A Brief History of the Harvard University Cyclotrons.
Mallinckrodt Research Professor of Physics
This is a brief history of the two cyclotrons built
at Harvard University and used between 1935 and
2002. It is a distinguished history and I, Richard
Wilson, am proud to have been a part of it for 47 of these
67 years. In addition to this web based history,
which can be added to at any time, a small hard copy book
is published. In addition there is a a
collection of 800 photographs of the cyclotron, its work,
its staff and its place in the community which have been
scanned and are avaliable for those who wish. Some
of them are available on an adjunct to this site.
. Of course the Harvard University Archives have
papers of many of the participants for the eager
historian, and several hardware items are in the
museum of scientific instruments. The work falls
naturally into four periods. The first period was
that of the construction and use of the first cyclotron from
1935 to 1943 when it was dismantled and taken away for war
work. The second is the construction and initial use of
the first cyclotron from 1945 to 1955. The third period
starts with a major upgrade in 1955 and continues until the
end of major physics research in 1968, and the fourth period
is of intensive use for radiotherapy until final closure in
summer 2002. Production of radioactive isotopes was an
important part of the operation of the first cyclotron, but
was only very
incidental in the second cyclotron. Further
deatil, often unedited, can be found on http://physics.harvard.edu/~wilson/cyclotron/
In the first third of the twentieth century the study of Physics at Harvard for both graduate and undergraduate students continued administratively under the Faculty of Arts and Sciences. The space occupied for study and experimentation grew with the construction of Lyman laboratory in the 1930s, one which included a research library. The First World War had initiated the Department of Physics' role in defense. Its members had taught military personnel, served in the military, and performed defense research. The 1930s saw increased interest and investigation into the fields of nuclear science and the beginnings of computer science. In order to meet the research needs of its faculty, the Physics Department oversaw construction of a particle accelerator - a cyclotron.
The cyclotron had been invented in Berkeley
California in 1929 by Ernest Lawrence and
constructed by Lawrence and his graduate student M.
Stanley Livingston. Although the first nuclear
disintegration experiments had been performed by Cockroft
and Walton in the Cavendish laboratory in Cambridge
UK, using a rectifier multiplication device which carries
their name, the cyclotrons proved to be very
useful in the 1930s in nuclear disintegration experiments,
and following the discovery of artificial radioactivity in
1934 by Joliot-Curie, were used widely in producing a
variety of radioactive nuclei. Some of
these radioactive nuclei were of interest in astrophysics,
some of interest in the study of nuclei themselves
and some were useful in nuclear medicine
-both in diagnosis and in treatment. It
seemed that every major university should have a
cyclotron and indeed they were built at a number of
places - Princeton, MIT (built by M. Stanley Livingston),
Cornell (built by Stanley Livingston), Rochester built by
S.N. Van Voorhis and Lee Dubridge and at Yale by E.
C. Pollard and H. L. Schultz.
Although there was agreement that Harvard University must have a cyclotron, there was less agreement on what such a device was. This is well illustrated in the following page of cartoons about the Cyclotron.
The First Harvard University Cyclotron
Harvard faculty began thinking about a cyclotron as early as 1935. It was to be built as a joint project between the Graduate School of Engineering, (now replaced by the Division of Engineering and Applied Physics) Professor Harry Mimno represented Electrical Engineering,and Associate Professors Kenneth Bainbridge and Jabez C. Street represented the physics department. Edward M. Purcell (later Nobel Laureate for Nuclear Magnetic resonance) was awared the PhD in 1938 for a theis on "The Focussing of Charged Particles by a Spherical Condenser." He became a Faculty Instructor in Physics, what was then the new title for what is now Assistant Professor, a five year term rank. In 1936 the construction of the cyclotron begun in the Gordon McKay laboratory, a wooden world war I building on the east side of Oxford Street. The magnet weighed 85 tons and had a 41minch diameter pole tip. It accelerated protons up to energy of 12 Mev. In 1960s a new Engineering Science building was built on the southern part of the Gordon McKay laboratory and the northern part was dismantled as a fire hazard in 1965 and in 2002 a new building is being finished in its location to house various administrative offices.
By 1938 the cyclotron construction was complete and a photograph shows Professor Street, left, posing with Professor Bainbridge, right, and a graduate student Dr R. W. Hickman (kneeling). Dr Hickman wrote his PhD thesis on the Franck-Hertz experiment. By 1943 he was Lecturer on Physics and Communication Engineering, Assistant Director of the Physics Laboratories (under T. L. Lyman) and Assistant Director of the wartime Radio Research Laboratory (under F. L. Terman from Stanford). Later he became Director of the Physics Laboratories until his retirement about 1968. Another photograph shows a scientist, probably Professor Street, showing on a blackboard the operation of the accelerating system of the two dees.
