T

he tick hunter was hopeful he had found the cause of the disabling illness, recently named Lyme disease, that was spreading anxiety through leafy communities east of New York City. At a government lab in Montana, Willy Burgdorfer typed a letter to a colleague, reporting that blood from Lyme patients showed “very strong reactions” on a test for an obscure, tick-borne bacterium. He called it the “Swiss Agent.”

But further studies raised doubts about whether he had the right culprit, and 18 months later, in 1981, Burgdorfer instead pinned Lyme on another microbe. The Swiss Agent test results were forgotten.

Now STAT has obtained those documents, including some discovered in boxes of Burgdorfer’s personal papers found in his garage after his death in 2014. The papers — including letters to collaborators, lab records, and blood test results — indicate that the Swiss Agent was infecting people in Connecticut and Long Island in the late 1970s.

And scientists who worked with Burgdorfer, and reviewed key portions of the documents at STAT’s request, said the bacteria might still be sickening an unknown number of Americans today.

While the evidence is hardly conclusive, patients and doctors might be mistaking under-the-radar Swiss Agent infections for Lyme, the infectious disease specialists said. Or the bacteria could be co-infecting some Lyme patients, exacerbating symptoms and complicating their treatment — and even stoking a bitter debate about whether Lyme often becomes a persistent and serious illness.

Swiss Agent, now called Rickettsia helvetica, is likely not a major health risk in the United States, in part because such bacteria typically respond to antibiotics. Still, several of Burgdorfer’s former colleagues called for infectious disease researchers to mount a search for the bacterium.

Burgdorfer letter
After initial tests, Burgdorfer suspected the Swiss Agent caused Lyme. He shared the strong evidence with a close colleague in Switzerland to see whether he could verify the findings in patients there. Alex Hogan/STAT

“It should be done,” said Jorge Benach, a professor emeritus at Stony Brook University and a coauthor of Burgdorfer’s seminal 1982 paper describing the detection of the Lyme microbe. Public health concerns warrant a new study, Benach said, and with today’s more advanced “weaponry for pathogen discovery, it would make perfect sense.”

Dr. Paul Mead, chief of epidemiology and surveillance for the Centers for Disease Control and Prevention’s Lyme disease program, said that he wasn’t familiar with Rickettsia helvetica, but that “new tick-borne pathogens could certainly be out there.” He cited several found in the years since Lyme’s cause was discovered. Any serious, common co-infection would usually, but not always, be noticed by physicians as a distinct problem in Lyme endemic areas, he said.

In Europe and Asia, Rickettsia helvetica has been recognized as a relatively rare but sometimes serious health threat if untreated. It’s been linked to a handful of sudden deaths from heart disease, as well as facial palsy, deafness, meningitis, chronic muscle weakness, and temporary paralysis. But US laboratories don’t test for the Swiss Agent.

STAT was approached with Burgdorfer’s archives by Kris Newby, who is writing a biography of Burgdorfer and produced an award-winning documentary that sympathetically depicts Lyme patients and doctors who challenged the medical establishment over its approach to Lyme diagnosis and treatment.

The documents offer a tantalizing glimpse into how disease detectives tracked down Lyme’s cause — and how potentially significant loose ends can sometimes be dropped by researchers pressed for time and funding or diverted by more promising leads.

Burgdorfer note
Note written by Burgdorfer Burgdorfer Archives

They show that Burgdorfer intended to look more deeply into the Swiss Agent, which he had discovered in 1978 in Switzerland, but never did. His former colleagues speculate that he set aside this research to focus on identifying the cause of Lyme. When the Swiss Agent turned out to be an unlikely candidate after all, he redeployed his limited time and resources to other prospects.

But the papers suggest that he might have gone to his grave harboring regret that he didn’t follow up on the Swiss Agent findings, as reasonable as the decision was, Benach said.

On the top of a stack of documents in his garage was a mysterious note, penned boldly in red ink in the scientist’s unmistakable handwriting. “I wondered why somebody didn’t do something,” it said. “Then I realized that I am somebody.”

The Lyme wars

Lyme has now become one of the most common infectious diseases in the United States — it’s been found in every state except Hawaii, and is rampant in the Northeast and parts of the Midwest. The CDC estimates that 329,000 people are infected annually.

