Aspergillus and Cannabis : History of Aspergillus

Before I start on what’s going to be a very long and very intense series of stories about state cannabis regulations about Aspergillus, I want to say a few things.

I’ve written about this before. In fact, I’ve written about it more than once, but the first article I wrote caused my email (and other social media) to be filled with bullying and vitriol from several Oregon cannabis farmers and others within the industry. The more I looked at the toxic discourse around this issue, the less I wanted to say anything more about it.

I don’t make a living from cannabis, I am not in the industry, and even if I was — it wouldn’t be worth the personal harassment I’ve endured.

But Vin Deschamps, a personal friend who owns 54 Green Acres Farm, an organic cannabis farm in Southern Oregon, asked me (twice) to do a more thorough dive on all the issues. 54 Green Acres has embarked on a journey to prevent Aspergillus and other microbial contaminants by investing in both their dry and cure spaces and are reevaluating all of their processing procedures.

Let me call out my own bias before I set it aside — I am a registered medical cannabis patient, which I use for CPTSD and migraines. I also have auto-immune issues (which is not the same as being immunocompromised, but it’s also not far off). I vaporized cannabis for the past several years, and almost exclusively from 54 Green Acres. As far as I know, I’ve never gotten sick from that cannabis.

There’s my bias. I have a friend who is a farmer, and I myself am a medical patient. I will make every effort to set these biases aside in this series of articles, but I want any reader to be aware of just exactly where I’m coming from.

I will not be giving my opinion on the facts I state, instead I seek to lay out all of the things that I know (and call out the things that I don’t) about Aspergillus and cannabis.

Approach

I plan to only review what is known about these issues, and as I said, I will remove my own bias by keeping my opinion on these facts out of the discussion. The articles are the following:

History of Aspergillus (This Article)

Cannabis and Aspergillus: A Medical Literature Overview.

How is Cannabis being tested and regulated for the presence of Aspergillus?

What’s a Farm to Do? Information on Prevention and Remediation

Case Study in Oregon: An Organic Oregon Farm Engaging in Aspergillus Prevention

This article was originally published on my Medium account, to an audience of cannabis medical patients and connoisseurs that follow me there. If you want to read the articles before I post them here, it’s a good idea to follow me there.

To understand the intersection of Aspergillus and cannabis, I think it’s important to understand what it is, and what we know about it. So let’s have a brief history lesson!

What is Aspergillus?

Historical Overview

Let’s go back to science class and remember a touch of nomenclature — Kingdom, phylum, class, order, family, genus, species, right? Well, aspergillus is a genus of the kingdom Fungi. They are of the division / phylum of Ascomycota, a division which is so named for its sacs (Greek, ascus) in which its non-mobile spores are formed. It is of the class Eurotiomycetes, which indicates a fruiting body. Its order, Eurotiales, identifies it as a green or blue mold. Its family, Trichocomaceae, indicates its an aggressively colonizing saprobe, which means that it feeds off of decaying matter.

The aspergillus genus itself contains hundreds of species of Aspergillus, but fewer than 20 -40 (estimates vary) are considered pathogenic, meaning only a relative few have been proven to make humans sick. Aspergillus fumigatus is the one most commonly linked to illness. It’s important to remember that science, by its nature, is constantly evolving in knowledge. Put a pin in that, we’ll be back to it.

This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #300. Image in Public Domain,

Aspergillus was identified in 1729 by botanist Pier Antonio Micheli, who is credited with discovering mushroom spores. He also happened to discover Botrytis, another fungus that impacts cannabis. Micheli, who was born to parents of very modest means (he was described as “illiteratus et pauper”) also happened to be a priest, which is explains why Aspergillus is named for an aspergillum, or holy water sprinkler (as he felt its shape resembled one.) His illustrated work, Nova plantarum genera, describes 1900 different species, most of which had not been discovered or discussed previously.