The cyclotron had an external beam which slowed and stopped as it passed through the air. This gives a dramatic picture of the ionization of the air. The external beam was used for producing radioactive isotopes for medical purposes. A photograph shows a technician handling one of the sources. The report of the physics department to the university in 1939 states that radioactive materials supplied to Harvard Medical School, New York Memorial Hospital and Massachusetts General Hospital in addition to uses for physics at Woods Hole Meteorological Station, MIT physics department and members of Williams College and Purdue University. It supported the work of 14 researchers in Harvard departments. Interestingly, there seemed to be no interest from the graduate school of engineering after the initial construction. In 1940 to 1941 the physics department reported that the cyclotron had been in operation for over 1,000 hours. But the end of this fruitful period, and of the first Harvard Cyclotron was near.
On September 3rd 1939 Great Britain and France declared war on Nazi Germany and after the Japanese attack on Pearl Harbor in December 1941 the United States joined the war -now called World war II. Again many members of the Harvard physics faculty served the war effort in various ways. Some faculty members, including Professor K.T Bainbridge, had already been called to help develop radar at the radiation laboratory at MIT by E. O. Lawrence on behalf of the NDRC. But in 1943 after the establishment of Los Alamos that Professor Bainbridge was recruited away to work on the Manhattan Project of the U.S. Army, at Los Alamos, New Mexico to join a highly secret team assembled by Robert Oppenheimer to work on the development of the first atomic bomb. While there it became clear that a cyclotron was needed to measure various nuclear reaction cross sections of interest, and supplement the work already being ably carried out at the Princeton cyclotron. Discussions began at a high administrative level, and top secret level, between Harvard President James B. Conant (then away from Cambridge) and General Groves and it was agreed that Harvard would sell the cyclotron to the US government for $1 with an informal promise of a cyclotron to replace it when the war was over. It appears that Paul Buck, then Provost of Harvard University, was not informed of these discussions and he later reported informally how much he agonized over making the decision to send the cyclotron.
The young scientist Robert R Wilson was sent to Harvard to negotiate the purchase and arrange the transfer. Since the atomic bomb project was top secret, the purpose of the purchase had to be disguised from those not cleared for secret information. A medical physicist, Dr Hymer Friedell, accompanied Robert Wilson. The "cover story" is that the cyclotron was needed for medical treatment of military personnel and it was sent to St Louis to be forwarded to an "unknown destination" (Los Alamos). Robert Wilson oversaw the shipment and Dr Hymer Friedell discusses this story in an oral history on record with US DOE . The late Professor John W. DeWire of Cornell told of being dispatched from Los Alamos to Cambridge where he took up residence whilst overseeing the dismantelment and shipping of the cyclotron to Los Alamos via St Louis.
From the files we show a photograph of Robert Wilson (center) discussing the issue with physics department chairman Percy Bridgman (right) with another man, believed but not confirmed to be, the late Hymer Friedell on the left. We can find no contemporary account of exactly what was said at the meeting but Bob Wilson who was well known for dramatic (but essentially accurate) summaries said 30 years later that Bridgeman's response was "if you want it for what you say you want it for you can't have it. If you want it for what I think you want it for, of course you can have it."
At the time of writing the source and amount of funds for this first cyclotron is still being researched. My memory from discussion with the late Roger Hickman is that the construction cost was about $40,000 of which about $20,000 came from the Rockefeller Foundation which then funded medical research.
The Second Harvard Cyclotron 1945-1955
Immediately following World War II, a new cyclotron and nuclear laboratory were planned. Professor Bainbridge, still at Los Alamos in the fall of 1945, wrote several letters (copies are available here1. 2. 3. 4) to colleagues at Harvard to plan a new building instead of Gordon McKay laboratory. The letters show that he was, at first, unsure whether the old cyclotron would be a new cyclotron would be built. Wasting no time, in 1945 Harvard University appropriated a sum of $425,000 to expand research facilities in Nuclear Physics. However, this amount was not enough to fund the construction of both a new cyclotron and a new laboratory. The U.S. Navy began a program of funding a program in basic science and through its Office of Naval Research (later a joint program of ONR and AEC administered by ONR) this department of the US government fulfilled the unwritten obligation of 1943 and offered the funding for the construction of a 160-ton cyclotron. Harvard provided the funds for the construction of a building to house both the cyclotron and a connecting laboratory. The building was originally called the Nuclear Laboratory and other nuclear facilities such as a betatron were contemplated.
We divide the history here into three phases. The first initial phase encompassed the design and initial construction, operation at 90 Mev and the research up until 1955. This work is encompassed in this chapter. The second phase began in 1955 when the energy was raised to 165 Mev, and the work done on nuclear physics for the next 12 years. Then we define a third phase of the 35 years from 1967 to 2002 years during which time the primary work was on medical treatment.
