Sit Down Before Reading: A Memoir by Dave Bexfield
There are good “perfect storms” and there are bad perfect storms. In 1993 as Laura and I were crossing the Pacific on the S.S. Universe—13 straight days at sea on a dated cruise ship without stabilizers—we ran into one such storm. Gusty winds and 30-foot swells meant barf bags lined the hallways, bumper guards were turned upward in the dining areas to prevent bowls and plates from committing seppuku, and finals were postponed because of the challenge of writing a decipherable sentence while simultaneously stomaching—for all intents and purposes—a nine-hour flume ride. In other words, a perfect storm … for adventurous college students on Semester at Sea at the end of a 100-day voyage around the world.
It was awesomely perfect.
You could put a soccer ball in the hallway and watch it careen down in the direction of the wave’s trough… and then sit back and observe it roll right past you when the ship climbed the next wave. Just walking the hallways turned into the height of adventure and sport, as one moment you would be screaming downhill all out of control, the next clawing the railings just to stay upright. The most intrepid of students, however, got the bright idea to, for lack of a better word, parasail. This requires an explanation.
Students mostly avoided the top deck on the circa 1953 ocean liner converted into a floating college campus, as its smokestack belched soot from its finicky boilers that stained clothing almost as well as the aging ship’s rusty washing machines did. But add in gale-force winds, bedsheets, and a little ingenuity? Death-defying entertainment! All you had to do was manage to climb the outside stairs without getting swept overboard, tie the corners of the bedsheet to each ankle (are you picturing this?), grab the other two corners with your hands behind your back to create a sort of cape, turn carefully into the wind, then—while spreading your arms to turn your sheet cape into a sail—JUMP! and take flight, taking care to let go of the bedsheet and land back on the top deck before you got swept overboard. Miraculously, everyone lived, defying Darwin.
Unfortunately, for every good perfect storm, there are copious not-so-good perfect storms, the kind where bad gets stacked atop more bad and then sandwiched between two slices of bad. I’m talking the kind of bad that requires you to unhinge your jaw just to take it all in, the kind of bad you can’t panini press your way out of. That’s what myriad specialists have warned that Lyme disease has turned into, a perfect storm.
Even they have no idea.
History Repeats
Perfect storms form gradually, methodically. The menacing clouds and whipping winds always appear manageable at the time, never alarming enough to prick up the hairs on the back of one’s neck. In medicine, researchers have repeatedly studied how these metaphorical storms gather, often a cavalcade of compounding errors before critical failure is realized. The description has become so ubiquitous, so overused in healthcare, that there has even been pushback for using the term, as the conclusion of the 2020 article “Not a Perfect Storm” in The New England Journal of Medicine tries to make clear.
If we treat each new epidemic as a perfect storm, it becomes that much harder to build the conviction that we can prepare for the next crisis. The path to strengthening our public health infrastructure will be challenging and will require systemic change. In the meantime, conceptualizing epidemics as perfect storms, even when well intentioned, will make it more difficult for us to move beyond calls for change to actual investment and implementation.
And yet. When Dr. Barry Marshall had his stomach ulcer/helicobacter pylori epiphany in the early 1980s, virtually every doctor was in lockstep agreement: that the Australian physician was plumb wrong. Embarrassingly wrong. You’d-have-to-be-a-gullible-sucker-to-swallow-that-nonsense wrong. He told a podcast that “it was such a tradition of believing that stress causes ulcers, really going back for nearly 100 years, that nobody questioned it anymore.” After all, it was inconceivable that bacteria could survive in the deeply acidic stomach. But here’s the thing, he reminds others: helicobacters in the gut had already been discovered by scientists. In 1892. Then again in 1917, 1940, 1950, 1957, 1957 again, 1966, 1973, 1973 again, 1975, 1978, and 1979 before Dr. Marshall made his “discovery.”
It was old news—really old news. But it was the 1940 discovery of twisty spirochetes in the stomach by Dr. Stone Freedberg, who later became a famous professor at Harvard, that received the full Lusitania treatment. The top pathologist in the United States at the time, Dr. Eddy Palmer at Walter Reed Hospital, released a report that torpedoed his findings, and others like it, for generations. “None of the 1180 specimens was found to contain spirochetes or any structure which could reasonably be considered to be of spirochetal nature.” Just one problem, observed Dr. Marshall. “Unfortunately, he had incompetent researchers working for him.” But it was too late. Most researchers had moved on, as “nobody bothered about it, it was just useless information.”
