From Jones and Bartlett, a book on Stem Cells from Dr. Ann A. Kiessling and Scott C. Anderson:

Selected Articles:

May 15, 2014

The Many Deaths of Vitalism

Still looking for the mysterious spark of life

God is an ever-receding pocket of scientific ignorance.

― Neil deGrasse Tyson

Recently, in a little-remarked but completely remarkable paper, researchers at Stanford published the secret to life. Well, the paper was just an overview: the actual secret resides in an open-source program they wrote called E-CELL. The program knows how to simulate every single function of a cell, from metabolism and protein production to gene reproduction. And it knows it down to the basic chemistry. The program runs until the cell splits in two. You can then pick one of those two cells and re-run the program. It represents the holy grail of computational biology. Oddly enough, at no point in the simulation is a miracle required.

The spark of life, the élan vitale, the qi, the soul… none of these subroutines were required in the making of this simulation. Does this deal a lethal blow to vitalism? Given the tenacity of vitalists, probably not, but it pushes it further into a linty corner of Neil deGrasse Tyson’s pocket.

The recurring death of vitalism comes as no surprise to most scientists. We’ve been aware for over two hundred years that organic substances can be made from inorganic chemicals. Nevertheless, that very statement betrays a vitalist victory in nomenclature: organic vs. inorganic chemistry is a complete artifact of the special spirit that vitalists granted to biological juices over inanimate powders. The modern definition of “organic” is thus completely tortured, meaning substances containing carbon, or maybe carbon and hydrogen, or possibly multiple carbons. With exceptions. The real meaning is that the subject of organic chemistry is the stuff of life, even if we have ultimately co-opted it with synthetic organics. If you’ve been following along, you know that to a true vitalist, “synthetic organics” is an oxymoron.

Vitalism seems silly to us today, but there have long been problems with organics, namely that it seemed impossible to make them in the lab. They were just too complicated, and the best chemists were stumped. When things don’t work with your basic premises, it’s not crazy to say that there may be another principle involved.  And really, when you look at a bird flying through the air, it’s hard to ignore that it is a lot more lifelike than a rock. Life is animated; the rest of the world is not, really. Maybe there was something extra to life.

Not only that, but when the old-timers burnt organics and inorganics, there was a difference: the inorganics could be reconstituted, but the organics were the humpty-dumpty’s that could not be put back together again. It seemed like something vital must have been lost in the fire.

The original vitalists held that organic compounds, like urea, were special and couldn’t be created from inorganic chemicals. But in 1828, Friedrich Wöhler destroyed this comfortable theory when he made urea from not one but two different reactions. Here is the letter he wrote to his old professor:

“I can no longer, so to speak, hold my chemical water and must tell you that I can make urea without the help of a kidney or even an animal, neither man nor dog. Ammonium cyanate is urea… I obtained the supposed ammonium cyanate very easily by treating lead cyanate with caustic ammonia. One can also prepare it with silver cyanate and ammonium chloride.”

This is a classic of scientific letters. Wöhler exclaims that he can barely hold his water. If you’re a scientist, you know what it means to be so excited about a discovery. Especially one that blows up a major dogma.

Wöhler knew he was shooting down vitalism, but he was poetically ambivalent. He wrote that his discovery represented “…the great tragedy of science, the slaying of a beautiful hypothesis by an ugly fact.” Yet, making urea from scratch was a terrific (and lucrative) accomplishment in itself, not to mention the start of a whole new world of organic chemistry. For such a simple experiment, it carried great import. Wöhler had imitated nature in his lab.

But that was just the first death of vitalism.

“Okay,” said the vitalists, “you can make pee, but you can’t make a real living creature with just a fancy chemistry set. Surely you don’t expect us to believe that a soaring bird or even a lowly scientist is made merely of chemicals? What animates them? There must still be a spark of life in the creature, if not its byproducts.”

But Craig Venter, who was also involved with the Stanford simulation group, put the lie to that with his blue mycoplasms. Venter created the DNA for a whole cell completely from scratch. And by scratch, I mean simply the four bases of DNA. Just for show, he encoded some famous quotes in his custom DNA, like this one from Richard Feynman:

"What I cannot build, I cannot understand"

That is a wonderfully reductionist sentiment, and although Venter was showing off, this was really an amazing triumph of biology and another blow to the vitalists.

“But”, cry the exceedingly wounded vitalists, “you still needed to stick the DNA into existing cytoplasm. Maybe the qi is in the cytoplasm!”

But the vitalists are wrong again, at least according to the Stanford simulation. Life, albeit that of a small cell, has been reduced to mere chemistry – including the cytoplasm. Given the right starting materials, life simply happens as chemicals cycle through complex reactions, over and over again. And yes, you need to specify starting chemicals. This is not yet a simulation of the origins of life, just the process of life. However, after running the simulation you are left with just the right materials to run the program again, but now with two cells and perhaps some mutations. This is life derived from chemistry, running in silicon. Chalk up another victory for reductionism.

So has vitalism reached its last gasp? Not by a long shot. God has been shaken out of many pockets, but science is still laboring on other extremely complex subjects, including the origin of life, developmental biology and consciousness. And wherever there is complexity, there you will find the vitalists.

“Surely, consciousness is just too complicated to be reduced to chemistry. This is where the secret sauce may lie!” say the vitalists. It is tempting to hand it to them here. After all, if consciousness is reducible to physics, and physics lays claim to determinism, did we just destroy free will? Yikes! Well, relax, physics also has a theory of uncertainty, and it wouldn’t be surprising if that turned out to be relevant to the free will debate.

