Rediscovering Golem

On the twentieth day of the month of Adar, in the year five thousand three hundred and forty after the creation of the world, in the fourth hour after midnight, the three men betook themselves to a river on the outskirts of the city on the banks of which they found a loam pit. Here they kneaded the soft clay and fashioned the figure of a man three ells high. They fashioned the features, hands and feet, and then placed the figure of clay on its back upon the ground…. At last the rabbi himself walked seven times round the figure, and the three men recited the following sentence from the history of creation in Genesis: "And the Lord God formed man of the dust of the ground, and breathed into his nostrils the breath of life; and man became a living soul."…. As soon as the three pious men had spoken these words, the eyes of the Golem opened and he gazed upon the rabbi and his pupils with eyes full of wonder. Rabbi Loew thereupon spoke aloud to the man of clay and commanded him to rise from the ground. The Golem at once obeyed and stood erect on his feet. The three men then arrayed the figure in the clothes they had brought with them, clothes worn by the beadles of the synagogues, and put shoes on his feet. —The Golem: A Jewish Legend

In the ancient Biblical legends, mud is animated by the name of god.

But what is life anyway, and how did it really happen upon this world? As a physical phenomenon, is life an accidental and rare occurrence? We know that living things beget living things, but where did the first living thing come from? In the remote history of our planet, there was a time before procreation, when the world was abundant only in energy, primordial mud, and gases, but utterly devoid of life.

While some scientists have tried to recreate the essential molecules of life in the laboratory, even their experiments with primordial gases and electricity don’t go far enough—the first strand of DNA or RNA must have required something like a living process to create it. So before the first living organism, before even the first molecules we understand as intrinsic to life had appeared, it would seem that life must have entered the mud, itself, like the stuff of myth. What light can science shed on this matter?

Dr. Eric Smith of the Santa Fe Institute has an interesting new insight into this confounding chicken-or-egg paradox. In his recent talk, "Inevitable Life?," broadcast on FORA.tv, he proposes a radically different way of  approaching these basic questions: Why is there life on earth at all? How and where did it originate? Why has it persisted? And does the biosphere contain relics of its emergence?

We can look at an evolutionary tree of life, he says, and see “family resemblances” and branchings that take us back to the earliest form of life. But it’s important to realize that the earliest form of life represented on such tree had a form; that is, we can trace the evolutionary relationships of organisms only to the earliest days of procreation. What about before procreation? Life must have existed before that. But life without form—what is that?

This brings us back to that most essential question, what is life? Many of us have by training and habit tended to believe that life is an organized system; it is the emergence of structures that enable control over the environment at a molecular level. But, Smith reminds us, there’s more to life than control.

“First thing, life lives in the non-living world of rocks in the atmosphere,” he asserts. “And in the non-living world, your carbon comes in the form of carbon dioxide molecules…. So the first thing life has to do is make carbon-carbon bonds.” And we know it does, along with oxygen, nitrogen, and hydrogen, to form a small set of small organic molecules. This set of molecules, perhaps 300 in all, comprised of anywhere from three to around twenty carbon atoms each, is the entire basic structure of the chemistry of life: fatty acids, amino acids, nucleic acids, sugars, and other cofactors. All the stuff of which known living things are made are made by stringing these smaller molecules together.

Taking a deeper look, Smith notes that there are essentially two different kinds of life on the earth, which differ in how they get their energy: either by oxidative metabolism, or by reductive metabolism. Most of what we generally think of as the living world—plants, animals, fungi—runs on oxidative metabolism. These organisms have access to oxygen and ultimately are able to harness the energy of sunlight. But some organisms, such as those that dwell near deep sea vents, away from oxygen and sunlight, depend on reductive metabolism.

But here’s the striking thing: the essential chemistry of oxidative and reductive metabolisms are identical; both pathways move through the same eleven simple organic compounds to produce their end products. In the oxidative process, sugars are broken down to carbon dioxide and water through a pathway is called the Krebs Cycle; in the reductive process, the Reverse Krebs Cycle, carbon dioxide and water are built up into sugars, without the use of sunlight as an energy source. (This is important, because while sunlight has a lot of energy, it’s difficult to capture and use in organic processes; plants, which are able to do this, are well advanced forms of life.)

