A Crack In Creation: A Nobel Prize Winner's Insight into the Future of Genetic Engineering

by Jennifer A. Doudna

they’re only the b...

Within the next few years, this new biotechnology will give us higher-yielding crops, healthier livestock, and more nutritious foods. Within a few decades, we might well have genetically engineered pigs that can serve as human organ donors—but we could also have woolly mammoths, winged lizards, and unicorns.

No, I am not kidding.

won’t be long before CRISPR allows us to bend nature to our will in the way that humans have dreamed of since prehistory.

researchers have harnessed CRISPR to generate

animal models of human disease with far greater precision and flexibility than before—not just in mice, but in whatever animals best exhibit the disease of interest,

whether it be monkeys for autism, pigs for Parkinson’s, or fe...

One of the most interesting aspects of the CRISPR technology is the way it enables the study of feature...

limb regeneration in Mexican ...

aging in killifish, and skeletal development i...

love the notes and pictures colleagues send me describing their CRISPR experiments—the beautiful butterfly-wing patterns whose genetic underpinnings they’ve uncovered, or the infectious yeast whose ability to invade human...

These kinds of experiments reveal new truths about the natural world and about the genetic similarities that bind all organisms togeth...

I was amazed to learn that several research teams are using CRISPR to “humanize” various genes in pigs in the hope that life-threatening organ-donor shortages might one day be solved by xenotransplantation—the transfer of organs grown in pigs (or other animals) into human recipients.

gene-editing technologies to create new designer pets,

gene-edited micropigs that never grow larger than small dogs.

And in a page taken straight out of a famous book-to-film sci-fi franchise, some laboratories are pursuing a venture known as de-extinction, which is nothing less than the resurrection of ext...

My friend Beth Shapiro, a professor at the University of California, Santa Cruz, is excited to use this strategy to re-create extinct species of birds for the purpose of ...

Along the same lines, efforts are already under way to convert the elephant genome into the woolly mammoth ge...

CRISPR might be employed to destroy entire species—an application I never could have imagined when my lab first entered the fledgling field of bacterial adaptive immune systems just ten years ago.

CRISPR gives us the power to radically and irreversibly alter the biosphere that we inhabit by providing a way to rewrite the very molecules of life any way we wish.

tinkering with the genetic underpinnings of our ecosystem could also have unintended consequences.

how to best harness gene editing in the natural world, before it’s too late.

In the few years since its inception, CRISPR has been harnessed to edit genes in rice that confer protection against bacterial blight; to endow corn, soybeans, and potatoes with natural resistance to herbicides; and to produce mushrooms that are impervious to browning and premature spoiling. Scientists have used CRISPR to edit the genome of sweet oranges, and a team of California researchers is now attempting to apply the technology to save the U.S. citrus industry from a bacterial plant disease called huanglongbing—a Chinese name that translates as “yellow dragon disease”—that has devastated parts of Asia and now threatens orchards in Florida, Texas, and California. In South Korea, scientist

Animal research is indispensable to the study of human disease, whether it’s used to confirm the genetic causes of certain disorders, to evaluate potential drugs, or to test the efficacy of medical interventions like surgery or cell therapy.

the common house mouse (Mus musculus), which shares 99 percent of its genes with humans.

Mice and humans exhibit similar physiological features, such as immune, nervous, cardiovascular, musculoskeletal, and other systems.

Mice can be bred in captivity and are easy and cheap to maintain because of their small siz...

Their accelerated lifespan—one mouse year equals roughly thirty human years—means that the entire life cycle can be studied in just a few years in the lab. And perhaps most important, mice can be genetically manipulated using a variety of approaches—CRISPR being the most powerful...

Millions of mice are bred and shipped each year to researchers worldwide, and there are well over thirty thousand unique mouse strains in existence that are used to study everything from can...

in early 2014, when a Chinese team created gene-edited cynomolgus monkeys by injecting CRISPR into one-cell embryos, much like the method used in mice one year earlier. In this study, the scientists programmed CRISPR to simultaneously target two genes: one associated with severe combined immunodeficiency in humans, the other associated with obesity, both of which have clear implications for human health.