Lyme has also provoked what’s often described as a “war” over diagnosis and treatment. If Rickettsia helvetica is in the United States, some experts consulted by STAT said, unrecognized infections might be one of several factors contributing to the controversy, by creating confusion over the cause of some patients’ illnesses.

The Infectious Diseases Society of America, the CDC, and many doctors view Lyme as generally easy to diagnose with its characteristic “bulls-eye” rash and pinpoint lab tests, and easy to cure with two-to-four weeks of antibiotics. If the disease is not diagnosed and treated early — in up to 30 percent of cases, there is no rash — patients can develop longer-lasting and more serious symptoms. But most infectious disease doctors say a short course of antibiotics will cure those patients.

But an insurgency of renegade doctors and patients disagrees. They argue that the diagnosis is frequently missed because of poor lab tests and other factors, and that Lyme becomes a chronic condition when untreated or inadequately treated. The patients describe symptoms that include incapacitating “brain fog” and weakness, intense anxiety, severe muscle pain, and paralyzing headaches. Many say that they required treatment with antibiotics lasting months or longer to be cured after years of misery.

Although the few small clinical trials that have examined long-term antibiotic therapy up to 90 days have shown few if any clear benefits, this camp has gained a passionate following, including a cadre of researchers who publish papers supporting this alternative view, and a medical group — the International Lyme and Associated Diseases Society.

The medical establishment mostly views “chronic Lyme” as the product of quack doctors exploiting desperate patients by offering unproven therapies. The patients sometimes need psychiatric care, these experts say, but in any case, chronic physical complaints are not caused by an active Lyme infection. Some state medical boards have gone so far as to revoke licenses of doctors who prescribe long-term antibiotics.

Steere letter
Dr. Allen Steere, then a professor at Yale who first identified Lyme disease in patients, was excited about initial lab tests that strongly suggested that the Swiss Agent was Lyme’s cause. Alex Hogan/STAT
Willy Burgdorfer
Burgdorfer in his lab. Burgdorfer Archives

It’s hard to overstate the animosity that characterizes this clash. A few angry patients have compared establishment Lyme experts — including Dr. Allen Steere, who collaborated with Burgdorfer and has received death threats — to the Nazi doctor Joseph Mengele.

How might the Swiss Agent add fuel to this conflict? Steere, a Massachusetts General Hospital researcher and among the world’s leading Lyme experts, said some patients who believe they have Lyme, but who test negative for the infection, might be suffering from an illness caused by one of several other microbes. Rickettsia helvetica could be among them, he said.

Ticks often carry more than one pathogen, so patients can also have co-infections along with Lyme, which frequently begin with similar symptoms, such as fever, neck stiffness, and headaches.

“You can’t tell them apart clinically” in the first several weeks, Steere said. Co-infections can cause “more severe early disease … a phenomenon of the summer, when the tick bites.” Longer term, the confusion would not last because of Lyme’s distinct symptoms, even if the infection were untreated, he added.

Other experts noted that Lyme and Rickettsia helvetica have co-infected patients in Europe. Antibiotics normally cure Rickettsia helvetica infections, but diagnosis can prove difficult because the microbe does not cause a rash. If untreated or inadequately treated, the two infections share overlapping, serious, and sometimes persistent symptoms, according to clinical researchers. These include debilitating fatigue, severe headaches, muscle weakness, meningitis, facial paralysis, and sarcoidosis — a chronic inflammatory disease that can cause lung and skin problems. Numerous studies have linked Rickettsia helvetica to such ailments, although it is not regarded as a major public health peril in Europe.

Andrew Main, who conducted Lyme research at Yale University in collaboration with Steere and Burgdorfer, had Lyme early on, before its cause was discovered, and was among patients who showed evidence of co-infection with the Swiss Agent — a result that was included in Burgdorfer’s papers but that Main knew nothing about until informed by STAT. The positive tests for the Swiss Agent among Lyme patients back then, he said, strongly support the idea that it might be a current threat.

Robert Lane, a University of California, Berkeley, medical entomologist and Lyme expert who worked closely with Burgdorfer, is respected by both sides in the Lyme wars. He said Rickettsia helvetica could be a significant hidden factor that worsens Lyme infections and makes them harder to cure.

