Among various types of charged particles, protons and carbon ions have been most widely employed for cancer therapy in the world. The energetic ion beam deposits much of its energy at the end of its range, resulting in what is called the Bragg peak (Fig. 1.1), so-named after Sir William Henry Bragg, a British physicist. He reported this phenomenon in 1904 [6]. Realizing the advantage of the Bragg peak, Robert R. Wilson (1914–2000) published his seminal paper on the rationale of using accelerated protons and heavier ions for human cancers in 1946 [7]. This was the first proposal to apply charged particles for medical use. He participated in the development of the atomic bomb in Los Alamos during World War II. After the war, he returned to Berkeley to look for peaceful atomic-energy projects, and he wrote a historic paper on the potential benefit of high-energy protons in cancer therapy. He later became the first director of the Fermi Laboratory, where clinical research of fast neutron therapy was conducted on more than 3,100 patients. Compared to conventional photon treatment, charged particle beams appeared to promise higher cure rates with smaller complications as they could deliver sufficient doses precisely, while lowering unwanted doses to normal tissues adjacent to the tumor. Wilson also hypothesized that carbon ions might be superior to proton beams.

Prior to Wilson’s proposal, Ernest Orlando Lawrence (1901–1958) discovered a method of accelerating particles to very high energy without the use of high voltage, which was actually the development of the cyclotron in 1929. The first model of Lawrence’s cyclotron was made of brass, wire, and sealing wax and was only 4 in. in diameter—it could literally be held in one hand. A photograph of Lawrence holding the first cyclotron in his hand appeared on the front cover of “Time” newsmagazine. Subsequently, higher-energy cyclotrons 11, 27, and 37 in. in diameter were constructed at Berkeley.

In 1938, the world’s first particle therapy was conducted on 24 patients with a single fraction of fast neutrons generated by the historic 37-inch cyclotron. This treatment was judged as successful, and then from 1938 to 1943 a total of 226 patients were treated with fractionated fast neutrons generated by a 60-inch cyclotron. Together with the clinical effects of fast neutron therapy, however, long-term side effects on normal tissues deemed were too high, and in 1948 Dr. Stone concluded that fast neutrons should not be used for cancer therapy [8].

A British group, however, evaluated fast neutron therapy again, and in 1965 Mary Catterall at Hammersmith Hospital in London once more began this therapy. By 1969, it was shown that for certain tumors, better local control could be achieved with neutron irradiation. Encouraged by these results, many other institutes in Europe, the USA, and Japan began neutron therapy research in the 1970s. However, the demand for fast neutron therapy decreased thereafter, and most of the institutions abandoned this therapy. Fast neutron therapy is currently conducted at only a few facilities for the treatment of selected tumors.

Incidentally, in the same year (1938) of the start of fast neutron therapy, Gerald Kruger, a physicist at the University of Illinois, came up with a new idea for cancer therapy using alpha particles emitted from boron when it captured neutrons. He proposed to saturate the tumor with a boron compound and then exposed it to a neutron beam. The boron capture cross section for thermal neutrons was about 100 times higher than that of other tissue compounds. This method came to be known as “neutron capture therapy.”