Spillover: Animal Infections and the Next Human Pandemic (30 page)

In late 2006, the attorney general of Connecticut (Richard Blumenthal, later a US senator) began an antitrust investigation into the IDSA and the way it formulated its Lyme treatment guidelines. Had there been conflicts of interest? Blumenthal thought so. The IDSA’s Lyme disease guideline panel undercut its own credibility, he said, “
by allowing individuals with financial interests
—in drug companies, Lyme disease diagnostic tests, patents and consulting arrangements with insurance companies—to exclude divergent medical evidence and opinion.” He emphasized, though, that his scrutiny was directed at the guideline formulation process, not at the science itself. Two years later the IDSA and Blumenthal agreed on a compromise settlement, whereby the guidelines would be reviewed by a new, independent panel. In 2010, the independent panel unanimously reaffirmed the original guidelines. They too saw “
no convincing evidence for the existence
of chronic Lyme infection.” Furthermore, they warned, long-term intravenous treatment with antibiotics was worse than useless; it could lead to deadly blood infections, severe drug reactions, disruption of normal gut flora (the beneficent bacteria that help people digest), consequent diarrhea as other bacteria took hold, and the creation of antibiotic-resistant “superbugs,” menacing not just to patients under such treatment but to all the rest of us also.

Another complication of the whole story is that, though Lyme disease seems like a new problem, unnoticed before 1975, it has probably been around for a long time, not just in the United States but also in Europe and Asia. For decades it was detected marginally and piecemeal, by some of its symptoms, but not recognized as a single syndrome with a single cause. Only in retrospect were the pieces assembled into a pattern with a name.

This prehistory period began in 1909, when a Swedish dermatologist named Arvid Afzelius reported the case of a woman, bitten by a sheep tick, who suffered a rosy rash that spread like concentric ripples. Afzelius called the condition
erythema migrans
(“spreading redness”) and wrote about it for a German journal devoted largely to syphilis, which was a major concern of dermatologists back then. (There was some similarity: Syphilis is caused by a bacterium of the type known as spirochetes, the same group of corkscrewing creatures that includes
Borrelia burgdorferi,
the Lyme disease pathogen.) Afzelius didn’t claim to know the cause of the woman’s rash, but over the next dozen years he saw a similar pattern in five more patients. Other physicians in Europe also began noticing such annular rashes, each resembling a target with a tiny red dot as the bull’s-eye. In some cases, the rash was associated with the bite of an unidentified arthropod (an insect, a spider, a tick?), and often it came with more serious symptoms. Sven Hellerstrom, another Swedish dermatologist, reported in 1930 seeing a man with the distinctive red rash, plus meningitis. As years passed, Hellerstrom found that annular rashes, resulting from tick bites and sometimes involving meningitis, were far from rare in the Stockholm area.

Almost two decades after his first report, Dr. Hellerstrom crossed the Atlantic to attend a medical conference in Cincinnati, where he described his continuing work. The cause of the rash-and-meningitis syndrome, he postulated, was a spirochete. Because the conference was sponsored by the Southern Medical Association, a printed version of Hellerstrom’s 1949 talk appeared in the
Southern Journal of Medicine,
an otherwise unlikely outlet for a Swedish clinician. These were not high-profile publications, neither the papers of Afzelius nor of Hellerstrom nor the others, and of course there was no Internet, no Google, no PubMed, nor any other such means by which to summon obscure citations at the touch of a few keys. But a good memory, broad education, and luck could serve the same purpose.

And eventually did. Twenty more years passed before Rudolph J. Scrimenti, still another dermatologist, practicing in Milwaukee, had reason to recall Hellerstrom’s paper, which he had read as a medical student. Scrimenti, in 1970, became the first physician to report a case of
erythema migrans
in America. His patient, a fellow physician, had been bitten by a tick while grouse hunting in central Wisconsin, and the rash grew outward from the site of the bite, eventually encircling much of his chest, right armpit, and back. Scrimenti treated the symptoms with penicillin. In his brief published report, he echoed Hellerstrom’s guess that it might have been caused by a spirochete, but Scrimenti hadn’t been able to find one.

This is all part of the medical groundwork that was available—though not conspicuously available—when doctors at the Yale School of Medicine heard about the cluster of juvenile arthritis cases in Lyme, Connecticut. One of those doctors was Allen C. Steere, a first-year fellow in the rheumatology division. Rheumatology is the science of joint disorders such as rheumatoid arthritis, which is an autoimmune condition, not an infectious disease. Juvenile rheumatoid arthritis, Steere recognized, should not be occurring in any such cluster. It didn’t pass from one patient to another. It didn’t infect people through their drinking water. It didn’t fly on the wind like Q fever . . . did it?

