Sunday, August 16, 2009

Dr Livingstone, I presume? (Frank, that is!)

Malaria may have killed or harmed more people than any other single cause of disease in our species' history. A new article by Rich et al. in PNAS uses newly available DNA sequence data to date the origin of a common virulent type of malarial parasite and its transfer from an ancestral chimpanzee host to humans.

Prior work had suggested the transfer was from a bird host, but primates seem now to be the guilty party. The relevant strains are Plasmodium falciparum and its close relative P. reichenowi, the chimp parasite. The idea of a recent transfer was supported hypothetically by the assumption that it's not in a parasite's long-term interests to be too virulent, but that the P. falciparum parasite hadn't had time to adapt more chronic effects.

Sequences of several samples of these and other Plasmodia show clearly that the human and chimp sequences form a single evolutionary clade (the top big branch in the figure, reproduced from the paper). That also supports the recent transfer to humans from a chimp source that is considerably older and geographically widespread in Africa, but not a much more ancient bird clade.

This paper properly relates the authors' new findings to a classic, elegant, and incredibly perceptive and integrative American Anthropologist paper in 1958 by the late anthropologist Frank B Livingstone (Anthropological implications of sickle cell gene duplication in West Africa, American Anthropologist, New Series, Vol. 60, No. 3 (Jun., 1958), pp. 533-562). He looked at the distribution of malaria, the population genetics of malarial resistance including the frequency and distribution of sickle cell and other hemoglobin variants, and how long a mutation with a selective advantage due to protection from malaria would take to reach its present distribution. He elegantly integrated these data with known patterns of language and culture in the malarial areas of Africa.

Frank concluded that malaria arose roughly 10,000 years ago with the advent of settled agriculture, that encroached on the chimpanzees' forest habitats, the proximity providing opportunity for transfer to humans. Settled agriculture led to cleared, stationary fields in which ponds of water could develop, providing enhanced or stably localized breeding grounds for the larval stage of the mosquito life cycle.

Sequence divergence between the human vs chimp parasite genes, plus the low level of divergence within the human clade, suggest to Rich et al. that the initial transfer may have occurred hundreds of thousands or even a few million years ago. It may have conferred only benign malaria on the 'human' hosts -- actually our species as such is only about 100,000 to 200,000 years old, so the transfer would have been to our very non-agricultural antecedents whose population structure was probably much more patchy, sparse, and in these senses chimp-like, if probably also less arboreal.

Sometime post-agriculture, there may have been human and/or parasite mutations that made the parasite much more virulent, and it then spread rapidly with agriculture. Whether the virulence directly helped the spread or not would be debatable.

This is a very nice paper of science, one that leads us to a somewhat related topic about science. Given the relatively crude state of genetics at the time, Livingstone's paper was quickly recognized as a classic, and that judgment persists....if only people these days weren't too impatient to read it. Rich et al. did, but that's not so typically the case.

With much media and journal ballyhoo, a recent paper in Science by Tishkoff et al. (Haplotype Diversity and Linkage Disequilibrium at Human G6PD: Recent Origin of Alleles That Confer Malarial Resistance, Science 20 July 2001: Vol. 293. no. 5529, pp. 455 - 462) studied the origins of the human G6PD mutation, also related to malarial resistance. The authors used population genetic analysis conceptually similar to Livingstone's, and estimated that the protective mutation arose less than 10,000 years, compatible with the earlier estimates and reasoning. This was solid genetics, and Tishkoff et al. did refer to Livingstone's hypothesis, though in a rather buried instead of featured way. The finding was strongly confirmatory, but not the transformative discovery that media hype gave the impression it was.

Science generates enough solid, interesting work without the hyperbole that these days has come to serve many interests. That gives a misleading impression that we're making 'paradigm shifts' in human knowledge on an almost daily basis, which is not true. In many ways, this is a kind of crying 'wolf!'. In the long run, science would be better off if routine or incremental findings were recognized as such, because that is how science mainly works, and the public who support us should know that. Authors should insist on tempered claims in the media and by the journals.

It is easy of course for us to be over-critical, and in the nature of full disclosure, although he never worked on malaria, Ken's PhD advisor was Livingstone himself. So we naturally knew of Livingstone's work.

But that doesn't change the fact which is all too symptomatic of our credit-hungry times that we and the media give more credit to ourselves as if new technology has obsolesced all previous knowledge, and are unwilling or in too much of a hurry to do like Stanley and make treks required to identify the source of the News. In this case, that would be Dr Livingstone, we presume.


Jennifer said...

So basically, Malaria is just revenge on humans for stealing the land of the chimpanzees. It's the result of bad karma. Hmmmmm.....

Anne Buchanan said...

That's about right!