Wikipedia:

“Spores and crystalline insecticidal proteins produced by B. thuringiensis have been used to control insect pests since the 1920s and are often applied as liquid sprays”.

That’s right: crystalline protein masses extracted from live bacteria and live spores of bacteria used to be sprayed around as pest-control agents.  Everywhere!  Moreover, from Wikipedia again,

“Because of their specificity, these pesticides are regarded as environmentally friendly, with little or no effect on humanswildlifepollinators, and most other beneficial insects and are used in Organic farming“.

Yes, really: actual Bt toxin, and actual spores that can develop into live bacteria, can be used in organic farming.  Now why would anyone have a problem with a technology that LIMITS exposure of the environment to a bacterial toxin, and most especially, to live bacteria, by containing the protein within the plant tissues?  Moreover, the amount of Bt in the edible seeds of maize is minimal, and people don’t eat cotton – so we are left with possible effects on wildlife, and cattle which eat the green parts of the plants.  And no-one has ever  shown any deleterious effects of Bt in GM plants on non-target organisms.  Oh, there was the Pusztai report, which claimed to have shown that snowdrop lectin-containing transgenic potatoes were toxic to mice – but this elicited the following comment:

“The [British] government’s Advisory Committee on Novel Foods and Processes(ACNFP) has dismissed Dr Pusztai’s findings as inconclusive and irrelevant due to serious doubts concerning the design of the study. The particular type of potatoes on which Dr Pusztai conducted his experiments would never have been approved for food use. Indeed, the ACNFP stated that had an application been submitted on the basis of the data collated from this flawed study, it would have undoubtedly been rejected”

A nice exploration of the pervasive effects of bad publicity following publication of bad science was published recently: this was “When bad science makes good headlines: Bt maize and regulatory bans“, in Nature Biotechnology.  These authors state that

“Numerous laboratory toxicity studies and field experiments, as well as years of field observations in countries where Bt maize is cultivated, have provided evidence that the Cry1Ab protein expressed in Bt maize does not cause adverse effects on arthropods outside the order Lepidoptera (butterflies and moths), the group that contains the target pests. Supporting data have been analyzed in reviews and meta-analyses”

Another point of contention is herbicide-resistant plants, which again, have not convincingly been shown to be toxic.  I say convincingly, because anti-GMO activist will immediately quote “the Seralini study” which purportedly showed deleterious effects on lab rats fed transgenic maize producing a protein which detoxifies the herbicide glyphosate as well as the herbicide itself – to which I reply by inviting you to read this rather damning report by the European Food Safety Authority, which opens with the following statement:

“Serious defects in the design and methodology of a paper by Séralini et al. mean it does not meet acceptable scientific standards and there is no need to re-examine previous safety evaluations of genetically modified maize NK603″

Now I will remind everyone that this is an agency which is NOT in Monsanto’s pocket – or anyone else’s – and which upholds high standards in safeguarding the general public.  As do the US Department of Agriculture (USDA) and the Food & Drug Administration of the USA, which also have no problems with GMOs (FDA statement; USDA information).  Here is a another comprehensive refutation of the “evidence of toxicity” of glyphosate-resistant soybeans, an unpublished study that is widely quoted by anti-GM lobby.

As for “ample evidence of harm” – I can only refer you to what we biotechnologists would regard as an authoritative source, which is the journal Nature Biotechnology.  In a recent article on GMOs entitled “How safe does transgenic food need to be?” by Laura DeFrancesco, the author asks the question:

“Why, after transgenic products have been in the human food chain for more than a decade without overt ill effects, do these doubts persist? And will it ever be possible to gather sufficient evidence to ameliorate the concerns of skeptics and the public at large that these products are as safe as any other foodstuff?”

Further on, she says:

“Critics and proponents of genetically modified organisms (GMOs) alike agree that genetically modified foods have failed to produce any untoward health effects, and that the risk to human health from foods contaminated with pathogens is far greater than from GMOs” [my emphasis]

I don’t think I need to belabour the point further: I am hopelessly compromised, in the eyes of some of the more rabid activists, by being a biotechnologist at all, and especially – Gasp!! – BECAUSE MY LAB MAKES GMOs!!!  However, if that makes me more amenable to believe actual evidence-based findings, rather than unsubstantiated media hype, then so be it.

