doi:10.1093/brain/awr123
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BRAIN
A JOURNAL OF NEUROLOGY
OCCASIONAL PAPER
William Ian McDonald: 1933–2006
Alastair Compston
Brain Editorial Office, ED Adrian Building, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge CB2 0PY, UK
Correspondence to: Alastair Compston,
Brain Editorial Office, ED Adrian Building, Department of Clinical Neurosciences,
University of Cambridge,
Forvie Site, Cambridge CB2 0PY, UK,
E-mail: [email protected]
The life and achievements are described of (William) Ian McDonald, BMedSc MBChB PhD FRACP FRCP FRCOpth FMedSci:
neurologist, National Hospital for Neurology and Neurosurgery (1966–98); physician, Moorfields Eye Hospital (1969–96); professor of neurology, Institute of Neurology and Institute of Ophthalmology, University of London (1974–98); Editor of Brain
(1991–97); Harveian Librarian, Royal College of Physicians of London (1996–2004); born Wellington, New Zealand, 15 April
1933; died London, 13 December 2006. At his death, Ian McDonald left 33 box files of largely unsorted material relating to his
private and professional life. The archive has not been catalogued but this biographical account of his life and work draws on
the material contained therein. Where possible the date and provenance of material are identified and cited in the text; his
curriculum vitae is provided as a supplementary file with individual papers identified by number within each category.
Professional career
As neurologist, clinician scientist and ambassador for his subject,
Ian McDonald attained the highest standards of academic medicine. In his work on multiple sclerosis, he moved research that had
been exploratory towards a more coherent and integrated discipline grounded in first-class clinical science. He saw multiple sclerosis as a challenge for medical science that needed understanding
at many levels. He recognized the burden this disease places on
the lives of affected individuals. His contributions were creative
and sustained over a period of nearly 50 years. These were recognized through markers of international acclaim; but it was
the manner in which McDonald strode the international stage
that endeared him to his contemporaries, and to younger and
older generations of neurologists. Early experiences shaped
McDonald’s subsequent direction. Especially important for his scientific methodology and respect for the historical perspective was
the influence of Archie McIntyre (1913–2002) in New Zealand; of
clinical neurologists, notably (Sir) Charles Symonds (1890–1978)
and Denis Brinton (1902–86), when McDonald moved to
England in 1963; of Derek Denny-Brown (1901–81) in endorsing
his appetite for scientific discovery; and of Roger Gilliatt (1922–91)
for whom McDonald was a friend and ally as Queen Square
strengthened its academic base from the 1960s. Later, he maintained close professional collaborations and social relationships
with many former students and his protégés: especially Kenneth
Smith (PhD 1979), Alan Thompson (MD 1985) and David Miller
(MD 1988). As a colleague at Queen Square and in retirement,
McDonald sought and enjoyed many reflective conversations with
Christopher Earl.
Ian McDonald grew up in Christchurch, New Zealand, and was
educated at St Andrew’s College, subsequently matriculating at
Knox College, University of New Zealand Otago, in 1952, and graduating in medicine in 1957 (Fig. 1). He worked first as research officer of the New Zealand Medical Research Council and then as
lecturer in medicine at Otago with Keith McLeod (1918–2006). In
an essay ‘On the relation of my previous education to the study of
surgery’, McDonald affirmed his commitment to the:
cardinal requirement of understanding how disease mechanisms
alter structure and function; and dependence on integrating
knowledge in basic science disciplines with skill in gaining the
patient’s confidence: a broad education at school instils a desire
to maintain wide interests and . . . leads to a sense of perspective
without which . . . medicine . . . loses much of its value (Archive:
unpublished typescript, c1956).
Received March 22, 2011. Revised April 18, 2011. Accepted April 25, 2011. Advance Access publication June 15, 2011
ß The Author (2011). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
For Permissions, please email: [email protected]
William Ian McDonald: 1933–2006
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McDonald worked for 3 years in Boston with Denny-Brown on
muscle spindles. This contact consolidated McDonald’s interest in
studying the pathophysiology and pathogenesis of demyelination
affecting the CNS. The visit also established lifelong friendships
with Denny-Brown and many who later became leaders of clinical
and experimental neurology in the USA. McDonald made copious
notes of Denny-Brown’s teaching and lectures, at various locations
but mainly in Boston, from February 1957 to April 1966. But
McIntyre wanted him back in New Zealand:
Figure 1 Ian McDonald, c1960.
In an interview with Annette Beasley, McDonald recalled
that his early interest in neurology stemmed from the teaching
of comparative anatomy in his first year at medical school
by, among others, Dick Hornabrook, lecturer in anatomy at
Knox College (Archive: unpublished typescript, 10 May 2004).
In his Swithin Meadows lecture entitled ‘Physicians, subsequence
and consequence’, McDonald acknowledged the influence of
meeting neurologists who were visiting New Zealand from
Queen Square. Specifically, he was deeply impressed by Swithin
Meadows (1902–93) who lectured on visual failure in Dunedin
(1962) on a visit with Douglas Northfield (1902–76). Matters
were clinched by a visit, also to Dunedin, from Symonds. Archie
McIntyre reinforced his ideas on the importance of disease mechanisms and encouraged McDonald to spend 3 years in full-time
physiology research before studying clinical neurology.
McDonald told ‘A neurologist’s tale’ at a meeting to celebrate
100 years of physiology in Otago (Archive: unpublished typescript,
30 April 2005). He explained McIntyre’s role in restoring activities
of the department following the departure of (Sir John) Eccles
(1903–97) to Canberra in 1952; the emphasis McIntyre placed
on meticulous attention to detail; the study of structure and function in their biological and historical contexts; and his mentorship
‘of younger people through generosity of spirit’. The lecture
focuses on the physiology of nerve conduction across the centuries
culminating in the work of (Sir Alan) Hodgkin (1914–98) and (Sir
Andrew) Huxley. McDonald explains how, in retrospect, his own
research on conduction in the peripheral nervous system provided
the basis for subsequent work on central pathways that aimed to
illuminate the mechanisms of relapse, remission and persistent deficit in multiple sclerosis.
But academic life in New Zealand had its limitations; and in
1963, McDonald moved to London where his aesthetic interests
were cultivated and his personality more easily expressed. For a
young New Zealander arriving in England in 1963, the National
Hospital was an inspiring yet intimidating place to work. Yet this
was a pivotal period in the evolution of an institution that needed
to move on from 100 years of descriptive neurology. Appointed
proleptically as consultant neurologist at Queen Square in 1966,
I’m very glad you got the fellowship even if it means you must
return to Queen Square for a while. However, there may be ways
out of this – such arrangements aren’t usually binding. Anyway,
should there be a possibility of your coming here, please let me
know . . . things often have to be jacked up well in advance, especially research posts (Archive: letter, 12 February 1965).
Transferring the discipline of classical neurology into investigative work was a major requirement for Queen Square at that time,
and McDonald was one of very few neurologists active in experimental work. His contributions were understood by the more
forward-looking of his senior colleagues and contemporaries. In
the 1960s, he characterized the physiology and morphology of
demyelination and remyelination in the CNS; in the 1970s, he pioneered laboratory methods for supplementing the clinical diagnosis of multiple sclerosis; in the 1980s he saw the possibility for
applying the techniques of MRI to the complex problems of inflammatory brain disease; and in the 1990s he used brain imaging and
spectroscopy to explore the pathogenesis of central demyelination
and the evaluation of new therapies. Each of these achievements
was substantial. Together, the work on multiple sclerosis represents
a major and lasting contribution to clinical neuroscience.
McDonald expected to succeed Roger Gilliatt on his retirement
as chairman of the University Department of Neurology in 1987;
but first David Marsden [(1938–98): 1988–95] and then Anita
Harding [(1952–95): 1995] were preferred. It was soon made
clear that while some independence was in order, McDonald
should not develop his own academic unit entirely separate from
that of Marsden, as McDonald had indicated was his preferred
position. Marsden explained that exposing trainees and visitors
solely to his own world of ‘funny jerks and jumps’ would not
provide a sufficient experience of neurology (Archive: letter,
27 January 1989). Reflecting more generally on Queen Square,
Marsden expressed concern that too few clinicians were full-time
and so able and willing to contribute to administration of the
hospital and Institute, warning McDonald that in due course he
would undoubtedly be required to act in one administrative capacity or another. In fact, McDonald had already been asked to
become Dean of the Institute of Neurology in 1986, soon after
Marsden’s election to the professorship, but declined; and in doing
so exposed the still sore wound:
I have always found administration a chore but . . . accepted the
necessity . . . in order to develop my clinical and research interests
and to provide for my research students . . . I decided in
1983 . . . that I wished in principle to be considered for the
Chair. I believed that the personal sacrifice of my research
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activity . . . would have been outweighed by the influence on neurology as a whole . . . in the event that sacrifice has not been necessary (Archive: letter, 19 May 1986).
But if his own institute was reluctant to elevate McDonald,
others were not and many offers were made before and after
the disappointment at Queen Square. The Institute of Psychiatry
invited McDonald to replace David Marsden after his move to
Queen Square but McDonald declined when it became clear
that no one in a position of influence would support his continued
involvement with the Nuclear Magnetic Resonance (NMR)
Research Unit at the Institute of Neurology which, by that time,
had become the major focus of his research (Archive: letter, 11
February 1987). McDonald had already declined offers, at least in
principle, of the chairmanship of neurology in Dallas (USA) and
the professorship of experimental medicine in Wellington, New
Zealand, both in 1972; a faculty position in the Department of
Anatomy in Iowa in 1973; head of neurology at the University of
Manitoba, chairman of neurology at Northwestern University,
Chicago, and the University of Cincinnati in 1974; chairman of
neurology at the Massachusetts General Hospital in 1977; and
neurologist-in-chief at the Montreal Neurological Institute in
1978 (Archive: various letters, 1972–78). A point often made in
replying to enquiring deans was frustration over the extent to
which his clinical responsibilities in London at that time restricted
research. Yet when McDonald applied formally for one of two
professorships supported by the National Fund for Research into
Crippling Diseases, his post to be held at the Institute of
Neurology, setting out his credentials and manifesto, Reginald
Kelly [(1917–90): dean] rejected as out of the question,
McDonald’s request that he should have access to 21 hospital
beds in which to manage his patients (Archive: letter, 17 May
1973). That application sets out his plan to develop work in
physiological, morphological, behavioural and clinical aspects of
the visual system and spinal cord because of their relevance to
the clinical problems of visual failure and paraplegia. But there is
no mention of multiple sclerosis.
In 1973, Professor EJ (Ephraim) Field (1915–2002) was removed
from his post as director of the Medical Research Council (MRC)
Demyelinating Diseases Unit in Newcastle by the secretary of the
MRC, Sir John Gray (1918–2011). On the advice of a
sub-committee, with John Walton and Gilliatt as members, Gray
offered McDonald the position:
Council have long hoped that clinical work would develop but
unfortunately this has not happened in recent years. They
would certainly encourage the plans you outlined to me to combine clinical research with laboratory studies in the general field
of demyelinating disease. Council do not confine this term to
multiple sclerosis (Archive: letter, 20 July 1973).
But again McDonald declined, not because of difficulties that
had arisen with respect to his role as a neurologist in Newcastle,
but for a different and surprising reason:
I am a career academic neurologist with an interest in the
pathophysiology of demyelinating disease. This has led me
A. Compston
recently to an increasing interest in multiple sclerosis, but this
has been a secondary interest arising from my primary research
activities. Having read around multiple sclerosis a good deal in
the past three months, and in particular having had the good
fortune of attending the MS symposium in Barcelona which was
so splendidly summed up by [Albert] Sabin [1906–93], it is clear
to me that the answer to the problem is most likely to come
from virology, most probably with an immunological contribution as well . . . I have no personal experience in these two fields’
(Archive: letter, 8 October 1973).
