Anonymoose---There's been more research into these vascular blockages in the brain--what Putnam saw through a microscope and surmised were emboli, show up on high-powered MRI as microvascular involvement, and are now being studied in MS and aging. So, therapeutic responses are being considered....150 years after Rindfleisch first noted this. Putnam used blood thinners to address what he saw, but he did not cure MS. Which is probably why the vascular theory was discarded for the immune theory.
Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis.
We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI.
These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response.
Research regarding fibrinogen as the first blood protein to cross the blood brain barrier in MS was first posited by Dr. Zamboni in his "Big Idea" paper of 2008, where he compared venous disease/ulcers of the legs with MS lesions, and showed the correlation between fibrin cuffs (or emboli), iron deposition and venous reflux. New research from Gladstone Labs confirms Dr. Zamboni's observation regarding fibrinogen.
Here's the history of Putnam, the vascular theory and MS. I'll copy what I wrote over from Facebook. It is a long read, but I hope worth it. Since you seem really interested, I hope this answers some questions about where we've been, and hopefully, where we may be going.
The history of the National Multiple Sclerosis Society in the United States, first called the Society for the Advancement of Multiple Sclerosis Research, is told in one very specific way, in a brochure published on the NMMS page. Their focus is on the immunology of MS.
With remarkable foresight, the very first research grant from what was then called The Society for the Advancement of Multiple Sclerosis Research was awarded to study the immunology of MS—the relationship between the body’s immune system and the central nervous system (the brain and spinal cord). This 1947 grant went to Dr. Elvin Kabat at Columbia University. He subsequently identifi ed abnormal immunologic proteins in the spinal fluid of people with MS. These proteins appeared in patterns known as oligoclonal bands.
But this is only part of the history. The founding neurologist and first honorary chairman of The Society for the Advancement of Multiple Sclerosis Research is never mentioned by the National MS Society. In fact, this neurologist was responsible for bringing immunology into MS research. He invited Dr. Elvin Kabat to work on MS research with him at Columbia University, and hired this young researcher in 1940. He was responsible for helping select him for the first research grant made by the MS Society.http://www.annualreviews.org/doi/pdf/10 ... 183.000245
Who was this neurologist? His name was Dr. Tracy J. Putnam, and he created an animal model of multiple sclerosis by occluding the venous sinus in dogs. He believed MS was a disease of blocked venous blood flow, which created the immune response in the central nervous system.
Dr. Tracy Putnam, American neurologist and chair of the medical advisory board for the National MS Society, experimented by obstructing venous outflow in dogs, only to find that the dogs quickly developed brain plaques similar to those found in MS patients. Putnam wrote about his observation, “The similarity between such lesions [in dogs] and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction is the essential immediate antecedent to the formation of typical sclerotic plaques.”
He is absent from the NMMS history. But we need to remember his name.
Here is a story about the founding of the National MS Society, printed in Time Magazine in 1946---
Time Magazine, 1946 "The Mystery Crippler"
The patient first notices a pins-&-needles sensation in his legs. After a time his head and shoulders may twitch, his eyeballs roll wildly, he sees double, reels when walking, stumbles in his speech, from time to time is seized by uncontrollable laughing or crying jags. In advanced stages he may be paralyzed.
The patient is not drunk. These are symptoms of a mysterious, widespread disease known as multiple sclerosis, a disorder of the nervous system. Doctors have recognized it for nearly 100 years (the German poet Heinrich Heine is believed to have died of it), but they have never discovered its cause or cure.
Last week the first concerted attack on the disease was launched by a new organization started by multiple sclerosis sufferers. Based in Manhattan, the Association for Advancement of Research on Multiple Sclerosis has enlisted some of the top U.S. neurologists (honorary chairman: Dr. Tracy J. Putnam, director of Columbia University's Neurological Institute).
Neurologists estimate that multiple sclerosis is more prevalent than infantile paralysis. The disease is characterized by sclerosis (hardening) of scattered patches of nerves in the central nervous system. It has been attributed variously to 1) clots in the small blood vessels of the nervous system; 2) spasmic contractions of the blood vessels 3) a spirochete (not the syphilis variety). But treatments based on these theories (e.g., anti-clotting and blood-vessel dilating drugs) do not cure the disease. It usually strikes between the ages of 20 and 35. It is seldom painful, and rarely fatal, but often cripples its victims.
