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Germs Germs and the City
Peter W. Huber
Two centuries of success against infectious disease have left us
complacent—and vulnerable.
There have been at work among us three great social agencies: the London
City Mission; the novels of Mr. Dickens; the cholera.” Historian
Gertrude Himmelfarb quotes this reductionist observation at the end of
her chapter on Charles Dickens in The Moral Imagination; her debt is to
an English nonconformist minister, addressing his flock in 1853. It
comes as no surprise to find the author of Hard Times and Oliver Twist
discussed alongside Edmund Burke and John Stuart Mill in a book on moral
history. Nor is it puzzling to see Dickens honored in his own day
alongside the City Mission, a movement founded to engage churches in
aiding the poor. But what’s V. cholerae doing up there on the dais
beside the Inimitable Boz? It’s being commended for the tens of millions
of lives it’s going to save. The nastiness of this vile little bacterium
has just transformed ancient sanitary rituals and taboos into a new
science of epidemiology. And that science is about to launch a
massive—and ultimately successful—public effort to rid the city of
infectious disease.
The year 1853, when a Victorian doctor worked out that cholera spread
through London’s water supply, was the turning point. Ordinary people
would spend the next century crowding into the cities, bearing many
children, and thus incubating and spreading infectious disease. Public
authorities would do all they could to wipe it out. For the rest of the
nineteenth century, they lost more ground than they gained, and microbes
thrived as never before. Then the germ killers caught up—and pulled
ahead. When Jonas Salk announced his polio vaccine to the press in April
1955, the war seemed all but over. “The time has come to close the book
on infectious disease,” declared William Stewart, the U.S. surgeon
general, a few years later. “We have basically wiped out infection in
the United States.”
By then, however, infectious diseases had completed their social
mission. Public authorities had taken over the germ-killing side of
medicine completely. The focus shifted from germs to money—from social
disease to social economics. As germs grew less dangerous, people
gradually lost interest in them, and ended up fearing germ-killing
medicines more than the germs themselves.
Government policies expressed that fear, putting the development,
composition, performance, manufacture, price, and marketing of
antibiotics and vaccines under closer scrutiny and control than any
public utility’s operations and services. The manufacturers of these
drugs, which took up the germ-killing mission where the sewer commission
left off, must today operate like big defense contractors, mirror images
of the insurers, regulatory agencies, and tort-litigation machines that
they answer to. Most drug companies aren’t developing any vaccines or
antibiotics any more. The industry’s critics discern no good reason for
this at all: as they tell it, the big drug companies just can’t be
bothered.
These problems capture our attention only now and again; they hardly
figure in the much louder debate about how much we spend on doctors and
drugs, and who should pay the bills. “Public health” (in the literal
sense) now seems to be one thing, and—occasional lurid headlines
notwithstanding—not a particularly important one, while “health care” is
quite another.
We will bitterly regret this shift, and probably sooner rather than
later. As another Victorian might have predicted—he published a book on
the subject in 1859—germs have evolved to exploit our new weakness.
Public authorities are ponderous and slow; the new germs are nimble and
fast. Drug regulators are paralyzed by the knowledge that error is
politically lethal; the new germs make genetic error—constant
mutation—the key to their survival. The new germs don’t have to be
smarter than our scientists, just faster than our lawyers. The demise of
cholera, one could say, has been one of the great antisocial
developments of modern times.
By withdrawing from the battlefield just long enough to let us drift
into this state of indifference, the germs have set the stage for their
own spectacular revival. Germs are never in fact defeated completely. If
they retire for a while, it’s only to search, in their ingeniously
stupid and methodically random way, for a bold new strategy. They’ve
also contrived, of late, to get human sociopaths to add thought and
order to the search. The germs will return. We won’t be ready.
Microbes discovered the joys of socialism long before Marx did, and in
matters of health, they made communists of us all. Since the dawn of
civilization, infectious disease has been the great equalizer, with the
city serving as septic womb, colony, and mortuary. Epidemic—“upon the
people”—is the democracy of rich and poor incinerated indiscriminately
by the same fever, or dying indistinguishably in puddles of their own
excrement.
