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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="1.3" xml:lang="en" article-type="review-article"><?properties open_access?><processing-meta base-tagset="archiving" mathml-version="3.0" table-model="xhtml" tagset-family="jats"><restricted-by>pmc</restricted-by></processing-meta><front><journal-meta><journal-id journal-id-type="nlm-ta">Emerg Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Emerg Infect Dis</journal-id><journal-id journal-id-type="publisher-id">EID</journal-id><journal-title-group><journal-title>Emerging Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1080-6040</issn><issn pub-type="epub">1080-6059</issn><publisher><publisher-name>Centers for Disease Control and Prevention</publisher-name></publisher></journal-meta>
<article-meta><article-id pub-id-type="pmc">10977855</article-id><article-id pub-id-type="publisher-id">23-0693</article-id><article-id pub-id-type="doi">10.3201/eid3004.230693</article-id><article-categories><subj-group subj-group-type="heading"><subject>Historical Review</subject></subj-group><subj-group subj-group-type="article-type"><subject>Historical Review</subject></subj-group><subj-group subj-group-type="TOC-title"><subject>Alfred Whitmore and the Discovery of Melioidosis</subject></subj-group></article-categories><title-group><article-title>Alfred Whitmore and the Discovery of Melioidosis</article-title><alt-title alt-title-type="running-head">Alfred Whitmore and the Discovery of Melioidosis</alt-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Savelkoel</surname><given-names>Jelmer</given-names></name></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Dance</surname><given-names>David A.B.</given-names></name></contrib><aff id="aff1">Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands (J. Savelkoel); </aff><aff id="aff2">Lao-Oxford-Mahosot Hospital&#x02013;Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Laos (D.A.B. Dance); </aff><aff id="aff3">University of Oxford, Oxford, UK (D.A.B. Dance); </aff><aff id="aff4">London School of Hygiene &#x00026; Tropical Medicine, London, UK (D.A.B. Dance)</aff></contrib-group><author-notes><corresp id="cor1">Address for correspondence: Jelmer Savelkoel, Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ, Rm T1.0-234, Amsterdam, the Netherlands; or David A.B. Dance; email: <email xlink:href="j.savelkoel@amsterdamumc.nl">j.savelkoel@amsterdamumc.nl</email> or <email xlink:href="david.d@tropmedres.ac">david.d@tropmedres.ac</email></corresp></author-notes><pub-date pub-type="ppub"><month>4</month><year>2024</year></pub-date><volume>30</volume><issue>4</issue><fpage>752</fpage><lpage>756</lpage><permissions><copyright-year>2024</copyright-year><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/" specific-use="textmining" content-type="ccbylicense">https://creativecommons.org/licenses/by/4.0/</ali:license_ref><license-p>Emerging Infectious Diseases is a publication of the U.S. Government. This publication is in the public domain and is therefore without copyright. All text from this work may be reprinted freely. Use of these materials should be properly cited.</license-p></license></permissions><abstract><p>We review the discovery of the tropical infectious disease melioidosis by Alfred Whitmore, a pathologist from England, and his assistant from India, C.S. Krishnaswami. We discuss how the subsequent disappearance of melioidosis from the medical literature of Burma holds parallels with the current neglect and under recognition of the disease. We urge global and national public health authorities to add melioidosis to existing neglected tropical diseases surveillance systems. </p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>Melioidosis</kwd><kwd>Burkholderia pseudomallei</kwd><kwd>bacteria</kwd><kwd>history</kwd></kwd-group></article-meta></front><body><p>&#x0201c;We have, and always will have, need of both Science and Art in medical practice; they are not antagonistic principles, but are mutually helpful; there is room, enough and to spare, for the free and energetic use of both; it is ignorance alone which sees them hostile, folly indeed which seeks their division.