Jennifer Doudna

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Yuval Noah Harari so calmly and clinically describes a fascistic, post-human future driven by algorithms and biotech that his prognostications seem fait accompli. His ideas should be read instead as cautionary tales. As Swift used the undersized and super-sized proportions of Lilliputians and Brobdingnags, respectively, to provoke, lecture and caution, Harari’s monstrous machines and microscopic laboratory manipulations should encourage debate about how even far less of a technological society than he envisions can still impact us with potentially negative consequences, intended or unintended.

In a Los Angeles Review of Books piece by Philip Kitcher, the writer reviews Harari’s most recent title, Homo Deus, along with Jennifer Doudna and Samuel Sternberg’s A Crack in Creation, two volumes dedicated to the next big thing: that moment when we co-opt evolution and become something like gods. Kitcher asserts rightly, I believe, that those who fear germline modifications of genes (changes made in the womb that would eradicate diseases from future generations) are worrying most likely needlessly, at least if we’re talking about truly awful outcomes and not just less-favorable ones (ALS as opposed to being somewhat less than average height).

His lack of concern about enhancement in general, however, seems, myopic to me. He can say in a vacuum that “genetic enhancement should not cater” to those who aim to turn out superior offspring, but in the competition among states and corporations, those neat lines of distinction will be blurred. It we got even foggier once the tools of the cell biologist’s trade are in the hands of the many—when they are fast, cheap and (perhaps) out of control.

An excerpt:

What of enhancement? Here, the case against using tools of gene editing appears even stronger. Nevertheless, as Doudna and Steinberg partly appreciate, revulsion stems from fixating on a specific type of example. When ambitious parents hope their children will exhibit particular characteristics — being tall or intelligent, for example — the desire is often comparative: they want the kids to be taller or smarter than their peers. Genetic enhancement should not cater to that sort of wish. A society in which privileged people buy further biological advantages for themselves and their dependents is an ethically hideous prospect, as exemplified by the alphas, betas, gammas, and deltas of Aldous Huxley’s Brave New World.

When competition plays no role, however, genetic enhancement can be harmless, even benign. The losses affecting us as we age are familiar facts of human life. Hearing becomes less sensitive, and memory declines. Although the causal details underlying these processes are not yet fully known, it is easy to imagine that they might be discovered — and that the discovery could allow somatic interventions to preserve our youthful capacities as we age. People benefiting from those interventions would be genetically enhanced, equipped with abilities no normal human being has ever had. If the interventions were available to all, parts of the standard health protections delivered by all (enlightened) societies, it is hard to see what objections could be leveled against them. …

Yuval Noah Harari is also interested in the threats attending the human future, and impressed with the possibilities of applying biological knowledge to modify human genomes. But in Homo Deus, he paints on a far larger canvas. Scientific advances have provided our species with godlike opportunities. Computer technology and molecular biology together will transform human lives and what it means to be human. Most members of our species will become redundant. All of us will have to face the fact that we are not, and have never been, autonomous agents. The flaws in humanism will be exposed. A new religion in which the flow of data becomes central — becomes the reigning deity — will triumph.

Or will it?•

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The ethical pitfalls of genetic engineering are many, but the upside is likely to go far beyond anything humans have ever done to improve our health, even the creation of vaccines. What’s most exciting about today’s announcement that CRISPR successfully edited mutations from genes in human embryos without provoking an unwanted chain reaction is that the fix wouldn’t only be individual. The lucky baby would no longer pass the hereditary illness on to future generations. 

It’s questionable if our species is equipped to control the many negative applications of a tool so powerful, but it can do much good and isn’t going away, so we need to apply ourselves to that challenging mission.

The opening of Pam Belluck’s NYT article on the breakthrough:

Scientists for the first time have successfully edited genes in human embryos to repair a common and serious disease-causing mutation, producing apparently healthy embryos, according to a study published on Wednesday.

The research marks a major milestone and, while a long way from clinical use, it raises the prospect that gene editing may one day protect babies from a variety of hereditary conditions.

But the achievement is also an example of genetic engineering, once feared and unthinkable, and is sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism.

The study, published in the journal Nature, comes just months after a national scientific committee recommended new guidelines for modifying embryos, easing blanket proscriptions but urging it be used only for dire medical problems.

“We’ve always said in the past gene editing shouldn’t be done, mostly because it couldn’t be done safely,” said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. “That’s still true, but now it looks like it’s going to be done safely soon,” he said, adding that the research is “a big breakthrough.”

Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells — not just some — were mutation-free, and they avoided creating unwanted extra mutations.

“It feels a bit like a ‘one small step for (hu)mans, one giant leap for (hu)mankind’ moment,” Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.•

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A decade ago, Freeman Dyson wrote “Our Biotech Future” for New York Review of Books, envisioning a not-so-far-off time when garages wouldn’t be hatching just start-ups but new life forms. He said this:

Domesticated biotechnology, once it gets into the hands of housewives and children, will give us an explosion of diversity of new living creatures, rather than the monoculture crops that the big corporations prefer. New lineages will proliferate to replace those that monoculture farming and deforestation have destroyed. Designing genomes will be a personal thing, a new art form as creative as painting or sculpture.

Few of the new creations will be masterpieces, but a great many will bring joy to their creators and variety to our fauna and flora. The final step in the domestication of biotechnology will be biotech games, designed like computer games for children down to kindergarten age but played with real eggs and seeds rather than with images on a screen. Playing such games, kids will acquire an intimate feeling for the organisms that they are growing. The winner could be the kid whose seed grows the prickliest cactus, or the kid whose egg hatches the cutest dinosaur. These games will be messy and possibly dangerous. Rules and regulations will be needed to make sure that our kids do not endanger themselves and others. The dangers of biotechnology are real and serious.

If domestication of biotechnology is the wave of the future, five important questions need to be answered. First, can it be stopped? Second, ought it to be stopped? Third, if stopping it is either impossible or undesirable, what are the appropriate limits that our society must impose on it? Fourth, how should the limits be decided? Fifth, how should the limits be enforced, nationally and internationally? I do not attempt to answer these questions here. I leave it to our children and grandchildren to supply the answers.•

In the ten years since, we haven’t gotten to the point of “domesticated biotechnology” on a wide scale, but CRISPR technology has now brought the possibilities at least to the laboratory. This new tool means that our genetic “encyclopedia” can not only be read but edited, reordered, erased. Not being an expert on the topic, I would assume such a process will have obstacles, at least initially, which may slow its progress, but it provides a new path forward, and regardless of what we may declare, it’s one we will head down sooner than later. Competition among nations almost demands a brisk walk–a headlong rush.

What awaits us at the other end? Even if we’re very careful–not a default human trait, especially with a process that will be decentralized–there will be immensely thorny ethical questions to be addressed. Never before has a system promised so much good and ill simultaneously. It may mean freedom from crippling illness and the emergence of a new type of mass terrorism–genocide, even. Days of miracle and wonders, indeed.

The NYRB has since revisited the topic many times, including the latest issue’s smart piece by zoologist Matthew Cobb, which reviews a slate of new titles on the topic, including A Crack in Creation, co-authored by Jennifer Doudna and Samuel H. Sternberg, which I mentioned last week. “We cannot unlearn what we have discovered,” the critic acknowledges, before suggesting some preemptive strikes against science run amok which may or may not prove adequate should we act on them.

An excerpt:

The possibilities of CRISPR are immense. If you know a DNA sequence from a given organism, you can chop it up, delete it, and change it at will, much like what a word-processing program can do with texts. You can even use CRISPR to introduce additional control elements—for example to engineer a gene so that it is activated by light stimulation. In experimental organisms this can provide an extraordinary degree of control in studies of gene function, enabling scientists to explore the consequences of gene expression at a particular moment in the organism’s life or in a particular environment.

There appear to be few limits to how CRISPR might be used. One is technical: it can be difficult to deliver the specially constructed CRISPR DNA sequences to specific cells in order to change their genes. But a larger and more intractable concern is ethical: Where and when should this technology be used? In 2016, the power of gene editing and the relative ease of its application led James Clapper, President Obama’s director of national intelligence, to describe CRISPRas a weapon of mass destruction. Well-meaning biohackers are already selling kits over the Internet that enable anyone with high school biology to edit the genes of bacteria. The plotline of a techno-thriller may be writing itself in real time. …

Already in the early days of her research, Doudna seems to have been haunted by the implications of her work—she describes a disturbing dream in which Hitler keenly asked her to explain the technique to him. Over the last couple of years, following meetings with patients suffering from genetic diseases, Doudna has shifted her position, and now feels that it would be unethical to legally forbid a family to, say, remove a defective portion of the gene that causes Huntington’s disease from an embryo, which otherwise would grow into an adult doomed to a horrible death.

