Jan 19 2015

Golden Rice Follow Up

There is a major anti-golden rice smear and disinformation campaign underway, spearheaded by Greenpeace with other anti-GMO activists on board. They themselves consider golden rice to be a “Trojan horse” for GM technology in general, so they essentially admit that their motivation is to oppose GM technology, even if that means opposing a technology that can save the sight and lives of poor children.

Golden rice is a genetically modified rice variety with enhanced production of beta carotene, the pro-vitamin of Vitamin A. The name derives from its golden color, provided by the beta carotene, the same thing that makes carrots orange. Carrots, by the way, were originally white and were modified through breeding to produce beta carotene, which was a very successful biofortified campaign in Europe that effectively combated vitamin A deficiency.

In response to my post from last week on biofortified GM crops, one commenter did a large “cut and paste” into the comments (generally considered a comment etiquette no-no, but I let it through because the topic is so important) with essentially the full anti-golden rice propaganda. The commenter seemed to think this constituted a “convincing” argument. Let’s see.

*GR IS STILL NOT READY

While there have been long delays in the development of GR since it was “invented” in 2000 (1), this has not been due to the activities of anti-GMO activists, but to basic R&D problems.

This is confirmed in a statement by the International Rice Research Institute, the main body working on the GR project (2). According to the Institute, the time frame for developing a new product is about 13 years, and GR is “still under development and evaluation”. In September 2013 the IRRI expected GR to take another two years before it was ready.

While this point is essentially correct, it is not an argument against the adoption of golden rice. Golden rice (GR) development began in the 1980s. By 2000 the first GR variety was ready, but it produced too little beta carotene to be effective. GR2, using different genes, was ready by 2005 and contained 23 times as much beta carotene as GR 1. This is enough to effectively combat vitamin A deficiency in cultures that consume rice as their primary staple.

So why has GR2 not been implemented 10 years later? This is a complex question, but after reading multiple sources it does seem that the primary reason is that further development is necessary. GR2 was developed from an American rice strain, and is not well adapted to the Asian countries that can most benefit from it. What is happening now is that GR2 is being bred with local varieties that are locally adapted (a process called introgression). The goal is to produce a strain with the beta carotene but also with local traits so that is can match existing cultivars in yield and disease resistance. This will be necessary for widespread acceptance by farmers.

This process is time consuming, partly because there are multiple strains of GR2 (representing different locations in which the new genes were inserted), and researchers don’t know which one will make the best cross with the local rice varieties. This is why field testing is so important.

But the story is not just that the scientific process of development takes time. Vandalizing of field trials in the Philippines, motivated by anti-GMO sentiments, has caused a delay in the research. Some also argue that the regulatory burden in many countries is excessive, and is motivated by public opposition to GM. 

This is a good example of the circular nature of many anti-GMO arguments – anti-GMO activism is slowing the development process for new GM varieties, which is then criticized as being slow.

In any case, by all accounts we are in the final stages of developing commercially viable strains of GR2 for Asian markets where they are most needed.

*GR IS NOT NEEDED

GR is an expensive and unproven ‘solution’ to a problem for which better solutions exist. It has swallowed millions in development money and yet is still not ready.

In contrast, World Health Organisation programs to combat vitamin A deficiency are cheap, already available – and proven to work. They focus on methods such as educating people to grow green leafy vegetables in kitchen gardens, encouraging breastfeeding of babies, and giving supplements and fortified foods when necessary.(3) Research by Dr Vandana Shiva’s organization Navdanya in India has calculated that green leafy vegetables are up to 3500% richer in beta-carotene than GR.(4)

These programs only need modest funding to roll out more widely. They have the additional advantage of simultaneously treating other nutritional deficiencies, as these do not occur in isolation. For example, beta-carotene can only be absorbed by the body if the person eats enough fat. Will GR proponents give out dietary fat with the GR to those who need it?

This is an absurd and factually challenged version of the Nirvana fallacy. Sure – if we fixed the problems of poverty, food distribution, and poor education we would solve malnutrition in general. Of course we should be working toward these broader goals, but they are obviously not going to be fixed any time soon (even if every dime spent on GR development were instead devoted to these underlying problems).

GR is also not expensive. It’s hard to come up with a single figure, but at the low end estimates are that $2.6 million has been spent on development so far. One study estimated that the total cost of bringing GR to market in India would be $21-$28 million for the next 30 years. This is less than $1 million per year, and most of those costs are for promotion and marketing.

