Feature Articles

by Jonathan Latham, PhD

For the benefit of those parts of the world where public acceptance of biotechnology is incomplete, a public relations blitz is at full tilt. It concerns an emerging set of methods for altering the DNA of living organisms. “Easy DNA Editing Will Remake the World. Buckle Up“; “We Have the Technology to Destroy All Zika Mosquitoes“; and “CRISPR: gene editing is just the beginning”. (CRISPR is short for CRISPR/cas9, which is short for Clustered Regularly-Interspaced Short Palindromic Repeats/CRISPR associated protein 9; Jinek et al., 2012. It is a combination of a guide RNA and a protein that can cut DNA.)More

by Jonathan Latham, PhD

Piecemeal, and at long last, chemical manufacturers have begun removing the endocrine-disrupting plastic bisphenol-A (BPA) from products they sell. Sunoco no longer sells BPA for products that might be used by children under three. France has a national ban on BPA food packaging. The EU has banned BPA from baby bottles. These bans and associated product withdrawals are the result of epic scientific research and some intensive environmental campaigning. But in truth these restrictions are not victories for human health. Nor are they even losses for the chemical industry.More

by Jonathan Latham, PhD

The GMO labeling issue has quieted down some but there is still plenty to discuss. Just this week the USDA proposed to redefine GMOs with new loopholes for gene editing. However, it is also possible for reasonable people to imagine that GMO labeling is a sideshow to the real business of the food movement. After all, most GMO foods and GMO crops are visually indistinguishable from non-GMOs, and tiny non-GMO labels can look pretty irrelevant on the side of a soda bottle containing whole cupfuls of sugar. Last week, Michael Pollan, Olivier de Schutter, Mark Bittman and Ricardo Salvador made that error, calling GMO labeling “parochial“. Granted, they wrote “important but parochial”, but qualifying the significance of GMO labeling in any way was a mistake.More

Jonathan Latham and Allison Wilson

Quite likely it surprised many regular readers of Nature Biotechnology that for the September (2007) issue their journal had invented a new article format specifically in order to describe, and then extensively criticise, the work of a researcher that most of them had never heard of before (1). That surprise will only increase if they read the translation, featured on our website, of a Nov 1st article (The excommunication of a heretic) in the Swiss Newspaper WOZ. Readers who thought this new format was simply a curious, if rather aggressive, literary innovation, can now see that this was a story with a disturbing history. Even more interesting however than the ethical shenanigans behind the publication of the interview with Dr Ermakova, is a point not raised by the Swiss newspaper article.

In science, opinions may differ, but it is not usual to attempt to embarrass opponents with overt public criticism. The existence (or imminent prospect) of reproducible data that will settle the issue is usually sufficient to ensure that most disputes never reach the printed page. So why has this dispute followed a different course?

Roundup Ready™ Soybeans, all of which are derived from a single transgene insertion event (40-3-2), have been on the market for approximately twelve years. They have been grown on millions of hectares and passed regulatory safety assessments in many countries. If a researcher makes a seemingly anomalous finding that RR Soy harms rats then surely all that should be necessary is for their critics to reach for the multitude of studies already in existence for a handy refutation? For Roundup Ready soy however, such a body of incontestable data does not exist. It is this remarkable data gap that seems to be behind the Nature Biotechnology interview with Dr Ermakova and quite probably it is for this reason that her unpublished study so alarms the biotech industry.

In the case of Roundup Ready soy, there is a single broadly comparable (i.e. multi-generational) study that examines similar endpoints in rodents (in this case mice) fed Roundup Ready Soy and that also supports the contention that mice are unaffected by Roundup Ready soy (Brake and Evenson 2004). The problem however is that this is only a single small study and, although published in a peer reviewed journal, it suffers from as many flaws as does the study carried out by Dr Ermakova. For those interested, we can recommend applying the Nature Biotechnology criticisms of Dr Ermakovas’ study, to the Brake and Evenson study.

For example, Dr Ermakova is criticised in the interview for having bought her seeds from ADM Netherlands, even though she says she tested to confirm that they contained the Roundup Ready (40-3-2) transgene. Brake and Evenson in contrast report that they relied on an unnamed seed dealer taking them to a single field of Roundup Ready soy and a single non-transgenic field, where they obtained soybeans from unspecified cultivars. Brake and Evenson report no attempt to verify the dealers’ identification of the soybeans as transgenic or otherwise (Brake and Evenson 2004). It is therefore hard to understand why Brake and Evenson’s should be considered a superior method for obtaining samples.

There is one further published study, not mentioned by the Nature Biotechnology critics, that is comparable (in the sense of being multigenerational) to those of Ermakova and Brake and Evenson. It reports histological studies on the offspring of mice fed Roundup Ready soy (Malatesta et al., 2002a). These authors reported ultrastructural alterations to hepatocytes only in the offspring of pregnant mice fed Roundup Ready soy, but no other differences (Malatesta et al., 2002a). A further paper from the same laboratory reported biochemical (but not visible) alterations to pancreatic cells of mice fed Roundup Ready soy for up to 8 months after weaning (Malatesta et al., 2002b). These two papers arguably offer some support for Dr Ermakova’s work in that effects of Roundup Ready soy were observed, although the effects seen were not the same. For example, no effects on offspring body weight or mortality were noted.

Perhaps the most important general point about all these multigenerational studies is that none of them used near-isogenic soybeans grown side-by-side, which is a prerequisite for a properly controlled test of the question that we all want answered: whether the 40-3-2 transformation event can be responsible for altered toxicological or nutritional properties of soybeans.

The critics’ challenges to Dr Ermakova’s work are mostly reasonable (2). They rest on demonstrating flaws in her methodology and also on the assertion that her work is further contradicted by four mammalian feeding studies of Roundup Ready soy, even though, unlike Dr Ermakova’s, all of these are single generation studies (Zhu et al., 2004; Teshima et al., 2000; Cromwell et al., 2002; Hammond et al., 1996). As in their comparison with the Brake and Evenson work however, the criticisms create the impression that these papers do not themselves suffer from the flaws noted in Dr Ermakova’s work. This is not the case however and from a toxicological perspective, the limitations of all these studies (summarised in Tables A and B) are strikingly similar to those pointed out by Dr Ermakova’s critics.

Table A details for each study the preparation and selection of soybeans for consumption (e.g. whether Roundup Ready and control soybeans were grown under the same conditions, whether isogenic lines were used, whether the presence/absence of the transgene was ascertained, etc.) while Table B details key attributes of the feeding studies themselves (such as how many animals were used, what percent soy was included in the diet etc). Looking at Tables A and B it is plain to see that, as a result of their collective limitations (which include short study durations, small numbers of animals and lack of replication), while no adverse effects were reported (though see footnote 3), their individual and collective limitations are highly significant.

These inadequacies, which are fundamental to any discussion about whether Dr Ermakova’s data are in conflict with the published literature, appear to have been missed entirely by the Nature Biotechnology critics. It is not the only mistake they make however. They seem to have been unaware of the Malatesta papers, they cite Teshima et al. and Zhu et al. in stating that “Previous reports in the literature have shown no effects of Roundup Ready soy on birth weights or pup mortality” (p983) yet neither paper studied birth weights, pregnant rats or pregnant mice. In fact, Teshima et al. started their study on rats and mice that were both seven weeks old and Zhu et al. started theirs on 28 day old rats. None of these are trivial errors and they make the question-raised by Roland Fischer of WOZ-of why Nature Biotechnology failed to use truly expert referees, a highly pertinent one.

Ultimately, more important than any misrepresentation of the evidence by these four critics, is a question that is central for regulators who are asked to approve and consumers who are offered Roundup Ready soy: does the existence of these seven flawed studies tell us anything useful about the safety or otherwise of Roundup Ready cultivars? This question is also an interesting one purely from a scientific perspective because current scientific understandings (especially in regulatory science) are very frequently constructed from small numbers of highly imperfect studies. The answer would seem to depend on at least three parameters, all of which are mutually dependent. Firstly, the precise nature of those flaws, because some, such as failing to positively determine the presence of the transgene in the treatments, and equally its’ absence from the controls, ought to invalidate any experiment regardless of the subsequent quality of data collected (4). The second significant parameter is whether the flaws in each paper are the same or overlapping. Flaws in one paper, and usually these will be data gaps, can sometimes be made up for by the results of another. Lastly, an experiment may be perfectly useful, but nevertheless not support the conclusions which the authors draw. Failure to use isogenic lines and/or to grow them side-by-side means that, whatever the title of a paper may imply, any effect seen in the treatment group cannot be attributed specifically to presence of the Roundup Ready transgene. Using these criteria, any conclusions about the safety of Roundup Ready soy based on these data must be extremely limited and highly provisional, and consequently deeply unsatisfactory.

All of which raises an issue for Nature Biotechnology as a scientific journal. The safety or otherwise of Roundup Ready soybeans is a matter of great public health significance. New research suggesting that it might not be safe, especially when the prior research is inconclusive at best, should be a matter of significant concern. Yet Nature Biotechnology saw Dr Ermakovas’ work only as an industry threat and publicised her work seemingly only in order to dismiss it. There is no difference at all between what Nature Biotechnology has done to Irina Ermakova and what Fox news did to Marion Nestle when they hired Steven Milloy, then at the Cato Institute, to review her book Food Politics: How the Food Industry Influences Nutrition and Health. And if there is no difference in behaviour between Fox News and Nature Biotechnology, what is the value of Nature Biotechnology as a journal of science?

It seems to us that this interview is part of a pattern and that Nature Biotechnology has for some time been unclear where the line that traditionally separates trade magazines from science journals lies (5). Its’ owner, Nature Publishing Group no doubt finds that publishing a magazine that does double duty, as a science journal and as a trade journal, is a highly profitable combination, but equally it is never going to be one that encourages disinterested science (6). Consider what Nature Biotechnology could have done to address the question of transgenic soya biosafety: it could have invited Dr Ermakova to submit her work formally and, whether it was accepted or rejected; it could have written an editorial calling for appropriately controlled high quality independent research to fill the data gaps. It could have pointed out that, if anything the existing data provides hints that there is a need for such experiments. The fact that Nature Biotechnology did none of these should be of deep concern to all its readers.

Footnotes
1) Marshall, A. (2007) Nature Biotechnology 25: 981-98
2) Not all of their points are fair though. For example, Dr Ermakova is criticised for not double-blinding her experiments, yet none of the studies discussed in Nature Biotechnology or in this commentary were double-blinded.
3) Interestingly, though Zhu et al. make no mention of it, for all time points tested and for both sexes their results show an almost perfect correlation of decreasing white blood cell counts as Roundup Ready soy replaces conventional soy in the diet fed to their rats.
4) Although the fact that in some papers the developers of RR Soy were also the experimenters might be considered to mitigate this defect (Table A). Equally however, their collaborators might have tested for their own satisfaction.
5) Compare the treatment of non-target effects of Bt in the review by Romeis et al. (2006) in Nature Biotechnology 24: 63-71 with that of Lovei and Arpaia (2005) in Entomologia Experimentalis et Applicata 114: 1-14 or Hilbeck and Schmidt (2006) in Biopesticides International 2: 1-50.
6) It is also interesting to note that, unlike most journals, NPG journals have no association with any scientific societies and no independent editorial board.

