Many remarkable, gutsy clinicians, scientists and thinkers merged together in a synchronistic way to birth what we now call Functional Medicine. Who are the pioneers? What key ideas influenced the FxMed revolution? Who came up with “antecedents, triggers and mediators” and the Matrix (roughed out on a napkin during a burst of inspiration)? What about recognizing the importance of the gut, the microbiome (the heretical term “leaky gut”) and the influence of the environment interfacing with genes on disease? From the early ideas of Archibald Garrod, Weston Price, Linus Pauling and Roger Williams to the many amazing FxMed leaders of today (check out the PLMI conference proceedings) – – listen to this remarkable conversation with Dr. Jeff Bland as he takes us on a journey through FxMed yesterday, today and tomorrow!
Quotes from Dr. Jeff Bland
“What if you were to have a magic wand and to wave it, what would medicine look like if it was the best you could make it … ?” – – Jeff Bland, quoting Susan Bland
“… don’t accept the norm as a standard of identity for the future… you’ve got to continually push forward in understanding and not get too comfortable with what you already know because it probably, in retrospect, will turn out to be fairly naïve” – – Dr. Jeff Bland
“We moved from [the] concept of separatism and compartmentalization to more and more thinking of the body as a system…” – – Dr. Jeff Bland
Podcast sponsored by the DrHRejoint
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FxMed Podcast Series sponsored by the Designs For Health
Dr. Fitzgerald: Hi everybody and welcome to New Frontiers in Functional Medicine. I’m Kara Fitzgerald. I’m so happy to be talking to Dr. Jeff Bland today. Many of you know Dr. Bland as the father of functional medicine. I certainly recognize him as such. He cofounded the Institute For Functional Medicine in 1991 and he’s been teaching extensively across the globe for the last 35 years. I have had the honor of learning from him on many occasions. Dr. Bland’s a biochemist by training. He’s a fellow at both the American College of Nutrition, where he’s a certified nutrition specialist and the Association for Clinical Biochemistry. Dr. Bland was the director of nutritional research at the Linus Pauling Institute of Science and Medicine in the early 1980s, working directly with 2-time Nobel Laureate Dr. Linus Pauling. I look forward to hearing about that today. He considers Dr. Pauling to be a lifelong mentor.
Dr. Bland has authored several books, most recently the Disease Delusion in 2014. He’s the principal author of over 120 peer-reviewed research papers on nutritional biochemistry and medicine. He’s self-published a monthly audio journal, Functional Medicine Update, for more than 30 years and that’s distributed to health practitioners globally. I believe Dr. Bland, actually, is going to be making some of those available to us for free. I’ve been listening to them for years and they’re a wonderful resource.
Dr. Bland founded in 2012 Personalized Lifestyle Medicine Institute, PLMI, a nonprofit organization based in Seattle, Washington, where he continues to serve as the president. He’s also president and CEO of KinDex Therapeutics, which researches molecules associated with genetic expression patterns in chronic disease. I will have his contact information, website, number, etc. on the podcast page, so you can reach out and access Dr. Bland and see what he’s doing over at PLMI, so without further adieu, Dr. Bland, Jeff, thank you so much for podcasting with me today.
Dr. Bland: Dr. Fitzgerald, it’s just an extraordinary treat and privilege to be a part of your remarkable program and you are one of my true bright stars in this whole field of functional medicine, so it’s a real privilege.
Dr. Fitzgerald: Thank you so much. Thank you. Yeah, it’s an honor to be able to learn from you. When I was thinking about what we could talk about, how we could best use our time, of course I want to jump forward and you’ve been publishing a lot on where functional medicine is heading. It’s rich, powerful, it’s exciting. We’re at this wild tipping point, this amazing tipping point in medicine right now and you’re at the forefront of that. I want to go there, but I thought let’s go back in our lineage. This is so near and dear to so many physicians and patients, people, this ability to transform to true wellness and moving the whole medical model away from the disease model. Anyway, so I wanted to go back in time and just talk about some of the roots of functional medicine and your heroes and mentors and so forth, so who are we?
Dr. Bland: Yeah, that’s a wonderful place to start. For me, I think I was very fortunate to have been born and moved into the field when I did because I think I was a bridging person in between founders of the concepts that underpin this new paradigm in healthcare that you’re talking about that we’re going to discuss in greater detail and then this new generation of researchers, clinicians, that are really making it happen, of course of which you are one of that group. I think I’ve been the continuity factor that bridges between people like Roger Williams and Linus Pauling, even going back to people like oh, I guess we want to go to Weston Price and his classic book Nutrition and Physical Degeneration.
All of these, the forefounders of our field, were individuals that I either had the fortune of meeting or knowing, except for Weston Price, who had previously passed away, or were actually, as you mentioned, fortunate enough to even work with them like I did with Linus Pauling. I think it was a really remarkable opportunity for me, with my background in biochemistry, to be this continuity factor between the founders and where we’re heading in this incredible age in the 21st Century.
