Paeaebo 2014 Basic Books
|Pääbo S (2014) Neanderthal man. In search of lost genomes. Basic Books, New York:275 pp.|
Abstract: 'The Neanderthals live on in many of us today' (p 199).
Neanderthal Man tells the story of geneticist Svante Pääbo's mission to answer this question, and recounts his ultimately successful efforts to genetically define what makes us different from our Neanderthal cousins. Beginning with the study of DNA in Egyptian mummies in the early 1980s and culminating in the sequencing of the Neanderthal genome in 2010, Neanderthal Man describes the events, intrigues, failures, and triumphs of these scientifically rich years through the lens of the pioneer and inventor of the field of ancient DNA.
We learn that Neanderthal genes offer a unique window into the lives of our hominin relatives and may hold the key to unlocking the mystery of why humans survived while Neanderthals went extinct. Drawing on genetic and fossil clues, Pääbo explores what is known about the origin of modern humans and their relationship to the Neanderthals and describes the fierce debate surrounding the nature of the two species' interactions. His findings have not only redrawn our family tree, but recast the fundamentals of human history—the biological beginnings of fully modern Homo sapiens, the direct ancestors of all people alive today.
A riveting story about a visionary researcher and the nature of scientific inquiry, Neanderthal Man offers rich insight into the fundamental question of who we are.
• Bioblast editor: Gnaiger E
- p 4: First, wee needed to repeat the experiment – not just the past step but all steps, .. And then a third step was necessary .. namely, repetition of the results in another lab, an unusual step in a typically competitive scientific field.
- p 16: .. our weekly lab meetings with the subgroup of my lab .. Throughout my career I have found these extensive discussions with scientists working in my lab to be very useful; indeed, I think they have been crucial to whatever success we have had. In such discussions, ideas that would never occur to people focusing solely on their own work are often hatched. Moreover, scientists without a personal stake in a project's outcome provide a reality check, since they are free of the wishful thinking all too common among those who are working on a project they love and on which their scientific future may depend.
- p 18: Nature .. Science .. They often seemed more interested in publishing papers that would give them coverage in the New York Times and other major media outlets than in making sure the results were sound and likely to hold up.
- p 33: To check on my experiment, I did controls – an essential thing in any laboratory experiment. For example, I repeated the exact process in parallel but added no mummy DNA to the plasmid, and also repeated the process but added modern human DNA.
- p 34: I needed to talk to my thesis adviser, .. I asked if he might perhaps want to be a co-author with me on the paper, in his capacity as my adviser. Obviously, I had underestimated the man. Rather then scolding me for what could have been seen a misappropriation of research funds and valuable time, he seemed amused. He promised to read the manuscript and said that, no, obviously he should not be the co-author of work that he hadn't even been aware of.
- This was what science was supposed to be about: reproducibility of results!
- p 51: We recommended that a "blank extract" – that is, an extract with no ancient tissue but containing all other reagents to be used – be processed in parallel every time extractions from old specimens were performed.
- p 52 .. the ancient DNA field tends to attract people without a firm background in molecular biology or biochemistry .. The practice what we in the lab liked to privately call "molecular biology without a license".
- p 56: As we were painstakingly developing methods to detect and eliminate contamination, we were frustrated by flashy publications in Nature and Science ..
- p 61: nevertheless, once results are published, it is even more difficult to show that they are wrong and explain where the contamination came from. .. "Let's stop playing the PCR police." We determined from then on to ignore those reports we thought were wrong and concentrate on our own work.
- p 65: As always, I insisted that we first pay attention to the technical side of things.
- p 86: I decided that the area where our departmental seminars and weekly research meetings were held should be open to the corridor, to do away with the feeling that a meeting was a closed affair for invited participants only. Anyone coming by should be able to listen in, contribute to the discussions, and leave again.
- p 115: doing all the analyses and experiments necessary to tell the complete story leaves you vulnerable to being beaten to press by those willing to publish a less complete story that nevertheless makes the major point you wanted to make. Even when you publish a better paper, you are seen as mopping up the details after someone who made the real breakthrough.
- p 116: I spent the entire flight to New York, as well as the first night in my tiny room, preparing my talk. .. I had given many talks there before and was used to watching most of the six hundred or so people in the room fiddle with their laptops as they checked through their own presentations or e-mailed colleagues – or dozed off due to the combined effects of jet lag and too many highly detailed talks. But this time was different.
- p 146: graduate students and postdocs know that their careers depend on the results they achieve and the papers thy publish, so three is always a certain amount of jockeying for opportunity to do the key experiments and to avoid doing those that may serve the group's aim but will probably not result in prominent authorship on an important publication. I had become used to the idea that budding scientists were largely driven by self-interest, and I recognized that my function was to strike a balance between what was good for someone's career and what was necessary for a project, weighing individual abilities in this regard. As the Neanderthal crisis loomed over the group, however, I was amazed to see how readily the self-centered dynamic gave way to a more group-centered one. The group was functioning as a unit, with everyone eagerly volunteering for thankless and laborious chores that would advance the project regardless of whether such chores would bring any personal glory. There was a strong sense of common purpose in what all felt was a historic endeavor.
- p 162: Unfortunately, Illumina did not operate its own sequencing center, ..
- p 170: – but we needed people willing to work full-time or almost full-time on the project for at lease a few months so that we could finish the analyses quickly. I had seen too many examples of genome projects that dragged on for months or years because crucial groups had multiple and conflicting commitments.
- p 208: The dirty little secret of genomics is that we still know next to nothing about how a genome translates into the particularities of a living and breathing individual.
- p 209: Indeed, despite the fact that most efforts to understand the genome have sprung from efforts to combat disease, for the vast majority of diseases, such as Alzheimer's, cancer, diabetes, or heart disease, our current understanding allows us only to assign vague probabilities to the likelihood that an individual will develop them.
- p 216: Some scientists are so driven by intellectual curiosity that once they've found the solution to a problem, they will be remiss in going through the tedium of writing it up and publishing it. This, of course, is very bad. Not only does the public, which has ultimately funded the research, have a right to learn about the results, but other scientists also need to know the details of how results were achieved so that they can improve and build on them. In fact, this is the main reason why, when scientists are being considered for appointments and promotions, they're judged not on how many interesting projects they have started but, instead, on how many projects they have finished and published.
- p 217: I suggested that each section of this supplementary material would have separate authors and include a corresponding author to whom any interested readers would be referred in case they had questions. .. People actually delivered their supplementary sections, which eventually swelled to 19 chapters and 174 pages. .. finally, in the first days of February 2010, Ed Green submitted everything to Science. .. the paper appeared on May 7, 2010.
- p 252: The way forward is, on the one hand, the introduction of human and Neanderthal genetic variants into the genomes of human and apes cells that can then be used not to clone individuals but to study their physiology in a plastic dish in the laboratory and, on the other hand, the introduction of such variants into laboratory mice.
- p 253: One can imagine putting such changes into cell lines, and into mice, alone and in different combinations, in order to "humanize" and "neanderthalize" biochemical pathways or intracellular structures, and then to study their effects.
- Gnaiger E (2021) Beyond counting papers – a mission and vision for scientific publication. Bioenerg Commun 2021.5. https://doi:10.26124/BEC:2021-0005
Labels: MiParea: mtDNA;mt-genetics, nDNA;cell genetics, mt-Awareness