“You would want to look at it both ways. Could that organism, if present in some of the Lyme-disease endemic areas, infect people and cause clinical illness on its own, or react in concert with (the microbe that causes Lyme) or some of the other agents,” Lane said. “If you are looking for one or a few agents in a tick, you may be overlooking others that contribute to the disease burden.”

 

Swiss Agent - ticks
Ticks from Burgdorfer’s archives Ron Lindorf/Burgdorfer Archives

 

Finding the Swiss Agent

The man who found Lyme’s cause devoted his career to studying creatures sometimes described as tiny living cesspools, for the infectious stew of microbes ticks carry and transmit while sucking blood from animals or people.

While training for his PhD in his native Basel, Switzerland, Burgdorfer became a preeminent “tick surgeon,” as he called himself — dissecting thousands with eye scalpels and Swiss watchmaker forceps. In 1951 he became a research fellow at the federal Rocky Mountain Laboratories, a remote outpost in Montana’s breathtaking Bitterroot Valley that specializes in infectious agents.

Burgdorfer fell in love with the Bitterroot and with Gertrude Dale See — a secretary and technician at the lab. She won the multilingual scientist’s heart with her ability to speak French. They married and had two sons, and Burgdorfer became a US citizen and permanent lab employee.

Newsletters

Sign up for our Morning Rounds newsletter

Please enter a valid email address.

He rose to lead the work on Rickettsia, rod-shaped bacteria spread by ticks that cause ailments such as Rocky Mountain Spotted Fever — which is sometimes deadly for patients in New England as well as the West. Burgdorfer built a global reputation for his knowledge of Rickettsia and Borrelia — corkscrew-shaped “spirochete” bacteria of the same group as the species known for causing syphilis.

On a trip back to Switzerland in 1978, Burgdorfer and a few colleagues discovered in local ticks the previously unknown Swiss Agent — later named Rickettsia helvetica (from Switzerland’s ancient Latin name, Helvetia). He found the microbe infectious for meadow voles — a small rodent common in Europe and the United States — and deadly to chicken embryos. No one knew then that it also caused illnesses in people.

Burgdorfer returned with samples of infected ticks and Swiss Agent antigen, molecules from the bacterium that can provoke an immune response, for further study. When mixed with blood sera — a part of the blood that doesn’t contain blood cells — the antigen can show whether a person has been infected.

By then, Steere, a young Yale professor, had for several years been aggressively investigating why some of his patients in Lyme, Conn., were reporting serious and strange symptoms of an apparently new illness. He had found “that many patients suffered not only of arthritis, but also of disorders affecting the skin, muscular, cardiac, and nervous systems,” Burgdorfer told his official biographer from the National Institutes of Health in 2001.

Steere asked Burgdorfer to join the hunt for a tick-borne microbe believed to be at the heart of Lyme. He sent samples of his patients’ blood sera to Rocky Mountain Laboratories for analysis.

Swiss agent test
Blood sera from Lyme patients showed infection with the Swiss Agent. Results of 64 or greater were considered firm evidence, as this test showed for 6 of 11 patients. The test showed no infections with other Rickettsia. Alex Hogan/STAT

Sera tests showed that at least a dozen Lyme patients had been infected with Swiss Agent, and that at least six others might have been infected. The records did not make clear how many Lyme patients had been tested overall. Burgdorfer told Steere and other colleagues that the results pointed to a potential cause of Lyme.

Steere sensed a breakthrough. “I am excited to pursue further the possibility of a rickettsial etiology of Lyme disease,” he wrote to another researcher.

Burgdorfer was encouraged, in part, because of the test’s specificity: A positive result strongly suggested that the person had been infected with the Swiss Agent and not a different Rickettsia such as the one that causes Rocky Mountain Spotted Fever.

But when a second test method showed inconsistencies, doubts crept in about whether Swiss Agent was linked to Lyme. About 18 months later, Burgdorfer broke through, providing a rare undisputed fact in what would become the most disputatious of diseases: A spirochete causes Lyme. Years later, the microbe was named in his honor, Borrelia burgdorferi.

But he hadn’t given up on Swiss Agent completely.

Newsletters

Sign up for our Daily Recap newsletter

Please enter a valid email address.

