INTRODUCTION
In the transcript of his Nobel Oration for the 1976 Award in Physiology or Medicine,
Baruch S. Blumberg refers to David Surrey Dane nine times.1 Dane joined the Queen’s
Belfast Microbiology Department in 1955. He was soon promoted to Senior Lecturer,
then Reader. In 1966 Dane was called to a Chair of Microbiology at the University
of London tenable at the Bland-Sutton Institute and the Middlesex Hospital. Baruch
S. (Barry) Blumberg (Fig. 1), David Surrey Dane (Fig. 2), Michael G.P. Stoker (Fig.
3) and Wolf Szmuness were responsible for wide-ranging advances in alleviation of
pandemic Hepatitis B. This quartet of physician scientists each had outstanding World
War II records and post-war guidance: each was a personable and talented leader2,3,4,5,6,7.
Fig 1
Baruch Samuel Blumberg (1925-2011). Oil on canvas, 1993 by Paul Brason, RP (b.1952),
118” X 86”, Balliol College Portraits Collection No. 174. Master of Balliol 1989-94.
Baruch Blumberg entered the U.S. Navy in 1942 and rose to command a U.S. Navy Landing
Ship (Tank). Blumberg was winner of the 1976 Nobel Prize and elucidator of the hepatitis
virus which still infects over 270 million persons. Reproduction rights granted solely
for this Medical History.
EDUCATION
David Maurice Surrey Dane was educated at Charterhouse School, Surrey, England. (Fig.2).
In October 1942 he was gazetted as a Second Lieutenant in the British Army8. In 1943,
Dane joined the British Parachute Regiment and was seconded to the Special Air Service
(SAS). Having been taught in Northern Ireland to organize the construction of clandestine
advanced landing strips, Dane wrote, “I saw a Coastal Command Hudson which crashed
and blew up in spectacular fashion when coming in to land at Aldergrove aerodrome
with a full load of depth charges on board” 9.
Fig 2
David Surrey Dane (1923-1998). Photograph reproduced with permission of Vox Sanguinis
18 exclusively for this Medical History. After a distinguished academic career at
Queen’s Belfast and London University, Professor David Surrey Dane contributed greatly
to donor screening protocols to assure the safety of the British blood supply. His
approach was always, “meticulous, patient and sensible”. For many years, until 1995,
DSD was advisor to the U.K. Ministers of Health.
Dane was dropped at 1:00 a.m. on 28th June 1944 from an RAF Stirling bomber into a
field 250 miles east of Normandy9,10. After exit, his parachute collapsed then reopened
at low level. As part of SAS Operation Bulbasket in Nazi-occupied France, Dane organized
the building of advanced landing strips; Dane’s main French strip was named Bon Bon.
On 7th August 1944 Wing Commander Alan Boxer and Flight Lieutenant Abbott flew two
Lockheed Hudsons into Bon Bon to evacuate Allied survivors of Bulbasket: thirty-five
out of fifty-five, 64 percent, had been lost9. Dane had to wait at Bon Bon for four
more days until a USAAF C-47 (DC3) arrived, piloted by Colonel Clifford Heflin who
picked up Dane, five USAAF pilots shot down by German forces, and two British signalmen9.
Colonel Heflin later became commander of the 216th Army Air Forces Base Unit Special
Airfield for the Manhattan Project and was awarded the Legion of Merit by Eisenhower,
and the French Cross of War and Legion of Honor11.
Fig 3
Sir Michael George Parke Stoker CBE FRS MD FRCP (4 July 1918 – 13 August 2013). Master
of Clare Hall, Cambridge University; elucidator of the polymorphism of viruses, bacteria
and cancers. Central panel of triptych, black-and-white drawing of three former Masters
of Clare Hall by Bob Tulloch (1950-), 1988, 13.5” by 10.25”. Reproduced with permission
of the artist and Clare Hall.
SAS HQ staff did not appreciate Boxer’s refusal to repeat flying an RAF Lockheed Hudson
into Bon Bon necessitating Colonel Heflin to fly in his C-47. SAS HQ telegrammed “Bulbaskets
to you Boxer”9,10. Boxer was later knighted. Boxer was technically correct: C-47s
were more suited to Bon Bon. By December 1943, one C-47 was being produced in the
United States every thirty minutes12 (Fig. 4).
