When Edward De Robertis was getting his Ph.D. in chemistry in Argentina, he met pioneering developmental biologist Sir John Gurdon, who was visiting from England. De Robertis spoke animatedly to Gurdon about the experiments he was doing before the visitor gave his lecture and then drove him to his hotel.
Three years later, when De Robertis was considering postdoctoral positions, he learned he had made quite an impression on Gurdon, and that Gurdon had arranged, without the 27-year-old's knowledge, a fellowship for him to pursue further studies anywhere in England. De Robertis swiftly moved to Gurdon's laboratory at the Medical Research Council (MRC) in Cambridge.
Gurdon's laboratory was "doing very exciting molecular biology," De Robertis explains, "studying molecules inside a living cell by using frog oocytes as a living test tube."
De Robertis flourished at the MRC and began developing the tools that would enable him to dissect the molecular machinery that governs the formation of an embryo. He later used these methods to discover molecules the embryo uses to shape itself from a single cell into a multitude of different tissues.
De Robertis always had a passion for science. As a young boy in Uruguay, his favorite book was Microbe Hunters (1926), which describes the discoveries of the great microbiologists, such as Louis Pasteur and Robert Koch. "I still give the book out to my postdocs when they leave," De Robertis says.
By age 13, he worked in a laboratory studying grasshopper chromosomes. Earlier, he had started peering through his father's microscope, beginning a lifelong love of the device. "I see life through the microscope," says De Robertis. "It is an extension of my brain." He currently operates on frog embryos through a dissecting microscope Tuesdays and Thursdays, and most of his best ideas originate during that time.
It is the microscope that has allowed De Robertis to make the important discoveries of his career. Employing it at the MRC, he showed that recombinant DNA put into the frog oocyte nucleus enabled the cell to make the protein encoded by the DNA. That was the first time DNA cloned by genetic engineering was shown to produce proteins.
De Robertis also revealed how chemicals in a salamander oocyte nucleus could reprogram cells in the body of a mature frog. With Gurdon, he injected hundreds of kidney nuclei, each of which contains the DNA and chromosomes of the mature cell, into a salamander oocyte. Rather than expressing kidney proteins, "the oocyte erased the genetic information in the mature kidney DNA." Such groundbreaking experiments helped lead to current gene reprogramming experiments in human stem cells.
After the MRC, De Robertis was appointed to the faculty at the University of Basel, Switzerland, where he began studying the molecules that determine embryo morphology. De Robertis isolated developmental genes called homeoboxes in the frog, collaborating with his colleague Walter Gehring, who in Basel first found such genes in fruit flies. "The frog homeobox gene was a turning point for embryology because it showed these development-controlling genes were not only acting in fruit flies," De Robertis explains. "Some fundamental toolkit creates the form and patterning of the embryo across the animal kingdom."
De Robertis then tackled a fundamental issue in embryology, first revealed by Hans Spemann in 1924. Spemann had discovered a region of the early embryo, called the organizer, that can induce tissues to form a separate organism, or a twin. Spemann received the Nobel Prize in Physiology or Medicine for his work on "embryonic induction," but scientists did not understand the chemistry by which the powerful organizer region acted to shape the developing embryo.
At the University of California, Los Angeles, De Robertis identified the first genes from organizer cells, goosecoid and chordin, and revealed an entirely new pathway of how cells communicate with each other. Since then, he has isolated many proteins from the organizer and characterized how they work in chemical terms.
De Robertis continues to study regulation of the organizer proteins and how the same genes are used by different organisms, including fruit flies and humans, in cell–cell signaling. Although he has focused on the gradients of proteins that control front-to-back orientation of the embryo, he is now trying to integrate that information with head-to-toe pattern formation. "Understanding the mechanism of embryo formation has become an obsession," De Robertis says. "I sometimes draw circuits and biochemical pathways all day long. Actually, it is a bit crazy. But what we are finding out about life is truly amazing."