Published as: The Royal Society and the Microscope, Notes and Records of the Royal Society, 55 (1): 29-49, January 2001.
Delivered as: The Microscope and the Royal Society, Inter Micro 2010, McCrone Research Institute, Chicago, 1415-1335h, 14 July 2010.


THE ROYAL SOCETY AND THE MICROSCOPE

by

BRIAN J. FORD

The modern world is powered by microscopes. A computer contains components of sub-bacterial dimensions. The genetic revolution is a subset of biological microscopy. Little wonder that the microscope is the instrument that uniquely symbolises science.


This instrument helped launch the Royal as a serious scientific society in its earliest years, and re-emerged as a continuing preoccupation during the century just ended. Yet many scientific histories unfold their story with little emphasis on the microscope, or see the Royal Society in terms of personalities rather than their works. Those that deal with instrumentation tend to feature telescopes, rather than microscopes. It is true that an interest in telescopes was burgeoning in the early years of the Royal Society, but research using telescopes is no match for the revelations that microscopy can offer.
Microscopes revealed forms of life that were entirely new to science; new universes and societal structures of which nobody could have dreamt. Telescopes maintain our remoteness from the universe, whereas microscopes allow the observer to penetrate the recesses of life, peer at atoms and molecules, watch the processes of living organisms, and discern the hidden nature of humankind. Telescopes hold you up to a window – microscopes open doors and invite one to explore within.


The earliest surviving sketch of a microscope dates from 1590, and microscopes were in production as ‘executive toys’ in the mid-seventeenth, but there was no exponent of microscopy until the Royal Society appointed Robert Hooke (1635-1703) to serve the Fellowship. Hooke was born on 18 July 1635 in Freshwater, Isle of Wight, and at the age of 25 became Robert Boyle’s technician. Boyle was engaged in scientific pursuits that kept him tactfully detached from the political turmoil then raging; in 1658, for example, Hooke was constructing an air-pump for experiments under Boyle’s direction. By the time that the Royal was granted its Official Charter on 13 August 1662, Hooke’s air-pump was already the subject of popular demonstration to the Fellows, and in November 1662 he was appointed to the official post of Curator of Experiments to the Royal Society.

On 25 March 1663 Hooke was ordered to prepare microscopical demonstrations for the fellowship, and on 8 April 1663 he showed a specimen of wall moss. Next week he demonstrated sections of cork, its cellular structure being clearly visible, and a week later, on 22 April, he presented blue mold on leather and ‘leeches’ in vinegar. Over the following weeks the demonstrations continued to present new visions to the Fellows:

29 April – Mine of Diamonds in a Flint.
06 May – Female and male Gnats.
20 May – Head of an Ant; Fly like a Gnat; Point of a Needle.
27 May – Pores in Petrified Wood; Male Gnat.
10 June – Sage-leaves appearing not to hjave cavities.
17 June – Pores in Petrified Wood.

On 6 July 1663 Hooke was commanded to present his observations in a book for King Charles II, and by November 1664 Hooke’s great book Micrographia was printed. This folio volume is the first work of popular science. Hooke did not merely set out his findings in a terse and academic style that might disenfranchise the outsider, but told the tale in a flowing and easy manner. His aim was to embrace a broad readership, and he was pre-eminently successful in this respect. A second edition appeared two years later, and the book is still available in paperback.

Hooke used a compound microscope, with objective and eyepiece lenses, and was concerned with making familiar objects appear larger – lice, fleas, the sting on a nettle, hairs, seeds and textiles. It was only when Hooke’s book was inspected by the Dutchman, Thonis Leeuwenhoek (1632-1723), that a true revolution in microscopy began. Leeuwenhoek, a drapery trader, paid a visit to London in 1666. Vivid figures of cloth appear in Micrographia, which was a major talking-point at the time and in the unnumbered pages of the Preface is a description of hand-held microscopes made with small metal plates containing a single hand-ground lens. Leeuwenhoek (known in his adult life as Antony and who adopted ‘van’ to precede his surname as a mark of social status in 1686) began to experiment by making microscopes of the kind Hooke described, and in 1673 he wrote a letter that was transmitted to the Society by Constantijn Huygens the elder. In the following year he sent a set of specimens, including fine hand-cut sections, and described his excitement at discovering living protozoa and algae in lake-water.
There can be no doubt that van Leeuwenhoek was inspired by Hooke’s book not only because of his use of Hooke’s design of simple (i.e. single-lens) microscope, but because of the nature of the specimens he sent to London: cork, elder-pith and the white material from a quill. These are the same specimens as Hooke himself described and, what is more, listed in the same order. This could not be by chance. Van Leeuwenhoek’s experiments (on fumigation, and the reconstruction of ‘heavenly paper’ using dried algal films) laid the groundwork for later investigators. He was the founder of microbiology and experimental microscopy.
The Royal Society elected van Leeuwenhoek to the Fellowship in 1680. Although the Society was not his patron, the pride that van Leeuwenhoek experienced is clearly evident (he asked whether his Fellowship would give him precedence over others in the seating at church in Delft) and, although he was never to visit to Society or to sign the roll, the existence of this contact with his peers proved to be of great encouragement in his future work.


