In the realm of genetic manipulation, Crispr technology emerges as a double-edged sword. Enabling precise gene editing, it holds promise for eradicating diseases like sickle cell through treatments like Casgevy. Yet, with the power to shape the very fabric of life, ethical concerns loom large. While some foresee a future free of genetic diseases, others fear unintended consequences such as designer babies, dangerous mutants, and military exploitation. As the Crispr saga unfolds, humanity treads a fine line between scientific advancement and the perils of playing with the code of life.
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All About Crispr, the DNA Tool Behind the New Sickle Cell Therapy
By John Lauerman
Humans have been manipulating genetics since early civilizations realized that certain traits of crops, animals and people themselves were hereditary. The modern-day mapping of all human genes raised the prospect of learning precisely which genes control which traits and then directly altering their DNA codes. After years of hit-and-miss efforts, a gene-editing system called Crispr that’s cheap, effective and easy to use promises to change our relationship with genetics — for better, worse or both. Its champions foresee using Crispr to control pests, increase food production and treat human diseases. They simultaneously worry that its use could unleash dangerous mutants, designer babies and new weapons of mass destruction. In the meantime, Crispr has given birth to a new biotechnology industry that’s beginning to fulfill its promise in treating intractable illnesses. Late this year, a treatment for sickle cell disease became the first Crispr-based therapy to gain regulatory approval.
1. What’s the approved Crispr therapy?
Because of Crispr’s ability to cut and paste individual genes, companies have been working to use the technology to rectify DNA flaws that lead to inherited disease. Those efforts came to fruition when two drugmakers, Vertex Pharmaceuticals Inc. and Crispr Therapeutics AG, gained approval to sell Casgevy, a Crispr-based treatment with the potential to cure sickle cell disease. UK authorities gave the green light in November, and US regulators followed in December.
2. How does the Crispr treatment for sickle cell disease work?
The companies’ approach, which involves removing blood stem cells and editing them in a lab, is viewed as a safer application of Crispr than editing cells’ genes in the body. Scientists can make sure they haven’t accidentally edited the wrong bits of DNA before replacing the edited cells. But there are trade-offs: To receive Casgevy, patients have to undergo a painful, draining bone-marrow procedure. Editing cells in the body, or “in vivo,” would remove those steps, making the therapy more convenient and avoiding the discomfort.
3. Has the in vivo approach been tried?
Some companies and researchers have already begun using Crispr in vivo experimentally. In October, Intellia Therapeutics Inc. got US regulators’ go-ahead to use the approach in a final-stage study of patients with a rare disease called transthyretin amyloidosis. Another example occurred in 2018, when Chinese scientist He Jiankui infamously announced that he’d used the technology to alter the genes of a pair of twins while they were embryos with the aim of making them resistant to HIV. Using Crispr to make changes to embryos and germline cells — sperm, eggs and zygotes — is especially contentious because the modifications are passed to progeny. His announcement resulted in an ethical outcry and further restrictions on manipulating the DNA of healthy embryos.
4. What’s Crispr technology based on?
Crispr technology is based on a rudimentary bacterial immune system that Japanese scientists first identified three decades ago and named Clustered Regularly Interspaced Short Palindromic Repeats. These sequences of genetic code destroy pathogens by cutting the DNA of the invader using enzymes called CAS nucleases, Cas9 being the most widely studied.
5. What’s the history of Crispr technology?
Understanding of how the system can chop through and then replace segments of DNA grew slowly until 2012, when researchers at the University of California, Berkeley published a paper on making molecular guides that allow Crispr to skim along DNA, targeting exactly the right spot to make a slice. Soon afterward, scientists at the Broad Institute in Cambridge, Massachusetts said they’d adapted Crispr for use in human cells. In 2020, pioneering scientists Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for their development of the gene-editing technology. A researcher with basic skills and just a few hundred dollars’ worth of equipment can employ Crispr, creating enormous space for innovation.
6. How well does Crispr work?
The gene-editing system isn’t perfect. It can make unintended cuts in DNA, with effects unknown. Scientists are working on minimizing these slip-ups. Newer methods of gene revision, called prime editing and base editing, are thought to produce fewer unwanted alterations.
A Bloomberg video explores the transformative power of Crispr
7. What are the risks of Crispr?
While Crispr offers enormous potential to improve human welfare, some of the risks are also immense.
- By improving so-called gene drives, experimental systems that increase the chance a certain gene is inherited, Crispr might one day, for instance, ensure that mosquitos can no longer host the Zika virus. Yet theoretically, the modifications could also allow the bugs to spread a more harmful pathogen.
- Germline editing raises similar issues. Potentially, a genetic disease could be eliminated from a family forever. But if something goes wrong, the consequences are potentially eternal, too, affecting future generations who would not have given their consent to the intervention. Some scientists worry that germline editing would invite enhancements of babies for non-medical reasons and could even lead to the division of humans into subspecies. Other commentators have argued that people bred to be supersmart could produce positive effects for society by generating innovations that would be used by everyone.
- Meanwhile, defense specialists fret over the possible military applications of Crispr. In its 2019 assessment of worldwide threats, US intelligence agencies warned of adversaries potentially using gene editing to “develop novel biological warfare agents, threaten food security, and enhance or degrade human performance.”
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The Reference Shelf
- Bloomberg columnist Lisa Jarvis analyzes the regulatory issues around the Crispr-based therapy for sickle cell disease.
- An article in Biochemistry (Moscow) explores the history of Crispr and ethical considerations of its use
- The call among scientists for a moratorium on heritable genome editing.
- An article in the Journal of Molecular Biology explores the moral considerations for using Crispr.
- A Congressional Research Service report on Crispr.
© 2023 Bloomberg L.P.
