June Almeida

Born 5th October, 1930 (Glasgow) - Died 1st December, 2007

Almeida has recently attracted a great deal of media attention in the midst of the COVID-19 crisis as the person responsible for the first visualisation of a human coronavirus. Yet, this barely scratches the surface of her achievements. Leaving school at the age of 16, Almeida managed to forge a major career based on her outstanding skills in electron microscopy. This she did in the midst of bearing a daughter and raising her as a single parent following divorce. Almeida's pioneering advances in immune electron microscopy put her at the forefront of many key breakthroughs in virology in the 1960s and 1970s.

June Almeida

Family

June Almeida was the eldest of two children born to Jane Dalziel Hart (née Steven) and Harry Leonard Hart. Her mother was born in Glasgow and her father in London. The couple met when Harry moved up to Glasgow to work as a bus driver and Jane was a shop assistant. With her parents having little money, Almeida was born and raised in a flat on the second floor of a tenement building on Duntroon Street in Dennistoun, a respectable working-class neighbourhood near the Glasgow Royal Infirmary. In 1940 the family was struck by tragedy when Almeida was ten years old. They lost her brother to diphtheria. He was just 6 years old. His death left a lasting impression on Almeida, helping to ignite her interest in the biological sciences (1).

Photograph taken of June Hart, c1950

Photograph taken of June Hart, c1950. Credit: Joyce Almeida. Almeida developed a strong passion for photography in her teenage years.

Photograph taken of June Hart, c1950

Photograph taken of June Hart in Scotland, c1950. Credit: Joyce Almeida. Almeida grew up very close to Alexandra Park, a public park in the East End of Glasgow.

In 1952, when Almeida was 22 years old, she moved with her parents to London. It was there that she met her first husband, Enrique Rosalio (known as Henry) Almeida, a Venezuelan artist who came to England in 1926 as a teenager. The two of them married in December 1954. They both shared a love of classical music and enjoyed playing the recorder together. In search of a better life, the couple decided to emigrate to Canada two years after marriage and settled in Toronto. In 1960, when Almeida was 30 years old, she gave birth to their baby daughter, Joyce. She returned to work soon afterwards because she and Henry could not afford to be without her salary. Two different nannies were hired to look after Joyce (1, 2).

Four years later Almeida moved back to London with Henry at his request. Fortunately she had received a job offer to work as an electron microscopist with Professor Waterson at St Thomas' Hospital. It did not take long, however, for Henry to regret the decision to leave Canada. Almeida refused to move yet again and the two of them divorced in 1967. Henry returned to Canada, leaving June behind to single handedly bring up their daughter who was just 7 years old. She had to do this while continuing her demanding job. It was the point just when her career was really taking off. Not having much in the way of money, Almeida was luckily able to call upon her parents' help with childcare. They were now based in the suburbs of London (1).

In 1982 Almeida married again. Her second husband was Phillip Gardner, a fellow clinical virologist who helped to demonstrate the immunofluorescence technique for the rapid diagnosis of many viral infections, especially those of the respiratory tract. The two of them originally met at a meeting organised by the European Group for Rapid Virus Diagnosis. Gardner was the founder and organiser of the Group and worked at the Central Public Health Laboratory in Colindale. The couple married three years after Gardner suffered a serious heart attack. Gardner was subsequently forced to take early retirement in 1984 because of his cardiovascular ill health. Following his retirement, he and Almeida bought and moved to a house in Bexhill, a seaside town which they originally discovered on a short holiday (3).

Once living in Bexhill full-time, Almeida learned how to restore fine china and started running yoga classes after qualifying as an instructor. This she did alongside running a small antique business with Gardner for a few years. Gardner died in 1994 (3). In her later years Almeida enjoyed taking care of her two granddaughters during school holidays for her daughter, who qualified as a consultant psychiatrist, and continued to occupy her inquisitive mind by learning computer skills and teaching herself the flute. She also embraced digital photography and kept up a strong involvement in local community life. Almeida kept busy until she died at home from a heart attack in 2007 (1, 2).