The Mao of microbes was smallpox, which killed 300 million people in the
twentieth century alone. Sometimes called the first urban virus, it
probably jumped from animals to humans in Egypt, Mesopotamia, or the
Indus River Valley, at about the same time that the rise of agriculture
began drawing people together in towns and cities. Smallpox has also
been called nature’s cruelest antidote to human vanity. Princes broke
out in the same pustules as paupers, reeked as foully of rotting flesh,
and oozed the same black blood from all their orifices. Alongside
millions of nameless dead lie kings of France and Spain, queens of
England and Sweden, one Austrian and two Japanese emperors, and a czar
of Russia.
While the germs reigned, there wasn’t much rest-of-medicine to speak of:
infections eclipsed every other cause of illness but malnutrition. And
when monarchs were dying, too, language and politics honestly tracked
medical reality. The “social” in “social disease” reflected an
epidemiological fact. It also pointed to a practical, collective
solution. Disease arose and spread when people converged to create
societies. It was caused by invisible agents that individuals could not
control on their own. It could be eradicated only by social means—public
sanitation, slum clearance, education, and, above all, a robust,
germ-hating culture. It took a city to erase a cholera.
This was the overarching insight that crystallized in the public
consciousness in the first half of the nineteenth century. “In the
Victorian version of the Puritan ethic,” Himmelfarb writes, “cleanliness
was, if not next to godliness, at least next to industriousness and
temperance.” For Dickens, as Himmelfarb and others have observed, the
filth in the Thames symbolized the city’s insidious taint, its
ubiquitous, effluvial corruption. What social historians often fail to
note, however, is that by the time Dickens was placing the Thames at the
center of London’s many ills, a new science had emerged to move the
river far beyond metaphor.
Epidemiology—the rigorous science of public health—was born with
physician William Farr’s appointment as controller of London’s General
Register Office in 1838. Directed to do something about the cholera
epidemic, Farr began systematically recording who was dying and where.
The most important things he discovered were negative. Wealth didn’t
protect you from cholera. Neither did occupation, or residing close to
the sea. What mattered was how high above the Thames you lived. Farr
concluded that the river’s horrendous stench caused the disease. Another
English doctor, John Snow, made the right connection in 1853: London’s
sewers emptied into the Thames, so the farther down-sewer you lived, the
more likely you were to drink foul water. A year later, Snow saved
countless lives by persuading parish authorities to remove the handle
from the Broad Street pump in Soho.
The rest is history. By pinning down the waterborne pathway of
contagion, Farr and Snow had transformed a devastating public disease
into a routine exercise in civil engineering. In 1858, Parliament passed
legislation, proposed by then-chancellor of the exchequer Benjamin
Disraeli, to finance new drains. Charles Dickens published his last
novel—Our Mutual Friend, in which the main character is the pestilential
Thames—in 1864. London suffered its last cholera epidemic in 1866.
This wasn’t the end of great plagues in the city, or even the beginning
of the end, but it was the end of the beginning. In 1872, Disraeli
rallied his Tory Party around what his Liberal opponents derided as a
“policy of sewage”—reforms involving housing, sanitation, factory
conditions, food, and the water supply—and while he served as prime
minister, these policies became law. For the next 50 years or so, in the
United States as in Britain, public health depended on city bureaucrats
above all. They wasted little time with sick patients, other than
sometimes ordering them to lock their doors and die alone. They focused
instead on eradicating germs before they reached the patient, and that
meant attending to the water, sewage, trash, and rats.
In a recent British Medical Journal survey, public sanitation was voted
the most important medical advance since the journal was established in
1840. If we don’t think of public sanitation as “medical” any more, it’s
only because the municipal bureaucrats who followed Farr cleaned things
up so well.
As they ran out their welcome in public spaces, microbes went private.
They still had to move from person to person, but there could be no more
carefree joyrides on rats or surfing through the water supply. People
themselves, however, are almost as infectious as their sewers. Clean
water alone could not eliminate coughs, dirty hands, and filthy food.
The systematic pursuit of germs into the flesh of patients didn’t really
begin until the very late nineteenth century. Jenner’s smallpox vaccine
was already a century old, but it owed its existence to the lucky fact
that the human pox had a weak cousin that infected cows. (We give our
kids the “cow treatment”—vacca is Latin for cow—every time we do as
Jenner did, and challenge their immune systems with a corpse, cousin, or
fragment of a horrible microbe.) The systematic production of other
vaccines had to await the arrival of Louis Pasteur and Robert Koch, who
developed procedures for isolating microbes and then crippling or
killing them.
