The Nobel Prize in Physiology or Medicine 2023

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Treating the World: The Katalin Karikó and Drew Weissman Story | National Inventors Hall of Fame

"We kept making advances, but the world wasn't interested." --Drew Weissman

Nobel Prize Winners Dr. Katalin Karikó and Dr. Drew Weissman | The Story Behind mRNA Vaccines

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This year’s Nobel Prize in physiology or medicine has been awarded jointly to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. More information, including a video of the announcement, is posted below.

Announcement of the 2022 Nobel Prize in Physiology or Medicine

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PRESS RELEASE (10-02-2023)
NOBEL ASSEMBLY

The Nobel Assembly at the Karolinska Institutet
has today decided to award
the 2023 Nobel Prize in Physiology or Medicine
jointly to
Katalin Karikó and Drew Weissman
for their discoveries concerning nucleoside base modifications that
enabled the development of effective mRNA vaccines against COVID-19

The discoveries by the two Nobel Laureates were critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020. Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.

Vaccines before the pandemic

Vaccination stimulates the formation of an immune response to a particular pathogen. This gives the body a head start in the fight against disease in the event of a later exposure. Vaccines based on killed or weakened viruses have long been available, exemplified by the vaccines against polio, measles, and yellow fever. In 1951, Max Theiler was awarded the Nobel Prize in Physiology or Medicine for developing the yellow fever vaccine.

Thanks to the progress in molecular biology in recent decades, vaccines based on individual viral components, rather than whole viruses, have been developed. Parts of the viral genetic code, usually encoding proteins found on the virus surface, are used to make proteins that stimulate the formation of virus-blocking antibodies. Examples are the vaccines against the hepatitis B virus and human papillomavirus. Alternatively, parts of the viral genetic code can be moved to a harmless carrier virus, a “vector.” This method is used in vaccines against the Ebola virus. When vector vaccines are injected, the selected viral protein is produced in our cells, stimulating an immune response against the targeted virus.

Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics. Therefore, researchers have long attempted to develop vaccine technologies independent of cell culture, but this proved challenging.

mRNA vaccines: A promising idea

In our cells, genetic information encoded in DNA is transferred to messenger RNA (mRNA), which is used as a template for protein production. During the 1980s, efficient methods for producing mRNA without cell culture were introduced, called in vitro transcription. This decisive step accelerated the development of molecular biology applications in several fields. Ideas of using mRNA technologies for vaccine and therapeutic purposes also took off, but roadblocks lay ahead. In vitro transcribed mRNA was considered unstable and challenging to deliver, requiring the development of sophisticated carrier lipid systems to encapsulate the mRNA. Moreover, in vitro-produced mRNA gave rise to inflammatory reactions. Enthusiasm for developing the mRNA technology for clinical purposes was, therefore, initially limited.

These obstacles did not discourage the Hungarian biochemist Katalin Karikó, who was devoted to developing methods to use mRNA for therapy. During the early 1990s, when she was an assistant professor at the University of Pennsylvania, she remained true to her vision of realizing mRNA as a therapeutic despite encountering difficulties in convincing research funders of the significance of her project. A new colleague of Karikó at her university was the immunologist Drew Weissman. He was interested in dendritic cells, which have important functions in immune surveillance and the activation of vaccine-induced immune responses. Spurred by new ideas, a fruitful collaboration between the two soon began, focusing on how different RNA types interact with the immune system.

The breakthrough

Karikó and Weissman noticed that dendritic cells recognize in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules. They wondered why the in vitro transcribed mRNA was recognized as foreign while mRNA from mammalian cells did not give rise to the same reaction. Karikó and Weissman realized that some critical properties must distinguish the different types of mRNA.

