Douglas Berg, PhD, soon-to-be professor emeritus of molecular microbiology, enjoys what he calls “scientific matchmaking.” He often reaches out to establish collaborations in different disciplines or among distant colleagues, sometimes suggesting scientific partnerships that do not directly involve his own research.
“They say one way of achieving immortality is to plant a tree,” says Stephen Beverley, PhD, Marvin A. Brennecke Professor and head of Molecular Microbiology. “All these collaborations that Doug has helped start are his trees, and they will be bearing fruit for many years to come.”
Berg speaks quietly but with enthusiasm for research and for the people he’s met and the places he’s visited in pursuit of scientific knowledge.
Starting out in science
Berg’s first collaborator was his older sister, the late Claire Berg, PhD. He traces their partnership in biology back to his years in elementary school. During summers, he and Claire would propagate plants from cuttings harvested at their house in the Bronx.
“We’d sell the plants to neighbors or to commuters at the local train station,” Berg says. “We also raised chickens and ducks and once a chipmunk that we found injured in the woodland of our aunt’s poultry farm. We had all sorts of projects like that.”
Years later, Claire would come home from college and recount the amazing things she was learning, particularly in genetics. Berg was hooked. He went to high school at the Bronx High School of Science, a renowned magnet school in New York, and later studied botany and genetics at Cornell University.
“I liked the speed with which one could ask interesting questions and get results,” he says. “Genetics also had the most interesting professors and students.”
Viruses and jumping genes
Berg earned his PhD in genetics in 1969 with Jon Gallant, PhD, at the University of Washington in Seattle.
“That was a very exciting time for molecular genetics,” Berg says. “Scientists were learning to use bacteria such as Escherichia coli (E. coli) and the viruses that infect them, known as phages, to model and understand the biology of microbes and also of higher organisms such as corn, flies and people.”
During his first postdoctoral appointment, with Dale Kaiser, PhD, at Stanford University, Berg studied phage lambda, which infects E. coli and often integrates itself into the bacterium’s DNA.
Berg’s second postdoctoral position was with Lucien Caro, PhD, at the University of Geneva in Switzerland, where he continued his phage lambda studies.
“It was exquisite, being so near to the Alps and in the heart of Europe,” he recalls. “My closest scientific collaborator, Grete Kellenberger-Gujer, patiently helped me learn French, a wonderful language full of forms of expression and sentiment that can be difficult to capture in English.”
In Berg’s fourth year in Geneva, he met Julian Davies, PhD, on sabbatical there from the University of Wisconsin-Madison. Berg had been impressed with Davies’ earlier research on enzymes that modified antibiotics and made bacteria resistant to treatment. He asked Davies for some of his most interesting antibiotic-resistant bacterial strains for his phage studies.
Berg infected Davies’ bacterial strains with his phages and selected phage variants that picked up the bacteria’s antibiotic resistance genes.
Berg and his collaborators expected to find new DNA segments of variable length inserted at only one site in the DNA of the variant phages. They were intrigued to discover, however, that the new DNAs were actually all the same length and sequence, and were inserted at multiple sites in the phages’ DNA.
“This indicated that we’d identified transposons, which are also known as ‘jumping genes,’” Berg explains. “Scientists had first discovered transposons in maize 30 years earlier. Those transposons had been intriguing researchers for decades, but didn’t contain selectable genetic markers that could help in their analysis. Now we suddenly had apparently equivalent elements with markers we could easily test for: the resistance genes.”
At that point in time, Berg notes, scientists had none of the technologies that today make it easy to insert genes into any DNAs of interest. That made their findings “cause for great excitement,” according to Berg. He remembers getting very little sleep that first night because he was thinking about the data and realizing that he and his colleagues had identified the resistance transposons.
“This was just so absolutely cool,” he says. “It was clear that these new elements would give us powerful tools for studying transposition processes and new ways to understand bacterial evolution and the spread of antibiotic resistance.”
Recent studies have shown that bacterial transposition has evolutionary connections to gene rearrangements that lead to antibody formation and to the DNA changes that underlie some human cancers. According to Berg, this has made bacterial transposition a topic of even greater scientific significance.
Uncovering stomach bacteria’s genetic tricks
Berg was recruited to Washington University in St. Louis by Joe Davie, MD, PhD, chair of the Department of Microbiology and Immunology. Berg joined the faculty in 1977.
He continued to study transposons, but working at the School of Medicine stimulated his interest in research on infectious diseases and public health. In the early 1990s, he began to study Helicobacter pylori, the bacterium that causes most peptic ulcer disease and stomach cancer. About half of all people are chronically infected with H. pylori.
“H. pylori is a particularly big problem in developing countries, where the great majority of people are chronically infected,” Berg says. “H. pylori spreads through contaminated food or water, and once an infection is established, it can persist in the infected person’s stomach for life.”
Among other findings, Berg and collaborator Thomas Boren, PhD, of the University of Umea in Sweden, showed that H. pylori can activate and deactivate an adhesin or glue-like protein that helps the bacteria hold onto cells in the stomach lining. This variability helps the bacteria establish themselves in the stomach, but it also leaves open the option to let go of the lining and to depart sites when immune system responses to infection have become particularly potent.
Move to San Diego
Berg and his wife, Dangeruta Kersulyte, PhD, have a daughter, Alisa, 19, who is now a freshman at Brown University. Berg and Kersulyte recently moved to San Diego, where he is now an adjunct professor of medicine at the University of California.
“I’ll leave WUSTL with mixed feelings,” Berg said the day before the Department of Molecular Microbiology focused its annual Marvin A. Brennecke symposium on his career. “The more than 35 years I spent here have been wonderful.”
Berg is staying active in science via research collaborations with colleagues in San Diego, Lima, Peru, and St. Louis. But he also will spend time out and about near his new home, exploring the coast and hiking and biking paths in the nearby mountains and deserts.
“If Doug Berg asks you to go on a hike, turn him down,” Julian Davies jokingly advised at the Brennecke symposium. “You’ll never be able to keep up with him.”