Dr. Fitzgerald: What did you glean from some of your mentors that prompted the movement, the development, of functional medicine? Can you point to some experiences with Dr. Pauling or maybe some books or papers or just concepts that were emerging for you?
Dr. Bland: That’s a really insightful question. I think first of all I’ll say it and then give you some specifics. I think in general, the thing that I learned from the people that I had the privilege of hanging out with is don’t accept the norm as a standard of identity for the future and that you’ve got to continually push forward in understanding and not get too comfortable with what you already know because it probably, in retrospect, will turn out to be fairly naïve. All the way through my PhD work and certainly into my young life as a assistant professor of chemistry and then later into my work with Linus Pauling and others, I had the fortune of meeting people who that was the way that they approached life. They were never comfortable with the status quo and they were willing to travel a sometimes difficult road of being an outlier and they recognized the responsibility of being an outlier doesn’t necessarily make you right. Again, of course, the heat on your back of finding a way to prove your point and to work hard to convince other people from evidence, not just from conceptualization.
I think that was a broad principle, but then we get down to the specifics and we get down to things like what is a disease. It was very interesting for me having spent some time with both Roger Williams and quite a bit of time with Linus Pauling in which they viewed disease in a very difficult way than I had learned, which was more of a histopathology-based, diagnostic-focused approach to understanding sickness and so we could put a name to that sickness and call it something. What I learned from them was these names that we put on these conditions are really just manifestations of our lack of complete understanding of the personal disturbances that occur at the physiological level in the individual and so we group people together in aggregates to make it simpler for us. We have groups like diabetes and groups like heart disease and groups like arthritis in which really each one of those individual people varies significantly different in the way that they are actually presenting the disturbances in their own physiology that give rise to those things that we call their disease.
Then that concept led into then say how do you actually understand what the differences are then in the individual versus the aggregate? Fortunately, at this time, in the 60s and 70s, new technologies were being developed that allowed analytics for the evaluation of all sorts of things that we knew existed, but didn’t know how to measure them accurately. I’m talking about various things that we now call metabolomics or proteomics where we’re actually starting to be able to explore the complex milieu of human physiology at the molecular level.
That gave rise to the whole birthing of a different way of using the clinical laboratory, moving away from just the assessment of a pathology by a variation in a certain indicator, something like a liver enzyme that indicates you have cirrhosis, to starting to look at something that indicates a disturbance in physiology like, say, cholesterol, which, as we all know, cholesterol in the blood is not really a diagnosis of anything, but it tells you something about the physiology of the individual in the biosynthesis and metabolism of cholesterol that then relates to their function.
That concept, which was really brought through both by Roger Williams with his concept of biochemical individuality and Linus Pauling, obviously, with his concept of molecular medicine, which both played off Archibald Garrod’s discovery the previous century of inner metabolism diseases. That all gave rise, to me, a whole new aha paradigm as to how people really got sick and how we would really define unique therapeutics based upon that individual’s own situation. Those are probably the driving forces in my learning early on in my career.
Dr. Fitzgerald: It’s so interesting and powerful. As you know, I worked at Metametrix. I had the privilege of doing post-doctorate training with Richard Lord and Andy Bralley. They were, I think, early adopters of organic acids attempting to identify nutritional insufficiencies, so looking at coenzymes and cofactors, rather than just looking at extremely elevated levels of organic acids. We know the various enzymes require minerals and vitamins to catalyze the reaction and if there’s an insufficiency there, we can tweak that reaction. I know that you had a big role in thinking through the utility of using organic acids and I think it goes back to Roger Williams and biochemical individuality and Linus Pauling’s work. Can you talk about that?
Dr. Bland: Yeah, thank you. That’s a part of the story that I don’t think I really ever talk much about, so it’s a privilege to have the chance to talk about it. In the late ’70s and early ’80s, a woman by the name of Bonnie Worthington was sponsoring very large meetings in Atlanta on complementary … It wasn’t called that at the time. I think it was more called alternative healthcare. These meetings were drawing fairly large audiences, 1000 or more people. I was invited to be a presenter and at the second one of her meetings, as I believe, which was probably around 1980, I would say, I had the privilege of meeting these 2 people, Andy and Caroline Bralley, he just having finished his PhD in biochemistry, who were interested in setting up a medical lab and they wanted to do so around the concepts that would focus on this newly emerging field rather than just a traditional pathology-based lab.
Andy and Caroline and I really established a very, very good friendship and [collegialship 00:12:21], I think, early on. I became then a consultant or colleague in the development of their lab. This was actually before Richard Lord joined the lab. Richard, at that point, I think was a instructor at Life Chiropractic College, if I’m not mistaken, in Georgia. We were looking at the methodologies that might help interrogate some of these unique facets of biochemical individuality.
