I, also, was too young to appreciate McClintock’s sentinel papers (in 1958 and 1960). Barbara retired from her position at Carnegie Institution in 1967, but then she worked as scientist emerita (working in her own lab, with grad students and postdocs) at Cold Spring Harbor (Long Island, NY), for another two decades after 1967 — receiving many awards and recognitions (including the National Medal of Science in 1970, the first woman ever to receive this award) — at least until 1993, a year after her death at age 90.
Interestingly, she wrote a letter to Oliver Nelson (a maize geneticist colleague) in 1973 — in reference to her decision 20 years earlier to “stop publishing detailed accounts of her work on controlling elements”: “Over the years I have found that it is difficult, if not impossible, to bring to consciousness of another person the nature of his tacit assumptions when, by some special experiences, I have been made aware of them. This became painfully evident to me in my attempts during the 1950s to convince geneticists that the action of genes had to be, and was, controlled. It is now equally painful to recognize the fixity of assumptions that many persons hold on the nature of controlling elements in maize and the manners of their operation. One must await the right time for conceptual change.”
When I attended (annual) mouse genetics meetings (at Bar Harbor, ME) between 1973 and 1983, I recall Professor McClintock giving talks there more than once. Ken Paigen, Director of Jackson Laboratory, had invited her; during this time period, Ken also visited her lab for a day or longer and I remember him saying “She’s discovered something very important and fundamental to genetics, but I cannot comprehend how her genetic-crossover experiments in maize — led her, ultimately, to her startling conclusions..!! ” 😊
From: John J Stegeman
Sent: Saturday, October 15, 2022 6:03 PM
Excellent examples, Dan..!! Two of these three, and Pääbo — all caught my attention immediately (I was too young at the time of McClintock’s first papers). All three awardees were/are “too cool” to be ignored. I remember clearly where I was, when I was first reading Prusiner’s paper. I met him once at an Academy function at Woods Hole.
John Stegeman, PhD
Senior Scientist, Woods Hole Oceanographic Institute, MA
From: Nebert, Daniel (nebertdw)
Sent: Saturday, October 15, 2022 6:50 PM
Subject: Geneticist who unmasked lives of ancient humans wins the 2022 Nobel Prize in Physiology or Medicine
This year’s prize is a GREAT example of what a Nobel Prize can be (or should be) — or what it has been, at least a few times over past decades [i.e., someone with a CRAZY idea that goes against the grain, he/she is convinced that they know they are correct, and they continue fighting the ~95 or 99% “consensus thinking” (or “groupthink”) who are certain he/she is wrong (or crazy). And then, after several, or many years, it turns out that the consensus groupthink was wrong — all along] … !!
Off the top of my head, three particularly outstanding examples come to mind.
 Barbara McClintock published her first paper on “jumping genes” in maize (genetic studies in corn; Bloomington, Indiana) in 1958 and her classic article in Proc Natl Acad Sci USA in 1960 — but she was regarded mostly as a “weirdo” and often laughed at, at scientific meetings. By the mid-1960s, steps leading from DNA transcription into mRNA, and translation of the messenger RNA into the amino acid sequences that make proteins, became well established (i.e., the genetic code was finally broken). Genes were no longer abstract concepts, but rather discrete molecular entities that could be manipulated in a test tube.
Mobile genetic elephants were then discovered in bacteriophages (viruses that infect bacteria) Soon, mobile elements were also discovered in bacteria, and eventually in the fruit fly Drosophila. The consensus scientific community gradually recognized that these “transposons” were real, and they were not just peculiar to maize, but were in fact widespread across species. McClintock was awarded the 1983 Nobel Prize for Medicine or Physiology — 35 years after her first published report of “transposition of genetic units”…!!
