The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

Vaccines are indispensable in the fight against pandemics like COVID-19, but they are not perfect. That is because vaccines rely on stimulating a person’s immune system, which can sometimes lead to hyperimmune responses. Antiviral therapies may be a good alternative for immunity-boosting treatments, since they attack the virus while sparing the immune system. And why look further than CRISPR, which bacteria have perfected as a virus-fighting mechanism?

Cameron Myhrvold is one of the scientists working on a CRISPR cure for COVID-19. Myhrvold collaborated with Zhang, Pardis Sabeti (a biologist), Omar Abudayyeh, and Jonathan Gootenberg to develop a CRISPR-Cas13 system to chop up dangerous viruses. The system has a catchy acronym: CARVER. Sabeti was able to get a DARPA grant to study CARVER as a virus-fighting mechanism in humans. In the lab, Myhrvold’s team could get CARVER to destroy the virus that causes severe flu, among others. Months after Myhrvold’s team published their findings, the coronavirus erupted on the global map.

Myhrvold decided to focus on using CRISPR as a diagnostic tool to deal with the pandemic rather than on adapting CARVER to COVID-19. That task was taken up by another team on a different coast—one that united Doudna protégé Stanley Qi, bioengineer Patrick Hsu, and postdocs Tim Abbot and Ross Wilson. Qi used an enzyme called Cas13d to target the coronavirus in human lung cells. He dubbed his system PAC-MAN, after the video game. PAC-MAN was seen to reduce coronavirus by 90% in a lab setting, but the problem of delivering it safely in human cells persists. The drawback of the viral delivery method is that the small viral particles limit the quantity of CRISPR proteins and guide RNA. One promising method is to deliver the CRISPR-Cas13 complex of CARVER or PAC-MAN inside synthetic molecules called lipitoids; another is to deliver it in the form of a nasal spray, much like inhaled corticosteroids for people with asthma.

Cold Spring Harbor Lab’s 2020 annual conference on CRISPR was held online in August. Much of the meeting focused on how CRISPR was being used to fight COVID-19, especially by the likes of Doudna, Zhang, and others. Another important topic was the 100th birth anniversary of Rosalind Franklin, whom Fyodor Urnov dubbed “the godmother of gene editing” (448). The conference also covered platforms like Chen and Harrington’s DETECTR, Qi’s PAC-MAN, and Zhang’s STOP, as well as the next generation of CRISPR innovations. The most important of these was the work of David Liu of Harvard. Liu had been developing “base editing,” a technique by which a change can be made in a single letter of DNA without cutting the double strand. An advance here is “prime editing,” where guide RNA can carry a long sequence to be edited into a targeted part of DNA, again with a single nick.

An important question raised at the virtual conference was the limited representation of African Americans in both COVID-19 vaccine trials and the field of biotechnology. One reason fewer African Americans enrolled for vaccine trials was their mistrust of clinical trials because of horrors like the Tuskegee experiments, in which Black sharecroppers suffering from syphilis were given placebos without their knowledge. Both clinical trials and the biotechnology field need to be made more inclusive of African Americans.

Important as the conference was, it lacked the energy that an in-person exchange of ideas brings. However, one virtual interaction was worth its salt: Doudna and Charpentier’s talk over Skype, moderated by Isaacson. As the two scientists spoke, the awkwardness quickly thawed. Soon they were swapping personal stories, and by the time the call ended, they had expressed a desire to work together again.

Doudna was woken up by her cellphone’s buzzing at around 3:00 a.m. on October 9, 2020. The call was from a reporter from Nature who wanted Doudna’s comment on the Nobel Prize. “Who won,” a groggy Doudna replied. It turned out Doudna and Emmanuelle Charpentier had won the 2020 Nobel Prize in Chemistry for their work on CRISPR.

As far as the Nobel Prize goes, Doudna and Charpentier’s recognition was swift, coming eight years after their pioneering paper in 2012. Additionally, the prize was granted to only two people instead of the usual three. It could have well included George Church, Feng Zhang, Francisco Mojica, or Virginijus Šikšnys, among others. It was also the first time the Nobel Prize for Chemistry went to a two-woman team, a milestone that will inspire girls and women to study science.

In fall 2020, Isaacson thought the pandemic was in temporary abeyance, though he knew more waves of more pandemics were yet to come. When he began writing The Code Breaker, he thought he was writing about the biotech revolution. The pandemic made him realize the biotech revolution was more necessary than even he had initially assumed, and it needed to penetrate homes. Like the coding of tech, children must be taught the code of life. Knowledge about genes and gene editing should become mainstream, and wonder in nature should be encouraged. Just as CRISPR was inspired by bacteria’s fight back against viruses, other technologies will arise when more and more people observe nature and try to understand its mechanisms. Moreover, navigating the field of gene editing ethically will require both scientists and humanists, and people like Doudna who straddle both worlds. Then, people can step into the future, hand in hand.