DNA Preparation Tubes Contaminated with Novel ssDNA Virus

21 September, 2013

See on Scoop.itVirology News

A novel virus thought to have come from human samples appears to have been derived from seawater during the manufacture of tubes used to extract DNA.  

Ed Rybicki‘s insight:

I have a problem with the original report, in J Virol (http://jvi.asm.org/content/early/2013/09/05/JVI.02323-13.abstract?related-urls=yes&legid=jvi;JVI.02323-13v1): not that they discovered it, because that was done well.  However, they essentially REdiscovered something that was ±100% identical to a virus already sequenced and named by Chinese researchers – who did not use the Qiagen kits, apparently – and then gave it a new name!

 

Sorry, that is simply bad practice!  It also smacks of scientific imperialism of a sort that characterised early discovery work on HTLVs and on HIV, when US researchers calmly treated earlier characterisations as if they had never happened.

 

There is another leap that I do not think is justified: the authors claim that

 

"Analysis of environmental metagenome libraries detected PHV sequences in coastal marine waters of North America, suggesting that a potential association between PHV and diatoms (algae) that generate the silica matrix used in the spin columns may have resulted in inadvertent viral contamination during manufacture".

Really?  On the basis of presence of a sequence in a metagenomic trawl?  No resampling with specific primers on a fresh sample?   And surely the generation of the silica matrix is done under conditions that would totally destroy adventitiious DNA?

So – an interesting paper, and a valuable notification (although it might have been nicer if they’d shared their findings informally, to save other people like our Virology Diagnostics lab time and money).  But flawed, in my opinion.

See on www.the-scientist.com

PLOS ONE: Tobacco Mosaic Virus in the Lungs of Mice following Intra-Tracheal Inoculation

13 February, 2013

See on Scoop.itVirology News

“Plant viruses are generally considered incapable of infecting vertebrates. Accordingly, they are not considered harmful for humans. However, a few studies questioned the certainty of this paradigm. Tobacco mosaic virus (TMV) RNA has been detected in human samples and TMV RNA translation has been described in animal cells. We sought to determine if TMV is detectable, persists, and remains viable in the lung tissues of mice following intratracheal inoculation, and we attempted to inoculate mouse macrophages with TMV. In the animal model, mice were intratracheally inoculated with 1011 viral particles and were sacrificed at different time points. The virus was detected in the mouse lungs using immunohistochemistry, electron microscopy, real-time RT-PCR and sequencing, and its viability was studied with an infectivity assay on plants. In the cellular model, the culture medium of murine bone marrow derived macrophages (BMDM) was inoculated with different concentrations of TMV, and the virus was detected with real-time RT-PCR and immunofluorescence. In addition, anti-TMV antibodies were detected in mouse sera with ELISA. We showed that infectious TMV could enter and persist in mouse lungs via the intratracheal route. Over 14 days, the TMV RNA level decreased by 5 log10 copies/ml in the mouse lungs and by 3.5 log10 in macrophages recovered from bronchoalveolar lavage. TMV was localized to lung tissue, and its infectivity was observed on plants until 3 days after inoculation. In addition, anti-TMV antibody seroconversions were observed in the sera from mice 7 days after inoculation. In the cellular model, we observed that TMV persisted over 15 days after inoculation and it was visualized in the cytoplasm of the BMDM. This work shows that a plant virus, Tobacco mosaic virus, could persist and enter in cells in mammals, which raises questions about the potential interactions between TMV and human hosts.”

Ed Rybicki‘s insight:

Interesting paper!  Which proves…which proves…which proves TMV is seriously resistant to degradation in animals and in mammalian cells; that it can enter macrophages; and that it…what?  What, exactly, are the “…questions about the possible interactions…”?  What would TMV do in mammalian cells?  Yes, it might be uncoated and be translated; it is far less likely that it MIGHT be able to replicate its RNA – and then?  While it can apparently be taken up quite efficiently by macrophages – a property which, incidentally, has led to its being trialled as an RNA vaccine delivery system – this is a dead end, and one that is quite normal for particles of any kind being introduced into mammals.

Which is something that happens every day, as we and our cousin mammals eat: it has been shown elsewhere that animals are actually quite good spreaders of plant viruses, some of which – like TMV and the even tougher Cauliflower mosaic virus – pass right through at high survival rates, and remain infectious.  We will all probably have eaten many grams of various viruses in our lives, and derived nothing more than nutrition from them.