 “Mad cow disease,” and the human equivalent Creutzfeldt-Jakob disease — in the 1970s were degenerative brain diseases of unknown cause. After ~10 years of experiments, neurologist Stanley Prusiner reported in 1982 that these diseases were caused by a virus-like protein which he named “prion” (derived from “protein” and “infectious”). Almost every scientist laughed, because “viruses were well known ‘always’ to be made of DNA or RNA.” Prusiner persisted, however, because he was convinced the consensus groupthink was wrong, and that he was right. He proved to be correct and was awarded the 1997 Nobel Prize for Medicine or Physiology for his novel discovery. Prions are now realized to have effects in tissues other than brain and, in fact, are found even in lower organisms such as yeast…!!
 For decades, peptic ulcer was believed by consensus groupthink to be caused by “mental stress and excess stomach acid.” Following many years of experiments, physicians Barry Marshall and Robin Warren reported in 1985 that peptic ulcer was caused by a bacterium, Heliobacter pylori…!! This finding forever changed the field of ulcer research: instead of treating ulcers with antacid medications and/or surgery, antibiotics could now kill the bacteria and cure the disease…!! Twenty years later, Marshall and Warren were awarded the 2005 Nobel Prize for Medicine or Physiology for this breakthrough.
Moral of the Story: If you know what you’ve found something very real, and you’re convinced that the consensus groupthink does NOT appreciate your breakthrough findings — stick to your guns, and (hopefully) “everything will eventually come out in the wash” and you will be eventually credited for that breakthrough. 😊
From: Olavi Pelkonen
Thanks very much for the information! I also have followed Pääbo’s papers. I remember the first time that I met him—somewhere in the late 1980’s in Uppsala or Umeå at a symposium. At that time, almost everyone in the audience (including myself) were pretty convinced that extracting readable ancient DNA from fossilized bones would be impossible, because of DNA degradation, combined with contamination of other biological materials in the dirt or mud—as well as any other problem of long exposures and processes occurring over many millennia.
It is good to know that all of us were completely wrong!
Olavi Pelkonen, PhD
eProfessor of Pharmacology
University of Oulu
From: Nebert, Daniel (nebertdw)
Sent: Saturday, October 8, 2022 5:16 PM
Because these GEITP pages have been sharing many of Svante Pääbo’s exciting breakthrough publications — over the past 14 years — we believe it is only appropriate to report on his winning the 2022 Nobel in Physiology or Medicine this past week. 😊 This [below] is a recent summary in the latest issue of Nature.
Geneticist who unmasked lives of ancient humans wins the 2022 Nobel Prize in Physiology or Medicine
Svante Pääbo has made stunning discoveries about human evolution using ancient DNA — and his work helped to spawn the competitive field of palaeogenomics.
Neanderthal researcher Svante Pääbo, recipient of 2022 Medicine nobel prize.
Svante Pääbo has been awarded a Nobel prize for discoveries about the genomes of extinct hominins and human evolution.
The 2022 Nobel Prize in Physiology or Medicine has been awarded for pioneering studies of human evolution that harnessed precious snippets of DNA found in fossils that are tens of thousands of years old.
The work of Svante Pääbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology (MPI-EVA) in Leipzig, Germany, led to the sequencing of the Neanderthal genome and the discovery of a new group of hominins called the Denisovans, and also spawned the fiercely competitive field of palaeogenomics.
By tracing how genes flowed between ancient hominin populations, researchers have been able to trace these groups’ migrations, as well as the origins of some aspects of modern human physiology, including features of the immune system and mechanisms of adaptation to life at high altitudes.
Pääbo’s Nobel win “is an extraordinary recognition of this field maturing and of what he did in putting together everything that needed to be done to accomplish this miracle, which is getting ancient DNA from human remains”, says David Reich, a population geneticist at Harvard Medical School in Boston, Massachusetts, who worked closely with Pääbo on the Neanderthal genome sequence.
At a press conference following the announcement, Pääbo said that he was still digesting the news, and didn’t initially believe he had won the Nobel when he got the call from Stockholm. He “at first thought it was an elaborate prank developed by people in my group”.
