Saturday, March 1, 2014


I much enjoyed reading Svante Pääbo’s Neanderthal Man: In Search of Ancient Genomes [Basic Books, 2014].  Pääbo is a founder of the field of palaeogenomics, which attempts to reconstruct and interpret the DNA of ancient and extinct organisms. Pääbo spent more than 20 years trying to work out the genome of first the mitochondrial DNA of Neanderthals and then the nuclear DNA of these cousins of our own species.  Pääbo uses a combination of memoir, log book, and narrative to give the year by year account of set-backs, new technologies, and constant rethinking of approaches to achieve these important contributions to human evolution and molecular biology.  Unlike Watson’s Double helix   account of the structure of DNA, Pääbo has a different challenge.  He knows that the cells of Neanderthals were virtually identical to living cells of humans because they would have mitochondria, mitochondrial DNA, nuclei, and DNA (very likely with 46 chromosomes largely syntenic in their sequences of genes).  In Watson’s quest, the structure was the unknown.  In Pääbo’s quest, the differences in genes and variations of the genes was the quest.  For both there was the firm conviction, going back to H.J. Muller in 1926 that the gene was the basis of life. 
              Pääbo was born in Stockholm, his father, Sune Bergsgtröm, was a physiologist who worked out the structure and function of prostaglandins, molecules that acted like hormones at the cellular or immediate tissue level. For that work he received a Nobel Prize in 1982.  He carries his mother’s last name, because Karin Pääbo (a biochemist from Estonia) conceived him in an affair she had with Bergstrom.  The young Pääbo rarely saw his biological father and took solace in being a nerd-like scholar, infatuated with Egyptology, after his mother took him to visit Egypt when he was thirteen.    He also complicated his life as a gay activist in Stockholm (although he turned out to be bisexual).  He chose medicine as a possible option for a career but as his father’s fame became more apparent, he began thinking of working as a biochemist, and shifted to a PhD program.  His mentor worked out the DNA sequences of genes involved in antibodies. This rekindled Pääbo’s idea of working with mummies, using their DNA as a way to study ancient genes.
              Pääbo found a sympathetic curator in East Germany during the Cold War and began working with mummified tissue in his laboratory at Uppsala.  He did this independently of his dissertation research and showed his results to his mentor who was impressed and encouraged his career. The publications led to postdoctoral opportunities in Berkeley with Alan Wilson and eventually an appointment as head of a new department at a Max Planck Institute in Leipzig. As his publications grew in number, his access to samples of fossil bones increased when he switched from mummified tissues of Egyptians to his quest for Neanderthal DNA. These are not easy chapters for those without a science background.  They reveal the enormous challenge of identifying Neanderthal DNA as an entity separate from contaminating bacteria and the sweat, dandruff, and other excreta of modern human contamination, often by those who first retrieved the bones from caves and burial sites.  We learn how Pääbo relied on a team of students and employees whose work he supervised but who formed a weekly seminar of criticism of everyone’s work and what it signified.  Those brainstorming sessions led to more sophisticated controls, inventions of new procedures, search of the literature for new technologies, and deeper insights than any individually had conceived.  In most fossil Neanderthal bones it is rare for more than a few percent of the DNA to be Neanderthal. Proving to skeptical molecular biologists that the sequences they reported were Neanderthal and not artifacts of the past or present was stunningly difficult.  It is worth reading through those chapters to see how difficult this field was for a careful investigator. 

              I have often argued in my books that the life sciences rarely work through paradigm shifts.  This book illustrates the incremental changes over 20 years – hundreds of them – that brought about the reality of a new field of science.  We like to believe in the Copernican moment, when a shift takes place and a new field or world view emerges. They are rare in all of science and most new science and theories we add to the field we call the life sciences, fall not into flashes of rare insight but into the hard work of identifying mistakes in our experimental designs, interpreting unexpected findings, identifying contaminating variables, and eventually building an edifice of evidence that meets all known challenges of one’s contemporaries.  That Pääbo has done.

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