The Quiet Scientist: Maureen Hanson
She is the tall, unassuming scientist whose polished delivery style sets her apart. She's also one of the hardest working and perhaps least well-known scientists in the M.E. field. She is now the director of a new M.E. research center in New York, the Cornell ENID Center. How it all came about is a tale of love, patience and persistence.
Maureen Hanson, a Harvard-trained Ph.D. whose doctorate is in cell and developmental biology, is a professor and lab head at the world mecca of plant biology, the Ivy League’s Cornell University in Ithaca, NY. It’s a liberal college town, sometimes called the Berkeley of the East, nestled amidst the lakes and working farms of upstate New York. Dr. Hanson has lived there near the industrial-sized (750 acres) if bucolic campus since she took her post as associate professor in 1985.
Until a few years ago, her focus was trained exclusively on the molecular genetics of plants. In 2007, however, Hanson slowly began expanding her lab’s focus to include the study of myalgic encephalomyelitis (M.E.), a disease of humans. The move was hardly as much of a stretch as one might imagine: the study of plant genetics and human genetics are in the most basic ways indistinguishable. “Most people don’t realize that research on plants can be biomedical research,” she notes. In addition, every modern technique of molecular biology—mass spectrometry, DNA sequencing and more—is used in the study of both plants and animals.
She turned few heads in her department at Cornell.
“Faculty have a great deal of freedom as to what research they want to do,” she said during a recent interview. “I don’t think many people even paid attention to the shift in research I was doing.”
Hanson continues to publish papers and present her research on plant biology around the world. In that academic universe, at least, she has been able to be highly productive, publishing an impressive 171 papers in the plant field. Her more recent addition to her lab’s portfolio, while not robustly funded, has led over time to a series of verbal presentations, posters and published papers on abnormalities in M.E., including mitochondria, the microbiome, the newly “hot” metabolomics and the so-called “post-exertional malaise” or “push-crash” phenomenon in M.E., all of which have served to raise her profile among those who suffer from the disease. She is pursuing several more avenues of investigation, including a sophisticated analysis of white blood cells in hopes of identifying a molecular profile for use in diagnosis.
(For more information on Hanson’s M.E. research, click here.)
She will, in addition, soon publish a pilot study on metabolomic abnormalities in women that in several ways replicates the recently published findings of Robert Naviaux’s larger study. Hanson applied for her first NIH grant to explore metabolomics in 2014, but was turned down. She’s hoping, given what appears to be a revved up interest in M.E., that the government will make more money available to investigators.
Nevertheless, she wishes the field was moving faster.
“I do think in these studies we are not seeing the cause but are recording the downstream damage from the disease,” she says during a recent interview.
Hanson, in fact, has provided evidence in at least one case for a more cohesive conception of M.E. in an era notable for its prevailing view of the disease as a collection of “subsets” that should be studied as such by stratifying patients according to symptoms as if they were suffering different maladies. Her investigation into the mitochondrial genomics of M.E. patients, published in January of this year in the Journal of Translational Medicine suggested otherwise.
“There is no evidence that M.E. is many diseases,” Hanson reported during a mesmerizing hour-long webinar recently hosted by the L.A.-based organization Solve ME/CFS Initiative. Instead, Hanson continued, “The diversity of symptoms can be due to mitochondrial DNA variations and nuclear genome differences (in individual patients).” One sufferer may be genetically predisposed to develop neuroinflammatory distress and chemical sensitivities, while another may be predisposed to develop gastrointestinal distress, according to Hanson’s research.
In conversation, she clarifies further:
“My point was that at least some of the differences among people as to symptoms may be your mitochondrial and likely nuclear genome,” she says. “I also think that some differences (in symptoms) have to do with your history. Mady Hornig’s group (at Columbia University) showed that there were immunological differences between people who had been sick for three years relative to people who had been sick longer. So, that is another instance—the disease progresses, changes. People also may have different co-infections, infections that modulate their illness. So there’s genetics, there’s history and let’s hypothetically say there’s a virus. Viruses also have genetic variation. Perhaps some of the people who got this disease had a genetic variation of the virus.
“I don’t think subsets give us any evidence that there’s a different fundamental cause to the disease or that there is a different fundamental biological disruption,” she adds. “There are people who think different stresses can cause M.E. for instance, but likely everyone who has M.E. has the same basic fundamental disruption, and all of these factors can mask that it’s the same biological disruption.”
