PE R S PE C T IV E
from tuberculosis.2 Yet Koch would time for the 100th anniversary of
no doubt find it rewarding that,
after a decades-long standstill, re-
newed interest in tuberculosis has
led to clinical trials of several new
candidate drugs and vaccines in
medical history
The Medical Detectives
Howard Markel, M.D., Ph.D.
O n a hot and steamy summer
day in Berlin August 4,
1890, to be precise the 10th Inter-
national Medical Congress opened
with a flair and fanfare that few
conference-weary doctors of the
21st century would recognize. At
the invitation of Kaiser Wilhelm
II, almost 6000 physicians from
around the globe flocked to the
city that represented the modernity
and optimism of medical progress.
Perhaps even more enticing was
the jam-packed program of lectures
delivered by a veritable whos who
of medical greats, including Joseph
Lister, Rudolf Virchow, and James
Paget.
Topping the bill two days lat-
er, on the afternoon of August 6,
was none other than Dr. Robert
Koch, perhaps the greatest med-
ical detective who ever lived. Dur-
ing the preceding 14 years, the
distinguished professor of hygiene
and bacteriology at the University
of Berlin had become a household
name as he successively discovered
the microbial causes of anthrax
(in 1876), tuberculosis (in 1882),
and cholera (in 1883). Although
Koch was never a commanding
speaker (he reputedly had a thin,
reedy voice and tended to infuse
his sentences with a distracting
number of ums and ers), his
colleagues had long since learned
to pay closer attention to his words
2426 n engl j med 353;23
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Copyright 2005 Massachusetts Medical Society. All rights reserved.
robert koch, the nobel prize, and the ongoing threat of tuberculosis
1. Koch R, Gaffky G, Pfuhl E. Gesammelte
his Nobel Prize.
Dr. Kaufmann is the director of the Depart-
ment of Immunology at the Max Planck In-
stitute for Infection Biology, Berlin.
than to his style of presentation,
knowing that still another demon-
stration of something spectacular
was likely to transpire.
The eager physicians filling the
seats of the stifling-hot auditorium
were not disappointed. Within mo-
ments after beginning his speech,
Koch announced that he had dis-
covered a remedy for tuberculo-
sis. As expected in a world con-
nected by telegraphs and multiple
editions of newspapers and mag-
azines and one in which tu-
berculosis was a leading cause of
death and illness Kochs discov-
ery made news around the world.
Hours after the lecture, physicians
began to clamor for supplies of
what was then called Kochs
lymph to treat their desperate pa-
tients. The excitement only inten-
sified when the lecture was for-
www.nejm.org december 8, 2005
The New England Journal of Medicine
Werke von Robert Koch. Leipzig, Germany:
Georg Thieme Verlag, 1912.
2. Kaufmann SHE, McMichael AJ. Annulling
a dangerous liaison: vaccination strategies
against AIDS and tuberculosis. Nat Med
2005;11:Suppl:S33-S44.
mally published in the November
13, 1890, issue of Deutsche Med-
izinische Wochenschrift and reprint-
ed, in English translation, in the
November 15, 1890, issue of the
British Medical Journal.1 The fol-
lowing day, the front page of the
New York Times heralded the rem-
edy as Kochs Great Triumph.
The Discovery Called a Greater One
Than Jenners.
Koch was careful never to
state explicitly that he had dis-
covered a cure. Instead, he re-
ported that his remedy destroyed
the tissue in which the tubercu-
losis germs had settled, so that
the entire diseased area would
simply be sloughed off and then
expelled through coughing. More-
over, Koch was careful to state that
the remedy worked best in cases
that were not too far advanced,
although he theorized that it might
be of some benefit in patients with
large pulmonary cavities.
One of the millions of people
reading about this incredible dis-
covery was a young general prac-
titioner who was struggling to
build a practice in Southsea, Great
Britain. During the long stretch-
es of time between appointments
with his patients, the doctor took
up his fountain pen and wrote
beautiful essays, stories, and even
novels. In 1887, only a few years
before Kochs announcement, the
PE R S PE C TI V E
young doctor had published a
novel entitled A Study in Scarlet in
Beetons Christmas Annual. It was a
compelling tale that introduced
the world to a character destined
to become the most famous de-
tective ever to grace the written
page. The sleuths name was Sher-
lock Holmes, and he employed a
method he called deductive rea-
soning, which was actually based
on the diagnostic approach of a
doctor. The physician author, of
course, was Arthur Conan Doyle.
