A GM cure for toxic maize

July 2017

Each year, some 16 million tons of maize are lost globally to contamination by 'aflatoxins' after infection by some species of Aspergillus fungus.

In the US alone, wastage due to aflatoxins is estimated to cost agriculture $270 million per annum. Added to this is the expense of essential regulation for safety, because some forms of aflatoxin are the most potent toxins on the planet.

The substance produced by Aspergillus isn't, in itself, harmful. Ironically, when it reaches the liver, the main organ of detoxification, aflatoxins are transformed into derivatives which are toxic at levels of very few parts per billion. At very high doses, aflatoxins can cause acute liver damage and death. More usually however, their effects are chronic. They have been linked to birth defects, impaired immune system and, in the young, stunted growth.

Aflatoxins also have the sinister ability to target DNA and, in particular, attack a specific gene which protects against cancer. The result is liver cancer.


In this respect, aflatoxins work synergistically with hepatitis B virus which also alters DNA in the liver and weakens the liver cells.

Globally, some 5 billion people are exposed to the toxin and 5 million children under 5 years of age die from it. Aflatoxin makes a major contribution to the 9% of all new cancers which now effect the liver. Ninety three percent of of liver cancer sufferers die within 12 months of diagnosis.

Animal health is also harmed by aflatoxins, not only from maize but also from cotton seed, another major feed ingredient susceptible to Aspergillus infection. Humans can in turn be poisoned by eating products from contaminated livestock.

In developed, resource-rich countries, established regulatory limits on aflatoxins in traded food, along with monitoring, testing facilities, and optimal drying and storage practices, have largely eliminated the risk. Indeed, the US National Cancer Institute noted in 2015 that "To date, no outbreak of human illness caused by aflatoxins has been reported in the United States."

In areas where the infrastructure doesn't exist to closely regulate food and trade, the situation is very different. Ambient high humidity and temperature make it particularly likely that Aspergillus-susceptible crops in the ground and in the market will be contaminated. Sub-optimal food drying and storage plus lack of controls make aflatoxin contamination endemic in many areas. Most rural dwellers can afford only a limited range of foods: in many areas maize and peanuts, both susceptible to Aspergillus, constitute a significant proportion of the diet. Prolonged storage and frequent food shortages often mean a highly contaminated diet is the only thing available. Such areas are also prone to a high incidence of hepatitis B virus.

Aflatoxin-free maize has long been a goal of science, and what better way to achieve this than GM maize which can block the production of the toxin's precursor in any Aspergillus which infects it?

A proof-of-concept trial of just such a maize has just been published. The novel maize uses the latest thing in GM technology, 'RNA interference' (a.k.a. RNAi or dsRNA [1]). In laboratory tests, it successfully prevented toxin production by the fungus.

To minimise the risk of side-effects on the transgenic maize plants themselves, the novel DNA was designed to be active in the kernels only: the outside of the ear and other parts of the plant could still harbour Aspergillus infection and aflatoxin contamination.

No aberrant DNA expression was detected in the GM kernels. However, the researchers are clear that "a lot of downstream testing will be required before (the GM maize) could be grown in the field", but they anticipate that "we could realistically see this corn in 10 to 20 years".

The GM maize is expected to have a positive financial impact in the US, but the lead scientist "is most excited about what it will do in undeveloped countries". She'd "love to see it go to Africa" where "It can save lives".

OUR COMMENT

Noting that the Bill and Melinda Gates Foundation financed the aflatoxin-free GM maize research with one of its 'Grand Challenges' grants made us double-check the paper for signs of PR dressed up as science. 

Sure enough, in the paper's introduction, the underlying justification for the GM crop is that "current prevention strategies" are "proving inadequate". This leaves GM, by default, as the only solution. 

Four 'current strategies' are listed.

First, conventional breeding of disease-resistant crops. The citation for this inadequate current strategy is dated 1995. It seems to have passed the Grand Challenges scientists by that in 2006 US Department of Agriculture scientists published details of aflatoxin-resistant maize strains they had developed. These have now been field-trialed and released. 

Second, control of toxic strains of Aspergillus with competing non-toxic strains. The citation for this inadequate current strategy is dated 1991. 