&#x0201d; So wrote Alfred Whitmore in 1914 (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). Whitmore was a remarkable man, not only in advocating what seems like a modern integration between laboratory and clinical work more than 100 years ago (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>) but also in achieving eponymous immortality by describing a novel disease (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>). He did this without specialist training and while working in relative isolation in his role as pathologist in Rangoon General Hospital (RGH), Burma (now Myanmar), in 1911 (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>,<xref rid="R3" ref-type="bibr"><italic>3</italic></xref>). Yet the way in which his findings were initially f&#x000ea;ted and subsequently forgotten holds strong parallels with the present day under recognition and ignorance of both Whitmore and the disease he described.</p><p>The disease discovered by Whitmore and his assistant, C.S. Krishnaswami, is now known as melioidosis but is still often referred to as Whitmore&#x02019;s disease (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>,<xref rid="R4" ref-type="bibr"><italic>4</italic></xref>). The name melioidosis was only later coined by A.T. Stanton and W. Fletcher in 1921 and is derived from a Greek word meaning glanders-like disease (<xref rid="R5" ref-type="bibr"><italic>5</italic></xref>,<xref rid="R6" ref-type="bibr"><italic>6</italic></xref>). Over the past few years, and captivated by Whitmore&#x02019;s wonderful prose style, one of us has been researching his life and work (<xref rid="R7" ref-type="bibr"><italic>7</italic></xref>&#x02013;<xref rid="R9" ref-type="bibr"><italic>9</italic></xref>). In this review, and the accompanying video (<xref rid="F3" ref-type="fig">Figure 3</xref>), we summarize some of our more recent findings about Whitmore&#x02019;s career. We discuss what happened to his discovery in the years after he made it, and how that relates to melioidosis today. The information included in this review is based on the references provided and documents kindly provided by the Whitmore family.</p><fig position="float" id="F3" fig-type="figure"><label>Figure 3</label><caption><p>David Dance describing his research journey into the life and times of Alfred Whitmore and the discovery of melioidosis. Dance&#x02019;s research included close collaboration with the Whitmore family and visits to archives in India, Myanmar, and the United Kingdom. (Video link: <ext-link xlink:href="https://vimeo.com/925317363?share=copy" ext-link-type="uri">https://vimeo.com/925317363?share=copy</ext-link>)</p></caption><graphic xlink:href="23-0693-F3" position="float"/></fig><p>Whitmore was born in Botcherby, in northwest England, in 1876 and grew up in Sebergham in Cumbria, where his father was rector (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>). Among his early hobbies, Whitmore studied the process of decay of animal carcasses, which might have presaged his later career. He attended St. Bees School in Cumbria, studied medicine at Gonville and Caius College at Cambridge University, and completed his medical training at St. Mary&#x02019;s Hospital in London, receiving scholarships and prizes along the way (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>). After qualifying as a doctor, he completed the Diploma in Public Health that was obligatory for entrants into the Indian Medical Service (IMS) and was commissioned as a lieutenant in January 1903 (<xref rid="F1" ref-type="fig">Figure 1</xref>) (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>,<xref rid="R11" ref-type="bibr"><italic>11</italic></xref>). His posting to the less fashionable center of Burma might have been influenced by his finishing last in the Diploma in Public Health exam. In later life he commented, &#x0201c;I entered the Service with no particular ambition, chiefly perhaps because I had no money&#x02014;a bad reason.&#x0201d; His mandatory 2 years of military service were spent in India and the Andaman Islands before he arrived in Rangoon, Burma, toward the end of 1905 (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>), little expecting that he would shortly unearth a novel infectious disease.</p><fig position="float" id="F1" fig-type="figure"><label>Figure 1</label><caption><p>Alfred Whitmore wearing his Indian Medical Service uniform, circa 1903.</p></caption><graphic xlink:href="23-0693-F1" position="float"/></fig><p>In the old, wooden RGH, Whitmore&#x02019;s initial responsibility was taking care of the dying patients on the &#x0201c;moribund ward,&#x0201d; without the aid of nurses and with hygiene that left much to be desired. He even mentioned rumors of patients&#x02019; feet being gnawed off by rats in a letter written to his son in January 1946, although adding that he could not &#x0201c;aver the truth of this.