Sound familiar? Contaminated specimens, spirochetes that can’t be found, research that can’t be replicated, scratches on the glass. Even the “pillars of truth” are similar in their blind allegiance. Just as no bacteria could survive in such an acidic environment, Lyme disease is a contained, regional disease, easily detected and easily dispatched. And multiple sclerosis has a direct connection to latitude and sunlight exposure, with a genetic component and no doubt a viral connection. Case closed, right?
History, tragically embodying the cliché, has repeated itself … all the way down to the microscopic spiral bacteria that has been corkscrewing its way, undetected and undeterred, through humanity for millennia.
History Repeats
Dr. W. H. Hoffmann summed up the advances in research succinctly in his piece The etiology of multiple sclerosis from the Laboratory of Medical Research at the fabled Las Animas Hospital in Havana, Cuba, made famous for its work on yellow fever. The year was 1921.
As the researches of the last years have shown, an always increasing number of diseases are found to be caused by spirochetes of different kinds; and in many cases it has become evident that the spirochetes attack by preference the central nervous system, which is involved in the disease much more than, from mere clinical observation, formerly could have been supposed. In the same sense it seems now that multiple sclerosis belongs to this most important group of nervous diseases produced by spirochetes.
After the Lancet published Dr. E. F. Buzzard’s Spirochetes in M.S. theory in 1911, the race was on to investigate his potential findings. Nearly two dozen studies examining the spirochete and MS connection—Spirochetes: The Cause of MS (1917), Spirochetes in the CSF of MS Patients (1922), Spirochetes in the Human Brain of MS Patients (1928), Spirochetes within the Ventricle Fluid of Monkeys Inoculated from Human MS (1948), Spirochete-like Formations in MS (1939), Acute Plaques in MS and the Pathogenic Role of Spirochetes as the Etiological Factor (1952), to name a few—were published by a wide range of researchers in the decades leading up to Dr. Ichelson’s seminal discovery in 1957. She even got the attention of Eleanor Roosevelt.
And then the dissenters descended.
Failure to isolate Spirochaeta myelophthora (Steiner) from cerebrospinal fluid in multiple sclerosis (1958)
An attempt has been made to duplicate the findings of Ichelson, who reported the presence of Spirochaeta myelophthora in cultures of cerebro-spinal fluid in 78 per cent of a group of patients with multiple sclerosis. Studies in 32 consecutive cases of multiple sclerosis failed to reveal any spirochetes. The probability that this failure resulted from chance alone is infinitesimal.
Cultures on anaerobic medium were made of the spinal fluids of 27 patients with multiple sclerosis and 13 controls after the method described recently by Ichelson. Where Ichelson found organisms resembling spirochetes in 78 per cent of patients with multiple sclerosis, we found some form of what appeared to be a living micro-organism in 18.5 per cent. The control fluids were all sterile. The work requires confirmation and amplification.
Using technics very similar to those proposed by Ichelson, a study was made of 28 persons with well documented diagnosis of multiple sclerosis, and 14 persons with other conditions which involved the central nervous system. We attempted to isolate a spirochete similar to the one which Ichelson claims to have found. We were unable to confirm her work. The possibility that this result could have occurred by chance alone is statistically invalid.
Cultures of cerebrospinal fluid from 12 patients with multiple sclerosis and 14 patients with other disorders, of which 9 and 11, respectively, were considered satisfactory, remained negative for evidence of growth of spirochetes during periods of incubation of at least thirty days. The failure to obtain growth of spirochetes in cultures of cerebrospinal-fluid specimens from patients with multiple sclerosis is at striking variance with a previous report of positive cultures in 78 per cent of such cases.
That last study was published in the New England Journal of Medicine. By the time that Dr. Kurland—himself a long believer that MS was caused by a virus—delivered his talk at the Miami Beach public health gathering in 1962, the very idea that MS could be associated with a bacteria, particularly a spirochete, was DOA. After all, multiple studies had failed to replicate Dr. Ichelson’s findings, so why beat a dead horse? Despite a plethora of papers published since with salaciously bold claims—Multiple Sclerosis is a chronic central nervous system infection by a spirochetal agent (1988), Bacterial infection as a cause of multiple sclerosis (2002), Chronic Lyme borreliosis at the root of multiple sclerosis – is a cure with antibiotics attainable? (2005)—the hypothesis has never been seriously revisited. Never.