RNA contains four bases, abbreviated A, U, G, and C, corresponding to A, T, G, and C in DNA, the letters of the genetic code. Karikó and Weissman knew that bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not. They wondered if the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction. To investigate this, they produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells. The results were striking: The inflammatory response was almost abolished when base modifications were included in the mRNA. This was a paradigm change in our understanding of how cells recognize and respond to different forms of mRNA. Karikó and Weissman immediately understood that their discovery had profound significance for using mRNA as therapy. These seminal results were published in 2005, fifteen years before the COVID-19 pandemic.

In further studies published in 2008 and 2010, Karikó and Weissman showed that the delivery of mRNA generated with base modifications markedly increased protein production compared to unmodified mRNA. The effect was due to the reduced activation of an enzyme that regulates protein production. Through their discoveries that base modifications both reduced inflammatory responses and increased protein production, Karikó and Weissman had eliminated critical obstacles on the way to clinical applications of mRNA.

mRNA vaccines realized their potential

Interest in mRNA technology began to pick up, and in 2010, several companies were working on developing the method. Vaccines against Zika virus and MERS-CoV were pursued; the latter is closely related to SARS-CoV-2. After the outbreak of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed. Protective effects of around 95% were reported, and both vaccines were approved as early as December 2020.

The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccines against other infectious diseases. In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types.

Several other vaccines against SARS-CoV-2, based on different methodologies, were also rapidly introduced, and together, more than 13 billion COVID-19 vaccine doses have been given globally. The vaccines have saved millions of lives and prevented severe disease in many more, allowing societies to open and return to normal conditions. Through their fundamental discoveries of the importance of base modifications in mRNA, this year’s Nobel laureates critically contributed to this transformative development during one of the biggest health crises of our time.

Key publications

Karikó, K., Buckstein, M., Ni, H. and Weissman, D. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005). [LINK TO PAPER]



Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 16, 1833–1840 (2008). [LINK TO FULL PAPER]



Anderson, B.R., Muramatsu, H., Nallagatla, S.R., Bevilacqua, P.C., Sansing, L.H., Weissman, D. and Karikó, K. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884–5892 (2010). [LINK TO FULL PAPER]



Katalin Karikó was born in 1955 in Szolnok, Hungary. She received her PhD from Szeged’s University in 1982 and performed postdoctoral research at the Hungarian Academy of Sciences in Szeged until 1985. She then conducted postdoctoral research at Temple University, Philadelphia, and the University of Health Science, Bethesda. In 1989, she was appointed Assistant Professor at the University of Pennsylvania, where she remained until 2013. After that, she became vice president and later senior vice president at BioNTech RNA Pharmaceuticals. Since 2021, she has been a Professor at Szeged University and an Adjunct Professor at Perelman School of Medicine at the University of Pennsylvania.

Drew Weissman was born in 1959 in Lexington, Massachusetts, USA. He received his MD, PhD degrees from Boston University in 1987. He did his clinical training at Beth Israel Deaconess Medical Center at Harvard Medical School and postdoctoral research at the National Institutes of Health. In 1997, Weissman established his research group at the Perelman School of Medicine at the University of Pennsylvania. He is the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovations.

Illustrations: © The Nobel Committee for Physiology or Medicine.
Illustrator: Mattias Karlén

The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humankind.

Nobel Prize® is the registered trademark of the Nobel Foundation

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Telephone Calls with the Winners

First reactions | Katalin Karikó, Nobel Prize in Physiology or Medicine 2023 | Telephone interview



The call from Stockholm woke Katalin Karikó at her home outside Philadelphia. Initially in disbelief, in this interview with Adam Smith, recorded soon after she had learnt of the award of the Nobel Prize for discoveries that accelerated the introduction of vaccines for Covid-19, she recalls her journey from Hungary and some of the setbacks on the path to the mRNA vaccines. "10 years ago I was here in October, because I was kicked out and forced to retire!" Her advice is to not to dwell on the problems: "You have to focus on the things you can change."