It was through that ultimately you might recall that Emory University Medical School in Atlanta had a program in molecular diseases that were associated with mitochondropathies and so we started looking at some of the things that they were doing to analyze, in their pediatric patients, the inborn areas of mitochondrial function and things like that, organic acid analysis, and started to come out as maybe a tool that if we were to look at it with a little bit finer structure, it could help guide us in understanding where the molecular uniquenesses are in that individual and then what are those that are reducible by modifying these cofactors as you indicated through looking at metabolic pathways from a functional perspective, not just from a bunch of lines on a piece of a textbook in biochemistry. I think Andy just became, and Caroline both, great students of this field and from that, Metametrix was born.
Dr. Fitzgerald: Right, the precursor to the omics revolution. It really was and I know that these tools, so looking at amino acids and looking at organic acids, there were certainly much smaller panels than what we’re looking at today in systems medicine, but beginning to look under the biochemical, look under the metabolic hood of the patient and infer metabolic activity. Yes, it just seemed so much more sensitive and thrilling and empowering looking at oxidative stress markers or accumulation of different amino acid ketabolites knowing that thiamines required or the tryptophan derivatives like quinolinate and knowing that there’s some sort of inflammation happening in the body and some of the far-reaching effects of that. I still use organic acids in my practice and amino acids and look at the fatty acids and continue to, as Richard would say, look at the dance of the molecules in his mind and consider those to be useful guides in treating the patient.
Then, of course, now we’ve got the advent of single nucleotide polymorphisms, which were marrying to this data and it evolved our understanding a little bit further and we’ve gone on from that. Any comments around the emergence of SNPs and the movement of medicine?
Dr. Bland: Yeah. I think you’ve done a really marvelous job of summarizing a tremendous transition, both in the technology and its application and then the implications of it, so if we center this period around 1980, the Pauling Institute had been trying to interface mass spectrometry in the ’60s with high-performance liquid chromatography, HPLC, to separate out all these molecules that were present in biological fluids, could be urine or it could be blood or whatever. All of the concepts that we’ve developed over the years were really being explored back then, the difficulties that we didn’t have the instrumental technology that we have today to measure a lot of these things sensitively and precisely.
Secondly, we didn’t have the computer-based power that we have today to handle these large data sets, but certainly what Pauling was doing if you go back and read his early papers from the ’60s in the emergence of this, or the micromedicine concept, was focused directly on what later became the technology that you’re describing. About 1980s, when they started to, I think, become more robust, Jon Pangborn was a champion for amino acid analysis and, of course, Andy and Richard with organic acid analysis.
Then, if you think about it, the first real push for omega-3 fatty acids as being an interesting therapeutic tool was about the same period, about 1980 and we started to see people with HPLC analyzing then fatty acid profiles in individuals. These tools started to provide a mosaic opportunity for evaluating the metabolomic characteristics of the person. The question is where did this metabolism come from and, of course, you’ve already described it came from all these various networks of inner conversion that we call biochemical pathways or networks, but where do those come from? Obviously, they came from the regulation, whether it’s proteins that were regulating the function. The proteins then came from proteins or enzymes and those, ultimately, were derived off the translation transcription of the genes.
We started to back ourselves into a more integrated approach towards looking at how [inaudible 00:18:16] in the individual emerges and then the big wild card, I think would call it disruptive concept, was the recognition that lo and behold, the environment that the person experiences, their own unique environment, which includes their diet and their thought patterns, their activity patterns, their exposure to various environmental agents, including radiation, influences how these genes are expressed and then regulates, to some extent, how the downstream metabolites are produced, so you really start looking at a theme that the metabolites are the smoke from the fire that occurred upstream from these expression patterns that occurred when the environment interfaced with an individual’s unique genome.
That then ultimately gave rise to the appearance of what we later call health or disease. This systems theory emerged that really birthed a whole different view of disease from that which most of us grew up with. Now it suddenly wasn’t just infection or trauma, it was disturbances of this interface between the genes of the individual and their environment, for which we then found many of these were correctable. If we just knew the right questions to ask, we could provide the right answers and that from which was born, in about 1990, functional medicine. That’s how the theme, I think, emerged to evolve over those 20 or so years.
Dr. Fitzgerald: It’s incredible and it’s very exciting, so we were moving away from our very limited histopathological understanding of disease, as you mentioned, and the drug interventions that are going to stop or block in this aggressive way. I think maybe you must have obviously been seeing the limitations of that all along. I think also, too, a big thing at the time was just forgetting about nutrition as a variable in medicine. That was largely gone and you and Dr. Pauling and Dr. Williams and Andy Bralley, all of the folks involved in ushering in this new medicine were completely shifting the paradigm and recognizing, as you said, the powerful influence of the individual’s environment, their diet, the micronutrients, their macronutrients, their lifestyle, the stress response.