An Aspergillum. By SCHREIBMAYR — Creative Commons licensing.

There are over 200 species of Aspergillus — many of which are beneficial. In Asia, Aspergillus oryzae and Aspergillus sojae had been put to use for centuries in the creation of sake (rice wine), miso (soy bean paste), and shoyu (soy sauce). Fungal production of citric acid dates back to the 19th century — and in 1917 James Currie perfected the use of Aspergillus nigerto create citric acid. Aspergillus terreus is also famous for what it produces — the statin Lovastatin (Mevacor). An enzyme produced by Aspergillus niger is used to produce ‘Beano.’ It’s obvious from the myriad of applications that many species of Aspergillus aren’t harmful at all — in fact they’re quite beneficial.

Not all of them are helpful, and the ones that aren’t can be wicked.

The first case of an Aspergillus-related infection was actually observed in 1789, during the French Revolution. A 22 year old solider named Jacques Thibault experienced severe facial pain and ‘elevation of his cheekbone and protrusion of his right eye.’ He was admitted to Paris Hospital, where the fungus was cauterized several times as it had started to fill his mouth cavity and entirely filled his right nostril. After a surgery and several more cauterizations with a branding iron, the fungus finally did not return. He was able to leave the hospital 134 days later.

It was in 1842 when John H. Bennet would describe pulmonary aspergillosis, where he noted a fungus in the lungs of a patient during a post-mortem. In 1856, Rudolf Virchow discovered that the aspergilli that had made animals sick was similar to cases of human disease he had observed. Aspergillus fumigatus, the most pathogenic of the Aspergillus species, was observed and described by J. B. Georg W. Fresenius in 1863. It was identified as an infection in birds, specifically Ovis tarda (The Great bustard), and it was in this work that the term ‘aspergillosis’ was first coined. In 1897, the first occupational aspergillosis cases were identified, mainly among squab feeders (people who would masticate grain for pigeons and then force it into their beaks) and wig cleaners. It was also in this year that the first book on Aspergillosis was published by Louis Renon. The book noted the rarity of the infection, and covered the disease’s impact on animals before describing it in humans, where he concluded it could be both a primary and a secondary infection. He also identified Aspergillus fumigatus as the most pathogenic species, a view shared by his contemporary, Thomas Rothwell (who was examining Aspergillus in skin infections). It was also around this time that due to the similarity between pulmonary aspergillosis and pulmonary tuberculosis, doctors started to take note. They needed to be able to differentiate between the two to effectively treat their patients.

Humphry Rolleston, an English physician who specialized in pulmonary tuberculosis, published information on pulmonary aspergillosis in 1898. He specified that it was a disease mainly associated with millers, agricultural laborers, and anyone who worked with / processed contaminated grains. He also stated that Aspergillus fumigatus and Aspergillus niger could infect the ears and skin in addition to the lungs.

For the next several decades, the focus on Aspergillus was on its proficiency in the creation of antibiotics and food production. Research expanded into fermentation, industrial applications, and was of huge interest to industrial chemists (who named the fungi ‘cell factories’), especially after the discovery of penicillin. By the end of the 1930’s, fungal spores were recognized as allergens.

It was in 1945 that James Duncan discussed aspergillosis as part of his fungal disease survey. Specifically he mentioned how it related to pulmonary aspergillosis and ‘farmer’s lung.’ A brief time later, in France, ‘Aspergillomas’ were discovered in lung x-rays — essentially aspergillus fungus balls found in the empty cavities found within the lungs of recovering tuberculosis patients — cavities formed by the healed tuberculosis lesions. The population of recovering tuberculosis patients was expanding due to the effectiveness of triple antibiotic treatment. Further investigation showed similar Aspergillomas in the lungs of other patients recovering from serious lung chronic lung conditions such as histoplasmosis and cavitating lung cancer.

We were still learning about fungi! Until around this time, the 1950’s, mycology was considered to be part of botany and fungi wouldn’t be recognized as a separate scientific kingdom until 1969.