As significant as Hanson’s mitochondrial DNA paper was, the research that garnered her by far the most attention was her June 2016 paper on abnormalities in the microbiome of M.E. sufferers. At last count, the number of Internet, magazine and newspaper reports describing the abnormalities Hanson and her colleagues found is approaching eighty. Hanson attributes the hoopla to the fact that microbiome research is “sexy” at the moment and has received “a lot of hype” given the accessibility of DNA sequencing to identify bacterial genes, not to any uptick in interest in M.E. Microbiome studies of medical problems ranging from obesity to kidney stones to disturbed circadian rhythms have flourished, many of them supported by the NIH’s Human Microbiome Project, though Hanson’s microbiome research was not funded by that program.
New York immunologist Sue Levine, Hanson’s clinical collaborator, shouldered the task of persuading 48 patients and 39 healthy people to send fecal samples to the Hanson Lab in Ithaca. All to the glory of science, Hanson’s team processed the samples to prepare them for DNA sequencing, but Hanson recalls a day when everyone was shaken out of their torpor by a sample that arrived accompanied by a beautifully handwritten note from an anonymous donor. It read, “Have a nice day!”
Ultimately, Hanson and her colleagues were able to identify M.E patients by their microbiome signature 87 percent of the time. As is probably well-known by now, the paper reported a surplus of pro-inflammatory bacteria and a deficit of “good” bacteria in the intestinal tracts of M.E. sufferers, as well as a loss of “species richness.” In the report, Hanson relayed the unhappy but hardly surprising news that the gastrointestinal tract of M.E. patients was a “pro-inflammatory environment…with ongoing damage to the gut mucosa.”
Whatever the reason for the wall-to-wall media coverage, Hanson never missed an opportunity when interviewed to state unequivocally that M.E. is a biological disease requiring urgent attention. That this seemingly obvious claim bears repeating thirty-five years after the M.E. epidemic began is its own tragedy, but Hanson is nothing if not a pragmatist and recognizes the concept still needs hammering home today as much as it did in 1986.
What’s commendable about Hanson is her decision to do so. In fact, her desire to communicate these realities to the public is so strong few can have missed the fact that she is making forays into the world of non-academic publishing and has written a series of op-eds for the lay public in influential or widely read venues. Last winter, she took advantage of a program offered by Cornell to its professors that encouraged them to abandon academic writing conventions and publish reader-friendly essays in their areas of expertise in lay publications. For Hanson, the transition wasn’t much of a stretch. While growing up in a Washington, D.C. suburb, she bonded with a revered uncle who was a writer and publisher.
For M.E. sufferers who’ve been paying attention, certainly, Hanson is fulfilling a long-frustrated hope that someone with scientific gravitas would start telling the rest of the world that, metaphorically speaking, the house is on fire. Her op-eds about both the funding shortage and the severity of the disease have appeared in publications like The Hill, an influential publication in Washington, D.C., and the ubiquitous Huffington Post, the online magazine. Most recently, she penned an essay for an online women’s magazine about the media’s failure to properly portray realistic images of M.E. in their choice of illustrations and photos accompanying their stories—using the very photographs that editors had chosen to illustrate her widely disseminated findings on microbiome abnormalities as her examples.
“No one would illustrate an article about either (cancer or multiple sclerosis) with someone sleeping at her computer, a woman snoozing with coffee cup in hand, or a woman who has evidently just come home from work, gazing wearily at children’s toys scattered around the floor,” Hanson wrote.
In general, the M.E. scientific culture of longstanding has been unfairly scarred by competition for scarce research funds and perpetually spooked by a federal health establishment so opaque that in the past it has reduced even the best-connected scientists to readers of tea leaves. Twenty-five years ago, one scientist lamented that the government’s indifference to the disease left researchers feeling like wild animals locked together in a cage. The measured reply of the National Cancer Institute’s Frank Ruscetti to this reporter, when asked in 2013 what people at NIH thought of M.E. patients was “They hate you.” Clear enough.
Hanson, by word and deed, has sought to heal that fraught culture through collaborative science.
For years, she has been creating bonds among institutions—her own, Ithaca College, Weill Cornell Medical College, the Workwell Foundation and others—networking with people she recognizes as change-makers or potential change-makers and reaching out to peers to join her in the field. She respects policy makers inside NIH who have begun to attempt to make sense of a disease they don’t understand.
During her Solve ME/CFS seminar Hanson revealed that Cornell will soon be home to a new and major center for M.E. research. That day has come: the new entity was formally announced on October 24th, 2016. Her university’s Center for Enervating Neuroimmune Disease (named by an M.E. patient), which thus far includes eighteen lab groups at eight institutions, exists largely as a result of Hanson’s determination to bring doctors and researchers together around this singular disease.
