I do not consider myself to have ever been in the field of particle therapy, comparable to my good friends Herman Suit, James Slater, and Nancy Mendenhall. I only dabbled occasionally.
When I was an undergraduate in physics at University College, London, in 1953, Professor Massey (Sir Harrie Stewart Wilson Massey, FRS) was head of the department. Because of his interest in the charged particles found in space, he was responsible for Britain's small contribution to the space program as well as my first exposure to high-energy charged particles.
I was not in the top 1% of the class who were offered research opportunities, however. Instead, I took a position in Medical Physics at the Churchill Hospital, Oxford, with Dr Frank Ellis. Dr Ellis taught me to challenge every idea, including those held by people with seniority in the department: Demand evidence, not a vague opinion. I flourished at Oxford as I had not done as an undergraduate in London.
I was also much influenced by the head of Oxford's Medical Research Council research group, Dr Laszlo Lajtha. He advised me to go into research. So, back to graduate school I went to obtain a doctorate from Oxford in radiobiology.
Career Turning Points
After Oxford, I was recruited by Columbia University to perform biological experiments with mammalian cells, using the monoenergetic neutron beams available at Brookhaven National Laboratory. In the 1970s, it was thought that the limitation of radiotherapy was the resistance of hypoxic cells to killing by X-rays; neutrons were introduced because they were characterized by a lower oxygen enhancement ratio (OER). With my experience at Brookhaven, I was well equipped to do intercomparison experiments on all of the clinical neutron machines in the United States, the United Kingdom, Europe, and Japan.
In 1972, the Princeton Particle accelerator generated the first beam of high-energy particles—a beam of 3.9-GeV nitrogen ions. The Columbia group had the first and only successful series of measurements in physics and biology before the facility was closed down due to government budget cuts, but we had been able to show the attractive physical characteristics of the beam. The disappointment was that the OER was little reduced in the spread-out Bragg peak and, in those days, the OER was all that mattered. Within a few months, the Berkeley Lab had also succeeded in accelerating nitrogen ions as well as the heavier particle argon, although the beams were unstable and frequently broke down. By sheer luck, our Columbia group achieved the first biological data for argon ions.
The OER in the spread-out Bragg peak was indeed comparable to that of neutrons, but the extent of fragmentation of the argon ions rendered them useless for radiotherapy. The Berkeley group underwent extensive experiments with 4 different ions; however, it was already obvious that no particle would combine the excellent dose distribution qualities of protons with the lower OER of neutrons.
It was about this time that protons—already in use for limited purposes at the Harvard cyclotron, where we were doing extensive relative biological effectiveness (RBE) measurements on the proton beam—became the most exciting possibility, with a hospital-based facility at Loma Linda. Microdosimetry measurements showed a small, albeit high, linear energy transfer (LET) contaminant in the beam. We, therefore, recommended scanned beams rather than the simpler scattered beams because of the problem of neutron contamination, since we know of the adverse biological effects of neutrons.
The Scientific Method and the Role of Particle Therapy Organizations
The biggest change I have witnessed in the field of particle therapy has been the introduction of the scientific method to medical research. Because every decision must ultimately be backed by data that are widely accepted, the important functions of particle therapy organizations are therefore to provide a forum to present the latest data and, in particular, to identify the problems that need to be addressed.
The Future of Particle Therapy: The Optimal Ion
Right now, particle therapy consists of (1) protons and (2) carbon ions. The former provide a good dose distribution, the latter some biological advantage but at greater cost.
Historically only 4 ions heavier than protons have been analyzed in any detail. I believe there is room for some additional research to answer 2 questions:
Are protons optimal for achieving the best dose distribution? Would helium or lithium be better, and worth the cost, since they allow sharper beams with a smaller penumbra?
Are carbon ions optimal for achieving a biological advantage? They have several attractive properties, including a larger RBE in the spread-out Bragg peak; however, we do not know if a slightly higher, or slightly lower, atomic number would be superior or less expensive.
The Japanese data for cure rates of pancreatic cancer pose the question of whether the high LET component in the beam confers an advantage of stimulating an immune response. This question also needs to be addressed and answered by carefully designed experiments.
Advice for the Next Generation
Being a scientist can sometimes be frustrating—consider becoming a surgeon! Just kidding.
I currently stay connected to young people in the field through my textbook (Radiobiology for the Radiologist, Harper & Row/Lippincott), which I try to keep up-to-date. I would advise them to take any opportunity—and I know this varies drastically across departments—to pursue a research project for as long as practical, which may not be more than 6 months or a year. When you return to patient care, you will be better able to see the problems of research and can more realistically weigh the results of imperfect clinical trials. For, as we know, there is always the problem of whom to believe.