Bacterial Sex: A building block for biotech

Circulating Now welcomes guest bloggers Diane Wendt and Mallory Warner from the Division of Medicine and Science at the Smithsonian National Museum of American History back for a final post in this series. As curators of our recent exhibition, From DNA to Beer: Harnessing Nature in Medicine and Industry, Diane and Mallory spent months researching four different microbes and the influence they’ve had on human life.

E.coli is a curious microorganism, a bug which lives peaceably in our gut most of the time, can make us violently ill in some cases, and which scientists have tweaked and tamed into the microbial equivalent of the common lab rat. What’s more, research on the sex life of E. coli eventually led to its development as world’s first commercially important genetically modified organism. Before we get into that, however, let’s take a look back at the history of this interesting little bug.

Formal photographic portrait.

Theodor Escherich
Wikimedia Commons

In 1885, a German pediatrician by the name of Theodor Escherich became the first to describe the bacteria. Escherich spent his days examining the microbial contents of infants’ diapers in the hopes of identifying the bug responsible for diarrhea, a major cause of infant mortality in the late 19th century. He named the rod-shaped intestine-dweller Bacterium coli communis, but by 1918, his scientific colleagues had rechristened it Escherichia coli, a tribute to its discoverer.

E. coli continued to be studied through the first half of the 20th century, but revelations about the bacteria’s sexual behavior turned it into a full-fledged lab superstar. In 1946, Joshua Lederberg, using E. coli samples given to him by Edward Tatum (with whom he would eventually share a Nobel Prize), began experiments to find evidence for the existence of bacterial sex.

At the time, the research was a shot in the dark. Commonly held belief pegged all bacteria as sexless creatures, reproducing through division to create two daughter cells which were genetic clones of the mother. Lederberg’s research, however, laid that belief to rest. His experiments mixed two mutant strains of E. coli each strain lacking the genes to produce two different vital nutrients. Without a steady supply of their requisite nutrients, the bacteria died. When the two strains were mixed together, however, Lederberg found some of their offspring were able to thrive on a medium with no added nutrients, indicating that somehow the bacteria were able to “mate” providing their progeny with the genes the other parent lacked.

Lederberg standing in a lab looking into a petri dish

Joshua Lederberg in his lab at the University of Wisconsin, October 1958.
He joined the University as an assistant professor in 1947, at the ripe old age of 22.
National Library of Medicine #B016808

Lederberg called this process “conjugation.” As microscopy improved in the years to come, it would eventually be possible to see this bacterial sex in action. Photomicrographs of conjugating bacteria showed the two cells interacting by means of a pilus, a thin appendage used to connect the two cells.

Further research on conjugation by Lederberg and others demonstrated that conjugation was not a perfect unicellular analogy of sexual reproduction. Rather than mixing the entirety of their genetic material to create offspring with characteristics of both parents, conjugation was more of a DNA donation. One bacterium gave another bacterium a special bonus loop of DNA, which Lederberg dubbed a plasmid. Plasmids, rather than containing all the information for everyday life, were essentially a power-boost, giving bacteria the ability to be better versions of themselves—making their own nutrients or acquiring resistance to a specific antibiotic for instance.

An electron microscope image of a two capsule shaped bacteria connected by a thin tube.

Bacterial Conjugation
Courtesy Charles C. Brinton Jr.

Continuing research on E. coli made it a darling of the science world, a new favorite research subject. Easy to grow in the lab and quick to reproduce, the bacteria were a perfect model organism for the newly developed field of bacterial genetics.

In the 1970s, scientists hoping to take genetics into the realm of science fiction turned to their knowledge of bacterial sex and plasmids to accomplish the earliest genetic engineering. Researchers found they could cut and paste sections of plasmids together using a special class of proteins called restriction enzymes. These plasmids, now containing whatever genes the scientists chose, could be reintroduced into bacteria. By the mid-1980s the method was applied to E. coli, engineering the bacteria to produce medicines from insulin to human growth hormone, products which helped establish the American biotechnology industry.

A tray of labeled plastic tubes with snap on caps.

Tubes used by biotech company Genentech to hold recombinant DNA plasmids, about 1980. Each tube is labeled with a code representing the kind of plasmid it contains and, on some tubes, a date.
Courtesy the National Museum of American History

Explore From DNA to Beer: Harnessing Nature in Medicine & Industry online for yourself at http://www.nlm.nih.gov/exhibition/fromdnatobeer/index.html. To book the traveling exhibition or see when it comes to your town, visit the traveling exhibition page at http://www.nlm.nih.gov/hmd/about/exhibition/fromdnatobeer-bookinfo.html. This is the final post in this series.