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Searching for, defining life

How complex does an assembly of molecules have to be before it comes alive? It is one of the great questions perplexing scientists.
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How complex does an assembly of molecules have to be before it comes alive?

It is one of the great questions perplexing scientists. Indeed, it could be argued that trying to define the difference between living and non-living has been a topic of debate for both science and philosophy for as long as there has been science and philosophy.

For a chemist, because we tend to think in terms of atoms and molecules, the question is one of molecular complexity. How many molecules and of how many different types must exist in the same spot at the same time before we have a living system?

Clearly the answer is more than just one atom or even one molecule regardless of how complex it may be. DNA, by itself, is not a living thing. But if not one molecule, then how many? A few hundred? A few thousand?

The answer depends to a certain extent on how we define the term living. For example, the concept of replication is not particularly useful in distinguishing living from non-living as most molecules are made in quantities that dwarf the imagination.

A single drop of water contains more molecules than stars in the universe. It is not hard to realize that any measurable quantity of material must have replicated an immense number of times - in some fashion.

Self-replication, as a criterion, is a little more stringent as it requires the system to generate off-spring directly as opposed to randomly. But simple self-replication has been accomplished at the level of a few dozen atoms. Very few scientists would try to argue these molecules constitute living entities although we sometimes speak as if they do.

Similarly, other criteria for life include such things as consumption of materials, aging of the complex, and death of the system. Generally the criteria to be a living entity is to eat, grow old, and die. All good and worthy considerations when considering the question of what constitutes life. Again, all of these criteria are possible with only a few dozen atoms and very simple molecular complexes.

I would submit, however, most scientists would include in their list of necessary properties the concept of heredity and evolution. The idea there must be a molecule such as DNA for an assemblage of atoms to be truly considered alive. DNA allows the transmission of information from one generation to the next. It also allows for the modification of that information over time through the general processes of evolution.

So, if we consider DNA or something like it as the criteria for whether an organism is alive, how much DNA must there be? More to the point, since DNA is just the coding for genes, how many genes does an organism need to function as a living entity? The answer is surprisingly few.

Many researchers have studied this question. Working on the symbiotic bacterium Carsonella ruddii which lives off of sap-feeding insects, researchers have identified its genome as consisting of 159,622 base pairs (or letters) and a paltry 182 protein-coding genes. This is much smaller than, say, the human genome with three billion base pairs and 30,000-plus protein-coding genes. Not surprisingly, the bacterium is much simpler than we are as well.

For the bacterium, Buchnera aphidicola, which is found in aphids, its genome has been determined to be just over 400,000 base pairs. Both are examples suggesting living organisms can be much simpler than we might have supposed. A review published in Nature Molecular Systems Biology posited the minimum genome for a living organism would be 113,000 base pairs and 151 genes. At the time of its publication, there was little evidence to back up this number.

Microbiologists have been working on the problem for decades. Craig Venter has devoted much of the past 20 years to creating the minimum genome. In 1995, his team was able to slim the number of genes in a functional bacterium to just 375.

But this year, the team announced the creation of a totally artificial life form with 531,000 base pairs and 473 genes. The organism has a respectable doubling time of only three hours. By any definition, it is alive.

However, its genome is not complete. It is still missing the capacity to make some of the essential amino acids. But before we get too smug or critical of the work, I should point out that we don't have a gene for producing tryptophan or 10 other amino acids and must get them as part of our diet.

With the development of synthetic biology - generating the components of life and stitching them together to create new creatures - scientists appear to be uncovering the minimum coding for a living organism and, in turn, finally answering the question of how complicated a system must be before it is alive.