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What Is Life?: Investigating the Nature of Life in the Age of Synthetic Biology

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In 1944, Austrian physicist Erwin Schroedinger published a book with the same name as the current volume: "What Is Life?"

Popular science writer Ed Regis points out that Schroedinger "wanted to challenge the notion that at the core of life was some impalpable excrescence that lay beyond the grasp of science."

This optimistic view holds that life can be explained in the same terms, and by the same laws of physics and chemistry, as those that pertain to everything else in nature. To be sure, life is exceptional, but it is rule-governed and law-abiding; there is nothing inherently magical or mystical about it. Ultimately, scientists will be able to unravel all of life's mysteries.

Present-day scientists are not so sanguine. The question, "What Is life?", Regis suggests, lies more in the realm of religion, philosophy, and metaphysics--and by extension, politics and ethics--than in the realm of science.

At first glance, a tangential approach to the question, "What is life?" promises a satisfying solution: "Unquestionably, if there was anything that appeared obvious about what it meant to be alive, it was possessing the ability to die."

One's hopeful expectations of an answer, however, are dashed by this consideration: There is no agreement concerning what death is. In between life and death there is often "a state of near-death, or pseudo-life."

If one insists on a scientific answer, Regis suggests the following, "Defining life as embodied metabolism . . . seems to be the most defensible theory we have at the present."

If you expect a definitive answer to the question "What is life?", this book will disappoint you.

Ed Regis holds a Ph.D. In philosophy from New York University and taught for many years at Howard University. He is now a full-time science writer, contributing to Scientific American, Harper's Magazine, Wired, Discover, and The New York Times, among other periodicals. He is the author of several books, including The Biology of Doom: The History of America's Secret Germ Warfare Project.

I had hoped to get from this short book a probing, thoughtful, current answer to the title question, especially given the subtitle of "In the Age of Synthetic Biology". I was disappointed: this is a brief and generalized historical survey. The end footnotes and bibliographical references are valuable, though, for guided further reading.

Regis says that Schrödinger in 1943 "discreetly refrained from answering" the question. If so, then Regis has refrained as well. Here is how Schrödinger answered the question in 1943: "What is the characteristic feature of life? When is a piece of matter said to be alive? When it goes on 'doing something', moving, exchanging material with its environment, and so forth, and that for a much longer period than we would expect of an inanimate piece of matter to 'keep going' under similar circumstances." I.e., metabolism and negative entropy over long stretches of time. Here is how Regis summarizes things 65 years later: "A reasonable answer ... seems to be: an embodied metabolism." Hardly different from Schrödinger, and less illuminating. Regis defines the essential term "embodied" only through a quote in a footnote buried at the end of the book: wrapped in a membrane, like a cell is.

To my mind, Regis is wrong and unfair to dismiss Margulis and Sagan's multiple, accumulating, descriptive answers in their 1995 book of the same title as being "figurative, flowery, or metaphorical ... entirely too many answers." Here is how Margulis and Sagan answer the fundamental question: "Life itself is these [metabolic] patterns of chemical conservation in a universe tending toward heat loss and disintegration", i.e. essentially the same definition as Schrödinger. They go further than Schrödinger, asserting that the cell is the smallest unit of life on Earth and that reproduction is a crucial feature of life on Earth.

Schrödinger addressed the question of what life ultimately amounts to from the standpoint of physics and chemistry. Margulis and Sagan addressed the question of what life on this planet actually is, from its core metabolic machinery up to the fullness of all living matter that we humans perceive. Left unaddressed is the question of what life HAS to be at a very minimum, not only to be manifestly alive on Earth for a generation like an infertile mule is, but to be able to persist and evolve, perhaps synthetically, for thousands or millions or billions of years in an environment that might not resemble Earth at all. Metabolism of some type appears to be mandatory, together with the ability to adapt to a changing environment whether through reproduction with random mutation or through some other mechanism.

Lest you think that synthetic life would be have to be uninteresting, take a look at robots that evolve altruistic behavior entirely on their own, by googling the phrase "Altruistic robots produced through evolution".