Then, of course, the impact of toxins, not just massive toxic dumps and these huge occupational exposure, but the perturbation of metabolic activity with what we would consider subclinical toxin exposures or the advent of using lots of plastics and the 80,000 chemicals and the synergistic effects. I think wouldn’t you say all of this, just this exciting, all of this was arising simultaneously in this systems milieu that you guys were really creating and birthing.
Dr. Bland: Yeah, I think you said it beautifully. I think what was happening, and I don’t think we actually fully understood this at the time, but it started to be more well-recognized is we were moving from a view of healthcare as isolated, segmented components, so we had all these different medical subspecialties that dealt with individual parts of the body and they owned that organ-specific physiology. They had their own nomenclature. They had their own drugs and procedures and they had their own guilds.
We moved from that concept of separatism and compartmentalization to more and more thinking of the body as a system and of course, another major contribution to this rising aha, this rising concept, was the recognition of the role that the gut played and the fact that the gut was really the seed of the immune system and the gut was interfacing with this living community of thousands of organisms and maybe as much as 3 pounds of living organisms in our gut that were communicating with the body, both in friendly ways and not-so-friendly ways.
We were some of the first groups … In fact, I think we invented the term leaky gut. That was considered a heretical term when we first used it. For the first 15 years, we were criticized heavily. Every time I would speak at a medical grand rounds meeting and I would use that term, people would look askance or if we talked about metabolic endotoxemia and that was … Endotoxemia was just a life-threatening condition that happened in emergency room hospital trauma centers. You didn’t have chronic endotoxemia, but over the years, this also became fairly well-documented. Now these are acceptable terms in immunology and gastroenterology.
I think that all of this took us into a much more systematic view of human function and, of course, then emerging more recently is even to recognize the importance that this microbiome has on all sorts of functions through crosstalk with our receptor systems and cellular signaling. I think we went from discreet segmented view of the body and sickness to this unified field theory of understanding of how the warp and weft of a function is altered by the experience that the person has in their life.
Dr. Fitzgerald: It’s so incredible, Jeff. It’s really great to hear it. It’s so big and clearly there were many individuals involved, many cogs in this machine expanding medicine, developing functional medicine. It’s very thrilling. I think that you guys were historians also. Going back into the medical literature, looking at the fact that Mechnikov wrote about lactic acid bacteria I think in the 1800s, if I’m not …
Dr. Bland: Yeah, that’s right. He won a Nobel Prize in physiology in [1901 00:24:43], so yeah. I think his Prolongation of Life book in which he describes instilling cultured bacteria into the rectum was published in like 1898.
Dr. Fitzgerald: It’s amazing. I think just an appreciation and an open-mindedness and a willingness to jump in and try something out and perhaps also too definitely trusting the body’s physiology, recognizing the importance of nutrients, and then since you guys happened to be scientists, you could develop the analytical know how to actually measure some of these things that you were talking about, looking at metabolism and … Go ahead.
Dr. Bland: Yeah, and I think we had such a great synchronicity in the cooperation among these people that were looking at the world from maybe a molecular perspective with some really, really great clinicians who were just very wise, people like Sid Baker, Leo Galland, David Jones. These were people who were willing to cross the boundary into discussing the science, but were very strong about the primacy and importance of making this clinically important and how it would really value the patient. I think that the marriage of very strong clinical news to use with these new tools of how to evaluate and understand the body at a different level really started to accelerate the development of this concept that we call functional medicine.
Dr. Fitzgerald: Yeah. Yup. It is. It was just wildly synergistic, all of these components coming together and creating or birthing this new medicine. How did functional medicine start?
Dr. Bland: What happened was we were all meeting at these various kind of meetings that were being presented by the different academies and the different societies and we’re all doing our own education thing. Then my wife Susan actually said to me, this would’ve been about 1989, she said, “Jeff, it seems like it would be really wise to have a conclave where you brought some of these great thought leaders that you’ve had the privilege of working with and knowing together to talk about the what if. What if you were to have a magic wand and to wave it, what would the medicine look like if it was the best you could make it and wouldn’t that be fun to have that kind of a discussion.”
We actually sponsored, thanks to her advocacy, 2 meetings in 1989 and 1990, I think it was, which were in Victoria, British Columbia on Vancouver Island. We brought people in and Andy was one of those people. I think we had about 35 different people including Wayne Matson from MIT, who is a systems biologist and analytical chemist and was very good in understanding some of the new statistic modeling that was being done with informatics that was take us into new things of dendritic analysis and cluster analysis and complex data set analysis.
We sat down, actually, for 3 days in Victoria to just discuss on a whiteboard what might be the ideal way of looking at health and the emergence of medicine. Then we followed that on with a second meeting in 1990. It was at that second meeting that I had this vision that really what we were talking about is function and even though function in medicine had a pejorative terminology that was related to psychosomatic illness or geriatric dysfunction, I thought maybe given what’s going on in the literature at that time, which was redefining function with functional radiology, functional cardiology, functional endocrinology, that maybe that with a good term if we were to look to the future. I proposed, in 1990, that we call this maybe functional medicine and out of that then was born the thought that let’s have an institute, so the Institute for Functional Medicine was born and then we had our first meeting in 1991.
