Reprinted with permission. A longer version of this article first appeared in the winter 2005 issue of the Howard Hughes Medical Institute Bulletin.
Can the insides of a tiny blind worm that lives in rotting vegetation and carrion be beautiful?
In the hands of Erika Hartwieg, who "paints" with an electron microscope on black-and-white film, the anatomy of the roundworm does indeed yield a finely detailed, luminous image with an appeal beyond the purely scientific. Hang one of her photographs on a wall, and it could pass for abstract art.
Hartwieg prepares and studies unimaginably thin slices of Caenorhabditis elegans, the workhorse worm of geneticists, in the laboratory of Professor H. Robert Horvitz at MIT. Horvitz, an HHMI investigator, received the Nobel Prize in physiology or medicine in 2002 for discovering genes in C. elegans that control apoptosis--naturally occurring, or programmed, cell death.
"Erika is indispensable," says Horvitz. "Few people in the world can match her ability at serial-section electron microscopy." Serial-section refers to making a series of thin cross-sections, each of which must be kept intact and unwrinkled to form an unbroken chain of slices.
When Hartwieg photographs these worm sections with the electron microscope (EM), they appear as highly magnified ovals filled with cells and organelles, membranes and cytoplasm, voids and channels and fibers. The textures range from lumpy to faintly stippled, the tones from darkest black to the most feathery of grays.
For the past 14 years, she has been the electron microscopist in the Horvitz lab. After earning a master's degree in biological research, she "fell into electron microscopy in the 1960s when it was the new thing," says Hartwieg. In today's biology lab, the EM seems almost passé beside newer glamour technologies--gene microarrays and high-throughput sequencing machines--but electron microscopy is still a key player in research that probes the fundamentals of animal development and behavior.
For example, a mutation may result in a worm that can't wiggle in its usual S-shaped pattern. Searching for the responsible anatomical defect within the nerve and muscle cells requires powerful magnification. Hartwieg can locate a particular cell of interest, enabling the scientists to precisely characterize the mutation-caused abnormality.
Hartwieg says the process of the specimen's preparation takes four or five days, working on five worms at a time. The average adult worm is 1 millimeter long, and lining up five of them in parallel within a drop of quick-jelling agar "is the most difficult step of all," she says.
After infusing the agar with a plastic resin to create a hard block, Hartwieg uses a microtome to cut a portion of each worm into cross-sections, which she likens to "pieces of salami." But these worm cold cuts are sliced by the microtome's diamond knife to a thickness of only 50 nanometers, as much as 2,000 times thinner than the width of a human hair.
Hartwieg uses a small tool tipped with an eyelash (of her own) to hold the ribbons of sections steady on a water surface for placement in a tiny copper grid. Then she washes the grid in succession with three types of stains, each containing different heavy metals that interact directly with the beam of electrons in the EM, resulting in scattering of the electrons with different energies, which form the image on the fluorescent screen.
Hartwieg also makes longitudinal slices: The finished photographs can be assembled in a mosaic to create a table-top-sized portrait of, say, the worm's nose.
A version of this article appeared in MIT Tech Talk on May 18, 2005 (download PDF).
