How Genetic Surgery Could Transform Biology

Scientific American Custom Media talks to 2018 Kavli Prize Laureate Jennifer Doudna about the future of gene editing
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Fred Sanger looking at an autoradiogram of DNA sequence

The dawn of genetic engineering

Since the 1970s, scientists like Fred Sanger have developed methods to modify the genes of many organisms—knocking them out, altering them, adding genes from one species to another. This has led to major scientific and technological advances.

Credit: MRC Laboratory of Molecular Biology
Dorsal view of a zebrafish brain

Genetic engineering has led to multiple advances

It has helped scientists visualize working neurons inside the brain, such as these shown in a zebrafish. It has also revealed the molecular roots of human disease, and enabled biotech companies to mass-produce the active ingredients of vaccines and insulin for diabetics. But altering genes was slow, error-prone and expensive. Some breakthroughs were slow to arrive, including safe and effective gene therapies, hardy crops that withstand drought and heat, and genetically modified livestock that produce organs for transplantation.

Credit: Monica Folgueira & Steve Wilson
Jennifer Doudna in her laboratory

Jennifer Doudna discovers precision gene editing

In 2011 Doudna, a professor of molecular and cell biology at the University of California, Berkeley, was investigating how bacteria fight off viruses. She instead discovered a new method of precision gene editing called CRISPR—for which she was eventually awarded the Kavli Prize.

Watch and learn how we can modify genes with CRISPR Credit: Nick Otto for The Washington Post via Getty Images
DNA strand
“CRISPR is a tool that gives people the power to control their own evolution and the evolution of our species. It's kind of an awesome thing to think about. … It's something that in the not too distant past would have been unimaginable because we had no idea that there would be a technology that would allow that kind of manipulation of DNA.”
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graphic showing how CRISPR technology works
CRISPR targets genes and modifies them In CRISPR technology, a protein called Cas9 (blue) binds to a small piece of RNA (beige) that’s engineered to match a specific stretch of DNA (turquoise) in the genome. The RNA guides Cas9 to that stretch of DNA. Cas9 cuts the DNA, disrupting the gene. Then the cell’s own DNA repair machinery inactivates the gene or edits in a customized DNA sequence. Credit: Falconieri Visuals
genetically engineered pigs

CRISPR technology takes off

Today CRISPR technology lets scientists insert genes, delete them, and rewrite them at will. This makes it fast, easy and inexpensive to edit the genome of any organism. Scientists are using CRISPR to develop gene therapies, hardier crops, and engineered cell and animal models to speed research on cancer and mental illness. But questions about the technology remain.

Credit: Imaginechina Limited/Alamy

CRISPR may be too error-prone for some clinical applications

In a recent study, scientists from the Wellcome Sanger Institute in Hinxton, UK, reported that CRISPR editing caused unexpected mutation in roughly 16 of every 50 cells examined. That ratio is represented here by healthy pigs (pink) to mutants (white), and it is far more than scientists had expected. Faulty editing of the human genome could lead to cancer or other diseases.

But researchers are engineering more accurate CRISPR systems

In 2019 a Duke team modified CRISPR’s guide RNA to make the system 50 times more accurate. Other researchers are genetically engineering the Cas9 protein to improve accuracy, and testing CRISPR systems that edit RNA but leave the genome untouched.

Should we make designer babies?

In 2018, Chinese scientist Jankui He said he used CRISPR while performing in vitro fertilization to create genetically modified human embryos, which developed into twin baby girls. The scientific world condemned him because the technology has not undergone proper testing. He was also prosecuted in China and sentenced to three years in prison.

Credit: Shutterstock

Should we allow CRISPR to alter entire species?

CRISPR-based gene drive technology can spread an altered gene through an entire population of organisms. This could stop mosquito-borne diseases like malaria. Scientists at Imperial College London have altered an entire population of mosquitoes in the lab. Meanwhile, the United Nations has called for limits on field tests, and DARPA is spending $65 million to learn how to control, counter and reverse gene drives.

Credit: Getty Images
To make sure CRISPR is used wisely, the National Academy of Sciences in 2017 recommended these safeguards:
  • • Limit clinical trials to treatment and prevention of serious diseases or disabilities.
  • • Use the regulatory processes already in place for human gene therapy.
  • • Don’t edit genes in germline (heritable) cells because the editing is not yet accurate enough.
  • • Permit clinical trials of gene editing on germline (heritable) cells only to treat or prevent serious disease, and only with stringent oversight.
Jennifer Doudna
“I’m still pinching myself about where we are today with genome editing. … It’s just a remarkable thing to think about the project as it began in our own lab with our collaborators. … To think about all that has happened over the last seven years since the original publication of our paper, I think that it's just been a remarkable journey.”
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This article was produced for The Kavli Prize by Scientific American Custom Media, a division separate from the magazine's board of editors. Share The Project