Evolutionary biology vs. evolved biology

Once, during a medical exam, the doctor asked me what I did. I said I was an evolutionary biologist, to which he replied, "oh, so not a creation biologist?" His tone of voice made it clear he thought it was funny that I had to specify evolutionary, as though a biologist in Berkeley could possibly not believe in evolution. Considering where his hands were at the time, I didn't stop to explain to him what the term "evolutionary biologist" means. Every biologist knows, or should, that Theodosius Dobzhansky wrote, "Nothing in biology makes sense except in the light of evolution." The vast majority of biologists, of all disciplines not only know about evolution, but accept it as a necessary part of any complete explanation for the things they study. But a large portion of biologists don't regularly think about evolution; it is not the part of the explanation they are interested in. A large (and I think increasing) proportion of biologists study the interactions of atoms, molecules, organelles, genes, cells, etc. And while they may connect their work to evolution in some way, they are not basically asking questions about evolution, but about the details of the proximate mechanisms which make organisms work. That these mechanisms are the result of evolution is often not particularly relevant to the present question.

An example: A couple of years ago I attended a workshop on bioinformatics in aging research. There was a dinner the night before the talks started, and the bioinformaticist organizing the workshop asked me about my training and research. I said, "well I study the evolution of demographic patterns, particularly how constraints on natural selection lead observed demographic patterns to differ from the predictions of evolutionary theory." He replied, "Oh, but you are also trained in biology?" What he meant by this, I discovered, was that I also had some training in the molecular nuts and bolts that to him are biology. Evolution is a process that shapes biology, but in his view, and I think the view of many of the people there, does not in itself count as biology. Asking him if he ever incorporated evolution into his work, he explained that he had, comparing how networks of gene interactions differed between fruit fly and nematode. Fair enough, comparative biology is surely the study of evolution, but his approach to it required no technique or concept from evolutionary theory. He produces good and useful science, and gives no more daily thought to evolution than I give to promoter regions. I am certain that he would not be offended to be described as a good biologist who believes in evolution, but is not an evolutionary biologist.

A definition from wikipedia: "Evolutionary biology is a sub-field of biology concerned with the study of the evolutionary processes that have given rise to the diversity of life." This is somewhat too narrow in my view, but it is close enough given that it is past my bedtime.

This has all come to mind because of the post I wrote yesterday, about weeds evolving resistance to Monsanto's best-selling herbicide, and the failure of Monsanto's biologists to predict this. A good friend of mine, who is deeply knowledgeable about matters environmental and agricultural, responded by asking how Monsanto's biologists could have failed to predict the apparently obvious facts I was pointing out unless they were A, Tools; B, Fools; or C, having their results manipulated by suits. This is a reasonable and interesting question, and I'll venture an answer. My guess is that they were neither A nor B, and that C went on but was not a major factor. Monsanto did have an enormous financial stake in convincing regulators that weeds would not evolve resistance to Roundup, but they also had an enormous stake in having weeds actually not evolve resistance to Roundup.  So my guess is they honestly thought it was a highly unlikely outcome.

Why did they think so, despite being smart, honest biologists? Because they weren't trained in, or primarily thinking about, evolution as it occurs in nature. They were plant geneticist and bioengineers, spending many years and countless millions of dollars to unravel the finest details of how Roundup kills plants and how to build a crop that will have resistance to it (without passing that resistance on to its offspring). That was an enormous challenge, and their success was unprecedented. They had achieved what many, even within their own company, must have thought was an impossible SciFi dream.

Surely someone was assigned to think deeply about the problem of whether weeds would evolve resistance, but surely that someone had been involved in the project for years, and was so wrapped up in the grotesque details of the genetic magic they had just achieved that no perspective was possible. In other words, they couldn't see the field for the soybeans. A person highly trained in artificial selection, and used to that way of thinking, will think of the evolution of weed resistance in those terms, despite the fact that natural selection has inherent advantages.

In hindsight, their logical errors are obvious, probably even to them. In foresight, reasonable and well intentioned people frequently fail to think of highly relevant and potentially obvious things. This is particularly likely if those things require a perspective they don't possess, doubly particularly if they are thinking deeply about the problem from a very different perspective. Monsanto had many biologists who knew about evolution, used a particular type of evolution as a tool, and thought about evolution. But my guess is they didn't have any evolutionary biologists.

Evolutionary challenges to gene engeneering a better human

My friend Terry is a bioengineer, as well as a part time futurist. Much of what people in his field work on (as judged by what Terry talks about when he puts on his futurist hat and has a couple of glasses of wine) is thinking about how to modify the human genome to increase our lifespan and healthspan (I just made up the word healthspan, but I bet someone out there is already using it). Much of my work is to understand how and why we evolved to have the lifespan and healthspan we currently do. My understanding of my work is not promising to my understanding of this part of Terry's colleagues' work. In my view, bioengineering a much longer lived human will be extraordinarily difficult for several reasons.

