1500 words

After I published my article Thoughts On Diseases of Civilization: Romanticizing the Hunter-Gatherer’s Diet the other day, someone dropped by and stated that we are ‘getting healthier and healthier’, citing an article by Berens, Cooper, and Lachance (2017) titled “The genomic health of ancient hominins” who show, through genetic analyses, that many of our ancestors had the ‘genes for’ diseases that plague us today in our societies. While this may be true, one important thing that the individual who left the paper did not say is that genotypic health does not equal phenotypic health.

The basic assumption of the paper is this: They genotyped the Altai Neanderthal, Denisovans, pastoralists and hunter-gatherers and computed their ‘GRS’ (genetic [disease] risk score). When focusing on the GRS, they found that the Altai Neanderthal had 97 percent worse ‘genomic health’ when compared to the genomes of people today, whereas Otzi man had a ‘genetic predisposition’ to cardiovascular and gastrointestinal disease.

Something important to keep in mind here is that GRS and sequencing the genomes of ancient hominins can only ‘predict’ what types of problems one would have based on their genomes; it cannot realiably state that this individual would have gotten/did get a certain disease because he had the alleles for it.

What they did was genotype ancient hominins and then compute their GRS and compare the ancient hominins GRS to that of a modern human and then match the set of “disease loci to generate standardized GRS percentiles“. The ancient samples they tested had a similar genetic risk when compared to modern samples, though the ancient samples may underestimate their genetic risk since there are numerous other alleles yet to be discovered that may cause or add to genetic disease risk.

Ancient hominins had lower risks for cancer, miscellaneous diseases and neurological/psychological diseases when compared to modern humans. According to their analysis, ancient hominins only had a higher risk for cardiovascular disease while  “Risks of allergy/autoimmune, morphological/muscular, metabolism/weight, and dental/periodontal diseases were not significantly different between ancient and modern hominins” (Berens, Cooper, and Lachance, 2017). So ancient hominins seemed to have a reduced risk of cancer, neurological disease and other unclassified diseases.

The Altai Neanderthal was at high risk of immunological diseases, cancers, gastrointestinal problems, morphological and muscular problems, and other metabolic disorders. However, and this is important, this is only what his genome showed. This is only a risk assessment and DOES NOT state anything about phenotypic health. The Altai Neanderthal, however, did have a lower GRS for cardiovascular disease and average risk for dental diseases. This is in contrast with Otzi man, who had a genetic risk for cardiovascular disease. Otzi also had a high GRS score on immuno-related diseases, gastrointestinal diseases and other metabolic disorders—which I would assume would be similar to type II diabetes mellitus. However, Otzi had ‘normal’ risk for morphological and neurological disease.

I had to wait all paper to read this:

We note that genomic health does not necessarily equate to phenotypic health. Genetic risk scores are not deterministic, instead they merely indicate whether an individual has a predisposition to a particular disease. In addition, alleles that contribute to disease in modern environments may not have had the same effects in past environments.

This makes it an open and shut case. Just because you have the ‘predisposition’ for something doesn’t mean that it will occur to you. For example, if someone has a ‘genetic predisposition’ to become and alcoholic and he never drinks alcohol, will he become an alcoholic? If someone is extremely sensitive to carbohydrate intake and more susceptible to the allure of sugar and more likely to get addicted to it, but they never eat the carbs will they become obese and insulin resistant? The genes-as-destiny paradigm is wrong—especially in regard to human disease. Human disease is extremely complex and doctors are even having problems with GWAS and what it shows for the genetic basis for disease.

Further, in regard to disease, GWAS has a huge problem in detecting genetic variants: “many GWAS hits have no specific biological relevance to disease and wouldn’t serve as good drug targets. Rather, these ‘peripheral’ variants probably act through complex biochemical regulatory networks to influence the activity of a few ‘core’ genes that are more directly connected to an illness.” See also Boyle and Pritchard (2017): An Expanded View of Complex Traits: From Polygenic to Omnigenic. Disease-nomics will be much more complicated than identifying one or a few genes; gene networks interact with the environment—whether by what we eat or our immediate surroundings—and diseases arise through a complex interaction between genes and environment: GxE.

