The Singling Out of Golden Rice

I saw earlier today that Steven Novella, MD, over at Neurlogica blog covered some controversy surrounding Golden Rice and it reminded me I had some thoughts to throw down about the GR issue. Dr Novella's post was in response to some of the claims made in a comment written on his post about a recent Nature Biotechnology paper on crop biofortification. This is an area I've seen a lot of commentary on, no doubt because Golden Rice is a transgenic crop. Dr Novella makes some good commentary in his post and I suggest reading it (here) before the rest of this post - it will contain some additional thoughts to Dr Novella's.

Dr Novella did a great job fielding the opposition to Golden Rice, which is something I've always found rather odd - I guess if you're vehemently opposed to a technology that represents a diverse array of methods (there's not one way to genetically engineer a plant) and innumerable potential outcomes (plants can be engineered for any number of traits), you've got to get creative with your reasons for universally disapproving of any crop categorized as a 'GMO'. There are certainly complications to Golden Rice, getting it to market and actually seeing a benefit from it - as Dr Novella points out, apart from the scientific complications of optimizing GR to the environment which it would be grown in, there are serious political steps to overcome (it might also help if activists aren't burning down your crops). I find the critiques of golden rice to be rather unfair, more than they are invalid. Sure, there many barriers to maintaining vitamin A status, and the deficiency is actually due to more complex socioeconomic/political issues, but these critiques don't invalidate the use of golden rice, nor are they specific to golden rice.

Harvestplus.org

Golden rice was created to provide a source of beta-carotene, which is further oxidized in the body to retinoic acid and retinaldehyde; these are essential for a whole host of functions including normal cell differentiation (critical to a developing fetus, and for immune function), and in the vision cycle. Inadequate intakes of this vitamin can lead to a number of clinical manifestations, including severe vision impairment, blindness and increased mortality from infections. The fallacy of the golden rice conversation is that its the only instance where beta-carotene has been the subject of biofortification. For all those making arguments about golden rice having issues with bioavailability, or adaptation to the local environment, or being too reductionist and not treating the causal issues of poverty/an un-diversified diet, your critique actually applies to the much broader field of plant science: both cassava and orange maize have been biofortified for higher beta carotene content through traditional breeding. A recent paper (1) in Advances in Nutrition was just published establishing the efficacy of these 2 biofortified crops in improving vitamin A status (note that where these contain 10-15ug/g of beta carotene, golden rice (GR2) contains 31ug/g).  I find it rather disingenuous when individuals critique only GR for the limitations mentioned by the commenter on Dr Novella's blog, when they apply more broadly to the field of plant breeding - checkout organizations like HarvestPlus, which do really awesome work with getting biofortified crops to those who need it (they support research for both transgenics and conventionally bred crops). I, personally, see both conventionally bred and transgenic crops as awesome ways to improve the nutrient status of staple crops, and while they're not fixing the problems that led to vitamin A deficiency, they can provide solutions to the deficiency while the more complex issues are sorted out (if they can be). My enthusiasm for transgenics, (more so than conventionally biofortified crops) comes from instances such as Naqvi et al's transgenic multivitamin corn (2) that contains increased amounts of beta carotene, folate, and acorbate (vitamin C) or HarvestPlus' biosorghum - while conventional breeding can be used to increase nutrient content, it always falls within the natural variation of the plant and is limited by that.

A point Dr. Novella doesn't address in his responses is the claim that biofortification is risky, because overdosing on vitamin A has been linked to birth defects and an increased risk of cancer in smokers. Dr Novella rightly notes that it would be near impossible to consume enough Golden Rice to reach toxicity limits, but there's a vital distinction here that needs to be made, and isn't in the commenters points. The commenter states that vitamin A is linked to birth defects, but they fail to mention that beta-carotene is not. Preformed vitamin A supplementation carries the risk for birth defects (3,4), whereas beta carotene has not been shown to. Beta-carotene's conversion to retinal is much more tightly regulated (5,6) and has been shown to be safe in trials (7), to the point that the IOM does not have an upper limit for beta carotene (8). The commenters note about smoking is true (though its not always a consistent observation (9)), but hopefully we aren't encouraging smoking alongside biofortified crops (and even these crops couldn't get you to the 20+milligram amounts that it takes to see a detrimental effect (10)). Actually, this commenters argument highlights the reality that supplementation programs present greater risk via their use of preformed vitamin A, and the role biofortified crops could play in safely delivering beta-carotene.

I think what annoys me most about these kinds of comments, and such criticisms made by GreenPeace, is that they act as though people are being unnecessary technological optimists, and that the hurdles associated with Golden Rice (and despite their not mentioning it, conventionally biofortified crops) aren't known by the organizations and researchers trying to get these products out there. Take a look at HarvestPlus' plans for 2008-2010 and you'll see that they're clearly aware of such issues as bioavailability, nutrient retention, and consumer acceptance. Researchers who are putting this into place aren't dumb; they've deemed these efforts to be worth the money, and superior to supplementation and fortification. Food-based approaches are already considered ideal (11) and efficacious (12), and discounting the role transgenics can play in this would be a shame; even worse, would be for an international organization to spread fear over a product that has not been shown to inflict any harm, and actually, has been demonstrated to improve health.

If you don't agree with me that Golden Rice can be a part of the solution for vitamin A deficiency, that's fine; I don't think it's unfair that some are critical about the future efficacy of GoldenRice - just be aware that many of the arguments against GoldenRice also work against traditional breeding efforts, and those should be included in your critiques. For those not persuaded either way, take a read through the WHO's guidelines for Vitamin A supplementation, and all that goes into monitoring those kinds of programs, and the idea of getting a successful biofortified crop to populations with low vitamin A intake might sound great, or at least an avenue worth trying out.


1. http://advances.nutrition.org/content/5/5/568.full.pdf+html
2. http://www.pnas.org/content/106/19/7762.full.pdf+html
3. http://www.who.int/nutrition/publications/vad_consequences.pdf
4. http://ods.od.nih.gov/factsheets/VitaminA-HealthProfessional/
5. http://www.ncbi.nlm.nih.gov/pubmed/16699835
6. http://www.ncbi.nlm.nih.gov/pubmed/23393141
7. http://www.ncbi.nlm.nih.gov/pubmed/10919941
8. http://www.nap.edu/openbook.php?record_id=10026&page=82
9. http://www.ncbi.nlm.nih.gov/pubmed/8602179
10. http://www.nejm.org/doi/full/10.1056/NEJM199404143301501
11. http://www.fao.org/docrep/004/Y2809E/y2809e08.htm
12.http://www.harvestplus.org/sites/default/files/Abstract%208_Food-based%20Approaches%20for%20Ensuring%20Adequate%20Vitamin%20A%20nutrition_0.pdf