Prime aims of AARMS: 1) raise funds for a full-dress research program; 2) determine the scope and prevalence of the disease.http://www.time.com/time/magazine/artic ... z0cF87aQQF
Dr. Tracy J. Putnam was the Director of Columbia University's Neurological Institute and the leading expert on Multiple Sclerosis in early 1946, when the Time Magazine article was published. Putnam was a neurosurgeon and a neurologist. He was the first major researcher to go public with a theory for MS. But by mid 1947, he was forced to resign from Columbia and left New York and his academic career in disgrace. Why? One reason is because Dr. Putnam did not cure MS.
Senator Charles W. Tobey of New Hampshire sponsored the National Multiple Sclerosis Act, which began hearings before the Senate Subcommittee on Health of the Committee on Labor and Public Welfare on May 10, 1949. Senator Tobey's own daughter had multiple sclerosis, and he sought the advice of the National Multiple Sclerosis Society in composing the legislation. When the proposal for a National MS Research Institute was included in hearings on a National Health Plan in the House of Representatives in 1949, Ralph I Straus, the president of the NMMS, gave testimony, as did Senator Tobey, Mrs. Lou Gehrig and Dr. Tracy Putnam, as well as a number of other doctors, family members and patients.
They were not entirely in agreement. Most of the laypeople present stated that no progress whatsoever had been made in the "fight" against MS and demanded the kind of government interventions that had made possible the mass production of penicillin, which in turn was credited tor the sustained health of Allied troops invading Nazi Europe. Putnam, who had been an active participant in MS research for the last two decades, was confronted by a discontented public who did not seem to know about the progress he and others had achieved since Cruveilhier and Carswell.
Putnam was the first major researcher to go public with a theory of MS cause and the prospect of a treatment in 1942, but in 1949 he could not claim great success for this treatment. Though he described further research into other medications, he was facing people who wanted results, no hypotheses.
From Multiple Sclerosis through history and human life by Richard M. Swiderski page 159 (google books)
Dr. Putnam only had his hypothesis of blocked veins, but he did not have success in treating MS with newly discovered anticoagulants. The public wanted results. They wanted a penicillin for MS. They wanted a vaccine, like the polio vaccine. They wanted a cure.
All Putnam had were theories, his published research, and a trial in pwMS using the drug dicoumarin. This drug had just been discovered in 1941; created from spoiled clover. It was found to be useful in dissolving blood clots. Dicoumarin was helpful for relieving symptoms in people with MS. But it was not a cure. The disease continued to progress. http://archneurpsyc.jamanetwork.com/art ... amp;page=1
It is important to state that this is why neurologists say, "We've already been down the vascular path in MS research. It was a dead end." Because Tracy Putnam did not cure MS with a newly discovered blood thinner. He had a decade for his vascular research, and it was dismissed. The EAE autoimmune model has had over six decades, and there is still no cure for MS.
Who was this brilliant man, and why has he been removed from the story of multiple sclerosis research? Why has his work been categorized as failure?
Dr. Putnam assumed the Directorship of Neurological Unit at the Boston City Hospital in 1934 as Professor of Neurology at Harvard. His intellect, scientific bent, and exceptional teaching and writing skills, all developed to the fullest in the exceptional period of Harvard’s eminence in the neurosciences, soon catapulted him into the international prominence.
During his research years at Harvard, he developed novel fields of study and surgical approaches to neurological disorders, he developed novel ideas about subdural hematoma, hydrocephalus, motor disorders and epilepsy, and participated in the early studies with Houston Merritt and others, eventually developing the drug Dilantin as he described in his book in 1970 “The Demonstration of the Specific Anticonvulsant Action of Diphenylhydantoin and Related Compounds.” He was appointed Professor of Neurology, Professor of Neurological Surgery, and Director of the Neurological Institute of New York in 1939, just before the onset of World War II and the departure of a number of the talented younger people who he brought as supporting staff to New York.
Dr. Putnam’s years at the Neurological Institute of New York were not happy ones for him, since World War II decimated the younger and potentially helpful members of his staff, and his gentility and generosity of spirit were commonly misunderstood as weakness and vulnerability.
He was beset by administrative and wartime personnel problems while at the same time maintaining a major editorship in Neurology and important governmental responsibilities.