Vaccines, health authorities quickly recognized, are quintessentially
public drugs. They expel germs not from the public water but from the
not-quite-private lungs, fluids, and intestines of the public itself.
When enough people get vaccinations, “herd immunity” protects the rest.
Five human vaccines arrived in the late nineteenth century, and many
others would follow in the twentieth. They weren’t developed quickly or
easily, but they did keep coming. In due course, and for the first time
in human history, serious people began to believe that infectious
disease might come to an end. Scientists could painstakingly isolate
germs that attacked humans. Drug companies then would find ways to
cultivate and cripple the germs, and mass-produce vaccines to immunize
the public. Disease would fall, one germ at a time, and when they were
all gone, good health would be pretty much shared by all.
New laws, vigorously enforced, drafted the healthy public into the war
on germs. England mandated universal smallpox vaccination in 1853.
Facing a smallpox outbreak, Cambridge, Massachusetts, decreed in
February 1902 that all the town’s inhabitants “be vaccinated or
revaccinated,” set up free vaccination centers, and empowered a
physician to enforce the measure. A certain Henning Jacobson refused to
comply, insisting on a constitutional right “to care for his own body
and health in such way as to him seems best.” The U.S. Supreme Court
disagreed, easily upholding the “power of a local community to protect
itself against an epidemic threatening the safety of all.” Later
enactments would require the vaccination of children before they could
attend public schools. Adults who traveled abroad had to be vaccinated
if they planned to come home. Albert Sabin’s polio vaccine took things
even further—the vaccine itself was infectious. A child swallowed a live
but weakened virus soaked into a sugar cube, and then went home and
vaccinated his siblings and parents, too.
The germ killers didn’t really get into the business of private
medicine—curing already-sick patients—until the development of sulfa
drugs in the 1930s, followed by antibiotics after World War II. Even
then, much of the cure still lay in preventing the infection of others.
The paramount objective with tuberculosis, for instance, was to wipe out
the tubercle bacillus so thoroughly that nobody would need streptomycin
any more, because nobody would come into contact with any other infected
person or animal.
Year by year, one segment or another of the public sector contrived to
take a little more control, directly or indirectly, over the
development, distribution, and price of vaccines. Soon after the
development of the polio vaccine in the 1950s, Washington launched a
program to promote and subsidize the vaccination of children nationwide.
At about the same time, the Soviet Union proposed a global campaign to
eradicate smallpox. The World Health Organization officially launched
the campaign in 1966, and it ended in triumph 20 years later.
A complete socialization of the war against germs seemed sensible. The
germs, after all, lived in the public water, floated through the public
air, and passed from hand to hand in the public square. Individuals
might buy their own vaccines, antibiotics, bottled water, and face
masks. But collective means could make all of that forever unnecessary.
And they did. Big government attacked the infectious microbes with
genocidal determination, expelling them, one by one, from human society.
Defiled by monstrous human fratricide, the first five decades of the
twentieth century were also the triumphant decades of public health.
To stay prepared, however, human culture apparently requires regular
booster shots of smallpox, cholera, plague, or some other serious
disease that indiscriminately sickens and kills. Without periodic
decimation, ordinary people apparently forget what germs can do, the
authorities grow complacent, scientists turn their attention elsewhere,
and private capital stops investing in the weapons of self-defense.
As Sherwin Nuland observes in How We Die, AIDS struck just when “the
final conquest of infectious disease seemed at last within sight.” In
1981, a weekly Centers for Disease Control report noted a sudden
increase in a specific strain of pneumonia in California and New York.
Before long, we had it on Oprah Winfrey’s authority that the germs were
back and were after us all. “One in five heterosexuals could be dead of
AIDS in the next three years,” she declared in February 1987.
Whatever they were thinking about HIV, the heterosexuals had, by that
point, plenty of other venereal diseases to worry about. A tragically
large number of young women had contracted chlamydial infections serious
enough to leave them infertile. Herpes, gonorrhea, syphilis, and some
types of sexually transmitted hepatitis were also on the rise. The
sexual revolution seems in retrospect to have been led by people who
took William Stewart at his word when he consigned infectious disease to
the dustbin of history. But rampant promiscuity packs people together
tighter than slums, and germs rush in where angels fear to tread. It has
taken a great deal of readily avoidable suffering and death to establish
that people do need sexual taboos—taboos at the very least robust enough
to thwart microbes, if not with less sex, then with more latex.