Dr. Fitzgerald: How did that we rely so much … I use in my practice with all of my patients the functional medicine matrix. I use the nodes. I think about antecedents, triggers, and mediators. We’ve since introduced the timeline, but how did you come up with the final matrix or how did you develop that? That’s just a work of genius.
Dr. Bland: What happened was Leo Galland was really the principal contributor to the patient-centered concept that was really the antecedents, triggers, mediators, signs, and symptoms model. We give him great attribution for his contribution to functional medicine in that formalism. Then as we started to teach … I think back to it it’s almost hilarious. We started applying functional medicine in clinical practice training programs and at that point, they were being held in Gig Harbor, which is where our offices were in Washington state and there were 2 sections of probably 6 days duration each. If you can imagine people were coming in twice for 6 days, but that’s the way we started AFMCP in Gig Harbor.
We would do these breakout sessions in the afternoons and mornings would be lectures at what we now would call the modules in IFM today. We’d do the lectures in the morning and then we would have in the afternoon case-based breakout sessions. It’d be about 10 people per session and we’d have these instructors and David would be one, I’d be one, Bob [inaudible 00:30:54] would be one and so forth. When we got into the clinical applications then of these concepts, we more and more started to try to put something together on a piece of paper that could be given out to the individuals that would try to codify this information when we do our case-based learning.
Over the course of a couple of years, that rough cut first level thing that David and I actually did on the back of a napkin, you know how that goes, then evolved over time to ultimately be more robust. I think David Jones actually was the guy that finally coined the term matrix. This was the time where The Matrix movies were really popular, so I think it was his definition of the functional medicine matrix. It was really after a couple of years of evolution of the way that we were teaching in the AFMCP that that was born.
Dr. Fitzgerald: Right. It’s an incredibly useful tool now to practice to apply systems medicine clinically. Probably around this time, the human genome was mapped, right, maybe a little after this time?
Dr. Bland: Yeah, I think that’s another interesting guidepost in the emergence and development of functional medicine. If you think of the Human Genome Project really starting in the late ’90s and with the final announcement of the deciphering of the first book of life in the Rose Garden in 2000, that we, of course, the founders of functional medicine were well aware of the importance that understanding more and more about this double helix and the information contained within it, how important it was going to be in us understanding the aspects of dysfunction and also function.
I want to emphasize that in our discussions about genome early on, it was more about the regulation of the pluripotentiality of the person than it was about trying to find the genes that were related to disease. I think that unfortunately, we’ve slipped into a disease mentality about human genome testing because what everybody wants to know is what genes do they have that are going to cause them to be sick. Really, the majority of the genome tells a person how they’re going to be well and respond to their environment. I think that we need to bring this genomic information back into the context that it’s not a roadmap to sickness. It’s a roadmap to function and function can be the death of function or it can be disturbed function depending upon the environment that the individual is exposed to.
I think we recognized that as we got more information coming out of the human genome project, it was going to more and more provide some granularity to our understanding of what Roger Williams with genetotrophic disease or Roger Williams with orthomolecular medicine had been talking about. Our concept was let’s make sure we don’t jump onto the bandwagon too quickly and say oh, boy, now we’re going to know genes that cause disease. Rather, let’s examine this genomic story from the perspective what does it tell us about function.
Dr. Fitzgerald: Right. It did seem to me that, and correct me if I’m wrong, that there was some sort of disappointment among the greater medical community that this one gene, one disease model was crushed after the genome was mapped, when they realized that it was there’s far less genes and it’s infinitely more complex. Didn’t systems medicine, as we understand it today, would you say … You were already building it, but systems medicine, there was a great leap forward with these recognitions. Would you say that’s true?
Dr. Bland: Absolutely. I think what you’re saying is right on target. If you think that preconceptions often spear how we see, how we interpret observations, so the preconception in medicine is you’re well until proven sick and disease is a binary function. It’s like an on-off switch. You’re well one moment and you have a heart disease the next moment and that genes are there like switches to turn on and off your wellness or your disease and so if you got bad genes that get turned on a disease, then you have that problem. Then we better find a drug to block whatever that process was that got turned on that caused that disease.
That’s all a consistent model until the human genome was deciphered and we recognized, as you said, that you can’t describe the nature of function one gene at a time. You have to look at these as systems of interacting, interrelated genes and that their different expression in different tissues at different times under different circumstances is what gives rise to our overall body function, so what’s going on with a hepatocyte is different than what’s going on in a neuron, even though they share the same genes.