&#x0201d; He thought the care that was provided was undignified for any human being. Thus, he tried to improve the lot of his patients by providing alcohol, which he described as the &#x0201c;best med of any that I have used,&#x0201d; as well as cheroots (a local type of cigar) and a wheeled bath that he later found being used as a fish tank. However, his role was about to change because plans were underway to build a new hospital, albeit without a laboratory (<xref rid="R12" ref-type="bibr"><italic>12</italic></xref>). That plan was contrary to Alfred&#x02019;s ideas. In a talk given in Cambridge following his return to England, he said he was &#x0201c;&#x02026; trained to believe that there was a &#x02018;Science&#x02019; as well as an &#x02018;Art&#x02019; of Medicine and that the laboratory was the High Altar, as it were, of that Science.&#x0201d; He convinced the authorities of the necessity of a laboratory, which was duly added, with Whitmore taking on the role of pathologist on condition that he would also undertake the medicolegal work in the capacity of police surgeon. He remained a passionate advocate for the integration of a laboratory within the hospital, believing that close collaboration between the clinic and laboratory were essential to good quality &#x0201c;Western medicine&#x0201d; (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>).</p><p>Whitmore worked as pathologist and police surgeon at RGH from 1909 until 1915, during which he discovered melioidosis (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>). Melioidosis, caused by the gram-negative bacterium <italic>Burkholderia pseudomallei</italic>, is now known as a disease that typically has clinical manifestations of pneumonia, sepsis, and abscess formation, predominantly in persons with underlying risk factors, details of which can be found elsewhere (<xref rid="R13" ref-type="bibr"><italic>13</italic></xref>). </p><p>In 1911, Whitmore and Krishnaswami, who had graduated as a licentiate in medicine and surgery from Madras Medical College (<xref rid="R14" ref-type="bibr"><italic>14</italic></xref>), undertook a postmortem examination that revealed &#x0201c;&#x02026;a peculiar consolidation of the lungs,&#x0201d; which they felt was consistent with glanders, a zoonotic disease of horses (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>). The victim, however, had no history of recent animal exposure, and cultures yielded a bacterium that they recognized as different from what was then known as <italic>Bacillus mallei </italic>(now <italic>Burkholderia mallei</italic>), the cause of glanders, in its rapid luxuriant growth and motility. In 1912, they published, in the Indian Medical Gazette, their microbiological and pathological findings from 38 cases of this recently discovered disease (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>). A more comprehensive report in the subsequent year, in which Whitmore first proposed the specific epithet pseudomallei, included additional information about each case, 31 of which were &#x0201c;morphine injectors&#x0201d; (<xref rid="R15" ref-type="bibr"><italic>15</italic></xref>). By 1914 the term morphia injectors&#x02019; septicaemia had been suggested for the disease name (<xref rid="R16" ref-type="bibr"><italic>16</italic></xref>). </p><p>Opioid injection is not currently recognized as a risk factor for melioidosis, and the reasons for such a strong association as that reported by Whitmore are unclear (<xref rid="R13" ref-type="bibr"><italic>13</italic></xref>). Whitmore himself initially felt the infection most likely was caused by the general debility associated with morphine injections (<xref rid="R15" ref-type="bibr"><italic>15</italic></xref>) but later appears to have favored contamination of the injections themselves, because 46 of the 52 cases in the 1914 report also bore evidence of morphine injection (<xref rid="R16" ref-type="bibr"><italic>16</italic></xref>). That finding would hardly have been surprising given the squalid conditions in which the drug users of the day were liable to have received their morphine (<xref rid="R17" ref-type="bibr"><italic>17</italic></xref>). </p><p>Then along came World War I, and as a member of the IMS, Whitmore was obliged to return to military service in British India (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>). Meanwhile, Krishnaswami continued to work on the disease until 1917, when he stated he had encountered some 200 cases (<xref rid="R18" ref-type="bibr"><italic>18</italic></xref>), but he subsequently moved to work in what was then known as the &#x0201c;Lunatic Asylum&#x0201d; system for the rest of his career in Burma (<xref rid="R14" ref-type="bibr"><italic>14</italic></xref>,<xref rid="R19" ref-type="bibr"><italic>19</italic></xref>).