Hooke and van Leeuwenhoek were not the only investigators with the early microscopes. Henry Power (1623-1668) was a pioneer of corpusculism, the idea that a corpuscular nature of life could be perceived through the microscope. Power was far less of a microscopist than Hooke, but wrote intriguingly of the ‘solary atoms of light’ and the ‘constant and tumultuary motion of the Atoms of all fluid Bodies’ whose ‘infinite, insensible Corpuscles . . . daily produce those prodigious (though common) effects amongst us’. Although such views have been widely disregarded, the later observations of Brownian movement and the growing understanding of the cellular nature of life and the atomic nature of matter should surely dignify such views with a certain prescience.
Interest in microscopical research waned after Hooke moved on to other topics and van Leeuwenhoek died in 1723. The philosophers’ interest in microorganisms diminished; there was no continuing school of microscopy. Grew, Catelan, Divini, Kircher, Malpighi, Swammerdam, Borel, Chérubin d’Orleans, King, Power, Willis, even Stelluti, whose pioneering images of bees remain remarkable for their innovative quality, had – with Hooke and van Leeuwenhoek – carried forward a tide of research and observation. By early in the eighteenth century they were dead, and the stream of microscopical work dwindled to a trickle. Leeuwenhoek’s daughter Maria sent to London a metal box containing a set of his instruments, but the Society was tardy in acknowledging the gift and the microscopes themselves were lost.


During the 1740’s, Abraham Trembley (1710-84) turned to Hydra as an object for study. Hydra had been studied by Leeuwenhoek and was drawn by his limner in December 1702. At the age of thirty Trembley was appointed tutor to the two young children of Count Bentinck of The Hague in the Netherlands, and he used the microscope in his classes. Trembley showed how Hydra could regenerate itself from small fragments of tissue, how tissues could be stained, how an animal without eyes could respond to light, and even described the cytoplasm of which each cell is made. His intriguing experiments were published in 1744 under the title of Mémoires d’un genre des polypes d’eau douce in Geneva, and were recently republished in an English translation. Trembley was elected to the Royal Society in 1743, and in the same year he was awarded the Copley Medal


One of the amateurs who studied Hydra was Henry Baker (1698-1774) of London. Baker was Daniel Defoe’s son-in-law and was preoccupied with the issues of inheritable succession that still concern us now. We are now familiar with a version of his words as a humourous poem that runs as follows:

Great fleas have little fleas
Upon their backs to bite ’em,
The little fleas have lesser fleas
And so ad infinitum.

Baker’s original was A Poem to Restrain the Pride of Man, published in 1727. This poem embodied Baker’s views on the implications of inheritance:

Each seed includes a plant: that Plant, again,
Has other Seeds, which other Plants contain:
Those other Plants have Seeds; and Those,
More Plants, again, successively inclose.
Thus, ev’ry single Berry that we find,
Has, really, in itself whole Forests of its Kind.

This weighty poem deserved the satire of Jonathan Swift, a prolific critic of the science of his day. Swift’s satire of 1733 was pointed:

So naturalists observe, a flea
Hath smaller fleas that on him prey;
And these have smaller fleas to bite ’em
and so proceed ad infinitum.
Thus, every poet, in his kind,
Is bit by him that comes behind.

Few people know this original version from the writings of Jonathan Swift - nor is it widely recognised that it reflects the weighty preoccupations of his time. Henry Baker ended his poem with what he called an ‘amazing thought’, concluding that Adam’s loins must have contained:

. . . his large posterity,
All people that have been, and all that e’er shall be.

Baker’s poetry bequeathed to us one of the little jokes in science that we like to pass on down the generations.

