How A Crazy Idea Was Transformed Into A Global Health Advancement

There is an important, but little-known safety feature of our food supply – we can enjoy foods like peanuts, tree nuts, and corn meal without being exposed to a poisonous and carcinogenic natural chemical called “aflatoxin” that is produced by a fungus called Aspergillus that can infect those crops. In the developed world we are protected from this toxin because our farmers employ diverse control measures to minimize this kind of infection during the growing season, and after harvest there are detection and sorting protocols that exclude contaminated lots from the food and feed supply. Millions of people in Africa are not so fortunate. Their staple food crops like maize and groundnuts are frequently contaminated with aflatoxin, leading to high rates of liver cirrhosis, cancer, childhood stunting, and even death by acute poisoning. Many of the control and exclusion strategies used in the developed world’s food system aren’t viable options for the small-holder farmers of Africa. Thus their crops are compromised both for their family’s own consumption and for sale in local or export markets.

However, there is a solution. African small-holder farmers in six nations have recently been able to significantly reduce aflatoxin contamination of their crops by using a biological control product called Aflasafe.® This technology was originally developed for crops in the US, but it has since been adapted in order to make it a viable, locally produced solution for the African farmers.

This major health advancement is a notable example of how agricultural innovation can work for the general good. It was enabled by a diverse set of players including public sector scientists, a grower organization, farmer/cooperators, regulators, a small company, a global agricultural technology company, international development agencies, a major philanthropic foundation, and country level researchers and private companies in Africa. In many ways it is remarkable that this has turned out to be a success story. It took three decades and along the way it involved some seriously “out of the box” thinking, some visionary investment by the farming community, and the navigation of uncharted regulatory territory. Finally it required farmer adoption and downstream customer acceptance. The story continues today as this new strategy has become a significant part of aflatoxin mitigation programs with benefits for farmers and consumers in both the developed and developing world.

The Back-story

The story begins with a conversation about the aflatoxin issue during a scientific meeting in 1990 between a USDA researcher named Peter Cotty who worked on cotton in at the University of Arizona and a University of California, Davis researcher named Themis Michailides who worked with tree nuts. Those are two of the crops that can be infected by a soil dwelling fungus called Aspergillus which can contaminate their yield with aflatoxin. That can be a big problem for the cotton industry because it can result in toxin contamination of the cotton seed meal, a protein-rich co-product of the fiber business. That meal is commonly used to feed dairy cattle and if it is contaminated with aflatoxin the poison can come through into the milk. Thus any contaminated seed meal lots are rejected, undermining profitability for the cotton growers. For tree nuts the fungal infection is associated with insect damage, so it is critical to control those pests. If the incidence of infection is low, any contaminated nuts can be detected and removed with a puff of air as they travel one at a time down a high throughput conveyor system. If there is too much infection the entire lot is rejected. Those total rejection scenarios are rare, but they are very costly for the farmers. That is why researchers are always looking for additional control methods.

What Cotty had discovered was an individual strain of the troublesome, Aspergillus pathogen which didn’t make any aflatoxin. He and Michailides brainstormed the possibility of introducing enough spores of this “atoxigenic” strain into a field or orchard to out-compete the dangerous strains. Intentionally spreading a plant pathogen was definitely an unconventional concept, but the researchers decided to gave it a try. They cooked grain and then used it to grow large amounts of the desired version of the fungus. They then spread it on the ground in test plots of each crop so that the spores could float up to the plants in the wind. After early results were positive larger scale experiments were conducted in cooperation with some adventurous cotton and tree nut farmers who had enough trust to allow the researchers to do what sounded like a way to ruin some of their crop.

What this publicly funded research phase demonstrated was that the atoxigenic strain could indeed become dominant and greatly reduce aflatoxin levels in the crop harvested from the treated area. Then it was time for commercial development. Cotty pitched this concept to a start-up biological control company in San Diego called Mycogen, but the company wasn’t willing to commit its limited resources to such an unusual concept. Instead the visionary funding for commercialization came from a grower organization called the Arizona Cotton Research and Protection Council (ACRPC) which licensed the USDA’s patent covering the atoxigenic strain called AF36 in 1998. It might seem non-intuitive for a government agency to patent a technology that came out of publicly funded research, but in fact that is a logical step because it makes it more likely that a commercial entity will later be willing to make an investment in further development of the technology. ACRPC ended up investing millions of dollars in a program they describe as being “for growers, by growers.” They pursued EPA registration which was also challenging because the agency had not previously dealt with a product that involved using a pest as a “pesticide.” Even so, in 2003 the EPA approved the use of AF36 on cotton in Arizona and Texas. Starting in 1998 ACRPC developed a facility which is now capable of generating enough colonized grain to treat 200,000 acres of crops in a year. Over the history of the program nearly a quarter of a million acres of cotton has been treated in Arizona and Texas. The USDA has continued to support this effort.

