However, as Levin continued to read up on the subject, he realized that, even though the brain uses electricity for information processing, no one seemed to be seriously investigating the role of bioelectricity in carrying information about a body’s development. Wouldn’t it be cool, he thought, if we could comprehend “how the tissues process information and what tissues were ‘thinking about’ before they evolved nervous systems and brains?”
He started digging deeper and ended up getting a biology doctorate at Harvard University in morphogenesis — the study of the development of shapes in living things. He worked in the tradition of scientists like Emil du Bois-Reymond, a 19th-century German physician who discovered the action potential of nerves. In the 1930s and ’40s, the American biologists Harold Burr and Elmer Lund measured electric properties of various organisms during their embryonic development and studied connections between bioelectricity and the shapes animals take. They were not able to prove a link, but they were moving in the right direction, Levin said.
Before Genes Reigned Supreme
The work of Burr and Lund occurred during a time of widespread interest in embryology. Even the English mathematician Alan Turing, famed for cracking the Enigma code, was fascinated by embryology. In 1952 he published a paper suggesting that body patterns like pigmented spots and zebra stripes arise from the chemical reactions of diffusing substances, which he called morphogens.
But organic explanations like morphogens and bioelectricity didn’t stay in the limelight for long. In 1953, James Watson and Francis Crick published the double helical structure of DNA, and in the decades since “the focus of developmental biology has been on DNA as the carrier of biological information, with cells thought to follow their own internal genetic programs, prompted by cues from their local environment and neighboring cells,” Huang said.
The rationale, according to Richard Nuccitelli, chief science officer at Pulse Biosciences and a former professor of molecular biology at the University of California, Davis, was that “since DNA is what is inherited, information stored in the genes must specify all that is needed to develop.” Tissues are told how to develop at the local level by neighboring tissues, it was thought, and each region patterns itself from information in the genomes of its cells.
The extreme form of this view is “to explain everything by saying ‘it is in the genes,’ or DNA, and this trend has been reinforced by the increasingly powerful and affordable DNA sequencing technologies,” Huang said. “But we need to zoom out: Before molecular biology imposed our myopic tunnel vision, biologists were much more open to organism-level principles.”
The tide now seems to be turning, according to Herrera-Rincon and others. “It’s too simplistic to consider the genome as the only source of biological information,” she said. Researchers continue to study morphogens as a source of developmental information in the nervous system, for example. Last November, Levin and Chris Fields, an independent scientist who works in the area where biology, physics and computing overlap, published a paper arguing that cells’ cytoplasm, cytoskeleton and both internal and external membranes also encode important patterning data — and serve as systems of inheritance alongside DNA.
And, crucially, bioelectricity has made a comeback as well. In the 1980s and ’90s, Nuccitelli, along with the late Lionel Jaffe at the Marine Biological Laboratory, Colin McCaig at the University of Aberdeen, and others, used applied electric fields to show that many cells are sensitive to bioelectric signals and that electricity can induce limb regeneration in nonregenerative species.
According to Masayuki Yamashita of the International University of Health and Welfare in Japan, many researchers forget that every living cell, not just neurons, generates electric potentials across the cell membrane. “This electrical signal works as an environmental cue for intercellular communication, orchestrating cell behaviors during morphogenesis and regeneration,” he said.
However, no one was really sure why or how this bioelectric signaling worked, said Levin, and most still believe that the flow of information is very local. “Applied electricity in earlier experiments directly interacts with something in cells, triggering their responses,” he said. But what it was interacting with and how the responses were triggered were mysteries.