John E. Heuser, MD, explains the process of quick-freeze deep-etch electron microscopy.
HE NEVER INTENDED TO MAKE ART.
Four decades ago, John E. Heuser, MD, professor of cell biology and physiology, wanted to find a way to peer through the murk inside the body and its cells and take clear pictures of key processes in action.
Heuser’s answer to the problem, a unique technique called quick-freeze deep-etch electron microscopy, has helped him answer many important scientific questions ever since. He also has worked to make it possible for other scientists around the world to put the process to use in their own laboratories.
Heuser has won wide appreciation for the artistic beauty often found in the images he produces. His micrographs are typically filled with otherworldly textures and patterns, magnificent micro-architectural structures, and the drama of fleeting but critical moments captured and frozen for eternity.
In recent years, Heuser’s scientific colleagues have recognized his broad contributions to cell and molecular biology by electing him to fellowship in the American Academy of Arts and Sciences, the American Academy of Microbiology, and the National Academy of Sciences. The artistic merits of his research were recognized recently in an on-campus exhibition of his electron micrographs organized by colleagues Paul C. Bridgman, PhD, professor of anatomy and neurobiology, and Krikor T. Dikranian, MD, PhD, associate professor of anatomy and of physical therapy.
The images are now permanently displayed on the third floor of the Farrell Learning and Teaching Center, near the histology labs where medical students will have some of their first encounters with the cells and tissue structures seen in Heuser’s micrographs.
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John E. Heuser, MD, devised a way to freeze cells in about one-ten-thousandth of a second by driving them onto a block of copper cooled to minus 450 degrees Fahrenheit. These “quick-frozen” cells can then be split open, “deep etched” to remove some of the ice, and coated with an ultrathin film of metallic platinum so they can be seen with an electron microscope. In this image of the junction or synapse between an elongated nerve (pale green) lying on the surface of a muscle fiber (darker green), the nerve is punctuated every ten-thousandth of an inch or so by bands of membrane activity (orange), the areas where communication occurs between nerve and muscle.
In further studies of the process of communication across the synapse, Heuser examined the interiors of nerves (blue) that he “quick-froze” at precisely the moment they were active. He found they were filled with hoards of tiny membranous spheres (yellow) — what are now called presynaptic vesicles.
Heuser also demonstrated that during synaptic communication, vesicles are not just discharged by the nerve but are also “recycled” by special molecular-uptake machinery that takes on a form very much like Buckminster Fuller’s classic geodesic architecture. In this image of the internal surface of a cell, Heuser showed that the geodesic domes can flex and bend. While they start out flat, they gradually curve inward until they completely pinch off the surface, and thereby “pull” the vesicles back inside the nerve.
Heuser has helped School of Medicine colleagues who are researching dangerous infectious diseases, including the infamous H1N1 influenza that threatened the world just two years ago. In this image, he showed the huge number of flu viruses that a sick cell can release (the enlargement shows how they bud out of a cell) and revealed that these viruses also stick to cells unusually tightly. This ultimately helped clinicians understand why this particular flu was so severe and so dangerous.