When our ancestors made the transition from a hunter-gatherer lifestyle to a more sedentary, agricultural one, this is what then started up the environmental mismatch between humans and our environments. Agriculturalists had the highest GRS for dental caries and other problems to do with dentition, though the number of alleles was small, it makes logical sense for the advent of agriculture to increase the incidence of dental caries and other problems with dentition, which would then be selected for due to the change of lifestyle from mobile hunter-gatherer to relatively sedentary agriculturalist. Hunter-gatherers have fewer dental caries than agriculturalists. It is also argued that when we began to eat fermentable plant foods, that this caused “changes in food processing caused an early shift toward a disease-associated oral microbiota in this population” (Humphrey et al, 2014). Adler et al (2013) also show that “Data from 34 early European skeletons indicate that the transition from hunter-gatherer to farming shifted the oral microbial community to a disease-associated configuration.” Clearly, the transition from the mobile hunter-gatherer lifestyle to the sedentary agriculturalist one was extremely bad for our health and dentition.

Though agriculture did increase the incidence of dental caries, evidence exists that, through dietary shifts in the Upper Paleolithic, dental caries appeared, probably due to the shift to more processed foods (keep in mind that processing food only has to mean, say, mashing food to make it easier to chew, not in the modern definition of ‘processing’). Nevertheless, the first toothpicks were discovered from the Late Upper Paleolithic, which implies that some human populations encountered some foods that then gave them dental caries to which our ancestors responded by making toothpicks (Oxilia et al, 2015). Hunter-gatherers had few—if any—dental caries which implies that their lifestyles did not give them the oral disease. It’s very peculiar that these have only been noticed, really, in populations that underwent the agricultural transformation. That’s yet another ‘disease of civilization’ that is low to nonexistent in those populations, which is attributed to their lifestyle and their diet.

Cultural evolution drives mismatch diseases as cultural evolution can greatly outstrip Darwinian evolution. This, especially in regard to our health, is bad for us since we did not have the time to biologically adapt to our new, novel diets. We still have yet to adapt genetically to the diets and lifestyle taken on by our ancestors 10kya, and I think it will be a long time—if ever—before we do adapt. I mean come on, can you really see whole groups of people adapting to constant insulin spikes brought on by highly processed carbohydrates and other foods? We are the running ape, so do you ever see us adapting to constantly sit? These are modern problems, which were brought on by our ancestors’ adoption of agriculture. I agree with Jared Diamond when he says that farming was ‘the worst mistake in the history of the human race‘, but, obviously not for the Marxist reasons he proposes. Clearly, hunter-gatherers had better phenotypic health while ours suffers.

In sum, the paper Berens, Cooper, and Lachance (2017) does not refute anything that I wrote in my previous article on diseases of civilization. If anything, most of what I wrote is strengthened, especially on the basis of genotypic health not equalling phenotypic health. This paper can be summed with three points:

1) genes aren’t destiny. 2) genes wouldn’t necessarily do the same things in different environments. 3) the GRS (genetic [disease] risk scores) are also not deterministic. This is the logical conclusion to draw. OK, so ancient hominins had a higher genetic risk for certain diseases. Here’s the catch: if they weren’t in the environments that would exacerbate the disease and cause it to express in the phenotype, does it really matter that they had ‘genetic predispositions’ for certain diseases? Of course it matters for us today due to our built food environments, but did it matter for them who did not have access to the novel environments that we do today?

This is a very interesting paper but my arguments on diseases of civilization still stand. Diseases of civilization will still plague our societies until we change the built food environment, but until then, we will have to live with the worst mistake we have made as a species: constructing obesogenic environments that then lead to a huge decrease in quality of life and life expectancy.