Jonathan Latham, PhD and Allison Wilson, PhD

You may not have heard of it, but a potential landmark document in the fields of development and agriculture (called by some the Intergovernmental Panel on Climate Change (IPCC) of agriculture) is currently in the late stages of reaching fruition.

Drafted by around 400 scientific and social science experts from around the world, it is called the International Assessment of Agricultural Science and Technology for Development (IAASTD). The IAASTD (www.agassessment.org/) is unusual in being a collaborative document evaluating solutions for agriculture, poverty and development that is actively inclusive. Thus, it is not only multi-disciplinary but also inclusive in terms of geography, institution and gender. As such, the IAASTD is potentially extraordinarily valuable as a uniquely representative and holistic document of the best current thinking in agriculture and development. In this it is a significant departure from most international agriculture reports that are typically dominated by one perspective, one government or one interest group (and which typically fails to help poverty for that reason).

In addition to the above, there is a further reason to value the IAASTD. It asserts repeatedly what it terms the multi-functionality of agriculture, by which it means that agriculture is not just a provider of food or fodder, but a provider also of social security, of ecosystem services, of landscape value, as well as other ‘outputs’.

Perhaps inevitably, given this broad and deep perspective, the current IAASTD draft adopts a more sophisticated analysis than is usual in international reports which have a habit of proposing solutions to poverty that resemble Escher’s impossible objects. Each report may be internally consistent but clashes with other goals. Thus agricultural objectives, for example, typically are incompatible with social objectives and environmental objectives for development. IAASTD, therefore, should be seen as a novel attempt to use an inclusive and multidisciplinary approach to circumvent these problems.

Therefore, instead of understanding agricultural development problems as principally functions of low yields and lack of productivity, the IAASTD considers wider issues such as food quality, sustainability, water use, land tenure, and energy use as crucially important components of any solution. Furthermore, it attempts to recognise the rights and needs of small farmers, women farmers and the hungry while also giving appropriate emphasis to the significance of power and its unequal distribution in the creation and maintenance of poverty. In line with this analysis the draft promotes special policy emphasis on small/poor farmers, the involvement of women in farming and non-chemical farming in order to promote food security.

If they are ever implemented, the lessons drawn by IAASTD (at least those in the current draft) would represent a remarkable break with current practices which typically emphasise farm consolidation and chemical-intensive agriculture (though these goals are often not described explicitly).

It is often lamented that our societies have an abundance of knowledge and a shortage of wisdom, but the current IAASTD draft comes as close to providing wise guidance for agriculture and development as we have yet seen. Its chief message is appropriately revolutionary: we have so far fed the world principally by depleting natural capital, and we must now look beyond business as usual if we really want to address poverty.

The GMO Angle

The IAASTD draft document is surprising for still another reason. Although supported by the World Bank, it does not offer much support for transgenic crops as the best hope, or even as a particularly useful tool, to alleviate the agricultural ills that beset developing countries, the hungry and the poor.

Most likely, inclusiveness and scarce support for GMOs by the IAASTD are in fact connected. It is probably no coincidence that a document arrived at transparently, using a tolerably democratic process (i.e. it was not written behind closed doors), and using a multidisciplinary approach, should conclude that GM crops have ‘lingering safety concerns’ and may even be harmful to rural development.

These conclusions in general, and the lack of support for GMOs in particular, are immensely unwelcome in some quarters. The publicity machines of Monsanto, Syngenta and others have not spent twenty years carefully positioning transgenics as the solution to every agricultural problem in order for them to be ignored by the largest and most diverse collection of agriculture and development policy experts ever assembled.

Last October, Monsanto and Syngenta resigned altogether from the IAASTD project. Though they gave no public reasons for their resignation, the industry body CropLife International told Nature magazine that an inability to make progress in arguing for GMOs was the fundamental reason (1).

A Tragedy for the Poor?

In a recent editorial, Nature magazine argued the interesting point that withdrawal of these companies was a tragic event. The companies, said Nature, were ‘deserting the poor’ (1). Leaving aside that Monsanto and Syngenta were a very small part of the IAASTD process, this statement is hard to support from a scientific point of view. Are Monsanto scientists more knowledgeable about poverty, development and the needs of developing country agriculture than university or government scientists? Probably not. Do Syngenta scientists have fore-knowledge of impending agricultural developments not available to the rest of us? They may have, but if so these are company secrets which have not so far been made available for discussion or disputation. Does Nature believe that academics and government scientists are unable to make the arguments for biotechnology? But if the scientific need for the companies’ presence was hardly overwhelming, it follows that neither is their loss a particularly significant one.

The inclusion of these company scientists was primarily a recognition, not of their expertise but of something else – most likely the power and influence of their employers, plus the company presence on the IAASTD steering committee and the companies’ financial support of the IAASTD. All of these are essentially political reasons for inclusion. Once included, it would be naive, however, not to have expected that their primary goal would be anything other than to ensure that the assessment erected no obstacles to the introduction of transgenics, and so it proved. It was predictable perhaps, but Monsanto and Syngenta were about as useful to the assessment as Exxon would have been at the IPCC.

The Real Motive for Withdrawal?

As the science media correctly asserted, the IAASTD is important (which begs the rather important question of why they have up to now ignored it). But if their accounts are to be believed, Syngenta and Monsanto’s withdrawal from the IAASTD can be fully explained by the frustration and difficulties of a handful of mid-level employees (2, 3). But is this really a plausible explanation? That multinational companies base strategic decisions on the ‘frustration’ or convenience of their employees? Far more likely surely, especially given that some negative publicity for the companies would (and did) accompany withdrawal, is that this explanation is not the real one. More plausible by far is the possibility that Monsanto and Syngenta’s withdrawal was carefully calculated.

History tells us that the most common reason participants abandon important but frustrating multi-party negotiations is when they believe they can better achieve their aims by abandoning, and therefore delegitimising, whatever agreement is eventually reached. And for maximum effect delegitimisation has to occur in public. If this was, in fact, their strategy, then Monsanto and Syngenta would have been very pleased indeed by what happened next.

Following their withdrawal, Nature Biotechnology devoted its full editorial page to questioning the credibility of the (post-corporate) assessment, reporting that IAASTD’s criticisms of GMOs were “unsubstantiated” and reflective of a “bias against top-down solutions” and further that the report was “skewed” and not “representative” (2). Nature’s editorial called the report “undoubtedly over-cautious and unbalanced” and agreed that the company defections were “a blow to the credibility” of the IAASTD (1). The largest article of all was a feature in Science (3). As with Nature Biotechnology, the core of the Science article focused on the “question of balance” and assertions that the outcome was negative because of “bias”. Science even reported the no doubt impartial molecular biologist Jonathan Gressel as saying “The whole thing was incredibly stacked”. Though giving more-or-less respectful attention and space to defenders of inclusiveness, Science gave no space at all, in four pages, to anyone prepared to argue the possibility that the IAASTD assessment of GMOs was fair and realistic. Perhaps what would have made Monsanto and Syngenta most pleased was the allegation by a person “who asked not to be named” that the “best scientists” were not on the IAASTD (3).

In placing the blame for the corporate boycott exclusively with the IAASTD, perhaps it never occurred to any of the journal editors that in so doing they were supporting a tiny handful of corporate biotechnologists against the aggregated views of 400 independent scientists?

Monsanto and Syngenta have so far won the media battle, but the real test of their strategy is still to come: will they attempt, and if they do, will they succeed, in derailing adoption (or modifying the text) of the final report? If they were to succeed that really would be a tragedy for the poor, because the IAASTD, at least in its draft form, is a potentially world-changing document. It offers a lot and it asks a lot: a chance to make a real improvement to livelihoods and sustainability in return for rethinking agriculture as usual. It is a shame that the science media would rather support (big) business as usual.

Download the draft executive summary of the IAASTD (called the Synthesis report)

Jonathan Latham, PhD and Allison Wilson, PhD

Commercially, insect-resistant transgenic (GMO) plants are made by inserting a gene coding for one of a family of toxins produced by the soil bacterium Bacillus thuringiensis. These Bt toxins are regarded by most regulators to be safer for the environment than externally applied synthetic pesticides and this is because, as plant-expressed proteins, they are considered specifically targeted to organisms that consume the crop (Glaser and Matten, 2003). As a result of this understanding Bt toxins expressed by transgenics are managed as a ‘public good’ by the US Environmental Protection Agency (US-EPA 1998).

However, Bt toxins are often expressed at high levels within plant tissues (typically for insertion event MON810 this means around 10ug/g fresh weight of Cry1Ab) and they persist in the soil, either within plant cells or as native protein (Baumgarte and Tebbe 2005; Griffiths et al., 2006). Therefore, contained within a field of Bt maize there can be many kilograms of a Bt protein at any one time. As a consequence, there is potential for significant exposure of non-target organisms, both in and around fields growing transgenic Bt crops.

Environmental risk assessments of transgenic crops have until now focused exclusively on consequences for non-aquatic organisms (NRC 2000). A recent study however, showed that debris and pollen of plants transgenic for Bt-toxins can enter nearby agricultural streams in large quantities (Rosi-Marshall et al., 2007). This same paper also reported that two caddisfly species, which are ecologically important stream organisms, are sensitive to Cry1Ab-containing leaves and pollen (Rosi-Marshall et al., 2007). As Bt researcher Angelika Hilbeck (ETH-Zurich) told the BSR News Service: “We have entirely overlooked aquatic ecosystem effects of transgenic toxins”.

Now, a further aspect of freshwater toxicology has been addressed by a study published in the journal Archives of Environmental Contamination and Toxicology. This study reports that Daphnia magna, a freshwater crustacean arthropod commonly used in toxicological investigations, can also be negatively affected by Bt transgenic plant debris containing the Bt toxin Cry1Ab (Bøhn et al. 2008). In this study, D. magna populations were fed either kernels of ground transgenic maize (containing event MON810) or non-modified isogenic maize kernels. The plant material for these experiments was grown in adjacent fields.

The Results

Bøhn et al. found that mortality, growth and fertility of D. magna were all negatively affected by the MON810-containing line compared to the control maize. Interestingly, however, the animals fed transgenic maize showed early maturation, indicating a likely toxic response to a component of the transgenic maize, rather than a response to malnutrition.

The authors suggest that their results reinforce the possibility that Cry1Ab transgenics may have significant implications for aquatic ecosystems. However, the mechanism by which the transgenic maize affects D. magna is not resolved by this data. One possibility is that the assumption that Cry1Ab is lepidopteran-specific may be inaccurate or, alternatively, Cry1Ab may be modified within the cellular environment of plants. In either case, transgenic Cry1Ab, and perhaps other cultivars containing different Bt toxins, may be toxic to non-target organisms to an unexpected degree. Cry proteins may thus be having effects on soil arthropods (for which there are no published studies on Bt toxin effects). Angelika Hilbeck however is cautious: “It is difficult to make cross-comparisons from water to land ecosystems, since they are such different environments”.

