Nobel Prize: Genetic Scissors Designed to Rewrite the Code of Life

This week the Royal Swedish Academy of Sciences, founded in 1739, confirmed its decision to award the Nobel Prize in Chemistry 2020 to Emmanuelle Charpentier, Max Planck Unit for the Science of Pathogens, Berlin, Germany, and Jennifer A. Doudna, University of California, Berkeley, USA, “for the development of a method for genome editing”.

The prize, SEK (Swedish kronor) 10 million (U.S. 1.14 million), is to be shared equally between the two Laureates.

Since the Nobel Prize was established in 1895, less than 60 women have received the prestigious award. This year, Emmanuelle Charpentier and Jennifer A. Doudna are among the 4 women receiving the prize.*[1]

Genome or gene-editing technologies have given scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome.

One of the approaches is CRISPR/Cas9, short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. Referred to as either genetic scissors or a Swiss-army knife, the technology allows researchers to alter the DNA of animals, plants, and microorganisms with extremely high precision.

In simple terms, the CRISPR/Cas9 gene-editing technology has the potential to dramatically reshape the treatment of genetic diseases by replacing or deleting problematic genes, allowing scientists to rewrite DNA — the code of life — in any organism with unprecedented efficiency and precision.

The groundbreaking power and versatility of CRISPR/Cas9 have opened up new and wide-ranging possibilities across biology, agriculture, and medicine, including the treatment of thousands of intractable diseases such as cancer and hematological malignancies. As a result, CRISPR/Cas9 has had a revolutionary impact on the life sciences, leading to a possible cure for these a number of inherited diseases.

Excitement
Since the early discovery and development, the CRISPR/Cas9 technology has generated excitement in the scientific community because is faster, cheaper, and above all, more accurate and efficient compared to other existing gene-editing tools.

CRISPR/Cas9, discovered by Emmanuelle Charpentier and Jennifer A. Doudna, was adapted from a naturally occurring genome editing system in bacteria. In this process, bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays.

These segments or arrays allow bacteria to ‘remember‘ the viruses and when these viruses attack again, the bacteria are able to produce RNA segments from the CRISPR arrays to target the viruses’ DNA. These bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disarms the virus.

Researchers need to modify genes in cells if they are to find out about life’s inner workings. This process used to be time-consuming, difficult, and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionized basic science but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” noted Claes Gustafsson, chair of the Nobel Committee for Chemistry.

“This great honor recognizes the history of CRISPR and the collaborative story of harnessing it into a profoundly powerful engineering technology that gives new hope and possibility to our society,” Doudna noted.

Unexpected discovery
As so often in science, the discovery of CRISPR/Cas9 was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with a vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

“What started as a curiosity‐driven, fundamental discovery project has now become the breakthrough strategy used by countless researchers working to help improve the human condition. I encourage continued support of fundamental science as well as public discourse about the ethical uses and responsible regulation of CRISPR technology,” Doudna said.

Rewriting DNA
In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognize DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 the use of the technology has exploded, contributing to many important discoveries in basic research.

Controversy
The discovery and use of CRISPR/Cas9 raise some difficult to answer moral and ethical questions and have, unfortunately, not been without controversy. For example, in November 2018, He Jiankui, Ph.D., an associate professor at the Southern University of Science and Technology in Shenzhen, China, shocked the global scientific community by announcing that he had used CRISPR/Cas9 to create the first ‘designer babies,’ twin girls Lulu and Nana, by editing their genome to remove a gene that produces a receptor for HIV, the virus that causes AIDS.

Following the announcement, Jiankui was condemned by many of his peers in the scientific community who raised ethical concerns, labeling the gene-editing experiments on humans as ‘monstrous’ and a ‘huge blow’ to the reputation of Chinese biomedical research.

Concerned with this approach, the Shenzhen Nanshan District People’s Court in Southern China sentenced Jiankui to three years behind bars and a 3 million yuan (U.S. $ 430,000.00) fine, called Jiankui ‘experiment… extremely abominable in nature‘, a brazen violation of Chinese law and regulations, shockingly and unacceptably breaching the scientific ethics and morality bottom line, failing to conform with the international scientific norm.

New therapies
In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. And beyond medicine, in plant research, scientists, using CRISPR/Cas9, have been able to develop crops that withstand mold, pests, and drought.

The main message learned from awarding the 2020 Nobel Prize in Chemistry to  Charpentier and Doudna is that novel technologies may really benefit the human race if used wisely. But to do that it’s important to truly understand these technologies, making sure that we stay within established ethical and moral boundaries.

Today, the CRISPR/Cas9 genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

Note
* The other female recipients this year were the American poet Louise Glück who was honored with the Nobel Prize in literature for “for her unmistakable poetic voice that with austere beauty makes individual existence universal,” and Andrea Ghez, who received the Nobel Prize in physics “for the discovery of a supermassive compact object at the center of our galaxy,” along with Roger Penrose and Reinhard Genzel.

Reference
[1] Nobel Prize awarded women. NobelPrize.org. Nobel Media AB 2020. Online. Last accessed Friday, October 9, 2020.

Featured illustration: ©Johan Jarnestad/The Royal Swedish Academy of Sciences. Used with permission.