Initially the driving force for the new cyclotron was Professor Kenneth Bainbridge. He persuaded Robert R Wilson to join the Harvard faculty as Associate Professor of Physics, on his departure from Los Alamos in Summer 1946, and head up the team for the design and construction. By agreement, Bob Wilson was to spend the year on leave at Berkeley working with staff there on cyclotron design while Ken Bainbridge was to keep things going at Cambridge. In 1947, Bob came to Cambridge but only spent 6 months before taking up a new post as Professor of Physics and head of the Laboratory for Nuclear Science at Cornell University. Bob later commented that one of the facts that influenced him in his departure was being asked to do double teaching duty to make up for his "goofing off" for a year in Berkeley! So Ken Bainbridge took over from him officially in 1946-7 as the Director of the Cyclotron. But Bob's year had been very productive. In addition to establishing the major design parameters, Bob wrote a famous small letter to the American Journal of Radiology which presaged the later medical work. He was motivated to give some time to medical application as “atonement for involvement in the development of ther bomb at Los Alamos".
At a conference in Cambridge, UK in
September 1946, which was attended by Richard
Wilson, then a graduate student at Oxford, Professor
Bainbridge described the plans for the new
cyclotron. It was to occupy an empty area (see photograph
) between the old Gordon McKay laboratory on the east side
of Oxford Street and the Divinity school on Divinity
Avenue. As Professor Bainbridge mischievously said,
the planned neutron beam would head straight for the
divinity school supposedly sending the occupants to the
heavens prematurely. At a group meeting
Mr (later Dr) David Bodansky remembers an
emphastic statement of Professor Bainbridge.
referring to the proposed medical work which was
envisaged to be merely the production of radioactive
isotopes, Bainbridge declared "There
will no rats running around THIS
cyclotron." Such blanket predictions are dangerous
and often soon contradicted.
Dr. R.B. "Tex" Holt, an Assistant Professor
at Harvard had a wife
who was doing medical research at one of the major Boston
hospitals. She irradiated some of her animals in the area
adjacent to the cyclotron soon after the first beam was obtained
in 1949. But this was an isolated study, and the
laboratory was free of the smell of animals until Dr.
Raymond (Ray) Kjellberg preformed his experiments on dogs and
monkeys in 1963 preparatory to his pioneering neurosurgery
In 1948 Professor Norman Ramsey was recruited from Columbia University and became director of the Cyclotron Laboratory. Lee Davenport, who had the nebulous title of "Coordinator" stayed on and provided an effective transition. He was given the title of Assciate Director (according to a written record) or Deputy Director (according to Professor Ramsey's memory). The 1947 - 1948 year was very productive. The main components of the cyclotron were installed. The 650 ton magnet iron had been fabricated in Pittsburgh, PA, and machined at the "local" Watertown Arsenal. It was 23 ft long, 15.5 ft high and 10 ft wide. The magnet was moved in 14 separate sections, on 3rd or 4th December 1947. The magnet was rigged into place by a special crew of riggers from California who had done much of the rigging for the cyclotron and other accelerators there. The set of photographs here shows the magnet assembly by Albert (Pop) Poperell with his special crew from Bigge Drayage Co. of California, as written up in the Boston Globe of January 11th 1948. The magnet coils, each weighing 37 tons, of which 30 tons was copper, were wound in the General Electric coil winding shop in Pittsfield, MA and were the largest coils (14 ft diameter) that could be shipped on the Boston and Maine Railroad to North Cambridge. Even then they could not come on the direct Boston and Albany mainline because of inadequate clearances. It was the clearance on this railroad that was the final arbiter of the cyclotron energy! When it became time for the coils to be shipped from Springfield, GE wanted a responsible Harvard person to "collect" them. It was arranged that the chairman of the Department would undertake this task. The chairman, Professor John H. Van Vleck, was a railroad buff from his boyhood and gladly agreed provided that he could ride on the footplate of the engine. Mr W.A. Williams, head of GE Power Transformer division accompanied the train with the first coil, and Van, with Harvard engineer Frank B. Robie accompanied the second coil. From the vantage point of the footplate Van took several photographs of the ride three of which are shown here.
From then on construction proceeded rapidly. The logbook shows that on June 3rd 1949 at 2:03 in the morning, the first beam was obtained. Present were Norman F. Ramsey, Al. J. Pote, Robert (Bob) Mack, G.P.W. (unknown), Peter Van Heerden, and Lee L. Davenport. At the celebratory party the champagne cork made a dent in the ceiling plaster board. This dent was carefully preserved until an unfortunate redecoration sometime about 1980 destroyed the historical dent. The first of this set of photographs shows Professor Ramsey and Associate Director Lee Davenport posing for the newspapers in the control room on June 10th just before the formal dedication of the cyclotron on June15th 1949. Later photographs in the set show how little it changed over the years. Provost Paul Buck was chairman of the dedication. There was a distinguished set of speakers at either the dedication or the subsequent dinner at the Harvard Club. In addition to Norman F. Ramsey, and Lee L. Davenport, Captain A.L. Pleasant, ONR, (Boston), Alan T. Waterman (ONR Washington), Dr Urner Lidell, H.M.Macneille, Division of Research of the US Atomic Energy Commission (AEC. The enthusiasm of Davenport and Ramsey was great. O:ne day, after a formal dinner with the President they returned to the cyclotron, in their dinner jackets, to find a leak using a new helium leak detector that had been delivered that afternoon. Alas no one else was present to take a photograph to record the event. A chart shows the staff during this construction period, and a photograph shows many of the staff. Many stories of this period were told at the 50th anniversary celebration by Norman Ramsey and Lee Davenport.