If a telephone interview with the other winner is published and/or a further discussion about the prize is published by the Nobel Committee, it will be added here. --editor

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Links to news articles (will be updated over the next 24 hours as new ones are published --editor) Laying the Groundwork for COVID-19 Vaccines: Dr. Drew Weissman and mRNA Technology at Penn Medicine | Penn Medicine



Nucleoside-modified mRNA-LNP Vaccines for Variants and Pancoronaviruses: Drew Weissman, MD, PhD | Penn Medicine



JCI’s Conversations with Giants in Medicine: Katalin Karikó | Journal of Clinical Investigation



• mRNA discovery that paved way for COVID-19 vaccines wins Nobel Prize in Physiology or Medicine [Science (American Association for the Advancement of Science)]

• mRNA COVID Vaccine Technology Wins 2023 Nobel Prize in Physiology or Medicine [Scientific American]

• From Covid to cancer: High hopes for Nobel mRNA vaccines [ASP (via Yahoo News)]

• Nobel in medicine goes to 2 scientists whose work enabled creation of mRNA vaccines against COVID-19 [AP News]

• Nobel Prize goes to scientists behind mRNA Covid vaccines [BBC News]

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Published at 8:30am on Monday, October 02, 2023
Author: Bobby Coggins

Read More

The Nobel Prize in Chemistry 2022

This year's Nobel Prize in Chemistry has been awarded to Carolyn R. Bertozzi, Morten Meldal, and K. Barry Sharpless for the development of click chemistry and bioorthogonal chemistry. More information, including a video of the announcement, is posted below.

Announcement of the 2022 Nobel Prize in Chemistry



A copy of the press release, illustrations, and links to where you can read more about the work that led to the prize, and articles about the work are posted below for your convenience.

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PRESS RELEASE (10-05-2022)
NOBEL ASSEMBLY

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2022 to
Carolyn R. Bertozzi
Stanford University, CA, USA

Morten Meldal
University of Copenhagen, Denmark

K. Barry Sharpless
Scripps Research, La Jolla, CA, USA

“for the development of click chemistry and bioorthogonal chemistry”

It just says click – and the molecules are coupled together

The Nobel Prize in Chemistry 2022 is about making difficult processes easier. Barry Sharpless and Morten Meldal have laid the foundation for a functional form of chemistry – click chemistry – in which molecular building blocks snap together quickly and efficiently. Carolyn Bertozzi has taken click chemistry to a new dimension and started utilising it in living organisms.

Chemists have long been driven by the desire to build increasingly complicated molecules. In pharmaceutical research, this has often involved artificially recreating natural molecules with medicinal properties. This has led to many admirable molecular constructions, but these are generally time consuming and very expensive to produce.

“This year’s Prize in Chemistry deals with not overcomplicating matters, instead working with what is easy and simple. Functional molecules can be built even by taking a straightforward route,” says Johan Åqvist, Chair of the Nobel Committee for Chemistry.

Barry Sharpless – who is now being awarded his second Nobel Prize in Chemistry – started the ball rolling. Around the year 2000, he coined the concept of click chemistry, which is a form of simple and reliable chemistry, where reactions occur quickly and unwanted by-products are avoided.

Shortly afterwards, Morten Meldal and Barry Sharpless – independently of each other – presented what is now the crown jewel of click chemistry: the copper catalysed azide-alkyne cycloaddition. This is an elegant and efficient chemical reaction that is now in widespread use. Among many other uses, it is utilised in the development of pharmaceuticals, for mapping DNA and creating materials that are more fit for purpose.

Carolyn Bertozzi took click chemistry to a new level. To map important but elusive biomolecules on the surface of cells – glycans – she developed click reactions that work inside living organisms. Her bioorthogonal reactions take place without disrupting the normal chemistry of the cell.

These reactions are now used globally to explore cells and track biological processes. Using bioorthogonal reactions, researchers have improved the targeting of cancer pharmaceuticals, which are now being tested in clinical trials.

Click chemistry and bioorthogonal reactions have taken chemistry into the era of functionalism. This is bringing the greatest benefit to humankind.