As social agents go, however, HIV and chlamydia accomplished far less
than cholera. It was the demise of a germ-hating culture that had helped
clear the way for new epidemics of venereal disease, and the
resurrection of that culture still has a long way to go. Many people in
positions of authority and influence continue to affirm the tattoo
artist’s expressive freedom, the bag lady’s right to sleep next to the
sewer, the mainliner’s right to share needles in an abandoned row house,
and the affluent parent’s right to interpose a “philosophical objection”
between his child and the vaccinations demanded by public schools. They
propound grand new principles of freedom, privacy, and personal autonomy
to protect septic suicide, even septic homicide. Social doctors in
Dickens’s day didn’t have to invade anyone’s privacy to track
smallpox—it announced itself on its victims’ faces. Tracking HIV, by
contrast, requires a blood test, and privacy police dominated the first
20 years of the fight over testing.
A legal system that affirms the individual’s right to do almost
everything at the germ-catching end now struggles to decide when, if
ever, we can force the Typhoid Marys of our day to stop pitching what
they catch. The law that once ordered a healthy Henning Jacobson to roll
up his sleeve can no longer compel a virulent celebrity to zip his fly.
Infectious lifestyle, once a crime, is now a constitutional right.
Many people just don’t care much, and it’s easy to see why. Habits and
lifestyles that the Victorians learned to shun look a lot less vile when
they lose not only their repulsive cankers, pustules, sputum, fevers,
diarrhea, dementia, and emaciation, but also their power to impose these
horrors on the neighbors. Just three months after Oprah warned
heterosexuals about AIDS, President Reagan thought it necessary to
remind us that we were battling a disease, not our fellow citizens.
Everyone knew why. The gay community had good reason to fear that many
Americans might be thinking: HIV isn’t my problem, it’s theirs. The new
choleras are indeed much less social than the old. Why shouldn’t they
forever remain so?
Over the morning coffee and toast, consumed in our tidy little kitchens,
we read that drug-resistant tuberculosis is a cause for growing
concern—but mainly in prisons. So too are new drug-resistant staph
infections—in tattoo parlors and the foulest of locker rooms. And it’s
in private drug dens, bedrooms, and bathhouses, of course, that
infectious germs have made their biggest comeback, contriving to get
themselves spread by not-quite-private needles and genitalia. True, the
germs incubated in abandoned houses, cardboard boxes, and other hovels
have drifted into run-down urban hospitals, whose emergency rooms often
provide primary care to the patients most likely to harbor the worst
germs. But they haven’t moved much farther than that. Sharing the city,
it seems, no longer means sharing smallpox and the plague.
The epidemiological facts—beyond serious dispute—support the complacent
majority. Germs used to ravage young bodies with inexperienced immune
systems; now they mainly take the old. Though death certificates still
quite often record an infection as the final cause of death, germs now
are mostly epitaph killers, moving in on immune systems terminally
crippled by old age, heart disease, cancer, stroke, and Alzheimer’s.
In the pantheon of disease and death, lifestyle and genes have
completely eclipsed germs. The great agent of social change today isn’t
cholera; it’s cholesterol. It propagates via drive-through windows, not
sewers. Crowds don’t flee the city when it strikes; they pay extra for a
supersize serving. In the heyday of public health, public money went to
clean up public filth. Today, we’re sick because we spend our private
money buying bad health by the pack, the bottle, and the Happy Meal.
Small wonder, then, that the germ-fighting social norms once ranked next
to godliness still seem to many as antiquated as the whalebone hoops
that defended Victorian virtue.
If we took the new microbes seriously, we could certainly beat them. The
science for tracking, immunizing against, and annihilating germs grows
more vigorous, innovative, and youthful with each passing year. But
insurers and regulators now control how we use that science, and as the
germ-phobic culture has decayed, they’ve grown increasingly slow and
rigid. Many competent people at the top echelons of government worry
deeply about this problem. Yet as they scramble to address it, they must
hack their way through laws and bureaucracies that have accumulated and
thickened since the 1960s. Technical know-how isn’t enough; collective
will is also necessary. Yet—paradoxical as it sounds—collective will is
what was lost as government took over the show.
