A Crack in Creation

1. CRISPR: From Bacterial Defense to Gene Editing Revolution

By the summer of 2015, the biotechnology that I’d helped establish only a few years before was growing at a pace that I could not have imagined.

Unexpected origins. Jennifer Doudna's journey into CRISPR began with an unlikely collaboration with geomicrobiologist Jillian Banfield, driven by curiosity about a bacterial immune system. This system, CRISPR-Cas, initially studied for its role in bacterial defense against viral infections, unexpectedly revealed a molecular machine capable of precise DNA manipulation.

CRISPR's function. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a bacterial defense mechanism that allows microbes to fight off viruses. Bacteria store snippets of viral DNA within their own genome, using this information to recognize and destroy those same invading phages during future infections. This system functions like a molecular vaccination card.

Revolutionary potential. The discovery that CRISPR could be repurposed for gene editing transformed the life sciences. This technology allows scientists to manipulate and rationally modify the genetic code of any species, including our own, with unprecedented ease and precision.

2. Unlocking the Genome: The Quest for Precision

For decades, long before I entered the field, women and men in the life sciences had labored to gain this know-how and develop these tools.

Early gene therapy. Early attempts at gene therapy involved using viruses to deliver therapeutic genes to humans. While these efforts were revolutionary, they were often hampered by safety concerns and limited effectiveness.

Gene targeting. Scientists developed gene targeting, also known as gene editing, which allowed them to precisely paste genes into matching sites in the genome. This approach, utilizing homologous recombination, offered a dramatic improvement over the randomness of gene splicing with viruses.

Programmable nucleases. The development of zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) marked a significant step forward. These designer nucleases could be programmed to target specific DNA sequences, enabling more precise gene editing.

3. Ethical Crossroads: The Germline Debate

Someday we may consider it unethical not to use germline editing to alleviate human suffering.

Germline vs. somatic editing. Germline editing, which involves altering the DNA of eggs, sperm, or early embryos, raises profound ethical questions because these changes are heritable, forever altering the genetic composition of humankind. Somatic cell editing, on the other hand, affects only the individual being treated and is not passed on to future generations.

Ethical concerns. The potential for unintended consequences, the risk of widening social or genetic inequalities, and the specter of a new eugenics movement are among the ethical concerns surrounding germline editing. Some view any form of genetic manipulation as a violation of the sacred laws of nature, while others argue that leaving human beings at the mercy of faulty genetics is immoral.

The moral imperative. Some argue that it may be unethical not to use germline editing to alleviate human suffering. This perspective highlights the potential to prevent devastating genetic disorders from being passed on to future generations.

4. CRISPR in the Wild: Modifying Ecosystems

The animal kingdom has been the first and, so far, the biggest proving ground for this new gene-editing tool.

Applications in flora and fauna. CRISPR has been widely deployed to edit crop genomes, paving the way for agricultural advances that could dramatically improve people’s diets and shore up the world’s food security. Scientists have also harnessed CRISPR to generate genetically enhanced versions of animals, such as supermuscular beagles and micropigs.

De-extinction. Geneticists are even using CRISPR to transform Asian elephant DNA into something that looks more and more like woolly mammoth DNA, with the hope of someday resurrecting this extinct beast. This raises questions about the ecological impact of reintroducing extinct species.

Ecological concerns. While applications in the planet’s flora and fauna are exciting, tinkering with the genetic underpinnings of our ecosystem could also have unintended consequences. It is important to consider the ramifications in advance and to engage in a global, public, and inclusive conversation about how to best harness gene editing in the natural world, before it’s too late.

5. Human Health: The Promise of Cures

Gene editing holds the promise of life-changing treatments and, in some cases, lifesaving cures.

Treating genetic diseases. CRISPR offers the potential to edit and repair mutated genes directly in human patients. In laboratory-grown human cells, this new gene-editing technology was used to correct the mutations responsible for cystic fibrosis, sickle cell disease, some forms of blindness, and severe combined immunodeficiency, among many other disorders.

Cancer immunotherapy. Physicians have already begun treating some cancers with souped-up immune cells whose genomes have been fortified with edited genes to help them hunt down cancerous cells. This approach harnesses the power of the body's own immune system to fight cancer.

Challenges and limitations. While CRISPR-based therapies hold great promise, there are still challenges to overcome before they can be widely available to human patients. These include ensuring the safety and accuracy of gene editing, as well as developing effective delivery methods.

6. The Power and Peril of Gene Drives

Given the suffering caused by some species, neither is it obviously one to be ignored.

Gene drives defined. Gene drives are a revolutionary technology that gives bioengineers a way to "drive" new genes—along with their associated traits—into wild populations at unprecedented speeds. This technology has the potential to alter entire ecosystems.

Potential benefits. Gene drives could be used to address global problems in agriculture, conservation, and human health. For example, they could be used to eradicate invasive species, control agricultural pests, and stamp out infectious diseases such as malaria.

Ethical concerns. The potential for unintended consequences and the risk of a gene drive getting out of control and disrupting an ecosystem's delicate balance are major concerns. There is also the risk that this incredibly powerful tool could wind up in the hands of people who have no compunction about using gene drives to cause harm.

7. Democratization of CRISPR: A Double-Edged Sword

Up until now, the CRISPR revolution has taken place largely behind the closed doors of laboratories and biotech startups.

Accessibility of CRISPR. CRISPR has made gene editing available to the masses, transforming this once-esoteric practice into a hobby or a craft. This democratization of CRISPR has been facilitated by inexpensive tools, online resources, and readily available information.

DIY biohacking. The rise of do-it-yourself biohackers, eager tech enthusiasts hoping to dabble in CRISPR-based gene editing in their own homes, raises concerns about safety and regulation. The potential for misuse and unintended consequences is a significant challenge.

Public involvement. Scientific progress requires more than research, investment, and innovation; public involvement is also key. It is essential to draw the CRISPR revolution into the light and engage in a global discussion about its implications.

8. Navigating the Future: A Call for Open Dialogue

The wave is coming. Let’s paddle out and ride it together.

The need for discussion. Gene editing forces us to grapple with the tricky issue of where to draw the line when manipulating human genetics. Some people view any form of genetic manipulation as heinous, while others see the genome simply as software that can be fixed, cleaned, updated, and upgraded.

Evolving views. The author's own views on the subject are still evolving, but she was struck by a comment made during a meeting to discuss human germline editing in embryos: "Someday we may consider it unethical not to use germline editing to alleviate human suffering." This remark turned the conversation on its head.

A global conversation. A global discussion about gene editing has already begun; it’s a historic debate about nothing less than the future of our world. It is essential to get as many sectors of society as possible involved in this conversation.

Last updated: February 20, 2025