This post originally appeared on July 14, 2019 here and was pre-ChatGPT which may only exacerbate the conclusions.
This title is a bit tongue in cheek but seems an appropriately suited introduction to the ensuing article – which is notably about how our environment and culture affect our genetic composition and selection. This topic is known in more recent academic publications as the study of cultural genomics and it bears particular relevance at this time with the advent of powerful genetic engineering technologies such as CRISPR and the concurrent discussion of how, when and why to consider using genetic engineering technologies on humans.
This discussion can be considered an updated version of the debate that began back in the ’70s when Genentech began commercializing engineered forms of biology in the first molecular biology revolution. This debate around the “naturalness”, safety and ethics of hacking up life and creating franken-cells (as it were) was by no means trivial and for a detailed, and rather entertaining account of this critical juncture in the relationship between humans and the biological world can be found in the book Genentech: The Beginnings of Biotech by Sally Smith Hughes1—a highly recommended read on the origins of biotech.
While the first molecular biology revolution dealt with our ability to manipulate other cells, we may now rightly consider ourselves in the middle of the second molecular (and cellular) revolution – if one does not count next generation sequencing which is generally more concerned with documenting or reading biology than it is with writing or engineering it. The development of powerful and precise engineering tools like CRISPR have made it both possible and practical to actually engineer our own cells, both somatic and germ line in very specific and very tunable ways. The power and potential of these technologies are extraordinary and equally as well controversial. With the first news of germ line editing taking place in China2 already and a potential second wave in Russia3, the debate has heightened about how to consider using these technologies. A crucial part of this debate also centers around cost, access, and the potential unknown consequences, particularly of editing the human germ line and, in a sense, manipulating the very foundations of evolution. This has given rise to the next iteration of the claims of “playing god” and so on that have peppered the biotech landscape for the last several decades. This article is aimed at mollifying many of these concerns with some practical and, perhaps misunderstood, realities about what genomics is and how it affects our lives. Specifically, this article is about how pretty much anything that happens in the world—and those that drive it, can be accused of playing god to the same extent. This is the concept of cultural genomics.
Playing God
Genomics is complex—this is a fundamental understatement that barely scratches the surface of what we actually understand about the basic coding of life. This lack of understanding, even one level up the central dogma becomes almost entirely untethered from an ability to make predictions about large scale implications. When we get to cells, we are lost, let alone microenvironments, organs, organ systems, animals, ecosystems or any other such complex system. We have no clear concepts of how these things are intertwined and affect each other. And let’s go one level deeper, just for fun. The concept of a genomic sequence, in and of itself, also means rather little. Layer on epigenetics at the DNA level (methylation, chromatin, etc), the RNA level, protein degradation and a host of other regulatory mechanisms and we have a very tenuous understanding of what actually does what. And one level deeper still – our genomics (both sequences and epigenetics) are constantly changing, with every cell division and every external stimulus. The concept that we have a “genomic” sequence is rather rudimentary at a technical level, we are all chimeras, and we are all evolving continuously.
So, with that stage set, let’s talk about the concept of playing god. This concept relates pretty heavily to the discussion of the influence of nature vs nurture on our overall development—notably the concept of “playing god” resides pretty exclusively on the “nature” side of things as a cultural reference (e.g., we don’t often hear it described that parents rearing their kids are playing god), yet this is a rather myopic perspective. We know pretty clearly that environments affect genetics through a wide variety of mechanisms, yet we don’t consider those that are creating, controlling or manipulating environments in the same category. This begs the question then, what does playing god really mean? What do we consider an undue influence on the genomic composition of our civilization? This latter question is particularly relevant in the study of cultural genomics—or how our culture affects the genomic composition of both individuals and populations. The classic example of this is lactase – an enzyme that is used to digest the lactose sugar in milk. In historical contexts, this enzyme has generally not been expressed in adults—typically the loss of the enzyme expression occurs after a baby stops breastfeeding. However, over time and with the cultural domestication of animals, and consumption of animal milk well into adulthood, genomic variants have arisen through various mechanisms that have allowed for the persistence of the expression of this enzyme and have become enriched in our gene pool4. Would one make the argument that domesticating animals is playing god? It is certainly an activity that is very “human” in nature—i.e., only humans are sufficiently evolved to domesticate other animals, so it cannot be claimed to be a simple feature of natural evolution (unless evolution entails the concept of the ability to control evolution—which is the point of this argument). And as a precondition, civilizations that domesticated animals and became enriched in lactase expression would have no ability to understand any other downstream, and perhaps negative consequences of this action, so it is entirely possible that the genomic changes that were a consequence of the extended expression of lactase would also have concomitant negative implications. There would be no way to know a priori. Yet we would not consider the domesticating peoples to be playing god. This is happening all the time, through everything, every day.