But it was 1960 that brought another lens to focus on Aspergillus — and it had to do with the deaths of over 100,000 turkeys in the south of England. The outbreak spread into other avian populations such as ducks and pheasants, but the entire incident went largely unnoticed by the press because of a viral outbreak among birds at the time. Experiments demonstrated that the disease mainly affected the liver, and that if the feed being used (groundnuts) was fed to rats similar symptoms appeared. In 1961 Unilever Research Laboratories (yes, that Unilever!), the major importer and processor of groundnuts, found that a toxin produced by Aspergillus flavus was to blame — and called it an ‘aflatoxin.’ Four aflatoxins were identified as part of this work and was able to identify Aflatoxin B1 as the most toxic, and it was linked to acute hepatitis, immunosuppression, and hepatocellular carcinoma.

What followed was called the ‘mycotoxin Gold Rush.’ Researchers raced to understand aflatoxins, and the American Society for Microbiology met on the topic in 1965. Scientists decided it was vital to understand the problem further in order to get a handle on its impact on issues like food storage.

In 1965, The aflatoxin scare inspired Samuel Asper and Andrew Heffernan to perform an intensive review of people diagnosed with aspergillosis from 1941 to 1963. They found it was relatively rare, and reviewed 26 autopsies, and were seeking to see if there was a higher incidence of liver disease in those cases. When they failed to make a correlation, they looked instead to the overall incidence of aspergillosis to see if there was an overall rise in cases, which they found.

Figure 5.1Incidence of fungal infections (including aspergillosis) found at autopsy at the Johns Hopkins Hospital, 1941–1963.

What was most interesting to them, however, was the increase in incidence in leukemia patients, especially as treatment regimens grew more intense. They said, “It may well be, as others have suggested, that unique forms of therapy for leukemia, which alter host-parasite relationships, are the factors responsible for the increasing incidence of aspergillosis. In the weeks before death, all the leukemic patients had received antibiotics and steroids and all but one had received cytotoxic agents.” Another literature review supported this finding mycoses in leukemia patients to be between 14% — 30%, and they speculated that antileukemic drugs could increase a leukemia patient’s susceptibility to infections’ In the 1970’s, the research of Richard Meyer and Memorial-Sloan Kettering found that ’41 per cent of the patients who died with acute leukemia had evidence of aspergillosis’. This is why aspergillosis is thought of as a ‘Disease of Modern Technology.’

This prompted physicians to look for better diagnostic methods — because of the ubiquity of Aspergilli, sputum tests could only be use to indicate the possibility of infection. Instead, they looked for antibodies in blood serum. It still presented issues, especially with possible environmental contamination, but seemed to be a far better indication.

Renal transplant patients were also identified as being at risk, and while aspergillosis was low in incidence among this patient population, it was high in mortality. Heart transplant patients were also susceptible, and the third heart transplant patient in Britain died of aspergillosis. Even though Amphotericin B had been identified as an effective treatment at this point, many doctors were reluctant to prescribe it because of the harshness of the treatment.

As the disease profile of aspergillosis grew throughout the 1980’s and 1990’s, so too did treatment options, but diagnosis remained a problem until a breakthrough method using the sugars produced by Aspergillus. Unfortunately, the medications were still only ‘gave complete cures’ in 27% of the patients.

Remember when I said science was still evolving? Well, for over 145 years, it was thought that Aspergillus fumigatus was an asexual reproducer, until a sexual cycle was discovered in 2008. Sit with that for a moment — it took over 100 years after discovery to determine that Aspergillus fumigatus was pathogenic — and around 250 years since its discovery to even understand that it had a sexual cycle.

Despite the fact that Aspergillus has gained attention due to technological innovations in medical science and our deepening understanding of it, we didn’t even fully understand how the most pathogenic species of Aspergillus reproduced until 15 years ago — and we’re still learning!