Good sewers, public sanitation, and fresh water are undoubtedly public
ends, best advanced by public means. Yet though germ killing begins in
public, it must, as the Victorians grasped, end in private, and this is
where the government’s attempt to take charge of everything has had
terrible consequences. The Victorians had nothing but culture to wield
against germs on private premises, so they taught that clean was
virtuous, and dirty sinful, and they taught it very persistently to
everyone. But the big, efficient, technocratic government agencies of
our day don’t do virtue and sin—they requisition, stockpile, subsidize,
proscribe, and mandate. And they teach—implicitly but persistently—that
germs are government’s responsibility, not yours. Socialized germ
killing makes it a lot easier for people to lose touch with the personal
side of germicide.
When the government then tries to clean up human bodies with the same
heavy hand that it uses to clean up the sewers, it can end up fighting
both amnesiacs and those who remember too well. The forgetful push back
because they are sick and tired of being hectored by the universal nanny
about washing hands, vaccinating kids, and countless other time-wasting
nuisances. The unforgetful seem to believe that the little routines and
habits of daily life are too important to entrust to a nanny perched on
the banks of the Potomac.
Consider, for example, the most important new vaccine recently licensed,
to protect against the human papillomavirus (HPV). Developed by
scientists at the National Cancer Institute, it’s designated a
“childhood” vaccine, which will give it some (by no means complete)
shelter from the tort lawyers. Merck licensed the vaccine, steered it
through the FDA, and will be responsible if anything goes wrong. The
firm is charging $300 or more for the three-shot dose—ten to 100 times
the inflation-adjusted cost of most vaccines in the 1950s. It may well
be worth it. This new kids’ vaccine protects against a sexually
transmitted virus that causes many cases of cervical cancer. To be
effective, however, vaccination must occur before exposure to the virus,
and each new sexual partner exposes a girl to a 15 percent chance of
infection. The Centers for Disease Control therefore plans to see to it
that girls are vaccinated before. That, the federal authorities have
concluded, would be before they are 12.
Quite a few parents have concluded that the federal authorities can go
to hell. The amnesiacs are beyond help; they’re probably skipping other
vaccines, too. As for the mnemonists—maybe some just remember that sex
spreads a lot of other germs, as well, and figure that they have a
scheme to protect their little girls from all of them. Others probably
aren’t making any conscious calculation about germs; they’re just
holding fast to a faith and culture that still seeks to protect little
girls from sex itself. People who believe government can achieve
anything will say that it should just have handled this one more
delicately. Perhaps—but the fact is, the government’s germ killers have
ended up at loggerheads with the people they most need as their closest
allies: parents who teach the taboos and rules that provide a crucial
line of defense against the most persistent and clever killers of
children on the face of the planet.
Even when it doesn’t reach the point of turning parents against
vaccines, the government takeover has left many people with a triple
sense of entitlement—to germ-free life, risk-free drugs, and wallet-free
insurance. This in turn has created an almost profit-free economic
environment for germ-hunting pharmaceutical companies, which still do
much of the basic science and take charge of the essential, delicate,
and difficult business of mass drug production.
The new drug law that President Kennedy signed on October 10, 1962,
codified a profound change in attitude. With infectious diseases all but
finished, the drugs of the future would target human chemistry. A
horrified world had just discovered that one such drug, which
effectively relieved morning sickness and helped people fall asleep,
also halted the growth of a baby’s limbs in the womb. Before, when
microbes were the enemy, drugs got the benefit of the doubt. After the
1962 Thalidomide amendments, the unknown cure was officially more
dangerous than the known disease. Very strong evidence would be
necessary to establish otherwise.
The 1962 drug-law amendments gave decisive weight to human tests and
clinical outcomes: a drug would not be deemed “effective” without
clinical trials in which human patients started out sick and finished up
healthy. Progressing in little steps from that seemingly sensible
starting point, the FDA has since reached the point of worrying more
about drugs evolving into sugar pills than about currently innocuous
germs evolving into plagues.
The FDA has long required that clinical tests demonstrate that a new
antibiotic is as good as or better than one already on the shelf, and it
wants these trials to be extremely thorough and convincing. It worries
that with too few patients tested, statistical anomalies might allow an
inferior antibiotic to win its license, and the new one might then
become the benchmark for a third even worse one, and so on until the
industry slouches its way down to licensed sugar pills. The agency calls
this scenario “biocreep.” It’s just the sort of logical but overly
theoretical concern that sneaks into government offices where the
paramount objective is to avoid mistakes. But nowadays, “no mistakes”
means no new drugs licensed until the germs start killing lots of people
again. Most serious infectious diseases are rare, and it’s unethical to
test a new drug on seriously ill patients when there’s an old, licensed
alternative in easy reach. This makes it all but impossible to assemble
enough sick-but-not-too-sick patients for statistically meaningful
clinical tests.