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”

Popular science background: Their functional chemistry works wonders (pdf)



Scientific Background: Click chemistry and bioorthogonal chemistry (pdf)



Carolyn R. Bertozzi, born 1966 in USA. PhD 1993 from UC Berkeley, CA, USA. Anne T. and Robert M. Bass Professor at Stanford University, CA, USA.

Morten Meldal, born 1954 in Denmark. PhD 1986 from Technical University of Denmark, Lyngby, Denmark. Professor at University of Copenhagen, Denmark.

K. Barry Sharpless, born 1941 in Philadelphia, PA, USA. PhD 1968 from Stanford University, CA, USA. W. M. Keck Professor at Scripps Research, La Jolla, CA, USA.

Prize amount: 10 million Swedish kronor, to be shared equally between the Laureates.

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INTERVIEWS "Methods to connect molecules in essentially the same way you build legos." Chemistry prize 2022.



Morten Meldal: “Reality is much more complex than we, as chemists, are able to imagine”



Carolyn Bertozzi: “When the world is in trouble, chemistry comes to the rescue”

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News Articles This section will be updated over the next several days --editor.

• 2022 Nobel Prize in Chemistry Awarded for a New Way of Building Molecules [Scientific American]

• Simple, reliable reactions that 'click' molecules together garner chemistry Nobel [Science: American Association for the Advancement of Science]

• Nobel prize for three chemists who made molecules 'click' [PHYS.ORG]

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Published at 9:35am on Wednesday, October 05, 2022
Author: Bobby Coggins

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The Nobel Prize in Physics 2022

This year's Nobel Prize in Physics has been awarded to Alain Aspect, John F. Clauser, and Anton Zeilinger for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science. More information, including a video of the announcement, is posted below.

Announcement of the 2022 Nobel Prize in Physics



A copy of the press release, illustrations, and links to where you can read more about the work that led to the prize, and articles about the work are posted below for your convenience.

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PRESS RELEASE (10-04-2022)
NOBEL ASSEMBLY

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2022 to
Alain Aspect
Université Paris-Saclay and
École Polytechnique, Palaiseau, France

John F. Clauser
J.F. Clauser & Assoc., Walnut Creek, CA, USA

Anton Zeilinger
University of Vienna, Austria

“for experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science”

Entangled states – from theory to technology

Alain Aspect, John Clauser and Anton Zeilinger have each conducted groundbreaking experiments using entangled quantum states, where two particles behave like a single unit even when they are separated. Their results have cleared the way for new technology based upon quantum information.

The ineffable effects of quantum mechanics are starting to find applications. There is now a large field of research that includes quantum computers, quantum networks and secure quantum encrypted communication.

One key factor in this development is how quantum mechanics allows two or more particles to exist in what is called an entangled state. What happens to one of the particles in an entangled pair determines what happens to the other particle, even if they are far apart.

For a long time, the question was whether the correlation was because the particles in an entangled pair contained hidden variables, instructions that tell them which result they should give in an experiment. In the 1960s, John Stewart Bell developed the mathematical inequality that is named after him. This states that if there are hidden variables, the correlation between the results of a large number of measurements will never exceed a certain value. However, quantum mechanics predicts that a certain type of experiment will violate Bell’s inequality, thus resulting in a stronger correlation than would otherwise be possible.

John Clauser developed John Bell’s ideas, leading to a practical experiment. When he took the measurements, they supported quantum mechanics by clearly violating a Bell inequality. This means that quantum mechanics cannot be replaced by a theory that uses hidden variables.

Some loopholes remained after John Clauser’s experiment. Alain Aspect developed the setup, using it in a way that closed an important loophole. He was able to switch the measurement settings after an entangled pair had left its source, so the setting that existed when they were emitted could not affect the result.

Using refined tools and long series of experiments, Anton Zeilinger started to use entangled quantum states. Among other things, his research group has demonstrated a phenomenon called quantum teleportation, which makes it possible to move a quantum state from one particle to one at a distance.