Other moves were considered. McDonald always maintained
that his unsuccessful application for the Action Research professorship of neurology in Oxford in 1970, when Bryan Matthews
(1920–2001) was elected, foundered on the casting vote of a
clergyman who felt that his nervous system would be in more
sympathetic hands with Matthews than McDonald (personal information). Although he never received formal notification of that
decision, McDonald was informed by the University that his subsequent application for the same post, when John Newsom-Davis
(1932–2007) was elected to replace Matthews, had not been successful (Archive: letter, 15 April 1986). Eventually, with the death
of Anita Harding in 1995, McDonald was appointed as head of
the university department at the Institute of Neurology until
reaching the retirement age in 1998.
In the 1990s, Queen Square felt that its tradition and independence were threatened by the National Health Service reforms,
which required hospitals to function within an internal market,
competing for trade and resources. Despite lacking a natural
catchment, the hospital resisted change and the need to strengthen its ‘National’ status through merger. McDonald subscribed to
the conservative stance on maintaining the status quo that
brought Queen Square to the brink of closure. The neurologist
representing the London Implementation Group was briefed: ‘no
change is not an option; don’t worry about closing Queen
Square’. McDonald mobilized international opinion asking several
dignitaries to write to Mrs Bottomley, Secretary of State for
Health; she turned a deaf ear, even to Lord Walton of Detchant
(Archive: letter, 16 February 1995) and initially failed to grant the
National Hospital ‘Trust status’. In the event, the London
Implementation Group recommended merger with University
College London and this created a world-renowned grouping
that was further strengthened by radical changes in organization
and research infrastructure by the newly appointed dean. These
were unpopular; but seen from the outside as strategic, even if
dependent on the methodology of ‘creative friction’.
The disappointments late in his career, expansion in the staff at
the National Hospital in response to the National Health Service
reforms and the perceived loss of independence both for the hospital and the Institute of Neurology led to McDonald drifting away
from Queen Square on retirement in 1998; and he became a
weekly visitor at another neurological centre. There, McDonald
revealed a range and depth of knowledge of clinical neurology
that extended well beyond the specialist topics on which he had
focused throughout most of his consultant career—multiple sclerosis and neuro-ophthalmology. But the draw of the institution in
William Ian McDonald: 1933–2006
which he had invested so much proved too strong; and again
McDonald started attending clinical meetings at Queen Square.
Studies on demyelination and
remyelination
McDonald was an experimental physiologist. The focus and style
of his work were set in the early 1950s. Question 2 in the examination for the degree of Bachelor of Medical Science, examined
by McIntyre read: ‘Discuss critically the extent to which experimental studies of peripheral nerve have helped to advance knowledge of central nervous function.’ The interest in multiple sclerosis
was not contemplated much before the mid-1970s, although
often claimed in retrospect. Reflecting in 1996 for a lecture on
‘Experience and the future’ given in Atlanta (USA), McDonald
recalled that his first experience of multiple sclerosis had been as
a locum house officer 40 years earlier when managing a patient
who died from organic arsenic toxicity:
a treatment that has been introduced on the basis of poorly
controlled observations that failed to take the natural history into account and before the formality of clinical trials
methodology was introduced by (Sir Austin) Bradford Hill
[1897–1991] in 1946 (Archive: lecture notes, 7 November
1996).
And in preparation for a public lecture given in Wellington, New
Zealand, he wrote:
My interest mainly throughout my career has been in multiple
sclerosis. From the time when I saw my first patient and I can
remember it perfectly well in 1953 it would have been in early
November and I saw my first patient with MS who was highly
inappropriately in a geriatric hospital at Parkside in
Dunedin . . . (Archive: lecture notes, 6 December 1998).
McDonald’s first substantive paper, written with McIntyre, was
entitled: ‘Observations on ascending long spinal reflexes’
(McDonald and McIntyre, 1956) (Supplementary material F1).
Citations are to the writings of (Sir) Charles Sherrington [(1857–
1952): two] and his student DPC (David) Lloyd (1911–85: two).
McDonald wrote dissertations on ‘Ascending long spinal reflexes’
(1955) (Supplementary material C1), and ‘An electrical investigation of the effects of reserpine on the neuromuscular junction’
(1956) (Supplementary material C2). His PhD (1962), also supervised by Macintyre, entitled ‘The effects of experimental demyelination on conduction in peripheral nerve: a histological and
electrophysiological study’ (Supplementary material C3), was
examined by Denny-Brown.
McDonald was invited to visit Queen Square by Gilliatt who—
on behalf of the editor, Lord Brain (1895–1966)—had refereed the
two influential papers in Brain describing histological and electrophysiological features of experimental diphtheritic neuropathy
in the cat, and showing delayed conduction or block in affected fibres (Supplementary material A4, A5). The historically
sensitive style is apparent. After rehearsing (Sir Francis) Walshe’s
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(1885–1973) views on physiological conduction block [Walshe
quickly mentioned his own paper on meeting McDonald at
Queen Square: ‘I think you know something of my work’ (personal information)], McDonald quotes verbatim (using the New
Sydenham Society translation) from Jean-Martin Charcot’s
(1825–1893) sophisticated prediction of the pathophysiology of
impulse conduction in demyelinated axons (Sylvia Denny-Brown
subsequently gave McDonald her late husband’s copy of a rare
author’s offprint of Charcot’s Leçon from 1868 on Histologie de la
sclérose en plaques), but not until the 1940s was the problem
investigated experimentally. Denny-Brown had shown that stimulation of a peripheral nerve above the site of a demyelinating
lesion caused by pressure fails to induce contraction in the
muscle it supplies, in contrast to stimulation below the lesion;
and concluded that, in this context, demyelination produces complete conduction block. McDonald obtained direct evidence by
recording from the feline dorsal root ganglion following demyelination induced by systemic injection of diphtheria toxin.
Conduction failed abruptly as the compound action potential
entered the ganglion. Later, with Tom Sears, McDonald demonstrated the same phenomenon in the spinal cord following local
injection of diphtheria toxin (Supplementary material A11, A13
and A14). But it was still necessary to study central conduction
directly. Focal injections of diphtheria toxin into the cat dorsal
columns of the spinal cord provided a model ripe for electrophysiological exploration; and, given similarity between the histology of the lesions, one of relevance to multiple sclerosis.
Compound action potentials and single-fibre studies in the posterior columns below, at and above the site of these lesions demonstrated the now classical electrophysiological features of complete
conduction block in a substantial number of fibres shown to retain
axonal continuity. Single-fibre studies revealed conduction velocity
reduced to 30% of that seen in the same fibres retaining normal
trajectories; and there was reduced safety factor for transmission
of the nerve impulse.
With Dick Gledhill and Barry Harrison, McDonald showed that
compression of the cat spinal cord produces lesions in the posterior
columns that repair with terminal cytoplasm-filled loops, attached
to the axolemma by transverse bands, having short (67–85 mm)
internodes and uniformly thin myelin sheaths (Supplementary material A26). The now classical morphological criteria for remyelination were defined: myelin embedded in a satellite cell with
a continuous membrane from the surface of the cell around
the axon, back to the surface again and compacted but inappropriately thin for the corresponding axon, and with a short
internode.
Showing commendable restraint on what could reasonably be
concluded from their electrophysiological data, McDonald and
Sears did not speculate excessively on the pathophysiology of
symptom production in multiple sclerosis; but they served notice
that the model might inform the electrophysiological study of recovery of function attributable to remyelination. That study was
published 11 years later based on work carried out as part of his
doctoral thesis by Kenneth Smith, supervised by McDonald and in
collaboration with William (‘Bill’) Blakemore (Supplementary material A58). Using the model of direct lysophosphatidyl choline
micro-injection into the spinal cord, in preference to diphtheria,
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Smith and colleagues showed that loss of conduction and its restoration coincide with the onsets of demyelination and remyelination, respectively; conduction was restored in fibres that were
previously blocked and had a prolonged refractory period for
transmission. Reflecting on these experiments in 2006,
McDonald recalled that:
the story was far from complete, not least because it could not
account for the striking recovery that follows some purely degenerative lesions. Filling in the gaps took a long time, requiring
as it did technical advances in experimental and clinical neurophysiology. Our physiological experiments rarely lasted less than
18 hours. With breaks in the Millepini restaurant in Queen
Square with Tom Sears, I often watched the dawn
breaking on the way home, knowing that I would be back for
a clinic at 9.00am. Now, the observations can be made comfortably during the ordinary working day – a much more satisfactory arrangement for all concerned (see Brain 2006: 129;
3141–6).
The introduction of evoked
potentials
McDonald’s work on the physiology of demyelination in the cat
led directly to the development of a first method for studying
conduction in people with demyelinating disorders affecting the
CNS. The exploration of human brain function by evoked potential
methods originates with the observations of George Dawson
(1912–83) at Queen Square. In 1972, McDonald and Martin
Halliday (1926–2008) introduced evoked potentials as a paraclinical laboratory method used to supplement clinical evidence for
the diagnosis of multiple sclerosis. At first, the work met with
scepticism, even from close colleagues. First presented at a meeting of the Association of British Neurologists in Cardiff (1972),
Gilliatt and Anthony Hopkins (1937–97) were worried at the discrepancy between the latency of potentials evoked by the alternating checker-board and by flash. Fred Plum (1924–2010) hailed
McDonald in the corridor and was delighted by the criticism:
‘I gather you’ve been called on that evoked potential thing not much use in that’—a view echoed by a consultant neurologist
from Queen Square who did not enjoy widespread respect
amongst his colleagues. Angered, McDonald retaliated that there
was no point in studying demyelination without making observations on the physiology of conduction (Archive: typescript,
undated).
The sequence of reduced amplitude followed by delayed conduction was first demonstrated as part of the natural history of acute
optic neuritis (Supplementary material A20). Subsequently, the
prevalence of abnormal visual evoked potentials was described in
multiple sclerosis (Supplementary material A27); distinctions were
made between the reduced amplitude with preserved latency that
characterizes compression of the anterior visual pathway
(Supplementary material A35); and it was established that, with
time, there may be a reduction towards normal in latency of the
evoked potential especially in childhood optic neuritis, suggesting
A. Compston
enhanced potential for remyelination and restoration of normal conduction velocity in the juvenile demyelinated optic nerve
(Supplementary material A94). The technique survives as the definitive marker of what happens physiologically when the myelin
sheath is lost from nerve fibres in the brain and spinal cord. Martin
Halliday wrote to McDonald, then visiting his family in New
Zealand:
One exciting bit of news is that we may have acquired our first
real opportunity for pathological correlation of the VEP data.
[William] Blackwood [1911–90] rang me up at the end of last
week to say that they were doing a PM on K[. . .] T[. . .]. She
turns out to be a good case, in whom we found a unilateral
delay, so that (unless she has had a further attack since) there is
a good chance of correlating the latency with the presence or
absence of lesions on the appropriate side (Archive: letter,
27 February 1975).
But there was a further dividend from the introduction of
evoked potentials with which McDonald became actively involved.
The observations brought objectivity to the diagnosis of multiple
sclerosis and stimulated the introduction of improved diagnostic
criteria.
