A Spin Through the Past: Early Centrifuges and Microtomes in The Rockefeller University’s Historic Lab
By Claire Warriner, @CLWarriner
A previous version of this article appeared in Natural Selections, Issue 99, June 2013
When learning about the accomplishments of past scientists, it seems natural to focus on their major findings while overlooking the arduous process of discovery, including the technologies that make it all possible. Of course, this paints an inaccurate picture of scientific research. Rather than a few, once-in-a-lifetime eureka moments, science is built on relatively tedious procedures- like sectioning tissue or waiting for centrifuge spins to finish.
To celebrate the tools and technology that paved the way for the progression of science, The Rockefeller University (RU) has opened an Historic Lab based on Dr. Carol Moberg’s new book, Entering the Unseen World: A Founding Laboratory and the Origins of Modern Cell Biology 1910-1974. This exhibit, curated by Dr. Moberg and Olga Nilova (RU outreach and special collections librarian), brings to life the birth of modern cell biology at what was then called The Rockefeller Institute for Medical Research.
It all began with a fundamental disagreement between Peyton Rous and James B. Murphy. Murphy believed that cancer’s cause was chemical in nature and originated from within the cell, whereas Rous believed that cancer was induced by a transmissible virus. Albert Claude, a Belgian post-doc under Murphy, dedicated his early career in the 1930s to cancer research, and aimed to validate Murphy’s hypothesis. He hoped to isolate the cancer-causing agent from malignant chicken tumors, which were later found to be caused by the Rous sarcoma virus (Rous was right!).
To carry out the set of experiments that would lead to his conclusion, 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 must be used in a cold room because it lacks a 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 from the malignant chicken tumors. He was further able to estimate the size and weight of this agent by comparing it with the size and weight of a known protein (hemocyanin), and the force and time necessary to extract it by centrifugation.
These findings were published in 1937, but what Claude did not immediately realize was that the isolated material was actually ribosomes. In later experiments, he isolated mitochondria, thus creating the highly useful 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. This implied an incomplete sample separation, and begged for better technology.
With these problems in mind, Josef Blum, an instrument maker at The Rockefeller Institute for Medical Research, engineered a centrifuge that is 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 rotor 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.
The centrifuge still needed 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 also tracks the development of the microtome. 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.
The 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 protects 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 evaporates at room temperature, allowing for residue-free tissue sections. The device could be fitted with a steel knife or razor blade, but these proved inconsistent or quick to dull. Though the Claude-Blum microtome was a technological step forward, more precise and consistent sectioning machines were required to improve the quality of electron microscope images.
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 then 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 never collected, despite its commercial popularity. Porter later explained that the work of The Rockefeller Institute for Medical Research, as cited in Dr. Moberg’s book, “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 is a must-see for anyone interested in RU’s history. The pieces in the exhibit transform an exciting scientific “birth-story” into something tangible. It reminds the viewer that new questions inspire an improvement in current technologies, which, in turn, provides 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 a historic lab? And, more importantly, will there be a story behind these artifacts worth telling?
Reference: Carol Moberg, Entering the Unseen World: A Founding Laboratory and the Origins of Modern Cell Biology 1910-1974 (New York: The Rockefeller University Press, 2012).
Photos courtesy Dr. Carol Moberg