fections, mould infections, infections due
to dimorphic fungi, cutaneous infections,
infections in compromised hosts, and
other mycoses. The target audience appears to be physicians who are interested
in infectious diseases and fungal infections, trainees in infectious diseases and
internal medicine, and medical students.
The book is well written and includes detail that will satisfy people with varying
levels of knowledge. It will serve as the
ultimate textbook reference for questions
related to diagnosis and treatment of fungal infections. Epidemiology, pathogenesis, clinical manifestations, diagnosis, and
treatment are reviewed for all fungal pathogens, including those that are rare. All of
the chapters are extensively referenced
and up-to-date.
Many of the chapters provide the reader
with definitive recommendations for therapy. A good example of this is the chapter
on cryptococcosis, which has 2 excellent
tables of recommendations for treating
patients with cryptococcal disease, one
table for patients infected with HIV and
the other for patients who are not. Other
chapters discuss treatment options, but
the author does not rank them. This is
particularly the case for diseases that are
less common, where data from controlled
clinical trials are not available. In that circumstance, expert opinions as to the recommended management would be welcomed. Finally, several important studies
of the treatment of fungal infections, particularly aspergillosis and candidemia,
were published about the time that the
chapters in this book were being written.
They are mentioned, but the results are
not well integrated in the management
recommendations.
In summary, this book can be recommended to all physicians interested in the
treatment of fungal infections. It is informative and provides a sound basis of
knowledge for diagnosis and treatment of
fungal infections. As the field continues to
move forward, supplementation of this
book with key research papers will allow
clinicians to provide state-of-the-art therapy to their patients.
Acknowledgments
Potential conflicts of interest. S.H.C.: no
conflicts.
Stuart H. Cohen
Division of Infectious Diseases,
University of California—Davis,
Sacramento, California
The Mold in Dr. Florey’s
Coat
By Eric Lax
New York: Henry Holt and Company, 2004.
308 pp. $25.00 (cloth).
In the John Wayne western film The Man
Who Shot Liberty Valance, a newspaper editor offers some sage advice to a naive reporter: “When the legend becomes a fact,
print the legend.” In The Mold in Dr. Florey’s Coat, Eric Lax attempts to debunk
the much-printed legend of the discovery
of penicillin by Alexander Fleming.
The teenage Fleming left the grinding
poverty of rural Scotland for the high road
to London, well trod by Scots before and
since his time. In 1906, after earning his
way through medical school on scholarships, he joined the foremost research laboratory in Britain, the Inoculation Department at St. Mary’s. Fleming spent the
next 49 years there, becoming an amiable, learned, and eccentric microbiologist
(Fleming amused himself by streaking pigmented bacteria onto culture plates so
they would bloom into little pictures, such
as a cottage in the woods and a mother
rocking a baby).
In 1928, Fleming noticed something
odd on returning from vacation. A plate
of Staphylococcus aureus had been contaminated by a mold, Penicillium notatum.
The bacterial colonies in the immediate
vicinity of the mold had lysed. This event
was made possible by a freakish coincidence: cool summer weather in London
arrested the growth of staphylococci while
permitting growth of the fungal contaminant. Moreover, Fleming returned just in
time to observe the bacterial lysis, before
the mold overgrew the plate completely.
Excited, Fleming named the inhibitory
factor “penicillin,” deciding that his initial
choice, “mould juice,” was insufficiently
catchy. Fleming demonstrated that penicillin was highly active against a range of
bacteria. His crude attempts to develop
penicillin clinically were thwarted by the
great difficulty of isolating the active substance. He published a paper in 1929 that
suggested penicillin might be a useful therapeutic drug, although he was more interested in its utility in the laboratory isolation of Haemophilus influenzae.
Penicillin was ignored until 1938, when
Ernest Chain stumbled across Fleming’s paper. Chain was a brilliant chemist and concert pianist who had fled Nazi Germany in
1933. The combustible, flamboyant Chain
struggled in England, sometimes a victim
of anti-Semitism, sometimes a victim of his
own blustering arrogance (one affectation
was an Albert Einstein haircut). Ultimately,
he found a tolerant home in Howard Florey’s laboratory at Oxford. Brutally ambitious, Florey excelled at both physiology
and academic politics and became Chair of
Pathology at Oxford when he was 36 years
old.
Despite Chain’s labors, it is doubtful he
would have gotten much farther than
Fleming if not for his collaborator Norman Heatley, a mild-mannered, tinkering
biochemist. Heatley’s crucial insight was
to use reverse extraction to purify penicillin. During the privations of wartime,
Heatley jury-rigged a countercurrent extraction device from rubbish, odds and
ends, and glass tubing of his own manufacture.
By 1941, enough penicillin was available
to treat 6 patients, which produced spectacular results, especially considering the
paltry amount of penicillin that had been
manufactured (a total of 4 million units!).
The responses were probably attributable
to the exquisite susceptibility of preanti-
BOOK REVIEWS • CID 2004:40 (1 March) • 777
biotic-era bacteria, and the parsimony and
ingenuity of the Oxford team in recycling
penicillin from patients’ urine.
