125 years of mycotoxin research

Swiss botanist Paracelsus, who is credited as the founder of toxicology, travelled all over Europe, Scandinavia and Russia and possibly even Constantinople. He advanced the idea that chemicals could both cause and cure diseases. Over to the next century those who studied natural history and medicine fell into 1 of 2 camps:

1. those that bought into that idea, and
2. those that did not.

In France, Dr Thullier the physician to the Duke of Sully was a believer. The Duke saw the effects of ergot on his estate, he was worried and he was Prime Minister. During the large epidemics of ergot during the first half of the 17th century in France, Dr Thullier pursued the cause of what we now know as egotism. He fed sclerotia to chickens, geese and pigs and they all died. His son (also a physician) and a botanist in Paris did further work and recommended that grain be sieved to prevent ergotism. Within 100 years, sieving affected grain was widely practiced. This was before the structure of the first pure alkaloid was determined a century later. More or less after all mills adopted appropriate sieving in the early 20th century, ergotism vanished as a serious public health problem.

The discovery of aflatoxin

It had been reported by the mid-1930s that people from groundnut consuming areas in Africa were more likely to get liver cancer. Similar observations were made all over Africa prior to the early 1960s. Scientists in the USA and Africa were aware that A. flavus made something quite toxic but the toxin eluded them. The discovery of aflatoxin by British and Dutch researchers might have been missed had it not been for the fact that virtually all the turkeys that were dying were within 100 miles of the Port of London. Thus the source of the feed could be easily traced to one cargo ship from Brazil. It was quickly shown that aflatoxin was present in food and feed in various parts of Africa and was toxic to children and domestic animals. In the United Sates, aflatoxin was identified as a problem in peanuts by 1963. By 1966, Federal inspectors learned to evaluate the presence of A. parasiticus-damaged nuts and thus exclude damaged lots. The following year (1967), sufficient data on aflatoxin in peanuts were gathered to make an exposure assessment. The US FDA regulated aflatoxin in 1969 at 20 ppb in food (the first IARC monograph on aflatoxin was in 1971). In this case, from discovery to effective regulation took less than a decade and again they did not need to know everything to make effective decisions. Regulation of the other 2 toxins important from a public health perspective in the USA and Canada, deoxynivalenol and fumonisin also took about a decade each from discovery to appropriate regulatory action.

Current influence of climate on toxins

Moving forward to the current situation there are 3 important societal expectations of mycotoxin researchers in the fully developed market economies.The first challenge that requires our attention is the influence of climate on the distribution of fungal toxins in crops and feeds. The next 10-20 years will see the need to create analytical capacity in geographic areas that had been used to stable patterns of contamination within the working careers of the scientists concerned. That is to say old toxins in new places. Thus compounds in cereals such as nivalenol, ergot alkaloids as well as aflatoxin and fumonisin in maize are appearing in areas where they have not been seen due to changing climate patterns.

The best evidence is that the genetics of the populations of key toxigenic fungi is being accelerated with climate change. The fungi that cause Fusarium head blight/Gibberella ear rot are changing. This is due in part to the movement of strains that make deoxynivalenol via the monoacetate at the 3 position into regions hitherto occupied by those that make the 15 acetate. Although of similar virulence, wheat infected by the 3ADON strains can contain slightly more deoxynivalenol. This may be due to differences in the ability of the plant to glycosylate the two monoacetates. It appears that small differences in temperature and moisture are primary determinants of the distribution of these two genotypes. Further there is clear evidence that these populations are recombining in unexpected ways. The concern is that maintaining a satisfactory margin of exposure below the TDI is already a challenge in some regions. This will require more refined exposure assessments (cheaper biomonitoring) to protect vulnerable populations even in Europe.

In subtropical and hot, dry climates, there is a similar concern for the species of Aspergillus that make aflatoxin. The regions where A. flavus can thrive appear to be expanding. The discovery of the sexual state of A. flavus challenges the present understanding of the behaviours of these fungi in the field. Sex within populations of the aflatoxigenic aspergillii may create additional difficulties for the control of aflatoxin in food and feed. If, as it is believed, that fungal sex is one response to ecological and environmental stress, then climate change might accelerate undesirable (certainly inconvenient) change. This must be understood.

Refine the tools for mycotoxin detection

In the face of these challenges, it seems likely it will become more common to divert lower quality grains into feed. Warmer winters in cool season areas where silage is a common feed source will increase the occurrence of the toxins from the species mainly of Penicillium that grow in silage. Not much is known about the effects of these toxins on animal health and productivity and their distribution in animal products (especially milk). Very few laboratories have the capacity to analyse compounds such as roquefortine C on a routine basis. Thus the third major challenge for the decades ahead is to refine the tools used through the feed value chain to minimise the impact of a greater risk of lower quality feeds on animal health and productivity.

Finally, it must be said that in parts of Africa, Latin America and Asia exposures to aflatoxin and/or fumonisin is at levels that affect the health of the population. This has been recognised for 50 and 20 years respectively, and if anything the problems are getting worse. Addressing this is perhaps one major expectation of all mycotoxin researchers now.

The critical issue is to create both knowledge and capacity to ensure that the public health is protected and minimise losses and disruption to the agricultural economy. Against these clear and present challenges, and no matter how academically interesting, there is little reason to allocate scarce public funds for mycotoxins to, for example, muse about the impact of co-exposures of the regulated toxins with a large margin exposure. Similarly, just because they can be detected, it is not helpful 
to call all fungal metabolites ‘mycotoxins’ when there is no material exposure and no evidence they affect human 
or animal health.