Education

Almeida was driven by a passion for knowledge from an early age and was a voracious reader of classics, fiction and nonfiction. After attending Alexandra Parade Primary School, Almeida went to Whitehill Senior Secondary School, where she received an excellent Scottish State education. She shone academically, and particularly enjoyed science. In 1947 she was awarded the Whitehill School's science prize. Despite Almeida's strong academic ability and her dream of going to university she was unable to do so because her family lacked the financial means and she had no means of getting a grant to support her. This meant that she had to leave school at the age of 16 to seek work (1).

After completing her Scottish Higher Leaving Certificate, in 1947, Almeida trained as a laboratory technician in the department of histopathology at the Glasgow Royal infirmary, a large teaching hospital. Paid a salary of 25 shillings a week, Almeida quickly became adept at using the microscopes to analyse tissue samples. The technique proved a perfect extension for the strong photography skills she had learnt as a teenager (2).

As well as giving her a wage, the job at Glasgow Royal Infirmary provided her with the time to study and in 1952 she obtained the technical qualification, Associate of the Institute of Medical Laboratory Technology (A.I.M.L.T) (1, 4). For many years, Almeida did not need a formal university degree for her work, but by the end of the 1960s it was clear that her future career would be hampered without one. In 1970 she completed an M.Phil thesis with London University. A year later she was awarded a DSc from The University of London based on the submission of her strong scientific publications (1, 5, 6).

Photograph taken of June Hart around 1950 in the histopathology laboratory at Glasgow Royal Infirmary

Photograph taken of June Hart around 1950 in the histopathology laboratory at Glasgow Royal Infirmary. Credit: Joyce Almeida.

Career

In 1952 Almeida was hired by John WS Blacklock, a professor of pathology at St Bartholomew's Hospital in London, to become his laboratory technician and research assistant. Like June, Blacklock had spent time at Glasgow Royal Infirmary. His expertise was in diagnostic tissue pathology, particularly tuberculosis, and he had a strong reputation as an enthusiastic teacher and for his attention to detail (7).

Following her marriage to Henry, Almeida took a career break for two years and then moved to Canada in 1956. Once in Toronto she took a job at the newly opened Ontario Cancer Institute (OCI). Affiliated to the University of Toronto, the Institute was Canada's first dedicated cancer hospital. While originally trained in histopathology, the only vacancy on offer to Almeida at the Institute was to work with the electron microscope. She took on the position of technician and research assistant with Allan F Howatson, an immunologist with expertise in electron microscopy in the Division of Biological Research (1, 5).

Little did Almeida realise on joining Howatson how much electron microscopy would shape the rest of her career. First developed by Ernst Ruska and Max Knoll, two German scientists, in 1931, the electron microscope provided a means to study the structure of a wide range of biological and inorganic specimens at a much higher magnification than previous microscopes. Seven years later, James Hillier and Albert Prebus, two scientists based at the University of Toronto, managed to adapt the German prototype to create a more compact device that was much cheaper and more effective for undertaking biological research. Able to produce an image 7,000 times the size of the object being investigated, the electron microscope worked by sending out a stream of electrons through magnetic coils. This provided a 'magnification three times more powerful than contemporary optical microscopes' (8).

With no prior experience of electron microscopy, by 1958 Almeida had successfully mastered the technique. She loved the physics behind electron microscopy (2). Almeida was fortunate to learn electron microscopy just at the moment when negative staining was introduced. This was a method developed by Sydney Brenner and R W Horne, two scientists based in the Cavendish Laboratory in Cambridge, UK, which involved the use of a solution of potassium phosphotungstate, a heavy metal, to stain a sample. The stain had the benefit that it could penetrate all the particles in a preparation and all the minute irregularities on their surfaces. This was important because the electron beam can only penetrate sites where the heavy metal is not present (9). Negative staining radically transformed the quality of the picture that could be produced, helping tiny virus particles to be visualised with sufficient clarity to enable them to be classified according to their shape. As Almeida recalled in an interview, conducted in 1993, negative staining 'allowed the electron microscope to become one of the fastest and most efficient means of identifying a virus'. The use of negative staining with the electron microscope also enabled direct studies of virus construction at the molecular level (6).

