Mutation in full flight

By Johnjoe McFadden, a professor of molecular genetics at the University of Surrey and author of Quantum Evolution (THE GUARDIAN, 13/04/06):

Creationists often claim that evolution is just a theory since no one has ever observed it. Being generally a slow process, it is hard to catch evolution in action. But it isn't always slow. For fast replicating pathogens, such as the bird flu virus, evolutionary change can be rapid and lethal. Even Darwin, the originator of the theory of natural selection, lamented the "clumsy, wasteful, blundering, low and horribly cruel" nature of its action. The evolution of the H5N1 strain of bird flu is now advancing on a million wings, and its course may seal the fate of many of us.

The snail's pace of animal evolution is usually tracked by examining changes in anatomical structures, such as the coil of a shell or the length of a bone. But microbes have neither bones nor shells, so evolutionary biologists have to make do with measuring molecular changes. Each time an organism replicates it must copy its genetic material - DNA or RNA (a close relative of DNA) - and there is the potential for introducing errors: mutations. Our cells devote a lot of resources to minimising copying errors, but viruses are less picky and tolerate higher mutation rates. The speed of evolution depends on the mutation rate and the frequency of replication. Large animals that take years to reproduce evolve slowly, but viruses that can replicate within minutes can evolve within hours.

A central tenet of evolutionary theory is that mutations are random. Each time the virus reproduces it rolls the genetic dice to generate progeny just a little different from itself. The grim reaper of natural selection then separates the wheat from the chaff of evolutionary innovation, favouring the survival of only the fittest progeny. So each time the bird flu virus replicates, it generates new mutants - any one of which may increase its fitness for humans. Much of the pathology of infectious diseases is the parasite's means of getting out of one host and into another. Respiratory pathogens make you cough because coughs and sneezes spread diseases. The H5N1 strain causes diarrhoea because the virus is often spread by bird droppings.

In every infected bird is a H5N1 virus busily replicating and throwing off mutants, any one of which may acquire the key that could unlock our respiratory cells. This will not be an advantage if it happens in a bird, but if the mutation emerges while the virus is replicating in a human victim, then natural selection will kick in to select mutant viruses that can replicate in the human respiratory tract. Once there, the virus could cause the coughs and sneezes that would allow its spread to lots more victims. At least two of the three previous pandemics of influenza this century (1957 and 1968) were caused by avian flu viruses.

So far there have been only about 200 cases of H5N1 influenza in humans, vastly fewer than the millions of cases estimated in birds, so the evolutionary dynamics of H5N1 are still firmly tied to their feathered hosts. However, each human victim is effectively a Darwinian roulette wheel, with natural selection acting as the banker ready to reward any new viruses capable of crossing the species barrier.

We aren't there yet. The fact that the H5N1 strain has infected only a few humans is testimony to its low rate of infectivity. Given enough time and enough human hosts a species jump becomes almost inevitable. But nobody knows how much time, or how many hosts are needed to generate a pandemic strain. An outbreak of the H5N1 disease in Hong Kong in 1997 was controlled by extensive culling of domestic fowl. Our best hope is that this outbreak will be similarly controlled or burn itself out before the evolutionary dynamics of H5N1 can shift to the human population.