Harnessing CRISPR to Revolutionize COVID Testing

This isn’t the first time that Pardis Sabeti, MD, DPhil, MSc, a Professor of Organismic and Evolutionary Biology at Harvard University, and newly elected member of the National Academy of Medicine, has worn the hat of viral genome detective in the earliest days of a deadly outbreak or viral disease. Sabeti and her team began sequencing Ebola samples just days after the virus was first detected in Sierra Leone during the 2013-2016 West African outbreak. Since January 2020, she has been working on diagnostics for COVID-19, developing models to predict the most sensitive and accurate assay design candidates for the rapid detection of SARS-CoV-2, including an assay that harnesses the powerful accuracy of CRISPR technology.

Describe the innovative, rapid COVID-19 test that you helped create—how does it work, and why is it an improvement on current testing methods?

Sabeti: Over the last several years, my lab, colleagues, and I have been developing an assortment of technologies for genomic surveillance of pathogens. In particular, we have been deeply invested in CRISPR technologies. CRISPR was first discovered within bacterial immune systems, where it is used to protect the bacteria from invading pathogens by rapidly identifying and targeting a genomic sequence with very high fidelity. Thus, it is immensely powerful as a diagnostic tool, since it can be designed to detect any sequence of genetic material with impressive accuracy.

It is an incredibly exciting technology: it is highly accurate, it would be able to rapidly detect pathogens using little equipment and a simple, paper-strip read-out, and it could be developed in a matter of days to detect newly discovered pathogens or new variants of known pathogens. Crucially, the test is also inexpensive to manufacture, which means it could be easily scaled and distributed as pathogens—or novel variants of pathogens—emerge.

Throughout the duration of the COVID-19 pandemic, some have suggested that testing is optional, unnecessary or unreliable—can you describe why the creation of rapid, reliable tests is so important?  Does that change depending on where we are in the infection curve?

Sabeti: Testing is extremely critical to fighting the spread of any infectious disease, and this has been demonstrated through history. However, testing technology has been achievable but not prioritized—if we had invested in this space after the SARS-CoV epidemic [the SARS outbreak in 2003], I believe we could have been poised to respond to SARS-CoV-2 before it spread throughout the world.

The need for diagnostics is critical everywhere, from pre-empting a pandemic, to response and recovery. To be as useful as possible, diagnostics must also be affordable and accessible to all—this is not just in infectious disease but throughout all medicine. The sooner individuals and communities have information, the better they can respond, enabling better outcomes.

You wrote a book last year entitled “Outbreak Culture.” Are there any key learnings from that book that can be applied to COVID or future pandemics?

Sabeti: In this book we argue that a dysfunctional “outbreak culture”—the collective mindset that develops among responders and communities that emerges in the chaos and crucible that is disease outbreaks—poses a great threat to our ability to curb outbreaks and save lives, and that we must continually watch for and dismantle toxic response systems where possible. This includes the data and resource hoarding, perverse capitalistic incentives, the spread of misinformation, and the loss of empathy and good citizenship. I think people are still just beginning to understand the gravity of outbreak culture and how it is operating amidst COVID. For example, we all now know the importance of detecting outbreaks, through track-and-trace methods, before they have the chance to spread widely. But what is given less attention is how those efforts can be sidelined or undermined by many surrounding societal and political forces.

I always advocate for a massively increased effort for empathy during outbreaks. We need resilient communities to be able to do the best work against infectious disease. With our trust in our fellow citizens, our leaders, and our scientists undermined during this time, it is crucial to work within the community and low to the ground. We must listen to others, respect their opinions, and understand their fears. For that reason, I believe we must double down on empathy when it comes to community participation. If we do not work with communities and support them in the right ways, we end up causing more harm than good.

Pardis Sabeti, MD, DPhil, MSc is a Professor at the Center for Systems Biology and Department of Organismic and Evolutionary Biology at Harvard University and the Department of Immunology and Infectious Disease at the Harvard School of Public Health.  She was a 2016 and 2017 Finalist for the Academy’s Blavatnik National Award for Young Scientists. To learn more about Dr. Sabeti and her work, click here to listen to the “Deciphering Zika” podcast or read the 2017 Blavatnik Science Symposium eBriefing.

On March 15, 2021, the New York Academy of Sciences will host the conference, CRISPR: New Frontiers. This meeting will bring together researchers uncovering the cellular, molecular, and biochemical pathways of CRISPR-associated proteins, DNA repair pathways, and applications in diverse organisms, including for human health and disease biology. Register today here.

On April 1, 2021, the New York Academy of Sciences will host the webinar, Long-Term Health Effects of COVID-19. In this 75-minute webinar, Long COVID experts Dr. Natalie Lambert and Dr. Avindra Nath will explore the symptoms and epidemiology of Long COVID, with a focus on current knowledge of demographics, risk factors, and prognosis. Register today here.