Florey personally visited North Africa
in 1943 to further test the effectiveness of
penicillin. A controversy broke out. Florey,
puritanically and perhaps hypocritically,
felt that scarce penicillin should be reserved for the treatment of battlefield
wounds. Others believed that penicillin
was most wisely used to treat the disabling
wounds acquired in the brothels of Tunis.
The dispute was taken right to the top;
Churchill made the unsentimental and
probably correct decision that the war effort was best served by restoring the many
gonorrheal soldiers to service for the upcoming invasion of Italy.
When it became clear that penicillin was
going to revolutionize the field of medicine, Chain urged Florey to patent it. Florey refused, stating it would be wrong to
make windfall profits from such a boon
to humanity. Chain thought this attitude
foolish and quixotic. Although it may have
been morally laudable, Florey’s stance
ironically resulted in Britain owing royalties to American pharmaceutical firms.
As fame of the wonder drug spread,
Fleet Street started knocking on Fleming’s
door. The genial Scot became a media darling, reenacting his accidental discovery
for reporters. Bemused by the attention,
Fleming kept a scrapbook of press clippings entitled, “Fleming Myth.” Florey was
mortified, but too aloof to condescend to
the press, even if it meant losing potential
publicity and funding.
Lax is guilty of oversimplification at
times, reducing the penicillin breakthrough to a question of which great man
should receive the lion’s share of the
credit. Science is a social and collaborative enterprise, requiring not only geniuses
who win prizes and doctorates, but the sacrifices of people such as the “Penicillin
Girls,” who toiled in Florey’s factory in incredibly unsafe and dangerous conditions.
Furthermore, I find it difficult to believe, as Lax apparently does, that Florey
and Chain’s contributions to the development of penicillin were neglected. Fleming, Florey, and Chain shared the Nobel
Prize for Medicine in 1945 (apparently,
neither Florey nor Chain considered sharing their Nobel Prize money with Heatley,
as Banting had done with Best for the discovery of insulin). Fleming, the son of an
Ayrshire sheep farmer, Florey, the son of
an Australian bankrupt, and the penniless
refugee Chain all received knighthoods.
Florey became Baron of Adelaide and
Marston, provost of Queen’s College, and
president of the Royal Society. Chain grew
rich by consulting for the pharmaceutical
industry, became a prominent philanthropist, and died on his estate, improbably
located in the Gaelic hinterland of County
Mayo.
Those with an interest in the history of
medicine will enjoy this well-written book,
with its dashes of intrigue (the title refers
to a plan to preserve penicillin from a possible Nazi invasion by concealing fungal
spores in clothing). Lax, better known as
a celebrity biographer, is fairly accurate, if
sometimes vague, when dealing with science. He is on firmer ground when dealing
with personalities and infighting between
scientists. Although Lax’s story contains
nobility and idealism, the British and
American scientists he describes are not
exempt from boorish behavior, including
selfish careerism, backstabbing, intellectual piracy, ingratitude, poor parenting,
and adultery. Making the flawed Florey the
focus of the penicillin story is a little misguided. Florey’s contributions to the discovery of penicillin were important but
largely administrative; he scrambled for
American dollars to keep his laboratory
afloat. Perhaps this book should really be
titled The Mold in Dr. Heatley’s Coat, after
the modest, indispensable man who was
most unjustly forgotten by the public and
his peers.
Acknowledgments
Potential conflicts of interest.
conflicts.
778 • CID 2004:40 (1 March) • BOOK REVIEWS
J.J.R.: no
John J. Ross
Caritas St. Elizabeth’s Medical Center,
Tufts University School of Medicine,
Boston, Massachusetts
AIDS Therapy, 2nd Edition
Edited by Raphael Dolin, Henry Masur,
and Michael S. Saag
Philadelphia: Churchill Livingstone, 2003.
1024 pp. $173.00 (cloth).
This is the second edition of a text that
was originally published in 1999. Especially notable updates include chapters
about new antiretroviral agents and immune-based therapies. The editors have
again assembled a thorough textbook on
the management of HIV infection and
AIDS, and they have enlisted many authors who are leading experts in their respective fields. The book consists of 8
sections on the diagnosis of HIV infection,
specific antiretroviral agents, immunebased therapies, alternative therapies, the
strategy of antiretroviral therapy, management of opportunistic infections according to etiology, syndromic presentations,
and drug administration and interactions.
Appendices include internet resources and
antiretroviral dosage guidelines.
The initial chapter, which is about the
diagnosis of HIV infection, is very complete and includes discussion of the limitations of serologic testing and indeterminate Western blot results, false positive
tests, and the utility for non–B clades.
Each of the antiretroviral agents that had
been approved by the time of the book’s
publication is the topic of a separate chapter, all of which are organized in a typical
format: mechanism of action, pharmacokinetics, toxicities, resistance, clinical
studies, interactions, and uses. The book’s
major limitation is most apparent in this
section; namely, that the inclusion of contemporary information in textbooks is difficult because of the rapid changes in the
field. Sizable chapters on drugs that are