Nobel Prizes 2023

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Press release: The Nobel Prize in Physiology or Medicine 2023 - NobelPrize.org
Awarded 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.

Vaccination has come a long way over the centuries. It started out as inoculation, based on the observation that someone who recovers from smallpox never suffers from that disease again. Inoculation was injection with a scab from a smallpox patient, in the hope of causing a mild case of smallpox. But it sometimes caused a much worse case of smallpox.

In 1796, Edward Jenner showed that inducing a case of cowpox makes one immune to smallpox. Another name for cowpox is vaccinia, thus "vaccination". Nearly two centuries later, mass vaccination enabled the end of smallpox outside of labs, and there are arguments about whether to destroy the last remaining stocks of the smallpox virus -- it would be deliberately causing the extinction of a species.

Vaccination has proved to be a very effective preventive measure, making many diseases much rarer in us and in domestic-animal species, and many vaccines are very safe.

There are several ways of making vaccines.

• Weakened but still living target
• Killed target
• Target parts
• Genetic instructions for making target parts

The first two have a risk factor of letting a fully-active target organism through, and they also require a lot of growing of the organism.

The third one became feasible with recombinant-DNA technology -- one makes some surface protein of the target organism by injecting the gene for that protein into some convenient organism, an organism that these makes that protein from that gene. The organism can be some organism in a factory, or else a "vector", a harmless virus that infects our cells, making them produce the protein from that gene.

The fourth one is making copies of such a gene itself and making our bodies make those proteins from those genes.

 

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Vaccines work by provoking an immune response that may then attack the vaccine's target organism. The immune response is a result of some of our white blood cells detecting something that should not be there, and then doing a lot of recombinant DNA in their genomes until they find an antibody molecule that will stick to that something, to tag it as something to be destroyed.

Back to the Nobel Prize press release.

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.

In particular, gene vaccines, using DNA or RNA copies of a gene.

Katalin Karikó and Drew Weissman got to work on gene vaccines, but they ran into a problem. Injecting genes into some lab rat (or mouse) didn't work very well; the animal's immune system attacked the genetic material. But mammalian RNA seemed to have no such trouble. What might make the difference? KK and DW the noticed that mammalian RNA often has modified nucleobases, while RNA from a lab has unmodified nucleobases. So they experimented with nucleobase modification until they found a sort of modification that would imitate mammalian RNA. They succeeded, an important step forward.

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.

 

[lpetrich]

Why mRNA Vaccine Researchers Won the Nobel Prize & Why We Can't Forget Novavax - YouTube -- Rebecca Watson explains how messenger-RNA vaccines were discovered.

The Nobel Prize in Physics 2023 - NobelPrize.org

The Nobel Prize in Physics 2023 was awarded jointly to Pierre Agostini, Ferenc Krausz and Anne L’Huillier "for experimental methods that generate attosecond pulses of light for the study of electron dynamics in matter"

It's the principle of a camera flash: making a pulse of light short enough so that the subject of one's photography will not move very much in the duration of that flash. Only in this case one is observing molecular-scale processes.

In 1987, Anne L’Huillier discovered that many different overtones of light arose when she transmitted infrared laser light through a noble gas. Each overtone is a light wave with a given number of cycles for each cycle in the laser light. They are caused by the laser light interacting with atoms in the gas; it gives some electrons extra energy that is then emitted as light. Anne L’Huillier has continued to explore this phenomenon, laying the ground for subsequent breakthroughs.

In 2001, Pierre Agostini succeeded in producing and investigating a series of consecutive light pulses, in which each pulse lasted just 250 attoseconds. At the same time, Ferenc Krausz was working with another type of experiment, one that made it possible to isolate a single light pulse that lasted 650 attoseconds.

Those pulses are not much longer than a wavelength of visible light.

The Nobel Prize in Chemistry 2023 - NobelPrize.org

The Nobel Prize in Chemistry 2023 was awarded to Moungi G. Bawendi, Louis E. Brus and Alexei I. Ekimov "for the discovery and synthesis of quantum dots"

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Everyone who studies chemistry learns that an element’s properties are governed by how many electrons it has. However, when matter shrinks to nano-dimensions quantum phenomena arise; these are governed by the size of the matter. The Nobel Laureates in Chemistry 2023 have succeeded in producing particles so small that their properties are determined by quantum phenomena. The particles, which are called quantum dots, are now of great importance in nanotechnology.

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Quantum dots now illuminate computer monitors and television screens based on QLED technology. They also add nuance to the light of some LED lamps, and biochemists and doctors use them to map biological tissue.