This is the essence of Smith’s new take on the origins of the chemistry of life: while others have focused on the emergence of structure—DNA, RNA, amino acids, or nucleic acids—as the essential molecules that suggest the origins of life, it is rather the chemistry of this metabolic pathway that’s caught Smith’s attention. Why? Because this chemistry is singularly common to all life on the planet since the beginning, some four billion years ago. “The Krebs' cycle is important because everything in the entire history of life has used it as the starting point to build every bio-molecule, no exceptions.” It is this that represents incipient life on the planet, or what might be called prebiotic life; it is this that might be called the “missing link” between the geological world and the animate world.

What’s more, Smith suggests that this process, the formation of these basic compounds and sugar, was inevitable, given the conditions of the early earth. He asks, “Why life? … What was so wrong with a non-living earth that it had to change?” He posits the question this way, rather than seeing the emergence of a phenomenon in terms of what benefit it provides (as we are generally accustomed to doing), because chemists tend to think of processes in terms of “what was it getting away from,” looking at systems as moving from higher energy to lower energy states.

So what was the unstable state of the early earth that would drive the production of sugar? He explains that the geochemistry of the early earth produced a lot of carbon dioxide and hydrogen, as thermal vents spewed these and other compounds into the environment, blazing with thermal energy.

Hydrogen and carbon dioxide have a lot of energy they could exchange; by putting as many hydrogens as you can around oxygen, to make water and methane, you can release the maximal amount of energy from this system. And as it turns out, the most efficient way to get from state A (excessive amounts of carbon dioxide and hydrogen) to state B (methane and water) is to go through the molecules of life, the Reverse Krebs Cycle (which Smith points out is the original Krebs Cycle; our oxidative reversal of it came along later).

Smith sums this up by saying, “…. if you want to know why is there sugar, there is sugar because sugar is [energetically] downhill from the stuff that makes sugar.” In other words, it’s inevitable. Not only is it inevitable, but given the way the chemistry works, once the cycle gets started, it propagates itself, for once it completes a round, the products of the cycle serve as substrates for another round of the cycle. So a single turn of the cycle can start up two more, each of which can start up two more, and so on.

By pointing out that metabolism is the most ancient piece of life, Smith upturns an assumption many of us have been accustomed to, namely that metablism arose to enable life. Most dramatically, he says,

Life arose and persists in order to enable metabolism…. We usually think that metabolism exists in order to enable life, that’s the sort of purpose-oriented thinking. In the chemical domain you get a completely different idea of what life even is; life is what can be built out of those eleven molecules when you have this amplifying cycles spewing them out from geochemistry. We get, to me, the very pleasing idea that the emergence of life was a form of collapse. The important  thing about this is that things do not come up off of the floor and rearrange themselves on the table. So if the transition from a non-living to a living earth was actually a collapse, that enables us to understand why life has been so stable. Species go extinct; eco-systems rearrange; life has never winked out; it’s been continuous all the way back and the chemistry has been invariant.

While not all of this has been experimentally proven, it is experimentally testable. And apparently, this is where the cutting edge research into the origins of life is heading.

Smith’s presentation is actually larger than my summary here, but this is my best understanding and interpretation of his central thesis, which to me is a fascinating and brand new take on the origins of life. If others can provide deeper critical insight into this matter, I’d be very interested to hear from you. While there was a time when I knew the Krebs Cycle and essential molecules of life like old friends (albeit, difficult friends) this is, sadly, no longer true; alas, biochemistry and I have become estranged. So if others listen to Smith’s talk and find flaws in my presentation, kindly point them out with explanation. Corrections, additions, and insights are most welcome.

Comments

[Ruchira Paul]

Fascinating. We came into being to perpetuate the Krebs Cycle? And why not? The "reason" for life, if there indeed is one, doesn't have to be exalted. Serving an infinite god's will is no more gratifying than being chained to an endless chemical pathway.

I am sending the link to Eric Smith's talk to a couple of science bloggers. Let's see what they have to say.

[Usha]

Thanks, Ruchira. I'll be very interested to hear thoughts from people who still live closer to this subject matter.

[Ruchira Paul]

The science bloggers are not biting .. yet. Will get back to you if I hear back from any of them.

[Ruchira Paul]

Some of the science blog email accounts were acting up. I did hear back from a couple. They have not much light to shed except to say, "anything is possible or plausible in this chicken & egg story." One of them wrote the following:

I haven't watched the whole thing, but it is plausible though I think it will take a while for anyone to push this far. The Santa Fe Institute has a reputation for forwarding really neat ideas which are hard to advance because of issues of tractability. In other words, they aren't cranks, but how do you prove 'em right?