In the lab during this period, Burgdorfer infected US ticks with the Swiss Agent, his lab books show. The records don’t state his experimental goal, but Rocky Mountain Lab scientists often studied which animals and arthropods could be infected with different agents, and thus might be reservoirs or vectors for disease. He also looked for Rickettsia in ticks in Lyme-endemic areas and found dozens of examples, but often neglected to determine the specific rickettsial species.

In December 1981, just a few months after discovering the Lyme spirochete, he wrote to a Swiss colleague who was overseeing a young investigator’s defense of his PhD thesis concerning the Swiss Agent. Burgdorfer suggested this question: “Do you feel that ‘Rickettsia suisse’ is the etiologic agent of (Lyme)? If so, how would you go about proving this?”

Burgdorfer and his colleagues reported their discovery of the cause of Lyme in the journal Science in 1982. In a handwritten draft found among Burgdorfer’s papers, he described identifying Rickettsia in Lyme patients’ sera and ticks, and his efforts to rule out Rickettsia as the cause of Lyme — without naming the Swiss Agent.

But in the final Science article, he made no mention of Rickettsia. Not a word about possibly finding the Swiss Agent in this country has ever been published.

Swiss agent
Slides of the Swiss Agent from Burgdorfer’s files Ron Lindorf/Burgdorfer Archives

Finishing the hunt

Burgdorfer retired in 1986 at age 60, just a few years after the successful Lyme hunt put him at the pinnacle of his field.

“I started to realize that the research I used to do and was successful in doing has changed its character,” he explained to a National Institutes of Health biographer in 2001. “Molecular and genetic biology have replaced the technologies I was able to apply,” he said. “Since I had no basic training in these fields … I was unable to speak and understand the completely new language.”

Those fluent in the “new language” of molecular biology and genetics will be able to finish Burgdorfer’s work, experts said. If the Swiss Agent is here, they can find it.

The CDC’s Mead said his agency is using molecular techniques to look for evidence of bacteria in 30,000 sera samples from people suspected to have contracted tick-borne illnesses. If Rickettsia helvetica is in some of the samples, it probably will be found, he said. That process will taken several more years to complete.

Dr. W. Ian Lipkin, who directs the Center for Infection and Immunity at Columbia University, is hunting for viruses as well as bacteria living in ticks that spread Lyme, partly to understand why antibiotics sometimes fail in apparent Lyme cases.

Lipkin’s group has collected 5,000 ticks from New York and Connecticut. With funding from the Steven and Alexandra Cohen Foundation, he has so far identified 20 new viruses in these ticks, and is exploring whether they have caused harmful infections in people, using tests that can search for a wide range of tick pathogens in a single sera sample. Eventually, Lipkin said, this process could make the tests affordable on a mass scale.

“Everyone wants to get to the bottom of this,” Lipkin said. “All of this is critical to … finding out why some people respond to antibiotics and some people don’t, and whether or not the antibiotics being used are appropriate, and trying to find ways to link different bacteria and different viruses to different syndromes.”

Lipkin is seeking funds to expand the work to tick-borne bacteria, including Rickettsia.

Asked whether his methods could find evidence of infections with the Swiss Agent, Lipkin replied without hesitation. “The answer is yes,” he said. “If this particular rickettsial species is present, I’m sure we will see it.”

Swiss agent
Negatives of microscopic images of the Swiss Agent, from Burgdorfer’s archive Kris Newby/National Archives and Records Administration archives

Willy’s last words

After he retired, Burgdorfer sent most of his voluminous personal files to the National Archives in Washington, D.C., where they were cataloged for public viewing. Those records contained some Swiss Agent documents. Many more lay untouched for decades in his garage and home office in Hamilton, Mont.

Late in life, Burgdorfer developed Parkinson’s disease and became increasingly infirm. A friend listened to his fears that his garage files might be lost to history. She urged Burgdorfer to contact Ron Lindorf, then an entrepreneur and business professor at Brigham Young University, who had been suggested by colleagues.

Early one morning in June 2014, an agitated Burgdorfer called Lindorf with an urgent request: “Come to Montana and get all my research, my files. I want to put it on the internet so people can see it,” Lindorf recalled him saying.

