Mycobacterium tuberculosis is an acid-fast pathogen that is a huge plague upon humanity, even within developed countries. Although this pathogen has a low rate of incidence in these countries now, a sign of its impact can be seen within the UK where Sanitoriums (long-term clinical facilities dedicated to the treatment of chronic diseases like tuberculosis) were still in use as recently as the 1970’s.
Tuberculosis (TB) is a chronic, highly contagious disease ensuing from the formation of scarring granulomas within the lungs. These fibrous growths, combined with the thick waxy capsules of the bacterium are nigh-on impervious to the host immune system, although the majority of the disease’s pathogenicity is a result of tissue damage from the activity of this system. TB is still a deadly and rampant killer in the developing world, being 2nd only to HIV/AIDS with 1.3 million deaths worldwide1.
But a new proposed hypothesis2 puts Mycobacterium tuberculosis into a new light, a position very different to its infamous pathogenic status. To understand this new idea, one must first look at past ideas and knowledge. Evidence suggests that the bacteria co-evolved with the ancestors of humanity, adapting to thrive while our ancestors did the same to overcome these microbial invaders. This occurred before our hunter ancestors migrated out of Africa, approximately 20, 000 years ago2.
At around this same time our ancestors’ brains dramatically increased in volume (and potentially brain-power) as a response to the switch from a vegetarian to a hunter-gatherer diet. Hunting is a mentally taxing activity with co-ordinating attacks, judging lunging and throwing distances and as such would require this increase in brain volume. From an evolutionary point of view this is a massive investment in nutrient sources, a gamble if it does not pay off, but it is a worthwhile one as meat is a rich and valuable food source. Two vital resources for brain growth are Tryptophan (an essential amino acid) and Nicotinimide; the precursor to NADPH (a reducing agent found in our cells required for a number of processes such as nucleic acid synthesis), both of which are found in abundance in meat. So if our ancestors were successful in their hunt, they fed well and could support the developing brain volume that allowed them to be such successful hunters.
But what if they weren’t successful? What if that deer or prey got away? Our ancestors would have needed to evolve a back-up mechanism in case they struck on hard times, to provide Tryptophan and Nicotinimide to support their larger brains. One way in which this could be facilitated could be by manipulating the natural microbiota of the body to produce these molecules, and in fact many bacteria are taken advantage of by the human body to this day; gastrointestinal Bacteroides species are exploited for example to provide short chain fatty acids that we cannot naturally produce, while we provide them with a suitable habitat and nutrients. Unfortunately no known human symbiont produces or secretes Nicotinimide- but Mycobacterium tuberculosis does2.
And now with that little bit of background under our belts, lets get down to the real business. Williams and Dunbar hypothesize that our ancestors co-evolved with Mycobacterium2 but did not evolve to completely eradicate this invading pathogen from their bodies. Instead, Mycobacterium tuberculosis may have been assimilated and utilised as a Nicotinimide ‘farm’ or storage system for short times of starvation. Over long periods of time the effects of starvation may have reverted the bacterium to its’ pathogenic state but otherwisethis co-evolution may have resulted in our ancestors’ immune systems dampening down their responses (potentially allowing for granuloma formation and a decreased production of anti-TB antibodies for TB survival) to allow the pathogen to live asymptomatically, and more importantly symbiotically, within its host. Here, it could provide secreted, supplementing Nicotinimide in short periods of failed hunting (i.e. no meat to support the increasing volume of the brain) but why would evolution choose a pathogen, a microbial killing machine, to be the partner in this relationship? Why aren’t we all dying of TB? Well:
- First off, 90-95% TB cases are asymptomatic2. They cause no disease, no symptoms, and live rather happily in the patients’ lungs (although arguably stress, immuno-compromisation and other unknown factors can activate a symptomatic infection),
- The bacterium resides close to dense capillary beds in the lungs that allow the secreted Nicotinimide to leech or be transported into the blood. Nicotinimide is also secreted to such a level that it is able to physiologically increase blood concentrations,
- Mycobacterium tuberculosis produces no known toxins (which are common virulence factors of many pathogens),
- The bacterium can divide in granulomas, which may potentially sequester the bacterium from the activity of the immune system but also prevent the dissemination of the pathogen around the hosts’ body,
- Nicotinimide can also inhibit the growth of Mycobacterium tuberculosis and could act as a regulation mechanism to dampen the pathogenicity of the microbe in temporarily poor diets.
Williams and Dunbar also present evidence that correlated UK TB mortality rates with meat consumption measured by meat import and consumption (i.e. a modern ‘hunting diet’.) during the period between 1850-19502. The researchers found a negative correlation between meat consumption and TB death rates, so that a higher consumption of meat correlated to a lower TB mortality rate. Applying this to the new hypothesis, this finding would be a product of the high meat diet resulting in a reduced need for TB ‘farms’ in the lungs of the population, as well as the immune-dampening of the pathogen in competent, healthy individuals. However while this strong correlation (found particularly in the upper social classes who could afford more meat2) is compelling evidence, it does have its limitations. This kind of study is retrospective, a method that can have its reliability questioned as it relies on records of the past to be accurate and not false, intact and un-tampered with. Experimental groups for this kind of research could not be ethically normalised or even created for a ‘cause-and-effect’ study (for example, taking TB patients and giving one group a high-meat diet and measuring an improvement against a low-meat diet group).
In summary this new hypothesis places Mycobacterium tuberculosis, the causative agent of TB, in a position that has influenced human evolution; one that has allowed our ancestors and us to evolve and maintain the larger brain volume needed for a hunting, meat-focused diet and potentially our higher brain power and function too. But regardless of whether this new idea holds true I believe it highlights an important fact- that the evolution of the small can influence the evolution of the large.
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1. WHO TB Facts, http://www.who.int/mediacentre/factsheets/fs104/en/
2. Adrian C. Williams and Robin I.M. Dunbar (2013.) “Big Brains, Meat, Tuberculosis, and the nicotinamide switches: co-evolutionary Relationships with Modern Repercussions?” Int. J. Tryptophan Res.; 6: 73–88.
Feature Image- BBC News Health, “Wrong Immune Response Aids TB”, http://www.bbc.co.uk/news/health-21619594