Thorotrast was a radiographic contrast agent first introduced in the late 1920s which contained the radioactive compound thorium dioxide. Originally used in angiography (the process of imaging blood vessels) neurosurgeon Geoffrey Jefferson and his team began using it in 1935 for ventriculography (a process for imaging the brain). Jefferson’s patient case files for this period are housed at the University of Manchester Library and demonstrate the development and use of this technique.
Two of Jefferson’s close colleagues, the radiologist Edward Twining and the neurosurgeon George Rowbotham, published an article in The Lancet illustrating how the injection of Thorotrast into the cerebral ventricles would work in comparison to the already existing method of injecting air during the process of ventriculography. It had been noted that injections of air often contributed to the instability of the patient’s condition and there could be noticeable immediate after effects, such as headaches, whereas patients receiving Thorotrast instead were much more stable in the short term. Radiographically the result was much improved too with increased clarity and definition.
The case discussed in Twining & Rowbotham’s article corresponds with patient 1935/99 in Jefferson’s case files, which contains much more detail about the patient’s medical history and resultant condition. It is believed that this patient is the first of Jefferson’s patients on which this new technique was tried out and Jefferson himself notes in this particular file that he believes it will change the whole outlook of ventriculography.
The safety of Thorotrast was soon brought into question and has since been described as the “most potent human leukemogen yet identified” (Aronson, 2006). Once administered it eventually settles in the reticulo-endothelial system, particularly the spleen and the liver, which was already known at the time of use in the 1930s but the resultant long-term effects had yet to be anticipated. At proceedings of the British Medical Association’s annual meeting in 1933, throium was referred to as a “feebly radioactive substance” yet the long biological half-life of Thorotrast meant that patients would be exposed to internal radiation for the rest of their lives. Follow up studies into patients in more recent years have shown very high incidents of liver cancers and leukaemias in particular. These effects were also investigated in Manchester and there is evidence in Jefferson’s case files of patients being followed up in the 1950s in an effort to determine the effects Thorotrast may have had.
The details in Jefferson’s patient files stand as a fantastic source for the development of radiographic imaging techniques, their long term effects, and the ethical considerations surrounding the use of new and as yet not fully understood techniques. During the current cataloguing process all patient files where there is definite evidence of Thorotrast having been used will be clearly marked for easy identification.
J.K. Aronson (Ed) Meyler’s Side Effects of Drugs (Fifteenth Edition) 2006, p.3401
S. Takekawa, Y. Ueda, Y. Hiramatsu, K. Komiyama, H. Munechika, ‘History note: tragedy of Thorotrast’, Japanese Journal of Radiology, 2015, Vol.33(11) pp.718-22
E.W. Twining & G.F. Rowbotham, ‘Ventriculography by opaque injection’, The Lancet, 1935, 226(5838), pp.122-5
‘Summary of Proceedings of the BMA at its 101st annual meeting – Proceedings of the Section of Radiology’, BMJ, 1933, 2(3787), pp.249-50