Bull's-Eye / Edition 2

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In this riveting account of medical sleuthing, Dr. Jonathan A. Edlow tells the history of the discovery of Lyme disease over centuries and continents. He also provides the latest information about the disease and its treatment, explaining the recent widespread outbreaks and examining the controversies that have swirled over the diagnosis, vaccine, treatment, and even definition of Lyme disease. In a new preface, Dr. Edlow updates recent developments and controversies in Lyme disease research, discusses reactions from the two "camps" of the Lyme disease community, and writes about some of the reactions of patients to the book.
"A valuable guide for dealing with emerging diseases. . . . The best thing of all about Bull's-Eye is that it lays out the unknowns along with the knowns, the mainstream view along with alternative readings, and thus reveals science for what it is: a perpetual, and admirable, work in progress."-Andrew C. Revkin, New York Times Book Review

"Bull's-eye is a compelling mystery and a riveting account of science in action."-Robert B. Parker

"The story of an emerging infection and its history. . . . Beautifully written. . . . Anyone who is curious about Lyme disease or medical discovery in general will find this book interesting reading."-Raymond Dattwyler, New England Journal of Medicine

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Editorial Reviews

The New York Times
The best thing of all about Bull's-Eye is that it lays out the unknowns along with the knowns, the mainstream view along with alternative readings, and thus reveals science for what it is: a perpetual, and admirable, work in progress. — Andrew C. Revkin
Library Journal
Most lay readers will here find more than they ever wished to know about the classification of American and European ticks and the details of a complicated and lengthy scientific investigation across two continents. However, specialized readers and public library patrons in affected areas will be grateful for this careful study of the history and current status of Lyme disease research and treatment. Edlow, who is affiliated with Beth Israel Deaconess Medical Center and the Harvard Medical School, is a frequent lecturer on Lyme disease and an accomplished medical writer for the popular press. He describes the determined citizens of Lyme, CT, who brought their mysterious symptoms to medical attention, the almost impossible process of identifying the cause of their symptoms, and the ecological context in which the outbreak emerged. The continuing controversies about diagnosing and treating this complicated disease conclude the monograph. For specialized and certain local libraries, Bull's-Eye will be an acquisition of lasting importance. For a more popular book on the topic, public libraries will want Polly Murray's The Widening Circle: A Lyme Disease Pioneer Tells Her Story.-Kathy Arsenault, Univ. of South Florida at St. Petersburg Lib. Copyright 2003 Reed Business Information.
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Product Details

  • ISBN-13: 9780300103700
  • Publisher: Yale University Press
  • Publication date: 4/1/2004
  • Edition description: Second Edition
  • Edition number: 2
  • Pages: 308
  • Product dimensions: 6.00 (w) x 9.00 (h) x 0.69 (d)

Read an Excerpt


Unraveling the Medical Mystery of Lyme Disease
By Jonathan A. Edlow

Yale University Press

Copyright © 2004 Jonathan A. Edlow
All right reserved.

ISBN: 0300103700

Chapter One

A Family Under Siege

For the Murray family of Lyme, Connecticut, things came to a head during the summer and fall of 1975.

Polly and Gil Murray and their four children lived on Joshuatown Road, a picture-postcard country road that Senator Ted Kennedy once called one of the prettiest in New England. Roughly paralleling the nearby Connecticut River, the rural road cuts through lush forest as it stretches from Whalebone Creek to Hamburg Cove. Low fieldstone walls randomly crisscross the woodland, marking ancient boundaries. The route to the Murray house from the main road meanders over hills that gently rise and fall and then rise again to another breathtaking view. When the forest is thick with leaves and growth, one can barely see the homes from the road.

By the mid-1970s, the Murrays had lived in this idyllic spot for more than fifteen years. And for most of that time, Mrs. Murray (Figure 1), an artist with a soft voice and gentle manner, began experiencing a baffling array of physical symptoms that eluded diagnosis by doctor after doctor. She suffered from odd rashes, unexplained neurological symptoms, and painful, swollen joints. All these symptoms got progressively worse during the late 1960s and early 1970s. The arthritis at times prevented her from painting. In 1971 alone, she was hospitalized three times.

