And scientists said, let there be life: Molecular biology is progressing so fast that within 100 years we may be able to create new life forms in the laboratory. Colin Tudge reports
Monday 27 June 1994
As it continues, we ought to be able to understand many of them in some detail: exactly what their structure is and what they do. Genes are not merely the 'blueprints' of life, for blueprints are put in a drawer and forgotten after a machine is constructed; they are the day-to- day operators that direct metabolism second by second throughout life. So when we understand the workings of the genome more fully we will have deeper insights not only into heredity but into our entire biology, in health and disease. A powerful vision indeed.
Yet, I suspect, within 100 years the Human Genome Project will seem quaint and old-fashioned. The rate of progress in molecular biology is astonishing. It is only 50 years since scientists acknowledged universally that genes are made of DNA; only 20 since the term 'genetic engineering' was coined. The scientists of 100 years' time will be embarking on the 'Life Creation Project'. Their aim will be to create bona fide self-perpetuating life forms from laboratory ingredients.
But to do that they will need to go far beyond considerations of genetics and DNA. They will have to think fundamentally - what exactly is life and how will we know it when we see it? After all, the kind of life of which we ourselves partake is only one possible version. Present- day life is essentially a dialogue between the administrative DNA and the executive proteins whose form it dictates, and which then carry out its 'orders': a dialogue mediated by RNA. But this dialogue is highly evolved and it cannot have been the first system on Earth that deserved to be called 'living'. It is merely the mechanism that has so far proved most robust and has emerged by natural selection. The first life systems that scientists create must be simpler.
More realistically, then, we should ask what characteristics we should look for that would lead us in the right direction. Some are obvious, such as the ability to grow and reproduce; but since crystals also grow and reproduce, we must ask for a great deal more than that. So, what else?
Well, it has been suggested that the key quality of life is the ability to evolve by natural selection. Thus some scientists have suggested that certain clays should be considered 'alive' because they are able to crystallise in a multitude of forms. Over time, successive generations of clays crystallise, becoming better and better adapted to the conditions; and this sounds very like the process that Charles Darwin described as the mechanism of evolution.
But I do not feel this is rigorous enough. We need something more to bridge the conceptual gap between ever- adapting clays and, say, an elephant. Of crucial importance is the ability of living things to process energy. The point here is that some molecules, including those that make up the crystals of clays, form 'passively'; it takes less energy for the component atoms to cling together than to stay apart, and the formation of such molecules is as easy, more or less literally, as falling off a log. But other molecules, including those of protein and DNA, cannot be formed unless energy is first introduced; like building a house. Plants trap light energy to build their own complex molecules, via photosynthesis; and animals utilise the energy entrapped in the complex molecules created by the plants to build their own molecular constituents. These molecular constituents are then the ones that grow, reproduce and exist in variable forms which can adapt to changing circumstance.
But this process - the harnessing of energy to create molecules that are thermodynamically unlikely - seems to me to require another quality which Lynn Margulis of Boston University has argued is the most important of all: that of dialogue. That is, a single kind of molecule cannot do all that is required; it cannot alone harness energy, reproduce, and all the rest. Various molecules are required, working together. This shows, as Dr Margulis says, that co-operation is at least as fundamental to the process of life as is competition, the quality which Darwin argued was the spur to all evolution. Another crucial point is lurking here. Some biologists have argued in recent years that the fundamental living molecule is not DNA or protein, but RNA, the one that mediates between them. This, they say, combines the ability of DNA to carry information, with the catalytic - 'executive' - abilities of proteins. This has led some to suggest that life on Earth might have begun with RNA, with DNA and proteins as later refinements. But RNA is itself thermodynamically unlikely: carefully packaged energy is required to make it. So it could not have evolved in isolation; RNA itself is a product of dialogue. Life creators cannot simply seek to make a single all-purpose 'living' molecule (like RNA), instead they must acknowledge that life is innately dialectic. A cooperative of molecules is required.
Two obvious forms of dialectic in existing organisms are the cascade and the cycle. In the cascade, molecule A makes molecule B which makes C, and so on. This is seen in the succession of proteins - 'factors' - that leads to the clotting of blood. Lack of any one such factor leads to haemophilia. In cycles, the molecule at the end of the cascade - say P - is the same as the one at the beginning, and so the cascade goes round and round. Raw materials and energy are added to the cycle as it proceeds, which are converted into more useful entities en passant. Thus, in respiration the energy-rich molecule ATP is generated by the activity of the Krebs cycle, while at the same time sugars are broken down into carbon dioxide and water.
So that's it. Life creators will know they are on the right lines when they have produced chemical systems that harness energy from the outside world and in so doing multiply themselves; but which are able to reproduce themselves in a variety of forms, and thus make themselves available for evolution by natural selection; and which consist essentially of self-perpetuating dialectics of different molecules that are mutually supportive. A system that has these qualities is bound to
be complex. A self-sustaining, energy- processing complex system that is also heterogeneous, and in which all the different parts are essential, can properly be called an organism.
I suspect that the only systems capable of generating and sustaining the necessary complexity will be based on the element carbon, just as life on Earth is carbon based. Carbon atoms are small but are able to combine with up to four other atoms, which enables them to form molecules of virtually infinite variety. No other atom has quite that versatility.
However, we need not assume that the first created living systems will be based on DNA, RNA and protein, all of which are highly evolved molecules. Neither need we assume that such a system - the kind on Earth - is the most efficient that could be devised. It will be extremely difficult to create life; but in the long term, molecular biologists may create life that operates more smoothly than the kind we are familiar with.
Many readers will find this discussion repellent. Some will say, 'But you are suggesting that all life is chemistry]' Well, in one sense it is. I also feel, however, that there is more to chemistry than has so far met the conventional scientific eye. But that is another story.
Colin Tudge discusses these ideas in 'The Engineer in the Garden' (Jonathan Cape, pounds 17.99), which was shortlisted for the 1994 Rhone-Poulenc Science Book of the Year.
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