NATURE MEDICINE • VOLUME 8 • NUMBER 1 • JANUARY 2002 11

BOOK REVIEW

Magic Bullets, LostHorizons: The Rise and

Fall of Antibiotics

by Sebastian G.B. AmyesTaylor & Francis Books, 272 pp, £40.00;

2001

REVIEWED BY CHRISTOPHER T. WALSH

Department of Biological Chemistryand Molecular Pharmacology

Harvard Medical SchoolBoston, Massachusetts, USA

Subsequent to the introduction of peni-cillins as life-saving drugs 60 years agoduring World War II, we take for grantedthat there will be one or more antibiotic,alone or as a combination, that will beavailable, safe and curative when wecome down with a bacterial infection. Inthe recent anthrax bioterror campaign in the United States, an almost talis-manic role of ciprofloxacin as a life-sav-ing treatment exemplifies the magicalqualities attributed to antibiotics in thisera. Sebastian Amyes, a medical microbi-ologist in the United Kingdom, distillinghis decades of experience with the devel-opment of antibiotic resistance in bacter-ial pathogens, has written a book whosesubtitle, The Rise and Fall of Antibiotics,should bring any reader up short.

After an initial two chapters on the dis-covery of antibiotics in the early part of the twentieth century, Amyesnotes that the golden age of antibioticswas in fact quite short, from the mid1940s to 1961, when the first quinolone,the progenitor to ciprofloxacin, was introduced into human medicine. Sincethen the widespread use of antibi-otics has led to the global spread of antibiotic resistance, detailed in a chap-ter called “Paradise Lost”. The later chap-ters are even less optimistic with titles orsubtitles of “the doomsday scenario”,“why we shall lose the battle against in-fection”, and “has resistance switchedout the light at the end of the tunnel”.The last page warns of the likelihoodthat “we are going to slip further into anabyss of uncontrollable infection.” Thisis a clarion call to pay attention, orrather a klaxon at high decibels.

Amyes has my attention and heshould have yours, as he explains howthe past 30 years have seen a complete

switch in our views about bacterial diseases. The optimism of the USSurgeon General in 1969—that the bookon infectious disease could be closed due to the power of antibiotics—hasbeen replaced by the current view thatthe antibiotic cupboard is bare. Amyes surmises, as others have in recent years, that the widespread acceptance of antibiotics by physiciansand patients, coupled with their excellent safety and low toxicity, led to an avalanche of use. With wide usage comes both inappropriate pre-scription and subtherapeutic dosing, resulting in the selection of drug-resis-tant bacteria and their subsequent globalspread. Amyes illustrates his argumentswith many clinical microbiological examples including methicillin-resistantStaphylococcus aureus (MRSA), van-comycin-resistant Enterococci (VRE), lactam-resistant Streptococcus pneumo-niae, and the currently emerging van-comycin-resistant Staph aureus (VRSA).There is also a chapter on the use of an-tibiotics in agriculture and their conse-quences for man, a topic of recurrentheated debate.

Amyes brings a lifetime of researchand clinical involvement to the subject and is authoritative in personal-izing the crisis of life-threatening, antibi-otic-resistant bacterialinfections. The book isrich with anecdote andinformation from thepractical, such as whatantibiotics Amyes travelswith, to molecular detailsof the evolution of mu-tant genes encoding theβ-lactamase enzymes thatdestroy penicillins andcephalosporins. This isnot meant to be a schol-arly work; for example,there are no referencesanywhere in the text. Ifound almost no errors ofcommission but would have liked to pe-ruse some subjects further. Also there arevery few figures and illustrations, and ingeneral those graphics are rather primi-tive. This seems a missed opportunity,and the lack of effective visuals makesthe textual details difficult for the non-expert reader to grasp.

With the potential microbial dooms-day scenarios well framed, I kept readingto see what solutions Amyes might offeras credible and likely. He offers few in-

sights, beyond better infection controlprocedures and more careful use of life-saving antibiotics. He addresses bacterialgenomics efforts to find new targetsbriefly and rather dismissively. In theend, the book serves as warning for im-pending disaster, but I had the sense thatAmyes did not make extensive effort toput the contemporary searches for newantibacterial drugs into an integratedperspective.

Amyes writes that the quinolones (of the ciprofloxacin family) intro-duced in 1961 were the last novel structural type of antibiotic. But this misses the oxazolidinone (trade name Linezolid) approved by the USFood and Drug Administration in early2000, perhaps after Amyes completed hismanuscript. It remains to be seen how ef-fective the oxazolidinone scaffold willbecome, but it represents the emergenceof significantly increased medicinalchemistry efforts in antibacterial drugsin the past seven or eight years by phar-maceutical companies. There are alsolipopeptide antibiotics in clinical trialsthat may prove useful and that Amyescould have noted.

There are many bacterial genome sequences now in public databases, in-cluding MRSA, VRSA, enterococcal,streptococcal, pseudomonal, tuberculo-

sis and plague genomes.Dozens to hundreds ofnew genes from thesepathogens have been de-termined to be essentialand/or required for viru-lence, so validated newtargets are now availableand real-time PCR maysoon allow a revolutionin pathogen diagnosisfor customized treat-ment. It is a long and un-certain road from a novelvalidated target to an an-tibacterial drug, and theutility of synthetic com-

binatorial chemical libraries to provideuseful starting points that can be turnedinto drug leads remains in question. Itmay be that these efforts will be ineffec-tive and Amyes and the rest of us can dis-tribute along the spectrum of direpessimism to muted optimism as our dis-positions permit. Magic Bullets, LostHorizons is another clarion call that wemust not take the antibiotic era forgranted or it will be a much-admired pe-riod of the past.

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