Third, improved post-harvest storage methods. The citation for this 'inadequate' prevention method is a book chapter entitled 'Pre- and post-harvest management of aflatoxin in maize: an African perspective' (2008). Its summary states "Sound crop management practices are an effective way of avoiding, or at least diminishing, infection by Aspergilus flavus and subsequent aflatoxin production", and there follows a list of examples of effective practices. The chapter goes on to describe apparently continuing work on these practices. 

An African-based study published a year before the book also seems to have passed the Grand Challenges scientists by. This concluded that "Simple post-harvest intervention strategies were successful in reducing aflatoxin exposure in a subsistence farm setting, providing a rationale for prevention of aflatoxin-related disease." The study "focused on post-harvest measures, because much of the contamination occurs at this stage and post-harvest approaches are generally simple and cheap compared with some other strategies; we particularly wished to consider methods that could be implemented at the subsistence farm level ..." The methods tested, and clearly not found inadequate, were listed. 

Fourth, the use of chemical "trapping agents" to block toxin uptake by the food. The citation describes a effective seed-surface treatment which destroys both Aspergillus and its aflatoxins. This strategy is not so much inadequate as irrelevant: it's only ever going to be practical on a small scale and on a harvest already in good condition because once the fungus has penetrated into a compromised seed, surface decontamination won't remove the toxin. 

Overall, the impression is that the excuses for developing this particular GM maize are way out of date, inappropriate, or untrue. 

Downstream testing is certainly needed to clarify whether the kernels in storage, especially those in suboptimal storage conditions, continue to be protected from Aspergillus in the long term, because GM maize sold as 'non-toxic' will likely be treated as such by the user no matter how, or for how long, it's been stored. 

Safety of food and feed containing RNAi is a very big question indeed: people and animals will be eating it, and it could interfere with their DNA expression too. 

Professor Jack Heinemann has published extensive concerns about the risks of applying RNAi to food, and has recommended they be subject to long-term feeding studies in at least two different animal species. These would have to be followed by clinical trials. A development time of 10-20 years is very short for the depth of testing needed to address the safety of a staple food crop on which so many people and livestock depend. 

Perhaps it would be better if a bit more of the Gates Foundation millions were poured into helping subsistence farmers to help themselves using the numerous low-tech, improved post-harvest storage methods already tried, tested, and found useful, relevant and sustainable, rather than fancy, very expensive, problem-ridden GM technology. 

GM food with RNAi is one class of food you definitely want to avoid. 

Background

[1] RNA MODIFIED FOOD - July 2013

SOURCES:

• Dhiraj Thakara, et al., March 2017, Aflatoxin-free transgenic maize using host-induced gene silencing, Science Advances 3
• Christopher Paul Wild, 2007, Aflatoxin exposure in developing countries: The critical interface of agriculture and health, Food and Nutrition Bulletin 28:2
• What are aflatoxins? National Cancer Institute, 20.03.15
• K. Hell and others, Pre- and post-harvest management of aflatoxin in maize: an African perspective, Chapter 19 in Mycotoxins: detection methods, management, public health and agricultural trade, 2008, ISBN 9781845930820
• Michael C. Kew, 2013, Aflatoxins as a Cause of Hepatocellular Carcinoma, Journal of Gastrointestinal Liver Disease 22:3
• New GMO to combat liver cancer - or untested risk to health? GM Watch 13.05.17
• Daniel Stolte, Aflatoxin: Researchers Use Transgenic Corn Plants to Prevent the Deadly Toxin, University of Arizona News, 24.03.17
• W. P. Williams, March 2006, Breeding for resistance to aflatoxin accumulation in maize, Mycotoxin Research, 22(1)
• IARC Monograph on Aflatoxins, current June 2017
• Sonja Begemann, New GMO to Reduce Cases of Liver Cancer, 3.05.17
• Global Grand Challenges partnership network, https://gcgh.grandchallenges.org
• Tetsuya Suzuki, et al., 2002, Decontamination of Aflatoxin-Forming Fungus and Elimination of Aflatoxin Mutagenicity with Electrolyzed NaCl Anode Solution, Journal of Agricultural and Food Chemistry 50
• Raymond J. St. Leger, 2000, Lack of Host Specialization in Aspergillus flavus, Applied and Environmental Microbiology, January
  
  
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