The following trial demonstrates the importance of entering a SHTF scenario in good health. Typically scurvy sets in within 4-6 weeks, but when subjects were pre-loaded with a 70 mg/day supplement for six weeks before the scorbutic diet was fed, it took 6-8 months for scurvy to set in. I just checked my generic multivitamin and they contain 60mg of Vitamin C.
ije.oxfordjournals.org/content/35/3/556.fullMedical experiments carried out in Sheffield on conscientious objectors to military service during the 1939–45 war
John Pemberton
+ Author Affiliations
Emeritus Professor of Social and Preventive Medicine, The Queen's University of Belfast, Belfast, UK and Clinican to the Medical Research Council Vitamin A and C deprivation research teams 1942–1946
Iona, Cannonfields, Hathersage, Hope Valley, Derbyshire S32 1AG, UK
Accepted January 25, 2006.
A number of medical experiments were carried out on conscientious objectors in Sheffield during the 1939–45 war. The subjects of these were pacifists nearly all of whom had been before tribunals and were allowed to volunteer for the experiments as an alternative to military service.
The first experiments were to study the transmission of scabies and to determine the water requirements of shipwrecked sailors. These were directed by Dr Kenneth Mellanby and were described by him in his book Human Guinea-pigs.1
The vitamin A and vitamin C deprivation experiments were initiated by the Medical Research Council at the request of the Ministry of Food because it was necessary to know, in planning food rationing, how much of these food factors were needed for health. They were funded first by the Ministry of Health and then by the Medical Research Council and were directed by the late Sir Hans Krebs.
A short report of the vitamin C experiment was published in the Lancet in 19482 and both vitamin deprivation experiments were reported fully in two Medical Research Council Special Reports Nos. 264 and 280.3,4
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The volunteers
These consisted of 32 young men and three young women all healthy at the start of the experiments that took place more than 60 years ago.
Most of the volunteers have now died or are untraceable and very few, if any, of the 20 or so research workers, apart from myself, are still living.
I would like to record a short account of the main experiments and pay tribute to the volunteers who often underwent considerable discomfort, pain, and, in a few cases, danger to life in the course of these and helped to make some valuable contributions to medical knowledge.
None of the volunteers died or had any permanent disability as the result of the experiments.
They lived together for up to 4 years in a large house in Sheffield, later known as the Sorby Research Institute. Some of them were able to continue in their civilian jobs, others did the domestic work in the house, and some helped in the collection and recording of data.
Because of these arrangements it was possible to control their diet very closely in the vitamin deprivation experiments, to take regular specimens of blood and urine and to carry out various tests and procedures.
One volunteer, the late Walter Bartley, who carried out some of the measurements and recorded data, later followed Hans Krebs as professor of biochemistry in the University of Sheffield.
Bearing in mind the strict requirements of the Declaration of Helsinki on medical research involving human subjects,5 it is unlikely that a similar opportunity for human experimentation under the conditions and on the scale of the Sheffield experiments will be available in the foreseeable future.
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Surviving volunteers
It seemed to me that it would be worthwhile to try and find out how any of the surviving volunteers, who would now be over 80, felt today about the experiments.
One of these, Norman Proctor, now aged 92, helped me to trace survivors among the 23 volunteers known to him.
Of these, 17 were known to have died, three were untraced, and three replied to my short questionnaire. Those who replied all thought that the experiments had been very worthwhile and stated that they would have volunteered again if required. From the beginning, in 1940, the volunteers had made it clear that they were not willing to take part in any experiments in which the main object was to assist in providing answers to purely military questions. They required that the research should be such that the answers should be of benefit to the general population.
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The experiments
The main experiments were to determine the minimum daily human requirements of vitamin A and C, to discover the way in which scabies is spread, and to study the effects of total deprivation of water and the requirements for survival: the Shipwreck Experiment. I was involved only with the vitamin experiments.
The vitamin C experiment (October 1944–February 1946)
The 20 volunteers taking part in this experiment were put on a diet that excluded all vitamin C-containing foods for 6 weeks, but included a daily supplement of 70 mg ascorbic acid. Then three of them continued on the supplement of 70 mg ascorbic acid daily, seven a supplement of 10 mg daily, and 10 were given none.
Detailed biochemical analyses of the urine and blood were carried out during the experiment. In those who received no vitamin C the blood plasma concentration of the vitamin declined rapidly and remained at 0–0.03 mg per 100 ml until the vitamin was restored to the diet. In those receiving the supplement of 70 mg per day, the figure averaged 0.55 mg throughout.
I was responsible for the clinical examinations that involved recording the known and suspected signs of scurvy as they appeared, the occurrence of any other illnesses, and carrying out some minor surgical operations. These consisted in making a 3 cm incision in the thighs of the volunteers under a local anaesthetic and closing the wounds with five sutures. The healing and breaking strength of the wounds was studied by excising the wounds at various stages, including the stage when scurvy had developed, and the stages of recovery. Photographs of the wounds at these various stages and the other signs of clinical scurvy observed are reproduced in the Medical Research Council Report.3
The development of scurvy
All the 10 volunteers deprived of vitamin C developed the signs of clinical scurvy in 6–8 months. These included petechial haemorrhages in the skin round the hair follicles, bleeding of the gums and, in one case, effusions into the knee joints. The wounds in this group tended to break down and bleed readily and their breaking strain was much reduced.