I also remember, even though it was very late at night, 31 years ago, and in a bar in Banff in Canada, a conversation with one Richard Zeyen.  He told me they had used ELISA to test everyone in their lab for antibodies for TMV, seeing as they worked with it, and had newly developed a test.  And everyone was immune – presumably, to aerosolised TMV that had been breathed in or otherwise ingested.  Proving…that oral vaccines based on TMV could work, and that most of us are probably immune to all sorts of viruses that don’t replicate in us – and nothing more!

Including, in the case of many people in the Eastern Cape Province of South Africa, sampled by one Don Hendry via the local blood bank, to a virus of Pine Emperor moths – because it multiples to such high levels in its host that anyone walking in the pine forests was bound to be exposed via the environment.

So this is an interesting paper – and no more.  It will, of course, lead to alarmist articles and blog posts, and people calling out for urgent surveillance of food, in which people will find many viruses.  And so what?  They have been with us for as long as we have been eating plant-derived food, and have NEVER been associated with any disease, transmissible or otherwise – so my best advice is that we ignore them.

See on www.plosone.org

Doctor, there’s a…pig virus in my vaccine??

6 June, 2010

rotavirus particle

I have for some time taught my third year students about how one must weigh relative risk vs. relative benefit when it comes to vaccination – with the Wyeth live rotavirus vaccine that was withdrawn in 2000 or so due to isolated incidents of intussusception (=telescoping of the bowel) as an object example.

Consider: the vaccine MAY have caused a couple of incidents (which granted, were serious) – but on the whole was protective, and well tolerated.  The publication referred to has this as the relative risk:

“…epidemiologic evidence supports a causal relationship, with a population attributable risk of ~1 per 10 000 (range of 1 in 5000 to 1 in 12 000) vaccine recipients.”

While this may be an unacceptable risk in a North American community – which is where it was tested, where children mostly just get sick from rotavirus infection – what about in a developing country, where the risk of an infant dying from rotavirus diarrhoea is far higher than 1 / 10 000?  Indeed, the same article says:

“Because perceptions of vaccine safety derive from the relative disease burdens of the illness prevented and adverse events induced, the acceptance of rare adverse events may vary substantially in different settings. [ my emphasis]“

Yes – like the vaccine may well have done a great deal of good, and very little harm, in a developing country setting where rehydration therapy is not the norm.  But it was pulled, and the world had to wait for Merck’s Rotateq pentavalent live vaccine and GSK’s Rotarix tetravalent live vaccine, YEARS later, and probably a lot of children died that may not have needed to.

I note that the Merck product has this as a warning, too:

“In post-marketing experience, intussusception (including death) and Kawasaki disease have been reported in infants who have received RotaTeq”.

So the vaccine has the same risk profile as Wyeth’s – yet it has been widely distributed, and is apparently highly effective – as is Rotarix.  In fact, in 2009 the WHO issued a recommendation “…that health authorities in all nations routinely vaccinate young children against rotavirus…”.

And then…news that must have made many a heart sink, in March 2010:

Pig virus contamination halts GSK Rotarix use

“GlaxoSmithKline’s oral rotavirus vaccine Rotarix has been temporarily shelved in the U.S. due to a pig-virus contamination. Researchers stumbled on DNA from porcine circovirus type 1–believed nonthreatening to humans–while using new molecular detection techniques. More work is being done to determine whether the whole virus or just DNA pieces are present.

Additional testing has confirmed presence of the matter in the cell bank and seed from which the vaccine is derived, in addition to the vaccine itself. So the vaccine has been contaminated since its early stages of development.”

The finding of the porcine circovirus type 1 (PCV-1) DNA in the vaccine was due to what seems to have been publication of an academic investigation in February 2010 of “Viral Nucleic Acids in Live-Attenuated Vaccines” by Eri L Delwart and team, mainly from Blood Systems Research Institute and University of California, San Francisco.  They used deep sequencing and microbial array technology to:

“…examine eight live-attenuated viral vaccines. Viral nucleic acids in trivalent oral poliovirus (OPV), rubella, measles, yellow fever, varicella-zoster, multivalent measles/mumps/rubella, and two rotavirus live vaccines were partially purified, randomly amplified, and pyrosequenced. Over half a million sequence reads were generated covering from 20 to 99% of the attenuated viral genomes at depths reaching up to 8,000 reads per nucleotides.”

