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Chemistry Nobelist Carolyn Bertozzi’s years at UC Berkeley
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 12/8/2022
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Carolyn R. Bertozzi: The Bioorthogonal Chemistry Journey, from Laboratory to Life Morten Meldal: Molecular Click Adventures, a Leap from Shoulders of Giants K. Barry Sharpless: Click Chemistry: the Certainty of Chance
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.
Carolyn Bertozzi as a young professor at UC Berkeley. (Photo courtesy of College of Chemistry)
Carolyn Bertozzi, a professor at Stanford University who today shared the 2022 Nobel Prize in Chemistry, spent her formative and most creative years at UC Berkeley.
After graduating from Harvard University in 1988, she earned her Ph.D. in chemistry from Berkeley in 1993 and, following postdoctoral and faculty positions elsewhere, returned to join the chemistry faculty and Berkeley Lab in 1996.
For 19 years, until 2015 — the year she left to help lead Stanford’s Sarafan ChEM-H institute — she developed at Berkeley the chemical biology techniques for which she received the Nobel Prize. She calls these techniques bioorthogonal chemistry, building off the “click chemistry” developed by her Nobel Prize co-winners, K. Barry Sharpless of Scripps Research in La Jolla, California, and Morten Meldal of the University of Copenhagen in Denmark.
“Carolyn Bertozzi is a true trailblazer in chemical biology,” said Doug Clark, dean of the College of Chemistry. “Her lab is among the most prolific in the field, consistently producing innovative and enabling chemical approaches, inspired by organic synthesis, for the study of complex biomolecules in living cells. Carolyn’s work and spirit embody what is best about the scientific tradition and history of the College of Chemistry and of UC Berkeley.”
Carolyn Bertozzi, now the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences and a professor of chemistry at Stanford University. (Photo courtesy of Stanford University)
During a video press conference this morning from Stanford, Bertozzi, 55, described bioorthogonal chemistry as chemical reactions “not interacting with or interfering with biology.”
“What that means in practice is that we basically develop pairs of chemical groups, and those pairs of groups are perfectly suited for each other,” she said. “And when they encounter each other, they want to react and form a bond, and they love each other so much that you can surround those chemical groups with thousands of other chemicals — that’s what you have in biological systems, in your cells, in your body, there’s thousands of chemicals — but these two chemicals that are bioorthogonal will ignore all of that. And they’ll find each other and form a bond with each other, do chemistry with each other.”
Bertozzi’s rationale for developing these reactions was to study the sugars that coat the outside of cells — a field called glycobiology — that has been a passion of hers since her graduate student days at Berkeley. At Berkeley, she worked in the lab of Mark Bednarski, a young assistant professor and a rising star in the field of chemical biology, at the time a relatively new field in which the biochemical processes inside cells are manipulated and studied using techniques of organic chemistry.
In a 2011 interview, Bertozzi discussed the role Berkeley played in her career.
“I credit the UC Berkeley environment for catalyzing my interests in chemical biology and glycobiology from the outset, as I first learned about the opportunities in these fields as a graduate student in this very department,” she said. “I was encouraged to join the lab of a new professor, Mark Bednarski, and he introduced me to the chemistry and biology of sugars. I have been enraptured by this still-burgeoning area of science ever since, in light of the critical roles that sugars play in cell signaling, organ development, immunobiology and in numerous diseases.”
A friend and former colleague of Bertozzi’s at Berkeley, Matt Francis, now chair of the Department of Chemistry, was one of the first to congratulate Bertozzi today after the streamed announcement from Stockholm at 2:45 a.m. PDT, which he was watching. He immediately texted her congratulations.
Carolyn Bertozzi in 2001. (Photo credit: Peg Skorpinski)
“As soon as I heard her name in Swedish, I sent it, and I got an emoji back immediately — the shocked face emoji,” he said. “She’s a total rock star, and this is well deserved.”
Francis came to Berkeley in 2001, when Bertozzi was already well known for her research, and she was a critical academic mentor, he said.
“She did more than just do great science. She really mentored a lot of us who are on the faculty now and helped us get our groups off the ground and was always there to talk to us,” he said. “She was just a great colleague.”
She is equally known for mentoring students at both Berkeley and Stanford. She and Berkeley chemistry colleague Judith Klinman also were instrumental in establishing a chemical biology major within the chemistry department, which currently enrolls half the 480 undergraduates majoring in chemistry in the department.
During the Stanford press conference, Bertozzi explained what led to her Nobel Prize-winning work.
“Bioorthogonal chemistry was a tool that my lab created originally to study cell surface sugars — in fact, to image cell surface sugars using microscopes,” she said. “But then, it turned out to be so useful just as a platform for studying biology that lots of other labs picked up on it and started using those same chemistries to study other molecules, like proteins DNA and RNA. And they, and it turns out you, can study these molecules in live cells and in laboratory animals. And the most exciting development is now there’s a pharmaceutical company doing these chemistries inside the body of human cancer patients as a means to deliver drugs to cancers. So, the field has really progressed a long way in the last 25 years, and it’s very exciting for me to see this.”
She emphasized that her work built on that of co-winners Sharpless and Meldal.
“Before the advent of bioorthogonal chemistry and the related chemistry that professors Sharpless and Meldal developed, which they call click chemistry, there was really no way to study certain biological processes. They were just invisible to the scientists,” she said. “But these chemistries make those processes visible, and we have benefited from that — specifically, to study cell surface sugars.”
A photo of Carolyn Bertozzi taken the morning of Oct. 5, 2022, shortly after she heard that she had won the 2022 Nobel Prize in Chemistry. (Image credit: Andrew Brodhead)
The click chemistry reactions Sharpless and Meldal developed involved copper, however, which is often toxic to living cells. According to Francis, Bertozzi found a novel way around using copper.
“Carolyn’s lab came up with a way around it where they built strain into one of the molecules. In other words, they spring-loaded that molecule so it made it much more readily reactive without the copper,” he said. “And that is now what most people use to label live cell surfaces. It’s called strain promoted click chemistry. She really changed the way people think about the chemistry that we could do in a living organism.”
Francis said that copper-based click chemistry is arguably still faster and is used today in situations without living cells, but Bertozzi’s copperless click chemistry — as well as her previous work on the Bertozzi-Staudinger ligation — is the only technique that works in living cells.