Since MON810 was the only Cry1Ab event studied by Bøhn et al., there remains an alternative mechanistic possibility, however, which is that the effects on D. magna are a result of some unanticipated consequence of transgene insertion or expression. Such unanticipated effects are not merely theoretical: Rosi-Marshall et al. normalised their results for C:N ratios because Cry1Ab containing Bt maize varieties have more lignin than non-Bt varieties (Saxena and Stotzky 2001). This normalisation was done to prevent any confounding influences of nutritional quality from affecting their results (Rosi-Marshall et al., 2007).

A recent paper detailing the first proteomic analysis of a MON810-containing cultivar may be relevant to this discussion. The authors found at least 43 significant protein expression differences between the MON810 line and a near-isogenic control (Zolla et al., 2008). Given this perhaps surprising degree of difference between a transgenic cultivar and a non-transgenic isoline, it becomes plausible to imagine that one of these differences might be responsible for the effects observed on D. magna.

A substantial equivalence connection?

Irrespective of whether Cry1Ab (or some other MON810 constituent) turns out to be the specific cause of increased D. magna mortality, Bøhn et al.’s result (and also the caddisfly result) constitute a challenge also to the regulatory doctrine of substantial equivalence. According to this principle, MON810 has been declared ‘substantially equivalent’ and it should be safe for all organisms (other than known targets of Cry1Ab), whether they are D. magna or H. sapiens. Instead, MON810 is apparently substantially equivalent but not safe.

These new results may stimulate discussion of the concept of substantial equivalence and its relationship to GMO safety. One possible interpretation of this data is that it disproves absolutely the existence of any fundamental relationship between substantial equivalence and safety. Instead, it supports the longstanding view that substantial equivalence never was a true scientific concept. Rather, it is a regulatory ‘principle’ associated with no biological relationship nor any theoretical validity (Millstone et al., 1999).

Other interpretations are also possible however: that substantial equivalence is still useful, even if the relationship with safety is not absolute. In this view recent results weaken the relationship but do not disprove it, rather like examples of differences between human and rat toxicology weaken, but do not wholly invalidate, the predictive power of that relationship. Either interpretation however accepts that it may no longer be appropriate to say that a transgenic crop is substantially equivalent and therefore safe.

Thomas Bøhn, however, takes a very different tack: his answer to this conundrum is that MON810 was originally determined incorrectly by US (and also EU) regulators as substantially equivalent. This answer, however, illustrates another apparent problem of substantial equivalence: that there is no agreed, universal or a priori set of criteria of what, in terms of crop composition, constitutes a finding of a substantial difference (Millstone et al., 1999).

Other things being equal, substantial equivalence, it seems, will either have to be reconsidered, or it will acquire the probably unique distinction of violating twice, Karl Popper’s falsifiability criteria of a scientific theory.

Put another way, is substantial equivalence so elastic, either in its specific determination for a particular crop, or in its application as a general measure of safety, that it is not in practice falsifiable?

Jonathan Latham, PhD and Allison Wilson, PhD

Gore Vidal once wrote that “I told you so,” is the most satisfying sentence in the English language. If so, then the imminent launch of Monsanto’s Roundup Ready 2 Yield soybean line is going to provide a lot of satisfaction, though not to supporters of Monsanto. The role of the new glyphosate-resistant line (insertion event MON88978) in the following story is to provide a single, but highly significant, new data point.

The new Roundup Ready 2 Yield line will supercede Monsanto’s original Roundup Ready transgenic soybean (event 40-3-2) and yet it confers the exact same trait and contains the exact same gene as Roundup Ready. So why would Monsanto feel the need, probably at substantial cost, to replace the original Roundup Ready?

A big clue, along with the advertising, is the name. Monsanto claims that Roundup Ready 2 Yield produces a 7-11% superior yield than the original Roundup Ready. This ought to be rather surprising since herbicide resistance is not a yield trait. But the answer is in fact simple: the introduction of Roundup Ready 2 Yield is an admission that the original Roundup Ready had a major yield drag, one of several unanticipated consequences of this insertion event.

What we argued

Many groups and individuals have argued that transgenic plants may be prone to unanticipated consequences, either due to pleiotropy or to effects of transgene insertion (Schubert 2002). Our review papers on the molecular characteristics of transgene insertion sites and the associated genetic consequences of plant transformation techniques provided the first, and still only, review of the mutagenic nature of plant transformation and the consequences for the biosafety of transgenic plants (Wilson et al. 2006; Latham et al. 2006).

Our analysis reached two principal conclusions. The first was that transgene insertions, especially those resulting from particle bombardment, are frequently complex and frequently disruptive, often of multiple coding regions. Secondly, current plant transformation techniques are typically associated with very large numbers of mutations, some of which will inevitably be closely linked to the transgene and therefore hard to separate genetically. Based on these observations we speculated that unanticipated phenotypic consequences were likely to be associated with transgenic plants, and furthermore, that these would sometimes be deleterious or otherwise harmful (see Nature Biotechnology correspondence Bradford et al. 2005; Wilson et al. 2006; Latham et al. 2006).

At the time, a frequent response from regulators, and others, was that, nevertheless, transgene insertion sites and/or linked mutations, were unlikely to result in phenotypic consequences of any significance. This point has been argued in print by Bradford et al. (2005), Altpeter et al. (2005) and Schouten and Jacobsen (2007).

The unanticipated traits of Roundup Ready soybean (event 40-3-2)

Launched in 1996, Roundup Ready soybeans, which express an enol pyruvate shikimate-3-phosphate synthase (EPSPS) gene from the microbe Agrobacterium tumefaciens (and contain no other transgenes), have been an undoubted commercial success. However, they have been controversial, both because of complaints from farmers and because of revelations of unanticipated physiological consequences. These have included stem splitting and probably lignin overproduction (Coghlan, 1999; Gertz and Vencill 1999), small seed size and a yield drag (Elmore et al. 2001; Nelson et al. 2002; Benbrook 1999; Gordon 2007), and last but certainly not least, a significant manganese (Mn) deficiency (Gordon 2007).

Two powerful arguments together suggest that of these unanticipated traits, the manganese deficiency and the yield drag, are caused specifically by the 40-3-2 insertion event, which is contained in all current commercial Roundup Ready soybeans. First, even though the 40-3-2 insertion event has been backcrossed into hundreds of soybean cultivars, Monsanto has consistently failed to separate the unanticipated traits from the transgene, suggesting that they are extremely closely linked to, or inseparable from, the actual site of insertion. This fact alone still allows, however, the possibility that the action of the EPSPS protein might be responsible for the unanticipated traits. The introduction of Roundup Ready 2 Yield, however, suggests that this is not the case. Although Roundup Ready 2 Yield contains different transgene promoter and termination sequences from Roundup Ready, the transgene product, the bacterial EPSPS protein, is identical in sequence (USDA petition 06-178-01p). Nevertheless, according to the same petition, Roundup Ready 2 Yield yields 7-11% over Roundup Ready, which just happens to approximate to the yield penalty that researchers have suggested Roundup Ready confers.

The learning curve

In principle, much could be learned from this story. The first, and perhaps the most significant, is to lay to rest the notion that unintended traits in transgenic plants are invariably unimportant and rare. Not only is 95% of the soybean crop of the United States currently yielding 7-11% less than it should, Roundup Ready soybeans can contain less than 40% of the Mn contained in isogenic lines (Gordon, 2007). Neither of these traits can reasonably be called insignificant.

Secondly, the original petition for Roundup Ready soybeans inadequately analysed the transgenic line prior to commercial approval. As was subsequently shown, the 40-3-2 insertion site of Roundup Ready had a complex and scrambled insertion site and a non-functional transcription termination sequence, which allowed aberrant transcripts to transcribe beyond the transgene and into scrambled DNA (Hernandez et al. 2003; Rang et al. 2005; Wilson et al. 2006). Additionally, the compositional and phenotypic analyses, which were supposed to demonstrate the identity of Roundup Ready to conventional soybeans, omitted important data points. Thus, the petition failed entirely to detect a deficiency in a major nutrient (Mn) as well as the assorted agronomic defects of Roundup Ready soybeans. Attention to any one of these data gaps might have alerted regulators to the problems.

Now available for public inspection is the Monsanto petition for Roundup Ready 2 Yield (USDA petition 06-178-01p). Monsanto, it appears, has learned from some of the mistakes of Roundup Ready. They have replaced the nos terminator, they have also avoided callus culture and instead used meristem culture, which should be much less mutagenic, and also transformed this time with Agrobacterium tumefaciens rather than particle bombardment.

For regulators, however, the learning curve is conspicuous by its absence. Regulators in the USA, the EU and China, as well as elsewhere have already approved Roundup Ready 2 Yield, even though the petition is again flawed. The petition again fails to present a DNA sequence for the insertion site or to analyse DNA flanking the insertion site; it fails to search for aberrant mRNA transcripts; and perhaps most remarkably, its compositional analysis fails to measure even a single mineral nutrient.

Of particular interest to us, the petition also demonstrates that the new Roundup Ready 2 Yield soybean has its own unanticipated plant trait: Roundup Ready 2 Yield plants are consistently 5% shorter than isogenic lines. Evidently, the regulators who have approved Roundup Ready 2 Yield (including the famously ‘stringent’ EU) have agreed with Monsanto’s conclusion that there is “no biological meaning” to this difference (USDA petition 06-178-01p). To us, however, this difference has, in fact, two biological meanings. On a practical level, as any farmer could have pointed out, crop stature is an important agronomic trait: as well as being typically an important weed suppression character; plant stature is important in mechanical harvesting; and also for disease susceptibility, where ground contact and foliage positioning affect in-crop humidity. Secondly, many commercial transgenic crops have unanticipated traits compared to their isogenic lines (e.g. Colyer et al. 2000; Escher et al. 2000; Brodie 2003; Poerschmann et al. 2005; Herrero et al. 2007). Unlike these, however, Roundup Ready 2 Yield used the best available plant transformation methods, yet still has at least one unanticipated trait.

Although Roundup Ready 2 Yield is now approved in many countries, the unsatisfactory nature of the petition means that obvious and important questions regarding its unanticipated traits are still unresolved. Is the reduced stature phenotype an indicator of other defects? Are there other independent unanticipated traits present in Roundup Ready 2 Yield soybeans? These are not unreasonable questions, yet it is difficult not to conclude that regulators are currently uninterested in them.

Perhaps the increasing evidence for unanticipated traits in commercial cultivars will change that and the precision myth of transgenic crops will fade into oblivion. In the meantime, Monsanto has a tricky decision to make, whether to charge farmers more for their ‘yield trait’.

by Jonathan Latham, PhD
Professor Pamela Ronald is probably the scientist most widely known for publicly defending genetically engineered (GE or GMO) crops. Her media persona, familiar to readers of the Boston Globe, the Wall Street Journal, the Economist, NPR, and many other global media outlets, is to take no prisoners.