Baker’s difficulties in observing Hydra took him to John Cuff, a London instrument-maker, with a request that he design a microscope free from the ‘jerks, which caused a difficulty in fixing it exactly in focus’. The new microscope was announced in 1744 and had many of the features of a modern instrument - a milled wheel for focusing, a solid stage mounted on a rigid body, and a mirror to direct light up through an aperture in the stage. One enthusiast was John Ellis (1710-1776), an Irish-born British government official based in Florida and Dominica, an enthusiastic amateur microscopist. He claimed to have seen tiny progeny within microbial cells. To Ellis, each generation enveloped those generations yet to come, just as Baker had proposed. John Needham (1713-81) propounded a theory of spontaneous generation in 1749, and claimed to prove it by keeping mutton soup in flasks and observing how microbes appeared in the brew. Long before the French chemist Louis Pasteur disproved spontaneous generation, the Italian cleric Lazarro Spallanzani used controlled experiments to prove that heat-sterilized broth remains sterile if kept free from contamination.


As the nineteenth century dawned, great scientific expeditions were under way, and one of the adventurous young scientists of the day gave us the next crucial coinage in the study of microscopical life - the cell nucleus. The recognition that cells contain a nucleus was made by Robert Brown (1773-1858), a Scottish doctor who travelled to Australia in search of new species with the 27-year-old Matthew Flinders. In his first three weeks in Australia, Brown described 500 plants - almost all of them new to science. His microscopical studied revealed that pollen grains could be utilised to classify flowering plants, a technique widely used today. He observed ‘Brownian Movement’ though this was not fully understood until Albert Einstein took the matter in hand and solved the problem mathematically in 1905.


To this day, there are people who doubt what Brown could have seen with his microscopes and Scientific American published a leading article concluding that Brown’s techniques were not up to the task. One of Brown’s microscopes is preserved at the Linnean Society of London, where it is my honour to act as Surveyor of Scientific Instruments, and another – drawn to my attention by Gren Lucas of the Kew Gardens Herbarium – is preserved at the Royal Botanic Gardens. I recreated Brown’s observations using these instruments and the view they provide is clear and unambiguous. Uniquely in the history of scientific instrumentation, where the passage of time ordinarily reveals unimaginable improvements in scale and efficiency, these pioneering microscopes could allow one to visualize structures as fine as 0.7µm – within a factor of four of the theoretical limits of an optical microscope.


Using these fine microscopes Brown proved that Brownian Movement was a physical phenomenon, not (as was at first thought) due to the energies of life. He coined the term cell nucleus whilst working on orchid tissue. His observations were privately printed in 1832:

‘In each cell a single circular areola, generally more opaque than the membrane of the cell, is observable . . . only one areola belongs to each cell. This areola, or nucleus of the cell as perhaps it might be termed, is not confined to the epidermis . . .’

Brown also observed the naked ovule of the gymnosperms, a most exacting piece of microscopy, and his work was extended by Carl Wilhelm von Nägeli (1817-1891) who made detailed study of the nucleus and identified the formation of chromosomes, which he termed ‘transitory cytoblasts’. Although von Nägeli was an admirable observer, he maintained a belief in spontaneous generation and was opposed to developing ideas on progressive evolution. Thus, when von Nägeli was sent a paper by Gregor Mendel, in which the laws of inheritance were first spelled out, he had no hesitation in rejecting it.

One of the greatest of the Royal Society’s Victorian microscopical observers was Franz Bauer (1758-1840) who, like his equally distinguished brother Ferdinand (1760-1826), became celebrated as a biological artist. Franz became entrained by one of the less scrupulous of the Royal Society’s Fellows, the surgeon Sir Everard Home, who was eager to obtain high-resolution microscopic images of human tissues. Home was given leave to take the van Leeuwenhoek microscopes home for use in his investigations, where they were intended to assist Bauer obtain the best images, but they were never returned. Home held documents from the estate of the anatomist John Hunter (1728-1793), among whose pupils was Sir Edward Jenner. Home had been publishing Hunter’s work as his own and – when pressed to return the documents to the Royal College of Surgeons – set them alight. His rooms at the Chelsea Hospital were destroyed in the process. Derek de Solla Price of Yale told me he felt that this resulted in the destruction the van Leeuwenhoek microscopes, which were made from silver.

Charles Darwin was recommending simple microscopes as late as 1848, but their demise was heralded by the development of achromatic compound lenses. The principle was developed by Joseph Jackson Lister (1786-1869) whose son Joseph (1827-1929) developed his own interests in microbiology to pioneer antisepsis. With achromatic microscopes readily available, research was soon directed to methods of making tissues more readily visible and Lionel Beale (1826-1906) pioneered differential staining. In 1852 he opened a laboratory at King’s College, London for ‘the use of the microscope’ and five years later was admitted a Fellow of the Royal Society.