The ‘Poser’ and ‘McDonald’
diagnostic criteria
Classifications for multiple sclerosis were introduced for epidemiological purposes in order to weigh the diagnosis in the absence of
pathological proof. Terms previously introduced included ‘early’,
‘probable’, ‘possible’, ‘definite’ and ‘discarded’ disseminated or
multiple sclerosis. The ‘McDonald and Halliday’ criteria
(Supplementary material B19) added a definition for ‘proven’ multiple sclerosis (evidence from autopsy or biopsy); refined the early
probable or latent cases (two episodes and a single affected site or
a single episode and two affected sites); and tackled the difficult
issues of ‘progressive probable’ (progressive history with multiple
sites affected), ‘progressive possible’ disease (progressive history
affecting a single site) and ‘suspected’ multiple sclerosis (one episode at a single site unless the optic nerves are affected).
A workshop was organized in Washington DC (USA) in 1982
under the sponsorship of the Department of Neurology of
Boston University at which experts in a range of disciplines were
mandated to ‘produce new diagnostic criteria to be used for research protocols’; and to ‘provide a detailed review of procedures
that have become available in the last decade . . . used to support
the diagnosis of [multiple sclerosis] MS’ (Supplementary material
A65). The ‘Poser’ committee [Charles Poser (1923–2010), Donald
Paty (1936–2004), Labe Scheinberg (1925–2004), McDonald and
George Ebers] proposed criteria that incorporated information available from laboratory investigations within the
categories of clinically definite and probable multiple sclerosis.
These gained widespread acceptance. The criteria had as their
gold standard for the diagnosis of multiple sclerosis two or
more attacks affecting two or more necessarily separate sites
William Ian McDonald: 1933–2006
within the CNS; but, for clinically deEnite disease, also allowed
clinical evidence to be replaced by laboratory abnormalities
at the second site. Imaging, electrophysiology and CSF examination were used to supplement evidence for the diagnosis in situations where clinical criteria were not met, either through
absence of the second clinical episode or because only one site
was affected. Not every patient could be accommodated neatly
within this classiEcation; and the patient with progressive disease proved especially difficult to evaluate. (Douglas) McAlpine
(1890–1981) had distinguished patients in whom a single episode is
followed some years later by progressive disease and designated
these as ‘transitional-progressive’ cases. This category was largely
ignored but the issue of a working definition for primary progressive multiple sclerosis was eventually tackled by Alan Thompson
working with McDonald (Supplementary material A212).
By the late 1990s a new need had arisen with respect to
diagnostic criteria; that was to bring forward the point at which
the diagnosis of multiple sclerosis can be made, with sufficient security, in the interests of informed discussions with
individual patients and as the basis for taking decisions on the
use of disease-modifying treatments early in the disease
course. Organized by Stephen Reingold of the National Multiple
Sclerosis Society, a panel met at the Royal College of Physicians
in London. A useful but exploratory discussion ensued throughout the morning at which point the committee broke for lunch.
In the early afternoon, a brief conversation took place that can
be summarized as: ‘the world consists of three types of person:
those who have multiple sclerosis; those who do not; and
those who might’. A little weary after lunching well, McDonald’s
eyelids lowered and he did not contribute further to the exchange for some time during which the ‘McDonald’ criteria were
quickly formulated. Subsequent discussion decorated these categories in medical language and defined the three groups, incorporating clinical details and laboratory markers weighted for their
predictive value. MRI features denoting dissemination in time
and space were incorporated and, in context, assigned the same
status as a clinical event (Supplementary material A213).
There was lively discussion of the criteria when the American
Academy of Neurology met in April 2001 and the view was expressed that these were overly complicated. In a letter to Stanley
van den Noort, McDonald argued:
If, as I firmly believe, we should use evidence-based criteria
when they exist, complexity is inevitable at the present time.
While you and I will predict (usually correctly, but sadly not
always so, even after 40 years in the business!) that a patient
in whom not all the criteria are fulfilled will turn out to have
MS, I don’t believe that our hunches constitute criteria . . . I’ve
also heard that you may be a signatory to another set of criteria . . . there will be something of a problem if there are significant
differences between the two sets (Archive: letter, 31 May
2001).
In the event, the ‘McDonald’ criteria were generally well accepted but have since been revised serially to reflect nuances of
interpretation and evidence on their utility.
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Studies on pathogenesis:
inflammation and axon
degeneration
In the 1980s, McDonald realized that MRI and spectroscopy could
be used to illuminate the nature of inflammatory brain disease.
Alan Davison (1925–93) had suggested that, as a senior investigator who had never held a grant from the Multiple Sclerosis
Society, and someone therefore who added value to their existing
research portfolio, McDonald would be the ideal person to develop a unit funded by the Society (Fig. 2). Resources were quickly
mobilized by the general secretary, John Walford. The chairman,
Reginald Kelly, was worried that the unit would not be dedicated
to multiple sclerosis research, and felt vindicated in that view
when the first paper was a letter to the Lancet on stroke
(Supplementary material F21). But the programme was nurtured
through its infancy to a state of lasting success and served as the
template for a global programme of imaging-based research that
systematically opened up new approaches to understanding the
natural history of multiple sclerosis, and (after McDonald’s retirement) provided surrogates for outcome measures in clinical trials
on an industrial scale. While to some extent his involvement may
originally have been opportunistic, McDonald invested time and
effort in this entirely new field of research, because he realized
that here was a means of understanding the pathogenesis of
multiple sclerosis without dependence on pathological studies,
even though neuropathology was needed as validation for
imaging-based observations made in life.
Reflecting on the work with McIntyre, McDonald noted that
had he not gone into clinical neurology, his interest would have
been in comparative physiology and morphology with a strong
behavioural input:
we are having an exciting time with the NMR Unit here. It is
rare for someone at this stage in my career to find that it is
possible to answer questions of a kind that never were thought
possible in man (Archive: letter, 25 July 1988).
Under McDonald’s leadership, the NMR Unit aimed to match
protocols for capturing images to those aspects of the pathology
that he had studied during an earlier phase of his career; and to
pursue the historical trail on which the critical observations
relating to inflammation, demyelination, astrocytosis, axon degeneration and remyelination had their origins. Over time, it was
shown that MRI can be used to distinguish inflammation
[gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhancement], axonal loss (atrophy and magnetic resonance spectroscopy), demyelination and remyelination (magnetization transfer
ratio), astrocytosis (T1-weighted relaxation time) and alterations
in ‘normal appearing’ white matter. The contributions were
based on painstaking comparisons of imaging appearances made
in autopsy material that was then subjected to neuropathological
examination (Supplementary material A124). The findings in
humans were supplemented by the first imaging studies of animals
with experimental allergic encephalomyelitis in which more
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A. Compston
Figure 2 The opening of the Multiple Sclerosis Society NMR Unit in 1985. From left in the foreground: Reginald Kelly, Ian McDonald,
HRH The Prince of Wales and George Du Boulay.
detailed but necessarily indirect observations on the evolution of
lesions could be made (Supplementary material A113, A123).
The most influential demonstration from this time, and the one
that proved visually so compelling when first demonstrated, was
the study of serial gadolinium-DTPA-enhanced images from a
cohort of patients in whom the life cycle of the individual lesion,
their number, location and dynamic properties, were illustrated
through the use of video in which 6 weeks was collapsed into a
few seconds creating a display of new lesions coming and going,
and with old ones occasionally burning bright for a while. Over
and above the pyrotechnics, to the informed observer this showed
in life what had long been assumed from the snapshots of pathological studies: the earliest stage of new lesion formation is brain
inflammation attributable to the passage of lymphocytes across
the blood–brain barrier, but not all lesions are expressed clinically.
McDonald often referred to the case provided by Dale McFarlin
(1936–92) who sent details of a patient in whom circumstances
made it possible to carry out pathological examination of the nervous system soon after MRI; this showed intense inflammation in
the areas of previous gadolinium enhancement (Archive: letter, 11
January 1991).
Reflecting his early interest in neuro-ophthalmology, and seeking to settle a long-standing clinical debate in multiple sclerosis,
McDonald carried out a study at Moorfields’ Eye Hospital of the
retina in patients with isolated optic neuritis (Supplementary
material A83). Conversion to multiple sclerosis was more likely,
and happened faster, in those with retinal abnormalities.
McDonald wrote:
Most neurologists have been reluctant to accept the observation, having failed to see it for themselves. Few however, are
experienced in the systematic examination of the periphery of
the retina and it should be emphasised that in only one of our
patients were abnormalities visible at the posterior pole through
the undilated pupil (Supplementary material A83).
He argued that sheathing of retinal vessels is the visible clinical
sign of the perivascular lymphocytic infiltration and accompanying
oedema that characterize the lesions of multiple sclerosis.
Importantly, this cuffing is seen at a site free of myelin and oligodendrocytes. Therefore, it cannot be secondary to demyelination
resulting from some other mechanism; rather, the primary events
in multiple sclerosis occur at the vascular endothelium.
These two lines of evidence coincided with emerging opportunities for treating multiple sclerosis by depletion or inhibition of
lymphocyte migration across endothelial barriers. Eventually these
showed that with immunosuppression, clinical and radiological disease activities are effectively suppressed; nonetheless, patients
continue to experience progression of pre-existing disability. The
likely explanation for this dissociation of effect in early and progressive multiple sclerosis was first suggested, along with other lines of
evidence, by the imaging studies that McDonald proposed. He
showed that T2 exponential decay analysis is not easily explained
by current notions on the pathology (Supplementary material
A120). The increase in mobile water cannot always be explained
by highly cellular gliotic lesions, and suggests some expansion in the
extracellular space that might be due to loss of axons.
McDonald’s work using magnetic resonance spectroscopy provided further evidence for axonal loss. The group showed that the
1
H spectrum from the brain of healthy individuals is dominated by
a peak due to N-acetyl aspartate, an abundant amino acid virtually
confined in the adult to neurons (including axons), where it is
mainly located in mitochondria. That a reduction in N-acetyl aspartate is associated with neuronal and axonal loss was shown by
William Ian McDonald: 1933–2006
Brain 2011: 134; 2158–2176
| 2165
the inverse correlation with cerebellar atrophy in dominantly inherited cerebellar ataxia (Supplementary material A160). In patients with multiple sclerosis manifesting severe ataxia, there is a
similar persistent reduction in N-acetyl aspartate, in association
with a measurable reduction in cerebellar volume, whereas the
N-acetyl aspartate and cerebellar volume are normal in non-ataxic
patients. McDonald interpreted the evidence as showing that neuroaxonal loss or damage occur in lesions and normal-appearing
tissues from very early stages of multiple sclerosis; and he summarized the situation with characteristic caution as:
Taken together, the evidence shows a correspondence between
irrecoverable deficit, atrophy and axonal loss in the central nervous system, which is graded in degree and progresses over the
course of a year or so. Although the evidence is gathered from
a variety of sources, none in itself definitive, it is reasonable
to conclude that axonal loss is an important mechanism
contributing to irrecoverable disability in multiple sclerosis
(Supplementary material A160).
On the pathogenesis of multiple sclerosis, no passage gave him
more satisfaction than that written in 1863 by (Eduard von)
Rindfleisch (1836–1908) and which a visitor, Sean Morrissey,
translated for him from the original text:
. . . in the middle of each individual focus [is] the lumen of a
small vessel in a state of chronic inflammation . . . three types
of changes occur in parallel, Erst the alterations of blood vessels,
secondly the atrophy of the nervous elements and third the
metamorphosis of the connective tissue . . . (Archive: annotated
typescript, not dated).
McDonald’s work illuminated all three in the modern era using
techniques unknown to his predecessors but exploring the same
concepts and ideas.
