Sir David Bruce
Biography of Sir David Bruce
Sir David Bruce won renown for discovering the bacterial cause of Malta fever and for extensive and fruitful researches on trypanosomiasis. His professional life was spent in the Army Medical Service and the Royal Army Medical Corps, in which he attained the special rank of surgeon general. With his wife he took part in breath-taking adventures in Zululand, Uganda and Natal. Despite hazards and difficulties confronting them, they carried out a series of meticulous experiments and laboratory work and founded the basis of understanding two devastating diseases – Malta fever and sleeping sickness. His closest collaborator was his wife, whose name appears on at least 30 of his 172 published papers.
David Bruce was born in Melbourne, the son of Scottish parents who had immigrated to Australia during the gold rush of the early 1850’s. His father, David Bruce, accompanied by his wife, Jane Hamilton, left Edinburgh to install a crushing plant in the Victoria goldfield. When he was five years old, David’s parents returned with him to Scotland and settled in Stirling, where he attended Stirling High School until the age of fourteen.
He subsequently began working for a warehouse firm in Manchester. However, a keen sportsman, tall and powerful, and a prizefighter, it was his ambition to become a professional athlete. This was frustrated by an attack of pneumonia at age seventeen, and in 1876 he resumed his studies, gaining admission to the University of Edinburgh.
As a schoolboy, Bruce became an enthusiastic ornithologist and planned a university course in zoology. After he had completed his first year at Edinburgh as medallist in natural history, a physician friend persuaded him to study medicine. He graduated M.B., C.M. in 1881, and subsequently assisted a doctor in Reigate, Surrey, where he met Mary Elizabeth Steele, six years his senior, daughter of Dr. John Sisson Steele, the previous owner of the practice. They were married in 1883. Although childless, their marriage was singularly fortunate, for Mary Bruce proved an indispensable helpmate - domestically, socially, and scientifically. Mary had inherited her father's ability for accurate painting and sketching. This she used to great effect in her laboratory drawings of Trypanosomes and other organisms.
After a brief spell in general practice, Bruce started his military medical career by entering the Army medical school at Netley, passing out top of top of the list in 1883, and in August that year was commissioned surgeon captain in the Army Medical Service. The following year he was posted to Malta, where he and his wife were quartered at the Valetta Hospital, which had no research facilities. Impressed by Robert Koch’s recent discovery of the tubercle bacillus, Bruce decided to investigate Malta fever, which annually hospitalised around a hundred soldiers of the British garrison, for an average of three months. Altogether Malta fever was responsible for approximately 120,000 days of disease each year.
The Bruces purchased a microscope and set up a laboratory to study the problem of the mysterious illness methodically. The affected person suffered from a relapsing fever and malaise. Usually the temperature rose at night, first to 39ºC, later to 41ºC, and fell by day. To begin with the fever gradually subsided, with recurrent bouts becoming less frequent, and the soldier returned to light duty. The average time for a soldier to be off duty was 90 days. Not everyone recovered, and in fatal cases the victim's fever became progressively worse, rising terminally to over 42ºC.
Investigations showed that the disease was scattered across many different districts of the three islands. The density of the population was one of the highest anywhere in the world, and most families were crowded together in tiny houses. Contaminated water and poor hygiene were blamed for the disease.
The Bruces searched in vain for the "organism of D'Ebert" which was responsible for typhoid. Instead they consistently found a Micrococcus that they had not previously seen. Late in 1886 he found «enormous numbers of single micrococci» in the spleen of a fatally ill patient. It measured 3 µm in diameter, was usually singled or paired, stained with gentian violet, and was Gram negative. It grew in peptone broth and could be obtained from the spleen, kidney and liver of a victim of the disease post mortem.
David Bruce inoculated three monkeys with Micrococcus organisms cultured for 24 hours. Sixteen days later one monkey's temperature rose to 41ºC and the monkey died. Post mortem the monkey showed congestion of the liver and spleen but no enlargement of Peyer's patches of the intestine characteristic of typhoid. Seven monkeys were inoculated, three by Bruce, and four by Dr. Hughes. Four died with the same symptoms as in man, and their organs grew the Micrococcus in pure culture. The other monkeys developed intermittent fever in two to three months, similar to that observed in man.