</p><p>Whitmore spent the war at various stations in British India (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>), frequently having brushes with authority because he did not tolerate fools, especially if they were senior officers issuing edicts from &#x0201c;the hill tops.&#x0201d; On returning to Rangoon, although he had hoped to resume his job as pathologist, he was appointed as a civil surgeon and never worked on melioidosis again (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>). He found his role as a civil surgeon exhausting, leaving him little time for the reading he considered essential to keep up to date with the latest developments. In 1922, he moved to become superintendent of the Burma Government Medical School, a role in which he remained until he returned to England on leave in 1924, eventually retiring from the IMS in 1927 (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>,<xref rid="R20" ref-type="bibr"><italic>20</italic></xref>&#x02013;<xref rid="R22" ref-type="bibr"><italic>22</italic></xref>). </p><p>After a brief spell in Paignton, Devon, UK, Whitmore moved to Madingley, near Cambridge, UK, where he remained involved in education and research until his death in 1946 (<xref rid="F2" ref-type="fig">Figure 2</xref>) (<xref rid="R23" ref-type="bibr"><italic>23</italic></xref>). People thought of him as an inspirational lecturer, and his obituary in the British Medical Journal described him as &#x0201c;&#x02026; a most lovable man with a very keen sense of humour, and all who knew him well were greatly attached to him. He seemed to radiate something buoyant and joyous, and the outlook always seemed brighter when he was about&#x0201d; (<xref rid="R23" ref-type="bibr"><italic>23</italic></xref>).</p><fig position="float" id="F2" fig-type="figure"><label>Figure 2</label><caption><p>Timeline of the life of Alfred Whitmore and the discovery of melioidosis. The timeline highlights Whitmore&#x02019;s personal and military achievements. IMS,&#x000a0;Indian Medical Service; MB,&#x000a0;bachelor of medicine degree; RGH,&#x000a0;Rangoon General Hospital; WWI,&#x000a0;World War I.</p></caption><graphic xlink:href="23-0693-F2" position="float"/></fig><p>Whitmore&#x02019;s discovery was initially celebrated by the colonial hierarchy in Burma and was specifically mentioned in the Report on the Administration of Burma for 2 consecutive years (1911&#x02013;12 and 1912&#x02013;13) (<xref rid="R24" ref-type="bibr"><italic>24</italic></xref>,<xref rid="R25" ref-type="bibr"><italic>25</italic></xref>). Lengthy debates about the appropriate form of bacteriologic support for the government in Burma had taken place, and some suggested that locating a laboratory in Rangoon would be impossible because of the climate; therefore, the authorities were doubtless keen to celebrate the success of this innovative venture (<xref rid="R12" ref-type="bibr"><italic>12</italic></xref>,<xref rid="R26" ref-type="bibr"><italic>26</italic></xref>). Yet, when World War I intervened, and Whitmore and Krishnaswami subsequently turned their attention to other duties, no one appears to have followed up on their findings: the next mention of melioidosis in Burma was in the 1940s (<xref rid="R27" ref-type="bibr"><italic>27</italic></xref>). At that time, the disease appeared almost exclusively to affect the &#x0201c;friendless wastrels&#x0201d; of Rangoon, primarily persons addicted to morphine, who were unlikely ever to be economically productive and who, through crime, might be a drain on colonial resources (<xref rid="R15" ref-type="bibr"><italic>15</italic></xref>,<xref rid="R28" ref-type="bibr"><italic>28</italic></xref>). In addition, up to that point, not a single case of melioidosis had been reported in a person of European heritage. Those factors must undoubtedly have been key in the apparent neglect of the disease by the colonial authorities as they struggled to restore order after the disruption of World War I.