Evolution & Disease: Interview with William B. Miller Jr., M.D., Evolutionary Biologist

Dr. Miller is a graduate of Northwestern University in Biology, Northwestern Medical School, and is a member of the medical honor society, Alpha Omega Alpha.  He currently serves as a scientific consultant to the microbiome industry. He is the author or co-author of three books  and over a dozen peer reviewed articles on evolutionary biology and the science of the microbiome. Besides his medical work, Dr. Miller  has been painting in oils since his teens. He now paints figurative works and portraits in his studio n Phoenix. Arizona and his figurative work is featured at Hilliard Gallery in Kansas City.

 NP: How would you define and or describe evolutionary biology and what led you the study of it, in particular becoming a proponent of cognitive-based evolution and its implications?

 Miller: I’m a physician by training and had been in academic and private practice for decades before I became interested in evolutionary biology. I owe that entire transition to a girl named Sue.  No, it was not a romantic liaison. Candidly, she was just not that into me, since Sue is the magnificent Tyrannosaurus Rex fossil specimen in the rotunda of the Field Museum in Chicago. Our meeting was chance. More than a decade ago, I was at a medical conference in Chicago. Toward the end of several consecutive days of lectures, I felt the need to take a break. I suggested to a friend that we go to the Field Museum near the end of the day for a change of pace.

Entering the museum that day, Sue commanded my attention. Of course, everybody notices how incredibly deficient her arms were. They were too small to be effective weapons, considering her size. However, what struck my particular interest was that T. Rex was a dominant predator for over 6 million years and those arms remained the same length relative to body size over that entire span. I was also struck by how much of T. Rex anatomy overlaps our own, given the colossal difference in size. More or less, its ribs looked like our human ribs, its vertebrae are basically similar to our own and, so too, the basic architecture of the pelvis, hip socket and each of the major arm and leg bones. Yet, T. Rex existed 80 million years ago.

At that time, my own acquaintance with evolutionary theory was scant. None of this made sense to me and I actually expressed these thoughts out loud to my companion.  On hearing that, he was entirely dismissive, proclaiming that it is simply a matter of time. His implication was that natural selection is the obvious solution to every evolutionary issue. I simply could not accept that and this discrepancy became a prodigious motivator, which eventually led to my first book, The Microcosm Within: Evolution and Extinction in the Hologenome. I was very fortunate. It attracted just a bit of academic interest which has led, over the years to several other books and nearly two-dozen peer-reviewed academic articles.

Jumping from medicine to evolutionary biology is not a common thrust, yet,  evolutionary biology is simply our attempt to understand ourselves from our biological origins forward. It is a rather natural derivative interest for someone interested in medicine. Nor is it a merely intellectual exercise. If the evolutionary paths that have led from the first cells to all the other glorious creatures on the planet, and then to ourselves, are  explicitly and accurately understood, then we would have a profound insight into our own human metabolism and physiology. This would naturally ramify as significant improvements in healthcare and a substantial enrichment of our ability to be proper stewards of the planet.

NP: Stephen J Gould, paleontologist and biologist wrote about punctuated equilibrium where there were junctures in evolution that witnessed unusually large amounts of evolutionary growth in short periods of time. What are your thoughts about that idea?

Miller: Gould and his collaborator Eldredge were giants of evolutionary biology. At a time when it was heretical to contradict conventional Darwinism, they were among the few that dared. Since the publication of the On the Origin of Species in 1859 by Charles Darwin – steady pillars have upheld conventional beliefs about evolutionary development on the planet. Evolution proceeds by the process of natural selection through the gradual modification of inherited features. It is an important feature of that theory that these successive modifications must necessarily be very small since these infinitesimal changes are thought to arise from random genetic errors during reproduction. Crucially, such genetic mutations would need to be quite small or their consequences would imperil survival. Gould and Eldredge went beyond that theory and examined the fossil record of the ‘Cambrian Explosion’ which occurred roughly 500 million years ago. During this period, there was a sudden and dramatic appearance of new body types, represented by well-preserved fossils, and many of these were novel types of organisms without clear-cut ancestors.

Gould suggested a remarkable solution to this gap between theory and actuality. No matter how cherished the theory, it must be adapted. He proposed that evolution does not proceed by infinitesimal steps but is instead a series of intermittent leaps, termed ‘punctuated equilibrium’. Species are stable for long periods and then, for reasons that were not then apparent, there could be bursts of evolutionary activity. This would then be followed by long periods of evolutionary quietude.

In the ensuing decades, the mechanisms that would enable these kinds of large genetic transformations that could permit these types of evolutionary transformations have been identified. Consequently, the theory that random genetic mutations are the source of evolutionary variation is slowly being eroded in favor of the accumulating evidence that genetic transitions can be abrupt and substantial. It had previously been believed that the central genome (that part of the genome that is studied by the Human Genome Project) is a stable sacrosanct compartment. Now, we know otherwise. The central  genome is a lively participant in many forms of genetic variation which are much more consequential than random reproductive genetic variations and permit all living organisms to consistently and flexibly confront environmental stresses.