The first project Almeida undertook with Howatson used the electron microscope to study cells growing on a glass surface (10). Soon after this, they used it to investigate the relationship between viruses and cancer, an area that was just beginning to gain scientific traction. The idea that viruses could cause cancer was first put forward as early as 1911 by Peyton Rous after he discovered a virus in chickens linked to leukaemia. Yet, his finding was hotly contested for many years because scientists struggled to replicate his work and because viral-induced leukaemia appeared to be rare in other animals. Most were convinced that leukaemia was a genetic disease and not transmissible. This thinking was overturned, however, in 1951 when Ludwig Gross, a Polish-American virologist working at the Bronx Veterans Administration Medical Center, demonstrated that it was possible to induce the cancer by injecting viral material from leukemic mice into an inbred strain of newborn mice known to be free of the disease (11).

Many were initially doubtful of the validity of Gross' experiments, because many laboratories had failed to reproduce his results. This did not stop OCI researchers wanting to investigate the matter further. Soon after launching a collaboration with Gross, Howatson managed to detect virus-like particles in the cytoplasm of the mouse mammary tumour with the help of the electron microscope. Following this, Ernest McCullough, also based at the OCI, managed to grow the virus in mouse kidney cell cultures and then introduced it into a carefully controlled mouse colony of non-inbred Swiss mice. Three months later the mice were found to have developed tumours in several of their organs. Soon after this the OCI team found that another virus showed the same characteristics under the electron microscope. The virus was associated with several types of tumours in rats, mice and hamsters. It had been cultivated by Elizabeth Stewart and Bernice Eddy, two scientists at the National Institutes of Health. The OCI group established that the two viruses belonged to the polyoma virus family. Once identified, the OCI researchers deployed the light and electron microscope to determine how the virus caused infection and cancer at the cellular level (11).

Almeida played an integral part throughout the research on the polyoma viruses. Her colleagues were so impressed by her technical and analytical skills with electron microscopy that they included her name on four of the peer-reviewed papers published on the subject in 1960 (12-15). These papers, together with conference presentations, helped to establish the OCI's reputation in the emerging field of tumour virology and structural virology (11).

Being in Canada, where there was less emphasis on formal academic degrees than in the UK, Almeida was rapidly promoted to the position of junior scientist and encouraged to pursue her own independent research. In 1962 she published several papers as lead author. These contained observations about the molecular structure of several viruses, including verruca vulgaris (the virus of the common wart), rabies virus and varicella (chickenpox) virus (5). In many cases this was the first time their shape and properties had been seen. The beautiful pictures Almeida produced of these viruses with the electron microscope was dependent on good sample preparation. This took a lot of fine-tuning and many hours of fiddly work. As Kenneth McIntosh, one of her contemporaries put it, 'It took attention to detail, not just with the eyes, but preparing the materials, everything had to be exactly right' (16). She quickly realised, however, that the morphological patterns of viruses revealed by the electron microscope provided an important tool for the classification of viruses. In 1963 she wrote a paper setting out a potential virus classification framework (9).

Classification scheme with electron micrograph images

Classification scheme with electron micrograph images as laid out in JD Almeida (Oct 1963) 'A classification of virus particles based on morphology', Canadian Medical Association Journal, 89/16, 787-98, figure 8.

Classification scheme with electron micrograph images

Classification scheme with electron micrograph images as laid out in JD Almeida (Oct 1963) 'A classification of virus particles based on morphology', Canadian Medical Association Journal, 89/16, 787-98, figure 9.

In the early 1960s Almeida realised that immune electron microscopy (IEM) could help extend the range of what was possible with negative staining. She was first introduced to the idea of IEM by an American visitor to the Ontario Cancer Institute. The technique was not new. It had been used as far back as 1941 for studying the tobacco mosaic virus (17, 18). IEM relies on the ability of antibodies to bind to specific receptors, known as antigens, found on the surface of a cell. In the case of electron microscopy the antibody provides a useful means to clump together small virus particles which otherwise are scattered and difficult to distinguish from other objects under the microscope. The virus is easy to pick out because the antibodies are much smaller than them and also have a different shape (19).