That conceptualization that came out of the disillusionment of oh, my word, we didn’t get as much out of this genome project as we thought, was a very naïve view of what I consider a revolutionary new concept that we’re still learning about, which is disease is much more than just one gene getting turned on or off. It is a complex orchestration of a dance of our unique genetic potential with the environment that goes that tissue or organ or cells are being exposed to. That, to me, opens up many more opportunities because it’s much less deterministic and it’s much more related to altering things that we can do each day to improve our function.
Dr. Fitzgerald: It’s so inspiring. I think functional medicine … I think that you and everybody who was developing the functional medicine model back then, scientists and clinicians and Linus Pauling, Roger Williams and the people going back, it was a real vindication, I’m thinking, as this emerged, some validation.
Dr. Bland: Yeah, it is. If you think of Linus Pauling, he had this article in a science magazine in 1949, which was the first article that I’m recalling that used the term molecular medicine and it was the definition of the genetic mutation that occurs in sickle cell anemia, so single amino acid substitution in a headed chain of hemoglobin. In that article, if you read it carefully, he cautions the reader to recognize it’s not that this says that all diseases are caused by one mutated gene, but rather that there’s this genetic variegation that is rich in its proposition that can be everything from what we call a genetic metabolism inborn error metabolism disease, like Tay-Sachs, Wilson’s, Gaucher’s, or phenylketonuria to much more variant forms of modification of the way the genes are functioning that gives rise to mild and less acute forms of illness that are modifiable by changing the environment.
Phenylketonuria is probably a good example of that, isn’t it, because you’ve got some cases where it’s very extreme. These children develop very serious retardation, developmental abnormalities early on and there are other children that have very mild forms of phenylketonuria, which just modifying the diet by lowering the phenylalanine content of the diet can preserve their function very, very nicely. I think this whole model was starting to really emerge out of the 1949 paper on sickle cell anemia, but it really took the Human Genome Project to really set it free.
Dr. Fitzgerald: Right. I guess I want to flash forward to present and the Institute for Systems Biology and the exploding pool of data that we’re now collecting and moving away from the double-blind, placebo-controlled trial and really attempting to measure, observe and measure and see what’s happening in real time, the genes, the proteomics, metabolomics, etc., things in action, the environment, the epigenome, etc. It’s an incredible leap forward and one that I feel I’m paying attention to, but we’re just touching upon it.
Dr. Bland: I think there is really the exciting … It’s like if you’re a skydiver, right before you jump out of a plane and you hope you got your parachute packed correctly because if you think of the genome and say in comparative genetics, how does the human genome differ from that of other plants and animals? It’s not so much that it differs in the number of genes. In fact, we have far fewer genes that code for protein in a human genome than a pinot grape has, but it’s this recognition now that only 2% of the human genome are related to genes that code for our proteins. That means 98% is what used to be called junk DNA.
I feel fairly good about this because early on, and I’m talking about going back into the 1980s and ’90s, I was very vehement about the use of junk DNA. I said, “I think we need to be very cautious to call this junk until we really know what’s going on.” By the way, I wasn’t the only one saying that. There were many others that were, as well, but now we recognize that the major difference that really constitutes the change between the human genome and all other plants and animals is in this what used to be called junk DNA, which were the regulatory reasons that actually control how genes are expressed through things like epigenetics and things like small inhibitory RNAs and various factors that are actually regulating the gene expression patterns as families. It really creates our function.
I think that as we now are gaining the tools to start looking at this what is called the genome’s dark matter, we really are starting to recognize that that what used to be called junk DNA is actually, to a great extent, the antennae that are out there receiving information from the outside environment to then translate that to the genome or to the coding portions the genes are what ones should be turned in and what cells and how we should function and so epigenetics is now seeming to play much more of an important role because it’s regulated to a great extent in the dark matter of the genome, this so-called junk DNA and the cell replication through the ribosomal RNA. It’s part of the junk DNA.
I think there’s all sorts of revelations now that this simplistic model that we had that we had this triplet code that was going to code for these 20 plus amino acids that would give rise to the sequence of various enzymes that regulated human function and it was all going to be worked out just on that kind of very simplistic model, we now have this much more robust model, which is it’s seen as the most significant factors that shape us, our HEA type, our health and disease patterns, are the interface of the dark matter of our genome with our lifestyles and our environment. Now there is a huge paradigm shift.
Dr. Fitzgerald: It’s incredible. It’s so exciting. I think in tandem or part of that is the emergence, again, a leap forward of analytical tools to be able to assess the high-throughput technology, being able to look at the proteome and the metabolome and the impact at the genome. We’re starting to see those things and I know clinically these are still in the research setting, but we’re really starting to blast forth in what we’re able to see and that’s awakening these awarenesses and concurrently, I think … Oh and actually, in addition to that and then we’re also having the emergence of all these new tools, these new systems tools, to analyze this massive data.
Dr. Bland: That’s right.