Much of her research while at Berkeley was done in collaboration with scientists at Berkeley Lab. She was one of six Berkeley Lab scientists who led the establishment of the Molecular Foundry, a nanoscience research facility that provides scientists from around the world with access to cutting-edge expertise and instrumentation, and she served as its director from 2006 until 2010.
“It was a privilege to watch how the success of her (Bertozzi’s) discoveries unfolded here on the Berkeley campus and beyond,” said Clark, who also is a faculty scientist at Berkeley Lab. “On behalf of the College of Chemistry community, we extend our heartiest congratulations to Carolyn for her spectacular work and this well-deserved honor.”
The Human Genome Gets Fully Sequenced: A Simplistic Take on Century Long Effort
Curator: Stephen J. Williams, PhD
Ever since the hard work by Rosalind Franklin to deduce structures of DNA and the coincidental work by Francis Crick and James Watson who modeled the basic building blocks of DNA, DNA has been considered as the basic unit of heredity and life, with the “Central Dogma” (DNA to RNA to Protein) at its core. These were the discoveries in the early twentieth century, and helped drive the transformational shift of biological experimentation, from protein isolation and characterization to cloning protein-encoding genes to characterizing how the genes are expressed temporally, spatially, and contextually.
Rosalind Franklin, who’s crystolagraphic data led to determination of DNA structure. Shown as 1953 Time cover as Time person of the Year
Dr Francis Crick and James Watson in front of their model structure of DNA
Up to this point (1970s-mid 80s) , it was felt that genetic information was rather static, and the goal was still to understand and characterize protein structure and function while an understanding of the underlying genetic information was more important for efforts like linkage analysis of genetic defects and tools for the rapidly developing field of molecular biology. But the development of the aforementioned molecular biology tools including DNA cloning, sequencing and synthesis, gave scientists the idea that a whole recording of the human genome might be possible and worth the effort.
How the Human Genome Project Expanded our View of Genes Genetic Material and Biological Processes
The Human Genome Project (HGP) refers to the international 13-year effort, formally begun in October 1990 and completed in 2003, to discover all the estimated 20,000-25,000 human genes and make them accessible for further biological study. Another project goal was to determine the complete sequence of the 3 billion DNA subunits (bases in the human genome). As part of the HGP, parallel studies were carried out on selected model organisms such as the bacterium E. coli and the mouse to help develop the technology and interpret human gene function. The DOE Human Genome Program and the NIH National Human Genome Research Institute (NHGRI) together sponsored the U.S. Human Genome Project.
Please see the following for goals, timelines, and funding for this project
Timeline: Major Events in the Human Genome Project
It is interesting to note that multiple government legislation is credited for the funding of such a massive project including
Project Enabling Legislation
The Atomic Energy Act of 1946 (P.L. 79-585) provided the initial charter for a comprehensive program of research and development related to the utilization of fissionable and radioactive materials for medical, biological, and health purposes.
The Atomic Energy Act of 1954 (P.L. 83-706) further authorized the AEC “to conduct research on the biologic effects of ionizing radiation.”
The Energy Reorganization Act of 1974 (P.L. 93-438) provided that responsibilities of the Energy Research and Development Administration (ERDA) shall include “engaging in and supporting environmental, biomedical, physical, and safety research related to the development of energy resources and utilization technologies.”
The Federal Non-nuclear Energy Research and Development Act of 1974 (P.L. 93-577) authorized ERDA to conduct a comprehensive non-nuclear energy research, development, and demonstration program to include the environmental and social consequences of the various technologies.
The DOE Organization Act of 1977 (P.L. 95-91) mandated the Department “to assure incorporation of national environmental protection goals in the formulation and implementation of energy programs; and to advance the goal of restoring, protecting, and enhancing environmental quality, and assuring public health and safety,” and to conduct “a comprehensive program of research and development on the environmental effects of energy technology and program.”
It should also be emphasized that the project was not JUST funded through NIH but also Department of Energy
For a great read on Dr. Craig Ventnor with interviews with the scientist see Dr. Larry Bernstein’s excellent post The Human Genome Project
By 2003 we had gained much information about the structure of DNA, genes, exons, introns and allowed us to gain more insights into the diversity of genetic material and the underlying protein coding genes as well as many of the gene-expression regulatory elements. However there was much uninvestigated material dispersed between genes, the then called “junk DNA” and, up to 2003 not much was known about the function of this ‘junk DNA’. In addition there were two other problems:
The reference DNA used was actually from one person (Craig Ventor who was the lead initiator of the project)
Multiple gaps in the DNA sequence existed, and needed to be filled in
It is important to note that a tremendous amount of diversity of protein has been realized from both transcriptomic and proteomic studies. Although about 20 to 25,000 coding genes exist the human proteome contains about 600,000 proteoforms (due to alternative splicing, posttranslational modifications etc.)
This expansion of the proteoform via alternate splicing into isoforms, gene duplication to paralogs has been shown to have major effects on, for example, cellular signaling pathways (1)
However just recently it has been reported that the FULL human genome has been sequenced and is complete and verified. This was the focus of a recent issue in the journal Science.
Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion–base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.
The current human reference genome was released by the Genome Reference Consortium (GRC) in 2013 and most recently patched in 2019 (GRCh38.p13) (1). This reference traces its origin to the publicly funded Human Genome Project (2) and has been continually improved over the past two decades. Unlike the competing Celera effort (3) and most modern sequencing projects based on “shotgun” sequence assembly (4), the GRC assembly was constructed from sequenced bacterial artificial chromosomes (BACs) that were ordered and oriented along the human genome by means of radiation hybrid, genetic linkage, and fingerprint maps. However, limitations of BAC cloning led to an underrepresentation of repetitive sequences, and the opportunistic assembly of BACs derived from multiple individuals resulted in a mosaic of haplotypes. As a result, several GRC assembly gaps are unsolvable because of incompatible structural polymorphisms on their flanks, and many other repetitive and polymorphic regions were left unfinished or incorrectly assembled (5).