Steere and his colleagues followed out the cases brought to their attention, did some further epidemiological legwork, found many more cases in roughly the same area, and
began calling the syndrome
“Lyme arthritis.” Steere’s group also took note of the associated symptom among a sizable fraction of the patients: a circular red rash. Other medical practitioners, in Connecticut and nearby parts of New York, also saw cases of this peculiar skin inflammation and began wondering. Was it caused by an insect bite? Was it the same condition,
erythema migrans,
that had been described in the literature from Europe? About that point, in the summer of 1976, a field biologist named Joe Dowhan, working in a forested area some miles east of Lyme, pulled a tick off his leg and dropped it into a jar. Dowhan had noticed the bite because, unlike most other tick attachments he’d experienced in his career, it registered as a small, painful nip. Three days later, he developed a rash. As the red circle grew, he remembered having seen an article about Allen Steere’s work. So he called, got an appointment, sat through an exam, and then handed Steere the tick.

Dowhan’s specimen was identified as
Ixodes scapularis
, commonly known as the deer tick, an arthropod widely distributed throughout the eastern and midwestern United States. This became an important but ambiguous clue in the Lyme disease story, leading both toward insight and into confusion. The insight came first. Fieldwork along the lower Connecticut River revealed that
Ixodes scapularis
ticks were far more numerous in small woodlands and brush on the east bank of the river—the bank on which sat the village of Lyme—than on the west bank. That finding, combined with the fact that human cases also were far more common on the east bank, pointed further suspicion at the “deer tick” as a vector of what even Steere and his rheumatologist colleagues, having dropped the term “Lyme arthritis,”
were now calling
“Lyme disease.”

The confusion grew more slowly. If the “deer tick” carried the pathogen (whatever it was) and infected people like Joe Dowhan by biting them, then the abundance of human cases must reflect the abundance of ticks, and the abundance of ticks must reflect the abundance of deer in those suburban woodlands of coastal Connecticut. Yes?

No. This was an ecological system with the intricacy of chess, not a board game with the clarity of checkers, and its cause-and-effect relations weren’t nearly so simple. The “deer tick,” as later research has shown, lives a complicated life.

49

W
illy Burgdorfer meanwhile made his crucial discovery of the pathogen itself, giving a name and a biological identity to the agent responsible for the mysterious clusters of cases.

Burgdorfer was a Swiss-born and Swiss-trained microbiologist with a shovel-wide jaw, a cagey smile, a great domed head like Niels Bohr, and a deep interest in medical entomology. He did his doctorate on a tick-borne spirochete,
Borrelia duttonii
, which in Africa causes an illness called relapsing fever. By the time he finished that project, Burgdorfer had dissected thousands of ticks to scrutinize their innards. He had also invented a quick, practical technique for determining whether a given tick carries spirochetes: snip off a leg and look through a microscope at the body juice (hemolymph) that dribbles out. Emigrating to the United States, in 1952 he joined the Rocky Mountain Laboratory, in Hamilton, Montana, the same facility where Herald Cox and Gordon Davis had done their work on Q fever. In fact, Davis became his early sponsor there, and for a couple years Burgdorfer continued to work on
Borrelia
spirochetes (and the variants of relapsing fever they cause in America) among captive tick colonies that Davis had established. Some laboratory scientists work with fruit flies, some with carefully inbred mice; Davis and Burgdorfer nurtured teeming cagefuls of ticks.

Then the winds changed: A high administrator told young Willy Burgdorfer that relapsing fever was “
a disease of the past,
” no longer justifying government-supported research, and advised him to pick a different specialty. By his own later account, Burgdorfer followed that advice only partially. He managed to stay at the Rocky Mountain Laboratory (which remained a leading research institution, despite its remote location), doing his primary work on plague, Rocky Mountain spotted fever, and other infamous diseases while pursuing his special interest in tick-borne spirochetes as “a moonlighting job.” When Gordon Davis retired, Burgdorfer inherited the elder man’s lab technician and his captive colonies of ticks. All of this qualified him well for the role he would eventually play with Lyme disease.