The beam for the next 6 years was not at the full design energy but at a reduced energy of 110 Mev, and sometimes as low as 95 Mev, because of a (temporary) failure to make the oscillator work over the full frequency range and the lack of obvious need for immediate work at a higher energy. Professor Ramsey, desirous of pursuing active research work at the cyclotron and even more productive work on molecular beams (which work later won him the 1989 Nobel prize in physics), arranged for Dr.R.B. Holt (Harvard PhD 1947) to become the director of the cyclotron from 1950 to 1952.
Several first rate students obtained their PhD from work at the cyclotron at this time. David Bodansky, Norton Hintz and Robert Birge were the first. The photograph shows two of them, Robert Birge and Ann Chamberlain (later Birge), looking at the counters on which their data was recorded. At the top of the equipment rack are two binary scalers (counters) based upon the 25 year old Eccles-Jordan circuit, modified by E.B. Lewis at Cambridge in 1935 for nuclear applications, and further developed at Los Alamos by Elmore and Sands. The student had to note the lamp which showed the state of each binary in this 64A fold scaler, and perform by slide rule the appropriate arithmetic. Dr Robert Birge, son of the University of California Physics Professor Raymond Birge, was destined later to become a senior research fellow himself at the University of California at Berkeley, and Ann Chamberlain, later to become Ann Birge, became a Professor at Hayward College in California. Other students include a South African, Dr David Hillman, who later became a biology Professor in Hebrew University in Jerusalem.
Nikolaas (Nico) Bloembergen, then a junior fellow in the Society of Fellows, also tried his hand at using the cyclotron. He, together with Peter van Heerden, measured range - energy relationships using the internal cyclotron beam and compared them to theory. But Nicholaas was to move on to win the 1981 Nobel Prize in physics with his paramagnetic maser and his research on non linear optics. In 1950 Professor Karl Strauch joined Harvard, firstly as a Junior Fellow until 1953 when he became an Assistant Professor. He worked tirelessly with the cyclotron for the next 10 years. Shortly there after Walter Selove was appointed Assistant Professor before moving on in 1956 to the University of Pennsylvania.
The ONR nuclear research contract, of which the cyclotron was the largest part, was the largest - and at first the only - government contract in the physics department. As a consequence the cyclotron laboratory became an employer of graduate students, even of those whose thesis work would be elsewhere. Two obtained their PhD before the cyclotron operated. William Cross worked on "The Conservation of Energy and Momentum in Compton Scattering (PhD 1950) and Leo Lavatelli on "Photoelectric Absorption" in 1951. Harold I. Ewen was also awarded the PhD in 1951. Ewen with Professor Purcell, used an antenna outside the south face of Lyman Laboratory to measure "Radiation from Galactic Hydrogen at 1420 Megacycles per Second" a direct proof of the existence of interstellar hydrogen. Another was Paul Martin, who was awarded the PhD in 1954 for a thesis on "Bound State Problems in Electrodynamics" and who later became Dean of Applied Sciences. He remembers working in the electronic shop. Other non-cyclotron guests were also welcomed. In 1955-1956 Harold Furth was building pulsed high field magnets before high field superconductors were known - but he was awarded the PhD in 1960 for a thesis on "Magnetic Analysis of K- interactions in nuclei".
Space for research was scarce so in 1951/2 the nuclear laboratory building was extended to the north side to make room for an expanded machine shop and a few offices. Other appointments of note at this time included Andreas M. (Andy) Koehler who was appointed at the cyclotron in some capacity that no one remembers, and which capacity Andy very quickly outgrew, and William (Bill) Preston (Ph.D. Harvard 1936) who remained as director for 20 years. At the memorial service for Bill, Richard Wilson gave a eulogy outlining his work as a scientific administrator.
The Second Harvard Cyclotron 1955-1967
By 1953 it was already becoming apparent that the energy of 95 Mev was too low for a long term program of nuclear and particle physics. The pi meson mass had been determined to be 137 Mev, and to produce pi mesons in appreciable numbers needed an energy of 300 Mev or more. In addition, measurements at other cyclotrons (Rochester, Harwell, Chicago) had shown that protons become polarized by scattering from nuclei and nucleons at energies of 130 Mev and above, but at 90 Mev the polarization is low. At the time this was merely an empirical observation, but it can be explained by noting that a nucleon of energy about 70 - 90 Mev suffers a phase change of 180 degrees as it passes through a heavy nucleus making the nucleus appear to be opaque (in atomic physics this is the Townsend-Ramsauer effect). In 1955 for example, Professor Mme Joliot-Curie increased the planned energy of the cyclotron being built at Orsay near Paris, for this reason. Before 1953 the way of obtaining an external proton beam was by scattering from an internal target, with a consequent large loss of intensity. But in 1953 a scheme was proposed by James Tuck and Lee Teng to extract the proton beam from the Chicago cyclotron by a regenerative oscillation scheme. The theory of this process was expanded by Le Couteur in Liverpool and used to extract the beam from the Liverpool cyclotron in 1954. In September 1955 it was decided, therefore, to rebuild the Harvard cyclotron. This rebuild coincided with the arrival at Harvard of Richard Wilson , the present historian, as Assistant Professor of Physics. Several steps were taken simultaneously:
- (1) The magnet was shimmed to allow cyclotron operation to a higher energy of 165 Mev.