Fig 4
“Green Light, Jump”. Oil on canvas, 1994, 18” x 36”. by Craig Kodera (1956-). Reproduction
courtesy of the Greenwich Workshop, Inc., Turnbull, CT, solely for this Medical History.
This painting depicts the arrival of C-47s into German-occupied France in June 1944.
In the spring of 1945, Dane took part in Operation Howard in which Regiment 1 of the
SAS under Royal Ulster Rifleman Lieutenant Colonel Blair (Paddy) Mayne covered the
4th Canadian Armoured Division as they advanced to the Baltic through Northern Germany13.
For exemplary heroism in bitter fighting, fellow Ulsterman Field Marshal Montgomery
recommended fellow Ulsterman Mayne for the Victoria Cross. In his Memoirs, Montgomery
writes “In the end we beat the Russians to Lübeck on the 2nd May 1945 and thus sealed
off the Danish peninsula with about six hours to spare before the Russians arrived”13
(Fig.5). Dane wrote for Field Marshal Montgomery one of three testimonials for Mayne’s
VC : finally it became, although almost unprecedented, a third bar to Mayne’s DSO14,15,16,17.
Dane arrived at Clare College, Cambridge in October 1945 to read Honours Natural Science
Tripos18,19. Unusual for an undergraduate, although he had been an active member of
the Charterhouse Bird Club20. While at Clare, Dane published three different papers
on epidemics in Manx shearwaters in Skomer and Skokholm islands off Pembrokeshire21,22,23
(Fig.6). The co-author of one paper was Michael G.P. Stoker, Dane’s and later my*
Clare Medical Tutor23,24,25 (Fig. 3). On 2 February 1948 Dane wrote from Clare College
to Ibis about the severe outbreaks of “disease among juvenile Manx shearwaters, Puffinus,
puffinus” in 1946 and 194722. Juvenile Manx shearwaters develop blisters on webs of
their feet and or conjunctivitis, frequently followed by early death before leaving
their natal burrow25,26.
It has been estimated that approximately half of the world’s Manx shearwaters are
born on the coasts of St. George’s and North Channels. The 300-acre Old Lighthouse
Island, situated two-and-a-quarter miles off the coast from Donaghadee North Down,
Northern Ireland, is the second most prolific site of hatching27.
About five weeks after hatching, parents leave the area, and the offspring a week
or so later. By banding it has been shown that Manx shearwaters migrate across the
Atlantic to Brazil and the United States27,28. On the way they seem to rest and refresh
at human watering holes like Biarritz and the beaches of Sao Paulo, Brazil. Currently,
twenty-six are visiting Cape Cod, Massachusetts28. Manx shearwaters can take as little
as twelve days to fly from Boston’s Logan Airport area beaches to Northern Ireland
or the West of Scotland—roughly the same time duration as the 1846 news of the success
of diethyl ether in anaesthesia and surgery29.
Fig 5
Field Marshal Bernard Law Montgomery (1887-1976), the First Viscount Montgomery of
Alamein, KG, GCB, DSO, Hon. LLD Queen’s University Belfast: son of the Rt Rev H.H.
Montgomery KCMG and Lady Montgomery, by Terence Tenison Cuneo (1907-1996), 1972, oil
on canvas, 125 cm x 100 cm. From the collections of the Defense Academy of the United
Kingdom, Watchfield, Shrivenham, Oxfordshire, and reproduced with their permission,
solely for this Medical History.
After passing Conjoint in 1951 from St. Thomas’s Hospital, Dane emigrated to Australia.
In the spring of 1955, Dane returned from the Institute of Medical and Veterinary
Science in Adelaide18,19,30 to Clare and Cambridge, from which in 1955 he received
an M.B., and I received a B.A. Also in 1955 David Surrey Dane married Veronica Tester
Hope, a widow, with two children Kerin and Alex. This family of four moved forthwith
to Belfast, where the Danes later had three additional children: Roland, Penelope
and Thomas18,19. That same year, 1955, Dane joined Professor George Dick’s Department
at Queen’s University, Belfast, where in the winter of 1956 they developed plans for
a Virus Reference Laboratory which became operational within the year18,19,30,31.
