Anything found to be true of E. coli must also be true of elephants.
A huge glow-in-the-dark replica of Escherichia coli will be on display in Manhattan’s City Hall Park through the fall. It’s part of an exhibition by Katja Novitskova showcasing life on this planet that appears otherworldly. The 3-D piece, at about twice my height, is not particularly beautiful. Nor is it likely to become a favorite among jaded New Yorkers. Still, like Novitskova, I appreciate—and in fact, I am in awe of—E. coli.
The microbe is used to notoriety. It’s the germ that most people associate with food poisoning. Yet there are thousands of strains of the bacterium, many of which are critical citizens of our microbiome and important to our gut health. Biologists like it because it’s easy to grow and to manipulate genetically, and its genome is now better understood than that of any other organism. The humble E. coli has played a vital role in biotechnology since the industry’s genesis, and its usefulness continues to astonish me.
In the 1960s, enzymes were discovered in E. coli that cleave the DNA of attacking viruses at restricted sites (hence they were called “restriction enzymes”). It was soon apparent that when purified, these enzymes could be used to manipulate any DNA, and this advance in basic science (recombinant DNA) ultimately gave birth to the trillion-dollar biotechnology industry. For the discovery and characterization of restriction enzymes, the 1978 Nobel Prize was awarded to Arber, Nathans, and Smith. Also in 1978, Pitt alumnus Herb Boyer, in San Francisco, inserted a human insulin gene into E. coli, thereby producing large amounts of synthetic insulin. That approach laid the groundwork for many effective treatments for human disease and mega-companies such as Genentech. In 2012, UT Southwestern’s James Chen, one of our Legacy Laureates, leaned on E. coli to identify a previously unknown pathway (cGAS-STING) that triggers an inflammatory and immune response when viral DNA is detected outside of the cell nucleus. This pathway appears to play a role in human tumor surveillance and autoimmunity, and it may help boost the effectiveness of vaccines.
Another of E. coli’s ancient defense mechanisms—CRISPR-Cas9, further developed as a biotechnology tool by our 2016 Dickson Prize winner Jennifer Doudna—has created extraordinary scientific and ethical interest. CRISPR (clustered regularly interspersed short palindromic repeats) are sequences in our DNA that in bacteria were originally derived from invading viruses. Subsequently, any attacking viral DNA that matched those sequences in the bacterial genome was cleaved by a CRISPR-associated enzyme (Cas). Now scientists can apply that system, together with a “guide RNA,” to target any gene that matches that RNA. Clearly, the technology can be used to edit genes that cause human disease—adding ones that are missing or disabling ones that cause a disease. And recently, labs in China and Oregon used this approach to alter the genes of very early human embryos in vitro. We will need to be vigilant in our ethics as we step into this precarious territory.
The idea that we have been able to carjack a seemingly simple bacterium’s multiple defenses against invading viruses to gain profound insight into human biology, and even alter that biology, truly is, as I noted before, astonishing. What a testament to basic science investigation, which the National Science Foundation defines as research with no apparent application when it is begun!
Arthur S. Levine, MD
Senior Vice Chancellor for the Health Sciences
John and Gertrude Petersen Dean, School of Medicine
Photo by Joshua Franzos