David Bruce sent his report to the Pasteur Institute in Paris. The Bruces' work had satisfied all the postulates that Robert Koch had promulgated as being necessary to establish the aetiology of a disease.
They had established the aetiology of the mysterious Malta fever. He later suggested the name Micrococcus melitensis for the organism.
In 1905 Themistohles Zammit (1864-), a Maltese member of the Commission for the Investigation of Mediterranean Fever, the twelve-man team of experts headed by Bruce, then back in Malta, implicated goat’s milk as the disseminating vehicle. The disease was conquered when goat’s milk was eliminated from the diet of the Malta garrison. The eponymous term «brucellosis» has now replaced such names as Malta, Mediterranean, and undulant fever.
Back in England
In 1889 Bruce returned to England on leave, spending time discoursing in Koch’s laboratory while his wife acquired the latest techniques in microscopy, staining, and media making. Bruce was appointed Assistant professor in Pathology at the Royal Army Medical School at Netley, where he introduced the experimental attitudes and bacteriological methods of Pasteur, Lister, and Koch. Now David worked with the eccentric genius Almroth Edward Wright (1861-1947) who is best known for advancing vaccination through the use of autogenous vaccines (prepared from the bacteria harboured by the patient) and through antityphoid immunization with typhoid bacilli killed by heat.
In 1894 Bruce was posted to Natal at the request of the governor, Sir Walter Hely Hutchison, who was a former lieutenant governor of Malta. Hutchison asked him to investigate an epizootic, nagana that was afflicting cattle in northern Zululand. Captain and Mrs. Bruce sailed for Pietermaritzburg, continuing the long journey to Umbumbo by oxcart, in much the same way as David Livingstone (1813-1873) had travelled some 40 years previously.
After trekking for five weeks, the Bruces arrived at Ubombo, where they lived for two months in a wattle-and-daub hut, using the veranda as a laboratory. The magistrate, his clerk, and the Bruces were the only white people there. They were surrounded by Zulus – who readily participated in their project.
Nagana, a devastating disease, was killing large numbers of the Zulu's cattle. This had serious implications, as the cattle were essential to their welfare and way of life. A similar disease had been described in West Africa and was known as surra. In India, likewise, a disease had been described that attacked horses, asses, mules, and camels. In 1877 a surgeon, Timothy Lewis of the Royal Army Medical Corps, discovered trypanosome in a rat whilst working in Bombay.
David Bruce gave a vivid description of nagana:
"The horse stares, he has a watery discharge from his eyes and nose. Shortly afterwards a slight swelling of the belly and puffiness of the sheath may be noticed, and the animal falls off in condition. The hind extremities also tend to become swollen; and these various swellings fluctuate, one day being less marked, or having disappeared. During this time the animal is becoming more and more emaciated, he looks dull and hangs his head, his coat becoming harsh and thin in places; the mucous membranes of the eyes and gums are pale, and probably slight cloudiness of the cornea is observable. In severe stages, a horse presents a miserable appearance. He is a mere scarecrow, covered by rough hair, which falls off in places. His hind extremities and sheath may be more or less swollen, sometimes to a great extent, and he may become blind. At last he falls to the ground and dies of exhaustion. During his illness he has shown no symptoms of pain, and up to the last days has had a good appetite.
Bacteriological examinations of affected oxen proved negative; but intensive microscopic study of blood specimens revealed a motile, vibrating haematozoom, which Bruce later concluded was a trypanosome. The relationship of this parasite to nagana was demonstrated by inoculating blood from infected cattle into healthy horses and dogs: they became acutely ill, and their blood swarmed with haematozoa. The natural way of transmission of the disease was revealed, as Bruce explained in his Croonian lectures (1915), when the oxen and several dogs, sent into a low-lying «fly-belt» for a fortnight, acquired this same parasite in their blood. He was now convinced that nagana was identical with the «tsetse fly disease» described by Livingstone in 1858, and that this fly transmitted the causal trypanosome.
This discovery led to his completing the work of the Italian physician and pathologist Aldo Castellani (1878-1971) who had demonstrated Trypanosomes in the cerebrospinal fluid of patients with sleeping sickness. Bruce demonstrated the organism in the blood and showed that they were transmitted from antelopes to cattle by the tsetse fly, Glossina morsitans. Bruce was thus the first to prove that an insect carried a protozoan of a pathological kind.
