Last month, an NYU Med School doc published an article saying that our gut bacteria might be evolved to promote our digestion when we’re young, but kill us when we’re old. This sounds like evolutionarily programmed death–just the kind of thesis that I have been promoting for 18 years. The article was picked up by Scientific American, Psychology Today, Science News, and Eurekalart of the AAAS. Why am I not cheering?
In 1966, a smart, confident young biologist named George Willliams wrote a book that changed the culture and methods of evolutionary biology. Up until that time, evolutionary biology had been primarily a qualitative, observational science, in the tradition of Darwin. (There is not a single equation in any of Darwin’s books.) Practitioners had absorbed the message that natural selection was about gaining an advantage in survival or reproduction, and this was the lens through which they looked at biological function and behaviors. When they found a subtle or unexpected advantage of this sort, evolutionary biologists were excited to report a new understanding of a phenomenon which perhaps had not made sense hitherto. This was wishy-washy, 19th Century science.
But on a parallel track, having almost no communication with the field biologists, there were a handful of evolutionary geeks–scientists who were trained in mathematics or physics, and who took up evolution in the same spirit, using methods borrowed from theoretical physics. In the early 20th Century there were Alfred Lotka and R. A. Fisher and Sewall Wright, and in the mid-century there was J. B. S. Haldane and Theodosius Dobzhansky (just to pronounce his name makes you fitter) and Wright just kept on keeping on, writing and researching until his death at age 98. These men had developed a quantitative science of evolution called “the new synthesis” or “neo-Darwinism” or “population genetics”, but their numbers were few and they tended to think abstractly, without a deep knowledge of biology in all its messiness, and so their influence on the larger biological community was quite limited.
Williams’s book heralded the merging of these two spheres of evolutionary science.
Williams was a biologist through and through, who earned his degree working with real fish in real habitats. But at a young age, he had also deeply absorbed the methhods and disciplines of the geeks. With a book boldly titled Adaptation and Natural Selection, he challenged his fellow evolutionists to
- think quantitatively about evolution, and
- think about the actual mechanisms by which an adaptation might evolve.
These were much needed disciplines, and Williams had the commanding, incisive writing style to bring his point home to a community that had become accustomed to field biology as a descriptive science.
But these are also difficult disciplines, requiring a fundamental shift in the thought process. As it happened, Williams’s message in Adaptation was caricatured, and for decades after the publication, it came to be transmitted to students of evolution in the Orwellianform,
“Individual selection, good; Group selection, bad.”
To be sure, Williams was not innocent of this message; nevertheless, his thinking was a lot more cogent and more comprehensive than the sound bytes that came to be transmitted in his name. The book was written as an appeal for more rigor in Williams’s colleagues. The part of his argument that survived concerned only group selection, and it went something like this:
Every new trait that appears begins life as a random mutation in one individual. If the mutation promotes survival or reproduction, it will spread through the population, otherwise it will gradually die out.
Suppose a mutation arises that is bad for the individual’s fitness, but offers a benefit to the community. (This is the definition of evolutionary altruism.) In theory, this trait might help a group to compete successfully against other groups that did not have the trait. But its first hurdle must be that it must come to dominate the group. But every individual who carries the trait is at a disadvantage compared to other individuals in the group. So the new gene faces an uphill battle in its first step, and it is likely never to get to the next step, where it can show its stuff in group-against-group competition.
Therefore altruistic traits are unlikely to survive natural selection.
(not a quote–this is my paraphrase)
This is a well-reasoned argument, worthy of attention and consideration, but it is not the end of the story. The argument is rooted in the mechanism of the Selfish Gene Model, which assumes that
- evolution works one-gene-at-a-time,
- genes contribute independently to fitness,
- populations are thoroughly mixed (random mating)
- genes rise and fall in a population quickly, while the population size (and everything else about the environment) changes slowly
When we write these assumptions out explicitly, it’s clear that sometimes they are true, and sometimes not. Sometimes the Selfish Gene model does fine, and sometimes a more complex and sophisticated model is called for.
If we take to heart Williams’s deeper message, then when we find traits in nature that look like altruism, we should consider all mechanisms by which it might have evolved, evaluate them quantitatively, and decide on the most plausible evolutionary explanation.