As the work of Beale led to the routine examination of tissue sections, Henry Sorby (1826-1908) developed a similar technique for geological material. In 1831 William Nichol of Edinburgh ground thin sections of fossilized wood, and Sorby developed the technique for routine research. His paper ‘On the Microscopical Structure of Crystals Indicating the Origins of Minerals and Rocks’ was published by the Geological Society in 1858, and served to found the science of petrology.

By the second half of the nineteenth century, great brass microscopes were a popular possession of well-educated British families. Many were replete with adjustments and features that no-one but an enthusiast could use. We may discern parallels between the status-conscious Victorian businessman’s microscope and the desktop computers of today, many of which are similarly endowed with facilities that the owner never investigates.


The society’s Victorian fellows remind us of the wide-ranging interdisciplinary interests of the early microscopists. William Carpenter (1813-1885) excelled in physiology, geology, medicine and microscopy, in addition to being a successful administrator and a devoted philanthropist. The Society published many of his papers before he wrote his great work The Microscope and its Revelations (first edition 1856). Carpenter pioneered public lectures on popular science, and traveled widely in hisd pursuit of greater public understanding. William Henry Dallinger (1842-1909), a Wesleyan clergyman, became renowned for lectures delivered with a sense of theatre and illustrated with hand-coloured lantern slides. He was President of the Royal Microscopical Society in 1884-7 and, although resident at the Wesley College in Sheffield throughout this time (over 160 miles from London), he regularly attended meetings. He was elected FRS in 1880, and his re-writing of Carpenter’s great book The Microscope served to introduce new generations of students to the marvels of microscopy.
Although the names of Brown, von Nägeli, Schleiden and Schwann remain rightly revered, some pioneering Fellows in the study of the cell are less well known. New insights into chromosome behaviour were first recorded by Reginald Ruggles Gates (1882-1962), a former schoolmaster from Canada, who came to London and was appointed Head of the Department of Botany in King’s College, London, in 1921. As early as 1906 he was lecturing on differing chromosome numbers within Oenothera, and first described the phenomenon of non-disjunction (in which unequal numbers of chromosomes migrate to the poles of a mitotic cell) in 1908. His book The mutation factor in evolution was published as early as 1915. In his later years he broadened his interests to incorporate human genetics and anthropology, publishing a 1500-page edition of Human Genetics in 1949.


Throughout twentieth century biological microscopy, a major thrust was towards the threat posed by pathogenic microorganisms. The introduction of Pasteurisation and the use of vaccination, following the writings of Jenner, had fuelled a desire to find antimicrobial agents. A great collector of microscopes, Henry (later Sir Henry) Wellcome established the Wellcome Research Laboratories in Physiology at Herne Hill in 1894. It seemed at first to have been a fruitless move, since little progress was made in physiology for a decade. Then Wellcome appointed Henry Dale as a research scientist. Dale, a lifelong admirer of Paul Ehrlich, spent ten years at the Wellcome and knew many of the most influential minds in the biology of his time – including Kenneth Mellanby and Clifford Dobell. Dale became the Director of the Laboratories and subsequently headed one of the Departments of the new National Institute for Medical Research at Hampstead, working on Salvarsan and subsequently on the flavine dyes as antiseptics. Flavine was hailed by the press as a wonder-cure but, although there were some applications, the promise was not fulfilled. Dale moved on to study anaphylaxis, the topic of his Croonian lecture to the Society in 1919.
However, he had spent much time cooperating with Clifford Dobell on amoebic dysentery. Dobell, who worked at Mill Hill and became well known as the biographer of van Leeuwenhoek, was a brilliant microbiologist who had an unsurpassed flair for culturing parasitic protozoa in vitro. His use of the microscope was diligent and precise, and he documented many non-mitotic figures in these organisms. For many decades they were dismissed as artifacts, and only in recent years have Dobell’s observations been confirmed.


Dobell’s father-in-law (strictly speaking, his wife’s stepfather) was William Bulloch. Although Bulloch, like Dobell, was a distinguished microbiologist, he too is best remembered for a great work in the field of the history of science. Bulloch’s History of Bacteriology stands with Dobell’s biography of Leeuwenhoek as crucial contributions to the study of science.