NP: There have been any number of studies focusing on coming plagues and genetic mutations of infectious diseases. Is it accurate to say that everyone in every part of the world will experience unwanted microbes in their body at some point in their life? How would you describe our scientific, social and political understanding of what is taking place in the world of disease and how it related to evolution as well as human evolution itself?

 Miller: The answer to the first question is an unequivocal ‘yes’. The history of life on this planet is centered on infectious interchanges. The entire process of evolution is dependent on it. Further yet, within our human context, infectious disease is the ultimate common denominator of our health and well-being. We, and all other creatures on the planet, are in eternal conflict with infectious disease.

Perhaps,  no better means of illustrating the enormous consequences of epidemic infectious disease on human history can be offered than the example of smallpox. The plague of Antonine (165-180AD) which has been attributed to smallpox resulted in the deaths of more than 7 million people and contributed to the decline of the Roman Empire. Similar horrific mortality was experienced in the New World in the 1500’s. Before to the Spanish conquistadors, smallpox was unknown. After its inadvertent introduction, the majority of the indigenous populations were wiped out leading to the collapse of the Aztec and Incan empires.

In 18th Century Europe, at least 400,000 people died annually from smallpox. One-third of the survivors went blind. Mortality rates were as high as  60% in some communities. Infant mortality was even more frightening, approaching 80% of infant deaths in London in the 17th century in epidemic waves.

The ultimate success of smallpox vaccination is credited to Sir Edward Jenner in England.  In 1796, he successfully introduced the technique of cowpox vaccination demonstrating its subsequent protective effect against smallpox. Today, due to the effectiveness of worldwide smallpox vaccination programs, that disease has been effectively eradicated from the planet.

In our modern era, we are just as susceptible to the epidemic spread of disease. For example, this year appears to be developing into a  hard-hitting flu season. The Centers for Disease Control has now issued disturbing reports of the flu deaths of previously healthy children and young adults. These may seem like atypical events, but unfortunately, they are not. The influenza virus has been our common affliction for thousands of years. If the full historical record is considered, these types of outcomes are not uncommon and should be taken seriously.

Our experience with seasonal flu in the last few decades has followed a comforting norm. While the previously healthy can be infected and suffer some uncomfortable symptoms, a quick recovery is to be expected. Most of the annual flu fatalities occur in the chronically ill and elderly.  However, that pattern is merely chance at work. At many other times in human history, influenza has been a deadly scourge for the young and otherwise healthy part of the population.

The Great Influenza Pandemic of 1918 was just such an instance,  occurring during the First World War and ravaging worldwide populations. It is believed that 500 million people were infected. The estimate of total deaths ranges from twenty to over fifty million. The pace of this infection was so astounding that more American troops in World War I died of influenza than in battle.

Even now, after much research, the dynamics of that infection are unclear. It is known that there had been mild outbreaks of influenza in the spring of 1918. Yet, few deaths had occurred. However, within a short interval, a new strain of influenza virus suddenly emerged that was incredibly lethal, often leading to death within hours. This pandemic was so unprecedented, and it exerted its worldwide effect with such fury, that a state of panic existed within many global communities. The pattern of fatalities was particularly alarming. The elderly and infirm were not its targets. Instead, it disproportionately afflicted young adults that had otherwise been entirely healthy.

More recently, the Ebola epidemic can be considered a clarion instance of how a future global emergency can suddenly arise. For the first time in human history, because of air travel, there can be nearly instantaneous spread of viruses over long distances. Both influenza and Ebola are zoonoses, just like the viruses that spread HIV, SARS (Severe Acute Respiratory Syndrome spread from civets), MERS (Middle East Respiratory Syndrome originating in camels), or West Nile Virus. A zoonosis is an infection spread from one animal species to another, such as swine flu. The majority of human pathogens and almost all emerging infectious diseases are zoonotic in origin. As an example, in today’s news, coronavirus is another instance of a zoonotic infection and there is a genuine alarm that this could become the next pandemic.

Despite having recounted these scourges, there is another aspect of the microbial realm that deserves emphasis. It is an error to exclusively regard microbes as enemies. Our bodies are made up of a combination of personal cells and a vast array of intimately associated microbes. Instead of a ‘one’ we are a vast deeply integrated ‘many’. Our bodies are vast cellular collaboratives that include an  immense amount of microbial life. Our cells and these necessary and partnering microbes combine into cellular ecologies which link together so seamlessly that we live within the illusion that we are only a single being.

Research has found that microbial cells that are in us and on us outnumber our personal cells by a factor of 10 to 1. If all the genetic material of these microbes was combined, it would amount to a quantity that overshadows our intrinsic genetic material by at least 40 to 1. We cannot survive without some of those microbes and they cannot be what they want to be without us. Furthermore, it is now understood that the exact composition of this enormous microbial constituency has a crucial impact on every aspect of our life.

We are dependent upon a vast array of microbial genes for our metabolism, growth and development and immune systems. They even partner in our reactions to stress, sleep-wake cycle and even more surprising – our moods, behaviors and attitudes.