Return to Africa
The next assignment for Bruce was to investigate the outbreak of enteric fever among British troops in South Africa during the Boer war (October 12, 1899 to May 31, 1902). Mary Elizabeth accompanied him and they both played a prominent role in the siege of Ladysmith, where he directed a hospital and performed successful surgery. The siege of Ladysmith was a prolonged battle in which British troops were locked in a desperate defending action from October 1899 until the arrival of relief by General Buller on March 1, 1900 – a dreary 180 days. Out of 563 deaths, 393 were due to typhoid. They returned home in October 1901.
Mary Bruce received the Royal Red Cross Medal for devoted work with the wounded, particularly as nursing sister in her husband’s operating theatre. Colonel Bruce was promoted and received a medal with seven clasps. He presented his report on dysentery to the Royal Society and Parliament in 1901.
Sleep not too well
In 1903 Bruce was chosen to head the Royal Society’s Sleeping Sickness Commission to Uganda, arriving in Entebbe on March 12 that year. An outbreak of this mysterious disease occurred in Uganda in 1900 amongst native workers and was thought to be somehow related to the tsetse fly. Sleeping sickness is a deadly disease that was widespread in Africa. Victims may be of any race or colour, suffer from a prolonged debilitating fever and after a few months become confused and stuporous. They often may develop enlarged lymph nodes and spleen, and may have to be roused from slumber to eat. Ultimately they relapse into a coma and die. Post-mortem examinations show pericardial and peritoneal effusion and evidence of meningitis.
On behalf of the Foreign Office and at Patrick Manson’s (1844-1922) urging, the Royal Society had organized a similar commission to investigate and epidemic in Uganda in 1902, but its activities were uncoordinated and two members had returned home. The Bruces reached Entebbe in March 1903, with Dr. David Nunes Nabarro (1874-) and a sergeant technician, and met the remaining representative of the first commission, a young bacteriologist, Dr. Aldo Castellani.
Manson’s tentative suggestion of Filaria perstans as the causal agent had proved untenable; but Castellani had recently noted trypanosomes in cerebrospinal fluid taken from five victims. Previously, he had grown streptococci from the cerebrospinal fluid and heart blood of more than thirty. Well aware of the potential significance of the trypanosomes, although perturbed at the conflicting evidence, Castellani did not wish to be ridiculed by Bruce, still less by Nabarro, who was little older than he and whose appointment to supersede him he resented. He therefore imparted his observations to Bruce, on condition that he - Castellani - should temporarily continue searching for trypanosomes, that he should then publish his findings as sole author, and that Nabarro should not be informed. When Castellani left Entebbe three weeks later, he had demonstrated trypanosomes in twenty additional cases. He had also taught Bruce the techniques of lumbar puncture and of examining the cerebrospinal fluid for trypanosomes.
When the Bruces arrived in Entebbe there were several reports that gave them a basis for their investigation into the deadly disease. Dr. Castellani had observed "haematozoma" in the cerebrospinal fluid of five cases of sleeping sickness, and in one of these he had seen them in the blood. He did not consider that they had and causal relationship. The finding, however, was thought to be highly significant by David Bruce, and his team immediately set to work to investigate. The team comprised Dr Moffat (probably a grandson of the missionary Robert Moffat [1795-1883], David Livingstone's father-in-law), Principal Medical Officer of Uganda, Dr Baker, resident Medical Officer in Entebbe, and Colonel and Mrs Bruce.
Cerebrospinal fluid was centrifuged, according to Castellani's technique, and examined for trypanosomes. By the time that Dr Castellani left for England on April 26, 34 cases of sleeping sickness and 12 controls had been studied. Trypanosomes were found in 70 percent of the former and none of the latter. Subsequently the commission continued their work and found trypanosomes in the cerebrospinal fluid in every case of 40 cases examined. Similar results were obtained in patients examined in Kavirondo, Uganda.
All patients with sleeping sickness were found also to have trypanosomes in the blood. This had also been found in West Africa, where patients with fever but no sleeping sickness occurred. David Bruce felt that trypanosomal fever and sleeping sickness were different stages of the same disease. He gives an example of a man who suffered from a mild fever accompanied by trypanosomes in the blood and developed aggravation of the disease some months later when trypanosomes were found in the cerebrospinal fluid.