- (2) The RF
oscillator was adjusted so that it would oscillate over the
full range of frequencies necessary-
- (3) A beam extraction system of the
LeCouteur design was constructed.
As the beam accelerated and occupied a larger diameter orbit in the cyclotron, the protons entered a regenerator (shown in the top left hand picture of this group of five pictures), consisting of two pieces of high saturation iron, one above and below the orbiting protons at one azimuth. The regenerator was adjusted to provide an increase of magnetic field with radius that was close to Le Couteur's recipe as shown in the top right drawing of the same group of five pictures. Shims we placed at a smaller radius (as shown in the bottom left picture) to compensate for an otherwise incorrect field profile at smaller radius. An oscillation was set up between the fall off the main magnetic field and the localized increased field of the regenerator. The bottom right picture of this group of five shows an extraction channel located at the maximum of the oscillation (at an azimuth just before the regenerator). These photographs were taken after dismantlement of the cyclotron. The rebuild had a feature unique to Harvard. It was realized that particles in the regenerator- field fall off oscillation would all have the same energy in contrast to the distribution of energies of protons striking a target under ordinary conditions. Two regenerators were constructed. One, together with the extraction channel, was used to extract the beam completely, and the other to make the monochromatic beam strike a carbon target at the other side of the cyclotron, from which target scattered, polarized, protons were brought out for experiments. This is illustrated in the fifth drawing in the bottom center. Which experimental program was in progress depended upon which regenerator was inserted into the magnet.
Typically the cyclotron was operated by the scientists
performing the experiment and at first only he or she would be
present on a night shift. Later it became clear that a
second person was important for safety: the experimenter
could fall down, drop a lead brick onto his toe, or otherwise
get hurt. The shift change was a typical time to discuss
data. On one Sunday morning Dr Allan Cormack had been on
night shift, Professor Norman Ramsey was coming on day shift,
and Professor Richard Wilson came by to discuss the data.
But priorities changed when it was noted that the beam had
disappeared, and the magnet current had gone up too high.
The magnet current was regulated by comparing the voltage across
a shunt with a reference, and amplifying the difference to run a
bidirectional (Selsyn) motor. The motor operated a
variable transformer (Variac) which controlled the DC field of
the DC generator. The drive for the variac was a chain
and sprocket system, with limit switches. The system had
failed, the limit switches failed to work, the chain had broken
and the motor was struggling against the stops. Dr
Cormack and Professor Ramsey sprang into action.
An instant redesign took place. An O ring was used
instead of the sprocket and chain drive, and two pulleys were
made, one each machined by Dr Cormack and Professor Ramsey.
No limit switches were needed because the O ring could
slip if the drive went too far. This system was
installed within the hour, and survived for about 20 years
before the motor-generator set was replaced by a rectifier
system acquired surplus when the Cambridge Electron Accelerator
shut down. Of the three persons present that
morning both Dr Cormack and Dr Ramsey were later awarded
the Nobel prize but neither of them for their skill as a
Assistant Professor Douglas Miller set out to use the polarized neutron beam (obtained by producing neutrons at an angle of 30 degrees from the incident protons) to study neutron proton scattering. This led to the PhD theses of Russell Hobbie, and Norman Strax. Later, this neutron beam was improved and was more monochromatic, by allowing the external proton beam to impinge on a liquid deuterium target, by Dr David Measday, a research fellow recruited from Oxford University, who later went to Canada and became director of the Triumpf laboratory. Other studies included proton-proton inelastic scattering showing collisions from deep shells (Gottschalk) small angle scattering (Steinberg), neutron crossections ( Carpenter); deuteron pickup reactions (Cooper).p-d elastic scattering (Postma) and inelastic scattering (Kuckes). Particularly notable was the first measurement of bremsstrahlung in proton-proton collisions by Shlaer and Gottshalk.
The Cyclotron staff, led by Bill Preston and Andy Koehler, continued to be outstanding. No prhotograph seems to exist of all the staff together, but some photographs have been located of individual machinists, assembly staff and electronic shop staff. Most of these were transferred to work on high energy experiments at the Cambridge Electron Accelerator and elsewhere as the program shifted its focus.
