The rapidity of the progress is mind boggling. In 1942 in Chicago, Enrico Fermi created the first chain reaction from fissionable material (plutonium 239). Only then did they discover that it really was possible. Just three years later, on July 16, 1945, we exploded the world’s first atomic bomb in Alamagordo, New Mexico.

The following month, we dropped two atomic bombs on Japan. The degree of destruction and loss of life is regrettable, but the effort to accomplish it is a marvel of brilliance, organization, and determination. Thousands of people did their small part, and a few people played very large parts. 

One of the youngest group leaders (in his 20s) working on the Manhattan Project (at Los Alamos) was Robert Rathbun Wilson. He greatly regretted the destruction caused by his efforts. So, in 1946, Wilson published a seminal paper, "Radiological Use of Fast Protons", which founded the medical field of proton therapy. I have read the paper, which is just a few pages long. The key, in my mind, is that he understood so intimately the working of cyclotrons and accelerated charged particles plus the fact that protons can stop at the intended target. 

Wilson joined a group of scientists and physicists in developing more powerful particle accelerators for diagnostic and medical purposes. Wilson believed protons could be used to reach previously untreatable tumors deep within the body. He helped design a new powerful cyclotron for Harvard, where he became an associate professor. Thus, for more than four decades, Harvard was the center of proton therapy research.

Above: Energy release of protons forming the Bragg’s Peak

The electron was discovered in 1897 by J. J. Thompson, and the proton by Ernest Rutherford (the father of nuclear physics) in 1911. The cyclotron (a type of particle accelerator) was invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley. All of these gentlemen earned Nobel prizes for their ground-breaking work.

The 1930s were a decade of important research and development into the nature and behavior of atoms. Vanderbilt University has detailed much of this history at this website: https://vanderbiltnuclearmedicine.com/era1/early-atomic-discoveries/.

Niels Bohr, a Danish Physicist, was a leading force in Rutherford’s lab at McGill University in Canada. I am reminded of a story of a visitor to Bohr’s office who noticed a horseshoe hung on the wall, with the opening upward. The visitor expressed surprise that as a scientist, Bohr would believe in such an esoteric practice. “You’re right,” Bohr replied. “As a scientist, I find it makes no sense. Fortunately, it works whether you believe in it or not.”

In 1954, the first human was treated with proton beams at the Lawrence Berkeley Laboratory in California (where the cyclotron had been invented). Eight years later, proton treatments began at the Harvard Cyclotron Laboratory, followed in the mid-1970s by treatments for ocular cancers and larger tumors. It was at Harvard that much of the physics and procedures used for proton therapy were formulated. I find this rather ironic as today one of the harshest critics of proton therapy comes from a doctor long associated with Harvard. Reportedly 9,116 patients were treated at Harvard before the cyclotron was shut down in 2002 and replaced the following year with the current proton center at Massachusetts General Hospital.

From Harvard, Robert Wilson had a stint at Cornell University and then became the director of the new Fermi National Accelerator Laboratory (named after Enrico Fermi), usually called Fermilab, outside of Batavia, Illinois. In the late 1980’s, FermiLab built a synchrotron (an accelerator that works a little differently from a cyclotron) and proton beam transport system for Loma Linda University Medical Center in California which had allotted a million and a half dollars to explore practical uses of proton therapy. That act of vision, in my mind, was the single most important step in the development of proton beam therapy as an accessible cancer treatment. The cost and installation became so high the United States government finally came to the rescue with twenty-five million additional dollars. Today, one of the limiting factors of proton therapy is still the cost of the technology and its utilization.