Success in the quest for antimicrobial agents was claimed by Alexander Fleming, whom Bulloch and Dobell knew well. Fleming’s accidentally contaminated agar plate has become well-known, though we should remember that his identification of the mould responsible was at first incorrect (Fleming believed it was Penicillium rubrum, but in fact it proved to be P. notatum, first discovered by Westling in 1911 on a pile of decaying hyssop in Scandinavia). The term ‘penicillin’ was originally applied by Fleming, not to the active component, but to the crude supernatant of the broth cultures. It fell to Howard Florey, Ernst Chain and Gordon Raistrick to purify the antibiotic and unravel the biochemistry and practical applications of penicillin. Florey’s first paper had been ‘Microscopical observations on the cerebral circulation’ in the Journal of Physiology of 1925. His continuing enthusiasms for microscopy led him to the introduction of antibiotic therapy, and to a revolution in the management of bacterial disease.


An enthusiasm for microscopy led Edgar Douglas Adrian (1889-1977) to innovate in broader and more fundamental fields. Douglas, later Baron Adrian of Cambridge and President of the Royal Society, had been influenced by Keith Lucas, his director of studies at Trinity, who propounded the ‘all-or-nothing’ law for the response of skeletal muscle. Through diligent microscopy and micromanipulation, Adrian studied the response of muscle fibres to stimulation, measuring the potential they generated. He went on to work on neurons and to develop the electroencephalograph, and was jointly (with Charles Sherrington) awarded the 1932 Nobel prize.


Meanwhile, new areas of optical microscopy were opened up by C. R. Burch (1910-1983) who developed a reflecting microscope equipped with aspheric mirrors of speculum metal that were aluminized to give a reflectance >75 per cent. Burch was an irascible character who had a purpose-built workshop in the bowels of the University of Bristol where he ground mirrors to fine tolerances. Although the machinery was mounted on rubber bushes, Burch found that passing traffic perturbed the process. He took amphetamines in order stay awake, and worked at night when the traffic was stilled. Carcases of his microscopes remained in the attic of his department when he retired, monuments to a unique endeavour.


Optical microscopists have continued to play a prominent role in the Royal Society. Sir Andrew Huxley records that one of the opportunities offered by his academic career was the furtherance of his lifelong interest in optical microscopy. His most conspicuous achievements relate to the structure and function of striated (voluntary) muscle, which called upon the utmost resolution of the microscope, and the development of pioneering interference microscopes. This concept, utilising parallel and perpendicular polarized beams produced by a Woollaston prism, is a refinement of the polarizing microscope. In 1952 Huxley published ‘Applications of an interference microscope’ in the Physiological Journal. A sequence of notable papers, in journals including Nature and the Physiological Journal, laid the groundwork for our understanding of muscle function. In many of them, Huxley was guided by publications of the previous century, where pioneering optical microscopists – like Dobell in his time – made accurate observations that were ignored by contemporaries. Huxley returned to the nature of discovery in a major paper for the Royal Society, based on his inaugural Florey lecture in Australia of 1982. He concluded with words that are singularly apposite in an era when books are being ‘de-accessioned’ from libraries, and old runs of journals discarded: ‘Ought some proportion of our scientific effort to be devoted to searching old books and journals . . ?’.


Huxley’s papers on the structure of the sarcoplasmic reticulum (from a 1959 paper in the Annals of the New York Academy of Sciences through to Journal of Muscle Research and Cell Motility for 1984) extended those earlier observations through the application of an instrument that was still relatively novel in the 1950’s: the electron microscope. The first British electron microscope was constructed for G P Thompson at Imperial College in 1933, and the young C R Burch was fascinated by the promise of this instrument. When Zernike constructed his ground-breaking phase contrast microscope one of the first people he visited in order to give a demonstration was Burch. The microscope was taken to St Bartholemews Hospital where some remarkable pictures of mitosis were taken. From there Zernike’s microscope went to an optical manufacturing company who did nothing with it for years. Burch meanwhile harnessed the principle of phase contrast to measure the surface curvature of his mirrors, and the Zernike test became a mainstay of the development of the reflecting microscope.
Reflecting microscopes could utilize ultra-violet as an illuminant, with a concomitant increase in resolution. Electron microscopes, however, could provide a resolving power thousands of times greater. G P Thompson had demonstrated the feasibility of an electron microscope in 1927. Until this time, electrons were conceived as exceedingly small particles, but Schrodinger proposed an alternative electron wave concept. This idea was soon accepted by G P Thompson, who realised that its validity could be demonstrated by a simple transmission diffraction experiment. The initial observations were apparently made on cellulose films and were not convincing, so Thompson moved on to study gold films soon after. The idea that the short wavelength of electrons opened up the prospect of electron microscopy did not occur to him until around 1933, by which time Knoll and Ruska had constructed a prototype in Berlin and taken micrographs with a resolution better than optical microscopy could provide.


