The following is a copy of an important article on the origin of life which appears not to be webbed anywhere else, Franklin M. Harold, "The Mother of All Problems," ASM News, American Society of Microbiology, December, 2001. Harold is Emeritus Professor of Biochemistry and Molecular Biology, Colorado State University, and author of "The Way of the Cell" (2001).
ASM News American Society of Microbiology December 2001 The Mother of All Problems Franklin M. Harold Slowly, and at times painfully, we are muddling towards an appreciation of how the molecular parts relate to the cell as a whole. We are also making progress in understanding cell evolution, and the genesis of that great tree of all life. By contrast, what remains altogether mysterious is just how living systems relate to the nonliving world of chemistry and physics from which they presumably sprang. The black hole at the very foundation of biological science is the origin of cells, and of life. Here again we have a conventional framework, parts of which go back to the 1930s, that structures our thinking. It calls for a broth of organic substances formed by chemical processes on the lifeless earth. Somehow, in a favorable locale, a selection of the "correct" precursors coalesced into a primordial cell; alternatively, a molecule capable of self-replication arose by chance, and somehow "learned" to make proteins and then cells. The notion that life began with free, self-replicating RNA molecules, which begat primordial cells based on ribozymes, holds particular fascination for molecular biologists. A voluminous literature records all sorts of variations on these themes, some of which claim support from laboratory experiments. Unfortunately, there is no pertinent evidence whatever from the geological record supporting this framework and, in its absence, gauging how seriously one should take all these imaginative tales proves practically impossible. To my mind, even the more persuasive tales come up woefully short on the central issue, which is the origin of cells. Whence came organized molecular assemblages that draw matter and energy into themselves, reproduce their own structure, and evolve over time? I do not mean to disparage serious scholars who are doing their level best to crack the hardest nut of all. Quite the contrary: I would argue that, if our purpose is to understand life, the origin of life is the most consequential question in all of biology. It holds the key to understanding the relationship between the living and the inanimate, the quick and the dead. Each new bit of evidence strengthens our belief that organisms obey the laws of chemistry and physics; and scientific investigations have turned up no traces of a vital force to nurture the wellspring of life. We assume, then, that cells are material systems that arose by some sort of evolutionary process four billion years ago here on earth (or conceivably, someplace else). I share this premise, but feel obliged to note that, in the absence of evidence as to how this came about (or even of a plausible hypothesis), this explanation is merely a belief-a leap of faith. Of all the gaps in our understanding of lhis one is the widest. Until we bridge it, we cannot lay to rest lingdoubts as to whether science has read nature's book of biology correctly. Well, here she comes again, that pesky teenager-and this time she wants an answer, not a meditation. Quickly now, how do we reply to the recurrent question, "what is life?" Perhaps along the following lines. Living things are so much part of everyday experience that we scarcely realize how strange they are, and how sharply they differ from inanimate objects. All organisms, from bacteria to humans, are exceedingly intricate molecular systems that have the unique capacity to make themselves. On the level of the individual, each one grows and reproduces its own kind. Collectively, on a timescale of millennia, they continuously make themselves over, adapting to changes in their external and internal environments. Nothing else in the known universe has such powers. Living things obey all the laws of chemistry and physics, and we have learned an enormous amount about the molecular mechanisms that underlie all biological operations. We know much less about how these components and processes are organized in space, and almost nothing about their origin when the world was young. Our knowledge is vast, but our understanding is partial and full of gaps; for all its familiarity and ubiquity, life remains fundamentally mysterious.
(Harold, F.M., "The Mother of All Problems," ASM News, American Society of Microbiology, December, 2001)
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