Welcome! This blog contains research & information on lifestyle, nutrition and health for those with MS, as well as continuing information on the understanding of the endothelium and heart-brain connection. This blog is informative only--all medical decisions should be discussed with your own physicians.

The posts are searchable---simply type in your topic of interest in the search box at the top left.

Almost all of MS research is initiated and funded by pharmaceutical companies. This maintains the EAE mouse model and the auto-immune paradigm of MS, and continues the 20 billion dollar a year MS treatment industry. But as we learn more about slowed blood flow, gray matter atrophy, and environmental links to MS progression and disability--all things the current drugs do not address--we're discovering more about how to help those with MS.

To learn how this journey began, read my first post from August, 2009. Be well! Joan

Showing posts with label Thomas Rivers. Show all posts
Showing posts with label Thomas Rivers. Show all posts

Tuesday, June 19, 2012

The History of the National MS Society--founded by Dr. Tracy Putnam


June 19, 2012 at 8:27am

The history of the National Multiple Sclerosis Society in the United States is told in a very specific way, in a brochure published on the NMMS page.   Their focus is on the immunology of MS, the EAE mouse model and the subsequent MS immune suppressing treatments.

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). 
http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-History-of-Multiple-Sclerosis.pdf

However, this is only part of the history.  The NMMS leaves out the real beginning.  Sylvia Lawry started the MS Society to help her brother who had MS.  She found the greatest medical mind of her generation, MS specialist and neurologist Dr. Tracy Putnam, and asked him to lead her new association.  Yet Dr. Putnam is never mentioned by the National MS Society.  It was Dr. Putnam who 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.  Yet Dr. Putnam is no longer mentioned by the NMMS.
http://www.annualreviews.org/doi/pdf/10.1146/annurev.iy.01.040183.000245

Why does the NMMS leave out Dr. Putnam?  Perhaps because his entire career he stated that MS had a vascular component.

Dr. Tracy J. Putnam 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.”
http://archneurpsyc.jamanetwork.com/article.aspx?articleid=646487
http://jnnp.bmj.com/content/s1-17/67/193.full.pdf
http://archneurpsyc.jamanetwork.com/article.aspx?articleid=648079

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).

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 the end of the 1940s, he was forced to resign from Columbia and left New York and his academic career.  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  

Dr. Putnam had his hypothesis of blocked veins, but he did not have success in curing 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.  

This is the primary reason why the research focus went to the EAE model of MS, created by Dr. Thomas Rivers at the Rockefeller Institute.  Rivers has worked on the polio vaccine, and his research was perceived as the "future."  He had discovered, while working on the polio vaccine, that immune cells, once activated by a foreign agent, could enter the central nervous system of monkeys and cause demyelination.
http://centennial.rucares.org/index.php?page=EAE

Putnam had his published research and a trial in pwMS using the drug dicoumarin.  This drug had just been discovered in 1941; it was a blood thinner 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 the hoped for cure.  The disease continued to progress.  At that time, there were no surgical or venoplasty treatments to address venous stenosis, nor were there machines to see venous occlusion in humans.


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 Dr. Tracy Putnam did not cure MS with a newly discovered blood thinner in the 1940s.   And the focus and research money went to neuroimmunology, creating a 20 billion dollar a year treatment industry.

Dr. Putnam had a decade for his vascular research.  The EAE autoimmune mouse model of MS has had over seven decades, and there is still no clearly defined disease aetiology for multiple sclerosis.

Who was this brilliant man, and why has he been removed from the story of NMMS multiple sclerosis research history? 

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.” 

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 in Dr. Putnam’s story.

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.

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.

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. 

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 and treatment with venoplasty.  

My husband had an occluded venous sinus, just like Dr. Putnam's poor dogs.  His sinus was stented and normalized flow has been returned.  He has had no MS progression, no new lesions, and reversal of his gray matter atrophy since treatment. 

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 and hypo perfusion.   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  the ISNVD www.isnvd.org and CCSVI Alliance, and help us carry on this work   www.ccsvi.org)

Thank you, Dr. Putnam.
Joan




Tuesday, April 13, 2010

Cognitive Dissonance and Credo


April 13, 2010 at 9:06am

My dear friend Marie, who has secondary progressive MS and was the second person treated at Stanford for venous malformations, taught me a very important concept when we started this journey together. 
"Joan, CCSVI and the vascular connection to MS will be tough for neurologists to accept. They will have cognitive dissonance."

As a musician, dissonance is something I know about. Hit two adjacent notes on the piano, and you get a dissonance. They "rub" each other. Move your fingers apart, to play a major third, and the ear is happier. You get consonance, resolution, or harmony.

Cognitive dissonance is when two opposing ideas rub in your brain at the same time, just like those notes.  This causes discomfort, so we humans try to avoid thinking about these things.
Some practical examples-
I know smoking is bad for me, but I'm addicted and need this cigarette.
The person I voted for is doing some pretty terrible stuff, but I picked them, so I have to keep supporting them.
I know this burger and fries aren't great for my health, but they are delicious, so the hell with it.
Yeah, that player may have beaten up his wife, but my team is having a great season, so I'll cheer for him.

The brain needs one of these ideas to win over the other, since both realities co-existing is painful.

Having a teenager in our house makes us deal with cognitive dissonance every single day.
"Mom, I know you tell me God is a loving creator, but why does He allow so much pain and suffering? What about Haiti???  What about Syria?  Does God will that?