Revisiting the Research
When new evidence comes into play—in this case the very existence of Lyme disease and the revelation that bacterial spirochetes fuel the disease and are spread by ticks—one would think that researchers would reevaluate related research, including research that was considered settled. After all, without this form of checks and balances, easily avoidable missteps might get compounded. Obvious opportunities to catch errors could get missed. Flagrantly flawed assumptions erroneously may even get elevated into canon. Alas, the trifecta hit: they were individually compounded, missed, and elevated.
But this is Lyme disease, the third rail of diseases.
Although Lyme disease was discovered in Connecticut in 1981, the lion’s share of cases at the time of its discovery occurred in nearby states like New York and Pennsylvania. Indeed, in 1988, New York state alone accounted for 56% of the cases nationwide, with Westchester and Suffolk counties racking up an eye-popping 44%. Cases in Pennsylvania were no doubt at the time also circulating at an aggressive clip, as today the state routinely leads the US in cases of Lyme disease.
Before Lyme disease started spreading more widely across the United States and around the world due to a confluence of factors, it was intensely local all the way down to the county, even city level. Like real estate, location matters in Lyme disease. It matters a lot a lot. People who come down with Lyme invariably have at least one of two things in common: they live (or lived) in an area with Lyme-infected blacklegged ticks, or they visited such an area (e.g., Northern Europe from South Africa). This truism, crucially, also applies to where patients are located when participating in clinical trials. Even armchair researchers should be able to see where this is going. It took all of five minutes, ten tops, to get to the root of the problem: where were these researchers doing their research?
In the 1950s, bacteriologist Rose Ichelson drew her patients—76 diagnosed with multiple sclerosis along with 28 negative controls—from the surrounds of Philadelphia, as little as a 2-hour drive from Westchester County, NY, and less than 4 hours from the popular beaches of Suffolk County and its tourist hotspots like the Hamptons, Fire Island, and Montauk. She was pulling people diagnosed with MS from tick Mecca circa 1950.
But Vermont in the 1950s? Highly unlikely to have any cases. Rochester, Minnesota? Not for another decade or two. Chicago? A stretch. San Francisco? Doubtful except among the cosmopolitan wealthy enough to enjoy cross-country air travel. These seemingly random locations were home to the very studies that purportedly debunked Dr. Ichelson’s discovery of spirochetes in the spinal fluid of MS patients. Only Berkley researchers out of California detected a smattering of maybe spirochetes (18.5%), the others laid goose eggs—wholly predictable results… if you knew about Lyme disease and the habitat for the ticks that carry the disease.
These conflicting studies were all deeply flawed and fated to fail at replicating Rose’s discovery given that they studied patients outside of tick endemic areas. And because of their exceedingly small sample sizes, with just a few corkscrew misses, the conclusion that “the probability that this failure resulted from chance alone is infinitesimal” turns laughably probable; the unfortunate Custer confidence among medical researchers sure runs deep. Even Rose’s shocking finding of 78% of MS cases being positive for spirochetes gets dinged due to scale, as chance can work both ways in research (that is, a small sample size can result in missing the true prevalence in a population on the low side or the high side).
All my estimates and analysis consistently point to a clear and repeatable number: approximately 30% of cases currently diagnosed as multiple sclerosis are, in fact, Lyme disease. While this is a worldwide average, the true misdiagnosis rate by region will fluctuate, and potentially wildly if one were to rewind 60, 70 years. Indeed, it is reasonable to assume that all the research studies highlighted above were largely accurate at the time for their regions. The small San Fran sample pool of just five positive cases of a “living micro-organism” no doubt included transplants from the Northeast. And Dr. Ichelson likely stumbled on a relative river of Lyme cases in her native Pennsylvania, skewing her numbers higher than expected.
The perfect storm raining on Rose’s multiple sclerosis research extends far beyond the laboratory and clinical trials. With these elusive spirochetes being extremely challenging to detect even in today’s time, it will take significant financial resources and technology to reliably search out and pinpoint the corkscrew marauder. But without the anticipated benefit of billion-dollar drug sales, no pharmaceutical company is going to invest in trying to find the bacteria, especially one that could swipe massive profits away from existing drugs that treat MS. In the US, that leaves the federal government as the responsible party, the federal government that just disbanded its Tick-borne Disease Working Group (TBDWG). The funding authorized by Congress as part of the 21st Century Cures Act was approved for only six years. Because that’s approximately how long it takes to cure stuff, apparently.