Other studies in multiple
sclerosis
By nature of the colleagues with whom he worked, and the need
for those based in laboratories to have access to samples from
people with multiple sclerosis, McDonald became involved in research that was removed from his main research interests in experimental physiology. Many of these academic discursions date
from the late 1970s (Fig. 3). These papers often reflected his main
clinical interest in neuro-ophthalmology and the connection with
Moorfields Eye Hospital. Others were planned around visits from
foreign trainees needing a short-term research project. Notable
among these occasional papers was the comparison of the phenotype of multiple sclerosis in Western Europe and Japan
(Supplementary material A57); and the role of stress as a trigger
for disease activity in multiple sclerosis (Supplementary material
A101). Others arose from the use of MRI in clinical contexts
that might mimic the clinical or radiological phenotype of multiple
sclerosis—phenylketonuria, Behçet’s disease, systemic lupus erythematosus and sarcoidosis (Supplementary material A92, A135,
Figure 3 Ian McDonald, c1980.
A141). Reflecting later on this interval between his physiological
research and the advent of MRI, McDonald quoted Eccles:
a lesson learned was not to linger in strange areas and where
the conceptual contribution was small. This was an interlude
before returning to my roots in research on the pathogenesis.
But my provision of cases and families to those who understood
the field was a contribution (personal communication).
In 1977, McDonald was interviewed by John Wilson for the
BBC World Service (‘The frontiers of knowledge’) on the genetics
of multiple sclerosis following a field trip to Jordan. With others he
had recently described specifically different human leucocyte antigen associations in Jordanian Arabs and white Europeans suggesting that this might reflect the interplay of genotype with more
than one viral trigger in initiating the disease process, or be explained by linkage disequilibrium with a shared but more relevant
allelic association (Supplementary material A39, A40).
Summarizing that phase of his work, McDonald felt able to conclude for listeners across the world:
our whole view of the nature of the disease has changed in the
1970s, and this represents the biggest change in the hundred
years in which the disease has been recognised (Archive: BBC
transcript, 27/77).
The origins of this interest lay in a conference organized by the
Medical Research Council in Belfast, Northern Ireland (17–18
October 1974), the proceedings of which McDonald edited with
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others, and where work was presented on the recent description
of an association between the human leucocyte antigen system
and multiple sclerosis (Supplementary material C4). McDonald met
Richard Batchelor and agreed to a collaboration that was soon
funded through support from the Medical Research Council.
They described the B lymphocyte-restricted allotype BT101—a
broad antigenic specificity later reclassified as DR15 and DQ6.
Through his international contacts the field trip was arranged to
Amman, Jordan, where McDonald and colleagues were guests of
the Jordanian army, took tea with King Hussein of Jordan
(1935–99) in the Royal Palace, peered through his telescope
trained on the Golan Heights, and were escorted across desert
routes taken by TE (Thomas Edward) Lawrence (of Arabia:
1888–1935), and to Petra—the ‘rose red city half as old as
time’. McDonald’s association with Moorfields Eye Hospital also
focused his work on the risk for conversion to multiple sclerosis
following a clinically isolated episode of optic neuritis. The cohort
recruited in 1975 was used in several follow-up studies as knowledge on the human leucocyte antigen system evolved in the
1980s (Supplementary material A46, A87). It also stimulated the
collection of an independent group studied by MRI at onset, followed prospectively and reported serially for conversion to multiple sclerosis over more than 20 years (Supplementary material
A98, A106; see also, Brain 2008: 131; 808–17).
McDonald contributed as editor or author to 18 books on neurology. Apart from the monograph on diagnostic criteria
(Supplementary material C5), and those written in his role as
Harveian Librarian at the Royal College of Physicians (see
below), he edited, with Art Asbury and Guy McKhann, Diseases
of the Nervous System (1986) drawing on an international community of 193 contributors (Supplementary material C7), and its
successors Diseases of the Nervous System: Clinical Neurobiology
(1992) (Supplementary material C11) and Diseases of the Nervous
System: Clinical Neuroscience and Therapeutic Principles (2002)
(Supplementary material C19). The aim was to provide a contemporary scientific basis for clinical neurology:
while [the] Balkanization of neurology has resulted in geometric
growth of knowledge, it has also made it difficult to keep
abreast . . . the purpose [is] to . . . bring together what scientific
enquiry has taught . . . about the phenomena of neurologic dysfunction . . . and to present in summary fashion an up-to-date
account of the major groups of neurological disorders, their
pathogenesis, and their management.
McDonald had always intended to write a book on multiple sclerosis; this was planned but never really started. Chapter 1 was to be
a general account in which the relevant disciplines—epidemiology,
genetics, immunology, biochemistry, cell biology, membrane biophysics and neurophysiology—were introduced.
I shall begin with an outline of the essential features of multiple
sclerosis, since many of those engaged in research on fundamental problems relevant to the disease are unfamiliar with it as
it affects patients. Later chapters will deal with the structural
changes which occur in multiple sclerosis, with the experimental
investigation of the effects of such changes on conduction and
A. Compston
on the application of physiological methods of the study of
patients with the disease. Finally I shall attempt an interpretation
of the clinical features of multiple sclerosis in the light of our
present understanding of the disordered pathology (Archive:
manuscripts and typescripts 30 April 1980).
After trying various versions, McDonald completed an outline of
‘The pathophysiology of multiple sclerosis’ with notes for the nine
chapters: introduction; the pathology of multiple sclerosis; conduction in abnormal nerve fibres; synaptic block; abnormal conduction
in multiple sclerosis; clinical application of evoked potentials;
symptomatology of multiple sclerosis; mechanism of symptom
production; and clinical physiology of multiple sclerosis.
Instead, McDonald edited a book on multiple sclerosis with Don
Silberberg (Supplementary material C6) and contributed to two
editions of McAlpine’s Multiple Sclerosis (1998; 2005). In what
was designated the third edition (1998), he drew on his recent
work to describe ‘diagnostic methods and investigation in multiple
sclerosis’ and on his earlier work in the chapter on ‘pathophysiology of multiple sclerosis’ (Supplementary material C15). In 2005,
McDonald co-authored chapters on the ‘story of multiple sclerosis’
adding many subtleties of interpretation and detail to that historical account; and he was primarily responsible for the chapter that
took forward the late Bryan Matthews’s pithy writing on ‘the
symptoms and signs of multiple sclerosis’; handing over as primary
contributor the chapters on ‘the diagnosis of multiple sclerosis’ and
the ‘pathophysiology of multiple sclerosis’ to his former students,
David Miller and Kenneth Smith, respectively; and adding his
name to the ‘synthesis of ideas on the origins of multiple sclerosis’
and a conspectus on ‘multiple sclerosis in the individual and in
groups’ (Supplementary material C21).
Adviser on academic neurology
McDonald reciprocated the substantial and sustained grant support provided by the Multiple Sclerosis Society over many years by
acting as Medical Adviser and ad hoc spokesman in conjunction
with a series of chairmen and other officers. He had particular
respect for John Walford who joined the Society in
February 1954; when Walford retired in 1994, £30 million had
been committed to research and a further £55 million to welfare.
But there were times at which this mutually supportive relationship between the leading exponent of multiple sclerosis research and the Society threatened to unravel. McDonald was
caught up in events surrounding the introduction to the United
Kingdom of the first disease-modifying treatments for multiple
sclerosis.
He was always at pains to declare himself ‘not a treating neurologist’ (personal communication) but took an interest in the early
development of therapies for the disease (Supplementary material
B88). A letter from Sylvia Lawry referred to the response to her
advertisement placed in the New York Times on 1 May 1945, on
behalf of her brother:
MULTIPLE SCLEROSIS. Will anyone recovered from it please
communicate with the patient. T272 TIMES
William Ian McDonald: 1933–2006
One respondent indicated that she had been paralysed until
treated by Professor Otto Marburg (1874–1948); and her
symptoms never recurred. Ms Lawry took her brother to see
Marburg, now at the New York Neurological Institute, who recalled that the treatment used had been nicotinic acid. This was
given, but without benefit, to Mr Lawry (Archive: letter, 4 May
1999). Then as now, putative treatments for multiple sclerosis
rarely had a sound theoretical basis for their use in patients.
Referring to a notorious episode from the 1920s, Denis Brinton
wrote to McDonald:
Many thanks for letting me see your Attitudes to the treatment
of multiple sclerosis. It’s a most admirable summary . . . I don’t
think you have been in any sense too tough with PS [Sir James
Purves Stewart (1869–1949)] or his relics . . . the hint [is] that
Purves Stewart was on the staff at Q Sq which he NEVER [was].
He was on the house with Wilf Harris [1869–1960], my old chief . . .
and on at the West End Hosp for ND [Nervous Diseases] as well as
the Westminster – NOT even (I speak as in the 1930s) at Maida
Vale (Archive: letter, 10 November 1982).
McDonald was against a proposed ‘Randomized controlled trial
of b-interferon in multiple sclerosis in the British Isles’ designed to
position the b-interferons with respect to sample size, inclusion
criteria and outcome measures, proposed in the mid-1990s.
McDonald warned the Department of Health that the cost of
introducing b-interferon, with a likely take-up of 50% of prevalent
patients, might be £210 million per annum (Archive: letter,
4 February 1994). He was caricatured by the press and radio
for being a ‘Jonah’ with respect to the usefulness of these
medications; and was hurt by the opinions expressed. Rita
Levi-Montalcini had sought his advice on behalf of the Italian
Multiple Sclerosis Society. McDonald advised caution based on
the unreliability of MRI as a surrogate, and the lack of evidence
for efficacy in progressive disease:
my conclusion is that at present a convincing clinical benefit of
any form of beta-interferon has not been demonstrated and it is
therefore premature to recommend its general use until we have
more information about its effectiveness (Archive: letter, 8
December 1993).
As a member of its Research Advisory Committee, the Multiple
Sclerosis Society initially endorsed McDonald’s view that:
the results of recent trials of potential treatments for MS should
be treated with caution . . . the size of the effect on those who
appear to benefit from the new treatments, and which patients
may be helped by them, remain to be determined (Archive:
typescript, 1 December 1994).
But views changed; and with respect to the introduction of
disease-modifying treatments, the Chief Executive Officer of the
Multiple Sclerosis Society was later quoted as saying that:
the failure of the professional association of neurologists
to speak out on behalf of patients has diminished its
Brain 2011: 134; 2158–2176
| 2167
stature in the eyes of the MS Society (Archive: letter, 6 April
1998).
As president of the Association of British Neurologists,
McDonald had expressed the view on interferon b–1b that in
the context of relapsing–remitting multiple sclerosis without
progression:
there is a substantial body of opinion that its usefulness in modifying the course of the disease even in this group is unproven . . . many patients find these facts disappointing. I try to
be as encouraging as I can (Archive: letter, 4 October 1995).
His opinion, used by Health Authorities to avoid funded prescriptions evoked the thinly veiled criticism of one consultant
colleague:
you might be fascinated to see a letter that has been circulated
concerning your interaction with my practice . . . may I have your
urgent comments to whether the way you have been quoted
criticising my care is actually what you said (Archive: letter, 10
September 1996).
More generally, after many years in which the Society worked
to create a reputation for research and made available significant
funding, tensions arose over the perception that the Research
Advisory Committee was self-serving in its allocation of funds;
and that research was motivated more by the interests of the
researchers than the real needs of members of the Society. From
1995, relationships started to deteriorate. McDonald complained
that invoices went unpaid or required burdensome administration
to secure reimbursements (Archive: letter, 28 September 1995).
Expenditure on research reached an all-time low at 8% in 1996.
