Miller, Urey and Venter

The Spark of Life

Life is a funny thing. Despite our primary connection and concern with it, life defies a simple definition. This seems absurd because it is intuitively obvious whether the dog lying at your feet is alive or dead. But do you use the same criteria in judging if the tree in the front lawn is alive? What about a frog frozen in the Siberian winter? Somehow the line still seems fairly bright – even if difficult to define.

You might be a little more hesitant if you’ve spent time in a biology classroom contemplating the fringes of life. Biologically, there are two general ideas that define life. The first is the ‘cell theory’ that defines the cell as life’s smallest unit. Second is a list of characteristics that life may possess. These include such things as organization, homeostasis, growth, response to stimulus and reproduction (among others.) Some simple thought experiments illustrate how some of these characteristics may exist in dead things, while others may be absent in living things.  But when taken together, they provide support for, or argue against a thing’s life. Consider: a fossil has evidence of both cellular structure and organization, but fails to respond to stimulus or grow; a single celled amoeba responds to stimulus but does not grow (at least not beyond its single cell ‘body’); a castrated bull that has almost all of the listed characteristics save reproductive ability. Which of these is alive?

In contrast, consider a virus. It fails almost all of the tests and is nearly always considered to be unliving, yet is very well organized, can reproduce when infecting a host cell and does respond to some stimuli as its DNA may harmlessly reside in a cell until conditions induce it to ‘awaken,’ start reproducing itself and finally kill the host cell as it bursts from the sheer number of virii produced.

Life, then, seems dangerously close to Justice Stewart’s 1964 definition of pornography – or rather, his failure to define it – “I know it when I see it.”

It’s amusing that the definition of life even eludes biologists. ‘Biology’ itself translates as ‘the study of life,’ yet those of us who study it can’t say exactly what it is in every case.

So it is doubly complicated when scientists puzzle the origin of life. We don’t know exactly what life is AND current estimates place the origin of life back 3.5 billion years. This leaves us with fossils, assumptions about the early Earth’s atmosphere and laboratory experiments meant to mimic early conditions. We are also in something of a quandary because of Louis Pasteur’s demonstration in 1862 that showed quite definitively that spontaneous generation does not occur  under present conditions– only life can beget life. Yet this must have happened once for us to be here pondering our origins.

In 1922 the soviet scientist, Alexander Oparin, was pondering the origin of life on Earth. At the time, evidence was beginning to suggest the environment of the early Earth as being a reducing environment consisting of ammonia, methane, hydrogen and water vapor. Oparin determined that this was ideal for the chemical evolution required to generate the amino acids and other complex molecules that could later make life possible. One reason this atmosphere was ideal was the lack of oxygen that can be very destructive to molecules that become oxidized in its presence.

Stanley Miller

It took thirty years for Oparin’s theory to be actually tested in a laboratory and it was not Oparin himself who did the experiment. Instead, it was the Americans, Stanley Miller and Harold Urey who, in 1952, constructed an apparatus that sterily re-created the Earth’s early atmosphere within a self-contained glass tubing. Water was heated to form vapor and an electrical spark was provided to simulate lightening. Under these conditions Miller and Urey witnessed the generation of five amino acids as well as a number of sugars and fats – all building blocks necessary for life.

This does not prove that the chemical precursors of life formed this way, but it does demonstrate that, under these conditions, molecules necessary for life could self-assemble. Regardless, this was not the generation of life in the laboratory, but only a step showing that macromolecules required for life can spontaneously form under the proper conditions.

Beyond this, we know some of the things that are required of life as we have defined it. There must be the generation of some device to carry information from one generation to another.  Why do we require this? Because there needs to be a way for the new organism to ‘know’ how to do the things it needs to do to stay alive. That way is through inherited information

It is interesting that from the beginning we assume that life must proceed in generations rather than as a single organism going on indefinitely – but considering how fragile a single life may be, generations may be the only way. This information is almost uniformly encoded in DNA. Further, the code used to store this information is also (for practical purposes) universal. Together, these facts argue strongly for the origin of life as a single event.

There must also be a compartmentalization of this information and the machinery required to replicate it within a membrane – thus creating a cell. It’s another interesting thought experiment to contemplate whether life is possible without a membrane. However, it is difficult to conceive how a lifeform could occur without the ability to concentrate itself and hide its resources away from potential predators.

So, life is difficult to define and we have only hints about how it originated. An interesting question is, ‘can we create life ourselves?’ The answer is: of course, it’s so easy that it doesn’t require a lab at all.  All our youthful energies are directed at making new life (or perhaps avoiding doing it so we can earn enough money to pay fertility doctors to do the same thing once we’ve gotten to old to do it ourselves.) But that’s not what I mean. More specifically, “Can we create life in the lab synthetically… from scratch?”

More than just an idle curiosity, this is more a question of testing what we know about life and its requirements. Biology has been a reductionist science since the structure of DNA was modeled by Watson and Crick in 1953 and developed as a tool of molecular biologists by the 1980s. Creating a living organism in the lab is a test of our ability to rejoin these reductionist ideas into a unified, functional model.

A step in this direction was taken in 2002, when Eckard Wimmer’s group made a synthetic poliovirus and demonstrated that DNA made in the lab was just as infectious as naturally derived poliovirus DNA. This advance was met with skepticism based on the fact that the only novel element of this work was the chemical source of the DNA. All other elements of the experiment had been previously demonstrated and were not at all unexpected (these are the two elements that make for good science– novelty and unexpectedness.) Furthermore, in terms of creating life, a virus is generally not accepted as alive for reasons we discussed above.

Craig Venter

Enter Craig Venter. In 2000, his Celera Genomics company was the first to sequence the entire human genome. Since then he founded the J. Craig Venter Institute and Synthetic Genomics as vehicles for deriving synthetic life. In 2010, his group was successful in generating an entire microbial genome chemically and then using it to direct life functions within a new cell that previously had its own DNA removed.

This might not sound like much of an advance over Wimmer’s work with a synthetic virus, but it certainly brought its own challenges, one of which originated from the fact that the ‘host’ cell used was not the same as the ‘donor’ DNA. This led to some trouble in overcoming certain molecular defenses set up by the cell in order to repel parasites such as viral infections. After overcoming these obstacles, the cells were observed replicating the introduced DNA, manufacturing the proteins it encoded and dividing into daughter cells.

This work also began to define just what genes were required to accomplish this goal and possibly address the question, “what are the minimal requirements for cellular life?”

A possible utility for the project would be tailoring this bacterium for the production of recombinant proteins, fats, etc. These bugs can then be used to make medicines, remediate ecological damage and perhaps even serve as medical therapies themselves. Since we have created it from scratch, we know that there is no danger of having it ‘escape’ and mutate back into a virulent form.

So, despite the difficulties associated with even knowing what life is and how it originated, we have not let these questions prevent us from using what we do know to accomplish amazing tasks that were unthinkable just a few short decades ago: creating life in the laboratory.