Almeida's first experiments with IEM were undertaken with Allan Howatson and Bernard Cinader to study the verruca vulgaris virus and polyoma virus. It involved them mixing virus preparations with antibodies raised in goats and rabbits to get a good concentration of viral particles together. To their delight the technique made smaller viral particles much more visible than previously thought possible (20). It also enabled the visualisation of semi-purified virus preparations. This was important because until then negative staining could only be done with purified suspensions of virus. The purification process had a major drawback - it could injure or even destroy virus particles. One of the advantages with the IEM method was that it made it possible to use negative staining directly on preparations of infected material without having to go through the steps of purification. It also enabled virus particles to be visualised in situ, that is as they occurred within the cell (9, 18). The technique also proved an invaluable tool for visualising and measuring the interaction between a virus and immune reactions (21).

By 1963 Almeida's micrographs had appeared in several major scientific publications and she had been promoted to assistant lecturer and research associate at the OCI. Indeed, her career was very busy, being called upon to give numerous presentations both locally and at scientific conferences abroad (1). Her innovative methods with IEM soon attracted the attention of Tony Waterson, a virologist, who by chance happened to visit Toronto in 1964. He had a forte for electron microscopy, particularly negative staining of viruses (22). Just appointed to the chair of microbiology at St Thomas' Hospital Medical School in London, Waterson invited Almeida to become his scientific assistant on a grant from the Medical Research Council. Waterson's offer was highly fortuitous because Henry wanted to move back to the United Kingdom (1).

Almeida arrived at St Thomas's in 1964, just as Waterson and Robert Curran, a newly appointed professor of pathology, were in the midst of reconfiguring a department on the back of one run for many years by Ronald Hare, a bacteriologist who back in the 1920s had worked on antibiotics with Alexander Fleming. Hare's department was in sore need of updating. It was housed in an asbestos shed on the roof of the medical school. Anyone who left the shed had to remember to close the windows to avoid its roof being blown off if it got too windy. The one redeeming feature of the shed was that it had a good view of the Houses of Parliament, so the scientists could time their experiments by looking at Big Ben. Waterson and Curran quickly moved the department into new premises. They did this by revamping the old pathology museum in the medical school. At the same time they brought in new technology. The new premises and equipment helped to transform the emphasis of the department from bacteriology to virology and move it into the era of molecular biology (22).

The first electron microscope appeared in the department just after Almeida arrived on the scene. It was put in the basement to prevent any problems with vibration. Getting access to the electron microscope was not easy because Curran regarded it as his preserve and anyone who wanted to use it needed his permission beforehand. This, however, did not deter Almeida who frequently used it when he was not around. Being very determined and not one to stand on ceremony, Almeida saw no reason to follow Curran's rules. While a source of annoyance for Curran, there was nothing he could do about it because of her forceful personality (22, 23).

Almeida eventually got her own electron microscope, made by Simens, which meant she no longer had to worry about protocol (22). Over the course of the next three years Almeida continued to advance her IEM skills and establish her expertise in the area. Her talent soon came to the attention of David Tyrrell, the head of the Health Common Cold Research Unit in Salisbury. He had been wrestling for a number of years to visualise a virus that he and his team had isolated from throat swabs and nasal washings taken from boarding school boys (aged 12-17) suffering from the common cold. While Tyrrell and his colleagues had managed to cultivate small quantities of the virus, labelled B814, in trachea-derived organ cultures they did not have an electron microscope to see it. On hearing about Almeida's abilities from Waterson, Tyrrell decided to send her a collection of organ tissue samples in bottles to investigate. The samples were infected with a variety of well-known viruses, including influenza, as well as B814 and another virus called 229E isolated from the respiratory tracts of medical students at Chicago School of medicine who had the common cold (24).

Photograph of June Almeida in the 1960s using a Philips electron EM300 microscope

Photograph of June Almeida in the 1960s using a Philips EM300 electron microscope. Credit: Joyce Almeida.