“It has become increasingly clear that a new kind of quantum technology is emerging. We can see that the laureates’ work with entangled states is of great importance, even beyond the fundamental questions about the interpretation of quantum mechanics,” says Anders Irbäck, Chair of the Nobel Committee for Physics.

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”.

Read more about this year’s prize

Popular science background: [How entanglement has become a powerful tool (pdf)]

Scientific Background: [“For experiments with entangled photons, establishing the violation of Bell inequalities and pioneering quantum information science” (pdf)]

Alain Aspect, born 1947 in Agen, France. PhD 1983 from Paris-Sud University, Orsay, France.
Professor at Université Paris-Saclay and École Polytechnique, Palaiseau, France.


John F. Clauser, born 1942 in Pasadena, CA, USA. PhD 1969 from Columbia University, New
York, USA. Research Physicist, J.F. Clauser & Assoc., Walnut Creek, CA, USA.

Anton Zeilinger, born 1945 in Ried im Innkreis, Austria. PhD 1971 from University of Vienna, Austria. Professor at University of Vienna, Austria.

Prize amount: 10 million Swedish kronor, to be shared equally between the laureates.

Nobel Prize® is a registered trademark of the Nobel Foundation.

END PRESS RELEASE

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Explaining the Theory That Given to 2022 Nobel Prize in Physics
(excerpt from the announcement)

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News Articles This section will be updated over the next several days --editor.

• Explorers of Quantum Entanglement Win 2022 Nobel Prize in Physics [Scientific American]

• Three scientists share Nobel Prize in Physics for work in quantum mechanics [PHYS.ORG]

• Nobel honors physicists who proved quantum weirdness can't be explained away but can be used [Science: American Association for the Advancement of Science]

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Background Information

The EPR Paradox and Bell's inequality explained simply



These Experiments Could Prove Einstein Wrong

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Published at 8:30am on Tuesday, October 04, 2022
Author: Bobby Coggins

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The Nobel Prize in Physiology or Medicine 2022

This year’s Nobel Prize in physiology or medicine has been awarded to Swedish scientist Svante Paabo for his discoveries on human evolution. More information, including a video of the announcement, is posted below.

Announcement of the 2022 Nobel Prize in Physiology or Medicine

A video of a telephone interview with Dr Pääbo and an interview discussing the impact of his work are embedded below the press release. 

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PRESS RELEASE (10-03-2022)
NOBEL ASSEMBLY

The Nobel Assembly at Karolinska Institutet

has today decided to award

the 2022 Nobel Prize in Physiology or Medicine

to

Svante Pääbo

for his discoveries concerning the genomes of extinct hominins and human evolution (Links to papers, news articles, and embedded videos added by Macon Media)

Humanity has always been intrigued by its origins. Where do we come from, and how are we related to those who came before us? What makes us, Homo sapiens, different from other hominins?

Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.

Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.

Where do we come from?

The question of our origin and what makes us unique has engaged humanity since ancient times. Paleontology and archeology are important for studies of human evolution. Research provided evidence that the anatomically modern human, Homo sapiens, first appeared in Africa approximately 300,000 years ago, while our closest known relatives, Neanderthals, developed outside Africa and populated Europe and Western Asia from around 400,000 years until 30,000 years ago, at which point they went extinct. About 70,000 years ago, groups of Homo sapiens migrated from Africa to the Middle East and, from there they spread to the rest of the world. Homo sapiens and Neanderthals thus coexisted in large parts of Eurasia for tens of thousands of years. But what do we know about our relationship with the extinct Neanderthals? Clues might be derived from genomic information. By the end of the 1990’s, almost the entire human genome had been sequenced. This was a considerable accomplishment, which allowed subsequent studies of the genetic relationship between different human populations. However, studies of the relationship between present-day humans and the extinct Neanderthals would require the sequencing of genomic DNA recovered from archaic specimens.