Funding was the most difficult task. Dr Ganz of MGH, pediatrician for Dr Kjellberg's children, suggested to Dr Charles Regan of Massachussets Eye and Ear hopsital that the proton beam was ideal for treating eye tumrs and in particular the heridatary tumor retinablastoma. Interestingly, we treated only a handful of retinablastomas, but in 2003 they are high on the list of new treatment modalities for NPTC. Dr Regan put in a proposal to NIH but it was turned down, largely because of inadequate communication between Mass. Eye and Ear and HCL. Dr Regan mistakenly described the alpha particle beam (not the proton beam) and Dr Preston felt only able to give suport that cost FAS nothing. Both these defects in the proposal were remedied in a new proposal that was finally successful, that involved Dr Ian Constable and Dr Evangelos Gragoudas. Nonetheless medical funding was slow in coming, so that the physicists Koehler, Preston and Wilson (called the Biomedical Group in the Harvard archives), started searching. On the principle of starting with the largest pocket, we approached the medical program of the Atomic Energy Commission which at the time were spending some $4 million a year on proton and alpha radiotherapy at Lawrence Berkeley Laboratory, hoping for a small fraction - perhaps 10% of this sum. No luck. But providentially the National Science Foundation started a new program, “Research Appropriate for National Needs” (RANN). The cyclotron received two grants for this work. The first was to adapt the Harvard Cyclotron and for clinical trials. The second was a pilot study of detecting calcium in the extremities of the body by proton bombardment producing the radioactive potassium K38 and detecting the characteristic 2.16 Mev gamma ray. In addition fees from the neurosurgery patients brought by Dr Kjellberg continued to arrive.
1972 Drs Suit commenced a program of clinically related
radiation biological experiments to assess the RBE value to be
employed. These were done by Drs. Robertson of the Harvard
School of Public Health, Raju of the Los Alamos Laboratory and
E. Hall of Columbia University. These were in vitro
studies. In parallel, a long series of RBE assays were performed
on intact tissues of the laboratory mouse by Drs. Urano and then
Tepper. The result was that 1.10 was chosen to serve as a
generic RBE value, viz all dose levels and tissues.
Then in February 1974, the first patient was treated using fractionated dose radiation therapy at the equivalent of about 2 Gy/fraction. This patient was a boy with a posterior pelvic sarcoma. The second was a woman with a skull base sarcoma. This category of tumors now includes some 800 with really impressive results. Namely, the 10 year control results are 95% and 45% for chondrosarcoma and chordoma, respectively. The principal clinicians included Drs Liebsch, Munzenrider, Austin Seymour, Hug and Suit. The important clinical physicists were Drs Goitein, Verhey and Smith. In 1975 the first of 2,979 patients was treated for ocular melanoma by a team comprised Drs Evanglos Gragoudas [ophthalmological surgeon of the MEEI], John Munzenrider [radiation oncologist of the MGH] and Michael Goitein [physicist at the MGH].. Dr Goitein developed the first 3D treatment planning software to be implemented in regular clinical work in many parts of the world. It was first designed for treatment of ocuilar melanoma. He also developed the concept of and brought into clincial practice: DVH, dose volume histogram, DRR [digital reconstructed radiograph], and the display of uncertainty bands around isodose contours.
1976 was the year for the start of funding of the first NCI grant for clinical study of proton beam radiation therapy. This funding has been continuous from 1976 to the present. This grant was critical for the conduct of this radiation oncology program. Drs Suit and Goitein served as Co Prini\cipal Investigators to 1976 to 1998 when Dr Jay Loeffler became the PI.
1975 Dr William Preston retired from his positions as
director of the cyclotron laboratory and director of the
physics laboratories. The staff now
Dr Robert J. Schneider, Dr Janet Sisterson, Ms
Kristen Johnson and Mr Miles Wagner in addition to
Andy Koehler as Assitant Director and Bill Preston as
Director emeritus. The management procedure was
changed. The management was vested in the acting
director of the laboratory, reviewed by a management
committee chaired by Professor Richard Wilson (other
members, Dr S.J Adelstein (Academic Dean HMS), Dr Herman
Suit and Dean Richard Leahy) . This committee reported
directly to the Dean of FAS and administratively bypassed
the physics department. By this time the
medical program at Harvard Cyclotron laboratory was well
under way. There were three basic prongs.
Each had its peculiarities both in funding and in
treatment. These differences sometimes led
to stressful problems.
One of the reasons for the overall success of the program was the ability of the Harvard Cyclotron staff to manouver independently of the rivalries and scientific and political differences of the three groups. Originally the relationship between the Cyclotron Laboratory and MGH was highly informal. By informal agreement with Dr William (Bill) Sweet, director of the neurosurgery department at MGH, Harvard Cyclotron was treated as an operating room for purposes of liability and responsibility of the surgeons. All Harvard cyclotron personnel were covered by medical malpractice insurance on the general Harvard University policy. But the increasing number of patients, and the fact there were three programs of which one, the neurosurgery program, was completely separated (on the hospital side) from the others made a more formal agreement necessary - if only to prevent quarrelling between the physicians and surgeons. This was forced by a stormy interchange in 1977 and made formal and legal. The cyclotron staff also had to be made aware of the demands of patient confidentiality Harvard University negotiated a one-sided agreement. MGH was responsible for any liability arising from the treatments, but nonetheless, anyone on the cyclotron staff had the authority to decide NOT to treat a patient if he felt that the planned treatment was inappropriate. Fortunately such an eventuality never occurred.