Commercial production began prior to the Second World War, though regular production was not possible until 1946. Within the following 20 years, 3 000 electron microscopes had been installed in laboratories around the world. Dennis Gabor is perhaps the only one of the pioneers of electron optics pioneers who was to fully embrace the wavelike properties of the electron. With Busch, Gabor was responsible for the introduction of the solenoidal magnetic lens, which was of crucial importance in the development of electron microscopy. In 1948, Gabor published the new concept of holography. This has had widespread ramifications through the development of lasers. Along with Brownian movement, Gabor’s holography is an example of the way in which work by microscopists has had a widespread effect on mainstream physics.


A scanning electron microscope had been envisaged by Manfred von Ardenne (1907-1997) and one was constructed by Vladimir K Zworykin (1889-1982) at the RCA Laboratories in 1942, but no further practical developments took place until the concept was revived at the Department of Engineering at Cambridge University by Charles Oatley in 1948. Over the following 15 years a series of five instruments was constructed by his research students until commercial production could begin at the Cambridge Instrument Company. Among Oatley's many students were Dennis McMullan, Oliver Wells, Haroon Ahmed and Ken Smith. However, relatively few of the pioneering microscopical engineers were elected to Fellowship of the Royal Society in comparison with the more scientific students who studied under Peter Hirsch.


The introduction of British scientists to scanning electron microscopes is recalled by Professor Miriam Rothschild. Like most microscopists, she had been introduced to the optical microscope in her teens. She used it in her pioneering observations on the motility of Pulex, the flea. Howard Hinton, one of Britain’s most illustrious entomologists, later introduced her to the scanning electron microscope. Cambridge Instruments had just begun production of their pioneering instrument when Miriam Rothschild presented some of her SEM studies of avian microanatomy at an Oxford conference in 1965 with 6000 delegates. Interest in the vivid images was considerable. Within three years Cambridge Instruments were producing 100 Stereoscan microscopes per annum; even larger amounts of SEMs were being produced by Japanese companies.


The youthful interests of Irene Manton were more focused: since reading E B Wilson in 1902 she resolved to study cytology. Her school career at St Paul’s Girls had been undistinguished (her parents had been advised to remove her because of her idleness) but she was to become influential to a generation of microscopists. Her arrival at Leeds, following publications on the spiral nature of chromosomes and their morphological changes during cell division, was greeted with something close to euphoria. In her quest for higher resolution she embraced electron microscopy in 1950, producing studies of flagella with previously unrecognized structural features – many of them, as she delighted in telling colleagues, recorded by Victorian microscopists.


One early British enthusiast for the electron microscope was V. Ellis Cosslett (1908-1990) who was influenced at Bristol University by J. W. McBain. McBain taught that there will always be a realm of knowledge we do not understand, and that our interpretation of experimental data is liable to be changed as knowledge expands. Cosslett was a left-wing radical and a member of the Communist party, an attitude strengthened by visiting Berlin in 1931. In Bristol during 1933, Cosslett was given, by R. M. Tyndall, reprints of papers by Knoll and Ruska: ‘Beitrag zur geometrischen Elektronoptik’ and ‘Das Elektronmikroskop’. Cosslett set out to build an electron microscope with considerable input from L C Martin who had a large group working on technical optics at Imperial College.
Cosslett’s time at Birkbeck College, London, brought him under the influence of P M S Blackett, later President of the Royal Society, who had himself been a research student of Lord Rutherford. Cosslett founded the Electron Microscopy section of the Cavendish Laboratory in 1946. He attracted people like Peter Hirsch and Sydney Brenner to use the facilities, and inspired several developments including high voltage electron microscopy and (under Deltrap) a bold but unsuccessful attempt to correct spherical aberration by using stacks of multipole lenses. With modern computer control, this last idea was revived and pushed to a successful conclusion at the Cavendish by Ondrej Krivanek. Krivanek, at Washington State University, Seattle, now runs his own company.


The observations of dislocations and their movement in thin metal foils by Peter Hirsch and his team were made on Cosslett’s equipment and led to notable work on diffraction contrast electron microscopy. This diffraction contrast school now includes a good many Fellows (Sir Peter Hirsch, Archie Howie, Robin Nicholson, Don Pashley, Mike Whelan, John Steeds, Mick Brown and David Cockayne). The first five named were joint authors of a classical textbook on the topic. As described in a symposium organised by the Microscopy Society of America in 1999, Howie and his students later made notable contributions to a variety of topics including the study of catalyst particles, energy loss spectroscopy and secondary electron imaging. These offer the prospect of obtaining information about electronic structure, variations in pH, etc., as well as atomic configuration.