These gene-edited monkeys can serve as reliable stand-ins for human patients, allowing scientists to hunt for disease cures without endangering human lives. The pig has become another popular animal model of human disease, thanks to CRISPR.

anatomic similarity to humans, its relatively short gestation period, and its large litter size.

Indeed, gene-edited pigs have already been used to model pigmentation defects, deafness syndromes, Parkinson’s disease, and immunological disorders, and the list will continue to grow. Many scientists see the pig itself as a potential source of medicine. Someday soon, we might be using pigs as bioreactors to produce valuable drugs like therapeutic human proteins, which are too complex to synthesize from scratch and can only be produced in living cells.

transgenic animals

biopharmaceutical drugs, or farmaceuticals, as they’re co...

The first such drug to be approved by the FDA is an anticoagulant called antithrombin, and it is secreted in the milk of genetically modified goats. Another approved drug is isolated from the milk of transgenic rabbits, and in 2015, the FDA gave the go-ahead for a protein...

For example, experiments in pigs have shown that CRISPR enables outright replacement of pig genes with their human gene counterparts, allowing for more efficient recovery of the therapeutic gene-encoded proteins. When you consider that many of the world’s bestselling drugs are protein-based, it’s clear that the potential for gene editing in this particular subfield of medicine is enormous.

Some scientists hope that pigs can offer even more: a vast, renewable source of whole organs for xenotransplantation into human recipients.

In the United States alone, more than 124,000 patients are currently on the waiting list for transplants, yet only approximately 28,000 procedures are carried out annually.

It’s been estimated that a new individual is added to the national transplant list every ten minutes and that an average of twenty-two people a day die while waiting for a transplant or become so sick that they are no longer eligible to receive a transplant. The shortage of donor organs is the biggest cause of this ongoing tragedy.

Previous advances focused on transferring human genes into the pig genome so that pig organs might escape the hyperacute immune rejection that threatens any xenotransplant.

Gene editing is now being harnessed to shut down pig genes that might provoke the human immune response and to eliminate the risk that porcine viruses embedded in the pig genome could hop over and infect humans during transplantation. Finally, cloning technologies offer a way to seamlessly combine the different genetic alterations into a single animal.

company called Revivicor has already outlined plans to breed a thousand pigs a year in state-of-the-art facilities with surgical theaters and helipads to deliver fresh organs whenever they’re needed.

Gene-edited animal models like mice and monkeys will advance our understanding of human disease, and gene-edited pigs may serve as future organ donors, but I hope that a shared respect for animal welfare will temper these and similar efforts.

Take the case of a brand-new breed of miniaturized pig—the so-called micropig. Created with gene editing at the Beijing Genomics Institute (BGI) in China, these adorable swine wowed crowds at the biotech summit where they were first unveiled.

The adult micropigs weigh in at about thirty pounds, similar to a medium-size dog,

slicing apart and inactivating the gene that responds to growth hormone, scientists produced stunted pigs that otherwise developed normally.

research—a Chinese group recently used CRISPR in micropigs to generate a human Parkinson’s disease model—BGI has also begun offering them as pets, with a price tag of around fifteen hundred dollars per pig. Someday, consumers might even have the option of selecting custom features, like varied colors or coat patterns, all made possible with gene editing.

Unlike micropigs, whose health is no different than their normal-size relatives, extensive inbreeding of dogs has had devastating health consequences.

late 2015, scientists in Guangzhou, China, reported the first application of CRISPR in beagles, using it to enhance muscle mass by knocking out the same myostatin gene linked to double muscling in whippet dogs and Belgian Blue cows. The two puppies that contained the intended mutations were named Hercules and Tiangou, in honor of the superhuman hero of Greek mythology and the heavenly dog in Chinese mythology.