On putting the samples under the microscope, Almeida quickly noticed that the B814 virus had an almost similar shape to that of influenza viral particles. They also bore some resemblance to some other viral particles she had seen in connection with mouse hepatitis liver inflammation and infectious bronchitis of chickens. Based on this she concluded that what they were seeing was a new family of viruses. What made them distinctive was their viral particles displayed short spikey projections on their outer surfaces. This gave them the appearance of a solar corona, which led Almeida, Tyrrell and Waterson to call the new group 'coronaviruses', derived from the Latin word 'corona' meaning 'crown' or 'halo' (24, 25).

Initially, the collaborators struggled to find a journal that would accept the new finding. This was because reviewers judged Almeida's micrographs of the B814 virus to be just poor images of influenza viral particles. Eventually Almeida and Tyrrell managed to get their work published in 1967. A year later the journal Nature reported that an informal group of virologists had recognised the name 'coronaviruses' for a new group of viruses (26).

Photograph of previously uncharacterised human respiratory viruses that grow in organ culture

Photograph of previously uncharacterised human respiratory viruses that grow in organ culture. Credit: Almeida Tyrrell. Each viral particle is surrounded by small projections on their outer surface, characteristic of a coronavirus. While B814 was the first human coronavirius to be visualised, it was not the first coronavrius to be found. For more on this history click here.

Despite having helped to identify the first human coronavirus, Almeida made little of it at the time and quickly moved on to looking at other viruses. This was because for a long time virologists regarded coronaviruses as no more than a curiosity because of their unique molecular structure. They were also not considered of much interest because most were associated with the common cold in humans, a condition usually associated with only mild symptoms and which was self-limited. It was only much later, with the outbreak of severe acute respiratory syndrome (SARS) in 2002, that their significance was fully grasped for human health (22).

Photograph taken of June Almeida in 1968

Photograph taken of June Almeida in 1968. Credit Joyce Almeida.

In 1967 Almeida and her colleagues produced the first immune electron micrograph of the rubella virus. This is a contagious pathogen which usually causes a mild infection, characterised by a red rash, but which if contracted in the first 12 months of pregnancy can cause severe birth defects like blindness in the unborn child. First grown in tissue culture in the laboratory in 1962, no one had so far managed to visualise the virus and work out its morphological characteristics. This had become a matter of urgency following the outbreak of a pandemic of rubella that swept through Western Europe and America between 1963 and 1965, leaving thousands of infants with tragic congenital deformities. The clear pictures of the rubella virus produced by Almeida and her team (27), helped pave the way to a better understanding of how it worked with the immune system.

After spending three productive years at St Thomas' Hospital, Almeida moved with Waterson to the Hammersmith Postgraduate Medical School in 1967 where she was appointed a research fellow in the department of virology. Almeida's first years at the Hammersmith were taken up with investigating the hepatitis B virus, a highly infectious pathogen linked to acute and chronic liver disease that frequently causes premature death. The scientific community was first alerted to the virus by the work of Baruch Blumberg, an American physician and geneticist based at the Fox Chase Cancer Center in Philadelphia. Between 1963 and 1964 he and his colleague, Harvey Alter, isolated an unusual protein in blood samples collected from an Australian Aborigines and people from Taiwan, Vietnam, Korea and the central Pacific (28). At first Blumberg thought that the protein, initially labelled 'Australian antigen', might be a genetic marker for leukaemia or a virus linked to the disease. This was because it appeared to be common in the blood of patients with leukaemia. In 1968 Alfred Prince, an American virologist working at a transfusion centre in New York, also discovered what appeared to be a similar antigen in the serum of patients with hepatitis B. Prince hypothesised that the antigen was probably a protein particle from the hepatitis B virus, leading him to call it the 'S-H antigen' (29) At the time it was not clear whether the antigens discovered by Blumberg and Prince were the same and whether they were actually an actual virus or a non-viral particle related to it (6). Many scientists were in fact doubtful they bore any relationship to hepatitis B (30).

By the end of the 1960s both Almeida and Waterson had become one of a number of researchers exploring Blumberg's Australian antigen under the electron microscope. Up to this point all detection of the antigen had been made using serological tests and immunoelectrophoresis. In the course of Almeida and Waterson's work, they were contacted by David Dane, a virologist based at Middlesex Hospital in London, who in 1969 had made an interesting discovery when examining the blood of a haemophiliac patient who complained of feeling 'liverish' and who had tested positive for the Australian antigen through an immunodiffusion test. On looking at the blood under the electron microscope he had observed an enormous number of small round and long antigen particles and other quite different particles which were much larger particles, measuring 42nm in diameter, which had a core surrounded by an outer coat. Dane wondered whether the larger particle was the infective virus and the other particles were its surplus coat (31).

