Monday, September 3, 2018

Luigi Luca Cavalli-Sforza (1922-2018), worth remembering

Luigi Luca Cavalli-Sforza has died, at age 96.  Who?  I wonder how many readers of this blog, or in general how many anthropologists or human geneticists of less than middle-age, know who he was.  We are not, these days, in the habit of crediting the past.  But Luca, at least, is worth remembering--for those who remember him.


Born in Italy, Luca received his MD there and then, when WWII ended, studied population genetics with RA Fisher in England.  He spent most of his career at Stanford, where he taught and did his creatively integrative and theoretical work on human variation and its evolution.  He collaborated with many colleagues from around the world.  He was, from my graduate-student years on, probably the leading human population geneticist in the world.  He developed numerical methods for analyzing human allele-frequency variation and relating the pattern of that variation to global population history, relating that variation to other kinds of data.  In particular, he was interested in the relationship of language patterns to genetics, and the causal relationship between cultural dynamics--such as the spread of agriculture--and genetic diversity, and he developed ways to analyze how the latter could be used to help reconstruct the former.

I was incredibly fortunate to have been able to spend a sabbatical in Luca's lab at Stanford, in the late '70s.   I had no particular 'project' to work on but, typically for him, he hosted me anyway.  It was enough for me to know that he and his associates were leaders in human population genetics, as a science per se, but also that they were so original and creative in relating genetic variation to cultural, language, and technological history.  His was a synthetic view.  He was technically original and advanced, but based on innovative and integrative thinking.

Luca wrote much, but his two most memorable and durable books, that encapsulated much or most of his interests are (1) The Genetics of Human Populations, with co-author Walter Bodmer (W. Freeman, 1970; and a subsequent watered-down version with author order reversed), and (2) the massive History and Geography of Human Genes, with P. Menozzi and A. Piazza (Princeton Press, 1994).  Both are still available, I think, the former in a Dover reprint.  The Genetics of Human Populations was a digestible, but sophisticated version of population genetics theory and method, suitable for understanding human origins, allele frequency variation, and evolution.  Many anthropologists and others learned their trade from this book.  The second book was the final word on traditional allele-frequency (rather than DNA sequence) based reconstructions of human global variation.

Luca worked on topics too numerous to go over here.  But this is very well described by John Hawks' fine summary of Luca's work and Wikipedia: Luigi Luca Cavalli-Sforza provides references.  For anyone even remotely interested in the history of anthropological genetics and its contribution to human evolution and culture history, it will be worth the effort to be familiar with these foundational contributions.

Luca was a central figure in the attempt to organize a worldwide, systematic sampling of human variation (called the Human Genome Diversity Project, or HGDP).  That project never took place as such, because, economically it came into funding conflict with the Human Genome Project, to generate a sequence of a representative complete human genome, and, politically because scurrilous accusations were leveled against the HGDP by those who saw it as a project to categorize people exploitively, much as racism does; this was grotesquely false and opportunistically culpable on the part of jealous or ignorant critics and scandal-thirsty journalists.  However, the stir provided NIH with a safe excuse not to fund the HGDP.  Instead of a formal, globally systematic project, Luca used the heterogeneous blood-group and protein variation data already collected over many years by various investigators around the world, to show global patterns of human gene frequencies.  His tome (#2 above) presented these data, much of which are still available.  Luca and colleagues developed methods for analyzing the pattern in relation to historical or prehistorical (assumed) human demographic behavior.

As science history often goes, this approach was soon to be pre-empted by DNA sequencing technology, and individual genome sequences supplanted protein and antibody-based allele-frequencies as the primary data for studying human variation and evolution (Ken Kidd at Yale, and a lifelong colleague of Luca's and an organizer of the HGDP effort, has maintained a very useful site for allele frequency and other data).  In this sense, historically, Luca's Big Volume was the last word on the earlier technology.  But of course similar attempts to reconstruct not just history itself but to integrate that with other aspects of human existence--are actively being pursued by many people, and this can now be extended far back in time thanks to the ability to extract DNA from fossils.  Nonetheless, in terms of the history of anatomically modern humans, the basic outlines in Luca et al.'s book, based on sample allele frequencies, I think still generally hold.

Ephemerality's children
I'm not sure how long Luca will be remembered.  What I write here is a paean to a wonderful person and terrific scientist.  But there is no single 'discovery' nor Cavalli-Sforza 'theorem' or the like, that will be, by being named for him, his lasting legacy.  He was not a grandstander, didn't play to the media, and his students and colleagues are now very senior.  The present formula in science has little interest in crediting the past (it's not good for careerism), and that generally also often means not reading its lore, either.  As happens in science, on technology supplants prior ones, and DNA sequence and other 'Big Data' and 'omics clearly and rightly have co-opted the less informative data types of Luca's era.  In some sense this does vitiate earlier methods as well as data.  The new data have also enabled publication that is very technical, but in part for the public glamor of technology is less closely tied to deeper, integrative, thought.  Nor was Luca the first to use population genetic data to look at human local or global history--studies of blood group variation, for example, well antedate his work, even if generally more crude in method and detail.

In that sense, Luca helped set the stage, but his timing was all wrong.  Ah, well.  Had he been starting now, with the technologies and database resources currently available, and the much more direct data of DNA sequence (and other 'omics), rather than allele frequencies from population samples, he would have made perhaps a more durable mark, and I suggest that he would have done so more deeply than was possible from the earlier data to which history limited his attention, and not in the hasty rush to print that is now so prevalent.

I fear these may be the hard realities of history.  But thoughtfulness, intelligence and, not least, personal grace only come along sporadically.

Cavalli was a gem of his time.

(This post has been edited to make minor typological corrections)

1 comment:

Charles Roseman said...

Thanks very much for this retrospective. You mentioned his substantial theoretical and methodological contributions. I’ve put together a brief, doubtlessly incomplete, list of some of his greatest hits in these categories.

1. He developed a substantial part of the basis of the phylogenetic estimation, including some of the earliest parsimony and maximum likelihood approaches (working with Edwards).

2. His realization that trees and covariance matrices had a natural mathematical relationship had wide ranging implications (with Piazza). When it came to his main interests, this insight allows for tests for treeness and, by extension, the ability to use allele frequencies to test hypotheses about the dynamics of population differentiation.

3. The above insight in 2 is also an important predicate for modern phylogenetic comparative methods.

4. He also undertook some of the earliest studies of isolation by distance and genetic drift. I recall him claiming (in perhaps a jest wrapped in a boast wrapped in a tall tale) he was the one who convinced Fisher that drift was happening.

5. His extensions (with Feldman) of quantitative genetics into cultural/structured environmental contexts forms the basis for ongoing advances in the study of behavior and multiple inheritance systems. This is important for both the IQ/heredity/society debate and for critically evaluating issues in epigenetics and things like the missing heritability problem.

I’ll do a bit more thinking to see if I can come up with more.