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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