Dane also started a research programme “which aimed at identifying human hepatitis
viruses by electron microscopy”32. In 1969, “some doubted whether Australian antigen
was specifically related to hepatitis B virus”2. In a letter invited by Eugene Garfield
to Current Contents in 1980, Dane wrote that he “thought that [by the 1960s] EM and
negative staining techniques had developed to the stage where they could be used by
virologists”32. Dane and his Belfast coworkers used specimens negatively stained with
“4% phosphotungstic acid at pH 6.5 and applied to formvar/carbon grids before examination
in an A.E.I. EM 801 electron microscope”3. Hepatitis B virus was found by Dane to
be a particle 42 nm in diameter with DNA and DNA polymerase3,32, later eponymously
named the “Dane particle”32. Dane wrote that “I never discovered whether the person
who originally referred to it this way was a well-wisher who thought we were right
or someone who hoped we were wrong”32.
OXONIAN MYSTERY
In 1978, 19 Manx shearwaters sick with puffinosis were transported live to Oxford
from Skomer and Skokholm islands. A homogenate from each freshly decapitated bird
was injected separately into Oxford Dunn Pathology mice randomly inbred since 1953.
One to 3 day old suckling mice were injected intracerebrally and subcutaneously. Eight
to 11 day old fertile hens’ eggs were injected as also were various cell cultures.
Two days after inoculation, two of the mice showed clinical signs of infection, one
with paralysis. Sera from the Manx shearwaters were not collected after inoculation
due to “difficulties keeping the birds” in Oxford26. The virus that was isolated differed
from that found in 1948 by Stoker33. Probably the coronavirus at Oxford they discovered
was from an Oxford Dunn School of Pathology mouse. Electron microscopy was non-diagnostic
of puffinosis. Nuttal and Harrap, whose work was funded by the National Environment
Research Council (NERC), stated “We are studying puffinosis because, unlike many epizootics
in wild animal populations detailed investigation is possible”26.
According to Michael Stoker on a visit to me at Harvard Medical School34, David Dane
thought that the Oxonians had wider aims. Stoker told me that the study had led to
Clare discussions. Did Oxford want to allot to Manx shearwaters the role of carrier
pigeons? Or were they manufacturing an opportunity to test their electron microscopy
specimen preparation and imaging techniques? We concluded, said Stoker, we should
not ascertain.
ADVANCES AGAINST HEPATITIS B IN THE U.S.
Warsaw-born Wolf Szmuness, who had studied medicine in Italy, returned to his family
in Poland after the 1939 German invasion. He then fled to the Soviet Union where he
was confined to a Siberian labour camp at which he was eventually assigned duties
of sanitation management and epidemiologic records. Post-release he received a medical
degree from the University of Tomsk in 1950, an advanced scientific degree from the
University of Kharkov in 1955 and an additional degree from the University of Lublin
in 1964. In 1968 he left Poland with his family and emigrated to the United States
where he met with Dr. Aaron Kellner, President of the New York Blood Center to discuss
career prospects2,4. They consulted Barry Blumberg (Fig.1) and together decided that
Szmuness should work as Kellner’s technician. Wolf Szmuness published in 1980 on the
efficacy of Blumberg anti-hepatitis B vaccine produced by Merck in a Controlled Clinical
Trial in a high-risk New York Population5.
DAVID SURREY DANE’S AND MY MEDICAL TUTOR AT CLARE
Michael Stoker was born in Taunton, Somerset on 4 July 1918 just after his Corkonian
physician father, Cork Medical School-educated, had returned from France with an M.C.24,35,36,37,38,39
and relocated the family to Market Harborough. Michael, aged 8, was sent as a boarder
to Oakham and thence to Sidney Sussex, where the pre- Cromwellian silver fascinated
him and Veronica English. They married in 1942, the year Michael passed conjoint.
In 1943 Michael was sent as an RAMC Lieutenant to the 3rd/9th Ghurkas in Northern
India39. Douglas Black, later PRCP, London, arranged for Stoker to enroll in a course
in laboratory medicine run by William Haye, a bacterial geneticist in Poona. Together
they studied virus activity in Herpes simplex and the bacterial antigenic variation
of Rickettsiae. After World War II, Henry Thirkill, M.C., Master of Clare, called
Michael Stoker and Veronica and their son to Clare, with Michael as Clare Medical
Tutor for Honours Natural Science Tripos.