In order to find out more Dane took a sample of the hepatitis B material over to Almeida. Working with colleagues from Northwick Park, Almeida managed to strip off the lipid (fatty) outer coat with detergent. This provided her with a good concentration of the core to start exploring under the electron microscope. It soon became clear to Almeida that the core was an infectious component of the virus, now known as a viron. She established that it had a polyhedral structure suggesting that it was the part of the virus that entered a host cell in order to insert its own nuclear material to replicate (32).

Soon after uncovering the structure of the hepatitis B core particle, Almeida was invited to join a closed meeting in the US to review the progress of research in hepatitis B and help resolve the confusion that had been sown by the discovery of the different antigens. Her clear pictures of the viral core were key to persuading the assembled experts that the hepatitis B virus had at least two separate and distinct antigens, one on its surface (HBsAg), found by both Blumberg and Prince, and the other internally (HBcAg), detected by Dane. They soon became convinced by her argument that the particle uncovered by Dane was the responsible for causing hepatitis B. Many were inspired by Almeida's micrographs to start unravelling the genetic material contained in the viral core (6).

As well as providing an important breakthrough in terms of the structural components of the hepatitis B virus, Almeida helped to clarify the immune response to the virus and the existence of apparently healthy carriers of the virus with no disease symptoms. A year after beginning work on the visualisation of the hepatitis B surface antigen under the electron microscope, Almeida was approached by Arie Zuckerman, professor of virology at the London School of Hygiene to examine three samples of sera from three different patients which had been saved some years before. The first came from a 20 year old nurse who had died four years after developing acute hepatitis B and the second from a 55 year old man with long-standing chronic hepatitis. The final one was from a 60 year old man who was a symptom-free carrier who had transmitted hepatitis 20 years before to three cases, one of whom died. All three sera had been found to contain the hepatitis B surface antigen using a method known as counter immunoelectrophoresis. Yet, each person had experienced very different responses to the antigen (21, 33).

Wondering if it could be linked in some way to their immune response, Almeida subjected the three samples to immune electron microscopy with Waterson. To their surprise they found that the carrier had produced no antibody against the antigen. This was in contrast to the dead patient whose blood sample showed an excess of antibodies, and that of the chronic hepatitis patient whose antibody production appeared to have reached a plateau. Based on these results, Almeida and Waterson hypothesised that the antigen did not do any damage without an immune response being mounted to it. Their finding underlined the need to understand individual responses to the antigen as much as to understand the nature of the antigen itself (21, 33).

By 1970 Almeida had risen to become Senior Lecturer at Hammersmith. She stayed on at the Hammersmith until 1972 when she was recruited by the Wellcome Research Laboratories in Beckenham, Kent, to help in their development of diagnostic assays and vaccines for different viruses, including hepatitis B. Almeida remained at the Wellcome until 1984, when she took early retirement. Almeida did not completely disappear from the scientific scene after retirement. In the 1980s she returned to St Thomas' Hospital to work one day a week in an advisory capacity. Together with colleagues she published some of the first high-quality images of the human immunodeficiency virus, the virus that causes AIDS (34).

Achievements

By 1984 Almeida had authored 103 articles and her micrographs had been published in many high-quality journals as well as many textbooks. This was a testament to her strong drive and focus. As her daughter points out, 'she was constantly on a quest' and eager to solve problems which she accomplished with a courage to follow her gut instinct and think outside the box. Described by her peers as having 'green fingers' for electron microscopy, Almeida was known for her 'attention to detail, patience and persistence', three qualities which she had 'in spades'. Almeida herself attributed her ability with electron microscopy to her desire to find and take a great photo. Part of her enjoyment of the technique was that it gave her a 'chance to see something no human had ever seen' before. She also had a great talent for composition and recognising patterns (3, 16, 22).