Because of the various pressures and other factors, he moved to California in June 1946 to become Director of Neurology at the Cedars of Lebanon Hospital. As Dr. Edward Schlesinger* has written, “Rarely has an individual brought so many talents to neurology and neurosurgery, or pointed out so many directions of ground-breaking research. Unfortunately, coincidences of time and place exacted a catastrophic toll on his career and he died on March 29, 1975.” http://neurosurgery.org/society/bio.aspx?MemberID=2839
There were rumblings about Dr. Putnam. He had hired many "non-Aryan" neurologists on the Columbia staff. He had brought in Jewish researchers, like Elvin Kabat, to help him understand MS. Putnam did not care about racial or religious divides. He only wanted to work with the best and brightest. For those of us who were not living during this time, it may be hard to comprehend, but anti-semitism in the US was very prevalent. Here is more on this part of the history---
Dr. Putnam was forced to resign in 1947, ending his career at Columbia. Colleagues at the time suspected several reasons, including a lack of administrative skills, enemies on the staff and the conflicts that arose from having a neurosurgeon running a neurological institute.
But Dr. Rowland unearthed another explanation. A New York newspaper of the era, called PM, reported in 1947 that Dr. Putnam had been told to fire all of the “non-Aryan” neurologists, something he was unwilling to do.
Dr. Rowland corroborated this story when he discovered a 1961 letter written by Dr. Putnam to a fellow physician. Dr. Putnam reported that Charles Cooper, then head of Columbia’s affiliated hospital, Presbyterian, had told him in 1945 “that I should get rid of all the Jews in my department or resign.”
Quotas for Jewish medical students and physicians disappeared fairly rapidly after World War II, partly in response to Nazi atrocities against the Jews. But Dr.Putnam’s quiet advocacy on behalf of Jewish physicians when such a stance was unpopular should not be forgotten.http://www.nytimes.com/2009/05/26/health/26quot.html
Another one of the Jewish MS researchers Dr. Putnam worked with and supported was Alexandra Adler-
Adler also contributed to the understanding of the neurological basis of multiple sclerosis. Adler and the Harvard neurosurgeon Tracy Jackson Putnam (Putnam & Adler, 1937) conducted a post-mortem study of the brain of a woman diagnosed with multiple sclerosis, demonstrating that cerebral plaques characteristically spread in a rather odd, specific relationship to large epiventricular veins and bizarrely altered the affluents of these veins. Illustrations from this article are routinely reproduced in the medical literature on multiple sclerosis.http://www.apadivisions.org/division-35 ... raphy.aspx
Dr. Tracy Putnam left Columbia University and academia behind. He moved to Beverly Hills, CA, and became Director of Neurology at the Cedars of Lebanon Hospital. and also began a private practice as a neurosurgeon and neurologist. He continued to treat MS patients with anticoagulants. But he was a broken man. He was bitter over his treatment at Columbia, he was disheartened that his research had been dismissed. He kept very detailed records on the MS patients he treated with anticoagulation therapy. He cared deeply about his patients, and wanted to be able to offer them more help and hope. http://www.oac.cdlib.org/findaid/ark:/13030/tf1n39n78s/
I've thought about Dr. Putnam many times during the past four years, wondering how he would respond to Dr. Schelling's book or the new doppler ultrasound technology and Dr. Zamboni's discovery of intraluminal venous malformations in people with MS.
We can see the parallels --the tossing aside of Dr. Putnam's research after a lack of a "cure" and the discontent with Dr. Zamboni's CCSVI research and the lack of an immediate cure. I worry that the immunological side of MS is given all of the research money and time, while the vascular connection remains underexplored and underfunded. I worry that the focus on a "cure" is put before the understanding of MS pathogenesis. How can we cure what we do not understand? It bothers me that there is not more curiosity in the neurological world regarding truncular venous malformations. As regular people, we can see the direct connection from Dr. Putnam's studies on veins in dogs, to Dr. Zamboni's discovery of intraluminal malformations in jugular veins, and the hemodynamic changes in blood flow in people with MS. Why is there not more curiosity in MS specialists? Where are the Tracy J. Putnams?
Let's keep Dr. Putnam's research and humanity alive. He may not be included in the National MS Society pages as a hero, but we can honor him in our own ways. By telling his story, by encouraging multi-disciplinary collaboration in MS research, by caring about those with MS, and by believing that the best and brightest- no matter their heritage, background or medical training-should be allowed to explore and understand this disease. (and maybe you can give to CCSVI Alliance, and help us carry on this work http://www.ccsvi.org
Thank you, Dr. Putnam.