Dr. Fitzgerald: It’s such an exiciting time to be part of this river or this ocean.
Dr. Bland: If you look just what’s happened within the past 2 years, so we started off first with the ISB Institute, systems biology, jumping ahead and starting the Pioneer 100 program, which I discuss in my presentation at the AIT meeting for IFM of which I was a participant, which was this measuring lots of stuff on people, a book from a genomic and proteomic and metabolomic perspective over the course of a year and then instructing people based on their data as to how to make modifications in certain factors of their diet or lifestyle that would tune up their physiology.
That was part of a bigger program that ISB wants to do, which is the program to get 10,000 people. This is the Framingham of the 21st Century Project that [Lee Hood 00:45:49] is advocating. Then from that, now we see Human Longevity Institute, which is Craig Venter’s company. Craig is one of the two pioneers of the Human Genome Project with Celera, so now we have his company doing their approach towards assembling … I think he wants to have 10,000 human genomes cataloged over the next 2 years, 10,000. Think of that when we just a few years ago to get one human genome done was a billion dollar enterprise.
Then we hear just last week an approval at NIH of this collaborative project in New York City to follow 10,000 people for 20 years with complete data set analysis of their lifestyle, their diet, their genomics, their proteomics, their metabolomics, and to run the serial database. Then we have what’s going on with Eric Schadt and his [inaudible 00:46:52], Stephen Friend, which is called the Resilience Project in which they’re measuring all these things on the genomes of individuals who have had family histories of very serious disease, but they’ve lived into their 80s and 90s completely free of disease and so they’re asking the question what in their genomes because they have these genes for disease that are inherited, why didn’t they ever get expressed? Why are they silenced?
If you look at how all this is happening in real time, it is creating a groundswell that you either get on the bus or you get run over because it is really a transforming period.
Dr. Fitzgerald: Yes, it is true, it is. I want to circle back and anchor this in the clinical because I do think it’s important and David Jones has been really instrumental in my life, mentoring me in thinking about myself as a clinician in practice. Anyway, so concurrently, as we catapult forward in the investigation, we’re also catapulting forward with the practice of medicine and having the Cleveland Clinic open, an institute, the Functional Medicine Center there and just the explosion of functional medicine and new clinicians finding it and coming in and patients getting better and asking for it, so really along with the genomic revolution, there is an equally vital and powerful clinical transition happening.
Dr. Bland: Yeah, I think you said it. This information is only as good as its ability to help people reduce the suffering of dysfunction, right, and disease, and so it has to sieved through clinicians that really know how to use the tools. The tools are only as good as their ability to be used. I think the Institute for Function Medicine has really done a very meritorious job in being, I hope, at the leading and not the bleeding edge of getting these tools starting to be brought into the practice of healthcare, even though we don’t know all the answers yet.
The question is when you’re early on in a scheme, what’s too early and what’s just at the right level of early? I think this is always a complicated question because there’s always an interest in bringing everything new in because you want to be at the front of the pack, but you have to be a little cautious not to bring too much that’s new that hasn’t been properly vetted and you don’t know exactly what you’re really dealing with and so later you’re having to say, “I made a mistake. I didn’t fully understand what was going on.”
I think that IFM is doing a very good job of really proctoring and evaluating how this information is to be interfaced into the clinical perspective and to really train docs about how to think in a systems way. If I was to really ask what’s the most important singular takeaway from the Institute for Functional Medicine curriculum, there’s a lot of good tools, a lot of good news to use, but it’s principally how to move our minds away from thinking of things as binary, as true/false, yes/no, multiple choice, disease or no disease into a systems way of evaluating interorgan communication, whole body network biology.
That thinking, which is inherent in the early human being, has been trained out of us by the way our educational systems worked, which was to strive for this digital answer to a question and recitation by memorization. I think that it’s exciting when you open up this dormant power that we all have to create understanding of connections. The human mind is probably better than even the most powerful supercomputer in seeing patterns, so how we reinforce that ability of a person to see patterns. I think that’s a really powerful part of the functional medicine curriculum that’s connected to systems biology and to network physiology.
Dr. Fitzgerald: The tools that we’re using in functional medicine so much of the time are diet, what we’re eating, how we’re navigating our lives, working with stress response and so forth. On one hand, we’re catapulting so forward with technology and so forth, but really there’s very grounding interventions that we’ve been using time immemorial, just recognizing the value and the importance of the micronutrients and macronutrients. I think that we embrace first do no harm wholly.
Dr. Bland: I think we trivialized for so many years in medicine these concepts, saying these are either soft science or they’re of low importance in ultimately understanding the origin of disease. I think in the emergency room situation, I think types of care it may be true that these things at the moment are not the most important issues, but in terms of the pattern of emergence of chronic disease, these are the most important things. They watch over our genes 24/7, 365. They’re always present. They’re omnipresent and even though they might have low signal strength, over time, they’re the big movers of change in shaping physiognomy and changing phenology of the phenotype, so my belief is that what we’re witnessing right now is an understanding at this basic science level of how these what were considered small signal strength perturbations like diet have enormous effects over long periods of time on function greater than any other thing.
