Roy J. Britten, a Caltech biologist who discovered that the mammalian genome includes large quantities of repetitive DNA sequences that do not serve as blueprints for genes, has died. He was 92.
Britten, who had pancreatic cancer, died Jan. 21 at his home in Costa Mesa, Caltech announced.
Britten and molecular biologist Eric Davidson, a Caltech colleague, also played a key role in the development of the field of evolutionary developmental biology, which demonstrated that most of the differences between species arise from changes in how similar genes are regulated, rather than from mutations in the genes themselves.
"He was one of the truly brilliant people I have known," Davidson said in a statement.
Maxine F. Singer, former president of the Carnegie Institution for Science in Washington, called Britten "a scientist's scientist."
Before the work of Britten and other researchers in the 1960s, scientists had thought that the massive genomes of animals and humans — the complete genetic blueprint of DNA required to produce an organism — were composed mainly of individual genes.
But Britten and colleague David Kohne, both then at the Carnegie Institution, demonstrated that such genomes were composed of not only genes but also unique stretches of DNA and long sequences of repetitive DNA that did not serve as blueprints for genes. Much of this material is interspersed in the middle of genes. This material was once considered to be "junk DNA," but research has since shown that it plays a critical role in the development and functioning of all animals.
Britten and Kohne used a process called renaturation, in which the double-stranded molecules of DNA in the genome were chopped into smaller segments and separated into individual strands. Because the two strands are complementary, they will reassemble themselves — become renatured — when they are in solution.
But because mammalian DNA is so long and complicated — comprising about 3 billion individual base pairs in humans — that process is very slow. Britten reasoned that if there were many repetitive sequences of DNA, renaturation would occur more quickly, at a rate dependent on the amount of repetition.
The pair's experiments, reported in 1968, showed that this was, indeed, the case, but they had to use extremely concentrated solutions of DNA and the process still required days. A key component of their work involved the use of the mineral hydroxyapatite to separate double-stranded DNA from single-stranded for analysis. Britten, Davidson noted, turned hydroxyapatite "into a laboratory workhorse."
It soon became clear that actual genes, which serve as the blueprint for proteins, enzymes and other cellular components, accounted for only a few percent of the genome. Britten's work "provided the most accurate images of what DNA is like until sequencing came along decades later," Davidson said.
In 1971, Britten moved to Caltech and began a quarter-century collaboration with Davidson. The pair demonstrated how repetitive and single-copy DNA are organized in animal genomes, measured the amount of single-copy DNA in genes that are expressed (turned on) during embryonic development and began the analysis of gene regulatory systems that underlie development. They found that only about 5% of single-copy DNA was actually genes.
That work helped create the field now known as evolutionary developmental biology, commonly known as "evo devo." The main tenet of the field is that it is the regulation of genes, rather than their structure, that provides most of the differences between species. Very similar genes, for example, are needed for the production of fins in fish and limbs in humans. It is the differences in how these genes are controlled by regulatory elements that determines what is actually produced.
Roy John Britten was born Oct. 1, 1919, in Washington and was raised in Arlington, Va. His father was a statistician at the Public Health Service and his mother worked at the National Research Council. His parents permitted Britten and his brother to set up a chemistry lab in their basement.
At 16, Britten enrolled at the University of Virginia to study physics, receiving his bachelor's degree in 1940. During World War II, he joined the Manhattan Project, where he attempted to use magnetic beam techniques to separate and purify isotopes of uranium. The project did not work, however, which he frequently noted pleased him because he was a committed pacifist.
After the war, he received a doctorate in nuclear physics in 1951 from Princeton University. His graduate work involved the development of the quadrupole magnet, which was made by placing four bar magnets at angles of 90 degrees to one another. Quadrupole magnets are now widely used in spectroscopy and in accelerators. Britten often lamented that he neglected to patent the idea.
A lifelong interest in biology, however, prompted Britten to switch his specialty to biophysics when he joined the Carnegie Institution in 1951.
An avid sailor, Britten voyaged around the world. For many years, he lived on his schooner, Tiercel, which was moored in Newport Bay near Caltech's Kerckhoff Marine Laboratory in Corona del Mar, where he did most of his research.
Divorced from his first wife, Britten married Jacqueline Reid in 1986. She died in 2001. He is survived by two sons from his first marriage, Kenneth of Winters, Calif., and Gregory of Penacook, N.H.
Maugh is a former Los Angeles Times staff writer.