“When I submitted my first grant proposal to NIH in 2008, at that time there was only one other lab at Cornell or Cornell’s medical school (in New York City) doing M.E. research, and that was Dikoma Shungu's, who currently has a grant to do brain imaging…I wanted to expand the number of people working on the disease, so I did that by starting up collaborations, and that’s what built up the community at Cornell.
“Betsy Keller (at Ithaca College) was also working on this, doing exercise testing." In 2009, Hanson joined forces with Keller. “And so from that start with one other person, we now have 20 people associated with the new Center. It shows one can expand the research community by collaboration. And having a center allows for more publicity for M.E., more awareness on campus and stimulates more research on working on it.”
As if on cue, the National Institute for Neurological Disorders and Stroke (NINDS) announced on October 21st, 2016, one week before a major medical conference on the disease in Florida, that it intends to request grant proposals for the creation of collaborative centers where M.E. research can be consolidated. (The institute has yet to commit any dollar amount, however, and the announcement itself specified that the NINDS will be closely involved with each center.)
“When I got into this field I wanted to establish myself as someone who could do quality research in CFS,” Hanson says. “I also wanted to participate in the CFS research community by serving on the NIH study sections (that review and score grant applications),” she adds. “And I wanted to participate as a reviewer for journal articles—there is a dearth of people able or willing to provide quality peer review and that’s another reason people are having trouble being published. The fourth thing I wanted to add to my efforts was trying to provide articles for the mainstream lay press.”
She goes further. “If I weren’t a scientist, I would certainly want to start up the M.E.-CFS version of Act Up. A lot of people (in the M.E. science community) privately think that the patient community needs to get going on stronger advocacy. I feel that as much as is possible given their physical limits and time constraints, ME patients and caregivers, physicians and researchers really need to be as active in demanding more research as the AIDS activists were. They are a very good model for what needs to be done.”
Hanson attended her first scientific conference on the disease in 2004 in Madison, Wisconsin. The meeting was held by the IACFS (then the AACFS). Given the myriad similar conferences held on M.E. over the last three decades, Hanson might be considered a relative newcomer to the field. The reality is more complicated. Why would a molecular biologist whose career had been devoted to plant studies travel to Wisconsin to attend a conference on an obscure medical disease in the first place?
“The reason was that in 2001 David Bell diagnosed my son with CFS. I wanted to learn about the disease,” Hanson says.
Five years earlier, when he was eleven, her avid soccer playing son was afflicted by intermittent migraines and "mysterious" daily headaches.. Other symptoms came and went but were harder to pin point.
“No one could figure out this mysterious illness because it was relapsing and remitting. The main symptoms were pain and the migraines, and general malaise more than fatigue—that wasn’t the primary symptom,” she says. “One of the things I would notice is that he would play a soccer game and then be sick for three days. I now recognize that was exercise intolerance.”
Although she had heard of “chronic fatigue syndrome," it never occurred to Hanson that her son's severe affliction might be a disease with such a mild-sounding name.
“What gradually happened is that there were fewer healthy periods, such that by the tenth grade he had to go to school part time. In fact, he had to spread his tenth grade course load over a span of two years,” Hanson continues. “…Earlier, it appeared that his problem was predominantly headaches. It was my hope that he would grow out of that—a lot of people do. By the time he was fifteen it was evident that the problem was more serious. One of his local doctors must have suspected CFS but was unwilling to make the diagnosis. He said, ‘I think you should take him to Dr. Bell in Lyndonville.’ He had probably sent other patients there and knew full well that my son had CFS but he didn’t want to be the one making the diagnosis. That’s why the Institute of Medicine criteria are so important. If they had been available, the doctor would not have been afraid to make the diagnosis.”
(The Institute of Medicine report on M.E. was undertaken by a small group of independent investigators appointed by the National Academy of Sciences. The government asked the panel to consider new criteria to define the disease. They released their report in 2015.)
David Bell, whose clinic in Lyndonville, NY was a three-hour car trip from Ithaca, was a name unknown to Hanson but she was eager for help. It wasn’t until Bell confirmed her son was suffering from CFS that Hanson started reading about the disease.
“I realized this was a very bad diagnosis. There were no treatments and the prognosis wasn’t very good.”
