Dr. Charles Akle
Chief Medical Officer
Funnily enough our story does not begin with M. aurum, but rather its two sister organisms, Mycobacterium vaccae (M. vaccae) and Mycobacterium obuense (M. obuense).
M. vaccae (NCTC 11659) is discovered in 1971 by Professor John Stanford on the shores of lake Kyoga in Uganda. Local people believed the mud from the lake could cure a number of diseases. After investigation, Stanford and his colleagues, including Professor Graham Rook, surmised that M. vaccae could act as an adjuvant for BCG in the fight to prevent Tuberculosis and Leprosy.
And so it begins...
From 1980, extensive research, from animal to human, is conducted on the effects of M. vaccae on Tuberculosis (TB) and Leprosy. Professors Stanford and Rook are assisted in their work by Professor John Grange.
Numerous trials are carried out. Initially, trials based on short and medium-term use of M. vaccae show mixed results, with seemingly better results for modest active resolution than disease prevention. A meta analysis published in 2011 (link below) produces a favourable dataset when looking at 54 reported studies involving hundreds of patients across the world.
Professor Grange surmises that M. vaccae might actually be effective in cancer therapy.
Side note: The precedent for this notion is that patients with TB rarely have cancer (Pearl, 1929), which led to the use of BCG (the TB vaccine) as a possible remedy for cancer. Interestingly, BCG has an initial effect on cancer, especially on melanoma, but it soons wears off and subsequent dosing actually seems to make the disease worse. This is because BCG is fundamentally a pathogen and triggers the wrong immune response, which is not ideal in cancer patients.
From 1995 onwards, a number of phase 1 and phase 2 studies using M. vaccae to treat cancer patients are conducted and published from 1998 onwards. These trials are very encouraging.
The largest study using M. vaccae is a phase 3 trial in NSCLC (Non Small Cell Lung Cancer) involving 419 patients (half as controls) led by Dr Mary O’Brien at the Royal Marsden Hospital, London. The first analysis published in 2004 showed no obvious survival difference, but a significant Quality of Life score.
Side note: how do you measure quality of life? Read about the Quality of Life Scale.
This confirms observations from studies in other cancers: that patients receiving mycobacteria have a better mood and coping attitude.
The results indicate to the team that M. vaccae may impact mental health, prompting Professor Chris Lowry to begin his research into the neurological effects of these mycobacteria.
Side note: A re-analysis by Dr O’Brien, Professor Grange and Professor Stanford published in 2008 showed that those lung cancer patients who had received multiple doses of M. vaccae did indeed benefit, with an average of 135 days extra life. This is considered a very significant benefit as there were few treatment options for lung cancer at the time.
It is now clear to the team that therapy with M. vaccae requires continual administration to maintain the effect.
In 2003, Professor Graham Rook publishes his Old Friends Hypothesis - an extension of the Hygiene Hypothesis. He posits that microorganisms and macroorganisms found in mud, animals and feces play a critical role in driving human immunoregulation.
His work explains how diseases and conditions of the modern era, including multiple sclerosis, type 1 diabetes, allergies, and depression and anxiety (when accompanied by raised inflammatory cytokine levels) involve disrupted immunoregulatory circuits, likely reﬂecting reduced exposures to “old friends” - environmental bacteria with which humans co-evolved.
The Quality of Life observation from the 2004 lung cancer phase 3 study prompts Chris Lowry and Graham Rook to explore the neurological effects of mycobacteria with a focus on the ‘Old Friends’ theory. This leads naturally to an increased interest in the microbiome.
Their research finds that reduced exposure to immunoregulation-inducing macro- and microorganisms and microbiota that accompanied mammalian evolution (aka our 'Old Friends') predisposes us to poor regulation of inflammation.
They delve into the link between inflammation and psychiatric disorders, showing how Inflammatory mediators modulate brain development, cognition and mood. The risk of all these conditions (chronic inflammatory and psychiatric) is increased in urban communities, as opposed to rural communities where people are more exposed to nature.
They investigate a specific strain of M. obuense, a sister organism of M. vaccae, selected for its immunological effects. This is important, given that mycobacteria do differ substantially even within strains.
Development is rapid and the team are quickly able to get to the major phase 2 Randomised Clinical Trial in advanced pancreatic cancer, publishing the data in 2016.
In all, 110 patients were involved. In the majority of patients (92 patients with secondary tumours), the survival benefit was significant. This was also accompanied by a good Quality of Life score as expected.
Following this, Dr Charles Akle moves his attention and efforts to the development of M. aurum.
Animal studies begin, using M. vaccae. Over the coming years many studies would be carried out, leading to numerous published articles between 2016 until 2019. Findings show M. vaccae to have anti-inflammatory, immunoregulatory and stress resilience properties. Immunisation with M. vaccae induces antiinflammatory responses in the brain and prevents stress induced exaggeration of microglial priming.
A key observation is the prophylactic power of mycobacteria to lessen the effects of stress and in doing so, improve coping behaviour.
The idea of a “stress vaccine” becomes a possibility.
The team turn their attention to address the ever increasing mental health crisis globally, studying a number of mycobacteria strains with a view to developing a more easily ingestible oral version of beneficial mycobacteria.
We now have a better understanding of the critical interaction between the gut and the brain - the Gut Brain Axis - as a two way system. The gut affects the brain and the brain affects the gut. Given the gut is the largest immune organ in the human body, and the mouth is the natural route of entry and interaction with it, an oral option is preferred. Not to mention this far more convenient than injections.
M. aurum shares 215 unique genes with M. obuense and M. vaccae that no other mycobacteria have. But while M. vaccae and M. obuense have undergone pharmaceutical development as injectables. M. aurum is able to be orally ingested. It can be suspended in olive oil - making it more accessible and safe when administered. It also proves to be easier to culture and stabilise.
The team gains a better understanding of the mode of action of M. aurum and how it works in the gut. We know it does not colonise the gut, but is passed through, hence the need for regular intake. The research is ongoing and we are getting even more information as to the effect it has on the huge variety of immune cells.
In 2018, M. aurum, M. vaccae and M. obuense are reclassified as mycolicibacteria - identifying them as non-pathogenic strains within the wider mycobacterial family.
You should beware of using just any mycobacterium, or just any strain. Not all these bacteria behave identically and it is vital to choose the right one for the right job.
Our Mycolicibacterium aurum is a highly purified form of the wild M. aurum, so we get the best efficacy from it. Extracts only perform part of the effect – you need the whole organism for maximal effect.
Our M. aurum is heat killed after cultivation, adding an additional layer of safety to ensure no human infection occurs, but as it still retains its cell structure, it still triggers the desired immune responses just as effectively. The compounds that trigger the immune response are part of the cell wall and survive the heat killing process intact. We believe you need all the compounds to get the best effect.
Just like an orchestra – you cannot understand Mozart’s 40th Symphony by listening to only the flute.