Chris Stringer, a palaeoanthropologist at the Natural History Museum in London, says that Pääbo’s work — including recovery of the oldest ancient human DNA on record, 430,000-year-old sequences from Spain1 — has revolutionized our understanding of the past. “It’s central to human evolutionary studies now,” Stringer says, adding that the Nobel win is “great news”.
Pääbo had to develop ways of analysing DNA that had been damaged by thousands of years of exposure to the elements, and contaminated with sequences from microorganisms and modern humans. He and his collaborators then put these techniques to work sequencing the Neanderthal genome, which was published in 20102. This genetic analysis led to the finding that Neanderthals and Homo sapiens interbred, and that 1–4% of the genome of modern humans of European or Asian descent can be traced back to the Neanderthals.
Pääbo’s techniques were also used to identify the origins of a 40,000-year-old finger bone found in a southern Siberian cave in 2008. DNA isolated from the bone indicated that it was from neither Neanderthals nor Homo sapiens, but came from an individual belonging to a new group of hominins3. The group was named the Denisovans, after the cave in which the bone was found. Ancient humans living in Asia interbred with this group, too, and Denisovan DNA can be found in the genomes of billions of people alive today.
During the early years of ancient DNA research — led by Pääbo and other scientists in the 1980s and 1990s — the field was plagued by concerns over contamination from modern human DNA (Pääbo has admitted that DNA he recovered early on from Egyptian mummy remains was probably his own). But, thanks to methods developed in Pääbo’s laboratory, as well as the advent of new sequencing technologies, contamination is no longer the ‘boogeyman’ it once was.
“When I started, we weren’t even sure you could work with ancient human DNA,” says Pontus Skoglund, a palaeogeneticst at the Francis Crick Institute in London. “But now, and I think led by Svante’s department, we have an approach where contamination is really not a major issue anymore.”
Pääbo’s work teasing out DNA from Neanderthals, Denisovans and other hominins also has important implications for modern medicine. Although the proportion of the human genome comprised of archaic DNA is small, this material seems to punch above its weight, making an important contribution to the risks of diseases ranging from schizophrenia4 to severe COVID-195. And people living on the Tibetan Plateau can thank Denisovans for gene variants linked to high-altitude adaptation6.
“The fact that a good fraction of the people running around in the world today have DNA from archaic humans like Neanderthals is of important consequence to who we are,” says Reich. “So I think that knowing that and trying to understand the implications of that for health is something that will be with us for the rest of our time as a species.”
With genomes from multiple Neanderthals and Denisovans available, it is now possible to identify uniquely human genes, says Johannes Krause, a palaeogeneticist at MPI-EVA. In September, researchers showed that a gene variant found in humans, but not in Neanderthals or Denisovans, is linked to greater neuronal growth in lab-grown brain organoids7. “We’ve never come so close to understanding what makes humans humans,” Krause says.
Researchers describe Pääbo as intense and driven, but also collegial and generous. His department at the Max Planck Institute for Evolutionary Anthropology has produced a generation of palaeogeneticists who are pushing the field ever further.
Viviane Slon, a palaeogeneticist at Tel Aviv University in Israel who did her PhD under Pääbo’s supervision, says her former mentor has an “uncanny” ability to see the larger picture while remaining laser-focused on details. When Slon was working on remains that turned out to be a first-generation Denisovan–Neanderthal hybrid, the sequence of maternally inherited mitochondrial DNA matched that of a Neanderthal. But, when publishing those results, Pääbo urged Slon to reserve judgment until they had sequenced nuclear DNA inherited from both parents. “He wouldn’t let me write that it’s a Neanderthal because we didn’t know that, and in fact it turned out to be a mixed offspring,” Slon says.
Reich says that working with Pääbo and the team he organized to sequence and analyse the first Neanderthal genome was inspirational. “It was the best consortium ever,” Reich says. “He recognized how special and unique this type of data they were producing was.” This eventually inspired Reich to set up his own ancient DNA laboratory.
Pääbo’s influence on ancient DNA work has been such that it’s hard to imagine where the field would be without him. “He’s the godfather of the field,” says Skoglund.
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