Lindorf was not a professional archivist, but agreed: His children had suffered from serious bouts of Lyme disease, he was eager to help the scientist who discovered Lyme’s cause, and he had the ability to take on the complex job. The next month Lindorf arrived in Hamilton, departing two days later with his SUV packed full of old files. That November, Burgdorfer died.

To better understand the Burgdorfer archive, Lindorf began collaborating with Newby, producer of “Under Our Skin,” the Lyme documentary. She shared the documents with STAT, hoping that an independent report would illuminate a possibly hidden risk for Lyme patients and others.

Lindorf returned to Montana last year to visit Burgdorfer’s second wife. She pointed across the garage to some additional boxes. Inside a cardboard portfolio covered in flowery fabric and closed by a metal clasp, he found more of the Swiss Agent archives, topped by Burgdorfer’s “I wondered why somebody didn’t do something” note.

“It made the hairs on the back of my neck stick up,” Lindorf said. “It felt like Willy talking from the grave.”

 

Leave a Reply to Shirley Gash Cancel reply

Please enter your name.
Please enter a comment.

  • Nice to see that many of those commenting are in the know. If you are a Lyme patient you are mostly left to your own devices to find solutions, articles and LLMDs that understand treatment options and downstream effects.
    24 years of Lyme, I have suffered in ways there are no words for (first 10 years after treatment I was “fine” until it returned and presented as Lyme plus additional nervous system & autoimmune problems). It is a horrible disease and the medical profession for the most part remains ignorant and unhelpful. Walter Taylor is correct in stating it is a National Disgrace.
    My dog has a vaccine and remains Lyme free, meanwhile I have nothing but pain, medical expenses and lost income.
    I am having some better experiences with Cowden protocol (Samento, Banderol, Cumadin, Burdux) , plus alternating antibiotic. Antifungals (fluconazole) actually bought me many good years– perhaps because it goes into the tissues (and in many cases Candida and mold sensitivity go hand in hand with Lyme). Lyme opens the door to many atypical immune problems. In many ways it is the new HIV.

  • I believe I have the “swiss agent”. The CDC in collaboration with a well known hospital facility have refused to recognize it even thou they found evidence of it in my Brain on a MRI scan. I am a Physical therapist by profession having studied at Quinnipiac University and doing some of my medical work while under study at Yale. I am sad, angry and disappointed that my own members of the medical field have failed me and what is going on in the attempt to cover-up something? More people need to speak out and how do we serve our Hippocratic oath by covering things up instead of moving forward to help those in need?!

  • Diagnosed and treated for Spotted Fever Group Rickettsia in 2010. Paired sera sample sent to California Department of Public Health & they detected IgG and IgM antibody titers, a seralogical confirmed case according to CDC 2010 SFGR criteria.
    CDPH forwarded paired sera sample to CDC Rickettsia Zoonoses Branch-Atlanta and the detected Rickettsia Rickettsia and Rickettsia akari. SFGR therapy was 8 weeks doxycycline therapy through UCLA Santa Monica Infectious Disease. Symptoms returned quickly post therapy and UCLA refused follow-up appointments. Remained IgG positive w/1:512 SFGR Ab titers one year post therapy (2011) and 1:256 SFGR Ab titers in 2014. CDC’s Guide to Clinicians states that SFGR IgG antibody titers disapate @ 7-8 months after (effective) therapy. Persisting symptoms are chronic polycythemia, chronic thrombocytopenia, chronic elevated creatine kinase (muscle inflammation), chronic headaches with episodic muscle cramps, double vision (diplopia), exophoria (eyes turning out), along with chronic sensory motor neuropathy and gate ataxia.

    ALL SYMPTOMS OF CHRONIC TYPHUS, A RICKETTSIAL BACTERIAL DISEASE.

    Had bone marrow biopsy at Mayo Clinic Arizona at end of November 2016 and physicians there refuse to test bone marrow for SFGR and refuse to include SFGR in differential diagnosis as potential cause of my blood abnormalities. Mayo Pathologist not told by clinic hematologists that patient was confirmed case of SFGR. Mayo Clinic Arizona Infectious Disease physician told hematology department that vector borne disease testing of recent bone marrow biopsy for patient’s past positive etiologies (SFGR, WNV, Bb (Lyme) is “unnecessary and unhelpful”. Patient’s previous 2013 bone marrow biopsy at Mayo Clinic Arizona (MCA) was tested for Bartonella infection, for which patient was hospitalized 40 days for acute glomerulonephritis in 1958. Patient has persistent SFGR antibody test (1:256) after MCA 2013 bone marrow biopsy but 2016 MCA Infectious Disease physician refuses all vector borne disease testing on current 2016 bone marrow biopsy.