(1) Neurosurgical (intercranial) lesions treated by the Neurosurgery department of MGH Dr Raymond N. Kjellberg and Dr Bernard Kliman, later Dr Chapman)
(2) Eye tumors treated by Massachusetts Eye and Ear Hospital. (Dr Ian Constable, Dr Evangelos Gragoudas )
(3) Larger tumors treated by the Radiation Medicine Department of MGH. (Dr Herman Suit, Dr Joel Tepper, Dr Michael Goitein, Dr Lynn Verhey)
We collect here some photographs of the various treatments
In the following 27 years each of these
groups made major contributions, and each was in its own way
essential to the whole program. However from the start
the physicians at MEEI
collaborated very closely with the
physicians at the Radiation Medicine Department at MGH and
in particular with the physicists (led by Michael Goitein)
at MGH. The software program for 3 dimensional
treatment planning which was developed by Michael Goiten was
used for both the ocular tumors and the large field tumors
as well as being the basis for similar programs at many
other medical centers worldwide. In
1981, Professor Richard Wilson went on leave and a change was
made. Dr S. James Adelstein, academic dean in the medical
school became Chairman of the management committee. The
reporting was changed to report to the Dean of Applied Sciences
instead of the Dean of FAS. Dr Adelstein remained Chairman
for the next 21 years until the shut down in 2002.
medical advanttage of all of the treatments followed the
point raised by Robert R. Wilson in 1947. The
aim of all radiation treatments is to destroy cancerous and
other unwanted tissue, while doing as little damage as
possible to the surrounding healthy, and, desired, tissue.
The proton beam succeeds in this for two reasons.
Firstly protons have a well defined range, with a shap
increase of ionization at the end of the range first pointed
out by Sir William
Bragg (the "Bragg peak"). They produce little or no
damage beyond the end of the range. Secondly protons
being heavy, scatter less than the electrons commonly used
for radiotherapy. If the tumor or other lesion is small,
(less than 1 cm diameter) as in treatments (1) and
(2) it is comparatively easy to install absorbers so
that the protons stop on the lesion. If the lesion is
large, as in treatments (3), it is much harder to obtain a
uniform dose distribution across the tumor. The photograph
shows a typical dose distribution across a pituitary gland.
large field arrangement was a simple one that was designed, as
was so much, by Andy Koehler. Firstly the beam impinged
on a scatterer to spread the beam. This resulted in a
beam that was non-uniform in intensity across the beam.
Then an absorber was paced in the center of this beam to
absorb the higher intensity portion. Finally there was a
second scatterer. This double scatterer technique produced
a remarkably uniform beam distribution. Then the range was
modulated by a set of absorbers on a wheel that rotated during
the treatment, allowing the proton beam to stop at various
depths in the tumor in turn. A plastic bolus was machined
for each treatment (photograph) and restricted the sidewise
extent of the beam.
More promising, perhaps, was the idea that
production of potassium (K38) by proton bombardment of
calcium, leading to a bioassay for calcium. Here the idea
is to locate calcium loss in the spine long before calcium loss
shows up in the extremities. In a PhD thesis, (also
funded by NSF in their RANN program) Dr Eilbert was able
to find a reproducability in a phantom, made of hamburger
surrounding fossil bones, of 1.5 %. However medical
support was not, at the time, forthcoming and the project was
abandoned. At that time also we tried to obtain funding from the
National Institutes of Health for a "facility" grant, for
keeping the cyclotron alive for a variety of medical purposes
including, of course, therapy. However, this also was
the beginning of this period onwards it was realized that the
Harvard cyclotron was not ideal for the medical work it
pioneered. Although the range of protons in tissue was
10-15 cms, this was not enough to reach all tumors from all
directions. In addition it is far preferable for a
cyclotron to be located at the hospital.
Already in 1973 Andy Koehler was thinking about small, cheaper,
specialized cyclotron designs. But it was already
realized that the cost of the cyclotron itself was a small part
of the total treatment cost.
Professor Bernard Gottschalk returned to the Harvard Cyclotron Laboratory as a Senior Research Fellow in 1982. One of the first tasks he undertook was to plan a new accelerator: his choice being a synchrotron because the energy is easily variable. Although attempts to obtain NIH funds for this new development failed, his design was useful in the design for the synchrotron at Loma Linda University Medical Center. That synchrotron was funded in large part by a special grant from the US Departmen of Energy. This grant was congressionally directed funding from the committee on energy in the House of representatives chaired by Representative Lindy Boggs of Louisiana. Ms Boggs was very sensitive to the need for proton radiotherapy since her daughter, Mayor of Princeton, died of a choroidal melanoma which metastasized. They became aware of our (Massachussetts Eye and Ear Infirmary, Massachusetts General Hospital and HCL) successful cures too late. We were asked by a committee staff member whether we would like to be included in the special appropriation, but Harvard University and MGH do not accept congressionally directed ("pork barrel") funds, so that a hospital based facility had to wait another 10 years.