From this contemporary understanding of our true biological nature,  a further conclusion is warranted. Human evolution has been a process of co-development with our microbes, for the benefit of both. There is no valid interpretation of evolutionary development  without taking  this vital fraction of our true selves into consideration.

NP: If you could assess the future based on where we are now in understanding evolution and the microbes within us where is the human species headed and how adaptable is the human body and mind to evolve further?

Miller: By way of an answer, let’s consider the recent movie, ‘War for the Planet of the Apes’. Although the movie is fictional, it contains some pertinent lessons about modern bioengineering. The Planet of the Apes series is one of the most successful franchises in Hollywood history. Since 1968, over six attention-grabbing movies, billions of dollars have flowed from audiences to Hollywood.  In the most recent film of that series, the narrative begins with ALZ-12, a drug designed to cure Alzheimer’s. In the movie, that drug is based on a specific type of viral vector, known as a retrovirus. Retroviruses easily infect cells. However, they also have another special trick. They can make a specialized copy of their own DNA that can be inserted into a target genome, like our own. In the movie, a retrovirus was inserted into the ape genome and the result was a permanent and dramatic change in those primates.

Just a movie scenario, right? Not entirely. This type of retroviral interaction with genomes has occurred throughout evolutionary history. It’s even happening right now. For example, HIV is a well-known retrovirus which has demonstrated an epidemic spread. A similar retrovirus, Koala retrovirus, has disseminated throughout the Koala population and  has successfully inserted itself into the Koala genome. It is now part if its heredity DNA. The shocking aspect of this occurrence is that we have only been aware of this type of retroviral infection for a few years and we have already seen a documented instance with evolutionary consequences in real-time.

Throughout our evolution, we, as humans, have not been spared. There is substantial evidence of overwhelming viral contributions to our human genome. It has been estimated that as much as 50% our genome can be considered viral in origin with at least 9% of it known to be specifically retroviral in origin.

In the ‘War for the Planet of the Ape’, a worldwide retroviral infection proves a boon to the apes. Non-human primates, and particularly the apes, became smarter and stronger and gain the ability to speak. Their reflexes and endurance are  improved. Even their eye color is changed. The outcome for the humans? Not so good. That same virus causes a mass human extinction. The few remaining humans that survive are immune but, arguably, not as clever as the apes.

Sounds like ridiculous science fiction? Yes, but only to a degree. Of course, no dramatic physical changes like those portrayed in the film are known to have occurred in our human history.  However, the manipulation of evolutionary processes to this degree is not scientifically unreasonable. There is growing scientific evidence that the standard Darwinian evolutionary narrative needs some contemporary adjustment, extending in a direction that would accommodate the type of ‘punctuated equilibrium’ that Gould was postulating in the 1970s to account for the Cambrian explosion. Retroviral epidemic infection is one mechanism for those types of evolutionary gaps to occur. In theory, a virus can insert in a genome and trigger a significant rearrangement of our underlying  genetic code. This coding switch might reveal cryptic faculties hidden in our genome, suppressed for now, and when released, which might confer substantial physical or metabolic differences.

Although this might seem far-fetched, CRISPR teaches us otherwise. CRISPR is a new and highly effective scientific technique for altering a genome with deliberate accuracy.  CRISPR is an acronym that stands for  particular specialized regions of DNA that are separated by spaces in a genome. It is these spaces that are the targets of that technique. Scientists have devised a means of inserting carefully tailored clusters of DNA into these areas by taking advantage of those repeating segments and the spaces in between them. Importantly though, those spaces are themselves a consequence of previously inserted viral code as a result of prior infectious assaults by viruses or retroviruses on our genome.  Throughout evolution, new viral attacks have yielded new spacers.  Now, scientists are using tailored genetic ‘viral’ segments to precisely insert or delete genetic code in these regions. Therefore, the  mechanics of CRISPR  is very similar to how infectious code has always interacted with our native DNA genomic endowment.

What does this mean for evolution? If mankind can do it, then Nature has always done it.  Despite our gifts, we are  not yet capable of devising a method of manipulating our genetic code in any manner in which Nature has not already provided. When scientists insert snippets of genetic code to correct a problem, they are mimicking a natural process and making adjustments to fit it to our ends.

From this emerging human capacity, salient questions arise. What parameters and controls ought to be placed on this technique that so powerfully mimics the actual mechanisms of evolution?  Do we, as yet, understand the entirety of its implications or are we inadvertently exposing ourselves to substantial unintended consequences? What might the ultimate outcomes our fledgling attempts be? How might these shape or alter our human destiny? Truly, no one knows. Even attempting to imagine a range of outcomes is harder than it might seem.

Indeed, there is a familiar quote that suits the complexity of this issue. It  is often attributed to Sir Arthur Eddington, the British astronomer, mathematician and physicist who devised and conducted the first experiment confirming Einstein’s Theory of Relativity: “Not only is the universe stranger than we imagine, it is stranger than we can imagine.” Perhaps, at least for this moment, the same must be said of any human bioengineering of life on earth.