Fig. 1. Summary of the complete T2T-CHM13 human genome assembly. (A) Ideogram of T2T-CHM13v1.1 assembly features. For each chromosome (chr), the following information is provided from bottom to top: gaps and issues in GRCh38 fixed by CHM13 overlaid with the density of genes exclusive to CHM13 in red; segmental duplications (SDs) (42) and centromeric satellites (CenSat) (30); and CHM13 ancestry predictions (EUR, European; SAS, South Asian; EAS, East Asian; AMR, ad-mixed American). Bottom scale is measured in Mbp. (B and C) Additional (nonsyntenic) bases in the CHM13 assembly relative to GRCh38 per chromosome, with the acrocentrics highlighted in black (B) and by sequence type (C). (Note that the CenSat and SD annotations overlap.) RepMask, RepeatMasker. (D) Total nongap bases in UCSC reference genome releases dating back to September 2000 (hg4) and ending with T2T-CHM13 in 2021. Mt/Y/Ns, mitochondria, chrY, and gaps.
Note in Figure 1D the exponential growth in genetic information.
Also very important is the ability to determine all the paralogs, isoforms, areas of potential epigenetic regulation, gene duplications, and transposable elements that exist within the human genome.
Analyses and resources
A number of companion studies were carried out to characterize the complete sequence of a human genome, including comprehensive analyses of centromeric satellites (30), segmental duplications (42), transcriptional (49) and epigenetic profiles (29), mobile elements (49), and variant calls (25). Up to 99% of the complete CHM13 genome can be confidently mapped with long-read sequencing, opening these regions of the genome to functional and variational analysis (23) (fig. S38 and table S14). We have produced a rich collection of annotations and omics datasets for CHM13—including RNA sequencing (RNA-seq) (30), Iso-seq (21), precision run-on sequencing (PRO-seq) (49), cleavage under targets and release using nuclease (CUT&RUN) (30), and ONT methylation (29) experiments—and have made these datasets available via a centralized University of California, Santa Cruz (UCSC), Assembly Hub genome browser (54).
To highlight the utility of these genetic and epigenetic resources mapped to a complete human genome, we provide the example of a segmentally duplicated region of the chromosome 4q subtelomere that is associated with facioscapulohumeral muscular dystrophy (FSHD) (55). This region includes FSHD region gene 1 (FRG1), FSHD region gene 2 (FRG2), and an intervening D4Z4 macrosatellite repeat containing the double homeobox 4 (DUX4) gene that has been implicated in the etiology of FSHD (56). Numerous duplications of this region throughout the genome have complicated past genetic analyses of FSHD.
The T2T-CHM13 assembly reveals 23 paralogs of FRG1 spread across all acrocentric chromosomes as well as chromosomes 9 and 20 (Fig. 5A). This gene appears to have undergone recent amplification in the great apes (57), and approximate locations of FRG1 paralogs were previously identified by FISH (58). However, only nine FRG1 paralogs are found in GRCh38, hampering sequence-based analysis.
Future of the human reference genome
The T2T-CHM13 assembly adds five full chromosome arms and more additional sequence than any genome reference release in the past 20 years (Fig. 1D). This 8% of the genome has not been overlooked because of a lack of importance but rather because of technological limitations. High-accuracy long-read sequencing has finally removed this technological barrier, enabling comprehensive studies of genomic variation across the entire human genome, which we expect to drive future discovery in human genomic health and disease. Such studies will necessarily require a complete and accurate human reference genome.
CHM13 lacks a Y chromosome, and homozygous Y-bearing CHMs are nonviable, so a different sample type will be required to complete this last remaining chromosome. However, given its haploid nature, it should be possible to assemble the Y chromosome from a male sample using the same methods described here and supplement the T2T-CHM13 reference assembly with a Y chromosome as needed.
Extending beyond the human reference genome, large-scale resequencing projects have revealed genomic variation across human populations. Our reanalyses of the 1KGP (25) and SGDP (42) datasets have already shown the advantages of T2T-CHM13, even for short-read analyses. However, these studies give only a glimpse of the extensive structural variation that lies within the most repetitive regions of the genome assembled here. Long-read resequencing studies are now needed to comprehensively survey polymorphic variation and reveal any phenotypic associations within these regions.
Although CHM13 represents a complete human haplotype, it does not capture the full diversity of human genetic variation. To address this bias, the Human Pangenome Reference Consortium (59) has joined with the T2T Consortium to build a collection of high-quality reference haplotypes from a diverse set of samples. Ideally, all genomes could be assembled at the quality achieved here, but automated T2T assembly of diploid genomes presents a difficult challenge that will require continued development. Until this goal is realized, and any human genome can be completely sequenced without error, the T2T-CHM13 assembly represents a more complete, representative, and accurate reference than GRCh38.
This paper was the focus of a Time article and their basis for making the lead authors part of their Time 100 people of the year.
The first human genome was mapped in 2001 as part of the Human Genome Project, but researchers knew it was neither complete nor completely accurate. Now, scientists have produced the most completely sequenced human genome to date, filling in gaps and correcting mistakes in the previous version.
The sequence is the most complete reference genome for any mammal so far. The findings from six new papers describing the genome, which were published in Science, should lead to a deeper understanding of human evolution and potentially reveal new targets for addressing a host of diseases.
A more precise human genome
“The Human Genome Project relied on DNA obtained through blood draws; that was the technology at the time,” says Adam Phillippy, head of genome informatics at the National Institutes of Health’s National Human Genome Research Institute (NHGRI) and senior author of one of the new papers. “The techniques at the time introduced errors and gaps that have persisted all of these years. It’s nice now to fill in those gaps and correct those mistakes.”
“We always knew there were parts missing, but I don’t think any of us appreciated how extensive they were, or how interesting,” says Michael Schatz, professor of computer science and biology at Johns Hopkins University and another senior author of the same paper.
The work is the result of the Telomere to Telomere consortium, which is supported by NHGRI and involves genetic and computational biology experts from dozens of institutes around the world. The group focused on filling in the 8% of the human genome that remained a genetic black hole from the first draft sequence. Since then, geneticists have been trying to add those missing portions bit by bit. The latest group of studies identifies about an entire chromosome’s worth of new sequences, representing 200 million more base pairs (the letters making up the genome) and 1,956 new genes.
NOTE: In 2001 many scientists postulated there were as much as 100,000 coding human genes however now we understand there are about 20,000 to 25,000 human coding genes. This does not however take into account the multiple diversity obtained from alternate splicing, gene duplications, SNPs, and chromosomal rearrangements.