Like many scientists and the vast majority of the general public, Doudna remains hostile to changing the germline in an attempt to make humans smarter, more beautiful, or stronger, but she recognizes that it is extremely difficult to draw a line between remedial action and enhancement. Reassuringly, both A Crack in Creation and DNA Is Not Destiny show that these eugenic fantasies will not succeed—such characteristics are highly complex, and to the extent that they have a genetic component, it is encoded by a large number of genes each of which has a very small effect, and which interact in unknown ways. We are not on the verge of the creation of a CRISPR master race.

Nevertheless, Doudna does accept that there is a danger that the new technology will “transcribe our societies’ financial inequality into our genetic code,” as the rich will be able to use it to enhance their offspring while the poor will not. Unfortunately, her only solution is to suggest that we should start planning for international guidelines governing germline gene editing, with researchers and lawmakers (the public are not mentioned) encouraged to find “the right balance between regulation and freedom.”•

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As I’ve written before, plenty of people will rush to have “CRISPR babies” and be willing recipients of makeovers that extend far further than skin-deep. Botox and fillers and cosmetic surgery apps are just a dress rehearsal for what’s to come, and it will arrive, whether China or Europe or the U.S. first begins experimenting in earnest with gene modification. There are currently many unintended consequences attending the process, but the “games” will eventually begin.

In regards to the proliferation of plastic surgery, here’s an excerpt from a BBC piece by Dominic Hughes about children being targeted with propaganda:

Prof. Jeanette Edwards, from the University of Manchester, who chaired the council’s inquiry into ethical issues surrounding cosmetic procedures, said some of the evidence around games aimed at younger children had surprised the panel.

“We’ve been shocked by some of the evidence we’ve seen, including make-over apps and cosmetic surgery ‘games’ that target girls as young as nine.

“There is a daily bombardment from advertising and through social media channels like Facebook, Instagram and Snapchat that relentlessly promote unrealistic and often discriminatory messages on how people, especially girls and women, ‘should’ look.”•

The next phase, the bold move toward “designer babies,” is addressed in Ed Yong’s smart Atlantic article about scientist Jennifer Doudna trying to reckon with her prominent role in the “CRISPR Revolution.” The opening:

Jennifer Doudna remembers a moment when she realized how important CRIPSR—the gene-editing technique that she co-discovered—was going to be. It was in 2014, and a Silicon Valley entrepreneur had contacted Sam Sternberg, a biochemist who was then working in Doudna’s lab. Sternberg met with the entrepreneur in a Berkeley cafe, and she told him, with what he later described to Doudna as “a very bright look in her eye that was also a little scary,” that she wanted to start applying CRISPR to humans. She wanted to be the mother of the first baby whose genome had been edited with the technique. And she wanted to establish a business that would offer a menu of such edits to parents.

Nothing of the kind could currently happen in the U.S., where editing the genomes of human embryos is still verboten. But the entrepreneur apparently had connections that would allow her to offer such services in other countries. “That’s a true story,” Doudna told a crowd at the Aspen Ideas Festival, which is co-hosted by the Aspen Institute and The Atlantic. “That blew my mind. It was a heads-up that people were already thinking about this—that at some point, someone might announce that they had the first CRISPR baby.”

The possibility had always been there. Bacteria have been using CRISPR for billions of years to slice apart the genetic material of viruses that invade their cells. In 2012, Doudna and others showed how this system could be used to deliberately engineer the genomes of bacteria, cutting their DNA with exceptional precision. In quick succession, researchers found that they could do the same in mammalian cells, mice, plants, and—in early 2014—monkeys. “I had all of this at the back of my mind,” Doudna told me after her panel. But Sternberg’s story about his meeting “was the moment where I said I needed to get involved in this conversation. I’m not going to feel good about myself if I don’t talk about it publicly.”

That has not been an easy journey. Doudna built her career on molecules and microbes. As few as five years ago, she was, by her own admission, working head-down in an ivory tower, with no plans of milking practical applications from her discoveries, and little engagement with the broader social impact of her work.

But CRISPR forcefully yanked Doudna out of that closeted environment, and dumped her into the midst of intense ethical debates about whether it’s ever okay to change the DNA of human embryos, whether eradicating mosquitoes is a good idea, and whether “fixing” the genes behind inherited diseases is a blow to disabled communities.•

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