By her son’s sixteenth year, she recalls, “…[T]here were no more healthy periods. He basically settled into more classic CFS with cognitive difficulties, migraines, muscle aches, low energy and PEM. By then, it would have been easy for anyone to diagnose him. David Bell describes this phenomenon in some of his books—sometimes it takes a while before the illness becomes obvious because the patient accumulates all the symptoms gradually. Remissions usually stop happening and the person reaches a steady state of illness.”
Although an A student, by the time he turned sixteen, the physical effort it cost Hanson's son to remain in school at last became impossible. That was fifteen years ago. Too sick to leave the house except for doctors' appointments, his life has been on hold ever since.
"Although housebound, my son isn't bed bound, making it possible for me to work long hours and travel when needed," Hanson commented.
Immediately after Bell rendered his diagnosis, Hanson says, “I began looking into the literature.” She was surprised at the small number of published papers about such a severe disease. “I did learn about the Lyndonville outbreak, so I became interested in the fact that it might be an infection—a virus or bacteria—I even considered it might be some toxic exposure. I considered all those things.
“One reason I went to the Madison meeting was to hear what the theories were about the source of the disease and also with the idea that I would be able to learn information that would help my son. I assumed there must be some (research) activity going on that hadn’t yet appeared in the literature. There’s usually a lag of several years before the research being done is published and if you go to a conference, you can learn what’s happening in the field because what’s being studied is described at those meetings.”
But Hanson was surprised at how little research was underway.
She notes quickly, “Now I know why—there was so little funding.”
Listening to the presentations in Madison, she recalls, was eye opening for other reasons.
“I was surprised by how small the research community was. This meeting occurred just every two years and yet there were so few scientists. And then I stepped into the patients’ conference and I was surprised at how sick everyone was. There were people in wheelchairs, people lying on cots at the back of the room, people using oxygen. It was the first time I had ever seen a large group of people who had CFS and it certainly brought home to me the seriousness of the disease. I wasn’t aware that people were in wheel chairs using oxygen.”
The content of the presentations, in addition, were startling to Hanson.
“To tell you the truth, I felt that a lot of the research was quite descriptive but was not getting at the underlying basis of the disease. There was some interesting work on RNase-L at that meeting. There was some worthwhile immunology. But a lot of the meeting was simply describing symptoms of the patients, characterizing the patients, yet not getting at what was causing the disease. I was surprised to discover that there was almost no molecular biology. It did help me to know that in fact the disease was a complete mystery,” she says. “This was a disease that was not understood at all and it was going to take a lot more research to figure out what was going on.”
Ultimately, for all those reasons, the Wisconsin meeting made an indelible impression on Hanson. Perhaps her most profound reaction to it was this: “It made me think that because there were so few molecular biologists, I should work on the disease, too.”
She continued to attend IACFS meetings—Ft. Lauderdale in 2007, Reno in 2009. Hanson had had another “ah ha!” moment as the result of a casual purchase in 2007 of a used book priced at $2 in a Ventura, CA bookstore. She had wandered into the store during a break from her attendance at a major plant biology conference.
“It looked to be a history of CFS so I thought, ‘I’ll just buy this book,’ but I didn’t read it for another year. After reading Osler’s Web, probably in 2008,” she says, “I realized for the first time that the government has not responded sufficiently to this disease and that was the reason I was not seeing the research I had expected at these meetings.”
Maureen Hanson grew up dreaming of becoming a scientist. “I can’t remember when I wasn’t interested in science, even in pre-school,” she says. In grade school, she was particularly inspired by a biography of Madame Curie, she says, “…who was probably, at that time, one of the very few role models for women."Like M.E. expert Dan Peterson, who was attending Carleton College in southern Minnesota at the time—and harboring private dreams of becoming a forest ranger—Hanson majored in botany while an undergraduate at Duke University. Even now, she exhibits a scholarly curiosity about the natural world. While attending scientific conferences on foreign ground she has been known to stop in her tracks to aim her camera directly at the ground should she come upon a plant she cannot assign to a family. Snap!
During the summer between her freshman and sophomore year, she held a “very low-level” lab position at the Beltsville (MD) Agricultural Research Center, a major research outpost of the U.S. Department of Agriculture. Low level as it was, her sights were raised by the experience. She spent the summer working on bacteriophage, a remarkable class of viruses that devours bacteria. The federal agency was exploring whether bacteriophage could be harnessed to kill bacteria decimating certain crops. Discovered early in the last century, bacteriophages were also early precursors to man-made antibiotics. “Phages,” as they are shorthanded, are plentiful in “locations populated by bacterial hosts, such as soil or the intestines of animals.”
“There are all these connections between what one does earlier and what one does later,” Hanson says.