Doctor after doctor meted out diagnosis after diagnosis, each one fitting some of the symptoms, but not others. Physicians in two states tested Mrs. Murray for every possible condition. When she didn't get satisfactory answers from her doctors, she set about researching the matter on her own in the medical library at the Yale University School of Medicine. There, she spent hours poring over volumes of thick medical textbooks. One of the diseases, systemic lupus erythematosus (lupus), seemed to fit some of her symptoms, but blood tests were negative.

As her medical record grew thicker and thicker, doctors began to suspect that hypochondria was behind the aches and pains that came and went seemingly at will. Some of Mrs. Murray's relatives who were not nearby to witness her health problems thought that all she needed was a restful vacation. At some of her lowest points, she described feeling alone, defeated, and misunderstood. But she never doubted the reality of her symptoms.

When a doctor sees a patient for any complaint, he has to come up with a diagnosis, or a cause for the patient's symptoms. Armed with the correct cause, the physician can initiate the proper therapy. Doctors call this exercise differential diagnosis-a lofty term for what could as easily be called problem solving or even puzzle solving. The patient gives the doctor pieces of a puzzle, and the doctor puts them together in a way that makes sense. A puzzle with few pieces is easier to put together than one with many pieces; one that has a defined outline or whose picture is shown on the box is easier than one whose outcome is unknown. A puzzle whose pieces are sharp and distinct is easier to solve than one whose pieces are fuzzy or ambiguous.

The physician begins by trying to find as many pieces to the puzzle as he can. A good doctor asks lots of questions and listens carefully to the answers to obtain the clearest and least ambiguous pieces. He pokes and prods when performing the physical examination to uncover additional clues. Armed with these bits of information, he forms a hypothesis about what illness troubles the patient.

At times, all of the pieces fit neatly together and a diagnosis is clear. At others times, even after the physician has obtained all of the relevant information, the diagnosis may still remain elusive because all of the pieces to the puzzle might not be in the box. Other pieces may be red herrings, or extra pieces that don't belong to a particular puzzle. Part of what distinguishes an excellent diagnostician from a less accomplished one is the ability to figure out which pieces belong to which puzzle.

A physician may be confident of his working diagnosis, as it is called, and decide to treat for that condition. This is called a therapeutic trial. If the patient improves, the diagnosis tends to be confirmed (although it does not prove the diagnosis because the patient may have gotten better without any treatment). Other times, the doctor may order laboratory tests or X rays to try to confirm or refute the initial hypothesis. The puzzle may be so unclear that the physician needs a few more pieces to be confident of the solution.

Take the example of a sore throat. Many conditions can cause a sore throat-some common, others unusual. It could simply be a viral or a bacterial infection. It might be an inflamed thyroid gland or perhaps a fish bone stuck in the throat. The doctor starts with a careful history to elicit information that will help him rank the possible diagnoses in order of likelihood. How long have the symptoms lasted? Has the patient been exposed to anyone with strep throat or mononucleosis? Has the patient had a fever? Does the patient have any history of thyroid problems?

The doctor then uses the physical examination to narrow the list of possibilities. An enlarged, tender thyroid gland suggests thyroiditis. Pus in the throat with fever suggests an infection-maybe mononucleosis, perhaps strep throat, or possibly thrush. Red spots on the roof of the mouth and swollen glands in the back of the neck make mono more likely, especially in a young person. Say the patient has had two days of sore throat, a fever of 102 degrees, and pus on the tonsils. The doctor may decide that the likeliest problem is strep throat (this is the working diagnosis) and prescribe antibiotics without further testing (a therapeutic trial). Or he may choose to get a throat culture or a blood test for mono to further increase the confidence in his diagnosis and then treat accordingly.

Polly Murray's doctors performed this exercise of differential diagnosis each time they saw her. The problem was that her symptoms simply didn't fit the pattern of any of the diseases with which they were familiar. She had some symptoms of one disease, other symptoms of another. Abnormal physical findings came and went. Lab tests and X rays couldn't pinpoint a specific diagnosis. Her illness simply was not consistent with what was written in the textbooks.