Don Pashley, in cooperation with the Hirsch team at Cambridge, has specialised in thin crystalline films and epitaxy. He gained his PhD by applying electron diffraction to the study of epitaxial growth in 1950, and was attracted to Cambridge in January 1956 by the arrival of a Siemens Elmiskop I electron microscope at the TI Research Laboratories. Pashley developed the use of electron microscopy to study dynamic phemomena in crystalline materials with James (later Sir James) Menter. John Steeds, now Professor in the Department of Physics at the University of Bristol, studied under Howie and Hirsch at Cambridge during the 1960s. Steeds was one of the invited contributors to the above mentioned symposium with an account of his pioneering studies of extended and point defects in diamond using combined electron microscopy and optical spectroscopy. Andrew Keller, a leading polymer physicist at Bristol, had used the transmission electron microscope to discover around 1956 the remarkable folded structure of polymer crystals.


The transmission electron microscope has been utilized for the study of dynamic phenomena in a host of alloys and other materials by Ray Smallman of the Faculty of Engineering at the University of Birmingham. His series of eight textbooks (the latest of which, Modern Physical Metallurgy and Materials Engineering, appeared in 1999) span 37 years of this fundamental area of research.


Professor Sir Alec Broers, who became Vice-Chancellor of the University of Cambridge in 1996, has extended on the application of electron, X-ray and ultra-violet microscopes, and (as a pioneer of nanotechnology) has since applied these techniques to the fabrication of microelectronic components. After many years with IBM He established the nanofabrication laboratory in Cambridge, in which the technology of miniaturisation has been extended to the atomic scale. Broers obtained his BSc in Physics and Electronics at Melbourne University followed by BA (Mechanical Sciences), PhD and ScD degrees in Electrical Engineering at Cambridge. He was elected Professor of Electrical Engineering (1984) and Fellow of Trinity College (1985) and subsequently Master of Churchill College and Head of the University Engineering Department.


Microscopy remains a preoccupation of today’s senior Fellows. The Treasurer, Sir Eric Ash CBE, has developed evanescent imaging with microwaves and the outgoing President, Sir Aaron Klug, has been involved in research into image analysis since the 1960s. He has pioneered a number of novel developments in diffraction and microscopical imaging, leading to the elucidation of many significant biological structures, particularly of viruses. Sir William Bragg and his son Sir Lawrence founded x-ray crystallography, which Sir Lawrence’s student Max Peruz in turn had used to reveal the structure of the haemoglobin molecule. All were Nobel prize winners. Sir Aaron had met Rosalind Franklin when he joined J D Bernal’s laboratory in 1954, and she introduced him to the intricacies of viruse structure. His historic work on the helical structure of tobacco mosaic virus was followed by three-dimensional image reconstruction of specimens including spherical viruses (such as human wart virus), bacteriophages and chromatin. One conspicuous result of Klug’s approach to three-dimensional image analysis was the principle of x-ray computerized axial tomography (CAT). The scanner utilizing the principle was developed by Godfrey Newbold Hounsfield, later Sir Godfrey, who shared the 1979 Nobel Prize for Physiology or Medicine with Allan Cormack for his part in developing the CAT scanner as diagnostic instrument. As Director of the Cambridge Laboratory for molecular Biology (the unit founded by Max Perutz) Sir Aaron went on to play a prominent rôle in developing the confocal scanning microscope.


Any idea that microscopy is an anachronistic discipline can be dismissed by a consideration of its prominence in the new Fellows. Apart from those referred to above, among the intake for last year were D T Delpy (infra-red imaging in medical physiology), J B Pethica (scanning transmission microscopy), Sir Peter Williams, whose PhD thesis was on scanning electron microscopy, G B Warren, who has advanced the electron microscopy of membrane organization and A J Trewavas (biological imaging).


It also included A M Donald, who is developing the application of the environmental scanning electron microscope at the Cavendish in Cambridge. To the pioneers of electron microscopy, the environmental SEM is a heresy. A hard vacuum was always seen as a prerequisite for electron beams, yet the environmental microscope is able to image time-dependent phenomena in an atmosphere. Emulsions can be observed as dynamic systems. The ESEM has become part of a major polymer programme launched by Sir Sam Edwards at Cambridge. Athene Donald has opened up fresh avenues for the application of this remarkable instrument with observations on the changes in the structure of bread during baking, the hardening of cement and the drying of paint.