If things had developed as they should…
It was right, of course, that the field biologists and the evolution geeks should talk to each other. They purported to be studying the same subject. But what should have happened (in my couterfactual history) when the biologists first compared notes with the mathematicians is that the biologists should have had the upper hand. “Here’s where your theory works–here’s where it doesn’t. Go back to the drawing board and give us a more complete theory that explains what we see.” We might have arrived at an understanding of the usefulness of the Selfish Gene, and also its limitations. Whenever there is a conflict between theory and observation, it is theory that must bend.
But in real life, this is not what happened. In real life, the mathematicians were smart and brash, and the field biologists were more tentative, nuanced in their understanding, a little embarrassed about the contradictions in their findings, and easily intimidated by formulas. All too often, the mathematicians simply told the field biologists they were wrong, that they were not seeing what they thought they were seeing, that theory forbids it.
The theory they invoked was the simplistic Selfish Gene theory, because this was a time before computer models, before the ideas of evolutionary ecology had a platform for development. Theorists did not keep in mind that the Selfish Gene model was just a model, and they insisted that it must explain everything.
The message of George Williams survived mostly in its caricatured form. The rigor he required proved to be too demanding for biologists, and two generations of evolutionists took the shortcut of affording credence to any explanation that looked to be based on individual benefit, and dismissed any explanation based in group selection.
So this became the era of the Selfish Gene, which is just now winding down, and an appreciation of Williams’s true message is finally spreading through the community.
Gut Bacteria and Programmed Death–What does the article say?
We circle back now and consider the article by Martin Blaser, microbiologist at NYU, andGlenn Webb, who does computer modeling of biological populations at Vanderbilt. The failed revolution of George Williams sets a stage for all that is effective and all that is missing in Blaser & Webb’s analysis.
The age structure of human populations is exceptional among animal species. Unlike with most species, human juvenility is extremely extended, and death is not coincident with the end of the reproductive period. We examine the age structure of early humans with models that reveal an extraordinary balance of human fertility and mortality. We hypothesize that the age structure of early humans was maintained by mechanisms incorporating the programmed death of senescent individuals, including by means of interactions with their indigenous microorganisms. First, before and during reproductive life, there was selection for microbes that preserve host function through regulation of energy homeostasis, promotion of fecundity, and defense against competing high-grade pathogens. Second, we hypothesize that after reproductive life, there was selection for organisms that contribute to host demise. While deleterious to the individual, the presence of such interplay may be salutary for the overall host population in terms of resource utilization, resistance to periodic diminutions in the food supply, and epidemics due to high-grade pathogens.
In particular, they cite H. pylori (famous for its connection to ulcers) as example of a bacterial strain that promotes digestion and good health for young humans, but that can lead to cancer of the stomach or esophagus late in life. Perhaps this bacteria serves the function of removing from the population older individuals who are no longer fertile, so that they are consuming scarce food, though they are unable to contribute to the reproductive rate that keeps the community viable.
I find the thesis unclear on several different levels.
- What is evolving here, the genome of the bacteria or of the humans?
- What is the mechanism by which intestinal bacteria spread through a community?
- What measure of fitness is applied in the model, and is it the fitness of the bacteria or of the humans?
To the credit of these authors, they do not categorically dismiss group selection or programmed aging from consideration. In fact, they claim in the paper’s Introduction to explicitly consider both. But I’ve had a devil of a time trying to figure out how their model works, let alone how it answers the standard broadsides against group selection and programmed aging. I find myself agreeing with Williams in his appeal for clarity and rigor.
“Who profits?” The title of the paper is Host Demise as a Beneficial Function of Indigenous Microbiota in Human Hosts, but whose benefit are they talking about? Certainly not the individual human who dies or esophageal cancer, nor the gut bacteria that die with him and relinquish their opportunity to be transmitted human-to-human.
The root of the unclarity is that our understanding of the relationship between gut bacteria and the host human is still quite hazy. There is enormous variability from one person to the next in the type and variety of gut bacteria. There are benefits to the host human from some combinations, and diseases that come from others. But it seems that there is no one optimal bacterial community that is right for everyone, but rather that the interactions among an individual’s metabolism, his environment, his diet, and his bacterial community form a complex system.
Do the bacteria in our guts serve at the pleasure of the host (that’s us), or are they opportunistic invaders? These are major open questions in the field of microbiology. The answer seems to be “neither”, and the ecology of each person’s bacterial community has an integrity and a logic all its own.