After New York Times chief food writer Mark Bittman advocated GMO labelling, she called him “a scourge on science” who “couches his nutty views in reasonable-sounding verbiage”. His opinions were “almost fact- and science-free” continued Ronald. In 2011 she claimed in an interview with the US Ambassador to New Zealand: “After 14 years of cultivation and a cumulative total of two billion acres planted, GE crops have not caused a single instance of harm to human health or the environment.”

This second career of Pamela Ronald’s, as advocate of GMOs (which also includes being a book author, and contributor to and board member of the blog Biofortified) is founded on her first career: at the University of California in Davis she is Professor in the Department of Plant Pathology, Director of the Laboratory for Crop Genetics Innovation, and Director of Grass Genetics at the Joint BioEnergy Institute, among other positions.

This background is relevant because Pamela Ronald is now also fighting on her home front. Her scientific research has become the central question in a controversy that may destroy both careers. In the last year Ronald’s laboratory at UC Davis has retracted two scientific papers (Lee et al. 2009 and Han et al 2011) and other researchers have raised questions about a third (Danna et al 2011). The two retracted papers form the core of her research programme into how rice plants detect specific bacterial pathogens (1).

When the mighty fall, others try to catch them

The first paper was retracted on January 29th 2013, from the journal PLoS One (Han et al 2011). News of the retraction was (belatedly) published on the 11th of September 2013 by the blog Retraction Watch under the headline: Doing the right thing: Researchers retract quorum sensing paper after public process (2). [CORRECTION: Jan 29th was the date the Ronald group notified PLoS One of probable errors. Retraction formally occurred on Sept 9th. Apologies to Retraction Watch as there was no delay to explain. Footnote 2 is therefore superfluous.]

The second retraction, from Science, was officially announced a month later, on October 11th 2013 (Lee et al 2009). This time, retraction was accompanied by a lengthy explanation (Anatomy of a Retraction, by Pamela Ronald) in the official blog of Scientific American. In this article, Ronald blamed the work of unnamed former lab members from Korea and Thailand. Retraction Watch reported the retraction as: Pamela Ronald does the right thing again. Also on the same day, The Scientist magazine quoted Pamela Ronald saying it was “just a mix-up” and repeating her claim that “Former lab members who had begun new positions as professors in Korea and Thailand were devastated to learn that [we] could not repeat their work.”

Scientifically, the two retractions mean that the molecule (Ax21), identified by Pamela Ronald’s group (in Lee et al 2009), is not after all what rice plants use to detect the pathogen rice blight (Xanthomonas oryzeae) and neither is it a ‘quorum sensing’ molecule, as described in Han et al 2011.

The media coverage of the retractions didn’t query Ronald’s mea non culpa. Instead, reports added, as UC Berkeley professor Jonathan Eisen put it, ‘Kudos to Pam’ for stepping forward.

Did Pamela Ronald jump, or was she pushed?

In fact, scientific doubts had been raised about Ronald-authored publications at least as far back as August 2012. In that month Ronald and co-authors responded in the scientific journal The Plant Cell to a critique from a German group. The German researchers had been unable to repeat Ronald’s discoveries in a third Ax21 paper (Danna et al 2011) and they suggested as a likely reason that her samples were contaminated (Mueller et al 2012).

Furthermore, the German paper also asserted that, for a theoretical reason (3), her group’s claims were inherently unlikely.

In conclusion, the German group wrote:

“While inadvertent contamination is a possible explanation, we cannot finally explain the obvious discrepancies to the results in..…..Danna et al. (2011)”

Pamela Ronald, however, did not concede any of the points raised by the German researchers and did not retract the Danna et al 2011 paper. Instead, she published a rebuttal (Danna et al 2012) (4).

The subsequent retractions, beginning in January 2013 (of Lee et al 2009 and Han et al 2011), however, confirm that in fact very sizable scientific errors were being made in the Ronald laboratory. But more importantly for the ‘Kudos to Pam’ story, it was not Pamela Ronald who initiated public discussion of the credibility of her research.

Was it “just a mix-up”?

Reporting of the retractions also accepted Pamela Ronald’s assertions that simple errors by two foreign and now-departed laboratory members were to blame. But her more detailed description of events, which appeared in Footnotes with technical details for those in the discipline below her Scientific American blog, contradict that notion.

Ronald’s footnotes admit two mislabellings, along with failures to establish and use replicable experimental conditions, and also minimally two failed complementation tests. Each mistake appears to have been compounded by a systemic failure to use basic experimental controls (5). Thus, leading up to the retractions were an assortment of practical errors, specific departures from standard scientific best practice, and lapses of judgement in failing to adequately question her labs’ unusual (and therefore newsworthy) results.

Who is responsible?

The International Committee of Medical Journal Editors (ICMJE ) published the first and most widely cited principles of authorial ethics in science. These recommendations are followed by thousands of medical and other scientific journals. The following is the first paragraph of the section regarding authorship:

“Authorship confers credit and has important academic, social, and financial implications. Authorship also implies responsibility and accountability for published work. The following recommendations are intended to ensure that contributors who have made substantive intellectual contributions to a paper are given credit as authors, but also that contributors credited as authors understand their role in taking responsibility and being accountable for what is published.” (italics added)

The ICMJE guidelines go on to state that authorship should not be conferred on those who do not agree to be accountable for all aspects of the accuracy and integrity of the work.

Some scientific journals, have their own policies that provide more specifics. The journal Arteriosclerosis, Thrombosis, and Vascular Biology states:

“Principal investigators are ultimately responsible for the integrity of their research data and, thus, every effort should be made to examine and question primary data.”

Likewise, Columbia University’s guidelines on responsible authorship and peer review concludes:

“Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content.”

Lastly, Science (publisher of Ronald’s retracted Lee et al 2009 paper) has this policy on authorship:

“The senior author from each group is required to have examined the raw data their group has produced.”

It is perhaps surprising then that a senior scientist should publicly disclaim responsibility for research carried out in their own laboratory.

Footnotes
(1) Pamela Ronald appeared to be a leader in understanding the mechanisms by which rice, and other plants, detect and resist important pathogens. She and others have (or in the case of Ronald, thought they had) identified specific molecules characteristic of each pathogen that are detected by dedicated receptors in plants. In this case, rice cultivars resistant to the bacterium Xanthomonas oryzeae detect a small protein molecule called Ax21 that derives from the pathogen. The ability to detect Ax21 enables rapid activation of defences and thus confers resistance to the pathogen. This line of research, as it pertains to Pamela Ronald and Ax21, is now retracted.
(2) Retraction Watch does not explain the delay of over 8 months between the retraction and their report of it. Neither is the “after public process” part of the headline explained.
(3) The theoretical reason is that molecules that warn of incipient plant pathogen infection (as Ax21 was supposed to do) are typically detected by receptors at very low concentrations–otherwise they wouldn’t serve as useful warning molecules. Yet in the experiments from Pamela Ronald’s laboratory (Lee et al. 2009 and Danna et al. 2011) Ax21 is required to be present at concentrations millions of fold higher than other elicitors to achieve the same effects (Mueller et al 2012).
(4) The rebuttal argued, among other points, that: “experimental differences may explain the failure of Mueller et al. (2012) to observe FLS2-dependent defense-related responses.” (Danna et al 2012).
(5) The errors noted by Pamela Ronald in her Scientific American blog were: a) “By careful sleuthing, [lab members] found that two out of 12 of the strains……were mislabeled.” b)“In the more recent experiments we found that although the modified (sulfated) Ax21 peptide did induce resistance in Xa21 plants, it also induced resistance in plants lacking the Xa21 immune receptor, an important control.” c) “Furthermore, results of the pretreatment test were highly dependent on greenhouse conditions.” d) “They also made mistakes in their complementation tests of the Ax21 insertion mutant with the wild-type Ax21 gene.” (italics added). e) These errors were not caught prior to publication because experiments in the Ronald lab lacked controls. Apparently: “When laboratory members first established the pretreatment assay years ago, they included diverse controls to optimize the assays. However, in subsequent experiments, some of the controls were dropped to reduce the size of the experiments.”

References
Danna CH, YA Millet, T Koller et al (2011) The Arabidopsis flagellin receptor FLS2 mediates the perception of Xanthomonas Ax21 secreted peptides. PNAS 108: 9286-9291.
Danna CH, XC Zhang, A Khatri, AF Bent et al (2012) FLS2-mediated responses to Ax21-derived peptides: response to the Mueller et al. commentary Plant Cell 24:3174-3176.
Han SW, M Sriariyanun SW Lee, Sharma, O Bahar, Z Bower, PC. Ronald (2011) Small Protein-Mediated Quorum Sensing in a Gram-Negative Bacterium. PLoS One
Lee SW, SW Han, M Sririyanum, CJ Park, YS Seo et al. (2009) A type I secreted, sulfated peptide triggers XA21-mediated innate immunity Science 326: 850-853.
Mueller K., Chinchilla D., Albert M., Jehle A.K., Kalbacher H., Boller T., Felix G. (2012). The flagellin receptor FLS2 is blind to peptides derived from CLV3 or Ax21 but perceives traces of contaminating flg22. Plant Cell 24: 3193–3197.

Jonathan Latham, PhD and Allison Wilson, PhD

Just before his appointment as head of the US National Institutes of Health (NIH), Francis Collins, the most prominent medical geneticist of our time, had his own genome scanned for disease susceptibility genes. He had decided, so he said, that the technology of personalised genomics was finally mature enough to yield meaningful results. Indeed, the outcome of his scan inspired The Language of Life, his recent book which urges every individual to do the same and secure their place on the personalised genomics bandwagon.

So, what knowledge did Collins’s scan produce? His results can be summarised very briefly. For North American males the probability of developing type 2 diabetes is 23%. Collins’s own risk was estimated at 29% and he highlighted this as the outstanding finding. For all other common diseases, however, including stroke, cancer, heart disease, and dementia, Collins’s likelihood of contracting them was average.

Predicting disease probability to within a percentage point might seem like a major scientific achievement. From the perspective of a professional geneticist, however, there is an obvious problem with these results. The hoped-for outcome is to detect genes that cause personal risk to deviate from the average. Otherwise, a genetic scan or even a whole genome sequence is showing nothing that wasn’t already known. The real story, therefore, of Collins’s personal genome scan is not its success, but rather its failure to reveal meaningful information about his long-term medical prospects. Moreover, Collins’s genome is unlikely to be an aberration. Contrary to expectations, the latest genetic research indicates that almost everyone’s genome will be similarly unrevealing.

We must assume that, as a geneticist as well as head of NIH, Francis Collins is more aware of this than anyone, but if so, he wrote The Language of Life not out of raw enthusiasm but because the genetics revolution (and not just personalised genomics) is in big trouble. He knows it is going to need all the boosters it can get.