For a while the Society started to withdraw from research altogether. It was agreed that, after 10 years, McDonald should resign
from the Medical Research Advisory Committee. For a while the
committee was formally disbanded. Later it reappeared with much
stronger representation of individuals familiar with the generic
issues of research but not close to the problem of multiple sclerosis
itself. McDonald remained critical that representatives of the
Multiple Sclerosis Society continued to state publicly that:
investigators have not been altogether responsible in the past
and without acknowledgement that any of the previous research funded by the Society has been useful (Archive: letter,
22 January 1997).
The decision was taken to review the research strategy in general and, by implication, the substantial investments in MRI.
McDonald became acutely concerned that funding for the NMR
Unit at Queen Square would lapse not through failure of the research to achieve international acclaim but as a result of strategic
decisions within the Multiple Sclerosis Society; and he sought reassurance informally from the neurologist, based in the USA, from
whom the Society had sought strategic advice (Archive: letter,
22 January 1997). The reply was intended to be fully reassuring
(Archive: letter, 27 January 1997) and, following scientific
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appraisal and review of its investments in 1997, funding for MRI
was maintained, although the Institute of Neurology lost support
for the Multiple Sclerosis Society Brain Bank and that facility was
moved to Charing Cross Hospital.
Nevertheless, there followed a bitter and wide-ranging exchange with the Society in which McDonald regretted that it
was no longer possible to reassure researchers about the perceived
withdrawal of interest and whether existing financial commitments
would be honoured; reference was made to slurs on the ability
and preparedness of researchers to communicate their work to
members; and distaste expressed at the stage-managing of unscheduled public debates on contentious issues such as the Cari
Loder (1961–2009) ‘treatment’. Finally the suggestion was apparently made that research on multiple sclerosis was in breach of the
Declaration of Helsinki. McDonald wrote to the Society:
I have been sadly disappointed at the failure to rebuild trust
between the research community and the Society (Archive:
letter, 27 April 1998)
As relationships between the Society and neurologists deteriorated, McDonald met the chairman, Michael Willis, who reassured
him of the continuing commitment of the Society to research, and
the security of their financial position at the time. This triggered a
fullsome and generous reply that sought to reassure McDonald
(Archive: letter, 23 June 1998); but he remained disillusioned
and unconvinced (personal communication).
In comparison, McDonald’s work for the National Multiple
Sclerosis Society as a member of the Research Programs
Advisory Committee (1991–96) was highly valued. On his retirement from that post, Stephen Reingold wrote:
when you speak it is with such (deserved) authority that the
impact of your comments is amplified in meaning and weight
(Archive: letter, 11 December 1996).
McDonald also joined the board of Multiple Sclerosis
International Federation and served as Chairman of its
International Medical Advisory Board for 5 years. Under the auspices of Multiple Sclerosis International Federation, he proposed
and established the Sylvia Lawry Centre for Multiple Sclerosis
Research and was instrumental in raising the £4 million necessary
to fund this project. Later, this also became a source of some
tension and anxiety. McDonald wrote to Mrs Christine Purdy
giving his impression of the Centre in advance of a visit by Sir
Michael Rawlins. McDonald was concerned at ‘mission drift’ from
the natural history database intended to provide a surrogate for
comparison of treated patients in clinical trials since the Centre
was established; and the introduction of ephemerous concepts
such as the ‘virtual patient matching the virtual placebo group’,
While some indices of success were apparent, McDonald expressed concern over the lack of peer-reviewed publications and
reasons he perceived for that deficiency (Archive: letter, 19
October 2004). It could not be said that the situation was much
improved when he received the annual report for 2005. This led to
a rigorous review that included the wise counsel of Julian Jack—a
lifelong friend and former colleague from New Zealand where
A. Compston
both had been graduate students in physiology with McIntyre—
and McDonald’s gradual withdrawal from the affairs of the Sylvia
Lawry Centre.
McDonald was a founder member of the European Neurological
Society ‘established in 1986 on the initiative of Gérard Said, Anita
Harding and PK Thomas (1926–2008) and modelled on the
American Academy of Neurology’. The aim was to break away
from national representation to membership on an individual basis.
McDonald served as president in 1995–96 when the fifth and sixth
annual scientific conferences were held in Munich and The Hague,
respectively. But even at this early stage in its career, the issue
arose of whether Europe needed two neurological organizations,
both ambitious for growth and each holding international scientific
congresses annually that competed for resources. McDonald felt
that he had successfully brokered a rapprochement between the
European Neurological Society and the European Federation of
Neurological Societies which would lead to merger; but in that
he was mistaken and felt exposed through having declared a position that could not be carried. McDonald regretted that what had
begun as a scientific society had taken an expansionist and somewhat commercial direction; and, in so doing, had compromised its
origins and threatened its future. As president of the Association
of British Neurologists (1994–95), McDonald was ably supported
by Susan Tann and he was proactive in developing policy through
Council. His presidency coincided with the National Health Service
reforms of the early 1990s introducing attitudes and arrangements
for training and the practice of neurology that were alien to
McDonald. These diverted much business of the Association towards services and standards. But through influence and personality, he retained the involvement of academics with the
Association. It was natural that McDonald should be asked to
serve as president of the World Congress of Neurology when
this was held in London in 2001. On all of these occasions
McDonald, as always, gave polished and carefully prepared
speeches at the ceremonies and dinners.
Brain: a journal of neurology
First published in 1878, and adopted in April 1887 as the official
organ of the Neurological Society of London, Brain (formed at a
meeting on 14 January 1886) became the responsibility of a group
of Guarantors in 1907 when the Neurological Society (now of
England) became the section of neurology within the newly
founded Royal Society of Medicine. The journal flourished scientifically although its finances were always somewhat precarious.
Appointed Honorary Secretary and Treasurer, taking over from
Samuel Nevin (1905–79), and elected as a Guarantor in 1970,
McDonald soon found himself in a position to negotiate a
change of publisher. The accounts show that between 1964 and
1975, the costs charged by Macmillan and Co. for publishing
Brain rose from £12 845 to £54 131 per annum without a commensurate increase in income to the Guarantors. On 3 September
1973, McDonald was in negotiation with senior staff at the
Clarendon Press comparing their printing with that of rival publishers also under consideration by the Guarantors (Archive: letter,
3 September 1973). Within a year of Charles Phillips (1916–95),
William Ian McDonald: 1933–2006
Dr Lee’s professor of anatomy in Oxford, becoming editor, publication for Volume XCIX of Brain moved to Oxford University
Press. Commenting many years later on an obituary of Charles
Phillips, McDonald recalled the opinion of Charles Symonds who
considered Phillips to have been an outstanding member of the
clinical neurological staff at St Hugh’s during World War II. A
fellow member of the Garrick Club, ‘a senior judge’ with whom
McDonald dined by chance confided that his flail limb and speech
mannerism were residues of a head injury from that time; and
how reassured he had been by the care and prognostic advice,
accurate as it turned out, given to him by Phillips at St Hugh’s in
Oxford (Archive: letter, 24 March 1997).
William Gooddy (1916–2004) wrote apologizing for not having
paid sufficient tribute to McDonald in managing the transfer from
Macmillan to Oxford University Press, and commenting at a meeting of the Guarantors on the:
extraordinarily successful way you managed the OUP [Oxford
University Press] takeover . . . I have suffered similarly from time
to time, because things are mentioned in my favour that mean
little to me whereas things I rather esteem myself for – not at all
many – often go unmentioned (Archive: letter, 11 November
1976).
McDonald succeeded PK Thomas as editor in August 1991 completing Volume CXIV (Parts V and VI); and he continued in that
role until July 1997. Elizabeth Macdougall (dates not known), the
long-standing assistant editor retired and was replaced by Carol
Lovelidge; and John Clark was appointed deputy editor in place of
Lawrence (Larry) Weiskrantz. The previous editorial team had
accumulated a large backlog of papers awaiting publication and
McDonald’s inaugural volume contained 2723 pages—the most
ever published by Brain in a single year—compared with around
1000, and often considerably less, until the late 1980s. His
declared editorial policy made reference to the length of articles
pointing out that brevity is often persuasive but that Brain would
continue to provide a forum for extended original articles; and he
aimed to publish material within 6 months of acceptance. Page
numbers reduced to 1612 per annum by 1993 but each issue
remained physically bulky and somewhat unmanageable; therefore, other tactics were needed to manage the increasing
number of submissions. From February 1994, with help from
friends in the world of the arts, and with input from Oxford
University Press, McDonald changed the format of Brain introducing larger, thinner and less glossy paper and using type of smaller
font printed in double columns. The contents were no longer
shown on the cover, which now bore a single image; and the
colour moved from Cambridge light blue in the direction of
Oxford dark blue. An editorial announced these changes and
that publication had reduced to 5.2 months from acceptance;
the emphasis of papers would be on neurological diseases and
their mechanisms signalling a change away from papers reporting
physiological observations; correspondence was introduced but
not as a surrogate means for presenting original data. Then,
with Volume CXX (January 1997), McDonald moved to monthly
publication so that the contents of each volume, now back at
2319 pages, were distributed across 12 issues, easy to handle
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| 2169
and each containing 200 pages. Editorial Board meetings (and
the Annual General Meeting of the Guarantors) were held at the
Garrick Club, and one each summer either at St Edmund’s Hall
(Oxford) or Jesus College (Cambridge). These were congenial. At
the Millennium, McDonald’s successor, John Newsom-Davis,
invited him to summarize the contents of Brain over the previous
122 years. McDonald’s survey starts with the 19th-century concept of neurology as a clinical subject embedded in internal medicine and as a scientific discipline embracing philosophy and
psychology as well as physiology and pathology in animals and
man. For McDonald, Brain as a journal publishing papers of lasting
value written by élite authors reached its zenith with the issue for
March 1907 dedicated by the Neurological Society of the United
Kingdom to Hughlings Jackson in celebration of his 50 years in
medical practice. The contents of the journal changed over succeeding decades as clinical disorders were described; human physiology and neuroanatomy continued to provide a basis for
understanding mechanisms of disease; laboratory methods were
developed that, in part, replaced the invariable need for pathological examination; the impact of genetics and immunology was
felt; and a new philosophy and altered concept of mental health,
with which Brain had started through discussions at the West
Riding Lunatic Asylum, emerged.
As with all else in his professional life, it was as much the nuances of interactions with people that spiced editing, an activity
that might otherwise have proved onerous for McDonald despite
the advantages of carrying the baton for an enterprise that connected him to the historical figures he so much admired. Peter
Nathan (1914–2002) wrote complaining that Brain had started
listing papers by John Hughlings Jackson (1835–1911) as
Hughlings-Jackson J not Jackson JH:
If you put him as Hughlings-Jackson you will introduce chaos
into the refs. . . . Let me assure you that when you die and stand
at the gates of heaven, God will condemn you for making his
world a worse place, by introducing chaos that was not there
(Archive: letter, 26 January 1995).
Carol Lovelidge annotated her copy of the reply indicating that
Jackson was himself responsible for the confusion, having appeared on the front cover as Hughlings-Jackson and published
papers in Brain up to 1888 as such, using the simpler JH
Jackson before and after, with the comment ‘all part of the job’;
to which McDonald added ‘the patient with a refraction error
has blurred vision. They need spectacles’. Later he unearthed a
letter from Jackson to the House Governor at Queen Square requesting that a hyphen be placed between the two parts of his
name (Archive: letter, 17 January 1995). McDonald delighted in a
typically Oxonian reply to his enquiry, as editor, on how to deal
with the epicene ‘he’ and the general issue of
gender-transcendence in material printed by Oxford University
Press (Archive: annotation, 1 September 2006; and letter, 29
October 1998).
