CRISPR/Cas contains the tracrRNA molecule, which cuts the DNA of viruses in order to destroy them.
Emmanuele Charpentier and Jennifer A. Doudna were awarded the Nobel Prize in Chemistry on October 7 for their work in 2012 on the gene-editing tool CRISPR Cas-9. CRISPR Cas-9 is a biomolecular technology that allows scientists to select and remove specific sections of plant and animal genomes. The technology’s possible applications range from editing the DNA of crops for drought resistance to developing new cancer treatment therapies.
When asked about the announcement of the winners, Nobel chemistry committee member Pernilla Wittung Stafshede said, “The ability to cut DNA where you want has revolutionized the life sciences. The ‘genetic scissors’ were discovered just eight years ago, but have already benefited humankind greatly.”
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology is modeled after prokaryotic microorganisms’ immune systems, such as bacteria and archaea. Cas9 is a specific protein within this defense system that acts as the genetic “scissors” used to cut out the DNA of invading viruses. It is bound by two molecules, tracrRNA and crRNA, which guide the Cas9 protein to its required destination on the viruses’ DNA.
Doudna discovered this previously unknown tracrRNA molecule during her studies in 2011 of the Streptococcus pyogenes bacteria. She published a paper on the molecule’s function the same year and began collaborating with Charpentier, an experienced biochemist. Together, they recreated the tracrRNA’s genetic scissors in a test tube. Though the molecule’s natural function is to fight viruses, Charpentier and Doudna proved that genetic scissors could cut DNA in a wide range of cells.
Compared to previous genetic editing technology, CRISPR is more efficient, precise, and easier to use, so its practical applications are vast. For example, a 2016 study by researchers at MIT on in vitro models showed that CRISPR proteins were effective in enabling “precise genetic dissection of neuronal circuits and modeling of neurological disorders.” Food industry scientists have also begun to test CRISPR on crops; in 2018, researchers at Cornell University announced they had genetically edited a groundberry bush to produce larger fruit and higher yields. The groundberry is closely related to the tomato, which researchers in 2016 discovered could be genetically edited using CRISPR to produce flowers more quickly.
Since its inception in 2012, however, the technology has aroused fears that a lack of genetic editing regulations could lead to unethical behavior. In 2015, CRISPR made the news when it was used by Chinese researchers to edit the genes of a human embryo to create resistance to a blood disease. Yet no attempts were made to fertilize and grow an embryo until 2018 when Chinese scientist He Jianku announced the birth of two twin girls that his lab had edited in vitro to be HIV resistant. Reactions in the global community were overwhelmingly adverse, with scientists calling Jianku’s behavior unethical. “It is profoundly unfortunate that the first apparent application of this powerful technique…has been carried out so irresponsibly,” said Dr. Francis Collins, director of the National Institutes of Health, as he called for limits to be set on genetic editing research, or “the world will face the serious risk of a deluge of similarly ill-considered and unethical projects.” In December of 2018, the WHO announced the creation of a committee “to develop global standards for governance and oversight of human genome editing.” Days later, He Jianku was sentenced to three years in prison and a $430,000 fine for “illegal medical practice.”
The technology is also the subject of a fierce patent battle between the recently awarded laureates’ team at the University of California Berkeley and a team from MIT working in Harvard’s Broad Institute. Both institutions claim their teams made the most relevant and important advancements in the project. “… There is indeed surprise that [the committee] elected to exclude all other pioneers who have made seminal contributions…some others well documented in the CRISPR literature who have been recognized by other award committees,” said Professor Rodolphe Barrangou of North Carolina State University, a researcher of CRISPR Cas-9 in bacteria.
This year’s Nobel prize announcements have also raised conversations about the diversity of Nobel laureates. Prize winners, across all categories, are predominantly white men. Charpentier and Doudna are the sixth and seventh female recipients of the prize and the first team consisting of only women to be awarded the prize. In the category’s 119 year history, only 3.8% of the Nobel Prize in Chemistry’s laureates have been women. Across all categories, 57 of the organization’s 934 laureates have been female. For people of color, the statistics are even smaller. Only 16 laureates across all categories have been black; additionally, there has never been a black recipient in any organization’s scientific categories. During her acceptance speech, Charpentier said that she hopes girls and young female scientists “understand that nothing is impossible.” They can “find great discoveries, great findings that can be impactful,” she said. “It’s independent of the gender.”
This year’s Nobel Prize in Chemistry has not only disrupted stereotypes about gender in science but moved a relatively new and controversial technology into the limelight. As research continues into the functions and possible uses of CRISPR and its proteins, the technique will take a more prominent place in the broader range of global scientific communities.
Photo from Shutterstock.
By Ruthie Collett