First, we have a great many systems that seem to fail at about the same age, and there are good evolutionary reasons why this should be. Why bother building a femur that last longer than your heart, or your brain, or your pancreas? So to engineer a much longer-lived human, one has to be prepared to make a large number of changes to see a small effect. Terry counters that there will inevitably be some low-hanging fruit, and I concede this point. Simply by editing out some of the purely harmful mutations in the human gene-pool, we can probably extend average life span by a few months or maybe a couple of years. But because so many things fail at similar ages, no one or two or 100 changes could give us healthy 150 year olds.

Second, many individual genes have an enormous number of different effects in a wide range of systems, tissues and traits. When a gene has more than one effect, this is called pleiotropy, and we are chock full of pleiotropies, most of which we don't yet know about or understand. DNA is not like a blueprint, where you can just erase one wall, re-route a few wires, and draw in a new door. It is more like a vastly sprawling and disorganized system of interacting computer applications, add-ons, duplicates, and operating systems (only without any comprehensible order, annotation or easily understood compartmentalization). Something which functions as part of an unnecessary application may also be used in several disparate parts of the operating system. Modify a line of code and all sorts of unintended things can happen. Evolution has fine-tuned this system of interactions through millions of generations of trial and error, with emphasis on the error. Our best computer simulations are barely able to comprehend the folding of a single amino acid string into a protein, let alone a whole cell or organ or human, and animal models only go so far. So the process to modify evolution's optimization would not be fun, fast or clean. Our various bits are tuned to work together, and most potential single modifications can only move us away from that local optimum.

Terry counters that in many cases what evolution was tuning was utility in the form of health/strength/life vs. cost in the form of calories. A large part of the theory of life-history evolution is based on models where developing organisms have limited nutritional resources to invest in important tasks like growing, healing and reproducing. If one assumes unlimited calories are available, one can theoretically grow, reproduce and heal maximally all at the same time. And in Terry's view (which I can't help but see the wisdom in) anyone who can afford to play with the human genome can also afford plenty of potato chips. For the relevant population, calories are no longer limiting. In fact, we go out of our way to burn extra calories now. Spending calories lavishly to buy a few extra years of life or more garish secondary sexual traits is a win-win. The bioengineers of the future will have the advantage over evolution, because they won't have to worry about one of the main constraints evolution was dealing with, calorie restriction. So we may have to change a few things at once to make it all work well together, but we can do that. We can, in my imagining of Terry's thinking, reengineer the organism to its new environment.

It occurred to me last night that there is third, bigger and more insurmountable barrier to re-tuning. One that is not just a technological limitation: Breeding. Humans have been known to breed with each other, and in doing so they mix their genomes. You have half the genome of your biological father and half the genome of your biological mother. Imagine if your uber-mench father had a carefully altered suite of genes, and your mother was a good old-fashioned non-GMO woman. What do you get? You get half a carefully altered genome mixed with genes they were never designed to interact with. Chances are, you have all sorts of wacky health problems, and greatly reduced longevity. It would be like taking half the code of Mac OS 9 and half the code of OS X and expecting a stable operating system.

This means that every change and group of changes would have to be carefully designed to be back-compatible. The alternatives are gene altering the entire human population (which would never ever ever ever work (and I very rarely use that many "ever"s in a row)) or engineering the longevous new humans to be incapable of interbreeding with the old model. They'd have to start by separating off one population as a seperate species, Homo terrii, and only thereafter get serious about reengineering.

So suppose the engineers decide they want to make everything back compatible?
I'm not convinced this would work either. Most mutations are bad for you not only because they break a piece of the system, but because they make a new piece that doesn't work with what is already there. Requiring back compatibility means we have to have every piece work with not only the old set of genes and the new set of genes, but every possible combination of old and new. Evolution, largely free from constraints of time, funding and ethics, accomplishes this by letting those individuals who have bad combinations die out until there are very few harmful combinations possible. To extend the computer code analogy, this would be like trying to write OS XI in such a way that if one blended the code with OS X, it would still work. It is possible to do, but XI would end up looking an awful lot like X, too similar to be more than a service update.

This leaves only the option of creating a population incapable of breeding with normal humans and altering their genes extensively to try to overcome a large number of age-limiting factors at once. Again my understanding of evolution suggests a major difficulty. To do this successfully, one would need a large population all gene-altered simultaneously, to avoid inbreeding effects. One can't start a new population with just a few individuals and expect that species to have a decent chance of surviving well. Even if the species does make it through, there is likely to be an extended period of decreased lifespan and healthspan while the inbreeding kinks work themselves out and the population increases in size and genetic diversity.

Without doubting that bioengineers will continue to make things that seem impossible become projects of undergraduates, I consider it highly unlikely they will achieve any very significant advances in human longevity in the next few decades.

(NOTE: I sent this to Terry for comment or objection some time ago but he has been busy with 'job' and 'editing the book.' I take his failure to offer a substantive reply as evidence that in some basement deep under campus, his department is already failing to build an immortal human.)