When you start to put that in context and then that’s how is that going to shape medical education and how will that shape medical therapeutics, how will that shape medical economics and the business of medicine? It’s going to have enormous effect on emerging on new industry, which is going to be a wellness-based industry that’s based on these parameters. We might have some kind of balance between a disease-based industry and a wellness-based industry as this particular or these concepts evolve to become more well-used and the informatics becomes more capable of picking out these patterns and defining uniqueness in the individual.
Dr. Fitzgerald: I think that’s a wonderful place for us to just close this journey that we took this morning. I appreciate you taking the time with me today to talk about who we are, where we came from, and an idea of where we’re heading. Thank you so much, Jeff.
Dr. Bland: If I could, I’d just like to close with I shared my experience that you and I just had within the last few months and that was the presentation by Moshe Szyf and Miguel on behavioral epigenetics. He’s credited with being the father, and Mike Meaney, his colleague, of that field. I think it is so powerful when you start looking at this data that says that the psychosocial environment that animals find themselves, of which we are one of those animals, can put materialistic marks, molecular marks, mental groups, onto our genome as a consequence of the experiences that we have from our observation of our world.
Now if you start thinking about that and you start asking questions about PTSD, post-traumatic stress syndrome, about behavioral abnormalities, about various disorders that now are so frequent in our society of depression, dysphoria, cognitive dysfunction, where might many of these things come from? What we’re starting to see through this new science that’s emerging is that even “simple things”, which are actually not so simple, which are the relationships we have, the joy of living, a sense of attribution, the feeling of purpose, locus control, all of these are variables that modulate at the molecular level how our genes are expressed through this dark matter that constitutes 98% of the human genome.
Now when I put all this together and you ask is this a frame of reference of just minor change or significant change in the way that medicine will be practiced in the future, I think it’s inevitable. These are huge disruptive technologies and discoveries that are going to change healthcare for the better.
Dr. Fitzgerald: So extraordinary. Yes, so extraordinary. The PLMI website will be up with this podcast and people can access Dr. Szyf’s lecture and the entire conference. I do recommend listening to them because it was an amazing conference that we had in October and I’m so glad that I went and I will certainly be there next year.
Dr. Bland: Awesome, thank you. I think many of those videos of the lectures, which are now free of charge on the PLMI website, people will find very interesting. I think there were several that were just mind-blowing. The one on stem cell physiology from the word … You can get a little glimpse as to where we’re heading by the application of this into the new world. It’s really amazing.
Dr. Fitzgerald: Right, it is, absolutely. Thanks again, Jeff. It’s been great to talk to you.
Dr. Bland: Thanks and you’re doing a great job. It’s such a privilege to have you as part of the field.
Dr. Fitzgerald: Thank you.
Dr. Bland: Thank you. Bye-bye.
Dr. Fitzgerald: Bye-bye.
JEFFREY S. BLAND, PhD, FACN, CNS, is an internationally recognized leader in the nutritional medicine field. He co-founded of the Institute for Functional Medicine in 1991 and is known to many as the “father of functional medicine.” Over the past 35 years, Dr. Bland has traveled more than six million miles teaching more than 100,000 health care practitioners in the USA, Canada, and 50 other countries about functional medicine.
A biochemist by training, Dr. Bland is a Fellow of the both the American College of Nutrition, where he is a Certified Nutrition Specialist, and the Association for Clinical Biochemistry. Dr. Bland served as Director of Nutritional Research at the Linus Pauling Institute of Science and Medicine in the early 1980’s, working directly with two-time Nobel Laureate Dr. Linus Pauling, whom he considers his lifelong mentor. Dr. Bland has authored several books about nutritional medicine both for the healthcare professional and for the general public, and he is also the principal author of over 120 peer-reviewed research papers on nutritional biochemistry and medicine. Dr. Bland has self-published a monthly audio journal, Functional Medicine Update, for more than 30 years that is distributed to health practitioners in 36 countries.
Dr. Bland was the founder and Chief Executive Officer of HealthComm International, a global company that became a leader in the development of medical foods, Chief Science Officer of Metagenics, Inc., and President of MetaProteomics, where he led a research team of more than 100 scientists in studying metabolic factors associated with chronic diseases. In 2012, Dr. Bland founded the Personalized Lifestyle Medicine Institute (PLMI), a nonprofit organization based in Seattle, Washington, where he continues to serve as President. He is also President and CEO of KinDex Therapeutics, which researches molecules associated with genetic expression patterns in chronic diseases. – See more at: https://www.functionalmedicine.org/page.aspx?id=179#sthash.xTHDnrRK.dpuf