Tweaking Life

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Scientists can now easily manipulate genes. Should they?

Kathy Krentz has played Mother Nature for most of her career, tinkering with the genomes of mice embryos before implanting the embryos in the wombs of recipient mother mice. After gestating for 20 days, the mutant litter is delivered to the researchers who ordered mice carrying a specific mutation.

“Mice make a good animal model because they reproduce very quickly, and you can get a cohort of animals that are genetically identical very quickly,” says Krentz, who runs UW-Madison’s Transgenic Animal Facility.

Aided by a powerful microscope, Krentz has injected hundreds of thousands of mice embryos with exogenous genes, inserted through a microscopic glass syringe. This process, known as transgenesis, was developed in the early 1970s. But it doesn’t always work.

Exogenous genes are expressed in offspring only if accepted by cells that store the biochemical units of heredity, known as the germline.

“The problem was that it would randomly insert DNA just anywhere on the genome,” she explains. “So as a cell divided, that piece of DNA would be incorporated into the dividing embryo, anywhere.”

In 2014, Krentz scrapped the laborious, error-prone process in favor of a new tool known as CRISPR-Cas9, despite her initial skepticism of the hype percolating around it.

“As we read scientific articles and looked at the data as to whether this was worth investing in, it became clear very quickly that CRISPR-Cas9 was going to be game changing,” she recalls. “And it has been.”