In our latest “People in ME/CFS Research” spotlight, I was fortunate to chat over the phone with Carol Isaacson Barash and interview her about her extensive background in genetics ethics and scientific consulting. Carol has her own consulting company, Helix Health Advisors, and is also an ME/CFS patient and has been applying her knowledge of science and ethics to the management of her illness. Read on to learn more about her scientific background, her experiences with getting a diagnosis and treatment, and her opinion of the ME/CFS field.
Hi Carol, thanks for meeting with me! You’re the Founder and Managing Partner of Helix Health Advisors, and you have a lot of experience in genomics innovation and personalized medicine, as well as ethical issues surrounding genetic discrimination. Can you tell me a little bit more about your scientific background?
Hi Courtney! First, let me thank you for your interest and this opportunity. Actually, my formal scientific background is limited to my undergraduate days, because my Ph.D. is in philosophy. I’ve always had a strong interest in medicine, in part because I come from a family with several generations of physicians. However, I’ve also been drawn to issues of logical reasoning, so I got my Ph.D. instead of an MD. I didn’t want to be an academic philosopher, but rather make a career in healthcare. Having left Chicago and come to Boston, I landed a Research Assistant job in science technology and policy at Boston University working on the Framingham Heart study, and then I worked as a Research/Policy Analyst for the think tank at Tufts Center for the Study of Drug Development. I then had the good fortune to fall into the job of Director of the first federally funded study of genetic discrimination, which was back in 1992. The Human Genome Project had just started and NIH and the Department of Energy established the Ethics, Legal & Social Implications Division, along with funding, to proactively identify ethical issues so that they could put preventive measures in place to prevent ethical abuses, such as genetic discrimination or privacy violations.
Our project, ‘Studies in Genetic Discrimination,’ was designed to identify the breadth of situations in which an individual experienced discrimination based on their genotype, but notably, not their phenotype. We included adults who were carriers of 1 of 4 well-established genetic diseases, based for example on having a child with the disease and adults who knew they had a familial risk for Huntington Disease (HD), since they had a first-degree relative with the disease. At the time, there was no test for HD. There was a lot of concern that society could create a genetic underclass that would lack societal entitlements and benefits based solely on their genotype or that, particularly in the case of adoption, people could be matched solely on the basis of their genetic makeup. I recall at least one instance where a private adoption agency refused to let ‘normal’ couples adopt a baby with a known risk for HD as the baby’s mother had the disease at a young age, but did permit a couple with one partner similarly at risk of HD to adopt the baby. Suffice it to say there’s a lot to analyze in that decision.
So I got hooked on genetic-ethical issues and related social justice issues, as well as the challenges of how to appropriately adopt genetic innovations. I had always wanted to work for myself, so I established Genetics, Ethics & Policy Consulting that later changed names to Helix Health Advisors. I began my consulting career working with the AAAS, to develop recommendations to UNESCO about how to advance genetics research while protecting human rights. I helped states write legislation for privacy protection and anti-discrimination laws, which didn’t exist at the time. I also consulted to a number of medical education projects through Special Projects of Regional or National Significance (SPRANS). HRSA was tasked with determining how best to train primary care doctors because they’re really the gatekeepers to genetic services. I was awarded one of their grants, which was designed to identify a physician’s ‘Need to Know’ genetics. In essence, we researched what does or doesn’t trigger suspicion of possible genetic involvement, and how clinicians make decisions and ultimately diagnose, refer, or do something else, in order to understand the barriers and drivers to appropriately applying new genetic knowledge in clinical decision making.
So, I would say that my scientific background is essentially self-taught, and that I’ve applied the analytic and thinking tools that I learned in studying philosophy to assess the veracity of research claims, to identify unmet needs, to help companies develop strategic solutions to meet those needs, and to really understand clinician, patient, and consumer literacy or lack-thereof. As a consultant, I’ve been fortunate to work exactly as I wanted to, namely on many different projects in a field driven by technological innovation, clinical need, and far-reaching ethical and social justice issues.
Wow, that’s a really interesting background. Science ethics is so fascinating! So, can you tell me about your own personal connection with ME/CFS?
Well, regrettably I have a very personal connection. One never expects to get seriously ill, until one does and even then the clinical challenges are but part of the road ahead. I was diagnosed with ME/CFS about 1.5 years ago but may well have had this disease for a while but just pushed through it. It’s not clear because I have an immune deficiency that’s plagued me throughout adulthood. For example, I get more sick than most people do, and it takes me longer to recover. For many years, PCPs sent me to infectious disease (ID) doctors, until one day an ID doctor referred me to an immunologist. She found that I had Mast Cell Activation Syndrome (MCAS) and Hashimoto’s antibodies, but neither are a big problem for me. Interestingly, I joined a Herbert Benson Institute Mind, Body, and Stress Reduction class in the evenings. I couldn’t always show up because of illness, but when I did go, often they looked at me and could see that I didn’t look well or feel well, but I couldn’t really articulate why. They pushed me to push my immunologist, who by the way I adore, and who agreed to do another test which identified an IgG subclass deficiency, and thus something that could be treated. IVIG has been helpful, but never did the trick for me like it does for so many. But nonetheless, I’ve been fortunate to have traveled extensively and led a busy professional and personal life with high energy and enthusiasm.
