Although eating whole-grain bread might make me feel virtuous, in my experience it just never seems to taste as good as white bread.
In 2016, I called The Gene: An Intimate History one of my favorite books of the year. The book’s author, Siddhartha Mukherjee, decided to write it largely because of a huge advance that had received far less attention than it deserved: Biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier’s discovery of “genetic scissors” that allow scientists to cut any DNA sequence with incredible precision. Doudna and Charpentier’s discovery earned them the 2020 Nobel Prize in Chemistry.
The “scissors” Doudna and Charpentier discovered are known as CRISPR (pronounced like “crisper”), which stands for Clustered Regularly Interspaced Short Palindromic Repeat. The CRISPR system is a sophisticated defense that bacteria evolved to disarm invading viruses, similar to the way fungi developed penicillin to protect themselves against bacterial infection. The CRISPR system makes it much easier for scientists to alter human and other genomes in beneficial ways, such as repairing gene mutations that cause awful diseases like cystic fibrosis.
In the five years since Mukherjee wrote his book, researchers have done a remarkable job of honing the CRISPR system for medical and agricultural applications, and my excitement about CRISPR has grown from super high to off the charts. CRISPR has fundamentally changed my thinking about what’s possible for improving the health and nutrition of families in poor countries—and how quickly. For example, it took more than 30 years to develop the first effective vaccine for malaria (which the Gates Foundation helped fund)—and that vaccine has an efficacy of only about 50 percent against severe malaria in the first year, dropping in subsequent years. Thanks to the CRISPR system, it’s very likely that our grantees will be able to develop much more effective vaccines in the next five years.
The foundation is investing in many other projects that use the CRISPR system, such as:
When I heard that one of my favorite authors, Walter Isaacson, was working on a book about CRISPR and its inventor, I was eager to read it. The title, The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, suggests that the book is a biography of Doudna, but its scope is broader than that. In fact, Isaacson goes into detail about every CRISPR researcher the foundation is supporting (and many others as well). I found the book to be valuable on a number of levels.
First, it’s great to read a story about scientific discovery with a woman at its center. As a dad, I was touched by the sections in which Doudna’s father, Martin, who was a professor, helps stoke his daughter’s passion for science and her confidence to pursue it at the highest levels. Unfortunately, Martin died of melanoma before his daughter achieved international fame.
Second, I thought Isaacson did a good job of highlighting the most important ethical questions that arise from the CRISPR revolution. Many applications of CRISPR are inarguably good, such as using it to cure blood diseases like sickle cell anemia and beta thalassemia. In these cases, scientists are alleviating human suffering in a way that does not alter the human germline. In other words, the edits affect only the person who receives them and do not get passed along to subsequent generations.
But some scientists are not treating the germline as a red line. As Isaacson covers with nuance, three years ago a Chinese researcher named He Jiankui used CRISPR to edit the genomes of human embryos and then implanted these embryos in women who consented to carrying them to term. Two babies, named Nana and Lulu, have now been born from those embryos. If Nana and Lulu someday have babies of their own, their babies will inherit the genetic modifications Nana and Lulu received. The Chinese researcher’s intentions were good—helping HIV-positive couples give birth to children who had a gene that would confer resistance to infection with HIV—but he disregarded scientific guardrails established by Chinese and American authorities.
While the foundation is not funding any CRISPR projects that involve germline editing, Doudna says it doesn’t make sense to ban germline editing outright. For one thing, she argues, editing that does not involve germline cells, known as “somatic editing,” has limitations. As I mentioned above, scientists are now able to cure sickle cell anemia, but that somatic approach is out of reach for the vast majority of the four million people who suffer from the disease, because it’s such a complex and expensive procedure and can only be done in top-tier hospitals. The germline version might be much less expensive and therefore much more accessible in low- and middle-income countries, which are home to most of the 300,000 babies born with sickle-cell disease each year.
But then another ethical dilemma arises. In Isaacson’s words, “Let’s suppose that researchers show that editing out the sickle-cell mutation is safe. Would there then be any reason to prohibit parents from having the gene edited out when they conceive children?” His answer: maybe. Isaacson introduces us to a California teen named David Sanchez, who gets sickle-cell crises so debilitating that he had to drop out of high school. When one of Sanchez’s doctors told him that “maybe one day with CRISPR they could go in and change the gene in the embryo so that the kid, when it’s born doesn’t have sickle cell,” Sanchez responded in a way you might not expect: “I think it should be up to the kid later,” he said. “There’s a lot of things that I learned having sickle cell. Because I had it, I learned patience with everyone.” The moral of the story: figuring out what’s right to edit into or out of a human genome is not clear cut.
The Code Breaker is highly accessible for non-scientists. And that’s super important, because the ethics of CRISPR’s use are not clear. Doudna is now spending a big portion of her time focused on these moral and ethical issues, especially the potential for genetic editing to exacerbate inequality. As she says to Isaacson, “If you think we face inequalities now, imagine what it would be like if society became genetically tiered along economic lines and we transcribed our financial inequality into our genetic code.”
As with artificial intelligence, facial recognition, and other digital technologies, the public should play an engaged role in drawing the ethical lines. That’s the best way to ensure that the world maximizes the potential for these remarkable innovations to improve the human condition.