For example, the FDA recently had to decide whether to approve the use
of Cubicin against a vicious germ that infects heart valves. Dubbed the
“Darth Vader” bacterium, it is stealthy, difficult to kill, and almost
always fatal if untreated. The FDA’s staff wasn’t convinced that enough
patients had been tested to establish that the drug was better than the
already existing alternatives—and argued that if it was too weak, the
germ might evolve into something beyond Darth, resistant to everything.
On the other hand, doctors were already using Cubicin
off-label—prescribing it in ways never officially vetted or approved by
the drug company or the regulator—but in low doses, thus possibly
creating an even greater beyond-Darth risk. In the end, the chief of the
FDA’s anti-infectives division overruled a staff recommendation and
granted the license. But every such decision is a fight, and all the
legal, political, and institutional cards are now stacked against quick,
bold action.
A letter coauthored by a doctor at Harvard’s medical school and
published in Clinical Infectious Diseases in 2002 bluntly linked the
FDA’s approach to “the end of antibiotics.” “For nearly two decades,” it
began, “antibacterial research has been the ‘Cinderella’ area in the
pharmaceutical industry.” Increasingly stringent demands for proof
efficacy, framed in ways that seem “innocent and technical,” the authors
argued, have thrown the industry “into a panic.” They have “wreaked
irreparable damage to our ability to provide a reliable pipeline of new
antibiotics for treatment of serious infections.” And they probably
helped propel Lilly and Bristol-Myers Squibb out of antibacterial
research and development.
Most fundamentally, the FDA has no mandate—none at all— to prepare us
for war against the next cholera. Its mandate is to make sure that we
don’t lose the battle against the next Thalidomide. “Safe” and
“effective,” the two key standards set out in the 1962 drug law, have
intelligible meaning only with a germ to fight and infected patients to
fight it in. The agency, in other words, actually needs thriving germs
to supply enough really sick patients to provide FDA-caliber evidence to
validate the drug that will wipe out the germs. Epidemics that lurk in
the future, waiting for germs still under construction, can’t be
officially considered at all. But those germs—the ones that don’t yet
exist, the ones still evolving, by chance or with human help in a
terrorist’s lab—should worry us most.
Today’s public health guardians have made things even harder for
vaccines than for antibiotics. Gene-splicing and other bioengineering
tools make it far easier today than ever before to build safe corpses,
cousins, or fragments of horrible microbes. But many vaccines that could
quite easily be developed haven’t been, and probably won’t be, because
no drug company will take them to market.
Political support for the FDA depends on the public perception that it’s
solving problems. When widely administered, as it must be, a vaccine
wipes out the disease that it targets. The disease can thus be eclipsed
in the public’s mind by the vaccine’s side effects, however rare or even
imaginary. The more effective the vaccine at the outset, the more likely
it will be condemned as unsafe at the end. Moreover, the FDA has an
acknowledged policy of being extra cautious in licensing any product
that healthy people will use, especially children. Nothing could better
suit the germs. Healthy children with undeveloped immune systems are
their favorite targets.
Judges and juries have even more trouble balancing the interests of the
individual who claims that a vaccine has injured him against those of
the rest of the disease-free community. New legal standards formulated
in the 1950s and ’60s made it much easier to sue vaccine manufacturers,
and relaxed rules of evidence soon made junk-science allegations much
more common than legitimate ones. When liability claims spiraled to the
point where they threatened to cut off the supply of some vaccines
entirely, Congress set up an alternative compensation system for
children (though not for adults) actually injured by their
immunizations, and imposed a broad-based vaccine tax to fund it.
But it was too little, too late. Enveloped in bureaucracy, the
germ-killing segment of the drug industry has lost much of its
flexibility, resilience, and reserve capacity—and has become painfully
slow in developing what new science makes possible. Short-term economics
and federal law have converged to create a systematic bias in favor of
the germicidal drug invented and licensed decades ago. The principal
fiscal concern is who should pay how much for the new, patented drug, or
whether the old, cheaper generic might not do as well. The principal
regulatory concern centers on the risks of the new drug, not the perils
of the new germ. Insurers are cost averse: wherever they can, they favor
cheap drugs with expired patents. The FDA is risk averse: when in doubt,
it sticks with the old and says no to the new.