In many ways this takes us back to the beginnings of microscopy: Hooke and van Leeuwenhoek were fascinated by dynamic phenomena – how gunpowder explodes, for instance – and the environmental SEM can provide graphic images which recall the eye-catching realism of Hooke’s engravings for Micrographia. Throughout its history, the Royal Society has promoted microscopy. Partly this has been through funding, as in the case of the Society’s administration of the Paul Instrument Fund. It has been through publication in journals like Philosophical Transactions, or the organisation of meetings. We commemorate the name of one of the greatest pioneers through the annual Leeuwenhoek Lecture, but the Society also hosts conferences like Mick Brown’s recent meeting on ‘Ultrafine Particles in the Atmosphere’ where microscopists and medical specialists pooled their knowledge on the nature of particulate air pollution and its repercussions.
In an era of molecular biology, it is microscopists who relate the findings of bioscientists to the living cellular systems in which the mechanisms operate. Richard Henderson, Director of the MRC Laboratory of Molecular Biology, Cambridge, collaborated with Nigel Unwin on the development of high-power electron microscopy into a method of structural determination of two-dimensional crystalline arrays. High-voltage electron microscopy seemed, in the 1970s, to be the most propitious technique for ultrastructural analysis. A book published by the Science Research Council in 1977 was filled with optimism about the idea, and featured the AEI EM7 megavolt microscope as an example of the way ahead. So much radiation damage results from high voltages that current research favours ultra low dose diffraction techniques.


Henderson originally went to visit the laboratory on the advice of William Cochrane at Edinburgh, who suggested he contact Max Perutz and arrange a visit. Henderson now says that he called in to see Perutz and his team on a dull Saturday, and found more work going on there than in other laboratories on a weekday. He resolved to join the Cambridge team. His work on seven-helix receptors and pumps within the living cell is revealing mechanisms that govern energy transfer within the cell. He remains a pure scientist at heart. Of pure research, Henderson says: ‘Its primary rôle is not to make money nor to transfer technology’.
As microscopists know, it is the love of new knowledge, and the thrill of imaging previously unseen phenomena, that provide the spur. It drove Hooke and van Leeuwenhoek three and a half centuries ago, and remains the intellectual challenge for the microscopists of tomorrow. Our era is extending the concept of visualization still further. Alongside optical microscopy in all its forms, and transmission, scanning and environmental electron microscopes, we now have a growing armoury of investigative tools. To electron and x-ray diffraction we can add nuclear magnetic resonance, spectroscopy and a rapidly growing list of others. They capture the imagination of modern investigators, fuelling our desire to visualize the realities that regulate our world. If the Royal Society can fund these people, encourage them, and above all offer them fellowship and a medium for publication of new findings, its rôle in fostering microscopy will remain paramount.

ACKNOWLEDGEMENTS

I have benefited greatly from personal discussions with Sir Aaron Klug, Sir Andrew Huxley, Professor Howard Lenhoff, Mr Gren Ll. Lucas, Dame Miriam Rothschild, the late Dr C.R. Burch, the late Dr Ellis Cosslett, the late Lord Howard Florey, the late Mr John Bunyan, the late Mrs Monica Dobell, the late Professor Irene Manton, Lord Perry of Walton, Professor Athene Donald, Dr Debbie Stokes and Sir Sam Edwards.

Professor Archie Howie, a much-admired colleague for many years, was kind enough to advise in detail on an earlier draft of this paper.

Among those who kindly forwarded collections of reprints and other papers are Sir Alec Broers, Sir Andrew Huxley, Sir Aaron Klug, Professor John Steeds, Professor Tom Mulvey, Professor R E Smallman, Sir Peter Hirsch, Professor Don Pashley, Professor Mike Whelan and Professor David Cockayne.

I am grateful for my Royal Literary Fellowship at the Open University which has allowed me time to compile this paper, and at the Royal Society I am indebted for help over many years to past and present members of staff including the late Professor Ronald Keay, Mr Norman Robinson, Mr Leslie Townsend, Mr Peter Cooper, Mrs Diana Herman, Ms Jill Nelson, Ms Sandra Cumming, Ms Mary Samson, Ms Jilliene Sellner and Ms Catherine Broad.

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See the web site for 2001 publications, or to the scientific bibliography listing papers and chapters for the decade.