Walter Isaacson is the author of “The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race.”
The B.1.1.7 variant first found in Britain is expected to become the predominant strain in the United States and elsewhere by the end of March. It and the other mutations first identified in South Africa, Brazil and the United States cause slight changes in the makeup of the virus’s spike protein, which is the target of the vaccines, thus rendering some of them less effective.
Fortunately, we’ve entered a new era of biotechnology which has shifted the balance of power between humans and viruses in our favor.
We’ve learned how to program and reprogram molecules like we do microchips. That means the day is approaching when we will rely on new genetic codings to fight viruses as well as cancers and other diseases.
Already, two of the authorized vaccines — from Pfizer/BioNTech and Moderna — work by coding snippets of RNA to direct our own cells to make proteins that mimic the coronavirus spike proteins, thus stimulating our immune systems to fight the real thing. If and when a spike protein mutates, its new genetic sequence can be used in a matter of days to devise a new set of messenger RNA instructions that can quickly produce updated vaccines.
In addition, the gene-editing tool CRISPR can be enlisted for this battle. CRISPR is a naturally occurring system that bacteria have been using for millions of years to fight successive waves of viruses. It uses another type of RNA molecule that can “guide” an enzyme to detect and destroy a targeted genetic sequence. Jennifer A. Doudna and Emmanuelle Charpentier won the Nobel Prize for chemistry in October for showing how we can program the “guide RNA” to edit specific genes.
DNA may be the world’s most famous molecule, but like many famous siblings, it doesn’t do much work. It mainly stays at home in the nucleus of our cells, not venturing forth, protecting the information it encodes and occasionally replicating itself.
RNA, on the other hand, has a much busier work-life. Instead of just sitting at home curating information, it makes real products, such as proteins.
When Doudna was a graduate student in the 1990s, most young biologists raced to map the genes that are coded by our DNA. Doudna was more interested in RNA. She studied RNA molecules that could replicate themselves, which raised the possibility that, in the stew of chemicals on this planet four billion years ago, they began to reproduce even before DNA came into being.
Doudna is one of many CRISPR pioneers who has turned her attention to finding the most promising molecular tools to fight covid. A year ago, just as the pandemic struck, she convened 50 scientists from the San Francisco area to form teams to find new ways to detect the coronavirus that causes covid, devise delivery tools for the new vaccines being developed and create CRISPR-based therapies for curing covid.
The emergence of new covid variants shows how important it is to have easily reprogrammable vaccines. But we are going to have to get beyond relying on vaccines. Instead, we will want to develop therapies and cures that directly destroy viruses. As vaccine makers have repeatedly discovered, the multilayered human immune system is very tricky to control. It contains no simple on-off switches, is full of mysteries and works through the interaction of complicated molecules that are not easy to calibrate.
That is where CRISPR will again come into play. The long-range solution to our fight against viruses will use CRISPR to guide a scissors-like enzyme to chop up the genetic material of a virus, without ever having to enlist the patient’s immune system.
The circles of scientists around Doudna and others have created new systems with colorful acronyms such as CARVER and PAC-MAN that, in a lab, can be programmed to target any virus and destroy it. The difficulty, for now, is designing a delivery mechanism that can get these systems into the right human cells. But eventually, such systems will be the ultimate weapon against unwanted viruses, bacterial infections and many types of cancer cells.
By honoring work on an RNA-based, virus-fighting system found in nature amid a virus pandemic, the Nobel committee reminded us how curiosity-driven basic research could end up having very practical applications.
“CRISPR evolved in bacteria because of their long-running war against viruses,” Doudna says. “We humans don’t have time to wait for our own cells to evolve natural resistance to this virus, so we have to use our ingenuity to do that. Isn’t it fitting that one of the tools is this ancient bacterial immune system called CRISPR? Nature is beautiful that way.”
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