About 3 years ago I had what some consider a classic ME/CFS presentation. I landed in the ER with a fever of 103 degrees and a bright rash. I stayed for 4 days, received two potent IV antibiotics, and left with normal results and no diagnosis. I got back into the swing of things, but probably 6 months later I told my doctor that I was tired all the time, regardless of whether I had an infection or not. He asked whether I’d ever been evaluated for ME/CFS. I hadn’t even come close to thinking about that possibility! How could I not have thought of that possibility when working in the health care field is strange, but none of my doctors along the road had either. I saw one expert’s NP who thought I had ME/CFS, but I disagreed because after all I had just flown to Hong Kong for the weekend and then on to the west coast after a one day layover in Boston. How could I be that sick if I could do that, let alone make 4 trips to Asia in a year? Denial may have its virtues after all! But, I felt myself weaken and so I went for a thorough workup, notably not in Boston. The day after the 2016 election was the last day I walked our dog around the 1.5 mile pond and that is when I got really sick. So yes, stress and anxiety really are physiological triggers! I went off the IVIG for a month to test my viral antibody load and on that basis was diagnosed at the end of 2016.
It’s been a rough ride since. I started anti-virals and to my utter amazement did not get one infection but had to stop them because they spiked my liver enzymes. However, I was able to clear my liver and I’m back on them, which helps, along with other meds for POTS, and a limited exercise program. Most importantly, but difficult to have all of the time, is emotional resilience. I’m hardly alone in saying this, I know, but having this disease is crushing, in part because I’m really driven by nature. I’ll get a project, and I have to get it done soon. So, doing nothing when I know I need to rest is extremely difficult for me. I’m used to a high-octane life, and it would be dishonest to say I don’t miss it. At least for the time being, the gears have switched to a vastly slower pace. There are advantages to slowing down for sure, particularly when the choice is voluntary. Doing a lot and sleeping only 8 hours aren’t in the cards now. I’ve had to let go of that, and that’s exceedingly hard, but doable with the help of loving friends and family. It’s not uncommon for people to go into the fear-avoidance zone, and flip-flop between that and the overdoing it zone. So I have had to learn how to separate my body from my higher self, if you will, and work with my higher self to not freak out when I overdo it.
Finding that balance must be really difficult! Did you face any obstacles in the process of getting a diagnosis and finding treatment?
Yes. First, there is a major obstacle in that there are no ME/CFS specialists in one of the nation’s top medical cities; Boston. Dr. Komaroff is now a Professor Emeritus and no longer sees patients. Despite his 30+ years of research as a Harvard physician and clinician, his work has not impacted Harvard or the Boston medical community enough for clinicians to believe that ME/CFS is a real disease, much less for them to take an interest in learning how to evaluate potential patients. There are many reasons why. In my experience, clinicians look at the research and conclude it’s not convincing. End of story. Thankfully, that is beginning to change with the collaboration of SCMI and Dr. David Systrom, BWH, who is studying the pulmonary, cardiovascular, autonomic and peripheral neuropathy features of ME/CFS, and the brand new Harvard ME/CFS Collaborative Research Center established by the Open Medicine Foundation. So hopefully the clinical scene vis-a-vis ME/CFS will change soon in Boston.
When I was trying to figure out if I had ME/CFS or not, I decided to see the top experts as well as see two local physicians, to see if there might be someone local I could continue care with; one a rheumatologist and the other a recommended ME/CFS expert/internist/rheumatologist. The first said I was tired all the time because I constantly got viruses. The second looked at me and said, “are you tired?” and I said yes, and he said, “well you have chronic fatigue.” And he proceeded to prescribe graded exercise, and took absolutely no interest in what I told him about the NIH’s current research, HRSA’s debunking of graded exercise, or the IOM meeting. During this period, my PCP, who I otherwise respected, told me “there is no disease that’s chronic fatigue. The research is unclear. It may be something, but nobody knows what it is.” He recommended a new antidepressant. So he didn’t believe in it. Those were definitive obstacles.
And it can even be hard with the ME/CFS experts too. Clinically, it’s extremely hard for all patients because the number of available clinicians is small, clinicians vary in their approaches, and the disease is not yet well understood so there are no best practices. This leaves the onus on patients to engage in a lot of experimentation to see what works for them and what doesn’t, and that’s not even getting into the daily physical, emotional, and financial issues that patients and their families face. In addition, experts are not always able to prescribe to out-of-state patients. A whole host of other obstacles exist that have been noted by many others, such as difficulty in obtaining disability entitlements and benefits, lack of insurance coverage for supplements and recommended treatments, like for example, glutathione. So there are many challenges, some of which are quite formidable for patients.
There being so few experts definitely does make it really hard for patients to get the treatment they need. What is your overall impression of the ME/CFS field at present?