Research labs do continue to come up with new vaccines, but that
decade-long process is now routinely followed by a second decade (at
least) before a commercial product makes it to market. No one doubts
that the extra time helps ensure that the vaccine eventually injected
into millions of arms is safer and more effective than it might
otherwise be. But the whole effort is long and costly, and the likely
profits waiting at the end, many manufacturers have concluded, are very
modest by comparison. In 1957, five important vaccines were being
supplied by 26 companies. By 2004, just four companies were supplying
12. Mergers accounted for some of the attrition, but most of it resulted
from companies getting out of the business. More than half of the
vaccines routinely given to young children in 2005 came from just one
manufacturer; four others had only two suppliers.
Having surrendered on all other social aspects of infectious disease,
the health authorities now focus principally on socializing costs.
Capping profits is the politically inevitable corollary. The federal
government now buys over half of all vaccines used in the United States,
and by taking on that role, it has effectively taken control of prices.
After the anthrax mail attacks in late 2001, federal authorities made it
clear that if push came to shove, they would rescind patents, too. Just
two years earlier, at the government’s specific request, Bayer had asked
the FDA to approve and label Cipro for use against inhalational anthrax.
The agency granted the license—the first ever for a drug for use in
responding to a deliberate biological attack—in a matter of months,
basing its approval not on human trials but on the antibiotic’s
effectiveness in inhibiting anthrax in rhesus monkeys. Then came the
2001 mail terror. Demand for Cipro soared—and prices collapsed. Yes,
collapsed.
It was politically unthinkable for Bayer to raise the retail price in
pharmacies, and federal authorities immediately demanded huge discounts
on the pills that they wanted to stockpile. The Canadian government
initiated its price negotiations by announcing that it would ignore
Bayer’s Canadian patent and order a million tablets of a generic version
of the drug from another company.
A couple of years later, Congress passed the 2004 BioShield law. It is
intended to create a federal stockpile of bioterror vaccines, and to
that end, it empowers the Pentagon to bypass certain aspects of the 1962
drug laws. Those provisions have already been invoked once, to cut off
litigation against military use of the anthrax vaccine. The federal
government also offered almost $1 billion of BioShield cash for the
development of a new anthrax vaccine and the provision of 75 million
doses. But established drug companies just weren’t interested. The
contract went to VaxGen, a tiny startup that had never brought a
licensed drug to market and that proposed to supply a bioengineered
vaccine that the army had already developed. VaxGen failed to deliver,
and last December, the government canceled the contract.
A decades-old alternative with various problems continues to be provided
by BioPort, whose declared mission is to develop products for use
against infectious diseases “with significant unmet or underserved
medical needs” and, most notably, “potential weapons of bioterrorism.”
That would mean anthrax, botulism, Ebola, and smallpox, among other
killers. BioPort employs about 450 people.
So what would a watchmaker have done—not a blind one, but one with keen
eyes and an excellent loupe—if called upon to design a microbe that
could thrive among people fortified by fistfuls of vaccines and backed
up by dozens of potent antibiotics? Nature got there, without the loupe.
Humans had spent a painstaking century developing vaccines. So nature
designed an “immunodeficiency” virus—an all-purpose anti-vaccine, so
tiny, quiet, slow, methodical, and gentle that it spread unnoticed for
decades, and so innocuous that it never quite gets around to killing you
at all. It leaves that to the old guard—the bacteria, protozoa, and
viruses that invade when your immune system shuts down, and feast on
your brain, lungs, blood, liver, heart, bone marrow, guts, skin, and the
surface of your eyes. In its final stages, AIDS is truly horrible.
When the blind watchmaker has been pulling such stunts for 4 billion
years, it’s reckless to suppose that HIV was its last or worst. Quite
the contrary: our casual willingness to tolerate a septic underclass, so
long as it remains insular and out of sight, is certain to hasten the
rise of much more and much worse. People as negligent with pills as they
are with germs have already helped spawn drug-resistant forms of
tuberculosis, by taking enough medicine to kill weaker strains, while
leaving hardy mutants alive to take over the business. HIV patients who
don’t strictly follow the complex, unpleasant drug regimen used to
suppress the virus become human petri dishes, in which microbes multiply
and evolve to resist the stew of antibiotics prescribed as a last
resort.
