Friday, April 15, 2022

Louis Harold Gray: A Founding Father of Radiobiology

Louis Harold Gray: A Founding Father of Radiobiology, by Sinclair Wynchank, superimposed on Intermediate Physics for Medicine and Biology.
Louis Harold Gray:
A Founding Father of Radiobiology
,
by Sinclair Wynchank.
Only great scientists have units named after them: the newton, the joule, the watt. An important unit in medical physics is the gray. Chapter 15 of Intermediate Physics for Medicine and Biology states
The absorbed dose is the expectation value of the energy imparted per unit mass:

D = dE/dm .            (15.68)

It is measured in joules per kilogram or gray (Gy).
Is the gray named after a scientist or does it have something to do with the color? And if a scientist, then just who is Dr. Gray? The answer can be found in Sinclair Wynchank’s scientific biography Louis Harold Gray: A Founding Father of Radiobiology (Springer, 2007). My summary of Gray’s life is taken from Wynchank’s excellent book.

Gray—known to his friends as “Hal”—was an English radiobiologist born in London in 1905. His parents were poor, and he attended high school at Christ’s Hospital, a British public boarding school established to help boys who could not afford other institutions. The school was noted for its excellent teaching of science. Gray thrived and performed well enough in the sciences that in 1924 he was awarded a scholarship to Trinity College, part of the University of Cambridge.

Cambridge was famous for being the home of the Cavendish Laboratory, headed by Ernest Rutherford. When Gray graduated with a bachelors degree in physics he joined the Cavendish as a graduate student. His thesis advisor was James Chadwick, who discovered the neutron and was Rutherford’s right-hand-man. As a graduate student, Gray derived the Bragg-Gray relationship (see Equation 16.35 in IPMB). Wynchank writes
Hal’s first scientific publication was in 1929 and it provided a method of calculating the dose of X-rays that were used to irradiate someone (the cavity ionisation principle). This was a most important piece of work, for it allows someone to have an X-ray picture taken and then for it to be known what X-ray dosage had been given. Excessive use of X-rays is very dangerous and in the early days of X-ray applications, some doctors and patients died because they had received excessive doses of this radiation… every reader of these words, who has had a chest, or any other X-ray, has benefited from this work of Hal. It is now known as the Bragg-Gray principle, since both Hal and Professor W. H. Bragg, a friend of Rutherford, a Nobelist, former exhibitioner of Trinity College and professor of physics at Leeds, had both independently described the principle. But Bragg had not realised its importance and its long range implications.

After obtaining his PhD in 1931, Gray remained at Cambridge but changed his research direction to study the interaction of radiation with biological materials. After Chadwick discovered the neutron in 1932, Gray became interested how neutrons interacted with tissue. In that same year, Gray married Frieda (Freye) Marjorie Picot, an English Literature major at Girton College, Cambridge.

Wynchank continues:

Hal’s work at Cambridge ended in 1933 when he took up a post of hospital physicist at the Mount Vernon Hospital in Northwood, on the northern edge of London... Hal’s principal reason for the move was to be able to do full time research in his newly chosen field, the study of ionising radiation to aid cancer treatment... [In February 1938, Hal built] the world’s first accelerator neutron source for biological research... Hal’s insight with regard to this crucial function of energy deposition in tissue irradiation led finally to the unit of absorbed dose of radiation being re-defined in terms of energy and being adopted internationally in 1953. Later the unit was posthumously named after him, being officially termed the “Gray”... In 2 years of slog and improvising most creatively, [Hal and his collaborator] built the neutron generator and then studied the relative effectiveness of various radiations: neutrons, alphas, X-rays and gammas, when they cause cellular damage... Hal found that his neutrons when irradiating mouse tumours were 17 times more effective than gammas.
Gray and Freye had two sons, born in 1939 and 1943. Gray was a firm pacifist. During World War II his work was considered so important that he was exempted from military duty.
At the start of 1946, Hal was appointed senior physicist in the Radiotherapy Research Unit (RRU) of the Medical Research Council (MRC), located at the large and very prestigious postgraduate Hammersmith Hospital in West London... Hal was the first to explain the oxygen enhancement effect, although others had previously suggested that some parts of a tumour might lack oxygen and so be able to resist destruction by ionising radiation... Radioactive atoms (radioisotopes) were also investigated at the RRU. Their valuable clinical applications resulted from collaborative studies at the Hammersmith Hospital and elsewhere. This was the beginning of a new medical speciality, nuclear medicine.
In 1953, after a dispute with his supervisor about the relative priority of clinical versus basic research, Gray abruptly left the RRU and accepted a new position in a London laboratory funded by the charity known as the British Empire Cancer Campaign (BECC).
Hal’s life work after Cambridge can be summed up as relating radiobiology to radiotherapy, so that more effective treatment of cancer would result. Almost single-handedly he was the initiator of the relevance of oxygen, stressing its potential importance to the treatment of patients. This oxygen effect (that is its presence) increased radiation’s destructive power. He made many radiotherapists appreciate the importance, where it was appropriate, of experimental results to the better understanding of how to manage their patients… Free radicals’ effects on the DNA molecule, a crucial component of life, were also studied by Hal and his colleagues… Ways of improving the action of radiation were studied and the findings allowed more effective treatment. One successful such approach was to find pharmaceuticals which, if located in the region to be irradiated, cause the radiation to kill more cancer cells. These pharmaceutical products are radiosensitisers and Hal was one of the first to investigate them.
Gray received many prestigious awards, including election as a Fellow of the Royal Society of London. He died in July 1965, at the age of 59, from a stroke. Had Gray not died so young, he might have eventually been awarded a Nobel Prize.

I’ll end with a tribute to Gray that readers of IPMB will appreciate. Gray was
“the first—and quite possibly the last—scientist to have had a thorough appreciation in all four sectors of radiation research: physics, chemistry, biology and medicine.”

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A personal note: Academically speaking I am descended from James Chadwick, so Louis Harold Gray is my academic great-great-great uncle. It’s good to know you better, Uncle Hal!

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