And if that wasn't bad enough, in the mid-1970s, the rest of her family began getting sick, too. In November 1974, her oldest son, Sandy, developed a rash and painful joints. Around Christmas, came a swollen and droopy left eyelid, ear pain, and severe pain and stiffness throughout his body, mostly on the left side. It even hurt for him to open his jaw. At that time, Mrs. Murray heard of a man in Lyme with a history of an expanding red rash who had what was first thought to be a stroke because of facial drooping. In the hospital, he was diagnosed with viral meningitis, although in retrospect, he probably had Bell's palsy.

Most cases of Bell's palsy are said to be idiopathic-that is, doctors don't know what causes it. What is known is that the facial nerve, which controls the muscles that make the human face so expressive, snakes its way through a narrow, bony canal as it exits the skull. There's no room to spare. So inflammation (which is thought to be due to viral infection) causes the nerve to swell, the resultant pressure chokes the nerve, and the facial muscles stop working, a condition that can be either temporary or permanent. More recent research has suggested that Bell's palsy is often caused by infection by a herpes-virus. Other causes of facial nerve paralysis include diseases such as sarcoidosis, multiple sclerosis, and Guillain-Barré syndrome or, of course, trauma to the nerve from a fracture.

In January of 1975, Gil Murray developed pain in his left knee, thought to be arthritis or tendonitis. But it didn't stop there. "In the early summer," recalls Mrs. Murray, "my youngest son, Todd, had an expanding red rash behind one of his knees, developed a severe headache and flulike illness, and then had multiple ringlike rashes all over his body." Later in the summer, Todd and Sandy were both on crutches because of severely swollen knees. Mr. Murray also had an odd red rash, and the Murrays' daughter, Wendy, had a bad sore throat. Todd, eleven years old that summer, remembers: "From the point of a view of a kid, it was also upsetting because I had been very athletic; it was pretty jarring to suddenly be using crutches off and on for months at a time and not [be] able to interact with my peers the way I had. It was scary in terms of having a disease that nobody knew how to fix. And as the symptoms progressed, there was a feeling of 'what will be next? What will be the next problem?'"

At one low point, the entire family was sick; even the family dogs suffered from rashes and lameness. Mrs. Murray estimates that from the beginning of their medical problems to their final diagnosis, she and her family consulted about thirty physicians.

The frustration was incredible; as Mrs. Murray wrote in a letter to the editor of the New England Journal of Medicine: "Some of the doctors whom I saw were supportive and open to the possibility of the unknown; however, they and medical science could not figure out what our trouble was. On the other hand, many of the physicians I encountered tended to fit me into the category of a hypochondriac. It was suggested that I was obsessed, bored, and depressed and that I was bothering busy doctors; some later suggested that the entire family had a psychogenic problem. I will admit that my behavior became insistent and constantly questioning."

Mrs. Murray's frustration was also fueled by the fact that she became aware of other cases of mystery symptoms in her community. Networking with other parents, she began compiling a list of people who had symptoms remarkably similar to those her own family was suffering. She was convinced that some unknown, maybe new, disease was affecting her family and her neighbors.

Among the doctors Polly Murray eventually consulted was a Harvard rheumatologist-immunologist named Dr. Peter Schur who had been supportive and believed that, although he couldn't satisfactorily explain or diagnose the condition, something real was going on. He understood her frustration, but logistically, it would have been difficult for a doctor in one state to pursue a major epidemiological undertaking in another state. "She saw me for another opinion," Dr. Schur says. "I remember she was very convincing in describing this cluster of kids with juvenile rheumatoid arthritis [JRA] in her community. I said that would be very intriguing because we're always looking for clusters of patients with JRA or lupus and these diseases [to try to find their cause]. I suggested she pursue it by contacting the CDC [Centers for Disease Control and Prevention] or the Connecticut health department."

Mrs. Murray sent Dr. Schur a follow-up letter on October 6, 1975, detailing the sequence of events. Partly at his suggestion, she called the Connecticut State Health Department on Thursday, October 16.