Investigation of 150 "hut tax workers" encamped upon the shores of the lake was undertaken. This was the "sleeping sickness area", and of 80 workers examined, 23 were found to have trypanosomes in their blood. Of 117 natives in a "non-sleeping-sickness" area, none were found to have positive blood findings.
Injection of cerebrospinal fluid from a patient with sleeping sickness into monkeys, resulted in a typical sleeping sickness in one monkey, but post-mortem examination of this monkey revealed that it also suffered from tuberculosis, so the result was not conclusive. Another monkey, in which the blood of patients suffering from trypanosomal fever was injected subcutaneously, developed sleeping sickness, from which it died. Post mortem there were trypanosomes in the central nervous system.
Fly, where art thou?
On their first arrival in Uganda, the Bruces could find no tsetse flies. Then Mary noticed two flies on David's back, which proved to be tsetse flies. A national fly hunt was organized, and flies were collected by the thousand. The bishops of Uganda participated in this quest and native "fly boys" collected flies and brought them to the laboratory.
Detailed examination was made of thousands of tsetse flies. They were dissected to study the development of trypanosomes and their evolution. The habitat and habits of the flies and their development from pupae into adults were also examined. Studies were made of blood taken from animals suffering from trypanosomal disease. Tsetse flies were allowed to feed on animals or persons suffering from trypanosomal disease and then on other animals to see if the disease had been transmitted.
On May 29, 1903, the Commission sent a preliminary report to the Royal Society, which was published in the British Medical Journal. The report concluded that sleeping sickness is caused by the entrance into the blood and cerebrospinal fluid of a species of trypanosome; and that this species is probably that discovered by Forde and described by Joseph Everett Dutton (1876-1905) in the West Coast of Africa and called by him Trypanosoma gambiense. The trypanosomes are transmitted from the sick to the healthy by a species of tsetse fly, Glossina palpalis, and it alone.
The Bruces left Africa on August 28, 1903, to continue their work on Malta fever in 1904.
The call of the Black Continent – once more
From 1908 to 1910, Bruce rejoined the Royal Societies continuing commission in Uganda, where he directed researches into conditions governing the transmissibility of T. gambiense by Glossina palpalis, and studied cattle and game as potential reservoirs of the parasites. The commission was closed when one of its members, Dr Lieutenant Forbes Tulloch, died of the disease
In 1911, now appointed Director of the Royal Societies Third Commission on Sleeping Sickness Bruce went to Nyasaland to investigate an epidemic amongst the natives of Kaviondo on the shores of Lake Nyasa, whose banks swarmed with flies. He immediately reorganized the laboratory, which was situated some distance from the lake. Cattle sheds were made for monkeys and proper hygiene and rainwater collection were organized. "Fly boys" were housed near the lake to supply 200-300 flies each day.
Flies caught by the native boys were put in cages brought to the laboratory and then fed in batches of 60 flies on three healthy animals: a dog, a monkey and a goat, each animal receiving 180 flies. In 56 experiments using 10.000 flies, 9 monkeys, 14 dogs and 11 goats were infected – an infectivity rate of 1/500. Thus, an inhabitant had a 1/500 chance of being bitten by an infected fly.
Bruce felt that wild game must act as a reservoir, and travelled Nyasaland to investigate the relationship between the diseases of the wild animals and those of humans and domestic herds. In 180 wild animals which were shot and whose blood was examined, 14 harboured the "nagana" parasite; the waterbuck, the hartebeest, the reedbuck and the duiker were the most commonly affected. Proof that the antelope harboured the disease had to wait for several years, when Mr Duke shot four sitatunga and found the animals were infected with Trypanosoma gambiense, which was transmitted to monkeys.
Two "fly boys" exposed to the flies in this region developed sleeping sickness.
Although the tsetse flies were responsible for transmitting sleeping sickness in most areas, occasionally an epidemic occurred in which the disease might be conveyed to cattle by direct contact with the ordinary horse fly, tanidae. This probably occurred when swarms of these flies surrounded the wretched animals. In one such epidemic some 3000 head of cattle died of trypanosomal disease in northern Rhodesia.
Sir David and Lady Bruce returned to England in 1913. David Bruce reported the results achieved by this Sleeping Sickness Commission of the Royal Society in the Croonian Lectures in 1915.
