by Claire Warriner
When learning about the accomplishments of past scientists, it seems natural to focus on their moments of discovery. Less often told are the stories of the arduous processes by which those discoveries were made and the technology that made them possible. Rather than a few, once-in-a-lifetime eureka moments, science’s great legacy is built on innumerable hours spent, for example, sectioning tissue or waiting for a spin to finish.
The Rockefeller University’s Historic Lab, located on the first floor of Flexner Hall, is exhibiting several scientific instruments highlighted in Dr. Carol Moberg’s book, Entering an Unseen World: A Founding Laboratory and Origins of Modern Cell Biology 1910-1974. The exhibit, curated by Dr. Moberg and Olga Nilova, Outreach and Special Collections Librarian, brings to life the birth of modern cell biology at what was then called The Rockefeller Institute. In addition to copies of historical letters, the exhibit features scientific tools, two centrifuges, and two microtomes, all of which played key roles in the development of this nascent science. Three of these four tools were designed at Rockefeller in response to specific research needs and were the prototypes for modern centrifuges and microtomes used in laboratories around the world today. The instruments are arranged in the display in a way that tells a chronological history, beginning with research done in the wake of Peyton Rous and James B. Murphy’s split over the origins of cancer and extending to the use of the electron microscope.
Albert Claude, a Belgian post-doc under Murphy, dedicated his early career in the 1930s to cancer research. He hoped to isolate the cancer-causing agent from malignant chicken tumors, later found to be caused by the Rous sarcoma virus. His goal was to validate Murphy’s chemical theory of cancer, a view that differed sharply from Rous’s viral theory. To carry out this task, Claude chose the model B size 1 International Equipment Corporation centrifuge (now present in the exhibit). This small, electrically driven tabletop centrifuge has a 51-degree angle rotor head, spins at a speed of 4,000 rpm, and has to be used in a cold room because it lacks its own refrigeration system to reduce frictional heat. As shown in the exhibit, an external pulley-equipped rotor can be added to the centrifuge to increase its maximum speed to 17,000 rpm. Using this tool, Claude isolated what he believed to be the tumor-causing agent. He was further able to estimate its size and weight by comparing it with the known weight and size of hemocyanin, and the force and time necessary to extract it by centrifugation. These findings were published in 1937, but what Claude did not know at the time was that the agent he had isolated was in fact the ribosome. In later experiments, he isolated the mitochondria, thus creating the technique of cell fractionation by differential centrifugation, and shedding light on the formerly unseen world of subcellular structures. But the centrifuge Claude used was imperfect. A tenth of his substance of interest was not recoverable and the boundaries of heavier fractions were blurred, implying incomplete sample separation. Better technology was required.
With these problems in mind, Josef Blum, an instrument maker at The Rockefeller Institute, engineered a centrifuge also on display in the exhibit. Completed in 1945, this motor-driven centrifuge reaches speeds of up to 20,000 rpm and features a specially angled Swedish-patented head. Its most noteworthy aspect is the self-centering direct drive mechanism that automatically balances samples of slightly uneven weight, allowing for greater stability during a spin. This centrifuge was still required to be run in a cold room, but, in 1946, Blum added an exterior vacuum and refrigeration system. This prototype (not shown in the exhibit) became the model for the commercially produced Blum-Sorvall centrifuge in late 1947. These centrifuges allowed for a more precise structural and chemical dissection of the cell and paved the way for the development of modern cell biology.
The exhibit tracks the development of the microtome as well. Crude sectioning devices have existed since the birth of the light microscope, but it was not until the advent of the electron microscope that the need for very thin tissue sections sparked the development of more advanced microtomes. In 1946, Josef Blum developed a prototype (present in the exhibit) for Albert Claude, which contains many features still found in modern microtomes. This hand-powered Claude-Blum microtome was the first to allow continuous movement of the tissue block and has a system of belts and pulleys that allow tissue to be sectioned at various thicknesses as thin as 0.1 micrometers. Other original features include a circular movement of the tissue block that protected it on the return stroke of the microtome blade and a trough of water into which the tissue sections fall. The embedding medium was a mix of camphor and naphthalene that is solid at or below 4° Celsius, requiring that it be used in a cold room, but which evaporates at room temperature, allowing for residue-free tissue sections. Blade choice was also an important factor in sectioning, but the steel knives and razor blades in use at the time proved inconsistent or quick to dull.
To ameliorate the quality of electron microscope images, tissue fixation had to be improved. With this in mind, the Porter-Blum microtome (present in the exhibit) was developed in 1952 by Keith Porter and Josef Blum. This new model was an improvement due in part to the use of a methacrylate embedding medium and an effective glass knife. The microtome also used a single-pass mechanism that guided the tissue block across the blade in a parallelogram-shaped motion. The tissue was moved towards the blade by the thermal expansion of a horizontal metal bar heated by a reading lamp, and ribbons of serial sections fell into a water bath below the blade. A revised version of this microtome that could cut sections from 25 to 500 nanometers was developed by Blum in 1953 and made commercially available through Ivan Sorvall. The Porter-Blum microtome proved more reliable and precise than its predecessor and allowed for electron microscope images of greater quality. Interestingly, the instrument was never patented and thus a profit was never collected, despite its commercial popularity. As cited in Dr. Moberg’s book, Porter later explained that the The Rockefeller Institute “was operated for the benefit of humanity,” a sentiment in keeping with the University’s motto.
The Historic Lab’s special exhibit on the tools that aided the founders of modern cell biology to carry out their seminal discoveries is a must-see for anyone interested in Rockefeller’s past and science history. The pieces in the exhibit transform the exciting story of the birth of this field into something tangible. It reminds the viewer that new questions are the impetus behind the development of improved technology, which in turn allows new answers to biological puzzles. Lastly, this exhibit may even dare us to wonder if in many years, when scientific technology has progressed beyond our twenty-first century imaginations, will our own laser-scanning microscope or bench-top sequencing machine sit in the corner of an historic lab? And, more importantly, will there be a story behind these artifacts worth telling?
To make an appointment to view this exhibit, contact Dr. Moberg or Ms. Nilova.
Reference: Carol Moberg, Entering an Unseen World: A Founding Laboratory and Origins of Modern Cell Biology 1910-1974 (New York: The Rockefeller University Press, 2012).