She recounted to the person on the phone the family saga, as well as the fact that she knew of other families that had been similarly affected. She also said that there were at least four children in the East Haddam elementary school with persistent joint problems and that some of them lived on the same street. She wondered aloud why, if JRA was such a rare disease, so much of it could be found in the local area. The response was simultaneously polite and noncommittal. Essentially, Mrs. Murray was told, arthritis is not a communicable disease; there's nothing we can do for you.

She had lived with this phenomenon for years and had begun to recognize its pattern-whatever the "it" was. First, a red rash would begin and spread to enormous proportions. Sometimes, the rash would look like a bull's-eye, with concentric red rings spreading out from a center. The rash was usually followed by neurological symptoms and swollen joints. All the symptoms would wax and wane. Sometimes, she would schedule an appointment with a specialist, and by the time the appointment would roll around, the symptom would have vanished. One can imagine what this does for a patient's credibility. But that was part of the pattern; symptoms would come and go for no apparent reason.

Some of the local physicians whom the Murrays consulted were interested and supportive; others acted as if they were threatened by their inability to solve the puzzle. One, whom Mrs. Murray calls Dr. Esbensen in her book The Widening Circle, referred to the family's symptoms as "annoying" and even said, "Oh no, not again," when another family member appeared with new symptoms. Polly Murray took her son Todd to see this doctor on the same October day that she telephoned the state health department. When Mrs. Murray told him of the call, she says, "He was incensed [and said] 'by whose authority did you do that? What are you doing, stirring up trouble?'" With that, he essentially dismissed them from his practice, telling Mrs. Murray that he wanted them to find another rheumatologist by their next appointment (which happened to be only five days later).

Todd, now a physician himself, still has a vivid memory of that interaction from the perspective of a young boy: "I remember that visit very clearly. The doctor had a bedside manner that was pretty abrupt. He didn't seem to respond well to my mom's questions about a possible connection between my illness, and my brother's and father's illnesses, despite the fact that he had seen both of them, too. Then I remember him doing the arthrocentesis on me." Arthrocentesis is a procedure whereby fluid is taken from a joint for analysis. The doctor paints the skin with iodine, numbs the area with local anesthetic, and then inserts a needle attached to a syringe. Once the needle is inside the joint space, the doctor aspirates the fluid. Mother and son had to silently endure this final insult after the man had already verbally assaulted them.

"Afterwards, as I recall, he basically kicked her out of his office," says Todd, "sort of 'don't come back.' He was pretty rude. He handed her the samples [of fluid] to drive over to the lab. And I remember my mom was in tears as we drove over."

Fortunately, both for the Murrays and for the medical profession, other physicians were far more supportive. One of those was a local doctor named David Nelligan. "He suggested going down to Yale to see what they could find out, and he helped arrange an appointment for me in their rheumatology clinic with a Dr. Robert Gifford," Mrs. Murray recalls. The date of the appointment was November 20, 1975.


Excerpted from Bull's-Eye by Jonathan A. Edlow Copyright © 2004 by Jonathan A. Edlow. Excerpted by permission.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

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Table of Contents

1 A Family Under Siege 1
2 A Little Girl's Knee 9
3 The Broad Street Pump 17
4 An Appointment in New Haven 28
5 An Outbreak of Arthritis 36
6 An Outbreak of Dermatitis 46
7 The European Connection 55
8 Further Work in Europe 62
9 The Blind Men and the Elephant 72
10 The Connection with Ticks 81
11 An Intersection of Investigations 90
12 From the Alps to the Rockies 102
13 To Treat or Not to Treat? 110
14 The Scramble for the Cause 118
15 The Culmination of Efforts 130
16 Progress to the End of the 1980s 141
17 A Geographical Expansion 150
18 The Diagnostician's Dilemma 160
19 Ambiguity in the Lab 170
20 A Tick with Two Toxins 179
21 Cracks in the Theory 188
22 Another Paradigm 199
23 Therapeutic Adventures 212
24 Genomes and Vaccines 221
25 Legal and Political Battles 231
26 An Independent Reality 243
Epilogue 251
App. A Symptoms of Lyme Disease 255
App. B Tick-Borne Diseases in Humans and Animals 256
Sources 259
Glossary 275
Index 279
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