Normally, faulty science combined with deficient funding would be enough to throttle any medical endeavor, but this is Lyme disease, the third rail of diseases. So, to amplify the odds of an MS misdiagnosis, you can tack on woefully inaccurate diagnostic testing of both diseases, neurologists who are profoundly unfamiliar with tickborne illnesses, health insurers who are dismissive of Lyme disease claims in non-endemic areas, inane policies that recommend against testing for Lyme disease in people diagnosed with MS in all but the rarest of cases, physicians who then ignore a positive test after someone shockingly manages to get a test … only to then hear from their doctor that it must be a false positive despite the fact that it’s an onerous two-tiered test that requires at least five very specific bands to appear on their Western blot (which in itself is like winning the Powerball), and then, in those exceedingly rare instances when a person gets both a Lyme disease test and a begrudgingly accepted positive result, a treatment regimen that inevitably will be too short and restrictive. Their Lyme disease will undoubtedly come back. And they’ll still carry a diagnosis of multiple sclerosis. Perfect.
Ding
More than a dozen new emails from members of ActiveMSers remained unopened. That’s okay. I had to zero in on one first. Randall the actuary had written with the subject line: Ceftriaxone Injectable. After early success with oral doxycycline, was he making progress with his treatment efforts?? Holy crap. He was.
I just got back from establishing care with a very open-minded MD. Apparently, ceftriaxone is available as an intramuscular injection. There is no difference in uptake compared to the IV version except that the IM has a better release profile lasting throughout the day instead of peaking at 2 hours post IV and getting washed out of the system via the kidneys.
His next email spelled out his doctor’s rationale for approving treatment, as he forwarded the message.
Dear Randall, I hope you are doing well. In preparation for the upcoming appointment please read the consent below and reply for compassionate use of ceftriaxone 1 gm daily intramuscular injection for 30 days. … The reason for the compassionate use or a trial of a non-FDA approved or evidence-based treatment is because all other treatment for your multiple sclerosis has failed so far and your symptoms [are] severe and progressing. You have reported that treatment with doxycycline has improved your urinary symptoms and the improvement seems to be lasting. There is no evidence that you have Lyme disease based on all available test results we have obtained so far. There is no evidence multiple sclerosis can be improved or cured by antibiotics such as ceftriaxone based on current medical evidence. The reason we are doing compassionate use of ceftriaxone injection is only because you have requested a trial and consent to the risk of such treatment.
The doctor then went on to document the potential risks of ceftriaxone, generally considered one of the safer antibiotics. But all medications harbor potential risk to the patient. After highlighting anaphylaxis and death, he proceeded to list all documented potential adverse reactions to the drug. As in, all of them, in a deft CYA maneuver should anything go wrong. He concluded by reminding Randall that “this compassionate treatment with ceftriaxone is requested by you and completely voluntary on your part and you are accepting the risks and consequences of ceftriaxone injection as discussed.” The treatment wasn’t covered by insurance, his first injection would be in his clinic, he’d be closely monitored throughout the course of antibiotics and for six weeks afterward, and the doctor could pull the plug at any time and for any reason. Capisce?
He capisced.
I’m not the jealous type, at least not usually. But damn. If my attempts with UNMH were ultimately to flatline, at least I had an alternative: Dr. Alternative, one of the few physicians willing to take the risk and treat me. Then, finally, after an interminable wait following my infectious disease appointment—let’s call it a day or two, I was particularly antsy—my cell phone started ringing. Caller ID said it was UNMH—it must be scheduling! I was worried there would be a delay, but no, they were clearly on top of my case. It was your standard Covid screening call before any medical appointment, a call I always ace because Laura and I have been religious about avoiding any possible risk, especially given that I was days away from treatment. I could almost recite the questionnaire verbatim…. Are you experiencing any symptoms? No. Have you had any recent exposure that you know of? No. See you soon!
“Mr. Bexfield, are you experiencing any Covid symptoms?” Nope! “That’s good to hear,” said the UNMH representative. “We are doing contact tracing, as the infectious disease doctor you saw recently was just diagnosed with Covid.”
I know what you're thinking, and yes, I proudly STILL HAVE A LANDLINE.
What did she just say? That’s not how the screening call was supposed to go. Not. At. All. The doctor responsible for initiating my IV antibiotics now had to get treated and overcome Covid, I still did not have a scheduled infusion date, and our 30th wedding anniversary—my promised deadline to my wife to start treatment—was only 10 days away. Oh, the humanity. I swear, Max Pruss had it easier. Mr. Pruss captained the Hindenburg.
He survived. Will I?