    Clinical “discovery” of chronic rickettsiosis is being actively circumvented by the very Infectious Disease physicians that vector borne illness patients seek healthcare from, while that patient’s other physicians sit back and watch it happen without comment or intervention! THIS IS A NATIONAL DISCRACE!!?

  • Please, someone help, even the strongest of the strong can hold on for only so long, add mold toxicity and life is pure hell on earth. If this isn’t hell, I’m not going there, the only reason I haven’t ended my misery of a life is the fact that hell will be worse.

  • I have had Lyme’s since 2001. Had a Bulls Eye like no other I have seen! Pulled a Tick off thinking it was a tab! Said, O well and forgot about it. One day at work after doing a Hair color, pulled off cape and there it was. Soft center size of nickel, big red bumps around and across inside of right elbow. What made it like no other was a white scale all around! Been a long haul, but I’m still here. Was doing Myers Cocktail IV’s but after moving I’m kind of on my own. Had Ovarian Cancer in 1975 and was never put on Hormons. Did chemo and had a second surgery two years later and no more cancer. I am now taking 1000 mg B 12 and women’s Irwin’s women naturals gel capes, on all Hormones, Gluent free diet. Have some head problems, and my Ears bop a lot. I am also Hypothyroid. Doing compounded T3 and T4.

  • For those with questions and/or looking for treatment options and physicians, suggest you turn to ILADS, https://www.ilads.org, and patient advocacy organizations such as https://www.lymedisease.org/, state-based Lyme groups, and Facebook groups addressing Lyme, where people share experiences. A great resource book is Dr. Richard I. Horowitz’s “Why Can’t I Get Better? Solving the Mystery of Lyme and Chronic Disease.” He has a new book coming out in February 2017, “How Can I Get Better? An Action Plan for Treating Resistant Lyme and Chronic Disease,” which you can pre-order on Amazon. Dr. Horowitz’ website is http://www.cangetbetter.com. Lyme literate doctors are typically members of ILADS.

  • I have been suffering for over 20 year’s now from Lyme ,and would be willing to be tested and if any experimental possibly treatments, been diagnosed by dr.horawitz, but infectious disease doctor said not true ,please help

    • Sorry this is not the reply your looking for ?, but I’m with you they can use me for any trail as well I’m with you , got nothing to lose, hugs to you let’s hope we can find something quick x

    • I would look into Stephen Harrod Buhner’s books about treating Lyme and coinfections with herbs. He has done a lot of research and I am about to give them a try. I also have some brain fog. You will have to spend some time with his books but I feel hopeful.

    • Please look at Stephen Buhner’s books…Healing Lyme: Natural healing of Lyme Borreliosis and the Confections Chlamydia and Spotted Fever Rickettsioses. He has a lot of good info and some treatment options for Brain fog…..pg219, but you need to read other sections cause it is more complex than one page of info.

    • I am suffering from Lyme disease with Rickettsia as a co-infection. Burbur and Pinella from NutraMedix help to detox the poison in the brain that causes brain fog. 8 drops of Burbur and 8 drops of Pinella on half a glass of water. Let it sit one minute before drinking it. Every 2 hours repeat. All Lyme patients should quit sugar and sugar containing fruits and “quick” carbohydrates. This feeds the bacteria, they live on glucose that is ready available!

  • Thank you for this article. It is refreshing to see Stat, a Boston Globe affiliate, dive into the rich complexities of Lyme and co-infections. I suggest it be required reading for the Globe’s editorial department. Interestingly, many area of health, disease, research, treatment guidelines, insurance coverage, and medical, dental and psychiatric care, diagnosis, treatment and recovery have rich complexities. Curiosity, humility, open-mindedness, persistence, and pivoting when warranted go a long way in advancing such fields toward the end goal of restoring health to patients, instead of symptom control to manage chronic diseases.

Sign up for our Biotech newsletter — The Readout

Your daily guide to what’s new in biotech.