Throughout his life, McDonald set aside time to engage with
the arts, and his wide circle of friends included many individuals
professionally active in music, dance, the visual arts, literature and
history. His passion was music. A manuscript diary records
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McDonald’s impression of a concert given by the National
Orchestra of New Zealand. The concert was disappointingly
uneven; neither the orchestra nor conductor on their best form;
and the playing earth-bound:
the first half comprising a string of short pieces is an unwise
practice . . . and gives me little satisfaction . . . one was longing for
a Brahms or Sibelius symphony; the tone picture throughout
was dull; Wagner’s Ride of the Valkyrie was very badly
played . . . so blurred as to make it difficult to hear an individual
note – the players seemed very tired or bored (Archive: diary,
9 September 1953).
Taught piano by Ernest Empson in New Zealand and by Gigi
Wild in London, McDonald considered himself to be ‘of average
competence, being a useful accompanist in lieder and chamber
music from the baroque classical and easier romantic repertories’.
Jurg Kesselring, himself an accomplished cellist, would go further:
‘as a member of a trio he was exceptional: certain in rhythm,
intensely musical in his ability to see a long phrase within a
theme, and with the fingers led by the ear’ (see Brain 2006:
129; 3141–3146). Therefore, it was poignant that a small stroke
in 2004 removed, for a while, his ability to understand music, read
a score and play the piano. McDonald had listed as one of the
most memorable papers published in Brain during the latter half of
the 20th century (Supplementary material B108), the account by
Alf Brodal (1910–88) of his own stroke written with detachment
and from a position of unrivalled neuroanatomical knowledge (see
Brain 1973: 96; 675–694). With some encouragement from
others, McDonald published a characteristically erudite account
of his own intensely personal episode (Supplementary material
A215). Recognition came slowly. At first, many friends trained in
neurology attributed the difficulties he began to describe to professorial foibles and mild professorial eccentricity, until the evidence became clear about 6 weeks after the event. McDonald
made comprehensive notes describing the evolution of his difficulties and their recovery (Archive: notebook, 11 January 2005,
et seq.). He lists 10 lectures or articles to which he had committed
in the previous few months. Speaking on multiple sclerosis was
especially worrying because he was starting to feel remote from
the subject after 3 years of full retirement. He slept badly and
had attacks of migraine headache. On 28 October 2004, he
noticed difficulty packing shopping items in the supermarket,
and bumped into objects on the left. Over the next few days,
guests were served under-cooked food. A lecture in Cambridge
on 1 November 2004 seemed to go badly but without McDonald
realizing that many of his slides (then still in use) were
upside-down:
I looked at a clock but could not tell the time . . . nor could I
subsequently unless the hour hand of my watch was exactly on
a number.
He considered this and other lectures and after dinner speeches
poor by his own standards. At home, he wore his trousers
inside-out and could not button his cardigan. He failed to
A. Compston
recognize familiar faces. He saw objects that were not there and
tested his own left lower visual field but found no deficit. He could
not follow a musical score or accompany other musicians. An initial neurological opinion focused on recurring headaches; and investigations were not thought necessary. When McDonald gave
the FitzPatrick lecture (Supplementary material D8) on 6
December 2004 several slides were out of order:
In the discussion, A[. . .] asked a question. He was sitting in my
low left visual field and I couldn’t find him in the audience.
This alarmed him and some of the other neurologists there.
A[. . .] advised McDonald to reconsult his former colleague at
Queen Square, and to have his fields checked—somewhat to
the irritation of another neurologist from that institution standing
alongside who explained that ‘physicians at Queen Square are well
able to manage their own cases’. MRI carried out 6 weeks after
the ictus revealed a right parietal infarction and ‘everything fitted
together’. McDonald felt that the emphasis of his paper should
reflect two types of defect: reading music for simultaneous performance having elements of topographical errors and poor
bar-length memory and impaired unconscious recall of learned
pages; and impairment of the instinctive grasp of the emotional
content of music and its welcome return in the company of two
close friends well placed to encourage but not delude McDonald
in his abilities.
Just as the work of McDonald’s youth was published in Brain,
so too were his final publications. Together he published 42 papers
in the journal between 1960 and 2007. The last appeared posthumously and included proof corrections made shortly before he
died. That was the text of his Gordon Holmes Lecture, the 11th
endowed by the Guarantors of Brain and delivered on 4 April
2000 in Exeter, UK (Supplementary material D9). McDonald
wanted to celebrate the style and legacy for the present generation that, unlike himself, had not benefited directly from those
taught neurology by Holmes, especially JE (‘Jock’) Caughey
(1904–2000) and Denny-Brown; and to summarize the contributions with an emphasis on how these had shaped or otherwise
influenced his own work. He wrote:
Our lineage is a fabric woven of strands from many sources . . . I
shall explore how the nineteenth century heritage had influenced [Holmes] and how, in turn, he contributes to ours in
the twenty-first century.
Lectures and miscellaneous
writings
McDonald was sought after as a clinician and renowned as a lecturer and writer. He had the ability to synthesize a complex story,
and to place his own achievements in the context of illustrious
predecessors. Apparently easy and usually faultless performance
was based on meticulous preparation and attention to detail concealing personal modesty and some uncertainty. He was a
William Ian McDonald: 1933–2006
seasoned traveller whose many friends encouraged and looked
forward to his frequent visits. He provided professional hospitality
for visitors to Queen Square from around the world and an opportunity for younger neurologists to understand and make a contribution to investigative neurology. For over 30 years,
international students sought to be part of his team at Queen
Square, many establishing productive research groups on return
to their own institutions. He trained by example, lifting less
gifted colleagues, and reflecting with generosity and uncomplicated pride on their achievements.
McDonald kept typescripts, manuscripts and extensive working
notes of around 150 lectures given between the mid-1960s and
2004. Some were reworked and improved over time as he polished these oral presentations often retaining the same title even
though no two lectures were identical. Denis Brinton wrote:
your inaugural lecture couldn’t have been bettered. Its content,
its construction and your delivery were all perfect (Archive:
letter, 2 October 1974).
Letters of congratulation were received on that occasion, among
others, from (Sir) Roger Bannister, Alan Davison and John Walton
(Archive: Letters 9, 11 and 12 May 1974). McDonald retained,
among others working drafts of many named lectures: the Culver
(1977), Sandoz (1980), Silversides (1981), Zimmerman (1981),
Doyne (1983); Gowers (1985), Bradshaw (1986), Robertson
(1988), Foster Bennett (1989), Charcot (1991), Erasmus Wilson
(1991), Kroc (1992), Oppenheim (1992), Moore (1993),
McKenzie (1994), Alpers (1996), Richard Cave (1996), Gordon
Holmes Society (1997), Meadows (1997), Rennie (1998), Dystel
(1999), Gordon Holmes (2000), Charcot lecture (2001), Fitzpatrick
(2004), Sedgwick (not dated) and Milton Shy lectures (not dated:
see Supplementary material for a list of other named lectures and
research prizes).
The topics usually reflected his current interests or drew on
recent research. Recurring themes were lectures on the pathophysiology of nerve conduction (30); the general nature of multiple sclerosis (20); ocular manifestations of multiple sclerosis
(14); the dynamics of lesion production in multiple sclerosis (8);
other aspects of neuro-ophthalmology (23); compression of the
nervous system (8); the treatment of multiple sclerosis (6); the
philosophy of neurology and neuroscience (10); and pieces with
an historical flavour (19). He wrote obituary notices (20) of
former colleagues or others of importance in the history of
ideas. In later years, McDonald often used two titles:
‘Physicians: subsequence and consequence’ and ‘Chance and
design’. The Swithin Meadows lecture opens with the quote
from Samuel Johnson (1709–84): ‘It is incident to physicians, I
am afraid, beyond all other men, to mistake subsequence for consequence’; but goes on to explain the many ways in which this
amusing and provocative caricature could not in any sense be
applied to Meadows and his work on the visual system
(Supplementary material D7, B106). From there the lecture gradually turns to McDonald’s own studies of optic neuritis framed
around the questions patients ask as the episode evolves (duration, recovery and future implications); incorporating the personal
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| 2171
accounts of Peter MacKarell (1933–88) and Augustus d’Este
(1794–1848); and exploring optic neuritis as a window on the
pathophysiology and pathogenesis of multiple sclerosis (Archive:
annotated typescript, 1997).
In the Dystel prize lecture (‘Understanding multiple sclerosis:
chance and design in progress’), McDonald ends with the quote
from (Louis) Pasteur (1822–1985) of chance favouring the prepared mind, but first sets out his stall:
It often seems that each new piece of knowledge has derived
ineluctably from a careful pre-conceived design. In reality,
chance plays an important part . . . shortly after I had seen my
first patient with multiple sclerosis in 1953 . . . I acquired an
over-riding interest in mechanism. This, applied to multiple sclerosis, yielded three questions which have been an abiding interest: what is the mechanism of relapse? What is the mechanism
of remission? And what is the mechanism of irrecoverable deficit? (Archive: annotated typescript 1999).
Such was the design. The chances included the work with
Halliday on evoked potentials; and the opportunity to work on
brain imaging. Much that followed was designed but, in retirement, McDonald planned to follow-up on a chance observation,
made in 1961, relating to improved function despite persistent
conduction block of the cat diphtheritic peripheral nerve, by studying plasticity of the visual cortex following axonal degeneration of
the visual pathway in multiple sclerosis. He wrote formally to
David Marsden asking permission to ‘borrow’ the Leitz microscope
that McDonald had bought in the 1960s with his first Medical
Research Council grant. This was duly approved (Archive: letters,
12 and 15 June 1998) but, in the event, the research did not
materialize. Rather, he focused on domestic matters and started
to increase his involvement with the history of ideas and of neurology; and, in particular, considered writing an autobiographical
memoir.
Activities in retirement
Having served as member of Council (1989–92), McDonald was
appointed Harveian Librarian (the 13th to hold that office) at the
Royal College of Physicians of London (1997–2004). With a deep
appreciation of the aesthetic quality of ‘things’ the opportunity to
curate an important collection of books, portraits and medical
ephemera brought much pleasure. As Harveian Librarian,
McDonald was responsible for volumes X (1999: the first to be
accessible through the Internet) and (with his successor) XI (2006)
of Munk’s Roll, writing (or having previously written) several notices himself [Derek Denny-Brown, Roger Gilliatt, Denis Williams
(1908–90), Reginald Kelly, Dorothy Hodgkin (1910–94), Norman
Ashton (1913–99), HRH Queen Elizabeth the Queen Mother
(1900–2002) and Peter Daniel (1910–98): Supplementary material
E1, E4–6, E12, E17, E19–22]; and always knowing from whom to
charm biographies, no easy matter as the size and longevity of the
fellowship increased, making informed notices less easy to conjure.
He helped through to publication Lord Briggs’s History of the
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Royal College of Physicians of London: Volume IV (2005). He
researched independently and spoke on ‘The College and the
Service’ being a history of the relationship between the College
of Physicians and services for providing healthcare especially in the
20th century (Archive: letter, 8 July 1998; and typescript, 1998);
and he was much involved in the Paduan celebrations during
November 2002 for the quatercentenary of William Harvey’s
(1578–1657) graduation (Supplementary material B122). In
2001, with Geoffrey Davenport and Caroline Moss-Gibbons,
McDonald edited The Royal College of Physicians and its collections: an illustrated history (London, Royal College of Physicians),
describing the heritage accumulated since the Marquis of
Dorchester bequeathed his library to replace that lost by fire in
1666 (Supplementary material C18). He persuaded Council to
invest not only in archiving and conservation but also physical
preservation of printed material through the provision of climate
controls. McDonald was a staunch defender of the responsibility
the College has to those of its Fellows who built up the heritage
collection, thereby honouring one of the two principles that led
Thomas Linacre first to provide premises in Knightrider Street—a
meeting room and a library—for a College of Physicians. When
the sale of important items such as the ‘Wilton Psalter’ was
mooted, McDonald was quick to impress upon colleagues that
future generations would not trust a College that failed to
honour the terms of its legacies. And he argued that the library,
eclectic in its holdings, illustrates how physicians learned and were
educated down the centuries. The item that gave him most pleasure—for professional and historical reasons—was the manuscript
casebook of Sir Augustus Frederick d’Este (1794–1848), the son of
Prince Augustus Frederick, Duke of Sussex, and Lady Augusta
Murray (descended from James II of Scotland and Edward IV of
England), and grandson of George III. This had come to the
College in 1940, rescued from a rubbish heap at the
Leatherhead School for the Blind in the drive for waste paper
during World War II; a form of acquisition that was later contested
by the School’s Governors and only resolved (in the College’s
favour) over lunch in 1996 (Archive: letter from Mr Geoffrey
Davenport, 18 July 1997). The Case of Augustus d’Este informed
the lecture on ‘A problematic grandson of the mad King George’
(1997) that McDonald delivered in different forms and on many
occasions (including: Supplementary material B119, B123, D5).