From Clare, Michael Stoker expanded the horizons of H.R. Dean’s Cambridge Department
of Pathology. Stoker used electron microscopes in the Cavendish Laboratory of Rutherford
and later Pippard40.
As we were Stoker’s tutees our job was to educate Stoker: subjects such as Antigenicity
versus Infectivity. Polymorphism—“have you chased the Beagle?” What about the scientific
verse of Grandfather Erasmus? What about Medical Management of the aftermath of the
Quetta Earthquake? 41,42 Much of these discussions took place in Veronica’s house,
not at Clare.
LONG TERM EDUCATION
After I went down from Cambridge, Stoker, for decades would send me, his “perpetual
student”, a postcard after I had published in the Scientific or Medical Literature.
Nearly all messages were short. “Congratulations.” “Surprising but believable”. “Talk
to Aage Bohr”. Re: our ICU and Thomas Huckle—“Do it”43,44.
In 1961-1962 while I worked on “impaired oxygenation in surgical patients” at Harvard45,46.
Michael Stoker, now Professor of Virology at Glasgow, advised as to the management
of viremia44. My Harvard Department Heads E.D. Churchill and H.K. Beecher47 along
with M.G. Stoker declined co-authorships:”that is not our style”44,46.
STOKER FAMILY RELOCATIONS
After Clare, the Stokers had nine years in Glasgow, then California, then great success
from 1968 at the Imperial Cancer Research Fund Laboratories introducing Genetics and
more fundamental Molecular Biology. Michael used to say his co-workers and tutees
converted him from Virology to Cell Biology. Knighted in 198048, from London he and
Veronica went back to head up Clare Hall for seven happy years. Then Michael returned
to his Cambridge Pathology Laboratory to continue work on hepatitis B and hepatocellular
cancer49,50,51,52.
Fig 6
Manx Shearwaters over the Sea, lithograph of 1967 painting by Keith Shackleton (1923-2015).
GLOBAL SITUATION
Each year an estimated 887,000 humans are killed by hepatitis B53; how many thousands
of non-humans we do not know. Hepatitis B has solely infected humans and other hominidae
and simian species for at least the last 7,000 years54,55. Currently hepatitis B infects
257 million people worldwide53,56. The “Northern Ireland Hepatitis B and C Managed
Clinical Network” has reported that Northern Ireland is a “very low prevalence country”
for hepatitis B57. Much progress has been made in vaccination of healthcare workers,
as well as mothers and their offspring58,59.
Investigators from the Regional Virus Laboratory at the Royal Victoria Hospital, Belfast,
with colleagues from the Liver Unit, Department of Genitourinary Medicine and HIV
and the Public Health Agency of Northern Ireland have recently suggested a higher
than expected rate of progression from acute to chronic hepatitis B among persons
aged 50 and over in Northern Ireland60. Patients co-infected with HIV show hepatitis
B chronicity rates as much as six times higher than hepatitis B patients who are HIV
seronegative. While such co-infection is relatively rare in Northern Ireland, the
overall aging of the population amid higher hepatitis B chronicity rates emphasizes
the importance of vaccination and provision of accurate information to patients.60
“This plague has come upon us by infection and will spread still further”61 †. Before
you travel to foreign parts ascertain your vaccination status56.
ACKNOWLEDGEMENTS
The authors wish to thank Ms. Anna Sander, Archivist and Curator of Manuscripts, and
Professor Seamus Perry, Balliol College Oxford, for assistance with permission to
reproduce the portrait of Baruch S. Blumberg. The authors wish to thank Mrs. Catherine
Smith, Archivist, Charterhouse School, for archival material about alumnus David M.
Surrey Dane. The authors wish to thank the editors of Vox Sanguinis for permission
to reproduce the photograph of David Surrey Dane. The authors wish to thank Prof.
Frances Spalding and the Fellows of Clare Hall, and artist Bob Tulloch for permission
to reproduce the portrait of Sir Michael Stoker. The authors wish to thank the staff
of the Defense Academy of the United Kingdom for permission to reproduce the portrait
of Field Marshal Montgomery. The authors wish to thank the representative of the estate
of the late Keith Shackleton, for permission to reproduce the lithograph based on
Shackleton’s 1976 painting “Manx Shearwaters over the Sea.”