Scientists were also able to sequence the long stretches of DNA that contained repeated sequences, which genetic experts originally thought were similar to copying errors and dismissed as so-called “junk DNA”. These repeated sequences, however, may play roles in certain human diseases. “Just because a sequence is repetitive doesn’t mean it’s junk,” says Eichler. He points out that critical genes are embedded in these repeated regions—genes that contribute to machinery that creates proteins, genes that dictate how cells divide and split their DNA evenly into their two daughter cells, and human-specific genes that might distinguish the human species from our closest evolutionary relatives, the primates. In one of the papers, for example, researchers found that primates have different numbers of copies of these repeated regions than humans, and that they appear in different parts of the genome.
“These are some of the most important functions that are essential to live, and for making us human,” says Eichler. “Clearly, if you get rid of these genes, you don’t live. That’s not junk to me.”
Deciphering what these repeated sections mean, if anything, and how the sequences of previously unsequenced regions like the centromeres will translate to new therapies or better understanding of human disease, is just starting, says Deanna Church, a vice president at Inscripta, a genome engineering company who wrote a commentary accompanying the scientific articles. Having the full sequence of a human genome is different from decoding it; she notes that currently, of people with suspected genetic disorders whose genomes are sequenced, about half can be traced to specific changes in their DNA. That means much of what the human genome does still remains a mystery.
The investigators in the Telomere to Telomere Consortium made the Time 100 People of the Year.
Michael Schatz, Karen Miga, Evan Eichler, and Adam Phillippy
Illustration by Brian Lutz for Time (Source Photos: Will Kirk—Johns Hopkins University; Nick Gonzales—UC Santa Cruz; Patrick Kehoe; National Human Genome Research Institute)
BY JENNIFER DOUDNA
MAY 23, 2022 6:08 AM EDT
Ever since the draft of the human genome became available in 2001, there has been a nagging question about the genome’s “dark matter”—the parts of the map that were missed the first time through, and what they contained. Now, thanks to Adam Phillippy, Karen Miga, Evan Eichler, Michael Schatz, and the entire Telomere-to-Telomere Consortium (T2T) of scientists that they led, we can see the full map of the human genomic landscape—and there’s much to explore.
In the scientific community, there wasn’t a consensus that mapping these missing parts was necessary. Some in the field felt there was already plenty to do using the data in hand. In addition, overcoming the technical challenges to getting the missing information wasn’t possible until recently. But the more we learn about the genome, the more we understand that every piece of the puzzle is meaningful.
I admire the
T2T group’s willingness to grapple with the technical demands of this project and their persistence in expanding the genome map into uncharted territory. The complete human genome sequence is an invaluable resource that may provide new insights into the origin of diseases and how we can treat them. It also offers the most complete look yet at the genetic script underlying the very nature of who we are as human beings.
Doudna is a biochemist and winner of the 2020 Nobel Prize in Chemistry
P. Scalia, A. Giordano, C. Martini, S. J. Williams, Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer. Biomolecules10, (Nov 30, 2020).
Benjamin List Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
David W.C. MacMillan Princeton University, USA
“for the development of asymmetric organocatalysis”
Meet UC’s 2021 Nobelists
Three UC-affiliated scientists have won Nobel Prizes this year: UCSF professor David Julius, UCLA alum Ardem Patapoutian and UC Irvine alum David W.C. MacMillan.
Three UC-affiliated scientists were awarded Nobel Prizes this week. UC San Francisco professor David Julius shared the Nobel Prize in physiology or medicine with UCLA alum Ardem Patapoutian. UC Irvine alum David W.C. MacMillan won in chemistry.
From: University of California <webeditor@ucop.edu> Reply-To: University of California <webeditor@ucop.edu> Date: Friday, October 8, 2021 at 1:02 PM To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu> Subject: 3 UC Nobel Prize winners!
Building molecules is a difficult art. Benjamin List and David MacMillan are awarded the Nobel Prize in Chemistry 2021 for their development of a precise new tool for molecular construction: organocatalysis. This has had a great impact on pharmaceutical research, and has made chemistry greener.
Many research areas and industries are dependent on chemists’ ability to construct molecules that can form elastic and durable materials, store energy in batteries or inhibit the progression of diseases. This work requires catalysts, which are substances that control and accelerate chemical reactions, without becoming part of the final product. For example, catalysts in cars transform toxic substances in exhaust fumes to harmless molecules. Our bodies also contain thousands of catalysts in the form of enzymes, which chisel out the molecules necessary for life.
Catalysts are thus fundamental tools for chemists, but researchers long believed that there were, in principle, just two types of catalysts available: metals and enzymes. Benjamin List and David MacMillan are awarded the Nobel Prize in Chemistry 2021 because in 2000 they, independent of each other, developed a third type of catalysis. It is called asymmetric organocatalysis and builds upon small organic molecules.
“This concept for catalysis is as simple as it is ingenious, and the fact is that many people have wondered why we didn’t think of it earlier,” says Johan Åqvist, who is chair of the Nobel Committee for Chemistry.
Organic catalysts have a stable framework of carbon atoms, to which more active chemical groups can attach. These often contain common elements such as oxygen, nitrogen, sulphur or phosphorus. This means that these catalysts are both environmentally friendly and cheap to produce.
The rapid expansion in the use of organic catalysts is primarily due to their ability to drive asymmetric catalysis. When molecules are being built, situations often occur where two different molecules can form, which – just like our hands – are each other’s mirror image. Chemists will often only want one of these, particularly when producing pharmaceuticals.
Organocatalysis has developed at an astounding speed since 2000. Benjamin List and David MacMillan remain leaders in the field, and have shown that organic catalysts can be used to drive multitudes of chemical reactions. Using these reactions, researchers can now more efficiently construct anything from new pharmaceuticals to molecules that can capture light in solar cells. In this way, organocatalysts are bringing the greatest benefit to humankind.
Benjamin List, born 1968 in Frankfurt, Germany. Ph.D. 1997 from Goethe University Frankfurt, Germany. Director of the Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany.
David W.C. MacMillan, born 1968 in Bellshill, UK. Ph.D. 1996 from University of California, Irvine, USA. Professor at Princeton University, USA.
The Nobel Prize in Physiology or Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch.”
