The lecture was every bit as engaging as its title suggests. He started by asking the question what is life?, and illustrated the answer by comparing a ‘cyberdog’ with the common-or-garden variety. At a basic level, both dog and cyberdog can be thought of as a network of transistors (or cells) that respond to input signals in different ways, but while the cyberdog is programmed to carry out whatever (presumably) menial tasks its owner demands, the dog is programmed for survival. This led to a formalised definition of ‘life’, as ‘a self-sustained chemical system capable of undergoing Darwinian evolution’. Furthermore, if you zoom in hundreds of millions of times, the dog’s equivalent of the cyberdog’s fundamentally uninteresting network of transistors is the bewildering complexity of ‘molecular machines’ inside every living cell. Examples of molecular machines that are studied in the PPS course include ATP synthase and the ribosome.
The question of ‘how life came to be’ is perhaps almost as old as humanity itself. At the dawn of the scientific age, a few centuries ago, speculations centred on the idea of ‘spontaneous generation’, suggesting that fish might have arisen from water or mice from hay. The development of pasteurisation in the mid-nineteenth century helped disprove this theory, shortly before Darwin published his theory of evolution. We now understand that all living (and extinct) organisms evolved from a simple organism known as LUCA – short for the Last Universal Common Ancestor – but this begs the question: where did LUCA come from? To find a short answer to this question, you need to go back to the kind of conditions that scientists believe to have existed on an early Earth: a chemically rich ‘warm puddle’ of liquid in an oxygen-poor environment, much like those found in underwater volcanoes today.
Biochemically, LUCA would have been a single-celled organism containing a minimum set of biomolecules necessary for life, all coded for by a minimal segment of DNA. For decades, scientists have been trying to recreate the process of ‘abiogenesis’ by providing simple molecules in this type of environment with energy and investigating whether more complex molecules, the ‘building blocks’ for LUCA’s DNA and proteins, might be able to form. So far, it has proved possible to make the basic building blocks of proteins, the amino acids, and even, in some circumstances, to join several amino acids into a short chain, but not to connect hundreds of them to form a complete protein. Nucleic acids, the building blocks of DNA, are proving even more intractable.
Building blocks become biomolecules through a process in which each two units – amino acids or nucleotides – are joined together with the loss of a water molecule. This process requires energy, but the opposite one, in which the bond between the units is broken, can be spontaneous. Salvador used a set of blocks known simply as A, B, C and D to illustrate how the populations of block sets change over time, as combinations such as ‘AB’ are ‘born’ and ‘die’. If AB, for example, is made ‘sticky’ so it attracts more copies of A and B, it becomes ‘autocatalytic’ (that is, it helps form itself) and the AB population burgeons. At least, it does until A or B is depleted, when an ‘extinction event’ occurs. The system becomes more complex with the addition of an energy supply and further building blocks, and it becomes possible to see how collections of units with specialist functions could evolve. Some types would specialise in storing information (the ancestors of nucleic acids) and others in promoting bond formation (the ancestors of proteins).
Top: ATP synthase; Bottom: Bacterial ribosome. From PDB-101 Molecule of the Month
This would be a resourceful molecular system, capable of building its own building blocks, but it would have one major disadvantage: its survival depends on the proximity of the different types of molecule. If it were in the ‘warm puddle’ of the early Earth, a single rainstorm could blow it away. Keeping the components together requires a third type of biomolecule. Lipids are molecules with a long ‘water-hating’ tail and a short ‘water-loving’ head, and in water they form double layers with the tails pointing towards each other. These lipid bilayers often form spherical vesicles, and any primitive biomolecules trapped inside such a vesicle will stay together come what may.
Vesicles containing both ‘DNA-like’ and ‘protein-like’ molecules can be thought of as ‘protocells’: or, if you like, putative ancestors of the ancestors of LUCA. Salvador explained that his own contribution to the evolving story of synthesising life was in exploring the chemistry inside such protocells. Something like a protocell is almost certain to have existed, and this will have evolved to be better programmed for survival through developing more efficient molecular ways of making use of resources, storing and using energy, and responding to stimuli. Reproducing this process by adding molecular machines and efficient, specialist switches to a blank vesicle or protocell can generate cell-like robots. Initially, these are likely to have a wide variety of useful but still quite mundane functions in, for example, targeted drug delivery, but eventually they might do more: ‘life, but not as we know it’, perhaps?
Salvador ended his talk by asking two questions: can we synthesise life, and if so, should we? Most of his audience agreed with him that the first was ‘not done yet, but seems likely in the near future’. Interestingly, however, a majority thought that it might be too risky to take far.
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