Lectures usually began with an image of the portrait in miniature
of d’Este who McDonald first introduced as ‘this charming lad’ in
his Doyne lecture given in Oxford (1983), provided for him by
Mrs Mollie Gillen (Archive: letters from Mrs Gillen, 9 January
1989; 25 March 1989). There followed an account of the circumstances leading to the whirlwind romance of Augustus’s parents,
their marriages [in April 1793 (Rome) and again in November of
that year (London)] and the morganatic status assigned to those
marriages, which were annulled by the King. Now nameless,
d’Este’s father selected one of the family titles by which
Augustus could be known without complication thereafter.
McDonald weaves a clever thread in moving from social to medical history with the story of a former d’Este who had his eyes put
out through fraternal jealousy, to the onset of bilateral optic neuritis on which McDonald had himself published (Supplementary
material A67, A169), and Augustus during December 1822.
A. Compston
Familiar extracts from the diary follow, describing the course of
an illness that can now be recognized as relapsing–remitting, followed by secondary progressive, multiple sclerosis.
McDonald resigned shortly before completing his 7-year tenure
as Harveian Librarian (Archive: letter to Dame Carol Black, 9
September 2003). Later he wrote summarizing his views of a
tense meeting at which the findings of a working group on the
governance of the College had been aired in the presence of
those whom it criticized, leading to views expressed ‘in stronger
terms than I can remember being used at a meeting amongst medical colleagues’. Acting as mediator, McDonald conceded that the
report was direct in its language and he suggested diplomatically
that disclosure of its contents and discussion with those implicated
might have been better handled (Archive: letter, 22 February 2004).
McDonald contributed much to the social life of the College.
Through his obvious interest in themselves as people, the staff
held him in high esteem. When representing the College regionally
and abroad, and when dining with the College Club, conversation
was lively and informed, revealing the warmth and wisdom of
someone who enjoyed the company of others; knew a great
deal about medicine, history, literature and the arts: received
and gave much in friendship; and assumed the best in everyone
(until proved otherwise).
The history of neurology and of
Queen Square
With his fascination for historical matters of neurological interest,
McDonald considered various projects that would secure the oral
tradition of which he was part through having interacted intimately with many who, like himself, valued the rich heritage at
Queen Square. McDonald took a keen interest in the history of
that institution and delighted in historical anecdotes. It was his
intention to write a history of British neurology in the 20th century
with Queen Square at the centre. But he was disappointed to
learn that the Association of British Neurologists had already
agreed that a PhD student from the Wellcome Institute for the
History of Medicine (Stephen Casper supervised by Stephen
Jacyna) should have access to such archival material as the
Association had in its possession in order to do much the same.
Nevertheless, McDonald made a start. He played with
Denny-Brown’s version of Stanley Cobb’s (1887–1968) ‘tree of
neurology’ recorded on a glossy photograph onto which
McDonald added in manuscript the name of Denny-Brown
(Fig. 4). A taped conversation with Chris Earl recalled the young
MJ (Sean) McArdle (1909–89) presenting his controversial account
of nocturnal acroparaesthesiae, previously assumed to be due
to traction on the cervical nerve roots, as resulting from compression of the median nerve in the carpal tunnel, and being told by
Walshe:
we do not come to the ABN to be given a lecture on anatomy
by a registrar . . . what would he know about heavy fur coats . . .
nor did Symonds accept this interpretation (Archive: tape, 3 July
1997; typescript, 9 October 2010).
William Ian McDonald: 1933–2006
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Figure 4 A scheme for the evolution of knowledge in basic neurophysiology and the applications into clinical neurology.
Much of that conversation centres on Denny-Brown as did an
undated taped interview with John Eccles:
At Queen Square he startled the various honoraries by his questioning and by his fundamental knowledge of what went on
and by his, shall we say, resistance to much of the tradition in
neurology . . . the work in Oxford was remarkable for the nature
of postural tone . . . he should have equal recognition to Adrian
and Bronk in Cambridge for this work . . . it was he who laid
the foundation of postural muscle and phasic muscle . . . antidromic stimulation of motor neurones . . . it was all in
Denny-Brown’s thesis but it was hard to discover what was in
that thesis because it was a tremendous mine of information
but at the same time a little disorganized . . . we always thought
of the units and the basis of movements in those terms . . . he
was more interested in the integrated performance of the whole
animal (Archive: tape, not dated; typescript, 9 October 2010).
McDonald prompts Eccles by suggesting that Denny-Brown was
the first person to provide clear evidence that demyelination produces conduction block. Eccles continues:
These experiments arose out of injuries during the second world
war . . . later he described the pure sensory degeneration
associated with carcinoma of the bronchus . . . he had
Dupuytren’s contracture and when he decided to have one of
his fingers removed he had the nerve crushed several days before . . . there was some disagreement in the literature between
Graham Weddell and Denny as to what length of time after the
crush that the nerve was examined, and I remember Denny
saying to me ‘Well, it was my bloody finger!’ (Archive: tape,
not dated; typescript, 9 October 2010).
McDonald researched individuals who had lived in Queen
Square and he lectured at Yale on the subject: Dr Charles
Burney (1726–1814) and his daughter Fanny (1752–1840);
Jonathan Richardson (1664–1745), Martin Folkes (1690–1754),
William Morris (1834–96), Thomas Coram (1658–1751), Thomas
Denman (1779–1854), (Sir) Rickman Godlee (1849–1925),
Hughlings Jackson, (CE) Brown-Séquard (1817–94), (RL)
Stevenson (1850–94), (Sir Thomas) Parker (1695–1784) and (Sir
James) Mansfield (1733–1821). He drafted notes, probably for a
lecture, setting out the structure of his proposed history: the origin
of the Square, and of the hospital placed in it; the distinctiveness
given the enterprise by the quality of its staff—making brief notes
on (Jabez) Ramskill (1824–97: ‘no major contribution’),
Brown-Séquard, Jackson, Gowers, Ferrier, Horsley, Holmes,
Wilson, Walshe, Symonds, (AE) Carmichael (1896–1978) and
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Denny-Brown with remarks made by those he had known personally on themselves and their own predecessors. Walshe had gone
to work with Sherrington after World War II but found himself
unable to cope with experimental work and, in his later writings,
attacked physiologists. McDonald concludes that ‘his [Walshe’s]
contribution was not great’. On Symonds, the apocryphal story
on the ideal case at Queen Square is rehearsed: Symonds to take
the history, Holmes to examine the patient, Wilson to deal with
the differential diagnosis and Adie to speak to the relatives.
McDonald was much exercised by the somewhat notorious
stance of physicians at Queen Square on hysteria. Symonds’s
views on low moral fibre were especially controversial. He had
lectured at Queen Square on 27 February 1970 immediately distancing himself from the views of Eliot Slater (1904–83) and quoting the latter’s Shorvon lecture:
The diagnosis of hysteria is a disguise for ignorance, and a fertile
source of clinical error. It is in fact not only a delusion but a
snare.
Symonds’s subsequent survey of prevailing views during two
World Wars and in civilian life was factual but unsympathetic:
She had lain in bed for seven years before I . . . brought her
gradually, and not without a good deal of distress and humiliation, to realise that she had been unconsciously exploiting illness to her own advantage . . . I had little experience of hysteria
in the second world war, a notable exception being a hysterical
paralysis of the upper limb in a naval officer who subsequently
became an admiral. You never know where hysteria may be
lurking! (Archive: annotated typescript, 27 February 1970;
letter, 10 March 1970).
Denis Brinton wrote thanking McDonald for a copy of Studies
in Neurology, which McDonald had prepared and edited for
Symonds:
I much look forward to discussing with you what he has to say
on flying-stress but not in writing. How it brings back to me
those extraordinary days – the only good thing about them
being that an acceptable procedure was devised to avoid the
penalty of execution which certainly was followed in the First
War. But what Pavlov’s supposedly scared dogs have to do with
petrified air-crew I fail to understand, except as a kind of apologia pro sua vita for our beloved but insensitive teacher. Next
time, if there is one, there will not be any need for this kind of
unconscious hypocrisy (Archive: letter, 10 January 1975).
Although Symonds was austere he was vulnerable with respect
to a disagreement at Guy’s in the 1930s over who should retain
responsibility for patients with psychiatric disease. Symonds’s routine of being driven up to the hospital and not alighting until his
chauffeur had removed the rug from his legs before he entered
was varied following a disagreement with (Robert Dick) Gillespie
(1897–1945) in the 1930s by the chauffeur first taking a thermos
of warm milk from the boot, which Symonds drank before entering the hospital, flanked by his assistant Denny-Brown so as to
A. Compston
brace himself for confronting his colleague (Archive: 3 July 1997;
typescript, 9 October 2010).
McDonald wrote extensive notes on his reading of Ben
Shepherd’s War on Nerves while travelling to Japan and New
Zealand, speculating on the extent to which Holmes’s rigid approach had resulted in less than the expected numbers of neuropsychiatric cases during the Blitz:
Either the estimates were falsely low; or remaining within the
family unit was influential. Holmes disliked neurotic patients and
regarded soldiers who had broken down as ‘cowards’ His approach to civilians was brusque and ‘no nonsense’ with encouragement and suggestion. Holmes’s contribution to the
management of psychiatric disorders in war and peace is at
best ambiguous. By temperament he was unsuited to the treatment of individual depressed and anxious pts. His legacy in the
second war is seen in the LMF [low moral fibre] episode. The
sections on Symonds in War on Nerves make it clear that he
disliked the term LMF believing that a punitive approach should
be adopted towards those who broke down under stress as a
deterrent to others. What is clear is that the no nonsense approach suited the temperament of Holmes and Symonds
(Archive: manuscript, 17 December 2000).
McDonald was much influenced in his own thinking on hysteria
by Slater; he wrote to Sir Martin Roth (1917–2006):
Slater had an interesting position in relation to psychoanalysis
and the operations of the unconscious. Though formally deeply
opposed to Freudian procedures – as so beautifully laid out in
his Mapother lecture – he nevertheless accepted as highly suggestive, if not valid, the consequences of some of the mental
processes that he was so cautious about . . . he told me that he
had done the Rorschach test himself and thought that ‘it hit
several nails squarely on the head’. . . Slater [concluded] . . . that
one could make a case for regarding psychoanalysis as a branch
of hermeneutics (Archive: 16 February 1996).