And they found:

“Mutations and minority variants, relative to vaccine strains, not known to affect attenuation were detected in OPV, mumps virus, and varicella-zoster virus. The anticipated detection of endogenous retroviral sequences from the producer avian and primate cells was confirmed. Avian leukosis virus (ALV), previously shown to be noninfectious for humans, was present as RNA in viral particles [!!], while simian retrovirus (SRV) was present as genetically defective DNA.”

Whooooo…possibly live animal retroviruses in human vaccines??  But most importantly for our purposes:

Rotarix, an orally administered rotavirus vaccine, contained porcine circovirus-1 (PCV1), a highly prevalent nonpathogenic pig virus, which has not been shown to be infectious in humans. Hybridization of vaccine nucleic acids to a panmicrobial microarray confirmed the presence of endogenous retroviral and PCV1 nucleic acids.”

I don’t know about you, but I’d be more worried about the retroviruses!  The authors concluded [my emphases in bold and red]:

“Given that live-attenuated viral vaccines are safe, effective, and relatively inexpensive, their use against human and animal pathogens should be encouraged. The application of high-throughput sequencing and microarrays provides effective means to interrogate current and future vaccines for genetic variants of the attenuated viruses and the presence of adventitious viruses. The wide range of sequences detectable by these methods (endogenous retroviruses, bacterial and other nucleic acids whose taxonomic origin cannot be determined, and adventitious viruses, such as PCV1) is an expected outcome of closer scrutiny to the nucleic acids present in vaccines and not necessarily a reflection of unsafe products. In view of the demonstrated benefit and safety of Rotarix, the >implications (if any) for current immunization policies of the detection of PCV1 DNA of unknown infectivity for humans need to be carefully considered.”

So they find all these bits of adventitious nucleic acids in a live human vaccine, then tell us it’s all right?  They go to say, however:

“As an added note, recent testing by GSK indicates that PCV1 was also present in the working cell bank and viral seed used for the generation of Rotarix used in the extensive clinical trials that demonstrated the safety and efficacy of this vaccine. These trials indicate a lack of detectable pathogenic effects from PCV1 DNA on vaccinees.”

So: a clinical trial in retrospect, then??  Interesting idea, that – it’s OK because they inadvertently tested it already and no obvious harm came of it!  Mind you, the same thing happened with SV40 in poliovirus vaccines over a lot longer period and on a much larger scale – and while the jury is still out on long-term effects, it appears as though there were none.

The first outcome of the finding, though, was that the FDA recommended in March that use of Rotarix be suspended, pending further investigations.

The same GSK press release reminds us that:

“Rotavirus is the leading cause of severe gastroenteritis among children below five years of age and it is estimated that more than half a million children die of rotavirus gastroenteritis each year – a child a minute [my bold - Ed]. It is predicted that rotavirus vaccination could prevent more than 2 million rotavirus deaths over the next decade. The continued availability of rotavirus vaccines around the world remains critical from a public health perspective to protect children from rotavirus disease. “

Cementing the risk/benefit argument very firmly and pre-emptively, then!

The next development was that Merck’s Rotateq, initially thought to be free of PCVs, was found to contain both PCV-1 AND PCV-2 DNA.  From their press release:

“In March 2010, an independent research team and the FDA tested for PCV DNA in rotavirus vaccines; at that time, PCV DNA was not detected in ROTATEQ by the assays that were used initially. Subsequently, Merck initiated PCV testing of ROTATEQ using highly sensitive assays. Merck’s testing detected low levels of DNA from PCV1 and PCV2 in ROTATEQ. Merck immediately shared these results with the FDA and other regulatory agencies.”

Alarming at first sight – but a variety of someones had done their relative risk calculations, and by mid-May, both vaccines had been cleared by the FDA – much to Merck and GSK stockholder relief, one imagines.

“The agency’s decision follows a May 7 recommendation from an FDA advisory panel, which said the PCV contamination didn’t appear to be harmful to humans and the vaccines’ benefits outweighed any “theoretical” risk the products might pose.

In announcing its decision, FDA said that both vaccines have strong safety records, including clinical trials of the vaccines in tens of thousands of patients, plus clinical experience with their administration in millions more. PCV isn’t known to cause illness in humans, whereas the rotavirus these vaccines ward off can cause severe illness and even death.”