I think the field is really energized now and it’s really committed to figuring out this complex disease. To some extent it has greater focus, but I think a significant problem is the fact that there are roughly 2.5 million people who are sick and yet we know so little about them because the studies are relatively small. Further, there are a lot of disparate studies going on around the world and it’s not yet clear what findings are truly definitive. I think one of the difficulties is that researchers identify something interesting to study and get funding to do it, but what seems to be missing is a coordinated ability to evaluate the meaning and validity of the findings. I look at the field as many, many puzzle pieces scattered across a table with a couple of pieces locked in here and there but many more pieces waiting to be connected, and it’s baffling to see how any single piece fits into any seemingly established clump. So you keep picking up 2 pieces that don’t fit one another. Progress seems slow and it’s not clear how to solve the puzzle. On the other hand, I find it exciting that more researchers are establishing collaborations and thus a coordinated effort to solving this puzzle. I’m hopeful that the commitment and energy to figuring out what causes ME/CFS, specifically its various subtypes, will soon lead to larger studies and veritable answers, if not treatment strategies sooner rather than later.
I also think there needs to be greater effort to collaborate on the research level. For example, last year the OMF had a really interesting meeting. They had researchers from around the world gather to discuss the most promising leads. To have people collectively deciding what the priorities are and what needs to be studied, would seem very useful and should be done more often. I’m always thinking about this cartoon that was in Science Magazine years ago that read something to the effect of “I’m on the verge of a major breakthrough, but I’m at the end of where chemistry can contribute and physics begins so I guess I’ll have to drop it all.” I only mean this to say that because ME/CFS is such a complicated, multi-organ disease, it’s one that really requires multi- and inter-disciplinary teams to work together to figure it out. I also think that researchers and clinicians need to work together more. Inclusion will help bring clinicians into it and ideally help to overcome the stigma that clinicians seem to have where they dismiss ME/CFS as a legitimate disease.
In your opinion, how could the various -omics fields help to characterize a complex disease such as ME/CFS?
First I think it’s an open question as to which -omics fields can help characterize the disease or provide meaningful answers, though the microbiome and metabolomics are showing great promise. I think proteomics and nutrigenomics may also play an important role in helping us understand the disease at a personal level since diet is being shown to be important to gene expression. And with the help of epigenetics and gene expression, we can hopefully understand the impact of environmental exposures and other exposures. I think that the data collected by the various -omics will be beneficial, and will need to be integrated in order to come up with a meaningful characterization, and personalized treatment regimens.
One of the limitations though is that studies are using different platforms and different methods, so that presents potential problems. I also think that more neuroscience and mitochondrial dysfunction research is needed, because there’s evidence that ME/CFS affects these areas. I’d like to see computational biologists take all the datasets that exist around the world and look at them. They might be able to find leads, potentially significant findings, were all the datasets that exist around the world made available to them. Similarly, perhaps there could be some benefit in machine learning combing through all published, and perhaps unpublished, research, to find things that might merit further investigation.
Do you think that genetic/genomics knowledge could be applied to ME/CFS clinical decision making and care?
No, not yet anyway. I don’t think there’s enough evidence. For example, despite all of the companies that say they know how to fix your microbiome, we really don’t know enough about the microbiome of ME/CFS patients to know which ‘type’ of patient needs what bacterial remedy. I wonder if a fecal transplant would work, but I think if you accept the notion that there are different ‘types’ of patients, some felled by Lyme disease, others by viral triggers, etc., that a one size fits all fix isn’t likely to exist. I think eventually we will get to a place where we can apply genomic knowledge to clinical care, but we just haven’t gathered enough knowledge yet.
We are very happy and grateful that you will be serving on the Community Impact Steering Committee for the JAX ME/CSF Collaborative Research Center. Do you have any ideas about the best way that we can engage with the patient community?
First of all, I’d like to thank you again for this terrific opportunity, which I’m very excited about as well as humbled to be included in. I do have some ideas. I think it’s important to find out what patients want because there is so much variability in patient knowledge and needs. I went to a meeting recently and I was absolutely struck by the level of questions that patients had. There is a huge range in what patients know, but also so much more they don’t know. Further, in addition to varying needs, patients have varying capabilities, so I think to effectively engage patients requires understanding how best to meet their needs. For example, reading is really difficult for some people, and maybe even impossible. So having as many audio versions of news and information available as possible would be great. Archiving information that is simple to find and will remain available for long time spans would be very helpful. I think it’s very easy to get excited about what information researchers can glean by developing a particular app, for example, without thinking whether it would be truly easy for a very ill person to use.
Having different versions of the same media is a really great idea! Do you have anything else that you would like to add?
Finally, I think there could be a benefit in developing and implementing a project to collect patient stories from around the world. This could be similar to Steven Spielberg’s SHOAH project for the memory of the Holocaust, for which there’s now a library. Jen Brea did the same thing in her amazing film, but clearly she could not capture every patient. An attempt to capture the stories of every patient around the world could have both medical, political, and activism benefits. These could also create the potential for data-mining. To document the stories of people in different locations, you might learn something about environmental exposures, etc. Importantly, you’d have a concrete collection of patient experiences around the world, and who knows what or where that could lead us!