In his 1924 autobiography,
Conan Doyle described the Koch
announcement and the events that
followed as life transforming.
Only a few hours after reading the
translation of Kochs paper in the
British Medical Journal, which was
accompanied by the notice of a
demonstration of the tuberculo-
sis remedy that was to take place
in Berlin later that week, Conan
Doyle dashed out of his house
and boarded a train for London
with the intention of getting to
Germany as soon as possible. He
later recollected, I could give no
clear reason for doing this, but
it was an irresistible impulse and
I at once determined to go. Had
I been a well-known doctor or a
specialist in consumption it would
have been more intelligible, but
I had, as a matter of fact, no great
interest in the more recent devel-
opments of my own profession.2
Once he reached London, the
doctors pragmatic side intervened,
and Conan Doyle stopped by the
offices of W.T. Snead, the editor
of the magazine Review of Reviews.
Securing letters of introduction
from Snead to prominent Berlin-
ers and, even more important, a
green light to write about the
event, Conan Doyle then hopped
a boat across the Channel. Once
in France, he secured a seat on the
Continental Express to Berlin and
n engl j med 353;23
The New England Journal of Medicine
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Copyright 2005 Massachusetts Medical Society. All rights reserved.
arrived on November 16. Almost
as soon as he stepped off the train
in Berlin, Conan Doyle set out
for the university building where
Kochs colleague, Dr. Ernst von
Bergmann, was scheduled to dem-
onstrate the miraculous tubercu-
sician to stop, glare through his
losis remedy the following morn-
ing. Alas, Conan Doyles trip
appeared to be for naught when
he learned that tickets to von Berg-
manns clinical demonstration
were simply not to be had and
neither money nor interest could
procure them. 2
At this point, the intrepid Conan
Doyle decided to seek out Koch
at his home, but he was told by
a butler that the professor was
unavailable. As Conan Doyle later
recounted, To the Englishman in
Berlin, and indeed to the German
also, it is at present very much
easier to see the bacillus of Koch
than to catch even the most fleet-
ing glimpse of its discoverer. 3
Indeed, the closest Conan Doyle
got to Koch was witnessing the
upended sacks of mail emptied on
the professors doorstep and the
thousands of letters from around
the world containing desperate
pleas regarding the sad broken
lives and wearied hearts which
were turning in hope to Berlin.2
Bright and early on the morn-
ing of November 17, Conan Doyle
went back to the medical audito-
www.nejm.org december 8, 2005
the medical detectives
rium at the University of Berlin.
But neither bribes nor his clum-
sy attempts at slipping by the tick-
et taker secured him entry. Real-
izing that his magazine story was
evaporating into thin air, Conan
Doyle patiently waited for von
Bergmann and literally threw
himself in the path of the formi-
dable physician, causing a pileup
of the younger doctors who made
up the professors faithful retinue
and academic rear guard.
I have come a thousand miles.
May I not come in? begged the
British medical journalist. The
query prompted the senior phy-
pince-nez spectacles, and haugh-
tily reply: Perhaps you would like
to take my place? That is the only
one vacant! Humiliated by the
laughs and jeers of those who
did possess the necessary coupons
for entry, Conan Doyle began to
turn around and leave the hospi-
tal. Fortunately, a tuberculosis
specialist from Detroit named
Henry J. Hartz was appalled by
von Bergmanns display of bad
behavior and lack of profession-
al collegiality. Hartz promised
to meet with Conan Doyle later
that afternoon and share his notes
on the demonstration. Even bet-
ter, the following morning, Hartz
quietly escorted Conan Doyle into
von Bergmanns clinical wards to
examine the patients who had re-
ceived Kochs lymph.
Within a day after analyzing
the mass of clinical data, however,
Conan Doyle came to a startling
conclusion: The whole thing was
experimental and premature.
What is more, he had the temer-
ity to make this statement pub-
licly, first in a letter to the editor,
published in the London Daily
Telegraph on November 20, 1890,4
and then, more definitively, in
his article in the Review of Reviews,
2427
PE R S PE C T IV E
which ran in December of that
year. While the rest of the world
rejoiced over the reported conquest
of tuberculosis, Conan Doyle ar-
gued that Kochs lymph might
remove traces of the enemy, but
it left deadly germs deep in the
invaded country. Its real value,
Conan Doyle asserted, was as an
admirable aid to diagnosis, in
that a single injection would help
doctors decide definitively wheth-
er a patient was in any way tuber-
cular.
