After seeing four patients in 2004 and helping them considerably with long-term Valcyte therapy, Montoya's commitment to the malady was bedrock. He knew enough about academia by then to comprehend what might be required to overcome years of deeply held bias among his colleagues. The harsh reality of academic medicine, its adherence to the 1940s dictum, "When you hear hoof beats think of horses, not zebras," had resulted in a hardline negative stance on a gravely important disease few in academia actually knew anything about. Years of dismissal of M.E. at Stanford was going to require that Montoya lay out, patiently and meticulously, a line of evidence to persuade the naysayers they were wrong.
“You can imagine," Montoya says, "if I had gone to the bone marrow from day one working on this, or I had gone to the spinal fluid from day one. They would have said, ‘What are you doing?’ Versus the easiest thing, which was to just get the blood. And then they start to say, ‘Wow,’ and ‘Oh wow,’ and eventually it was just one ‘Wow’ after another."
Montoya suspected a pathogen, specifically a virus, was causing the disease after seeing his first patient in 2004. Nothing he has seen or read since has caused him to deviate from that hypothesis. And yet, transmission, viral etiology--although theorized by many clinicians and researchers who study M.E.--is rarely if ever broached in public settings, even at IACFS conferences where one would expect researchers to discuss the subject in depth. It's the 800 pound gorilla in the room, the third rail of M.E. science. It's almost de riguere to discuss genetic susceptibilities instead, avoiding the fact that most people with the disease are not related by blood and that the not atypical phenomenon of transmission in families is more likely to occur as a result of close or intimate contact.
Surely, it was not a dialogue Montoya could have with his Stanford colleagues in the mid-2000s. He had to get them past the shock that he was even seeing patients and that he believed the patients were suffering from a disease. A year after he published his first paper on Valcyte therapy, Montoya admitted nonetheless that he was bringing patients into the Stanford infectious disease clinic "...through the back door."
Since receiving $5 million from an anonymous donor in the mid-2000s, Montoya currently has created at Stanford a robust "ME/CFS Initiative" with multiple collaborators. He also has co-authored studies with NYC's Ian Lipkin at Columbia in the realm of cytokines and he will be among the investigators named on Columbia's grant submission to the NIH on May 2 for funding to create Centers for Research. He will also be named on the Open Medicine Foundation grant application to the NIH. And he is applying on behalf of his Stanford Initiative for his own center. Thus, it seems possible that Montoya will be participating in more than one center. No fewer than nine groups are applying for a center; no one yet knows how many there will be. Competition is fierce. In future NIH bureaucrats will find it difficult to justify their failure to fund on their tread worn complaint that too few researchers are applying for grants or that not enough scientists are interested or qualified.
The distance Montoya has come since 2004 was on full display in 2014 when he served as host of a day-long conference at Stanford on M.E. featuring a series of presentations from colleagues. The only false note was a presentation by cardiologists who reported they were unable to find any heart abnormalities in M.E. patients. On questioning from a patient in the audience, it turned out the cardiologists had chosen as their subjects people who could perform on exercise equipment for lengthy periods without difficulty. Needless to say, the cardiology piece has moved forward and Stanford is looking at heart endothelial cell function. A team of neuropsychologists, Marcie and Mark Zinn, now at DePaul in Chicago, presented their work on encephalopathy in M.E.
"You have to find the best people for each of the pieces," Montoya says. "If you pretend to be the expert on everything that you are working with, it's doomed to failure--or if not failure, it goes lower. The best thing is to have a vision, a big umbrella with an overarching vision, and then all the other pieces working with that. You cannot condescend or patronize, because everyone has the expertise and everyone is moving. And your vision can change. But if you said 'My ultimate dream is to eradicate M.E. from the surface of the earth,' nobody would argue with you. And then if you move closer to earth, and you say 'My ultimate goal is to find a cure for M.E.,' nobody would argue. If you go even smaller--'My ultimate goal is to find an effective treatment for M.E., not even necessarily a cure.' So--if you have that crafted--then it's easy to align people around you. But if you say, 'My ultimate goal is to find an immune abnormality,' then you exclude the geneticist, you exclude the pathogen discovery.
"So I have created this at Stanford. This is a huge umbrella that makes sense, is very consistent, where all the experts can fit in."
My first glimpse of Jose Montoya occurred in 2007 at an IACFS conference in Ft. Lauderdale. He seemed surrounded by an entourage at all times, a person of importance, but at the same time, a newbie. I suspect now that he was holding back. He is not a cunning person, but his sunniness should not be taken for naivete, either. He knows the political lay of the land; he is strategic and wisely so. His talk on M.E. took place in a medium-sized room filled with occupied chairs and more patients standing along the sides and rear of the room. They knew Montoya was treating sufferers with antivirals. His first paper on the subject had appeared the year before and seemed to offer the first real hope since Ampligen--a worthy drug that the FDA has been loathe to approve for thirty years. Valcyte, on the other hand, was readily available. The proverbial pin drop could have been heard while Montoya spoke. There seemed little question that he was someone who was going to try hard, very hard, to make a difference.
Ten years later, he has created an atmosphere at Stanford where he can propose to look for pathogens in the bone marrow, in spinal fluid, and in cell compartments without causing his co-investigators to flinch.
His ideas come to him in moments of rare solitude and quiet.
"Again, this comes at dark, all night, alone," Montoya says. "If you give me an immune cell that may be compromised in M.E., what comes to your mind?"
"NK cells?" I respond.
"NK cells," he affirms. "Everybody mentions NK cells. And nobody has ever thought about looking for the pathogen in the NK cell. It's like, you have a pathogen that has a target where the NK cell gets in and either destroys it. Or, if (NK cells) don't go through the floor they will be dysfunctional. Well--what about looking in the NK cells? I have a collaboration that I'm very excited about."