By all accounts GR would be a highly cost effective solution to vitamin A deficiency, even more cost effective than the alternatives promoted by anti-GMO activists.

Of course, we should continue to pursue other solutions as well, such as supplementation and introducing more crop varieties to local farmers. These efforts are under way, and they have an effect, it’s just not enough.

These objections sound very similar to those by anti-fluoridationists – we don’t need fluoride in the water because brushing with toothpaste and other dental hygiene interventions are effective. This is the same fallacy – universal public health measures have the advantage of being universal and automatic. Historically they are therefore much more effective. They are particularly effective for the target populations, such as the poor.

 Other problems with GR include:

1. Hidden Information on GR’s Genetic Makeup

There has been no adequate characterisation of GR in the peer-reviewed literature (5). Where there is secrecy, there is mistrust.

No information is hidden. GR development programs are open source. Here is a detailed description of the metabolic pathways altered in GR. The genes inserted and their locations are known. This is simply a false accusation.

2. Breeding Problems

The early varieties of Golden Rice were GR1 and GR2 — both bred from Japonica rice varieties because of severe difficulties with breeding from Indica varieties. In the areas which are being initially targeted – India, Sri Lanka, Bangladesh, Philippines – the vast majority of the population eats Indica, not Japonica varieties. Testing of a GR Indica variety did not start until 2010 and outdoor trials appear to be confined to the Philippines. There is still no published data available as to the stability, uniformity, yields or beta-carotene levels of either the older or newer versions of GR.

There are no breeding “problems” with GR. The researchers used the rice varieties that are commonly used in research, and are therefore well understood, and now are crossing the GR varieties with locally adapted varieties. Field trials were initially in the US, because of regulatory red tape elsewhere, and now are taking place in the Philippines, which is more appropriate. Essentially the argument here is that – science is taking time, and regulatory hurdles are slowing the process. None of this has anything to do with the safety, effectiveness, and cost effectiveness of GR.

3. Beta-carotene Persistence

No one knows how much beta-carotene will remain in GR over time when stored in normal domestic conditions. When some GR1 was sent in 2001 to scientists in Germany, they found that the level of beta-carotene was less than 1% of what it should have been. After cooking the level declined further, by 50%. This finding set back the project by many years.

Persistence of beta carotene over time is certainly an issue that needs to be monitored. However, researchers at the International Rice Research Institute have found that the beta carotene levels remain high in rice stored for three months. There is no reason to think they will drop off dramatically after that.

Like most of the other objections, this is not a known issue with GR. Opponents are simply raising every possible thing that could theoretically go wrong with a new technology as if it is a deal-breaker. If this becomes an issue, then scientists will address it. Right now it is not known to be a problem.

4. Bioavailability

No one knows how “bioavailable” the beta-carotene in GR will prove. Only two published human feeding studies have been conducted to test this – a controversial child-feeding study published in 2012 and an earlier feeding study involving adults, published in 2009 (see point 7 below). Both these “proof of principle” studies fail to give information on whether GR would work in a real-life situation. For example, the GR samples were stored at -80 degrees C and -70 degrees C respectively, prior to their use in the trials. This was to delay any decline in beta-carotene levels. The studies gave no information as to the usefulness of GR in real domestic situations and in a typical diet. Also, the adult feeding study was designed to maximise the absorption of beta-carotene through the addition of 10% butter to the test diet – an unrealistic scenario with respect to the poor people of Asia.

There are currently two published studies looking at bioavailability of vitamin A from GR. The first was a test in 5 healthy adults and showed good absorption. The second study was in 68 children aged 6-8 and compared GR to spinach to oil-based vitamin A capsules. They fount that the GR was as effective as the supplements, and more effective than spinach at increasing vitamin A levels. While these studies are limited and preliminary, they do indicate great bioavailability for vitamin A from GR. There is also no reason to suspect otherwise.

The objections above are not convincing. The child study, the larger and more definitive of the two, did involve real world situation, with only the addition of GR. The fact that the rice was refrigerated has nothing to do with bioavailability – that is just repeating the concern of persistence of beta carotene with storage, which again is likely not an issue.

Also, just a correction, in the adult study the rice was given with 10 g of butter, not “10%” butter.