The recent book by Ed Regis, "What is Life? Investigating the Nature of Life in the Age of Synthetic Biology", may be considered the third of a series. In 1945, Edwin Schrodinger, of the "Schrodinger Equation" that can (with strenuous labor) calculate the properties of any atom's electron cloud, and whose eponymous Cat defines the dilemma of quantum phenomena in a macroscopic world, wrote "What is life? The Physical Aspect of the Living Cell", in which he did not answer the title question, but explored life phenomena from a strictly chemical and physical aspect. He predicted crucial aspects of the genetic code a decade or two in advance of their discovery. Then in 1995 Lynn Margulis brought certain of the same themes more up to date in "What is Life?", shortly thereafter revised and reprinted with her son Dorian Sagan as co-author. As Ed Regis reports, Margulis and Sagan answered the question in so many ways that it is not answered at all.

Author Regis begins his book with a look at the formation of a four-way consortium in 2002, with the aim of specifically creating a living cell not based on previously living matter. To date, the effort has not succeeded, but as Edison would have said, they are learning a great number of things that don't work...and a few that offer tantalizing clues to what might work. So much so, that the government is now interested, as evidenced by the Los Alamos Protocells web site (protocells.lanl.gov) and its link to protocell.org, a jumping-off place to a handful of major efforts in the Synthetic Life arena.

Regis does home in on an answer, a minimalist definition that life is "embodied metabolism". A few caveats are needed, such as a measure of autonomy and of self-repair, for example: An automobile consumes fuel and moves about, but does not direct its own motions nor maintain itself, while a portion of the metabolism of living cells goes to structural regeneration and growth. And "embodied" is needed to distinguish living matter from open flames.

More generally speaking, living things not only metabolize, they also reproduce and evolve. Not every individual will do so, but all can do so. And, specifically for all life that we know, all life processes are directed by coded instructions. DNA carries the instructions, while RNA plus proteins carry them out. Synthetic cells could be based on DNA, RNA and proteins, or it could instead use different chemistry, perhaps not even based on carbon. But whenever a wholly synthetic "embodied metabolism" gets cranked up, performing as cells perform, I suppose we'll have to dub it "living".

This is quite a step beyond our fearsome archetype, the Frankenstein monster. That creature was supposedly produced by re-animating a sewn-together collection of bits of corpses. Certain partial successes in the synthetic life area have been analogous to this. But the goal is to create living cells from chemicals, not from various bits taken from other cells.

The rub comes if the creators of synthetic life endow it with the ability to reproduce; the ability to evolve will come along as baggage immediately. At that point, no matter what precautions they may take, SynLife (not my term: Google yields 3,770 hits) will most certainly escape into "our" environment, evolve so as to take advantage of it, and then we'll REALLY learn what it is like to live with invasive alien species! Sparrows, multiflora roses, and zebra mussels will probably pale by comparison.

I suggest that, really early on, SynLife cells be presented as a challenge to a large variety of prokaryotes, so they'll have a chance to develop resistance mechanisms and chemicals that we can later exploit when we need AntiSynBiotics!!

I started reading the last chapter of this interesting summary of the What Is Life - debate with great expectations. But got rather disappointed.

Why did Regis not take the opportunity to, at least, present some of the recent views based on a more holistisk biology/physics consideration ?

When settling for the metabolic explanation he could as well have called it the 2nd - thermodynamic - law - explanation?

Shouldn't he have give ample recognition to the `life is a particular pattern of energy flow/transformation' expressed in: Into The Cool by Schneider/Sagan; instead of pretending that he had not read that account?

Then an idea on how `life' started -- simultaneously with the Big Bang, or Big Bounce, if you want -- and that the entropy production and feeding on neg - entropy reality defines the starting point as well as what so many call `life'.

This debate needs such a broadening.

Ake Eckerwall

"What is the meaning of life?" is a question all must ponder at some point or other. But that's too fancy; try the even more basic, "What is life?" In 1944, Nobel prizewinner and quantum physicist Erwin Schrödinger published a small book with that question as a title, and it has been enormously influential, cited and debated ever since. There have even been other books with the same title since then, trying to definitively corral a huge and amorphous subject. Now science writer Ed Regis has added another, to take in the philosophical and biological efforts of our times: _What Is Life?: Investigating the Nature of Life in the Age of Synthetic Biology_ (Farrar, Straus, and Giroux). My guess is that it is not going to be the last book of the title; the definition game demands that new discoveries and ideas have to play their roles in our understanding of what life is. However, we are on the brink of making cells out of basic molecules, and Regis has a good introduction for those of us who are living through an extraordinary time in experimental molecular biology.

