Novel CRISPR snips itself a Nobel

By Daniel Varias (Isochore)

Since the advent of the novel CRISPR technology, the world not only witnessed a cascade of events it has never seen before, but also hoped for what has never been envisioned.

One would point out how the historical events in Genetics are as antiparallel as the DNA molecule. History narrates how in 1962, all laurels land on a duo of men who elucidated the double-helix structure of the DNA, while the woman with the x-ray crystallography photograph integral to the success stay behind in the shadow. However, 58 years later, it is a true novelty in history for a duo of highly deserving women to earn the 2020 Nobel Prize in chemistry for the development of CRISPR, a novel technology for genome editing, while a man who had his fair share of contributing to the technology remain unrecognized.

Some speculate the message sent by the Royal Swedish Academy of Sciences by awarding University of California, Berkeley’s Jennifer Doudna and Max Planck Institute for Infection Biology’s Emmanuelle Charpentier the Nobel prize over Broad Institute, Massachusetts Institute of Technology’s Feng Zhang, since the award is large enough to have Zhang share the glory with the two women.

Is this a decision to rectify history? In 2016, the Broad Institute’s President and founding director Eric Lander published an inaccurate article entitled “The Heroes of CRISPR” in the Cell journal, which claims that the men are solely responsible for discovering CRISPR/Cas9. The article places Zhang in the pedestal as the man of the hour, while downplaying the contribution of the women. History often narrates how women are often the hidden figures in science, such as the case for Rosalind Franklin of the DNA structure, Katherine Johnson, Dorothy Vaughan, and Mary Jackson of the Space Race, and other women devoid of glory for their contributions. With a groundbreaking decision to award the women over men along with the past records of gender imbalance in accolades, it is no wonder these speculations spring out.

With the conflicting claims of patents between Doudna and Zhang, where Doudna is winning patents in EU while Zhang wins his in the US through Broad, some wonder whether the decision is for the legal system, thus a political one. Some speculate that bioethics affected the decision, since Doudna and Charpentier use CRISPR in solutions while Zhang uses the technology in human samples, thus paving the way for “designer babies” or human genome editing. However, George Church, a Harvard University chemist who also works on CRISPR, believes that the committee prefers to reward discoveries rather than inventions, where Doudna and Charpentier are discoverers, while Zhang is an inventor.

Recognizing and empowering two women in science, particularly in genetics, is a fresh, progressive sight in the year 2020. This shows the long path women have take in the field known to be dominated my men in history, and such feat shall continue to empower women to progress the field. Nevertheless, Doudna, in her unbothered self, modestly receives the award as she abruptly learned about the news post-slumber and currently enjoys the free parking space in UC, Berkeley as one of the perks of her achievement.

Doudna and Charpentier’s achievement and its impacts, however, transcends a free parking space. Clusters of Regularly Interspaced Short Palindromic Repeats or CRISPR genome editing technology exploits the immune system of prokaryotes against phages where the prokaryote slices the viral genetic material from its genome and acquires immunity against the same virus. Doudna and Charpentier’s discovery of CRISPR as a genome editing tool by modifying the Cas9 protein, enabling the system to “cut-and-paste” DNA sequences in a genome.

In their works in CRISPR, Doudna and Charpentier complemented one another in terms of skills. Doudna, a biochemist with extensive work in RNA, hit the road with Charpentier whom she met at a meeting in San Juan, Puerto Rico. Charpentier, who was working with CRISPR/Cas9 in the flesh-eating Streptococcus pyogenes, fascinated Doudna with the mechanism of the system. The latter religiously delved into the system the former introduced, and there went her eureka moment—CRISPR/Cas9 can be converted into a programmable genome editing tool.

Since its discovery, the published articles regarding the use of the CRISPR technology reached beyond 20,000, proving how CRISPR swept the entire scientific community by the possibilities and applications it entails. CRISPR enabled scientists around the world to genetically modify food and livestock organisms to optimize their yield, quality, fitness, desirability to humans, etc., with never-before seen ease. The discovery also brought an upsurge of attempts in utilizing CRISPR in clinical trials to develop drugs and vaccines and correct disorders in humans, such as sickle cell anemia, thalassemia, inherited childhood blindness, and cancer. This phenomenon, according to Doudna, is the democratization of technology.

Researchers are also eyeing CRISPR as a key solution in the lengthy and expensive testing during the COVID-19 pandemic, as the technology also has the potential to detect SARS-CoV-2 in five minutes. The current view in this innovation in motion is the synthesis of an RNA complementary to the RNA sequence unique to SARS-CoV-2 and cutting the target RNA. This enables a release of fluorescent particles, which lights up when hit with a laser light. With the stocks on CRISPR biotechnology skyrocketing in the advent of the award, we can expect financial support from investors in ensuring the realization of such feats.

CRISPR, however, has limitations and challenges amid its brilliance. The system poses technical limitations, such as risks of inaccurate and unintentional splicing of regions of the genome, thus modifying the genome off-target, and difficulty in delivering the CRISPR material to mature cells in large quantities. Bioethical concerns are another consequence of the discovery of CRISPR, where the technology is open for abusive and questionable application, such as He Jiankui’s shocking use of CRISPR in editing the genome of human embryos. Nevertheless, Doudna invokes the international response to that incident, where there has been an effort to ensure global transparency and responsible use of the technology.

Though a technology with technical and ethical considerations, the discovery of CRISPR as a novel genome editing technology catalyzed even the most novel of events: the world witnessing both the rapid progression of science and technology through genome editing and the historical and progressive awarding of an all-woman team to hold the credit for such feat.