What has changed scientifically in the last three years is the accumulating inability of a new whole-genome scanning technique (called Genome-Wide Association studies; GWAs) to find important genes for disease in human populations¹. In study after study, applying GWAs to every common (non-infectious) physical disease and mental disorder, the results have been remarkably consistent: only genes with very minor effects have been uncovered (summarised in Manolio et al 2009; Dermitzakis and Clark 2009). In other words, the genetic variation confidently expected by medical geneticists to explain common diseases, cannot be found.

There are, nevertheless, certain exceptions to this blanket statement. One group are the single gene, mostly rare, genetic disorders whose discovery predated GWA studies². These include cystic fibrosis, sickle cell anaemia and Huntington’s disease. A second class of exceptions are a handful of genetic contributors to common diseases and whose discovery also predated GWAs. They are few enough to list individually: a fairly common single gene variant for Alzheimer’s disease, and the two breast cancer genes BRCA 1 and 2 (Miki et al. 1994; Reiman et al. 1996). Lastly, GWA studies themselves have identified five genes each with a significant role in the common degenerative eye disease called age-related macular degeneration (AMD). With these exceptions duly noted, however, we can reiterate that according to the best available data, genetic predispositions (i.e. causes) have a negligible role in heart disease, cancer³, stroke, autoimmune diseases, obesity, autism, Parkinson’s disease, depression, schizophrenia and many other common mental and physical illnesses that are the major killers in Western countries⁴.

For anyone who has read about ‘genes for’ nearly every disease and the deluge of medical advances predicted to follow these discoveries, the negative results of the GWA studies will likely come as a surprise. They may even appear to contradict everything we know about the role of genes in disease. This disbelief is in fact the prevailing view of medical geneticists. They do not dispute the GWA results themselves but are now assuming that genes predisposing to common diseases must somehow have been missed by the GWA methodology. There is a big problem, however, in that geneticists have been unable to agree on where this ‘dark matter of DNA’ might be hiding.

If, instead of invoking missing genes, we take the GWA studies at face value, then apart from the exceptions noted above, genetic predispositions as significant factors in the prevalence of common diseases are refuted. If true, this would be a discovery of truly enormous significance. Medical progress will have to do without genetics providing “a complete transformation in therapeutic medicine” (Francis Collins, White House Press Release, June 26, 2000). Secondly, as Francis Collins found, genetic testing will never predict an individual’s personal risk of common diseases. And of course, if the enormous death toll from common Western diseases cannot be attributed to genetic predispositions it must predominantly originate in our wider environment. In other words, diet, lifestyle and chemical exposures, to name a few of the possibilities.

The question, therefore, of whether medical geneticists are acting reasonably in proposing some hitherto unexpected genetic hiding place, or are simply grasping at straws, is a hugely significant one. And there is more than one problem with the medical geneticists’ position. Firstly, as lack of agreement implies, they have been unable to hypothesise a genetic hiding place that is both plausible and large enough to conceal the necessary human genetic variation for disease. Furthermore, for most common diseases there exists plentiful evidence that environment, and not genes, can satisfactorily explain their existence. Finally, the oddity of denying the significance of results they have spent many billions of dollars generating can be explained by realising that a shortage of genes for disease means an impending oversupply of medical geneticists.

You will not, however, gather this from the popular or even scientific media, or even the science journals themselves. No-one so far has been prepared to point out the weaknesses in the medical geneticist’s position. The closest up to now is from science journalist Nicholas Wade in the New York Times who has suggested that genetic researchers have “gone back to square one.” Even this is a massive understatement, however. Human genetic research is not merely at an impasse, it would seem to have excluded inherited DNA, its central subject, as a major explanation of most diseases.

The failure to find major ‘disease genes’

Advances in medical genetics have historically centered on the search for genetic variants conferring susceptibility to rare diseases. Such genes are most easily detected when their effects are very strong (in genetics this is called highly penetrant), or a gene variant is present in unusually inbred human populations such as Icelanders or Ashkenazi Jews. This strategy, based on traditional genetics, has uncovered genes for cystic fibrosis, Huntington’s disease, the breast cancer susceptibility genes BRCA 1 and 2, and many others. Important though these discoveries have been, these defective genetic variants are relatively rare, meaning they do not account for disease in most people². To find the genes expected to perform analogous roles in more common diseases, different genetic tools were needed, ones that were more statistical in nature.

The technique of genome wide association (GWA) was not merely the latest hot thing in genetics. It was in many ways the logical extension of the human genome sequencing project. The original project sequenced just one genome but, genetically speaking, we are all different. These differences are, for many geneticists, the real interest of human DNA. Many thousands of minor genetic differences between individuals have now been catalogued and medical geneticists wanted to use this seemingly random variation to tag disease genes. Using these minor DNA differences to screen large human populations, GWA studies were going to identify the precise location of the gene variants associated with susceptibility to common disorders and diseases.

To date, more than 700 separate GWA studies have been completed, covering about 80 different diseases. Every common disease, including dozens of cancers, heart disease, stroke, diabetes, mental illnesses, autism, and others, has had one or more GWA study associated with it (Hindorff et al. 2009). At a combined cost of billions of dollars, it was expected at last to reveal the genes behind human illness. And, once identified, these gene variants would become the launchpad for the personalised genomic revolution.

But it didn’t work out that way. Only for one disease, AMD, have geneticists found any of the major-effect genes they expected and, of the remaining diseases, only for type 2 diabetes does the genetic contribution of the genes with minor effects come anywhere close to being of any public health significance (Dermitzakis and Clark 2009; Manolio et al. 2009). In the case of AMD, the five genes determine approximately half the predicted genetic risk (Maller et al. 2006). Apart from these, GWA studies have found little genetic variation for disease. The few conclusive examples in which genes have a significant predisposing influence on a common disease remain the gene variant associated with Alzheimer’s disease and the breast cancer genes BRCA1 and 2, all of which were discovered well before the GWA era (Miki et al. 1994 and Reiman et al. 1996).

Though they have not found what their designers hoped they would, the results of the GWA studies of common diseases do support two distinct conclusions, both with far-reaching implications. First, apart from the exceptions noted, the genetic contribution to major diseases is small, accounting at most for around 5 or 10% of all disease cases (Manolio et al. 2009). Secondly, and equally important, this genetic contribution is distributed among large numbers of genes, each with only a minute effect (Hindorff et al. 2009). For example, the human population contains at least 40 distinct genes associated with type I diabetes (Barrett et al. 2009). Prostate cancer is associated with 27 genes (Ioannidis et al. 2010); and Crohn’s disease with 32 (Barrett et al. 2008).

The implications for understanding how each person’s health is affected by their genetic inheritance are remarkable. For each disease, even if a person was born with every known ‘bad’ (or ‘good’) genetic variant, which is statistically highly unlikely, their probability of contracting the disease would still only be minimally altered from the average.

DNA is not the language of life or death

This dearth of disease-causing genes is without question a scientific discovery of tremendous significance. It is comparable in stature to the discovery of vaccination, of antibiotics, or of the nature of infectious diseases, because it tells us that most disease, most of the time, is essentially environmental in origin.

But such significance leaves a puzzle. Huge quantities of newspaper space has been devoted to genes, or even to hints of genes for various diseases⁵. By rights then, reports of the GWA results should have filled the front pages of every world newspaper for a week. So, why has this coverage not occurred?

It is possible to conceive of excuses for lack of coverage: refutation is inherently less interesting, and the GWA results have been reported piecemeal, but the more likely reason is the disturbing implications for medical geneticists who are its discoverers. The GWA studies were not envisaged as a test of the hypothesis: do genes cause common diseases? Rather, they were expected merely to straightaway identify the guilty genes that everyone “knew” were there. By apparently refuting the entire concept of genes for common diseases, the GWA studies raise fundamental questions about money spent, hopes raised, and judgments made by medical researchers.

In the first place, the GWA results raise what are probably insurmountable questions for the prospective ‘genetic revolution’ in healthcare. What use will personalised DNA testing (or sequencing) be if genes cannot predict disease for the vast majority of people? Are genes with only extremely minor effects going to be of value as drug targets? How hard is it going to be to untangle their roles in disease when they have hardly any measurable effect? Should we still suppose that pouring more resources into human genetic research is going to rescue industry’s faltering drug development pipelines? All of a sudden, the future of medicine, especially in the specialities dealing with degenerative diseases and mental illness, looks very different and a lot less promising. We no longer have a ‘complete transformation’ to look forward to, only a continuation of the incremental improvements and setbacks that have characterised medicine for the last fifty years.

Shoring up the good ship medical genetics

In a rare public sign of the struggle to come to terms with this genetically impoverished world-view, the authors of a brief review in Science magazine, Andrew Clark of Cornell University and Emmanouil Dermitzakis of the University of Geneva Medical School, Switzerland have been alone in stating the case even partly straightforwardly. According to them, the GWA studies tell us that “the magnitude of genetic effects is uniformly very small” and therefore “common variants provide little help in predicting risk” (Dermitzakis and Clark 2009). Consequently, the likelihood that personalised genomics will ever predict the occurrence of common diseases is “bleak”. This aim, they believe, will have to be abandoned altogether.

The first conclusion to be drawn from these quotes is that such directness implies that if the GWA findings are not finding their way to the front page the reason is not ambiguity in the results themselves. From a scientific perspective the GWA results, though negative, are robust and clear.

Most human geneticists view the GWA results somewhat differently, however. An invited workshop, convened by Collins and others, discussed the then-accumulating results in February 2009. The most visible outcome of this workshop was a lengthy review published in Nature and titled: “Finding the Missing Heritability of Complex Diseases.” (Manolio et al. 2009).

For a review paper that does not lay out any new concepts or directions, 27 senior scientists as coauthors might be considered overkill. “Finding the Missing Heritability”, however, should be understood not so much as a scientific contribution but as an effort to conceal the gaping hole in the science of medical genetics.

In their Science article, which was published almost simultaneously, Dermitzakis and Clark paused only briefly to consider whether so many genes could have been overlooked. Apparently, they thought it an unlikely possibility. Manolio et al., however, frame this as the central issue. According to them, since heritability measurements suggest that genes for disease must exist, they must be hiding under some as-yet-unturned genetic rock. They list several possible hiding places: there may be very many genes with exceedingly small effects; genes for disease may be highly represented by rare variants with large effects; disease genes may have complex genetic architectures; or they may exist as gene Copy Number Variants (CNVs). Since Manolio et al. presented their list, the scientific literature has seen further suggestions for where disease genes might be hiding. These include in mitochondrial DNA, epigenetics and in statistical anomalies (e.g. Eichler et al. 2010; Petronis 2010).

A problem for all these hypotheses, however, is that anyone wishing to take them seriously needs to consider one important question. How likely is it that a quantity of genetic variation that could only be called enormous (i.e. more than 90-95% of that for 80 human diseases) is all hiding in what until now had been considered genetically unlikely places? In other words, they all require the science of genetics to be turned on its head. For epigenetics, for example, there is scant evidence that important traits can be inherited through acquired modifications of DNA. Similarly, if rare variants with strong effects keep appearing in the population and causing major illnesses, why is there no evidence for this phenomenon, since it must have been occurring in the past? With unanswered questions such as these, it is unsurprising that none of the mooted explanations has attracted any kind of consensus among geneticists and in fact the CNV explanation is already looking highly unlikely (Conrad et al. 2010; The Wellcome Trust Case Control Consortium 2010). As the first of these two papers summarised “we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by CNVs” (Conrad et al. 2010).