A seemingly impossible task

Early in his career, Svante Pääbo became fascinated by the possibility of utilizing modern genetic methods to study the DNA of Neanderthals. However, he soon realized the extreme technical challenges, because with time DNA becomes chemically modified and degrades into short fragments. After thousands of years, only trace amounts of DNA are left, and what remains is massively contaminated with DNA from bacteria and contemporary humans (Figure 1). As a postdoctoral student with Allan Wilson, a pioneer in the field of evolutionary biology, Pääbo started to develop methods to study DNA from Neanderthals, an endeavor that lasted several decades.

Figure 1. DNA is localized in two different compartments in the cell. Nuclear DNA harbors most of the genetic information, while the much smaller mitochondrial genome is present in thousands of copies. After death, DNA is degraded over time and ultimately only small amounts remain. It also becomes contaminated with DNA from e.g. bacteria and contemporary humans.

In 1990, Pääbo was recruited to University of Munich, where, as a newly appointed Professor, he continued his work on archaic DNA. He decided to analyze DNA from Neanderthal mitochondria – organelles in cells that contain their own DNA. The mitochondrial genome is small and contains only a fraction of the genetic information in the cell, but it is present in thousands of copies, increasing the chance of success. With his refined methods, Pääbo managed to sequence a region of mitochondrial DNA from a 40,000-year-old piece of bone. Thus, for the first time, we had access to a sequence from an extinct relative. Comparisons with contemporary humans and chimpanzees demonstrated that Neanderthals were genetically distinct.

Sequencing the Neanderthal genome

As analyses of the small mitochondrial genome gave only limited information, Pääbo now took on the enormous challenge of sequencing the Neanderthal nuclear genome. At this time, he was offered the chance to establish a Max Planck Institute in Leipzig, Germany. At the new Institute, Pääbo and his team steadily improved the methods to isolate and analyze DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA highly efficient. Pääbo also engaged several critical collaborators with expertise on population genetics and advanced sequence analyses. His efforts were successful. Pääbo accomplished the seemingly impossible and could publish the first Neanderthal genome sequence in 2010. Comparative analyses demonstrated that the most recent common ancestor of Neanderthals and Homo sapiens lived around 800,000 years ago.

Figure 2. A. Pääbo extracted DNA from bone specimens from extinct hominins. He first obtained a bone fragment from Neandertal in Germany, the site that gave name to the Neanderthals. Later, he used a finger bone from the Denisova Cave in southern Siberia, the site that gave name to Denisovans. B. Phylogenetic tree showing the evolution and relationship between Homo sapiens and the extinct hominins. The phylogenetic tree also illustrates the gene flows discovered by Pääbo.

Pääbo and his co-workers could now investigate the relationship between Neanderthals and modern-day humans from different parts of the world. Comparative analyses showed that DNA sequences from Neanderthals were more similar to sequences from contemporary humans originating from Europe or Asia than to contemporary humans originating from Africa. This means that Neanderthals and Homo sapiens interbred during their millennia of coexistence. In modern day humans with European or Asian descent, approximately 1-4% of the genome originates from the Neanderthals (Figure 2).

A sensational discovery: Denisova

In 2008, a 40,000-year-old fragment from a finger bone was discovered in the Denisova cave in the southern part of Siberia. The bone contained exceptionally well-preserved DNA, which Pääbo’s team sequenced. The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans. Pääbo had discovered a previously unknown hominin, which was given the name Denisova. Comparisons with sequences from contemporary humans from different parts of the world showed that gene flow had also occurred between Denisova and Homo sapiens. This relationship was first seen in populations in Melanesia and other parts of South East Asia, where individuals carry up to 6% Denisova DNA.

Pääbo’s discoveries have generated new understanding of our evolutionary history. At the time when Homo sapiens migrated out of Africa, at least two extinct hominin populations inhabited Eurasia. Neanderthals lived in western Eurasia, whereas Denisovans populated the eastern parts of the continent. During the expansion of Homo sapiens outside Africa and their migration east, they not only encountered and interbred with Neanderthals, but also with Denisovans (Figure 3).