Schrödinger's book was a last stand against vitalism, the idea that there was something going on within creatures, organs, and cells that science could not understand. Life chemistry was thoroughly within known laws of thermodynamics. If what goes on in a cell is really only the jostling, linking, and breaking up of atoms and molecules, it makes sense that scientists could just get the right atoms and molecules together and get the whole thing going from scratch. The problem, of course, is that the whole mess is extraordinarily complicated even for the simplest of cells. Regis gives a good short history of how we came to know how complicated it all was. Definitions of life have been said to include necessarily reproduction (but mules are sterile, and are still alive) and also evolution (but evolved or evolving or not, any particular animal is still alive). What really needs to be taken into account in a definition of life is metabolism, the sum total of bodily chemical processes, including molecules into a body and molecules out of it. "Embodied metabolism" is, Regis writes, "at least as adequate as any other definition of life that has been offered to date." Adequate, but like any other definition, it gets iffy at the edges. What about viruses, that do have bodies, if you can call a chemical capsule a body, but are just inert chemically until they find a cell to latch upon and infect?

There is something disconcerting about just chemicals connecting and disconnecting being all there is to the living process. By some changes in degree, inert carbon, hydrogen, oxygen, and the rest, eventually become living creatures, and even develop consciousness. And yet, vitalism is dead; "There must be more to life" is true on philosophical levels, but not biological or biochemical ones. That this is more clearly becoming true is shown in Regis's fascinating descriptions of current efforts in synthetic biology. Using synthetic gene sequences alone, scientists were able to manufacture a polio virus in 2002. Making a virus, which has characteristics both of being alive and inert, was one step; tinkering with living cells to rewire their function (like getting _E. coli_ to manufacture an antimalarial drug) is another sort of step, and also has the potential for becoming a big business. Making a cell from scratch, though, is the goal of firms like ProtoLife, whose business plan "is founded on an attempt to start life over, to begin from the beginning." ProtoLife's goal of creating artificial cells is not just so that we will learn more about how natural genetics and metabolism work and regulate themselves, though we are sure to do that along the way. ProtoLife is in it for the money, hoping someday to sell manufactured cells that might produce drugs, clean up waste, grab carbon dioxide from the atmosphere, and who knows what else. Regis's review cannot have the canonical status of Schrödinger's influential work, but serves wonderfully as a clearly written update and introduction to new ways of looking at a vital question.

This is an easy-to-understand delightful little book (which can be read in a couple of days). Taking the title from the seminal work of Erwin Schröedinger, which inspired Nobelists such as Watson and Crick, the author reviews the recent history of biology major steps: the chemical nature of genes, the structure of the DNA molecule and the genetic code together with the heroes behind these milestones. The real goal of the book is to define something such as undefinable as life, something that Schröedinger did not answer. There is no doubt that metabolism, replication and evolution are three characteristics of life, but there are exceptions and it would seem that metabolism is the most fundamental, although some machines, such as cars, function in a way reminiscent of metabolism, but they do not grow or repair themselves such as living beings do. So the question has not yet a clear answer and it is hoped that ET life or artificial life will eventually help to clarify the notion of life which at present is perhaps too earth centric. Naturally there is the added problem (without having a clear definition) to certify when something artificial is deemed to be defined as living. A proposed solution is "à la Touring". When an artificial cell is recognized by other natural cells as living it should be taken as living.

The book describes some of the recent efforts in the direction to create artificial life or synthetize the elements of living organisms. Having been published in 2008 it misses some the most recent results such as those of Sutherland, but this is normal in such rapidly advancing field.

That's a didatic book about the history of the chemical and biological discoveries about life and the meaning of life's concept. Sometimes it's boring, because of the didatism, but, in general, it's a good book, specially to those who like science history and its development.