Now, it is not impossible that human diseases follow unique genetic rules, but the apparently overlooked possibility is that the GWA studies are indicating a simple truth: that genes are not important causes of major diseases.

As stated so far, the case against the importance of genes for disease seems strong. However, the ‘missing heritability’ argument is based on numerous predictions of a large genetic contribution to human diseases that are derived from heritability measurements. These heritability estimates are obtained from the study of identical and non-identical twins. A crucial question becomes, therefore, are these estimates truly reliable?

How robust is the historical evidence for genetic causation?

A perennial feature of research into human health has always been the mountain of evidence that environment is overwhelmingly important in disease. People who migrate acquire the spectrum of diseases of their adopted country. Populations who take up Western habits, or move to cities with Western lifestyles, acquire Western diseases, and so on (e.g. Campbell and Campbell 2008). These data are hard to refute, not least because they are so simple, but geneticists, when discussing them, invariably wheel out their own version of incontrovertible evidence: twin studies of the heritability of complex diseases. When Francis Collins talks about ‘missing heritability’ it is to studies such as these that he is referring. They provide the basic evidence for genetic influences on human disease.

A classic example of this contradiction is myopia. A large body of evidence suggests that myopia is an environment-induced disorder caused by some combination of night lighting, close reading, lack of distance viewing and diet (e.g. Quinn et al. 1999). Moreover, under the influence of Westernisation, genetically unchanged populations, for example, are known to have switched in a single generation from close to 0% to a prevalence of myopia of over 80% (Morgan 2003). And myopia is only one of many examples of diseases with very strong evidence for its environmental origin. In 2009, for example, researchers demonstrated that very moderate improvements in lifestyle could reduce an individual’s probability of contracting type 2 diabetes by 89% (Mozzafarian et al. 2009). The subjects of this study just had to smoke less than the average, keep trim, exercise moderately and not eat too much fat.

In stark contrast, twin studies (which compare the extent of similarity exhibited by identical and non-identical twins) estimate that myopia is a disease with a heritability (called h²) of about 0.8 (out of a possible 1.0), indicating that for myopia genetic causes dominate environmental ones. These findings are clearly incompatible with the available epidemiological data on myopia and no satisfactory resolution to them has ever been proposed (e.g. Rose et al. 2002; Morgan 2003). This contradiction, between the results of twin studies and the results of epidemiological and clinical research, is repeated for almost every human disease.

A meaningful resolution to these contradictions is, nevertheless, necessary. Since it is unlikely that the many observations identifying environment as a dominant disease-causing factor are all incorrect, the parsimonious solution to the conundrum, even before the GWA studies were reported, was to propose that heritability studies of twins are inherently mistaken or misinterpreted.

Studies of human twins estimate heritability (h²) by calculating disease incidence in monozygotic (genetically identical) twins versus dizygotic (fraternal) twins (who share 50% of their DNA). If monozygotic twin pairs share disorders more frequently than do dizygotic twins, it is presumed that a genetic factor must be involved. A problem arises, however, when the number resulting from this calculation is considered to be an estimate of the relative contribution of genes and environment over the whole population (and environment) from which the twins were selected. This is because the measurements are done in a series of pairwise comparisons, meaning that only the variation within each twin pair is actually being measured. Consequently, the method implicitly defines as environment only the difference within each twin pair. Since each twin pair normally shares location, parenting styles, food, schooling, etc., much of the environmental variability that exists between individuals in the wider population is de facto excluded from the analysis. In other words, heritability (h²), when calculated this way, fails to adequately incorporate environmental variation and inflates the relative importance of genes.

Heritability studies of humans are classic experiments that have been conducted many times and they have strong defenders among modern geneticists (e.g. Visscher et al. 2008). Nevertheless, criticisms such as those above are not novel. They are a specific example of the general problem, formulated by Richard Lewontin (of Harvard University), that the contributions of genes to a trait normally depend on the particular environment. And further, that susceptibility to environment depends on genes. In consequence, there can be no universal constant (such as h²) that defines their relationship to one another (Lewontin, Rose and Kamin 1984; Lewontin 1993). Lewontin is not alone among geneticists in his dismissal of heritability as it is used in human genetics. Martin Bobrow of Cambridge University, for example, has called human heritability “a poisonous concept” and “almost uninterpretable”⁶.

If one accepts either that h² is consistently inflated, or that it is essentially meaningless, even “poisonous”, then the only current evidence supporting genetic susceptibility as a major cause of disease disappears. “The Missing Heritability of Complex Diseases”, DNAs’ so-called ‘dark matter’, becomes simply an artefact arising from overinterpretation of twin studies.

A mutually convenient untruth

Genetic determinist ideas, especially in the form of explanations for health and disease, are powerful forces in our society (Lewontin 1993). Their pervasive influence, however, requires some explanation because the purely scientific evidence for genetic causation has always been weak, since it depended heavily on disputed heritability studies. To understand the significance a repudiation of inherited DNA as a disease explanation has, it is first necessary to understand the role genetic determinism plays in consolidating the social order.

Politicians like genetic determinism as a theory of disease because it substantially reduces their responsibility for people’s ill-health. By shifting blame towards individuals and their genetic ‘predispositions’ it greatly dilutes the pressure they may feel to regulate, ban, or tax harmful products and contaminants, courses of action that typically offend their business constituents. For a politician, therefore, spending tax dollars on medical genetics is an easy and even popular decision.

Corporations like genetic determinism, again because it shifts blame. The Salt Institute website, for example, currently maintains that diseases linked to salt reflect the existence of a small number of highly predisposed individuals. This assertion, sandwiched (on the website) between other questions about salt and health, is clearly intended to undermine efforts to restrict salt in the diet. For the same reason, the tobacco industry has for many years encouraged research into the genetics of nicotine addiction (Gundle et al. 2010). This same reasoning, that disease is the fault of the victim’s genes, also protects corporate defendants from after-the-fact liability. If lung cancer patients, for example, suffer from even the possibility of a genetic predisposition, suing tobacco companies is very much harder than it would be otherwise (Tokuhata and Lilienfeld, 1963). There is evidence, too, that genetic determinism influences decisions well before the full facts are known. At least sometimes, it can even encourage the vendor knowingly to place on the market products with harmful effects (Gundle et al. 2010).

Medical researchers are also partial to genetic determinism. They have noticed that whenever they focus on genetic causation, they can raise research dollars with relative ease. The last fifteen years, coinciding with the rise of medical genetics, have seen unprecedented sums of money directed at medical research. At the same time, research on pollution, nutrition and epidemiology has not benefited in any comparable way. It is hard not to conclude that this funding disparity is strongly influenced by the fit of genetics to the needs of businesses and politicians. In the words of Homer Simpson, “It takes two to lie, Marge. One to lie and one to listen”.

Recognising their value, these groups have tended to elevate genetic explanations for disease to the status of unquestioned scientific facts, thus making their dominance of official discussions of health and disease seem natural and logical. This same mindset is accurately reflected in the media where even strong environmental links to disease often receive little attention, while speculative genetic associations can be front page news. It is astonishing to think that all this has occurred in spite of the reality that genes for common diseases were essentially hypothetical entities.

Mutually convenient or not, by the criteria normally applied in science, the hypothesis that genes are significant causes of common diseases stands refuted. The history of scientific refutation, however, is that adherents of established theories construct ever more elaborate or unlikely explanations to fend off their critics (Ziman 2000). The invocation of genetic ‘dark matter’ and the search for ‘hiding’ genetic variation shows that the process of special pleading is already well underway (e.g. Manolio et al. 2009; Eichler et al. 2010). Implausible though the suggested hiding places seem, it is nevertheless going to be difficult to rule them all out in the near future. Consequently, those geneticists wishing to do so will have the opportunity to obfuscate for some while yet.

Needed: A declaration of dependence

In societies, including our own, much of the social fabric is arranged around our conception of the ‘proper’ place of death and disease. Confidence in the genetic paradigm has led us to explain non-infectious disease as primarily a natural manifestation of genetic predispositions and thus a normal outcome of aging. This normalisation of diseases has obscured the contrary evidence that these same diseases can be all but absent in other cultures and often were rare in historical times. With the GWA results confirming the epidemiological studies, however, we are confronted with the necessity of constructing a new narrative. To be consistent with the facts, this new narrative must incorporate Western diseases not as unavoidable, but as indicators of human fragility in the face of industrialisation and modern life.

That we are so vulnerable to our social and physical surroundings, is an uncompromising message. But to the very best of our scientific knowledge it is the truth. Fortunately, it is a truth that offers hope. If we can change our environment for the worse, we can also change it for the better. And if a magic medical cure-all pill is not going to materialise after all, it may be that it wasn’t needed in the first place.

Change for better health can occur in part through individual effort. The new understanding implies that we are not fated to develop any of the common diseases and that the efforts we make to eat well and live a healthy life will be amply rewarded. We should not be surprised if specific lifestyle changes can reverse decades of disease progression (Esselstyn et al. 1995). Or that Seventh Day Adventists, who are non-smoking, non-drinking vegetarians, live on average to 88, eight years beyond the average American’s life expectancy (Fraser and Shavlik 2001). These examples suggest what can be achieved with relatively modest lifestyle changes. By focusing more exclusively on health-related lifestyle modifications than even Seventh Day Adventists do, we could probably extend our life expectancy still further. Exactly how much further is now a much more interesting question than we previously thought.

For most people, life expectancy is only truly of value if it is accompanied by life quality. We should expect, however, any future diminution of the burden of degenerative diseases from lifestyle modification to both extend life expectancy and enhance life quality⁷. If so, it might make the most common end-of-life experience very different from the actual prospect facing most Westerners for whom old age is commonly a process of ever more aggressive medical intervention culminating in a hospital room attached to drips and electrodes.

While individual effort has a place, many positive lifestyle and social changes require the cooperation of the state. Nevertheless, most governments cooperate far more, for example, with their food industries than with those who wish to eat a healthy diet. The laying to rest of genetic determinism for disease, however, provides an opportunity to shift this cynical political calculus. It raises the stakes by confronting policy-makers as never before with the fact that they have every opportunity, through promoting food labeling, taxing junk food, or funding unbiased research, to help their electorates make enormously positive lifestyle choices. And, when their constituents realise that current policies are robbing every one of them of perhaps whole decades of healthy living, these citizens might start to apply the necessary political pressure.