Field results were also encouraging in the California tree nut industry and EPA approval for those crops followed in 2012. The tree nut industry now purchases AF36 from the cotton council. The Pistachio industry was the first to adopt this technology at scale because they have had historical issues with aflatoxin-related shipment rejections particularly in the EU. When AF36 was commercialized the EU sent 12 scientists to the US to learn about this technology and how it is used. Once they were convinced of the safety and efficacy of this approach, it opened the door for that important export market. AF36 is now being applied to more than 40% of the pistachio crop and it has been possible to document an overall shift in the Aspergillus population towards the safe strain.

There is increasing interest in this approach within the California Almond industry, and they have been funding additional research. AF36 can also be used on figs. A study has also shown that the AF36 strain is endemic to Mexico which should make it possible to get regulatory approval to use it on crops in that country.

There is a parallel “chapter” to this story which also started with public sector researchers – in this case Joe Dorner and Bruce Horn who worked at the USDA’s National Peanut Research Laboratory in Dawson, Georgia. Their goal was to develop another atoxigenic strain of Aspergillus which would be adapted for use in peanut and corn crops in the Southeastern US which can also have aflatoxin contamination issues. While the AF36 strain involves a single mutation in a key enzyme involved in aflatoxin production, this new strain is missing two entire gene clusters related to making aflatoxin and also another mycotoxin called cyclopiazonic acid. Their strain was patented as NRRL 21882 and it was soon licensed by a small company called Circle One Global which then pursued EPA approval and built a production facility. In 2004 they launched a product called AFLA-GUARD® for commercial use on peanuts and corn. In 2009, the global crop protection company Syngenta
SYT acquired Circle One specifically for this technology and they have plans for expanded commercialization of this strain in other parts of the world.

The US phase of the process is summarized in the graphic below.

Phase 2: The Developing World

Based on the efficacy and safety of this technology in US markets, there was interest in extending it to farmers in the developing world where aflatoxin-related health issues are sadly commonplace. This turned out to be a 15-year process enabled by an addition set of players. The project was started under the leadership of IFPRI – the International Food Policy Institute. Funding was supplied by the Bill & Melinda Gates foundation and the US Agency for International Development (USAIUSAI
D). The USDA was also involved as were national institutions in each country.

Early on, the decision was made to find native African non-toxin forming Aspergillus strains so that they would be well adapted to the environment in each target country. This process was aided by the knowledge about strain genetics from the two US products. Once early field experiments had confirmed efficacy the strains, they had to be approved by the regulators in each country. Once again that was “uncharted territory” for those agencies. Once that hurdle had been crossed, there was a handoff to local companies for production and distribution. However, the international supporters of the projects were still involved in the effort to educate the small-scale farmers and their customers. As the IITC’s summary document puts it, “a marketing strategy for an entirely new product segment addressing a significant but little-known public health risk is more than a sales strategy – it requires a strategic, collaborative approach. Dialogue for alignment with national goals is essential.”

These biocontrol agents are now commercially available in Africa under the trade name Aflasafe®. It is approved for maize in 10 countries, groundnuts in 9, and sorghum in one. Commercial partnerships are in place in Nigeria, Kenya, Senegal, Gambia, Burkina Faso, Ghana and Tanzania. Efforts are underway to expand to three South African countries and to Rwanda. There have been a number of success stories. Gambia was able to re-launch its groundnut export industry with non-contaminated product. In Kenya there was a 2,000 hectare food security project to produce maize for food-insecure populations; the maize from the treated area was 99% below 4 parts per billion aflatoxin while in neighboring areas aflatoxin was often above 1,000 parts per billion. 100,000 farmers in Nigeria were able to get a $5 million price premium for the non-contaminated maize. Total usage of Aflasafe in Africa is now in the range of 500,000 hectares. There is a detailed diagram on a CGIAR website showing the entities involved in the Africa chapter of this story.

Conclusions:

The three decades that it took to fully implement this control method might seem like a long time, but it must be remembered that each field experiment takes a year and that there were unprecedented conceptual, regulatory, manufacturing and communication challenges along the way. The net effect is that we in the developed world continue to be protected from carcinogenic aflatoxin in our food and growers suffer fewer losses in the process. People in the developing world now enjoy better access to a qualitatively safer supply of groundnuts and maize. There were key roles along the way for the public and private sector, for regulators, international agencies and a philanthropic organization. What started as an almost crazy idea turned out to be a notable example of how beneficial advancement can occur.