Conan Doyle was right. Kochs
lymph, or what we now refer to
as tuberculin, was essentially a
glycerin extract of a pure culture
of tuberculosis germs. In the dec-
ades before the development of
the much safer purified-protein-
derivative test for tuberculosis, it
Remembering Berton Rouech Master of Medical Mysteries
Barron H. Lerner, M.D., Ph.D.
He was never going to sleep
again. Sleep was a waste of time.
Then he got the idea I was trying
to poison him. He didnt trust me,
he said, and if I didnt leave him
alone, he would tear off his clothes
and run out in the street naked.1
Fifty years ago, these words
taught the public about a horri-
fying side effect of the new won-
der drug cortisone: mania. The
speaker was the wife of a man
who had been treated with cor-
tisone for his previously incurable
periarteritis nodosa, and the au-
thor quoting her was Berton Roue-
ch, who wrote the Annals of
Medicine feature in the New Yorker
magazine from the 1940s until
the 1980s.
Rouech developed his inno-
vative approach to medical writ-
2428 n engl j med 353;23
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Copyright 2005 Massachusetts Medical Society. All rights reserved.
became an essential diagnostic
tool. A few months later, in ear-
ly 1891, after several highly pub-
licized treatment failures, many
exacerbated cases of tuberculo-
sis, and not a few deaths closely
associated with the administra-
tion of the so-called curative med-
ication, Koch publicly retracted
his even-tempered announcement
of a remedy for tuberculosis and
announced that although Kochs
lymph was an excellent means of
diagnosing tuberculosis, the ac-
tual cure was nowhere in sight.5
One cannot help but be im-
pressed by the way in which the
young Conan Doyle, the creator of
the greatest detective in English
literature, figured out what took
Koch, one of the most illustrious
medical detectives in history, and
ing at a time when two important
transformations were occurring
in American medicine: the emer-
gence of clinical epidemiology
and the growth of media cover-
age of medical topics. Rouech
was an immensely talented writ-
er and storyteller, and his writings
introduced not only laypersons
but also future generations of phy-
sicians to the art of medicine.
Rouech was born in Kansas
City, Missouri, in 1911, to a busi-
nessman and his wife. His fam-
ily and friends recall him as an
easygoing, soft-spoken man who
loved to read and write. In 1936,
he married Katherine Eisenhow-
er, niece of the future president.
Rouech worked as a journalist
in Kansas City and St. Louis un-
til his articles caught the eye of
www.nejm.org december 8, 2005
The New England Journal of Medicine
the medical detectives
his accomplished colleagues many
more months to realize. Sadly, the
paper trail ends before we can
definitively ascertain how Conan
Doyle cracked The Case of Kochs
Lymph.
Dr. Markel is director of the Center for the
History of Medicine and a professor of pedi-
atrics and communicable diseases and the
history of medicine at the University of
Michigan Medical School, Ann Arbor.
1. Koch R. A further communication on a
remedy for tuberculosis. BMJ 1890;4:1193-
201.
2. Conan Doyle A. Memories and adven-
tures. London: Hodder and Stroughton, 1924:
82-93.
3. Idem. Dr. Koch and his cure. Rev Revs
1890;2:552-6.
4. Idem. The consumption cure. London Daily
Telegraph. November 20, 1890:3.
5. Koch R. Professor Kochs remedy for tu-
berculosis. BMJ 1891;1:125-7.
William Shawn, editor of the New
Yorker, who hired him as a staff
writer in 1944.
Rouechs first medical story,
probably his most famous piece,
occurred by happenstance. He had
heard of a group of gravely ill men
who had shown up at a New York
hospital, blue with cyanosis. The
article he wrote about them, Elev-
en Blue Men, published in 1947,
described how local health offi-
cials deduced the cause of the
malady the inadvertent use of
sodium nitrite, in lieu of sodium
chloride, to season the oatmeal
at the Eclipse Cafeteria in New
Yorks Bowery district.
Eleven Blue Men spawned
dozens of other stories over the
years, many of which were later
collected in books.2,3 The Orange