In “A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution,” biochemists Jennifer Doudna and Samuel Sternberg describe how stunning advancements in their field can bring a wide array of benefits, as well as the risks they pose to our society and planet. Doudna is a professor of biomedical science at University of California, Berkeley and in 2020 won the Nobel Prize in chemistry, along with Emmanuelle Charpentier, for their work in genome editing. Sternberg runs a research laboratory at Columbia University, where he is also a professor in the department of biochemistry and molecular biophysics. They wrote the book together, but it focuses on Doudna’s work developing gene-editing technology.
In the first half of the book, the authors simplify the science behind their work, making it understandable to the average reader. With no background in biochemistry, I was at times confused by their story but still found it fascinating. The authors describe how changes happen in nature through random mutation and natural selection. They then detailed the history of science in this area, which led to scientific gene manipulation or, more simply, gene editing.
Next, the authors reviewed the latest gene-editing technology, known as “clustered regularly interspaced short palindromic repeats” (CRISPR). Doudna explained that on Earth there are “10 million trillion trillion” phages — viruses that attack and kill bacteria. Bacteria have developed defense mechanisms to fight off these viruses. In one of these mechanisms, the bacteria steal snippets of an attacking phage’s DNA during the infection to mount a future immune response, designed to target and destroy the phage. The bacteria’s RNA works with proteins to cut up the DNA of the virus. Doudna describes this as “a virus-seeking missile that can strike quickly and with incredible precision.” It’s an amazing defense mechanism that evolved over eons.
Doudna runs a lab at Berkeley, where her team studied CRISPR and how to use it as a highly effective genetic engineering tool. Thanks to CRISPR, an organism’s entire DNA is now almost as easy to edit as a piece of text.
CRISPR enables scientists to find and fix single incorrect DNA strands out of the 3.2 billion letters that make up the human genome. Through this method, by rationally and deliberately correcting misspellings in the genome, the effects of genetic disease can effectively be reversed. As long as scientists know the genetic code for a particular trait, they can use CRISPR to insert, edit or delete a gene in virtually any living plant or animal’s genome. Gene editing holds the promise of life-changing treatments and cures and may also be able to prevent certain diseases in future humans. Basically, Doudna claims that scientists can now rewrite the “code of life.”
Doudna states that CRISPR could help cure many diseases, including sickle cell disease, cystic fibrosis, muscular dystrophy, malaria, cancer, Parkinsons and HIV/AIDS. CRISPR could help plants withstand the impacts of climate change. Scientists could use the technology to create “ultra-muscular” and healthier animals, higher-yielding crops and disease-resistant and more nutritious food. CRISPR could help make agriculture more sustainable, productive and humane. The potential benefits are enormous. Amazingly, CRISPR is low cost and easy to use.
CRISPR can be injected into any species’ germ cells (eggs and sperm) or embryos, causing genetic changes that will be copied into all cells and forever transmitted to future offspring. Thus, someday CRISPR could be used to change the human genome in ways that are inheritable, altering the composition of humankind, directing the evolution of our species. Clearly, this is a slippery slope.
Doudna asks many critical questions. How do we weigh costs and benefits of tampering with our own genetic code? How do we prevent CRISPR from being abused, with unintentional or calamitous consequences? Will people embrace gene-edited crops? Will “bad guys” develop “gene bombs” that can be militarized and weaponized to target the human microbiome or major food sources? Is using CRISPR technology admirable, deplorable or something in between?
To discuss these issues and find consensus in the scientific community on a best path forward, Doudna has organized multiple forums and panels. Generally, these groups have asked scientists to refrain from attempting to make inheritable changes to the human genome, yet some scientists already have. Doudna is concerned about two concrete hazards: first, reckless experiments that prematurely implement CRISPR without proper oversight or risk consideration and, second, nefarious uses of the technology, since it’s so cheap. Somewhat ironically, Doudna has cofounded multiple companies to make money off CRISPR. Where will the drive for profit lead? Who decides what is nefarious? Is Frankenstein around the corner?
Doudna implores us to keep an open mind. She states that once a game-changing technology is released in the world, you can’t contain it. She believes that germline editing will eventually be safe enough to use outside of the laboratory, such as in a clinic. That’s the big jump. She expects some scientists will try to create human enhancements with CRISPR, but she doesn’t believe a new movement of eugenics will happen. Doudna claims, if America doesn’t lead on this, another country will. Finally, she stresses a greater need for an open line of communication between science and the populace than ever.
Some people view any form of genetic manipulation as horrible; others see the genome as software that can be fixed and improved. The U.S. intelligence community has described genome editing as one of the six weapons of mass destruction and proliferation that nation-states might try to develop, at great risk to Americans. Currently, America is split on whether to use germline editing to reduce the risk of disease. I’m torn as well. But, given that our culture has refused to take meaningful steps to mitigate climate change, within a couple decades we might not have any better or lower-risk options.
Although technically difficult reading at times, understanding this technology and its impact is important. I suggest giving it a shot.
Read more of the July 28 - Aug. 3, 2021 issue.