Addendum:
Following publication of ‘The Great DNA Data Deficit’ various readers have contacted us with relevant publications and books of which we were unaware. These important contributions to the issue of whether genes might cause disease extend or otherwise support the discussion considerably. They are listed below in chronological order. Our sincere thanks to readers for sending these in:

Clerget-Darpoux, F. and Cambon-Thomsen, A. (2010) How seriously should we take risk predictions for multifactorial illnesses? Text endorsed by a community of 11 French professional societies involved in genetic issues.
Jay Joseph and Carl Ratner (2010) The Fruitless Search for Genes in Psychiatry and Psychology: Time to Re-examine a Paradigm?
Claudia Chaufan (2007) How much can a large population study on genes, environments, their interactions and common diseases contribute to the health of the American people? Social Science & Medicine 65: 1730-1741.
Helen M. Wallace (2006) A model for gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype. Theoretical Biology and Medical Modelling 3: 35-58.
Jay Joseph The Missing Gene (2006)
Buchanan, A; Weiss K and Fullerton S Dissecting complex disease: the quest for the Philosopher’s Stone? (2005)
Jay Joseph The Gene Illusion (2004)
Jay Joseph (2002) Twin studies in psychiatry and psychology: science or pseudoscience? Psychiatric Quarterly 73: 71-82.
Joseph D Terwilliger and Kenneth M Weiss Linkage disequilibrium mapping of complex disease: fantasy or reality? Current Opinion in Biotechnology 9: 578-594 (1998)

Footnotes

(1) ‘Genes for’ disease is shorthand for genetic variants predisposing the carrier to disease.

(2) The definition of a genetically rare disease is usually that it affects fewer than 1 in 1,000 people. Approximately 6,000 rare diseases have been identified in humans.

(3) The famous alleles BRCA 1 and 2 are important in some families and populations but otherwise are fairly rare.

(4) According to the World Health Organisation, heart disease causes 17.1% of all deaths worldwide. Cancer causes 15% of all deaths. Stroke causes 10% of all deaths. WHO factsheet.

(5) The explanation of the contradiction between the GWA studies and the newspaper reports is that much of this coverage was hype. Almost without exception these newspaper reports covered discoveries whose significance could be questioned. Typically, they concerned unsubstantiated results, or the genes were for very minor diseases or the medical and genetic implications of the discovery were substantially overplayed.

(6) Why geneticists disagree about heritability has a historical context that usefully illuminates this issue. Once upon a time the term heritability was used differently. When Sewall Wright, one of the founders of genetics, developed the concept of heritability, he titled a key paper “The Relative Importance of Heredity and Environment in Determining the Piebald Pattern of Guinea Pigs” (Wright, 1920). He used this title even though all animals in the study were kept in identical conditions. Clearly, therefore, he wasn’t defining ‘environment’ as we now do. Instead, in that paper he explicitly defined environment as “the irregularities of development due to the intangible sorts of causes to which the word chance is applied”. All of the subsequent questions (like Lewontin’s) surrounding the validity of twin studies have arisen precisely because Wright’s method, which defined heritability in opposition to chance variations in development, was extended to populations of humans living in variable and varying environments.

(7) In popular speech, aging and degeneration are often conflated, leading sometimes to a rejection of health advice as simply life-span extension. However, aging, by definition, is simply the passage of time and research shows that typically, extended life expectancy is correlated with improved health, when age is taken into account (Fraser and Shavlik 2001). In case one is tempted to confuse aging and disease, it may be helpful to think of children. For them, aging is a process of becoming stronger.

Jonathan Latham, PhD (Photo Credit: auspices)

Imagine an international mega-deal. The global organic food industry agrees to support international agribusiness in clearing as much tropical rainforest as they want for farming. In return, agribusiness agrees to farm the now-deforested land using organic methods, and the organic industry encourages its supporters to buy the resulting timber and food under the newly devised “Rainforest Plus” label. There would surely be an international outcry.

Virtually unnoticed, however, even by their own memberships, the world’s biggest wildlife conservation groups have agreed exactly to such a scenario, only in reverse. Led by the World Wide Fund for Nature (WWF), many of the biggest conservation nonprofits including Conservation International and the Nature Conservancy have already agreed to a series of global bargains with international agribusiness. In exchange for vague promises of habitat protection, sustainability and social justice, these conservation groups are offering to greenwash industrial commodity agriculture.

The big conservation nonprofits don’t see it that way of course. According to WWF ‘Vice President for Market Transformation’ Jason Clay, the new conservation strategy arose from two fundamental realizations.

The first was that agriculture and food production are the key drivers of almost every environmental concern. From issues as diverse as habitat destruction to over-use of water, from climate change to ocean dead zones, agriculture and food production are globally the primary culprits. To take one example, 80-90% of all fresh water abstracted by humans is for agriculture (e.g. FAO’s State of the World’s Land and Water report ).

This point was emphasized once again in a recent analysis published in the scientific journal Nature. The lead author of this study was Professor Jonathan Foley (Foley et al 2011). Not only is Foley the director of the University of Minnesota-based Institute on the Environment, but he is also a science board member of the Nature Conservancy.

The second crucial realization for WWF was that forest destroyers typically are not peasants with machetes but national and international agribusinesses with bulldozers. It is the latter who deforest tens of thousands of acres at a time. Land clearance on this scale is an ecological disaster, but Claire Robinson of Earth Open Source points out it is also “incredibly socially destructive”, as peasants are driven off their land and communities are destroyed. According to the UN Permanent Forum on Indigenous Issues 60 million people worldwide risk losing their land and means of subsistence from palm plantations.

By about 2004, WWF had come to appreciate the true impacts of industrial agriculture. Instead of informing their membership and initiating protests and boycotts, however, they embarked on a partnership strategy they call ‘market transformation’.

Market Transformation

With WWF leading the way, the conservation nonprofits have negotiated approval schemes for “Responsible” and “Sustainable” farmed commodity crops. According to Clay, the plan is to have agribusinesses sign up to reduce the 4-6 most serious negative impacts of each commodity crop by 70-80%. And if enough growers and suppliers sign up, then the Indonesian rainforests or the Brazilian Cerrado will be saved.

The ambition of market transformation is on a grand scale. There are schemes for palm oil (the Roundtable on Sustainable Palm Oil; RSPO), soybeans (the Round Table on Responsible Soy; RTRS), biofuels (the Roundtable on Sustainable Biofuels), Sugar (Bonsucro) and also for cotton, shrimp, cocoa and farmed salmon. These are markets each worth many billions of dollars annually and the intention is for these new responsible and sustainable certified products to dominate them.

The reward for producers and supermarkets will be that, reinforced on every shopping trip, “Responsible” and “Sustainable” logos and marketing can be expected to have major effects on public perception of the global food supply chain. And the ultimate goal is that, if these schemes are successful, human rights, critical habitats, and global sustainability will receive a huge and globally significant boost.

The role of WWF and other nonprofits in these schemes is to offer their knowledge to negotiate standards, to provide credibility, and to lubricate entry of certified products into international markets. On its UK website, for example, WWF offers its members the chance to “Save the Cerrado” by emailing supermarkets to buy “Responsible Soy”. What WWF argues will be a major leap forward in environmental and social responsibility has already started. “Sustainable” and “Responsible” products are already entering global supply chains.

Reputational Risk

For conservation nonprofits these plans entail risk, one of which is simple guilt by association. The Round Table on Responsible Soy (RTRS) scheme is typical of these certification schemes. Its membership includes WWF, Conservation International, Fauna and Flora International, the Nature Conservancy, and other prominent nonprofits. Corporate members include repeatedly vilified members of the industrial food chain. As of January 2012, there are 102 members, including Monsanto, Cargill, ADM, Nestle, BP, and UK supermarket ASDA.

That is not the only risk. Membership in the scheme, which includes signatures on press-releases and sometimes on labels, indicates approval for activities that are widely opposed. The RTRS, for example, certifies soybeans grown in large-scale chemical-intensive monocultures. They are usually GMOs. They are mostly fed to animals. And they originate from countries with hungry populations. When 52% of Americans think GMOs are unsafe and 93% think GMOs ought to be labeled, for example, this is a risk most organizations dependent on their reputations probably would not consider.

The remedy for such reputational risk is high standards, rigorous certification and watertight traceability procedures. Only credibility at every step can deflect the seemingly obvious suspicion that the conservation nonprofits have been hoodwinked or have somehow ‘sold out’.

So, which one is it? Are “Responsible” and “Sustainable” certifications indicative of a genuine strategic success by WWF and its fellows, or are the schemes nothing more than business as usual with industrial scale greenwashing and a social justice varnish?

Low and Ambiguous Standards

The first place to look is the standards themselves. RTRS standards (version 1, June 2010), to continue with the example of soybeans, cover five ‘principles’. Principle 1 is: Legal Compliance and Good Business Practices. Principle 2 is: Responsible Labour Conditions. Principle 3 is: Responsible Community Relations. Principle 4 is Environmental Responsibility. Principle 5 is Good Agricultural Practice.

Language typical of the standards includes, under Principle 2, Responsible Labour Conditions, section 2.1.1 “No forced, compulsory, bonded, trafficked. or otherwise involuntary labor is used at any stage of production”, while section 2.4.4 states “Workers are not hindered from interacting with external parties outside working hours.”

Under Principle 3: Responsible Community Relations, section 3.3.3 states: “Any complaints and grievances received are dealt with in a timely manner.”

Under Principle 4: Environmental Responsibility, section 4.2 states “Pollution is minimized and production waste is managed responsibly” and section 4.4 states “Expansion of soy cultivation is responsible”.

Under Principle 5: Good Agricultural Practice, Section 5.9 states “Appropriate measures are implemented to prevent the drift of agrochemicals to neighboring areas.”

These samples illustrate the tone of the RTRS principles and guidance.

There are two ways to read these standards. The generous interpretation is to recognize that the sentiments expressed are higher than what are actually practiced in many countries where soybeans are grown, in that the standards broadly follow common practice in Europe or North America. Nevertheless, they are far lower than organic or fairtrade standards; for example they don’t require crop rotation, or prohibit pesticides. Even a generous reading also needs to acknowledge the crucial point that adherence to similar requirements in Europe and North America has contaminated wells, depleted aquifers, degraded rivers, eroded the soil, polluted the oceans, driven species to extinction and depopulated the countryside—to mention only a few well-documented downsides.

There is also a less generous interpretation of the standards. Much of the content is either in the form of statements, or it is merely advice. Thus section 4.2 reads “Pollution is minimized and production waste is managed responsibly.” Imperatives, such as: must, may never, will, etc., are mostly lacking from the document. Worse, key terms such as “pollution”, “minimized”, “responsible” and “timely” (see above) are left undefined. This chronic vagueness means that both certifiers and producers possess effectively infinite latitude to implement or judge the standards. They could never be enforced, in or out of court.

Dubious Verification and Enforcement

Unfortunately, the flaws of RTRS certification do not end there. They include the use of an internal verification system. The RTRS uses professional certifiers, but only those who are members of RTRS. This means that the conservation nonprofits are relying on third parties for compliance information. It also means that only RTRS members can judge whether a principle was adhered to. And even if they consider it was not, there is nothing they can do, since the RTRS has no legal status or sanctions.