Paleogenomics and its relevance

Through his groundbreaking research, Svante Pääbo established an entirely new scientific discipline, paleogenomics. Following the initial discoveries, his group has completed analyses of several additional genome sequences from extinct hominins. Pääbo’s discoveries have established a unique resource, which is utilized extensively by the scientific community to better understand human evolution and migration. New powerful methods for sequence analysis indicate that archaic hominins may also have mixed with Homo sapiens in Africa. However, no genomes from extinct hominins in Africa have yet been sequenced due to accelerated degradation of archaic DNA in tropical climates.

Thanks to Svante Pääbo’s discoveries, we now understand that archaic gene sequences from our extinct relatives influence the physiology of present-day humans. One such example is the Denisovan version of the gene EPAS1, which confers an advantage for survival at high altitude and is common among present-day Tibetans. Other examples are Neanderthal genes that affect our immune response to different types of infections.

Figure 3. Pääbo’s discoveries have provided important information on how the world was populated at the time when Homo sapiens migrated out of Africa and spread to the rest of the world. Neanderthals lived in the west and Denisovans in the east on the Eurasian continent. Interbreeding occurred when Homo sapiens spread across the continent, leaving traces that remain in our DNA.

What makes us uniquely human?

Homo sapiens is characterized by its unique capacity to create complex cultures, advanced innovations and figurative art, as well as by the ability to cross open water and spread to all parts of our planet (Figure 4). Neanderthals also lived in groups and had big brains (Figure 4). They also utilized tools, but these developed very little during hundreds of thousands of years. The genetic differences between Homo sapiens and our closest extinct relatives were unknown until they were identified through Pääbo’s seminal work. Intense ongoing research focuses on analyzing the functional implications of these differences with the ultimate goal of explaining what makes us uniquely human.

Figure 4. Pääbo’s seminal work provides a basis for explaining what makes us uniquely human.

Key publications

Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. Neandertal DNA sequences and the origin of modern humans. Cell. 1997:90:19-30.
[LINK TO PAPER]

Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Ž, Gušic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PLF, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010:328:710-722.
[LINK TO PAPER]

Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Pääbo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature. 2010:464:894-897.
[LINK TO PAPER]

Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010:468:1053-1060.
[LINK TO PAPER]

Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012:338:222-226.
[LINK TO PAPER]

Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelso J, Pääbo S. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 2014:505: 43-49.
[LINK TO PAPER (PDF)]

>Svante Pääbo was born 1955 in Stockholm, Sweden. He defended his PhD thesis in 1986 at Uppsala University and was a postdoctoral fellow at University of Zürich, Switzerland and later at University of California, Berkeley, USA. He became Professor at the University of Munich, Germany in 1990. In 1999 he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany where he is still active. He also holds a position as adjunct Professor at Okinawa Institute of Science and Technology, Japan.

Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén

The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humankind.


Nobel Prize® is the registered trademark of the Nobel Foundation

Svante Pääbo: “There were almost always other types of humans around”



Professor Nils-Göran Larsson, Chair of the Nobel Committee

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Links to news articles (will be updated over the next 24 hours as new ones are published --editor)

• The Nobel Prize in Physiology or Medicine [Nobel Prize Committee]

• Svante Pääbo Wins Nobel Prize In Medicine For Discoveries On Human Evolution [Huff Post]

• Nobel win for Swede who unlocked secrets of Neanderthal DNA [AP News]

• Ancient DNA hunter who sequenced first Neanderthal genome wins Nobel Prize for medicine [CNN]

• Nobel Prize in Medicine Awarded to Swedish Scientist Svante Pääbo for Research on Evolution [Time Magazine]

• Genetics of human evolution wins 2022 Nobel Prize in physiology or medicine [Science News]

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Published at 10:00am on Monday, October 03, 2022
Author: Bobby Coggins

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