The Primary Fear
The primary fear and concern around the concept of genetic engineering as a deliberate tool is that we don’t know how to understand the outcomes or implications. But as a specific fear, this should equally as well be applied to anything we do. We could consider that we don’t understand the long-term genetic implications of modern medicine keeping people alive and through reproductive ages with infirmities that might have previously been sorted out via early death. We are thus enriching for genomic defects through medical care. One of the most egregious examples of this is the rise in the rates of cancer and degenerative disorders—well-characterized diseases of age. The longer we stay alive, the more prone we are to developing then. What a terrible outcome of modern medicine. The primary fear of genetic engineering seems to be that it is deliberate at the source point (e.g., the genome) vs being directed via external selective powers (whose outcomes are not well understood) and consequently no particular selective mechanism, or person can be blamed. But in the case of precision genetic engineering, fingers can be pointed if things go awry. This seems to be a case of distributed (and ambiguous) guilt or lack thereof, and the ability to lay specific blame, which seems to be more of a sociological issue than a scientific one. A second issue that is raised, which is also a bit of a misguided concern is whether the specific genetic engineering events relate to somatic mutations or germline mutations. The concept is whether one is specifically engineering changes that would affect downstream generations and the overall gene pool, but this discussion as well is misguided. If, for example, one was to consider a genetic therapy for a childhood congenital disorder that was inheritable, that therapy, somatic in nature, would nonetheless provide the potential for the sustaining of a defective genetic condition in the gene pool if such a condition did not affect the ability of the individual to reproduce or the germline genetic composition. The issue of germline vs somatic is muddled in this manner. Somatic therapies for genetic conditions, like modern medicine as a whole, serve to impact the genetic composition of future generations by providing the potential for reproductive capacity of detrimental mutations in the germline. We cannot deconvolute our abilities to affect the genetics of future generations through any actions that we undertake, but if we can blame something—it at least provides some psychological comfort.
Back to Siri
The issue of cultural genomics is rather complex and intensely interesting particularly as it relates to environmental changes. Over the past few decades, the rate of change of our environment has vastly exceeded the passage of generations (which is a proxy for the evolution of a genetic clock) and as such the rate of fitness functions and genetic compositions, expressions and predispositions that yield success in our current society may be changing equally as rapidly and may, in fact, be favoring certain attributes more than others—a consequence whose implications are impossible to fathom. One interesting example of this that was recently discussed is the concept of the brain’s capacity to recognize friend or foe. This has been a critically important, and extraordinarily complex development in the evolution of the human brain in conjunction with complex societies and, indeed, the human ability to perform facial recognition has only recently been even approximated by artificial computers. However, what happens to this complex function if we all start wearing headsets that perform this for us? Our google glasses might just as easily be able to tell us who our friends and who our enemies are, and we will be able to offload this capability. We are already seeing this trend in the retention of memory—with people offloading their requirements to actually remember things to their devices. How do we imagine this is changing the physical structures, expression levels, and genomic variants that enrich for a different set of characteristics. Will there be a new genomic definition of “smart” in the future? Will we want to specifically engineer this into embryos? Are we already selecting for it culturally via the pervasive adoption, and indeed reliance on technology? Should we be accusing technology developers of maliciously altering the genetics of future generations?
The point of all of this is that we need to think deeper about how we classify these challenges and philosophical issues and not simply take a superficial strike at the mechanisms that allow us to place blame or point fingers as being the most relevant approaches.
https://www.amazon.com/Genentech-Beginnings-Sally-Smith-Hughes/dp/022604551X
https://www.sciencenews.org/article/chinese-scientists-raise-ethical-questions-first-crispr-gene-edited-babies
https://www.nature.com/articles/d41586-019-01770-x
https://pubmed.ncbi.nlm.nih.gov/28426286/