At the IACFS meeting in Florida, one of her lab members, Ludovic Giloteaux, is giving a talk about bacteriophage in the gut in M.E. patients.
After graduating from Duke, Hanson moved to Cambridge to attend Harvard. Once she earned her Ph.D. she moved to a second lab at Harvard where she spent three years as an NIH post-doctoral fellow, after which she launched her academic career as an assistant professor and lab chief at the University of Virginia. For the next six years she researched the molecular genetic basis of a particular mitochondrial defect in plants. Hanson found what would turn out to be her long-term professional commitment in Ithaca. Cornell is the epicenter of plant science and Hanson joined what was then the school’s section of Genetics and Development, now expanded to become the Department of Molecular Biology and Genetics. In 1991, Cornell named Hanson a full professor. Four years later, in 1995, her College honored her with its Liberty Hyde Bailey chair, named for the Cornell botanist and Dean responsible for turning what had been a gentlemanly study of horticulture at the turn of the last century into the applied sciences of genetics and plant pathology.
In the last decade, Hanson has given a great deal of thought to the history of the disease as well as to its future. She has mused on the flaws inherent in the government’s funding process, yet she has persisted in her efforts to obtain grants rather than walk away as less motivated scientists have done in years past. She has served on the government's grant funding committee because she thinks it is important for NIH to have reviewers who comprehend the seriousness of the disease. Without question, she has a firm grasp of the harsh realities of the past.
“I would say that in 1985 the outbreaks were a huge missed opportunity,” she says. “It might have been possible to identify an infectious or environmental cause if those outbreaks had been properly investigated. (But) I think there has been so much more attention now to the disease…especially as a result of the 2015 Institute of Medicine Study, and with some high profile cases of M.E. becoming known to NIH officials—I think if an outbreak did occur it would be investigated properly. I believe CDC would be very interested and would devote resources to any new outbreak.
“Scientists know that it is absolutely essential that we investigate an outbreak anywhere in the world…(and) I think we would be able to investigate one in a much better manner because molecular biology has developed tremendously since 1985. We couldn’t have imagined then the tools we have now that would allow us to identify an infectious agent in those outbreaks.”
As to the quest for biomarkers, an oft-cited reason for slow progress in the disease, Hanson says, “Anytime someone publishes a paper that replicates a finding, you’ve got a biomarker. Anyone who says there are no biomarkers is just ignorant. A problem is that none of the biomarkers we have to date have told us what’s going fundamentally wrong in this disease.
“The fact is,” she continues, “what we need are biomarkers that are easily assayed so that one can develop a diagnostic test that doesn’t require any knowledge on the part of the physician. The data from the two-day exercise test is a biomarker, but that’s not a simple test for patients or doctors. You need to find a biomarker that can be made into a test that can be performed by Lab Corp or Quest.”
It’s hardly a secret that the most passionate and effective advocates in the M.E. cosmos have been parents of children who fall ill, especially those with considerable fortunes. I think of the late Ted Van Zelst, father to an adult daughter with M.E., who in the mid-1980s, recognizing that the Centers for Disease Control was not interested in M.E., pledged money to undertake early, critical epidemiology on this then-emerging disease; the Whittemore family, whose daughter’s illness drove efforts to create a medical institute at the University of Nevada; the New York hedge fund chief with an ailing family member who invested $10 million to launch the Chronic Fatigue Initiative at Columbia’s Mailman School of Public Health six years ago.
Doctors and scientists, too, have hardly been immune to watching their hopes for their children’s lives nearly carried away by this disease. John Chia, an enterovirus specialist, whose son fell ill, is one. Clinician-researcher Lucinda Bateman’s late sister suffered from M.E. Stanford geneticist Ron Davis has posted his son’s agonized portrait to social media sites as a way of representing a generation of young adults similarly afflicted. Simultaneously, Davis is following his own hunches in this historically orphaned field of inquiry. It may turn out that most doctors or investigators who enter the fray with the kind of passion exhibited by those named above will be found to have children or spouses or siblings for whom time may be running out—or who may be ill themselves.
Since her entry into the M.E. field, Hanson has preferred to maintain her son’s privacy. Her decision to discuss her son’s illness arose as her higher profile sparked curiosity in the patient community about the genesis of her interest in M.E.
One can hope for a future when scores of doctors and investigators demonstrating similar endurance in this field are not just loving relatives of sufferers, but are drawn to the study of M.E. because it cuts such an expensive, life-consuming swath across all known demographics—and because it is a challenging scientific puzzle. Hanson, for one, is not leaving.