5. Biofortification is Risky

GR is a “biofortified” product. But there are issues with “nutritional enhancement” and fortification. Due to differences between individuals (old and young, healthy and ill, male and female, overweight and undernourished), some people in the population will get too little of the nutrient and others too much. Overdosing on vitamin A has been linked to an increased risk of birth defects, and in the case of smokers to an increased cancer risk. (6)

This, again, is the same objection that anti-fluoridationists use. Biofortification is not inherently risky. Such programs have a long history of safety and effectiveness, from iodine in salt to calcium and vitamin D in milk. It would be nearly impossible to consume so much GR that it results in vitamin A toxicity. Some people might not get enough, but no one is claiming that this one intervention will end vitamin A deficiency. It is simply one additional tool among several to address this serious problem.

6. No Proof that GR is Safe to Eat

Genetic modification can result in novel toxins or allergens being created in plants, or changes in nutritional value. New toxins or allergens can appear even if the gene of interest is taken from a non-toxic source, since changes can happen after the gene is inserted into the new host plant. Such unexpected changes are difficult to detect without dedicated animal feeding safety trials. One potential hazard, as pointed out by Prof David Schubert of the Salk Institute in the USA, is associated with retinoic acid, a vitamin A derivative which can damage human fetuses and cause birth defects. (7)

The study above in 68 children showed no adverse effects from eating GR, so that is evidence of safety. Sure, there are potential unforeseen consequences from any new cultivar, whether from breeding, mutation breeding, or GM technology. That is why testing is appropriate. So far there hasn’t been a single case of allergic reaction to a GM variety, nor has there been any adverse health outcomes.

This is the core of anti-GMO fearmongering, an absurd application of the precautionary principle. Any potential fear is exaggerated, rather than taking a rational risk vs benefit analysis. There is no such thing as zero risk, but the science and history of GM technology has shown the risks to be very low. Compare this to the known morbidity and mortality of vitamin A deficiency.

7. Unethical Trials on Humans

Even though GR has not been tested for unexpected toxins or allergens in animal feeding trials, the Golden Rice Humanitarian Board, in conjunction with Tufts University, has conducted three feeding experiments on humans. One included the use of children “without adequate vitamin A nutrition” (10). In 2009 a group of 32 scientists (11) complained to Tufts about this breach of medical ethics and the Nuremburg Code. When the research resulted in the publication of two papers (in 2009 and 2012), there was a furore in China due to the use of children in one experiment without informed consent. The revelation led to the sacking of three Chinese officials and the forced retirement of the lead researcher at Tufts.

This is an excellent example of generating controversy in order to demonize a safe and effective technology. The real story here is that the Chinese trial was thoroughly reviewed by Tufts, and as reported by Science:

The reviews found no evidence of health or safety problems in the children fed golden rice; they also concluded that the study’s data were scientifically accurate and valid. Indeed, Souvaine’s letter to the USDA stresses that the results “have important public health and nutrition implications, for China and other parts of the world.”

However, there were issues with the informed consent and Chinese oversight of the study. While this is unfortunate, it has absolutely nothing to do with the scientific validity of the study. Nor is this an indictment of GR research in general. The 32 scientists were anti-GMO activists, but their objections are presented in a way to make it seem like the scientific community objected to the study. This is all an attempt to distract from the actual results of the study, which show that GR is an effective method of increasing vitamin A levels.

Conclusion

It is easy to raise objections to any new scientific research or technology. There are always many potential problems, research is never perfect, individuals make mistakes, and new technologies always seem to take more time than initially promised or that it seems like they should.

Any new technology or proposed solution can therefore be made to seem like a boondoggle if you obsess over the problems and make every effort to exaggerate them. You can make vaccines seem unsafe, fluoride in public water to be irresponsible, evolution to be uncertain, global warming to be a hoax, psychiatry to be a crime against humanity, or whatever suits your ideological agenda.

We are best served, however, not by ideological attacks but by a fair and thorough assessment of risks and benefits and cost effectiveness.

The available science and assessments indicate that GR is an extremely promising technology that gives every indication of being safe, effective, and cost-effective. It has the potential to save millions of children from going blind and thousands from dying .

Rather than opposing this technology, we should be providing public funding to support the corporate and charitable funding already being used. Field trials should be accelerated and GR should be fast-tracked, while conducting the extensive studies necessary to address every potential aspect of the technology. The potential humanitarian benefit is huge and worth the investment.

The misinformation campaign by anti-GMO groups serves only to slow the development and adoption of golden rice. In this case there is a measurable body count and human cost associated with their ideological opposition.

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