The 2020 Nobel Prizes in Sciences

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by Kamal Pratap Singh

Emmanuelle Charpentier, now at the Max Planck Unit for the Science of Pathogens in Berlin, and Jennifer Doudna, at the University of California, Berkeley were awarded the Nobel Prize in Chemistry 2020 for discovering one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. And The 2020 Nobel Prize in Physiology or Medicine was jointly awarded to Harvey J. Alter, Michael Houghton and Charles M. Rice for the discovery of Hepatitis C virus.

Using components of the CRISPR system, researchers can add, remove, or even alter specific DNA sequences. This technology has introduced new opportunities in cancer therapies, curing inherited diseases and also in plant inbreeding. CRISPR is an abbreviation for clustered regularly interspaced short palindromic repeats.

Emmanuelle Charpentier who was studying a bacteria called Streptococcus pyogenes, noticed a previously unknown molecule called tracrRNA. Further studies revealed that this tracrRNA was part of the bacteria’s immune system and it helps the bacteria destroy viral DNA. She published this discovery in 2011.
The same year, along with Jennifer Doudnathey, she succeeded in recreating the bacteria’s scissors and reprogramming it. Charpentier and Doudna then proved that they can now use these scissors to cut any DNA molecule at a required site.

Doudna and Charpentier and their colleagues did critical early work characterizing the system, but several other researchers have been cited — and recognized in other high-profile awards — as key contributors in the development of CRISPR. They include Feng Zhang at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, George Church at Harvard Medical School in Boston, Massachusetts, and biochemist Virginijus Siksnys at Vilnius University in Lithuania.

CRISPR (clustered regularly interspaced short palindromic repeats) is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral (i.e. anti-phage) defense system of prokaryotes.

RNA harboring the spacer sequence helps Cas (CRISPR-associated) proteins recognize and cut foreign pathogenic DNA. Other RNA-guided Cas proteins cut foreign RNA. CRISPR are found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.
CRISPR technology has been applied in the food and farming industries to engineer probiotic cultures and to immunize industrial cultures (for yogurt, for instance) versus infections. It is also being used in crops to enhance yield, drought tolerance and nutritional homes.

By the end of 2014 some 1000 research papers had been published that mentioned CRISPR. The technology had been used to functionally inactivate genes in human cell lines and cells, to study Candida albicans, to modify yeasts used to make biofuels and to genetically modify crop strains. CRISPR can also be used to change mosquitos so they cannot transmit diseases such as malaria. CRISPR-based approaches utilizing Cas12a have recently been utilized in the successful modification of a broad number of plant species.

In July 2019, CRISPR was used to experimentally treat a patient with a genetic disorder. The patient was a 34-year-old woman with sickle cell disease. In March 2020, CRISPR-modified virus was injected into a patient’s eye in an attempt to treat Leber congenital amaurosis.

The 2020 Nobel Prize in Physiology or Medicine was jointly awarded to Harvey J. Alter, Michael Houghton and Charles M. Rice for the discovery of Hepatitis C virus

Alter, an American, is a medical researcher for the National Institutes of Health in Maryland. Born in 1935 in New York City, he earned a medical degree at the University of Rochester before joining the NIH in 1961.

Hepatitis C is a blood-borne virus and causes Hepatitis C disease which affects the liver. According to WHO, “globally, an estimated 71 million people have chronic hepatitis C virus infection and a significant number develop cirrhosis or liver cancer.” In 2016, it was estimated that approximately 3,99,000 people died globally from hepatitis C.

Harvey J. Alter who was studying hepatitis in patients who had received blood transfusions, found many unexplained infections. Tests for Hepatitis A and Hepatitis B virus infection showed that they were not the cause. His team demonstrated that blood from these patients could transmit the disease to chimpanzees, and more studies showed that an unknown infectious agent was behind this. The mysterious new illness was termed “non-A, non-B” hepatitis.

This new virus could not be isolated for several years using the traditional techniques for virus isolation. Michael Houghton and his team created a collection of DNA fragments from the blood of an infected chimpanzee and thoroughly searched it. They found a novel RNA virus belonging to the Flavivirus family and named it the Hepatitis C virus.

To understand if this new virus alone could cause hepatitis, Charles M. Rice used genetic engineering, generated an RNA variant of the virus and injected it into the liver of chimpanzees. The virus was detected in the blood and the chimpanzees exhibited changes similar to those seen in humans with the disease. This was the final proof that the virus alone was the cause behind the unexplained cases of transfusion-mediated hepatitis. Rice, born in Sacramento, California, in 1952, is a professor at Rockefeller University in New York. From 2001-18, he was the scientific and executive director at the Center for the Study of Hepatitis C. He earned his doctorate from the California Institute of Technology in 1981.

The discoveries by the three Nobel laureates have helped design sensitive blood tests that have eliminated the risk of transfusion-transmitted hepatitis. Their discovery also helped develop antiviral drugs directed at hepatitis C. This has now raised hopes of eradicating the virus from the world population.

Houghton, born in Britain, is a Canada Excellence Research Chair in Virology and the Li Ka Shing professor of virology at the University of Alberta. He is also director of the Li Ka Shing Applied Virology Institute at the university. He earned his doctorate from King’s College London in 1977.

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