Almeida's first images of many previously unseen viruses made a significant contribution to understanding their structure and interaction with the immune system. Her pioneering developments with IEM also helped lay the foundation for a new classification and naming system for viruses. Launched officially in 1966, through the creation of the International Committee on Taxonomy of Viruses, the new system relied on the morphology of viruses to group them. This could not have been done without the advances Almeida brought about with IEM (35).

Overall Almeida's work helped to open up a whole new era in virology, moving it from a field of theoretical interest towards clinical applications. In addition to providing a new tool for classification and naming, Almeida's pioneering IEM techniques paved the way to the rapid detection and identification of otherwise elusive viruses directly in clinical samples.

Despite her achievements, Almeida was always very modest about them. Tellingly, when asked in 1993 how she came to make her breakthrough in hepatitis B research, she answered that she just 'happened to be in the right place at the right time'. From her point of view she had the advantage of having landed up in 'a position to benefit from the experience of those around her, to learn new [electron microscopy] techniques and to apply them in excellent laboratory surroundings'. She also claimed to have had the right contacts with the people who could provide her with the right material to enable her to visualise viruses that had eluded many others. What she failed to mention was that many of these people approached her because of her deep expertise in electron microscopy. Working in what was then becoming a fiercely competitive sub-discipline in which there were few women, Almeida 'succeeded in winning cooperation from a wider range of co-workers than most in the field'. Her ability to gain such trust from so many different people was aided by the fact that she appeared to be less threatening because she had started her career as a laboratory technician. It would be a mistake, however, to see her as a 'shy retiring flower'. Indeed she was a 'forceful personality who expected due respect' (6).

Throughout her career Almeida was known for her enthusiasm, fun and friendliness as well as her energy. She had a strong ability to connect equally well with different colleagues regardless of their status, whether they be technicians, scientists or medical practitioners. In part this was informed by her own humble origins, which made her very conscious of the degree to which a lack of money restricted choices. As her daughter recalled, 'she valued individuals in their own right, not for their standing in life' and she counted professors and secretaries equally as her friends (2, 22).

In addition to her outstanding research, Almeida taught the fundamental and clinical aspects of virology and IEM to many different students and colleagues. One of those she helped train was Albert Kapikian, an Armenian-American virologist, who spent six months sabbatical in her laboratory in 1970. Two years later he succeeded in using the IEM technique she had taught him to identify a viral pathogen responsible for a sudden outbreak of vomiting, diarrhoea and acute stomach pain among students in a school in Nowalk, Ohio that had taken place in 1968. Called the Norwalk virus, this was the first norovirus to be identified. Noroviruses are now known to be the leading cause of acute gastroenteritis in all age groups. They account for half of all food-borne illnesses (36).

Almeida was equally at home communicating her ideas to one or two people sitting beside her as she was talking to an audience of several hundred. She passed on her skills to many laboratory workers, who, with the help of her training, were able to quickly identify viruses in clinical specimens (34). The lantern slides and models she left behind, now deposited in the Science Museum in London, show a high degree of creativity and ability to communicate complex ideas simply (37).

Photograph of the virus models Almeida built out of polystyrene for teaching purposes

Photograph of the virus models Almeida built out of polystyrene for teaching purposes. From left to right: model of herpes virus (1970-75); model of wart viruses; model of unknown virus. Credit: Science Museum.

Publication date: 15 May 2020

Author

Dr Lara Marks, Visiting Research Fellow, Department of Medicine, University of Cambridge and Managing editor of WhatisBiotechnology.org.

Acknowledgements

This article benefited enormously from the generosity of June Almeida's daughter, Joyce, who shared with me her mother's CV and many of her papers. What also proved invaluable was Joyce's written personal recollection of her mother and the rich collection of photos she provided. I also appreciate the careful editing Joyce provided for the piece. Thanks also go to Professors Hugh Pennington, David Rowlands and Fred Murphy for sharing their memories of June Almeida and checking the science in the article. I am also grateful to Katie Dabin for providing a number of critical materials from the Science Museum where June Almeida's archival collection is stored.