The new infectious diseases are already very good at this sort of
adaptation—they have evolved to be as nimble as we are now
institutionally stolid, as flexible as we are rigid. The influenza virus
evolves exceptionally fast, using pigs as its genetic mixing bowl. HIV
mutates constantly—one drug-resistant strain of the virus now apparently
depends for its survival on a chemical constituent of the drug widely
prescribed to stop its advance. Stubbornly persistent pelvic infections
are on the rise, along with drug-resistant gonorrhea and even syphilis.
A certain staph bacterium responsible for the most common infection
acquired in hospitals has developed ways to pass the gene that produces
a lethal toxin from one strain to the next and also to certain viruses
that can spread it further still.
It’s because the threat is so grave that one must avoid the temptation
to propose a simpleminded checklist of reforms to shoehorn somewhere
into the middle of the next 1,000-page revision of the federal drug laws
and FDA regulations. Germs are terrorists: they let the dead past bury
its dead, they are always changing, and the ones you know aren’t the
ones that will kill you. If we somehow revive a tough, germ-fearing
culture, the risk-averse drug regulators, penny-pinching insurers,
overreaching judges, clueless juries, and preening, industry-bashing
congressional committees will fall into line. If we don’t, no tinkering
will make much difference.
What we need is quite simple. We need many people to be much more
frightened than they currently are. And we need a robust, flexible,
innovative portfolio of drug companies to sink a lot of new capital into
highly speculative ventures, almost all of which will lose money, with
just one or two ending up embraced by regulators, eagerly paid for by
insurers, vindicated every time by judges and juries, lauded by
nonconformist preachers, and so spectacularly profitable for investors
that they crowd in to fund more.
If we can’t drum up concern by other means, some dreadful germ will
materialize and do the job for us. Nobody knows which one; that’s why we
so desperately need the right popular culture and vigorous private
enterprise. If the germs in the tattoo parlors today were both virulent
and untreatable with current medicine, you wouldn’t be reading this, at
least not in the heart of any big city. You’d be heading for the
country.
That’s what the rich did when epidemics struck in Dickens’s day. They
knew what they were fleeing—the urban pathologies described in Our
Mutual Friend in 1864 were as familiar to Londoners as the Thames. And
familiar not just to the boatmen who made a living fishing human corpses
out of the river but also to the middle class, decimated by a violent
cholera outbreak in Soho at the end of August 1854; to the entrepreneurs
who made fortunes collecting and sorting mountains of trash; to members
of Parliament, who, in June 1858, had to evacuate the House of Commons
to escape the pestilential stench of the river; and to Queen Victoria,
who lost her husband to another waterborne disease, typhoid fever, in
1861. Small wonder that cholera was a great agency for social change. In
the time of cholera, the bacterium itself loved everyone.
Anthrax prefers goats; it finds its way into human bodies only very
occasionally, through open wounds. The spores can be inhaled, too, but
ordinarily they clump together and don’t spread well through the air.
They become mass killers only when people painstakingly coat them with
other materials and take special efforts to disperse them. The spores
that struck 11 Americans (and killed five) in Washington, D.C., and New
York in late 2001 weren’t dispersed through the Potomac or Hudson
Rivers; they arrived by U.S. mail. A few pounds, suitably prepared and
dispersed in the New York subway, could kill 100,000 people. If cholera
is a social disease, weaponized anthrax defines the antisocial bottom of
contagion—it’s a microbe that infects humans only with the help of
sociopaths.
But we live in an age of sociopaths, and there remains much that we
don’t know about germs. Viruses and prions may play a far larger role in
genetic malfunctions than we yet fully understand. HIV and influenza
demonstrate the boundless viral capacity to mutate and evolve. And while
anthrax could never make it on its own in New York, murderous people are
scheming to give it help. One way or another, germs will contrive to
horrify us again, in some very nasty way. A society’s only real defense
is to stay horrified, well ahead of the curve.
Peter Huber is a Manhattan Institute senior fellow. His books include
Hard Green: Saving the Environment from the Environmentalists and
Galileo’s Revenge: Junk Science in the Courtroom. |