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 12/18/2021
Nobel Prize Lecture in Stockholm, Sweden, 12/7/2021
UPDATED on 10/14/2021
49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research
for their remarkable contributions to our understanding of the sensations of temperature, pain and touch
David Julius – 49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research
for their remarkable contributions to our understanding of the sensations of temperature, pain and touch
(2021 Nobel Prize) Morris Herzstein Chair in Molecular Biology and Medicine Professor and Chair, Department of Physiology School of Medicine The University of California, San Francisco San Francisco, CA USA
Ardem Patapoutian – 49th (2019) – Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research for their remarkable contributions to our understanding of the sensations of temperature, pain and touch
(2021 Nobel Prize) Investigator, Howard Hughes Medical Institute Professor, Department of Neuroscience The Scripps Research Institute La Jolla, CA USA
David Julius was born in 1955 in New York, USA. He received a Ph.D. in 1984 from University of California, Berkeley and was a postdoctoral fellow at Columbia University, in New York. David Julius was recruited to the University of California, San Francisco in 1989 where he is now Professor.
Ardem Patapoutian was born in 1967 in Beirut, Lebanon. In his youth, he moved from a war-torn Beirut to Los Angeles, USA and received a Ph.D. in 1996 from California Institute of Technology, Pasadena, USA. He was a postdoctoral fellow at the University of California, San Francisco. Since 2000, he is a scientist at Scripps Research, La Jolla, California where he is now Professor. He is a Howard Hughes Medical Institute Investigator since 2014.
Meet UC’s 2021 Nobelists
Three UC-affiliated scientists have won Nobel Prizes this year: UCSF professor David Julius, UCLA alum Ardem Patapoutian and UC Irvine alum David W.C. MacMillan.
Three UC-affiliated scientists were awarded Nobel Prizes this week. UC San Francisco professor David Julius shared the Nobel Prize in physiology or medicine with UCLA alum Ardem Patapoutian. UC Irvine alum David W.C. MacMillan won in chemistry.
From: University of California <webeditor@ucop.edu> Reply-To: University of California <webeditor@ucop.edu> Date: Friday, October 8, 2021 at 1:02 PM To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu> Subject: 3 UC Nobel Prize winners!
Key publications
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997:389:816-824.
Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998:21:531-543.
Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000:288:306-313
McKemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 2002:416:52-58
Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell 2002:108:705-715
Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 2010:330: 55-60
Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, Wilson AJ, Francisco AG, Reddy K, Qiu Z, Wood JN, Lewin GR, Patapoutian A. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 2014:516:121-125
Figure 4 The seminal discoveries by this year’s Nobel Prize laureates have explained how heat, cold and touch can initiate signals in our nervous system. The identified ion channels are important for many physiological processes and disease conditions.
In the latter part of the 1990’s, David Julius at the University of California, San Francisco, USA, saw the possibility for major advances by analyzing how the chemical compound capsaicin causes the burning sensation we feel when we come into contact with chili peppers. Capsaicin was already known to activate nerve cells causing pain sensations, but how this chemical actually exerted this function was an unsolved riddle. Julius and his co-workers created a library of millions of DNA fragments corresponding to genes that are expressed in the sensory neurons which can react to pain, heat, and touch. Julius and colleagues hypothesized that the library would include a DNA fragment encoding the protein capable of reacting to capsaicin. They expressed individual genes from this collection in cultured cells that normally do not react to capsaicin. After a laborious search, a single gene was identified that was able to make cells capsaicin sensitive (Figure 2). The gene for capsaicin sensing had been found! Further experiments revealed that the identified gene encoded a novel ion channel protein and this newly discovered capsaicin receptor was later named TRPV1. When Julius investigated the protein’s ability to respond to heat, he realized that he had discovered a heat-sensing receptor that is activated at temperatures perceived as painful (Figure 2).
Figure 2 David Julius used capsaicin from chili peppers to identify TRPV1, an ion channel activated by painful heat. Additional related ion channels were identified and we now understand how different temperatures can induce electrical signals in the nervous system.
The discovery of TRPV1 was a major breakthrough leading the way to the unravelling of additional temperature-sensing receptors. Independently of one another, both David Julius and Ardem Patapoutian used the chemical substance menthol to identify TRPM8, a receptor that was shown to be activated by cold. Additional ion channels related to TRPV1 and TRPM8 were identified and found to be activated by a range of different temperatures. Many laboratories pursued research programs to investigate the roles of these channels in thermal sensation by using genetically manipulated mice that lacked these newly discovered genes. David Julius’ discovery of TRPV1 was the breakthrough that allowed us to understand how differences in temperature can induce electrical signals in the nervous system.
In an announcement televised on C-Span, President Elect Joseph Biden announced his new Science Team to advise on science policy matters, as part of the White House Advisory Committee on Science and Technology. Below is a video clip and the transcript, also available at
2020 Nobel Prize in Economic Sciences for improvements to auction theory and inventions of new auction formats to Paul R. Milgrom and Robert B. Wilson
Reporter: Aviva Lev- Ari, PhD, RN
UPDATED on 10/16/2020
The Nobel Prize for economic sciences this year went to Paul MIlgrom and Robert Wilson. Milgrom is recognized as one of the world’s great experts in auction theory, and I interviewed him for my book In the Plex (finally out in paper next February!) about Google’s clever AdWords approach to bidding, which was crafted by Google engineer Eric Veach along with his boss Salar Kamangar. I’d asked Milgrom to compare the AdWords system to the competitor, Overture:
One fan of Veach’s system was the top auction theorist, Stanford economist Paul Milgrom. “Overture’s auctions were much less successful,” says Milgrom. “In that world, you bid by the slot. If you wanted to be in third position, you put in a bid for third. If there’s an obvious guy to win the first position, nobody would bid against him, and he’d get it cheap. If you wanted to be in every position, you had to make bids for each of them. But Google simplified the auction. Instead of making eight bids for the eight positions, you made one single bid. The competition for second position will automatically raise the price for the first position. So the simplification thickens the market. The effect is that it guarantees that there’s competition for the top positions.”
Veach and Kamangar’s implementation was so impressive that it changed even Milgrom’s way of thinking. “Once I saw this from Google, I began seeing it everywhere,” he says, citing examples in spectrum auctions, diamond markets, and the competition between Kenyan and Rwandan coffee beans. “I’ve begun to realize that Google somehow or other introduced a level of simplification to ad auctions that was not included before.” And it wasn’t just a theoretical advance. “Google immediately started getting higher prices for advertising than Overture was getting,” he notes.
Subject: Clarence Thomas wants to rethink internet speech. Be afraid
Paul Milgrom (left) and Robert Wilson share the 2020 Nobel prize in economic sciences for improvements to auction theory and invention of new auction formats.
Image Credit: Elena Zhukova for the Stanford Graduate School of Business
The 2020 Nobel prize in economic sciences rewards work on an ancient form of transaction that has acquired new complexity and urgency in the modern age: the auction.
Insights in auction theory made by Paul Milgrom and Robert Wilson, both of Stanford University in California, have found applications ranging from the pricing of government bonds to the licensing of radio-spectrum bands in telecommunications.
Diane Coyle of the University of Cambridge, UK, says that the Nobel, announced on 12 October, will be widely welcomed. “These two not only did foundational work themselves”, she says, “but also inspired cohorts of younger researchers.”
Economist Preston McAfee of Google agrees. “I, and thousands like me, use the fruits of their work on a daily basis to make markets work better — to improve pricing, to manage incentives, to facilitate decision-making, to increase efficiency.”
Their research has intersected with computer science and communications engineering to lay the foundations for many online platforms, Coyle adds.
Economist John Kagel of Ohio State University in Columbus, USA, called it “an outstanding selection”.
Online platforms such as eBay have raised public awareness of some of the complexities of auctions. There are many ways to stage them: for example, in a so-called “English auction” the item on offer simply goes to the highest bidder; whereas in a “Dutch auction” the selling starts from a high price, and bidders submit the price they are willing to pay.
But bidding is affected by many more factors that might reduce the seller’s final profit, cause losses for the winning bidder, create inefficiencies of allocation, or harm the public good. The work of the two laureates has helped to reduce these problems and to suggest new, more efficient ways for auctions to be conducted.
One problem is that different bidders can have different degrees of knowledge about an item for sale. For example, in a property auction, all bidders for a property will have access to some public information such as its resale value. But other kinds of information — such as hidden structural damage — will be private and not known to everyone.
A bidder who does not have such information might end up overpaying if they want to buy the property. They might be able to infer what others know about the value if bids are public – and people start to drop out – but not if bids are private.
In the late 1960s and 1970s, Wilson showed what happens to prices and profits in auctions when bidders have different degrees of private information.
Furthermore, if information about a property is highly uncertain — if the nature of the neighbourhood is rapidly changing, say — that could make buyers cautious and reduce the seller’s profit. In the 1980s, Milgrom — a former doctoral student of Wilson’s — developed models (partly in conjunction with Robert Weber of Northwestern University) that showed there is then an incentive for sellers to gather and share expert information with bidders, within different auction formats. The predictions of how such public information helps prevent losses to sellers and increases their revenue have been born out by experiments, says Kagel.
A spectrum of options
Auctions can be more complex when the goods for sale are divisible into parts or batches — for example, when governments sell licenses to companies bidding to operate in energy, telecommunications or transportation markets. One issue for such auctions is that sellers are vulnerable to collusion between buyers to keep the buying price down. Wilson’s work in the 1970s helped to identify these problems and to design new auctions to avoid them, for example in markets for electricity provision.
The sales of items might also be interdependent. A classic example in the 1990s was the sale of radio-frequency bands to telecom companies for mobile-phone networks — which many countries decided was best done through auctions.
If rights to frequency bands were simply auctioned region by region, a national telecoms company couldn’t be sure of acquiring the same frequency everywhere. And the value to them for one region would depend on whether they could buy the same frequency band elsewhere. The resulting patchwork of coverage would be inconvenient for users too.
To tackle such problems, Milgrom and Wilson (and independently, McAfee) devised the simultaneous multiple-round auction (SMRA). Here, bidders can place bids over several rounds of bidding. This gives them a chance to glean something about others’ private information while bidding, creating fairer and more efficient outcomes.
This approach was used in 1994 for auctioning telecom licenses in the United States, and has been adopted in Canada, India, and several European and Scandinavian countries. Milgrom has also devised other formats that ease some of the shortcomings of the SMRA.
“Unlike many theoreticians, Wilson and Milgrom brought their work to the real world, and transformed government policies toward auctions around the world,” says McAfee.
“There was no question that these two would win the Nobel prize at some point,” says economist Paul Klemperer of the University of Oxford. “It could have happened at any time in the past 20 years.”
“One could even imagine Paul Milgrom having a second Nobel prize,” he adds, for his work in information economics and industrial organization. Milgrom has given a Nobel acceptance speech before: in 1996, as a stand-in for William Vickery, who died three days after the announcement of his prize for laying the foundations of auction theory in the 1960s.
The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel 2020 was awarded jointly to Paul R. Milgrom and Robert B. Wilson “for improvements to auction theory and inventions of new auction formats.”
Prize announcement
Announcement of the 2020 Prize in Economic Sciences by Professor Göran K. Hansson, Secretary General of the Royal Swedish Academy of Sciences, on 12 October 2020.
“This prize is about avoiding the winner’s curse”
Immediately after the announcement, Tommy Andersson, member of the committee for the Prize in Economic Sciences, was interviewed by freelance journalist Joanna Rose regarding the 2020 Prize in Economic Sciences.
Press release: The Prize in Economic Sciences 2020
“for improvements to auction theory and inventions of new auction formats”
Their theoretical discoveries have improved auctions in practice
This year’s Laureates, Paul Milgrom and Robert Wilson, have studied how auctions work. They have also used their insights to design new auction formats for goods and services that are difficult to sell in a traditional way, such as radio frequencies. Their discoveries have benefitted sellers, buyers and taxpayers around the world.
People have always sold things to the highest bidder, or bought them from whoever makes the cheapest offer. Nowadays, objects worth astronomical sums of money change hands every day in auctions, not only household objects, art and antiquities, but also securities, minerals and energy. Public procurements can also be conducted as auctions.
Using auction theory, researchers try to understand the outcomes of different rules for bidding and final prices, the auction format. The analysis is difficult, because bidders behave strategically, based on the available information. They take into consideration both what they know themselves and what they believe other bidders to know.
Robert Wilson developed the theory for auctions of objects with a common value – a value which is uncertain beforehand but, in the end, is the same for everyone. Examples include the future value of radio frequencies or the volume of minerals in a particular area. Wilson showed why rational bidders tend to place bids below their own best estimate of the common value: they are worried about the winner’s curse – that is, about paying too much and losing out.
Paul Milgrom formulated a more general theory of auctions that not only allows common values, but also private values that vary from bidder to bidder. He analysed the bidding strategies in a number of well-known auction formats, demonstrating that a format will give the seller higher expected revenue when bidders learn more about each other’s estimated values during bidding.
Over time, societies have allocated ever more complex objects among users, such as landing slots and radio frequencies. In response, Milgrom and Wilson invented new formats for auctioning off many interrelated objects simultaneously, on behalf of a seller motivated by broad societal benefit rather than maximal revenue. In 1994, the US authorities first used one of their auction formats to sell radio frequencies to telecom operators. Since then, many other countries have followed suit.
“This year’s Laureates in Economic Sciences started out with fundamental theory and later used their results in practical applications, which have spread globally. Their discoveries are of great benefit to society,” says Peter Fredriksson, chair of the Prize Committee.
Paul R. Milgrom, born 1948 in Detroit, USA. Ph.D. 1979 from Stanford University, Stanford, USA. Shirley and Leonard Ely Jr. Professor of Humanities and Sciences, Stanford University, USA.
Robert B. Wilson, born 1937 in Geneva, USA. D.B.A. 1963 from Harvard University, Cambridge, USA. Adams Distinguished Professor of Management, Emeritus, Stanford University, USA.
The Prize amount: 10 million Swedish kronor, to be shared equally between the Laureates. Further information: www.kva.se and http://www.nobelprize.org Press contact: Eva Nevelius, Press Secretary, +46 70 878 67 63, eva.nevelius@kva.se Experts: Tommy Andersson, +46 73 358 26 54, tommy.andersson@nek.lu.se, Tore Ellingsen, +46 70 796 10 49, tore.ellingsen@hhs.se, Torsten Persson, +46 79 313 39 04, torsten.persson@iies.su.se, Committee for the Prize in Economic Sciences in Memory of Alfred Nobel
The University of California has a proud legacy of winning Nobel Prizes, 68 faculty and staff have been awarded 69 Nobel Prizes.
Reporter: Aviva Lev-Ari, PhD, RN
PREVIOUS PRIZE WINNERS
The University of California has a proud legacy of winning Nobel Prizes that stretches all the way back to 1939, when Ernest O. Lawrence was awarded the prize in physics for his invention of the cyclotron. In the years since, dozens of other University of California faculty and staff have been awarded this highest international honor for their contributions in medicine, economics, physics and more.
Today, 68 faculty and staff have been awarded 69 Nobel Prizes.
View as grid
Name
Campus affiliation
Field of study
Year of award
Jennifer Doudna
UC Berkeley
Chemistry
2020
Andrea Ghez
UCLA
Physics
2020
Reinhard Genzel
UC Berkeley
Physics
2020
Randy Schekman
UC Berkeley
Physiology or medicine
2013
Lloyd Shapley
UCLA
Economics
2012
Shinya Yamanaka
UC San Francisco
Physiology or medicine
2012
Saul Perlmutter
UC Berkeley/Berkeley Lab
Physics
2011
Elizabeth Blackburn
UC San Francisco
Physiology or medicine
2009
Oliver E. Williamson
UC Berkeley
Economics
2009
Roger Y. Tsien
UC San Diego
Chemistry
2008
George Smoot
UC Berkeley/Berkeley Lab
Physics
2006
Richard R. Schrock
UC Riverside
Chemistry
2005
David Gross
UC Santa Barbara
Physics
2004
Finn E. Kydland
UC Santa Barbara
Economic sciences
2004
Irwin Rose
UC Irvine
Chemistry
2004
Robert F. Engle
UC San Diego
Economic sciences
2003
Clive Granger
UC San Diego
Economic sciences
2003
Sydney Brenner
UC San Diego
Physiology or medicine
2002
George Akerlof
UC Berkeley
Economic sciences
2001
Alan J. Heeger
UC Santa Barbara
Chemistry
2000
Herbert Kroemer
UC Santa Barbara
Physics
2000
Daniel McFadden
UC Berkeley
Economic sciences
2000
Louis J. Ignarro
UCLA
Physiology or medicine
1998
Walter Kohn
UC Santa Barbara
Chemistry
1998
Robert B. Laughlin
UC Livermore Lab
Physics
1998
Paul D. Boyer
UCLA
Chemistry
1997
Steven Chu
UC Berkeley/Berkeley Lab
Physics
1997
Stanley B. Prusiner
UC San Francisco
Physiology or medicine
1997
Paul Crutzen
UC San Diego
Chemistry
1995
Mario J. Molina
UC San Diego
Chemistry
1995
Frederick Reines
UC Irvine
Physics
1995
F. Sherwood Rowland
UC Irvine
Chemistry
1995
John Harsanyi
UC Berkeley
Economic sciences
1994
Harry Markowitz
UC San Diego
Economic sciences
1990
J. Michael Bishop
UC San Francisco
Physiology or medicine
1989
Harold E. Varmus
UC San Francisco
Physiology or medicine
1989
Donald J. Cram
UCLA
Chemistry
1987
Yuan T. Lee
UC Berkeley/Berkeley Lab
Chemistry
1986
Gerard Debreu
UC Berkeley
Economic sciences
1983
Czeslaw Milosz
UC Berkeley
Literature
1980
Roger Guillemin
UC San Diego
Physiology or medicine
1977
Renato Dulbecco
UC San Diego
Physiology or medicine
1975
George Emil Palade
UC San Diego
Physiology or medicine
1974
John Robert Schrieffer
UC Santa Barbara
Physics
1972
Hannes Alfven
UC San Diego
Physics
1970
Luis Walter Alvarez
UC Berkeley/Berkeley Lab
Physics
1968
Robert W. Holley
UC San Diego
Physiology or medicine
1968
Julian Schwinger
UCLA
Physics
1965
Charles H. Townes
UC Berkeley
Physics
1964
Maria Goeppert-Mayer
UC San Diego
Physics
1963
Francis Crick
UC San Diego
Physiology or medicine
1962
Melvin Calvin
UC Berkeley/Berkeley Lab
Chemistry
1961
Donald A. Glaser
UC Berkeley/Berkeley Lab
Physics
1960
Willard Libby
UCLA
Chemistry
1960
Owen Chamberlain
UC Berkeley/Berkeley Lab
Physics
1959
Emilio Segrè
UC Berkeley/Berkeley Lab
Chemistry
1959
Linus Pauling
UC San Diego
Chemistry, Peace
1954, 1962
Edwin McMillan
UC Berkeley/Berkeley Lab
Chemistry
1951
Glenn T. Seaborg
UC Berkeley/Berkeley Lab
Chemistry
1951
William Giauque
UC Berkeley
Chemistry
1949
John Howard Northrop
UC Berkeley
Chemistry
1946
Wendell Meredith Stanley
UC Berkeley
Chemistry
1946
Ernest Lawrence
UC Berkeley/Berkeley Lab
Physics
1939
Harold Urey
UC San Diego
Chemistry
1934
HOW UC NOBEL LAUREATES ARE COUNTED
Our list of Nobel Prize winners includes University of California faculty and staff who were affiliated with UC when they received their award. It also includes faculty and staff who joined UC after receiving their Nobel Prize. And although we are immensely proud of the many UC alumni who have gone on to receive Nobel Prizes, they are not counted here. Nor are visiting scholars or others who had short-term assignments with UC. Finally, our Nobelist list is a “lifetime” list and includes those living, retired or deceased.