Publication date: 15 May 2020

References

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(3) Anon (5 Oct 1994) 'PS Gardiner Obituary', British Medical Journal, 309, 950-51.

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(11) McCullough, Ernest A (2003), Ontario Cancer Institute: Successes and Reverse at Sherbourne Street.

(12) Howatson, AF, McCulloch, EA, Almeida, J D, Siminovitch, L, Axelrad, AA, Ham AW (1960), 'Studies In Vitro, In Vivo, and by Electron Microscope of a Virus Recovered From a C3H Mouse Mammary Tumor: Relationship to Polyoma Virus', Journal of the National Cancer Institute, 24, 1131-51.

(13) Howatson, AF, Almeida JD (July 1960), 'An electron microscope study of polyoma virus in hamster kidney', Journal Biophysics Biochemical Cytology, 7/4, 753-60.

(14) Howatson, AF, Almeida, JD (Dec 1960), 'Observations on the fine structure of polyoma virus', Journal of Biophysical and Biochemical Cytology, 8/3, 828-34.

(15) Howatson, AF, Almeida, JD (1960), 'Studies of polyoma virus in hamster kidney', Proceedings of European Regional Conference on Electron Microscopy, Vol II, 986.

(16) Gellene, D (8 May 2020) 'Overlooked No More: June Almeida, scientist who identified the first coronavirus', The New York Times.

(17) Anderson, TF, Stanley, WM (1941), 'A study by means of the electron microscope of the reaction between tobacco mosaic virus and its antiserum', Journal Biology Chemistry, 139, 339-44.

(18) Almeida, JD, Waterson AP (1969), 'The morphology of virus-antibody interaction', Advances in Virus Research, 15, 307-38.

(19) Chenesky, MA (7 April 1982), Clinical Immunology Newsletter, 3/7 .

(20) Almeida, J, Cinader, B, Howatson, A (1993), 'The structure of antigen-antibody complexes: A study by electron microscopy', Journal of Experimental medicine, 118, 327-40.

(21) Almeida, JD, Waterson AP (Nov 1969), 'Immune complexes in hepatitis', The Lancet, 2,983-6.

(22) Pennington, Hugh (7 April 2020), interviewed by Lara Marks.

(23) Pennington, Hugh (2005) 'E.coli, smallpox and other things', in P Henderson Scott, ed., Spirits of the Age).

(24) Tyrrell, DA, Fielder, M (2002) Cold Wars: The Fight against the Common Cold.

(25) Almeida, JD, Tyrrell, DAJ (1967), 'The morphology of three previously uncharacterised human respiratory viruses that grow in organ culture', Journal General Virology, 1, 175-78.

(26) Anon (16 Nov 1968), Nature, 220, 650.

(27) Best JM, Banatvala, JE, Almeida, JD, Waterson, AP (July 1967), 'Morphological characteristics of rubella virus', The Lancet, 237-39.

(28) Blumberg, B (2002) The Hunt for a Killer Virus..

(29) Offitt, P (2007) Vaccinated: One Man's Quest to Defeat the World's Deadliest Disease.

(30) Dane DS (10 Nov 1980) Current Contents Life Sciences, No. 45, Letter, Oct 17, 1980. This Week's Citation Classic.

(31) Dane DS, Cameron CH, Briggs M (1970) 'Virus-like particles in serum of patients with Australiaantigen-associated hepatitis', Lancet 1, 695-8.

(32) Almeida, JD, Rubenstein, D, Stott, EJ (4 Dec 1971), 'New antigen-antibody system in Australia-antigen-positive hepatitis', The Lancet, 1225-27.

(33) Almeida, J (1980) 'This week's citation classic: Almeida, JD, Waterson AP (1969), 'Immune complexes in hepatitis', The Lancet, 2,983-6.

(34) Almeida, Joyce (28 June 2008), 'June Almeida (née Hart)', British Medical Journal, 336/7659, 1511.

(35) Rowlands, David (25 April 2020), interviewed by Lara Marks.

(36) Green, KY (2014)'In Appreciation of Albert Z. Kapikian', Clinical Microbiology and Infection.

(37)Dabin, Katie (1 May 2020), discussion with Lara Marks.

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