On Denny-Brown and the foundation professorship of clinical
neurology at the Institute of Neurology, McDonald wrote:
in decade and ½ following WW II it was a common place to say
that QS was not what it was. The problem was that it was what
it was – immensely distinguished clinically, with physicians of
highest calibre who were selected by great figures of the earlier
20th century but as replicas of themselves. What it lacked was
imagination and flexibility. The major contributions were not in
neurology but in pathology. Greenfield was at his zenith and
radiology grew in stature under Hugh Davies [1905–67] and
James Bull [1911–87]. The major reason for neurology being
static at QS was the lack of a proper academic base. This was
largely due to opposition of older staff to the notion of a professor. When Carmichael was offered a chair, as a junior physician and secretary of the medical committee, he was told that it
was the wish of his colleagues that he should decline it. Finally,
the University insisted. Denny-Brown turned down the invitation
but in doing so set out what a modern department of neurology
William Ian McDonald: 1933–2006
should be. Denny-Brown vouchsafed that RWG was the only
hope for QS . . . ‘I do not think it too much to say that that hope
has been realised in ample measure’. That letter was influential
because so great was Denny-Brown’s prestige that the powerful
forces of clinical reaction yielded when it was managed with
consummate skill by Gilliatt and the Deans early in his period.
It will be for someone else a decade hence to say whether QS
has retained its flexibility to shift its emphasis in response to the
shift in the most promising fields of neuroscience to the molecular level on the one hand and the integration of physiological function and its disorders and those of the brain on the other
as Jackson foresaw (Archive: manuscript, July 1987).
McDonald opened one of his notebooks on the proposed history of Queen Square with various anecdotes: the arrogant style
of the 1950s; Mrs Greenfield commenting in 1967 when lunching
with McDonald and his mother that ‘she had never been to
Queen Square’; (Samuel Alexander) Kinnier-Wilson (1874–1937)
telling his colleagues that it would not be necessary for them to
write a textbook of neurology since the matter was already in
hand; and anger over the precociousness of Russell Brain in writing
a textbook of neurology that was not from Queen Square. The
key post-war events were establishment of the Medical Research
Council Unit directed by Carmichael [(John) Bates, (Pat) Merton
(1920–2000), Dawson and Halliday)], the closure of the animal
house, the contributions of Slater, (James) Purdon-Martin (1893–
1984), CS (Charles) Hallpike (1900–79), Davies and Bull. He researched progress though Annual Reports of the Institute of
Neurology throughout the 1950s listing some of the people who
passed through, and their work, but without comment (Archive:
manuscript, not dated). The memoir he wrote on Julius Althaus
(1833–1900) for a volume on the founders of child neurology was
rejected by the editor, Stephen Ashwal, as being ‘superfluous to
the requirements of the book’.
A great collector of ephemera relating to the National Hospital,
Maggie Magnusson, ward sister, passed on to McDonald
her material relating to the early history of nursing, and the
proposed establishment of a convalescent home at Ramsgate in
1868, eventually established at Finchley in 1870 using houses
sold by a Mrs McDonald (no relation). McDonald also kept
material relating to the centenary celebrations in 1960: the
programme for June 1960; the exhibition organized by William
Gooddy, Richard Hunter (1923–81) and (John) Hamilton
Paterson (1915–62) with help from Macdonald Critchley; and
Critchley’s article on the ‘Beginnings of the National Hospital,
Queen Square’ published in the British Medical Journal for 18
June 1960.
The book was to include interviews with selected neurologists in
order to record their views on the history of British neurology in
the 20th century; and McDonald held a series of meetings with
Christopher Earl and George Du Boulay (1922–2009) to discuss
changes in neurology over the previous 50 years. Gooddy considered that an interview could not do justice to his own contribution—as the first-ever regular user of penicillin at St Hugh’s
College in Oxford. He hinted that this history was a matter for
someone of his own generation, such as John Potter (1922–2002)
from Oxford to relate; and, in any case, Gooddy was unable to
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| 2175
travel to London because of phobia and polymyalgia rheumatica.
John Walton was enthusiastic about telling the story of neurology
in Newcastle; and their conversation was taped (but is lost). (John)
Ian Simpson (1922–2009) remembered having to lecture, many
years earlier, on how neurology might develop and expressed
interest in comparing his predictions with a retrospective assessment. Peter Nathan felt that he had not been involved in any
important contributions but suggested that imaging, antibiotics,
rational pharmacology, measurement of nerve conduction and
drug treatment of schizophrenia were the main advances.
Elsewhere Peter Nathan recalled the enmity between Holmes
and (Thomas) Grainger Stewart (1877–1957) who had fought
physically in the hall of the Hospital. When a patient with hysteria
was in one of Holmes’s beds he would tell the resident ‘that Dr
Stewart should see this patient’. Wilfred Trotter (1872–1939) was
acerbic in theatre when addressing a poor trainee, or in referring
to his consultant colleague, Walshe:
‘we have reached a difficult stage, I shall not be needing your
assistance . . . surely Mr anaesthetist, you can stay awake if the
patient can’ . . . ‘Walshe, challenged by a case and remarking
that it was time he gave up neurology; “why don’t you take
it up?” ’ (Archive: letter, 13 May 1996).
Bryan Matthews pointed out that he had never worked at
Queen Square and most of his memories were therefore of provincial figures. Edwin Bickerstaff (1920–2007) was enthusiastic but
mentioned that he no longer understood much of academic neurology; the title of papers at the Association of British Neurologists
being incomprehensible compared with talks such as ‘on syringomyelia’. McDonald interviewed the nonagenarian Barney Alcock
(1909–2006) in the Royal Clarence Hotel, Exeter. At Queen
Square, Alcock had:
imposed himself on Greenfield . . . Purdon Martin was someone
you needed to talk to find out what he thought but as soon as
he started lecturing, it was v. dull . . . he had a facility for making
it duller than anyone else . . . [William] Adie [1886–1935] quite
the nicest person I met amongst the consultants . . . when
George Vth died in 1935 Holmes said we’ll walk over to
Southampton Row to see the coffin on its way from Euston
With PoW walking behind . . . crown fell off the coffin . . . SAK
Wilson was magnificent . . . relationships between consultants
‘guarded’ . . . Symonds aloof and very well dressed . . . 1930s
practically no neurology outside London apart from some
in Manchester and Newcastle (Archive: manuscript, 20 July
2001).
There were stories from Richard (Dick) Chambers:
Walshe wrote the review of protopathic and epicritic sensation
about 1921/2 and showed it to Wilfred Trotter who said not to
publish it until after Henry Head had died; it appeared in Brain
in the early 1940s [see Walshe FMR The anatomy and physiology of cutaneous sensibility: a critical review. Brain 1942: 65;
48–112] . . . Paul Yakolev told Chambers that [Joseph] Babinski
[1857–1932] stayed with Henry Head in London. He spoke no
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| Brain 2011: 134; 2158–2176
English but on retiring wanted to use a bidet and summoned
the butler who spoke no French; he therefore used sign language to indicate what he wanted and the butler construed the
gestures as Babinski propositioning him and resigned from the
household (Archive: manuscript, 17 May 1996).
Ronald Henson (1915–94) acquired an extensive archive of correspondence between Henry Head and his future wife Ruth
Mayhew covering the years 1897–1904 given to him by Head’s
sister, Mrs Hester Marsden-Smedley. These were edited but the
piece unfinished when a stroke prevented Henson from continuing
with his work. The letters were passed to the Wellcome Library.
McDonald’s interest in history led to a request in 1995 from
Frances Henson that he might use the biographical material collected by her late husband, and publish a paper on Head. In time,
McDonald crafted a piece of lasting value from the already comprehensive and insightful working notes (Supplementary material
B98). ‘Henry Head: man of culture, compassion and science’ appeared in 1998. One figure shows a cartoon of Head drawn in
1913 by a medical student, William Morris (later ENT Surgeon to
the London Hospital; dates not known), who also wrote on James
Parkinson: Head is stroking the plantar responses and exclaiming
sotto voce ‘Ah . . . ! Ty . . . pi . . . cal, ty . . . pi . . . cal!’, evidently a
verbal mannerism mimicked by the students and finding its way
into Robert Graves’s (1895–1985) autobiography (Goodbye to All
That). The image of Head and (WHR) Rivers (1864–1922), originally in the possession of Oliver Zangwill (1913–87), that
McDonald reproduces, is not the one with both quietly contemplating the experiment that appears in Henson’s paper on ‘Head
and sensation’ (see Brain 1961:84;535–550); rather it is a rare
shot showing Head grimacing as Rivers applies the stimulus. The
phrase ‘all of whom were patients’, present in the manuscript in
connection with the names of (William Ernest) Henley (1849–
1903), Siegfried Sassoon (1886–1967), Graves and Robert
Nichols (1893–1944) (Archive: letter, 1 September 1997), is
omitted from the printed version.
Outside the realm of British neurology, McDonald pursued, for
a while, an interest in the nature of the illness affecting AWN
Pugin (1812–52: English architect, designer and theorist of
design). Rosemary Hill provided much archival material. (Sir)
Richard Bayliss (1917–2006) wrote at length arguing that Pugin
had syphilis. McDonald suggested bipolar disease as an alternative,
based on his work on John Ruskin (1819–1900); he sought Pugin’s
medical records from Bethlem Hospital, and the advice of colleagues working in neuropsychiatry who suggested that the
answer might be mercury poisoning (Archive: letters, 31 August
2004; 1 September 2004).
At the time of his death McDonald had drafted notes for a
manuscript that suggested Charles Édouard Brown-Sequard
(1817–94) as the role model for Dr Jekyll and Mr Hyde, published
by Robert Louis Stevenson (1850–94) in 1886 (Archive: notebook,
2006). McDonald’s researches were thoughtful but preliminary
and summarized only as working notes that he had typed up
A. Compston
headed ‘Was Dr Jekyll a neurologist?’ but did not develop further
(see Brain 2011:134;1869–1871) This will be the July editorial.
In retrospect
Contacts outside medicine cultivated by McDonald and his civil
partner, Stanley Hamilton, were important. Several revolved
around the Garrick Club (London), membership of which he cherished. They provided a reference point for his professional work
and a rich source of information and anecdote that he used in
conversation, and to decorate his own writings and lectures. His
conversation was lively. He was assiduous in sending handwritten
notes expressing gratitude or appreciation, often attaching items
that he considered wry or amusing, culled from the many sources
he accessed on a regular basis, and which revealed his affection—
occasionally waspish—for the foibles and witticisms of social intercourse in public and private life. And he did not forget the more
frail and retiring of those friends with whom he had engaged in
medicine and the arts down the years. Because he was so widely
read, McDonald was a clever wordsmith. He was particularly
pleased to be elected Foreign Member of the Venetian Institute
of Science, Arts and Letters; and the connection with Venice was
evident in the enthusiastic review he wrote of a tricky case solved
by Commissario Brunetti (Through a Glass Darkly) by the
thriller-writer he much admired, Donna Leon, in the Times
Literary Supplement (Supplementary material F209).
Whereas his friends were surprised at the lack of public and
professional recognition for his contributions in the form of a
civil honour and other indicators of professional achievement in
the sciences, these omissions soon became matters of lofty indifference to McDonald, who well understood the hits and misses of
accolades in professional life. By nature a romantic, steeped in
history, McDonald absorbed the legacies of those that came
before, sought to carry the banner for a while himself, and
hoped that the attitudes and style he espoused would survive in
the activities of the school he created. Ian McDonald’s lasting
contribution is to have illuminated the clinical science of multiple
sclerosis. For nearly half a century, people with that difficult disease had no better a professional friend.
Acknowledgements
Short passages of this article, especially ‘In restrospect’, are reproduced verbatim from various Obituary notices written by the
author soon after McDonald’s death in December 2006; these
are not otherwise identified.
Supplementary material
Supplementary material is available at Brain online.