Nevertheless, there is always an opportunity for vitalism to inject itself, like a tranquilizer dart, into the neck of the next complex situation. The main point of many vitalists is to cast doubt on the ability of ordinary science to explain it all. Certainly, it is hard to see how physics underlies consciousness. And in truth, physics will definitely not be the language of choice to deal with consciousness as we start to unravel it. But, like many complicated systems, it can be seductive to just throw up our hands and say it’s a completely different phenomenon and will require new science.

For instance, how can your mind, which must obey the rules of biology, chemistry and ultimately physics, exert an influence back onto your own mind? For instance, when someone decides to take antidepressants, aren’t we talking about a system that can make changes to itself? Surely that can’t be reduced to mere chemicals! But, in fact this is just an example of feedback. Ridiculously complicated feedback, but feedback nonetheless.

Like the water clocks invented over two thousand years ago, a feedback system is designed to keep things humming smoothly in a tight range. The precursor to the humble toilet flusher, the rising water in one of these clocks is designed to lift a float that shuts off a valve. When the water falls, the valve opens and lets more water in. It sounds like the valve is controlling itself, and in a sense it is. But as clever as feedback loops are, we don’t think of a water clock as alive or even terribly mystifying.

A valve that controls itself does seem irreducible, if you take it as a single entity. But it’s not. Upon closer observation, you can always find a separation (in time or location) that reveals the multiple components. The valve doesn’t “know” anything about the float or vice versa, yet their concerted action forces the system to maintain itself. Each part relates to the other, on the level of simple physics.

Closely coupled events are a staple of nature, both in living and purely physical systems. For instance, certain aspects of climate are controlled by basic physical principles of feedback: when ice melts, it exposes darker rock, which absorbs heat and causes more melting.  Like a lot of physical systems, this is positive feedback. Similarly, fission in plutonium sends particles flying that hit other atoms and cause more fission. Positive feedback causes runaway reactions that, once started, take off exponentially until the system is exhausted.

Living systems, on the other hand, are fond of negative feedback. They exhibit homeostasis, where negative feedback is used to keep the delicate machinery of life running within carefully proscribed limits. Getting cold? Move to a warmer spot. Getting hungry? Eat.

In this sense, negative feedback seems very lifelike, but it really isn’t unphysical. Feedback typically requires some kind of cycling, which would seem unlikely if it weren’t for those spinning, orbiting chemical laboratories we call planets. Basic physics guarantees a gravity-driven ballet of planetary pirouettes all throughout the universe. The resulting hot-cold cycles can run reactions for billions of years. Interestingly, hot-cold cycles are used in a lab to reproduce DNA, so it’s not hard to imagine that cycling planets could easily brew up some interesting broths.

This is tricky and complex, yes, but so far none of this requires a deus ex machina to swoop in and save the day. Unfortunately for the vitalists, more and more of the world seems to be based on some pretty straightforward physics and chemistry, including feedback.

Today, the last redoubts of the vitalists are mainly in alternative medicine, where auras, touch-at-a-distance, qi, and all sorts of wondrous notions rule. All these phenomena involve an unseen energy field that the practitioners can sense, but that scientists can’t. In fact, according to most adherents, science will never see these energy fields because they are not normal phenomena. They are, however, very delicate. The slightest whiff of skepticism can simply evaporate these tenuous fields.

In fact, some of these phenomena are explainable by science, but not in the way its adherents might wish. Auras, for instance are fairly well established as visual hallucinations experienced by many epileptics and migraine sufferers. As an example of how auras are becoming devitalized, there is now a gene we can point to: People who get migraines with an aura have almost twice the chance of having the “DRD2 Nco I C” gene.

Actually, most of these vitalistic theories today seem oddly pedestrian, perhaps because they are trying so hard to look main-stream. This is not a massive miracle like the parting of the Red Sea; it’s just invisible fields, which seem easier to swallow.

Meanwhile, the true inner workings of nature, revealed by reductionist science, are marvelous. The “essence of life” has been exposed as an amazing choreography of proteins, sugars, lipids and DNA. Once it got started in some ancient incubator, it may have been hard to stop. Far from prosaic, that runaway chemical reaction has managed to coat the entire planet with a breathtaking array of creatures. For a scientist, there is a great deal of awe in knowing that the rules of chemistry are complicated enough to produce something that can crawl right out of a gene machine.

Far from ruining the mystery, it only deepens the excitement of what more we might do, now that we know the rules.

For more information on the Stanford Cell Simulator, check out these references:

Karr, Jonathan R., Jayodita C. Sanghvi, Derek N. Macklin, Miriam V. Gutschow, Jared M. Jacobs, Benjamin Bolival Jr., Nacyra Assad-Garcia, John I. Glass, and Markus W. Covert. “A Whole-Cell Computational Model Predicts Phenotype from Genotype.” Cell 150, no. 2 (July 20, 2012): 389–401. doi:10.1016/j.cell.2012.05.044.

Peroutka, Stephen J., Tara Wilhoit, and Keith Jones. “Clinical Susceptibility to Migraine with Aura Is Modified by Dopamine D2 Receptor (DRD2) Nco I Alleles.” Neurology 49, no. 1 (July 1, 1997): 201–206. doi:10.1212/WNL.49.1.201.

Gibson, Daniel G., John I. Glass, Carole Lartigue, Vladimir N. Noskov, Ray-Yuan Chuang, Mikkel A. Algire, Gwynedd A. Benders, et al. “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome.” Science 329, no. 5987 (July 2, 2010): 52–56. doi:10.1126/science.1190719.

Copyright © 2000-2014 by Scott Anderson
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Here are some other suggested readings in synthetic biology: