Are Chemistry and Biology clicking? At least there’s good chemistry.
- Carolyn Bertozzi of Stanford University, USA
- Morten Meldal of the University of Copenhagen, Denmark
- Barry Sharpless of La Jolla, California’s Scripps Research Institute, USA
Who won—and why?
Scientists Carolyn Bertozzi, a scientific advisor for Colossal, Morten Meldal and Barry Sharpless were awarded the 2022 Nobel Prize in Chemistry “for the development of click chemistry and bioorthogonal chemistry”.
Nature is hands-down the best chemist: she builds and breaks down with ease complex carbon-based molecules that underpin life.
As for us? Albeit devoid of Nature’s intrinsic gift, chemists have developed an astonishingly ingenious alternative to Nature’s —simply exploit highly energetic “spring-loaded” reactants.
First coined in 2001, a click reaction “is so much downhill in terms of energy, that it never goes back”.
In so doing, Meldal and Sharpless independently discovered what has been recognized as the Holy Grail of click chemistry: A copper-catalyzed linkage of what are known as an azide group (formed by three nitrogen atoms) and an alkyne group (formed by a carbon-carbon triple bond) (1,2) .
So what’s the caveat? Copper being toxic to cells, applications in living tissues are limited.
Bertozzi’s solution? To put a ring on it.
After digging through the dusty archives and a 40-year-old German paper corroborating their intuition, Bertozzi’s group confirmed that the strain placed on a nearby molecular ring could be effectively released in the form of a click chemistry reaction (3). And crucially, such bioorthogonal reactions — “orthogonal” to, or independent of biological processes — could thus be carried out inside living tissues without disturbing them (4).
What makes this so radical—and why do we care?
An array of fantastic applications
Probing biology: Scientists have used Bertozzi’s biorthogonal reactions to map how cells function. Specifically, Bertozzi herself has been able to successfully “click” a fluorescent tag onto cell surface sugar molecules (glycans) in order to visualize them (5). Similar click chemistry methods are being used, in parallel, by neurobiologists to track dividing cells in regenerating brain tissue.
Optimizing biology: Also cleverly capitalizing on click chemistry reactions, researchers have improved the efficacy of cancer treatments, now being tested in clinical trials.
Building biology—from DNA/RNA to proteins and tissues: Remarkably, click chemistry can now be used to make both synthetic yet functional DNA and RNA (6). Not only that, but research recently found a way for a click chemistry reaction to produce a library of guide RNAs useful for CRISPR-based genetic engineering (7). Meanwhile, yet another lab is using click chemistry to create hydrogels for culturing cells in 3D for tissue regeneration, while industries have harnessed these reactions to develop everything from plastics to pharmaceuticals.
Modular molecular LEGOs©
Click chemistry has opened the floodgates of combinatorial chemistry when it comes to the building blocks of life—in a manner unprecedented in terms of its modularity, flexibility, and diversity (8–10).
Physiology or Medicine
Who are we, anyway? The secret life of Homo sapiens.
“Men go abroad to wonder at the heights of mountains, at the huge waves of the sea, at the long courses of the rivers, at the vast compass of the ocean, at the circular motions of the stars, and they pass by themselves without wondering.” – St. Augustine (354-430)
- Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology, Germany
Who won—and why?
Svante Pääbo was awarded the 2022 Nobel Prize in Physiology or Medicine “for his discoveries concerning the genomes of extinct hominins and human evolution”.
Through his advanced sequencing and DNA analytic methods, Pääbo was successful in sequencing the full genome of our extinct relative the Neanderthal (11,12).
Why is this sensational? Pääbo had to develop ways of analyzing DNA that had been not only damaged by thousands of years of exposure, but also been contaminated by the DNA of both microorganisms and modern humans.
(Testifying to the difficulty of the task, he has commented that DNA he had recovered early on in his career from an Egyptian mummy remains was probably his own.)
These genetic analyses led to the conclusion that Neanderthals and Homo sapiens had interbred—and astonishingly, nearly 4% of modern European or Asian Homo sapiens genomes can be traced back to the Neanderthals.
As if that wasn’t enough? Pääbo further discovered and sequenced an entirely novel hominin, the Denisovans, from a small seed-sized bone specimen (13).
(Denisovan DNA can now be identified in the genomes of billions of people.)
What makes this so radical—and why do we care?
Insights into our unique Humanity—our DNA as a memoir of our past
First and foremost, Pääbo’s research gave rise to the entirely new scientific discipline of paleogenomics.
Second, by revealing genetic differences that discriminate modern humans from extinct hominins, his discoveries have shed light on what contributes to making us uniquely human. This includes the discovery of human lineage-specific genes involved in cell division in certain regions of the developing brain—underpinning our complex cognition (14).
Not only this, but Pääbo’s work has further exposed our shared family tree—providing a window of insight into the very fabric of our genetic and geographical heritage—underpinning where we came from, who we are now, and where we are going.
The complex Art of ancient DNA science
Philosophically, this award enroots not only the importance of genetics, but the importance of ancient DNA science—deciphering the past to harness the future.
Practically, Pääbo was instrumental in advancing the ancient DNA sequencing technologies which are indispensable to the field and which are applicable to any ancient DNA specimen.
An entangled trio specifying the very nature of our reality.
- Alain Aspect of the Université Paris Saclay and École Polytechnique, France
- John F. Clauser of F. Clauser & Associates, USA
- Anton Zeilinger of the University of Vienna, Austria
Who won—and why?
Alain Aspect, John F. Clauser and Anton Zeilinger were awarded the 2022 Nobel Prize in Physics “for their pioneering experiments in quantum information science”.
An entangled reality?
Turns out Einstein was wrong.
Yes, he was pivotal in developing quantum mechanics—now a pillar of modern physics. However, he felt that quantum mechanics could not be complete in light of one of its important implications—whereby two objects can affect each other’s behavior instantly across vast distances —i.e. “spooky action at a distance”, or quantum entanglement (15). There must be some hidden variables somewhere to explain this.
However, Irish physicist John Bell proposed in the 1960s a mathematical test, known as Bell’s inequality, whereby if experimental results were correlated beyond a certain degree, this would not be possible due to some hidden variables—and only be possible through quantum entanglement. And thus experimental tests began.
Teamwork in the serial closing of loopholes
Clauser was the first to successfully develop a practical experiment in which he took measurements that disproved the existence of Bell’s inequalities, confirming quantum entanglement (16). Aspect then advanced the setup in a way that closed an important loophole, after which Zeilinger started to actually use entangled quantum states with the help of refined tools and very long experiments.
What makes this so radical—and why do we care?
Phenomenal applications across fields
Not only does this work contribute to unveiling the probabilistic nature of reality, but the array of applications is transformative.
Galvanizing the field quantum science, physicists have since demonstrated quantum teleportation, making it possible to move a quantum state from one particle to one at a distance (17,18)—succeeding in teleporting electrons, atoms, and even superconducting circuits (19).
As for quantum information science, it is sure to revolutionize cryptography and the transfer of information through a quantum internet, among other applications,
Computational hardware and software—a crux to progress
As for quantum computers? The power of quantum computers increases exponentially in relation to their parts (known as qubits)—and a quantum computer 100 million times faster than any classical computer has already been announced. Scalable, the efficiency of quantum computing will only propel forward the available possibilities. Dare we speak of a new industrial revolution?
Persevering with radically disruptive solutions
Fighting the tide, Clauser advanced the experimental implementation of testing Bell’s inequalities. Ironically enough, “people would say [to Clauser], in writing, that this isn’t real physics—that the topic isn’t worthy”. Meanwhile, of Zeilinger, it was said, “whenever we presented him with new ideas, he would challenge us to go further, think more outside the box, be more imaginative”.
Radical, disruptive convictions met with perseverance breed success.
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- Pinson A, Xing L, Namba T, Kalebic N, Peters J, Oegema CE, et al. Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science (80- ). 2022 Sep 9;377(6611).
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