Genetic scissors: a tool for rewriting the code of life
Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.
Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.
“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.
As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.
Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.
In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.
Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.
Emmanuelle Charpentier, born 1968 in Juvisy-sur-Orge, France. Ph.D. 1995 from Institut Pasteur, Paris, France. Director of the Max Planck Unit for the Science of Pathogens, Berlin, Germany.
Jennifer A. Doudna, born 1964 in Washington, D.C, USA. Ph.D. 1989 from Harvard Medical School, Boston, USA. Professor at the University of California, Berkeley, USA and Investigator, Howard Hughes Medical Institute.
Other Articles on the Nobel Prize in this Open Access Journal Include:
2020 Nobel Prize for Physiology and Medicine for Hepatitis C Discovery goes to British scientist Michael Houghton and US researchers Harvey Alter and Charles Rice
The Nobel Prize in Physiology or Medicine 2020 was awarded jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice “for the discovery of Hepatitis C virus.”
Nobel Prize for Medicine goes to Hepatitis C discovery
By James Gallagher Health and science correspondent
The winners are British scientist Michael Houghton and US researchers Harvey Alter and Charles Rice.
The Nobel Prize committee said their discoveries ultimately “saved millions of lives”. The virus is a common cause of liver cancer and a major reason why people need a liver transplant.
In the 1960s, there was huge concern that people receiving donated blood were getting chronic hepatitis (liver inflammation) from an unknown, mysterious disease. The Nobel Prize committee said a blood transfusion at the time was like “Russian roulette”. Highly sensitive blood tests mean such cases have now been eliminated in many parts of the world, and effective anti-viral drugs have also been developed. “For the first time in history, the disease can now be cured, raising hopes of eradicating Hepatitis C virus from the world,” the prize committee said. However, the 70 million people are currently living with the virus, which still kills around 400,000 a year.
The mystery killer
The viruses Hepatitis A and Hepatitis B had been discovered by the mid-1960s.
But Prof Harvey Alter, while studying transfusion patients at the US National Institutes of Health in 1972, showed there was another, mystery, infection at work. Patients were still getting sick after receiving donated blood. He showed that giving blood from infected patients to chimpanzees led to them developing the disease.
The mysterious illness became known as “non-A, non-B” hepatitis in and the hunt was now on.
Prof Michael Houghton, while at the pharmaceutical firm Chiron, managed to isolated the genetic sequence of the virus in 1989. This showed it was a type of flavivirus and it was named Hepatitis C.
And Prof Charles Rice, while at Washington University in St. Louis, applied the finishing touches in 1997. He injected a genetically engineered Hepatitis C virus into the liver of chimpanzees and showed this could lead to hepatitis.
The History, Uses, and Future of the Nobel Prize, 1:00pm – 6:00pm, Thursday, October 4, 2018, Harvard Medical School
Reporter in Real Time: Aviva Lev-Ari, PhD, RN
Center for the History of Medicine
Francis A. Countway Library of Medicine
invites you to register for
The History, Uses, and Future of the Nobel Prize
1:00pm – 6:00pm, Thursday, October 4, 2018
A half-day symposium bringing together an international group of historians and Nobel laureates to consider the history of the Nobel Prize and its enduring social, political, and scientific roles
PROGRAM
Panel I: Scientific Credit and the History of the Nobel Prize
Chair:Allan Brandt (Harvard Medical School and Harvard University) /
Jacalyn M. Duffin (Queen’s University): Commemorating Excellence: the Nobel Prize and the Historical Sociology of Science /
Nils Hansson, Thorsten Halling, and
Heiner Fangerau(Heinrich Heine-University): The First US-American Nobel Prize Nominees in Medicine (and why they failed) /
Jeffrey Flier(Harvard Medical School): The Past, Present, and Future of Scientific Credit in Biomedicine
Panel II: The Nobel – and Ig Nobel – Prize in Practice
Chair: David S. Jones (Harvard Medical School and Harvard University) /
David Kaiser(Massachusetts Institute of Technology): But Does it Scale? Awarding Nobel Prizes in Physics amid Exponential Growth /
Marc Abrahams (Annals of Improbable Research/Ig Nobel Prizes): Ig Nobel: Research that Makes You Laugh, then Makes You Think
Panel III: The Uses and Future of the Nobel Prize
Chair: Scott H. Podolsky(Harvard Medical School) /
Eric Chivian, Ira Helfand,
Bernard Lown,
James Muller, and
John Pastore(leadership of IPPNW, recipient of the Nobel Peace Prize, 1985): Decreasing the Nuclear Threat to Humanity – Nobel Peace Prizes to IPPNW in 1985 and ICAN in 2017 /
Torsten Wiesel (recipient, Nobel Prize in Physiology or Medicine, 1981): Nobel – Excellence Forever /
Jack Szostak (recipient, Nobel Prize in Physiology or Medicine, 2009): Opportunities and Responsibilities that Come with Winning the Nobel Prize
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