Because Jeff and I are Christian, we point our son to the New Testament, where we learn that Jesus came, not as a wealthy and powerful king, but as a poor, suffering servant. He taught us to take care of others first, before pursuing our personal happiness, and that pain is a natural part of life, but it is never in vain.  If we were Jewish, we would point him to the Torah, and teach him that life is full of suffering, but we respond by caring for others, following the law, and worshipping our Creator. If we were Buddhist, we'd teach him about detachment from earthly cares and the path to enlightenment. Muslim; we would point to the Qur'an and how the Prophet came to teach us to care for others and worship Allah. If we were atheists, we'd agree with him; how could a loving God let so many people suffer? Religion (or the lack of) can often provide a solution to the cognitive dissonance of life. So can philosophy, so can therapy, so can nature.

I mention religion, because right now in Toronto, a medical establishment has gathered to profess their group "credo", which simply means "I believe."  These neurologists believe in the theory proposed in the 1940s by Dr. Rivers: that MS is an autoimmune disease best modeled in mice by EAE. All of the medications and therapies they offer are based on this credo. All of the lectures they attend, all of the textbooks and research written, all of the speakers, and all of the fine meals are financed by this credo.

And now here come a bunch of outsiders asking that they open up their minds to another viewpoint. MS could be caused by a malformation in the venous system--as evidenced by reflux of blood and stenosis in most MS patients. Cognitive dissonance is the result. How can their theory stand up to a completely new model? These two thoughts cannot co-exist in the mind, so one must be annihiliated. Guess which one they are going to kill?

In the beginning of all of this, I had hoped that the neurologists would be thrilled to investigate a new model of MS...afterall, they are healers, and surely they want to look into any theories of the potential causation of MS, right? But in talking with Dr. Schelling, I learned from history. Nothing has really changed in thirty years, except everything has changed.

We now have each other thru the internet, and the potential to take this research (which is compounding evidence daily) to vascular doctors and interventional radiologists. They do not have any conflicting views, no cognitive dissonance for them. They are willing to test this new theory, because it makes sense to them. They see how neurovascular diseases work everyday. They understand the importance of venous return. We have consonance. Harmony.

I've included a recording to listen to....I love ancient music, because the idea of dissonance transforming into harmony is so beautifully illustrated in this era. Gesualdo was considered "crazy" in his time, because of the dissonances he used in his compositions. Listen to how the rough, unexpected notes, rubbing against each other, give way to consonance and resolution.

Remember cognitive dissonance when you try to explain CCSVI to your neurologist. Feel compassion for them.  This is going to be a very difficult concept to consider. Try to find a doctor who understands what you are looking for. If your neurologist is open minded enough to accept the rub of dissonance--you are a lucky individual!

Joan

Saturday, January 9, 2010

EAE: How MS became classified as an immune disease


January 9, 2010 at 2:12pm

Let's try to understand how the vascular connection to MS was dismissed, and why.
It's all about EAE (experimental autoimmune encephalomyelitis) and drugs.

Up until the 1930s, the prevailing thought was that MS was initiated by venous congestion. Dr. Tracy Putnam was at the center of this theory, blocking veins in dogs and creating MS-like lesions. Until a new doctor found a new, "simpler" animal model---


"In the early 1930s, Thomas Rivers and colleagues provided the first evidence that immune cells can attack the brain. Their simple experiments established what is now the most well-studied model of autoimmunity—the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
Studies had shown that injection of foreign brain tissues into the brains of rabbits could cause paralysis (2). Intrigued, Rivers—then a virologist at The Rockefeller Institute—set out to duplicate these studies in monkeys. Rivers and his colleagues injected Rhesus macaques with normal brain extracts from rabbits and showed that most of the monkeys developed acute CNS disease with immune cell infiltration and demyelinating lesions. No infectious agent could be cultured from the animals, putting to rest suspicions of an infectious etiology. Rivers' group also noted that the disease-inducing capacity of the brain extracts paralleled their myelin content, providing the first hint that myelin was involved in disease induction. Thus, the experimental allergic (now “autoimmune”) encephalomyelitis (EAE) model was born. The group published these observations in three articles in the Journal of Experimental Medicine (3–5)."
+++++++++++++++++++++++++++++++++++++++++

EAE continues to be the medical model neurologists and immunologists study today, even though this model for MS is deeply flawed. Researchers continue to give mice EAE by injecting them with antigen, and then try to "cure" them with a variety of immune blocking or modulating medicines.

++++++++++++++++++++++++++++++++++++++++++

Here's a paper from 2005

"Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certai n approaches. The reasons underlying such failures are discussed here.

Many scientists interested in developing new therapies for MS criticize the EAE model for its poor record of predicting outcomes in the clinic, especially for those instances when promising therapies indicate that they are beneficial in models of EAE, yet then fail in subsequent clinical trials.
Nevertheless, the EAE models are rapid, and can quickly give indications of whether a particular mechanism of action of a specific drug has merit when taken into an in vivo model that recapitulates many aspects of the human disease, MS"
+++++++++++++++++++++++++++++++++++++

So, the reason we still use the EAE model for MS is because it is a RAPID proof of DRUGS? 
Because these drugs can cure mice of EAE?

MS researchers continue to use this disease model, to the exclusion of other research, even in light of the fact that these treatments appear to cure mice of EAE...but FAIL IN CLINICAL TRIALS OF HUMANS WITH MS.

Insanity is repeating the same action over and over again and expecting different results. We have had seventy five years of EAE research, and we are not closer to understanding MS.

Perhaps we need to find a new model?
Joan