</p><p>Today, melioidosis remains a little-known disease, even within the countries where it is endemic (<xref rid="R29" ref-type="bibr"><italic>29</italic></xref>). Melioidosis endemic regions include northern Australia, many countries in South and Southeast Asia, sub-Saharan Africa, and tropical and subtropical areas of the Americas (<xref rid="R30" ref-type="bibr"><italic>30</italic></xref>,<xref rid="R31" ref-type="bibr"><italic>31</italic></xref>). Melioidosis is not yet formally recognized by the World Health Organization as a neglected tropical disease (NTD), despite the growing evidence that it is widespread throughout the tropics, is estimated to cause nearly 90,000 deaths a year globally, and has a disease burden considerably greater than that of many officially recognized NTDs (<xref rid="R31" ref-type="bibr"><italic>31</italic></xref>&#x02013;<xref rid="R33" ref-type="bibr"><italic>33</italic></xref>). However, as a disease that mainly affects lower income populations living in rural areas, another marginalized group, melioidosis remains underdiagnosed and excluded from the mandatory surveillance systems of most countries where it is endemic. A 2021 multistate outbreak in the United States from an imported aromatherapy spray and a 2022 report of isolation of <italic>B. pseudomallei</italic> from the environment in Mississippi, USA, for the first time, might have temporarily boosted the profile of melioidosis (<xref rid="R34" ref-type="bibr"><italic>34</italic></xref>,<xref rid="R35" ref-type="bibr"><italic>35</italic></xref>). Perhaps the increased attention resulting from those incidents will benefit the communities that suffer from this deadly disease. </p><p>In conclusion, global and national public health authorities should act to add melioidosis to NTD surveillance systems so that we do not again fail to follow the path initially signposted by Whitmore. We need to prevent history from repeating itself and make sure that both melioidosis, and Alfred Whitmore, are no longer forgotten.</p></body><back><ack><title>Acknowledgments</title><p>We are eternally grateful to the Whitmore family, particularly Margaret Davison, Alfred Whitmore&#x02019;s granddaughter, for providing access to their family records; pictures from the Whitmore records used throughout the multimedia article were reproduced with her permission. We also express our gratitude to all national archives for their cooperation, and the International Melioidosis Network for their continued support. </p><p>J.S. was funded by an Amsterdam UMC PhD scholarship and a Grassroot Grant of the University of Amsterdam. D.A.B. Dance was funded by the Wellcome Trust for his work on melioidosis during 1986&#x000ad;&#x02013;2019. The funders had no role in the writing of the manuscript or the decision to submit it for publication. </p><p>D.A.B. Dance acts as a consultant to InBios International Inc. in relation to the development of diagnostic methods for melioidosis and to MerLion Pharmaceuticals GmbH and Venatorx Pharmaceuticals, Inc. in relation to the development of new therapies for melioidosis.</p></ack><fn-group><fn fn-type="other"><p><italic>Suggested citation for this article</italic>: Savelkoel J, Dance DAB. Alfred Whitmore and the discovery of melioidosis. Emerg Infect Dis. 2024 Apr [<italic>date cited</italic>]. <ext-link xlink:href="https://doi.org/10.3201/eid3004.230693" ext-link-type="uri">https://doi.org/10.3201/eid3004.230693</ext-link></p></fn></fn-group><bio id="d66e324"><p>Mr. Savelkoel is a researcher at the Center for Experimental and Molecular Medicine of Amsterdam UMC, the Netherlands. His research interests include the global distribution and global health aspects of melioidosis. Prof. Dance is a retired medical microbiologist affiliated with the Lao-Oxford-Mahosot Hospital&#x02013;Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Laos. He has a longstanding interest in melioidosis, previously worked in Thailand and Laos, and has been researching the life and works of Alfred Whitmore and the discovery of melioidosis.</p></bio><ref-list><title>References</title><ref id="R1"><label>1. </label><mixed-citation publication-type="journal"><string-name><surname>Whitmore</surname>
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