In 1990 after application to NIH design funds were made available for a complete new proton therapy facility - accelerator, beam lines, treatment rooms - the lot. Professor Michael Goitein, at MGH and Harvard Medical School was the PI of the grant and undertook the design. Construction funds were made available in 1994. The contractor for the fine building was Bechtel, and for the cyclotron and beam lines, IBA of Belgium. This became the Northeast Proton Therapy Center (NPTC) at MGH built in the exercize yard of the old Charles Street jail. The building and the first operation of the cyclotron came in on schedule, but reliable operation of the beam, beam transport and gantries was elusive. After much travail, the first patient was treated in November 2001 and the whole proton therapy program began the switch to NPTC in November 2001, and NPTC picked up the full load by April 2002.
By 1993 Andy Koehler (shown here in his office) had been with the laboratory 40 years, many of them as acting director or director. He asked to be relieved of his duties as director, remaining a senior research fellow. But there was plenty of able talent. Miles Wagner took over as director and led the program for the next 9 years. In 1999 the Harvard cyclotron had been operating for 50 years. This was a record for cyclotrons, many of which had shut down as nuclear physics and high energy particle physics developed. We had already had many major parties. A "final closing" party in 1967; another "closing party" in 1970, and a 40th anniversary party. We had to celebrate once again. We did so with a one day symposium followed by a dinner at which Andy Koehler's formal retirement was announced. But With Andy, as with so many loyal Harvard people retirement did not mean stopping work.
Wednesday April 10th 2002 the Harvard cyclotron treated its last
patient - the 9,115th. The patient was a young
boy with bilateral retinoblastoma - a heriditary cancer of
the eye. Starting when he
was 2 months old and continuing till he was 4 months
old, he received 22 irradiations to each eye.
We anticipate that he will be cured. A total of 2,979 eye tumors
have been treated along with 3,687 neurosurgical lesions
and 2,449 large tumors at various sites. A dedicated group of
professors, physicians, physicists, nurses, operators and
technicians from Harvard and MGH attended a
small celebration of this work in the
evening. The last
photographs were taken at this celebration.
But the sucess of the therapy program is not merely the success
of the local sucessor (NPTC) at MGH. It is the success of
other locations where the HCL/MGH treatments have
been copied or are planned.
first use of the cyclotron for radiation damage studies came
when ATT needed to test their transistors to see whether they
would survive in space. In space there are a number of
cosmic ray protons with a peak in the spectrum around 150
Mev. In 1961 a former graduate student of Professor Robert
Pound, Dr Walter Brown, then at Bell Telephone Laboratories in
Murray Hill, NJ, brought some of the equipment to be bombarded
with 150 Mev protons in the cyclotron. The equipment
survived the test, and so did the equipment on board the
Telestar satellite. NASA also realized that there
was a need to understand not only how equipment behaved in the
radiation environment of space, but so also was there a need to
understand how people behaved. That was the
primary reason that NASA funded the construction of the Medical
Annex to the cyclotron. NASA also
funded a special cyclotron with an energy of about 500 Mev in
Newport News, Virginia to perform radiation damage studies for
satellite communication equipment and components. But the
NASA cyclotron proved too cumbersome for the task and it was
shut down in the late 1960s. Over the years,
NASA directly, and contractors for NASA, regularly
brought equipment to Harvard Cyclotron laboratory for test.
The scientists would typically have the cyclotron to
themselves for the whole weekend (when medical work was not
being done) with a cyclotron staff member, most recently Mr
Ethan Cascio, to help them.
The University wanted
the space occupied by the cyclotron for a large
underground parking garage and new science buildings on
top. Although the last patient was treated on April 10th
2002 the cyclotron kept going 7 more weeks.
The University was not quite ready to
begin the process of decommisioning. In the meantime
a backlog of radiation damage studies were performed.
Cascio, one of the many loyal staff members
over the years, was in charge of these radiation damge
studies in the last years, and was responsible for
the last operation of the cyclotron performing studies for
Minneapolis Honneywell which came an end was at
approximately 9 am on Sunday morning June 2nd 2002 when
the last radiation damage study was concluded, and the
cyclotron was shut down by Harvard administrative staff a
day earlier than agreed and switched off for ever.
This was 53 years and 7 hours after the first
beam was observed.to an untimely end on June 2nd
2002 when the cycotron . By October 2002 the
office building had been emptied and dismantled and in
November 2002 the shield walls and other material in the
cyclotron vault itself were being removed. The
magnet shims cut by hand with tin shears by Professors
Strauch and Wilson on Christmas Eve 1955 were still in
place. The regenerator and beam extraction
equipment were the same as those installed rapidly in
summer 1956. The magnet, the rigging of which took
so much trouble and care to install in 1947 was cut up
into small pieces and sold as scrap material. The
radiation levels were smaller than had been feared.
In summer 2003 the cyclotron vault is being removed.
But the work lives on. Although Harvard was not the first cyclotron to use protons for radiotherapy it was for many years the most successful, largely because of the close cooperation between the physics department, the cyclotron staff, and the physicians at MGH. As we write there are perhaps 19 other institutions now using proton radiotherapy. In them the Harvard cyclotrons live on.