The ‘culture’ of deforestation is also important to the standards. Rainforest clearance is often questionably legal, or actively illegal, and usually requires removing existing occupants from the land. It is a world of private armies and bribery. This operating environment makes very relevant the irony under which RTRS members, under Principle 1, volunteer to obey the law. The concept of volunteering to obey the law begs more than a few questions. If an organization is not already obeying the law, what makes WWF suppose that a voluntary code of conduct will persuade it? And does obeying the law meaningfully contribute to a marketing campaign based on responsibility?

Of equal concern is the absence of a clear certification trail. Under the “Mass Balance” system offered by RTRS, soybeans (or derived products) can be sold as “Responsible” that were never grown under the system. Mass Balance means vendors can transfer the certification quantity purchased, to non-RTRS soybeans. Such an opportunity raises the inherent difficulties of traceability and verification to new levels.

How Will Certification Save Wild Habitats?

A key stated goal of WWF is to halt deforestation through the use of maps identifying priority habitat areas that are off-limits to RTRS members. There are crucial questions over these maps, however. Firstly, even though RTRS soybeans are already being traded they have yet to be drawn up. Secondly, the maps are to be drawn up by RTRS members themselves. Thirdly, under the scheme RTRS maps can be periodically redrawn. Fourthly, RTRS members need not certify all of their production acreage. This means they can certify part of their acreage as “Responsible”, but still sell (as “Irresponsible”?) soybeans from formerly virgin habitat. This means WWF’s target for year 2020 of 25% coverage globally and 75% in WWF’s ‘priority areas’ would still allow 25% of the Brazilian soybean harvest to come from newly deforested land. And of course, the scheme cannot prevent non-members, or even non-certified subsidiaries, from specializing in deforestation (1).

These are certification schemes, therefore, with low standards, no methods of enforcement, and enormous loopholes (2). Pete Riley of UK GM Freeze dubs their instigator the “World Wide Fund for naiveté” and believes “the chances of Responsible soy saving the Cerrado are zero.” (3). Claire Robinson agrees: “The RTRS standard will not protect the forests and other sensitive ecosystems. Additionally, it greenwashes soy that’s genetically modified to survive being sprayed with quantities of herbicide that endanger human health and the environment.” There is even a website (www.toxicsoy.org) dedicated to exposing the greenwashing of GMO Soy.

Many other groups apparently share that view. More than 250 large and small sustainable farming, social justice and rainforest preservation groups from all over the world signed a “Letter of Critical Opposition to the RTRS” in 2009. Signatories included the Global Forest Coalition, Friends of the Earth, Food First, the British Soil Association and the World Development Movement.

Other commodity certifications involving WWF have also received strong criticism. The Mangrove Action Project in 2008 published a ‘Public Declaration Against the Process of Certification of Industrial Shrimp Aquaculture’ while the World Rainforest Movement issued the ‘Declaration against the Roundtable on Sustainable Palm Oil (RSPO)’, signed by 256 organizations in October 2008.

What Really Drives Commodity Certification?

Commodity certification is in many ways a strange departure for conservation nonprofits. In the first place the big conservation nonprofits are more normally active in acquiring and researching wild habitats. Secondly, as membership organizations it is hard to envisage these schemes energizing the membership—how many members of the Nature Conservancy will be pleased to find that their organization has been working with Monsanto to promote GM crops as “Responsible”? Indeed, one can argue that these programs are being actively concealed from their members, donors and the public. From their advertising, their websites, and their educational materials, one would presume that poachers, population growth and ignorance are the chief threats to wildlife in developing countries. It is not true, however, and as Jason Clay and the very existence of these certification schemes make clear, senior management knows it well.

In public, the conservation nonprofits justify market transformation as cooperative; they wish to work with others, not against them. However, they have chosen to work preferentially with powerful and wealthy corporations. Why not cooperate instead with small farmers’ movements, indigenous groups, and already successful standards, such as fairtrade, organic and non-GMO? These are causes that could use the help of big international organizations. Why not, with WWF help, embed into organic standards a rainforest conservation element? Why not cooperate with your membership to create engaged consumer power against habitat destruction, monoculture, and industrial farming? Instead, the new “Responsible” and “Sustainable” standards threaten organic, fairtrade, and local food systems—which are some of the environmental movement’s biggest successes.

One clue to the enthusiasm for ‘market transformation’ may be that financial rewards are available. According to Nina Holland of Corporate Europe Observatory, certification is “now a core business” for WWF. Indeed, WWF and the Dutch nonprofit Solidaridad are currently receiving millions of euros from the Dutch government (under its Sustainable Trade Action Plan) to support these schemes. According to the plan 67 million euros have already been committed, and similar amounts are promised (4).

The Threat From the Food Movement

Commodity certification schemes like RTRS can be seen as an inability of global conservation leadership to work constructively with the ordinary people who live in and around wild areas of the globe; or they can be seen as a disregard for fairtrade and organic labels; or as a lost opportunity to inform and energize members and potential members as to the true causes of habitat destruction; or even as a cynical moneymaking scheme. These are all plausible explanations of the enthusiasm for certification schemes and probably each plays a part. None, however, explains why conservation nonprofits would sign up to schemes whose standards and credibility are so low. Especially when, as never before, agribusiness is under pressure to change its destructive social and environmental practices.

The context of these schemes is that we live at an historic moment. Positive alternatives to industrial agriculture, such as fairtrade, organic agriculture, agroecology and the System of Rice Intensification, have shown they can feed the planet, without destroying it, even with a greater population. Consequently, there is now a substantial international consensus of informed opinion (IAASTD) that industrial agriculture is a principal cause of the current environmental crisis and the chief obstacle to hunger eradication.

This consensus is one of several roots of the international food movement. As a powerful synergism of social justice, environmental, sustainability and food quality concerns, the food movement is a clear threat to the long-term existence of the industrial food system. (Incidentally, this is why big multinationals have been buying up ethical brands.)

Under these circumstances, evading the blame for the environmental devastation of the Amazon, Asia and elsewhere, undermining organic and other genuine certification schemes, and splitting the environmental movement must be a dream come true for members of the industrial food system. A true cynic might surmise that the food industry could hardly have engineered it better had they planned it themselves.

Who Runs Big Conservation?

To guard against such possibilities, nonprofits are required to have boards of directors whose primary legal function is to guard the mission of the organization and to protect its good name. In practice, for conservation nonprofits this means overseeing potential financial conflicts and preventing the organization from lending its name to greenwashing.

So, who are the individuals guarding the mission of global conservation nonprofits? US-WWF boasts (literally) that its new vice-chair was the last CEO of Coca-Cola, Inc. (a member of Bonsucro) and that another board member is Charles O. Holliday Jr., the current chairman of the board of Bank of America, who was formerly CEO of DuPont (owner of Pioneer Hi-Bred International, a major player in the GMO industry). The current chair of the executive board at Conservation International, is Rob Walton, better known as chair of the board of WalMart (which now sells ‘sustainably sourced’ food and owns the supermarket chain ASDA). The boards of WWF and Conservation International do have more than a sprinkling of members with conservation-related careers. But they are heavily outnumbered by business representatives. On the board of Conservation International, for example, are GAP, Intel, Northrop Grumman, JP Morgan, Starbucks and UPS, among others.

At the Nature Conservancy its board of directors has only two members (out of 22) who list an active affiliation to a conservation organization in their board CV (Prof Gretchen Daly and Cristian Samper, head of the US Museum of Natural History). Only one other member even mentions among their qualifications an interest in the subject of conservation. The remaining members are, like Shona Brown, an employee of Google and a board member of Pepsico, or Margaret Whitman who is the current President and CEO of Hewlett-Packard, or Muneer A Satter, a managing director of Goldman Sachs.

So, was market transformation developed with the support of these boards or against their wishes? The latter is hardly likely. The key question then becomes: did these boards in fact instigate market transformation? Did it come from the very top?

Never Ending

Leaving aside whether conservation was ever their true intention, it seems highly unlikely that WWF and its fellow conservation groups will leverage a positive transformation of the food system by bestowing “Sustainable” and “Responsible” standards on agribusiness.  Instead, it appears much more likely that, by undermining existing standards and offering worthless standards of their own, habitat destruction and human misery will only increase.

Market transformation, as envisaged by WWF, nevertheless might have worked. However, WWF neglected to consider that successful certification schemes historically have started from the ground up. Organic and fairtrade began with a large base of committed farmers determined to fashion a better food system. Producers willingly signed up to high standards and clear requirements because they believed in them. Indeed, many already were practicing high standards without certification. But when big players in the food industry have tried to climb on board, game the system and manipulate standards, problems have resulted, even with credible standards like fairtrade and organic. At some point big players will probably undermine these standards. They seem already to be well on the way, but if they succeed their efforts will only have proved that certification standards can never be a substitute for trust, commitment and individual integrity.

The only good news in this story is that it contradicts fundamentally the defeatist arguments of the WWF. Old-fashioned activist strategies, of shaming bad practice, boycotting products and encouraging alternatives, do work. The market opportunity presently being exploited by WWF and company resulted from the success of these strategies, not their failure. Multinational corporations, we should conclude, really do fear activists, non-profits, informed consumers, and small producers, when they all work together.

Footnotes
(1) RSPO standards don’t make much use of maps in their Criterion 7 on “Responsible development of new plantings”. Instead, they rely on “Environmental Impact Assessments” and identifying “High Conservation Value” areas. However, these are every bit as questionable as RTRS maps. According to the UN forum on indigenous peoples, loggers frequently use designations of oil palm plantations as an excuse to log. RSPO, in its guidance notes to Criterion 7.3 under “Responsible development of new plantings”, the standard states: “Development should actively seek to utilise previously cleared and/or degraded land.” It is not a secret therefore, that RSPO plantations offer logging as an excuse to expand.
(2) These standards are also strewn with loopholes. Under RTRS standards, for example, members are allowed to justify why they dont meet a particular standard. Also under RTRS, farming principles called Integrated Crop Management are “voluntarily adopted”. Annex 5 of the standards states that: “The table below presents a non-exhaustive list of measures and practices that can be used”, i.e. use is optional. Under Bonsucro standards, on the other hand, members must meet 80% of them.
(3) The US version of WWF still calls itself the World Wildlife Fund.
(4) The role of the Dutch Government in financing and otherwise supporting sustainable certification is important to this story. On Dec 16th 2011 The Dutch Trade ministry announced that Dutch imports of soybeans would be 100% “Responsible” within four years. Dutch WWF, which is coordinating much of the program, is receiving money from the Dutch Government because Holland is a key player in international agriculture. The Dutch government’s sustainable food strategy notes the following: “Although the Netherlands is a small country, it plays a key role in food production and is the second largest exporter of agricultural products in the world, the largest exporter of seed and propagating material and breeding animals and internationally it is a prominent centre of knowledge.”
A second important Dutch consideration is that Rotterdam is the largest destination for importation of produce and commodity crops into Europe.

References

Foley, J et al (2011) Solutions for a Cultivated Planet Nature 478: 337–342