From The Attic — For a Kinder, Cooler America
Like many raised near the beach, Jennifer Doudna dreams of waves. A giant wave is sweeping toward shore. She frantically grabs a surfboard, paddles out, catches the wave and rides, wild and free. And safe.
In her 2017 book, A Crack in Creation, Doudna (pronounced DOWD-na) issued a prophecy: our future is about to be changed, and perhaps our DNA. “The wave is coming. Let’s paddle out and ride it together.”
So. . . Got vaxx? Since December, some 600 million human arms have received one COVID vaccination or another. Just a year ago, as the virus filled morgues and ICUs, vaccination was only a dream, not expected for 18 months or more. The death toll soared.
But Jennifer Doudna and her colleagues had a tool for tinkering with viruses. They call it CRISPR, and its gene splicing precision led to the first COVID tests last spring, and by November, the first vaccines. Last fall, CRISPR also earned the wave makers the Nobel Prize in Chemistry.
It seems impossible to overstate CRISPR’s potential. “The invention of CRISPR and the plague of COVID,” biographer Walter Isaacson wrote, “will hasten our transition to the third great revolution of modern times.” (Relativity and quantum theory were the first, digital tech second.)
But Jennifer Doudna did not dream of revolution. Growing up in Hawaii, she was shy but intensely curious. Hawaii’s wonderland was the ideal lab and Doudna’s father, who taught American lit, encouraged questions. What made spiders in caves eyeless? How did tropical “sleeping grass” move when touched?
Doudna’s curiosity found a focus when she came home from sixth grade one day to find a book on her bed. The Phantom Tollbooth? Alice in Wonderland? No, Martin Doudna thought his whipsmart daughter might like The Double Helix. He was right.
Doudna dove into the bio-mystery story, reading how James Watson and Francis Crick decoded DNA. But for a curious girl, the book contained a parallel discovery. Though Watson and Crick dismissed — even hid — Rosalind Franklin’s contribution, Doudna saw the light. “Girls can do science!”
Doudna’s climb up DNA’s spiral stair — from Hawaii to UC Berkeley to the Nobel — is the stuff of dreams and waves. And the ascent is clogged with genetics’ mutated vocabulary. Prokaryotic and eukaryotic. Group 1 catalytic intron and RNA polymerase ribozymes. So let’s cut to the Cas-9 (the protein that attacks DNA like a scalpel.)
CRISPR stands for (take a breath) Clustered Regularly Interspaced Short Palindromic Repeats. What that means, students, is that among 3.2 billion coded bits that make up the human genome, Doudna and others noticed certain repeats. Decades more research revealed that microbes rewrite their own DNA, storing genetic patterns to ward off viruses. The rewriting uses a handy gene splicer evolved over eons.
“In the course of our research on a bacterial immune system called CRISPR-Cas,” Doudna wrote, “we uncovered the workings of an incredible molecular machine that could slice apart viral DNA with exquisite precision.”
CRISPR edits DNA’s double helix, adding or removing genetic material. In 2012, when Doudna and collaborator Emmanuelle Charpentier announced the breakthrough, the few who understood it were agog. “This technology has utterly transformed the way we do research in basic science,” said NIH director Francis Collins. But there were “issues.”
Genetically modified life? Sounds like another dream, the nightmare of Mary Shelley’s Frankenstein. And CRISPR soon created muscular beagles and mini-pigs, disease-resistant rice and long lasting tomatoes. Then a Chinese geneticist used CRISPR on unborn twins, deleting the HIV receptor to make them AIDS immune. Alarmed, Doudna came out of the lab and into the public arena.
“Should we begin editing genes in unborn children to lower their lifetime risk of heart disease, Alzheimer’s, diabetes, or cancer? The quest for perfection seems almost intrinsic to human nature, but if we start down this slippery slope, we may not like where we end up.”
Doudna explained CRISPR to politicians, pundits, journalists, then organized an international conference. Sure, CRISPR could slice out hereditary diseases — sickle cell, cystic fibrosis, hemophilia. But it could also. . . The debate stopped short when one scientist, peering far into the future, warned, “Someday we may consider it unethical not to use germline editing to alleviate human suffering.”
The debate was still raging when COVID struck. The day after UC Berkeley locked down, Doudna, sensing government response as, shall we say, inadequate, convened colleagues. “This is not something that academics typically do,” she said. “We need to step up.”
By May, CRISPR had jump-started rapid, swab-based COVID tests. Meanwhile, scientists around the world shared CRISPR research, failures, successes. And in November, the vaccines, and the wave, arrived.
“This year’s prize,” the Nobel committee announced, “is about rewriting the code of life.” Learning of her Nobel, Doudna was “over the moon,” but she was soon back in the lab. Wondering. Probing. Surfing.
“CRISPR evolved in bacteria because of their long-running war against viruses. . . Isn’t it fitting that one of the tools is this ancient bacterial immune system? Nature is beautiful that way.”