The vitamin C experiment also disclosed a serious and unexpected risk for those with scurvy. One man who had developed the disease after 31 weeks on the depleted diet complained one morning of severe pain in the lower sternal region. His pulse became rapid and the blood pressure fell to 80/40 mg Hg. The clinical picture resembled that of a coronary thrombosis. He was given 1 g of ascorbic acid intravenously and recovered in a few days. He was thought to have had a haemorrhage into his heart muscle or pericardium.
Another man in the deprived group who had developed signs of scurvy also experienced a constrictive pain in the chest and was found to have an extension of the PR interval in an electrocardiogram. Haemorrhage into the heart muscle or pericardium was also suspected in this case.
These cases illustrated that in scurvy, bleeding can occur not only in the skin, gums and old wounds, as described by Lind in 1753,6 but in internal organs as well.
A search of the literature since 1945 revealed very few studies of human vitamin C deprivation continued to the stage of clinical scurvy and none that had so many subjects as in the Sheffield experiment or that included a control group and continued for as long. Hodges et al.7 fed, through a gastric tube, five prisoner volunteers in the Iowa State Prison, on a diet containing no vitamin C for 84–99 days. They reported that the first sign of clinical scurvy, petechial haemorrhages in the skin, appeared after 29 days of deprivation compared with 182–238 days in the Sheffield study. The longer period in the latter may have been due to the fact that all the Sheffield volunteers had been on a diet containing 70 mg vitamin C daily for the 6 weeks before the deprivation period started. The Sheffield study showed that scurvy could be prevented or cured by a daily intake of 10 mg of vitamin C. The Iowa group found the same.
It has been suggested that the daily consumption of vitamin C should be much higher than the 30 mg recommended as a minimum requirement by the Sheffield group. However, no differences were found in the Sheffield study in the health of those receiving 70 mg a day compared with the group receiving only 10 mg a day and Jacob8 could find no biological or physiological markers to indicate a condition of vitamin C deficiency in the absence of signs of clinical scurvy.
Vitamin A deprivation experiment (August 1942–July 1944)
A study, similar to the vitamin C experiment, was carried out on 23 of the volunteers to determine the human requirements of vitamin A.4 The only specific effect that developed in those deprived of vitamin A and its precursors was some loss of night vision after ∼8 months. There was no difference in the incidence of coughs and colds in the deprived and control groups but one man in the deprived group developed severe impetigo and two developed tuberculosis, one in the spine and one in the pleura. Both made a full recovery.
No cases of impetigo or tuberculosis occurred in the control group. Because of the small numbers involved, these differences could not be ascribed to the lack of vitamin A in the diet of the deprived group, although in the case of tuberculosis this was a possibility. The two studies of the effects of deprivation of vitamins C and A were reported in detail in the Medical Research Council reports.3,4
Scabies 1941
In the study aimed at discovering the mode of transmission of scabies, it was found very difficult to achieve the passage of the mite from one man to another. Wearing the used underclothes from an infected person was found to be successful on some occasions. The itching experienced by the infected men was described as almost intolerable.1
The ‘shipwreck’ experiment 1942
The ‘shipwreck’ experiment was regarded by the volunteers as the most unpleasant. It was designed to study the minimum requirements for water of shipwrecked sailors. As part of the study they were allowed no fluid at all for three and a half days. Their diet consisted of the dried food that was packed in lifeboats for shipwrecked sailors, namely, ships biscuits, pemmican (dried pulverized meat), malted milk tablets, and plain chocolate.1
How valuable were the experiments that were carried out on the Sheffield volunteers?
The vitamin C experiment showed that young adults could remain healthy for more than a year on a daily intake of only 10 mg of vitamin C. The Medical Research Council Vitamin C sub-committee finally recommended an intake of not <30 mg as the daily requirement for adults to allow for a safety margin and for individual variations. This provides a valuable guide for those planning a diet for any group for which vitamin C-containing foods are in short supply as was the case with fresh fruit during the war and that led to the supply of free orange juice for children.
The results in the vitamin A deprivation experiment were not so clear-cut as in the vitamin C experiment. On the basis of the observations on changes in dark adaptation of the eye during depletion and repletion of the vitamin and its precursors, 2500 IU of vitamin A was recommended as the daily requirement for an adult and would again be a useful guide in conditions of shortage.
The scabies experiment showed that very close contact with a person with scabies was necessary before the transmission of the mite could occur. Lack of personal cleanliness and the close contact that may occur, for example, when children share the same bed should, if possible, be avoided.
The ‘shipwreck’ experiment was designed to improve the chances of survival of shipwrecked sailors by determining the minimum daily amount of water required. It was shown that more water should be stored in lifeboats even at the expense of less food if necessary.
The Sheffield conscientious objectors demonstrated once again, how valuable medical knowledge can be obtained by human experimentation, and sometimes in no other way, if volunteers can be found who are willing to undergo considerable discomfort, pain, and even serious risks to their health.
The contributions of the Sheffield volunteers to medical knowledge during the 1939–45 war should not be forgotten.
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Acknowledgments
J.P. is a clinician to the Medical Research Council Vitamin A and C deprivation research teams 1942–46. I would like to thank John Eyers of the London School of Hygiene and Tropical Medicine, Mary Mowat, librarian at the Rowett Research Institute, Aberdeen, and Dr Brian Williams for help in searching the literature on vitamin C deprivation, and Norman Proctor, Joe Woodhouse, and Harold Garling, among the last surviving subjects of the Sheffield experiments, for helping me to compile this footnote to medical history.
Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2006; all rights reserved.