Fly hunter goes to war
In 1912 Bruce was promoted to Major General, and in 1914 was appointed Commandant of the Royal Army Medical College at Netley.
During the war, his administrative abilities were fully utilized, especially as director of scientific research and as chairman of committees for the study of tetanus and trench fever. He headed the commission to review the effectiveness of typhoid and tetanus inoculation, and give recommendations for its use.
At the outbreak of World War I inoculation against typhoid was still a controversial subject. Professor Almrod Wright, who had invented the vaccine, was convinced that inoculation was effective, but reports from the South Africa warfront were far from reassuring. Detailed analysis revealed that whilst the incidence of typhoid was reduced, the mortality rate of inoculated soldiers was actually higher than in the inoculated soldiers. Conditions for the inoculation of troops were unsatisfactory.
In the Royal Army Medical Corps journal in 1905, the commission reported: "Inoculation of troops with prophylactic fluid before arriving in an area where enteric is rife, renders certain soldiers more prone to acquire the disease. Antityphoid inoculation should be performed under very careful safeguards". Despite this warning Sir Almrod Wright continued actively to advocate inoculation of the army. The breakthrough came when the method of sterilization of vaccine was modified by the Scottish pathologist Sir William Boog Leishman (1865-1926).
The vaccine was given to troops who volunteered in 1904-1905. Statistics showed an impressive reduction of enteric fever. Typhoid inoculation was then used extensively in the British Army during the Great War. Sir David Bruce gave statistics, which convincingly showed that when correctly performed, typhoid inoculation saved lives:
"What the number of cases and death rate in the huge armies might have been had it not been for preventive medicine is impossible to say. I may therefore conclude that antityphoid inoculation constituted one of the greatest triumphs in the prevention of disease during the Great War."
The severe soft-tissue injuries of battles fought on the muddy contaminated fields of France brought a high risk of tetanus. As a result of the commission's work, antitetanus inoculation was introduced in September and October 1914. Each soldier received an injection of antiserum as soon as he was wounded. In September 1914 the incidence of tetanus in wounded soldiers was six times that in November of the same year. The mortality rate in the British Army fell from 58 % in 1914 to 31 % in 1916.
Bruce, who retired in 1919, suffered recurrent lung infections and wintered in Madeira. He died of cancer in his seventy-seventh year. His wife, who accompanied her husband on all his arduous trips, working self-effacingly beside him as technician, microscopist, and draftswoman, predeceased him by four days. Sir David Bruce passed away at his home in London whilst the funeral service for his beloved wife was in progress at Christ Church, Westminster. On his deathbed, he requested "should any notice appear about myself, you must see that my wife gets credit for all the work she has done". She was awarded the Order of the British Empire for her scientific work.
A man of honours
David Bruce was awash in honours and awards, with countless honourable memberships. He was appointed C.B. in 1905, knighted in 1908, and made K.C.B. in 1918. His abrupt manner, blunt speech, and egotistical personality endeared him to few; but his great energies and talents were dedicated to mankind’s health and welfare, and he died poor.
Although Sir David was an outstanding figure, he did attract some sarcastic comments from Harvey Cushing in his book «From a surgeon’s journal» concerning the research committee on which he and Cushing served. «General Sir David Bruce sank into a divan, stretched out his highly polished boots into the middle of the room, inserted his spurs into the rug, drew his John Bull visage deep into his clothes, turtle fashion, and slept profoundly which was good for the general and also helped the meeting.»
«If any notice is taken of my scientific work when I am gone, I should like it to be known that Mary is entitled to as much of the credit as I am.»
Quoted in Annals of Internal Medicine, 1965: 115: 351.
«We are all children of one father. The advance of knowledge in the causation and prevention of disease is not for the benefits of any one country, but for all - for the lonely African native, deserted by his tribe, dying in the jungle of sleeping sickness, or the Indian or Chinese coolie dying miserably of beriberi, just as much as the citizens of our towns.»
"It must no longer be said that the man was so sick that he had to send for the doctor. The medical practitioner of the future must examine the man while he is apparently well, to detect any incipient departure from normal and to teach and urge modes of living comfortable to the laws of personal health, and the public health authorities that man's environment is in accordance with scientific teaching."
From his address On the prevention of Disease delivered in Toronto, Canada in 1924 when
he was elected President of the British Association for the Advancement of Science.