Mammals harbour a complex gut microbiome, comprising bacteria that confer immunological, metabolic and neurological benefits. Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes used by symbiotic bacteria to stably colonize the gastrointestinal tract…the gut normally contains hundreds of bacterial species… [Ref]
It has been a central thesis of my own work that entire ecosystems evolve together. The present example is as strong a case as I can imagine. Each bacterial species much be able to hold its own in the gut ecosystem, and the entire colony must serve the digestive needs of the individual human host, because if the host dies he takes the bacterial colony with him.
There is a great deal of selfishness and a great deal of cooperation involved in this dynamic, in a mixture that cannot easily be disentangled. Suppose it is in the interest of the human community to eliminate its non-reproducing elders, but if the H pylori kill their host, then they are missing out on the opportunity to continue spreading from this one individual to others, perhaps younger family members who are sharing food. I look for this issue to be discussed in the paper, and I don’t find it.
Indigenous microbial populations that contribute to the health not only of the individual but also of the host group will be most strongly selected…If indigenous organisms contribute to programmed host death in senescent individuals but not to the death of reproductively active individuals, there may be selection for their maintenance.
Yes, “there may be selection”…but at what level, and by what mechanism? My guess is that indivdual selection for each bacterial strain and for the human host are all important, and that the communal function of the bacterial colony is also essential, as is the welfare of the human community, and all combinations of interactions among these.
This is simply a linear model for projecting the population age distribution from one year to the next. If you have this many 1-year-olds this year, then next year, this many of them will die, and the rest will be 2-year-olds. If you have this many 2-year-olds…, etc. If you have this many women of child-bearing age in the population, then this is how many newborns you can expect in the coming year…
This is a standard model for calculating population dynamics, (introduced by Patrick Leslie, 1945). It is the model used by Glenn Webb in the current paper. But missing from this model is the dynamic of population overshoot, followed by famine. This is at once the gravest and most ordinary danger to any population, and the one that (in my view) aging was evolved to defend against. So I worry that Blaser and Webb have left out something important.
Loss of Fertility and Loss of Life
(or reproductive senescence and mortality acceleration)
In many animals (including us) there are two independent aspects of aging:
- loss of fertility, leading to sterility
- loss of strength, viability and robustness, leading to death
It is a prediction of classical evolutionary theory that these two should occur at the same time. Why should an individual go on living after it is no longer able to reproduce? It can be of no use either to itself or its community. But in the biosophere, we find this prediction is routinely violated.
Of course, human females undergo menopause, and can live for decades thereafter. For theoretical reasons, post-reproductive life span has been thought to be unique to humans, or perhaps a few other social mammals that take care of their grandchildren.
But field studies show that this isn’t true. In fact post-reproductive life is widespread in nature–perhaps it is the rule rather than the exception. C elegans worms don’t take care of their grandchildren, nor do quails or yeast cells; yet all of these have been observed to outlive their fertility. Add whales, elephants, opossums, parakeets and guppies to the list as well.
How to understand post-reproductive life span is a topic for another week, but Charles Goodnight and I have written about the subject (in journalese) here.
In addition to this, there is another paper I suggest that Blaser and Webb might have benefited from assimilating.
Once fertility has ended, there is a natural selection to kill the non-reproducing individual, because it is consuming food, taking up space in the niche without contributing to sustaining the community. This idea goes back to Weismann 120 years ago, but in modern times it has been modeled and explained most thoroughly by my colleague, Justin Travis.
Curiously, there is also a communal reason to keep the post-reproductive members alive for awhile, in a weakened state, assuming that community has excess reproductive capacity. The post-reproductive segment of the population serves as a buffer to prevent population overshoot and whip-sawing that can lead to extinction. They consumes food when there is plenty, and thus they help keep the population from growing too fast. Then, when food is scarce, they are the first to die because they are old and weak. This is the idea that Goodnight and I modeled and published (2012).
The bottom line
For me, the upshot is that I don’t understand enough of how their model works to judge whether they are on to something. I’m tempted to add that computer modeling of aging is my specialty field, and if I can’t understand their model, for whom are they writing?
In controversial fields like this, where there has been so much confusion and misunderstanding, it behooves us all to be extra careful to follow Williams’s directives: think (and write) in terms of explicit mechanisms of heredity and selection.
Most readers of this work are already pre-disposed to pre-emptively dismiss the ideas of programmed aging and group selection. Let’s not give them an excuse to do that.
This article originally appeared in Josh’s blog Aging Matters here.