Almost three decades later, near the end of his own career, Burgdorfer’s lifelong interest became urgently relevant. By the late 1970s, Allen Steere and others had begun to suspect that what they had first called “Lyme arthritis” was actually a tick-borne infectious disease, which had affected 512 patients, mostly along the northeastern seacoast and in Wisconsin. Hundreds more cases would soon be reported by the CDC. Around the same time, a family practitioner on Shelter Island, New York, just across the Long Island Sound from Lyme, was treating patients with similar histories—unusual feverish ailments that seemed to have been transmitted by ticks. Other tick-borne diseases also occurred on Shelter Island, a small but insalubrious place, so Lyme disease there was just one hypothesis among several. Then a batch of ticks, collected from low vegetation on Shelter Island, was sent out to Burgdorfer’s lab in Montana, where he dissected their gut cavities and found more than 60 percent of them harboring some sort of spirochete. “
No longer did we hear, ‘get out
of the spirochete business,’ ” Burgdorfer recalled later. Spirochetology was back in fashion. These ticks were alive with tiny corkscrewing forms.

When Burgdorfer and his colleagues allowed infected ticks to feed on white laboratory rabbits, the rabbits developed circular skin rashes that grew outward like ripples from the bites, replicating the telltale annular pattern seen so often in human cases. Burgdorfer’s group also cultured the spirochete from ticks and then tested it against antibodies in blood sera from Lyme patients. The positive results in those tests, plus the rabbit reactions, constituted evidence that they had found the agent of Lyme disease. This was how Burgdorfer earned his place in what he
later jovially called the
“lymelight.” When other researchers wrote up a formal identification of the spirochete, shortly afterward, they named it
Borrelia burgdorferi
in his honor. The only hitch in this tale of elegant lab science is that the identity of the ticks was still a matter of confusion.

50

I
t was confused in two ways, one of which is more interesting for our purposes than the other. The uninteresting confusion involved the scientific name. Was it
Ixodes scapularis
carrying the Lyme spirochete in those coastal New England habitats, or did the creature belong to a similar but undescribed species, which should be given its own scientific identity? For a while the Lyme-bearing tick became known as
Ixodes dammini
, until further taxonomic scrutiny invalidated that distinction, in 1993, and restored it to
Ixodes scapularis.
This back-and-forthing was merely a matter of taxonomic practice, reflecting the chronic tension between splitters (who like to delineate many species and subspecies) and lumpers (who prefer fewer). The splitters won a temporary victory; the lumpers prevailed.

A second sort of confusion, more consequential, derived from uncertainty over the tick’s less formal label. As
Ixodes scapularis
, it had been familiarly known as the blacklegged tick. When it was mistakenly split off into a new species, it received also a new common (but not
very
common) name, “
Dammin’s northeastern deer ixodid
.” That clumsy phrase was later shortened to “deer tick.” Name-giving influences perception, of course, and “deer tick” reinforced a misunderstanding about the little beast in question: that this blood-sucking, disease-transmitting arthropod is somehow uniquely associated with deer. Wrong.

Calling it the “deer tick” led to a mistake of circularity. If white-tailed deer are the host animals from which “deer ticks” draw their crucial sustenance, and “deer ticks” are the vectors that transmit Lyme disease to humans, it would seem to follow logically that high deer populations must contribute to high levels of human infection. It
does
follow logically—but erroneously. The syllogism would be sound, except that its first premise is oversimplified and misleading. “Deer ticks” of the species
Ixodes scapularis
do not draw their crucial sustenance from deer.

An ecologist named Richard S. Ostfeld has done much to untangle this confusion. Ostfeld made a two-decade investigation of one ecosystem, in suburban New York, within which
Borrelia burgdorferi
lives. He also reviewed the research done elsewhere and the conclusions that had been (sometimes erroneously) drawn. White-tailed deer, he found, are a misleading distraction. Ostfeld’s book on the subject,
Lyme Disease: The Ecology of a Complex System
, appeared in 2011. “
The notion that Lyme disease risk is closely tied
to the abundance of deer arose from field studies that began shortly after the discoveries of the bacterial agent of Lyme disease and the involvement of ticks as vectors of these bacteria,” he wrote. Those studies were thorough and energetic, he noted, but perhaps driven too much by desire for a simple answer from which public health actions could be taken. Their context was “the hunt for the culprits—the
critical species
.”
One journal article had called white-tailed deer
“the definitive host” of the tick. According to another study, the deer was “the one indispensable piece” of the Lyme disease puzzle in North America. An overview account, otherwise excellent and written by a doctor with an acute sense of the medical issues, had pounced on the same conclusion as a way of explaining why Lyme seemed to be a newly emergent disease: “If the Lyme spirochete had been around for so long, why did it begin to surface as a recognized medical entity only in the past few decades? This question can be answered in one word—deer.” They all agreed: deer deer deer. The one-word answer seemed to point toward a pragmatic solution to the problem of Lyme disease: Reduce the number of infected ticks by reducing the number of white-tailed deer.