COVID Advances Win Groundbreaking US $ 3 Million Prizes

The techniques that have armed scientists in the battle against COVID-19 have won two of five US $ 3 million Breakthrough Awards – the highest-grossing science and math awards. A prize was awarded to biochemists who have discovered how to pass genetic material called messenger RNA into cells, leading to the development of a new class of vaccines. Another was picked up by chemists who developed the next-generation sequencing technique that was used to rapidly track variants of the SARS-CoV-2 coronavirus. The price was announced on September 9.

“These two awards recognize research that has had such an impact on the world that they elevate the stature of the Breakthrough Prize,” said Yamuna Krishnan, a chemical biologist at the University of Chicago in Illinois. “They have saved lives by the millions. “

The vaccines developed by the Pfizer-BioNTech and Moderna collaboration, which were administered worldwide this year, deliver mRNA that instructs cells to create the spike protein for SARS-CoV-2, which in turn stimulates the body to make antibodies. But for decades, mRNA vaccines were considered impractical because the injection of mRNA triggered an unwanted immune response that immediately destroyed the mRNA. Award winners – Katalin Karikó at the University of Pennsylvania (UPenn) in Philadelphia and BioNTech in Mainz, Germany, and Drew Weissman, also at UPenn – demonstrated in the mid-2000s that the exchange of a type molecule in mRNA, called uridine, with a similar one called pseudouridin bypasses this immune reaction¹.

“It’s a fantastic and incredibly timely reward for the work that started it all,” said Nobel Prize-winning chemical biologist Jack Szostak of Harvard University in Cambridge, Massachusetts, who is a science adviser to Moderna. “It’s particularly inspiring because at first no one believed it would be useful.

Many refusals

Karikó recalls the skepticism surrounding her work in the 1990s which led to many rejections of grant and paper proposals (including the 2005 paper for which she is now recognized), and forced her to undergo a demotion. and a reduction in salary. “It certainly wasn’t ‘warp speed,’ she said. Karikó hopes to put some of the prize money back into research into future vaccines and mRNA therapies, for example, to fight cancer. “I am happy to be one of the people who have contributed to this [vaccine], but it is mind-boggling to see how many advances have had to be made over the decades, in many areas, ”says Karikó. “My respect goes to the hundreds of people involved. “

Shankar Balasubramanian and David Klenerman from the University of Cambridge, UK, and Pascal Mayer from research firm Alphanosos in Riom, France, share an award for inventing a technique in the mid-2000s that allows imaging and read billions of DNA fragments. parallel, speeding up sequencing 10 million times. “I was shocked and deeply honored that we won,” said Balasubramanian.

He recalls his enthusiasm in the 1990s for the Human Genome Project, which relied on Sanger sequencing – the original method of gene sequencing – to sequence one piece of DNA at a time. But he soon realized that gene sequencing needed a “gigantic transformation to expand it and make it faster and cheaper for healthcare.”

Krishnan compares the switch from Sanger sequencing to next-generation sequencing to the switch from the Wright brothers’ plane to a Boeing plane. She notes that rapid and efficient sequencing is also essential to genetic medicine and to fundamental advancements in illuminating protein structure and dynamics, in CRISPR gene editing technologies, and in human biology. RNA.

A third Life Sciences Prize went to chemical biologist Jeffrey Kelly of Scripps Research in La Jolla, Calif., For determining the role of protein misfolding in amyloidosis, a disease that can affect organs, including understood the heart and cause neurodegeneration – and to develop an effective treatment for them.

perfect timing

The Breakthrough Prize in Fundamental Physics is shared by optical physicists Hidetoshi Katori of the University of Tokyo and Jun Ye of the US National Institute of Standards and Technology in Boulder, Colorado, for inventing the optical lattice clock – a device which would lose less than a second over 15 billion years^2,3, improving the accuracy of time measurements by 10,000 times.

The award is “richly deserved,” says Helen Margolis, optical physicist at the National Physical Laboratory in Teddington, UK.

Previous state-of-the-art cesium clocks are based on measuring the microwaves emitted as atoms transition between two energy states – a process triggered by the falling clouds of atoms and their bombardment with microwaves. . Rather, optical lattice clocks strike strontium atoms with optical light and measure the emitted optical light, which has a frequency 100,000 times that of microwaves. “This means you can measure ticks faster,” Ye explains.

Clocks also use lasers to immobilize thousands of atoms, in a lattice structure, for even greater precision – but that raises a new challenge. “The very act of trapping the atom can disrupt it,” Ye says. Each energy state is usually distorted by a different amount. A key trick was to find two energy states that happen to be disturbed by the same amount, so that when the difference between them is measured, that distortion cancels out.

With their increased precision and stability, “optical lattice clocks can be used to probe effects never seen before,” says Margolis. In 2020, Katori and his colleagues reported working using two clocks, one placed at the foot of Tokyo’s Skytree Tower and the other 450 meters above, at the top of the tower, to perform the most accurate ground test to date of the General Theory of Relativity⁴. Meanwhile, Ye’s team is researching the effect of the presence of a particular candidate for dark matter – the mysterious substance believed to make up most of the Universe’s matter – on the tics of an optical clock.⁵. Such clocks could also help improve early detection of seismic and volcanic activity and precision measurements of sea level rise.

The Breakthrough Prize in Mathematics was awarded to Takuro Mochizuki of Kyoto University in Japan, for extending the understanding of algebraic structures called “holonomic D modules” – which are related to certain types of differential equations – to deal with points to which the equations under consideration are not well defined.

Yuri Milner, a Russian Israeli billionaire, founded the Breakthrough Awards in 2012. They are now sponsored by Milner and other internet entrepreneurs, including Facebook CEO Mark Zuckerberg.