All in all, what appears to be a sensible, logical decision, based on evidence – whether collected in retrospect or not – and common sense.  After all, as GSK points out in a press release,

“[PCV] is found in everyday meat products and is frequently eaten with no resulting disease or illness.”

Like plant viruses in vegetables, retroviruses in undercooked chicken and other meat, and a myriad other viruses and bacteria that live in, on, and with us – you really can’t keep away from everything.

But there’s still a good case to be made for killed vaccines….

Plant therapy creeping in….

8 September, 2009

The August issue of Nature Biotechnology has a very interesting snippet of news – from two points of view. From a strict virology point of view, it is interesting that commercial production of a therapeutic enzyme in an industrial plant can be shut down because of infection of their mammalian cell line with a contaminating mammalian virus.

From the second point of view…well, our lab has a very strong interest in producing recombinant proteins (and especially candidate vaccine proteins) in plants – and here is a story showing just why plants may be a really good alternative means of production for pharmaceuticals.  First, the story:

Nature Biotechnology 27, 681 (2009) doi:10.1038/nbt0809-681a
Virus stalls Genzyme plant by Victor Bethencourt

Genzyme of Cambridge, Massachusetts, faces millions in lost revenue from its top-selling specialty drugs Cerezyme and Fabrazyme as result of a viral contamination at its Allston, Massachusetts plant. The company has announced that it will temporarily shut down the facility owing to a bioreactor contamination with Vesivirus 2117 [my emphasis - Ed], which does not cause human infections, but impairs growth of the biologics-producing Chinese hamster ovary (CHO) cells. It reportedly originated from tainted nutrient medium and belongs to the same strain that caused delays at the Allston site and its European biologics plant in Belgium last year. Genzyme anticipates supply constraints of Cerezyme (imiglucerase), a treatment for Gaucher disease, and Fabrazyme (agalsidase beta), used to treat Fabry disease, while the facility shuts down for 6 to 8 weeks to allow decontamination.

OK, really interesting, that: a vesivirus – genus Vesivirus, family Caliciviridae, nice link here for structure, and here for Genzyme’s press release - that is being transmitted around via cell culture media, between manufacturing plants.  One of the perils of using mammalian cells to make things…!

http://www.caliciviridae.com/vesivirus/vesivirus.htm

Vesivirus via kwout

The article goes on:

…With sales of $1.2 billion for Cerezyme and $494 million for Fabryzyme in 2008, analysts estimate the manufacturing crisis will result in $100–300 million in lost sales. The US Food and Drug Administration (FDA) has contacted rival manufacturers Shire of Basingstoke, UK, and Carmiel, Israel–based Protalix, who have enzyme replacement therapies for Gaucher disease in clinical trials, to file treatment protocols, which would allow physicians to use their drugs ahead of approval.

And of course, Protalix makes its glucocerebrocidase in cultured carrot cells, in disposable “bioreactor bags”….  In completely defined chemical media, with no risk of plant virus contamination – not that plant viruses can infect cultured plants cells, by any means short of being shot in on gold beads!  Their web site Press Room page had this to say as of 25th August:

Aug. 25, 2009 (Business Wire) — Protalix BioTherapeutics, Inc. (NYSE-Amex:PLX), announced today that it has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for prGCD, the Company’s proprietary plant-cell expressed recombinant form of glucocerebrosidase (GCD) for the treatment of Gaucher disease.

I wrote the following about Protalix after attending the Plant-Based Vaccines and Antibodies Conference in Verona in June this year (September issue of Expert Rev Vaccines, 8: 1151-1155, 2009):

“Einat Almon-Brill (Protalix Biotherapeutics, Israel) described their production of recombinant human glucocerebrosidase (rGCD) as a therapy for Gaucher disease, caused by a hereditary mitochondrial defect.  They used a contained disposable bioreactor system with suspension-cultured carrot or tobacco cells, and claimed there were no mammalian cell culture risk factors; they obtained uniform glycosylation, and the exposed mannose allowed rapid macrophage uptake.  The rGCD half-life was twice as long as commercial product, and had been trialled in Europe, Israel, South Africa, and North and South America.”

I wish I’d bought stock…or had the money to, or knew how to!  The time of plant-made pharmaceuticals – PMPs – is coming.

Be ready…B-)


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