James Maskell: 00:07 Hello and welcome back to the Big Bold Health Podcast, making health personal in a world of disease. Today, we are going to be talking about measuring health and diagnostics. And, I imagine, Jeff, that in a parallel to us right now, the Big Bold Health Podcast is actually hosted by Dr. Jeffrey Bland, and maybe Elizabeth Holmes as Big Bold Health people changing the world. You know, the Theranos story has been in the papers, has been sort of at top of mind for anyone who’s interested in the facilitation of health creation. And so, as we get into this conversation about diagnostics, I thought maybe we could start there. What was it about the Theranos story that was so compelling to so many people for so long?
Jeffrey Bland: 00:55 Yeah, I think, James, that this is a wonderful case history for where we are, where we’re going, and some of the opportunities that are before us. The aspect that measuring things in our blood can give us insight into the status of health of the individual, has been a longstanding principle within clinical chemistry and within medical diagnoses. And, it may not be well understood by most people that in the early days of medicine in the United States, the concept of taking your blood and analyzing stuff in it to see how you were doing was not usual and customary at all. In fact, the chemistries that we use to do those tests were not really that available.
Jeffrey Bland: 01:36 The first group in the world to actually do these routinely, were this group in Minnesota, way up out in the middle of nowhere, Rochester, Minnesota, the Mayo Brothers, who thought that these developing concepts of chemistry—which in the early part of the 20th century was still kind of a new concept of applying chemistry to biology—that the measurement of stuff in the blood, chemical stuff in the blood, could be very important in developing a prognostic understanding of the patient’s status of health or disease. And, that was really what kind of differentiated the Mayo Clinic from all other clinics in the United States, maybe even in the world at large. And, they gained a reputation, because they were isolated up there in the North lands of Minnesota, they could kind of do this, and they developed a reputation that people started coming to them, hearing about their reputation. And, it became more and more of a growing theme, in which later that kind of clicked over to become a standard of care which people said, “Well really, measuring some of these things in the blood is very important,” like blood sugar to get a definition of diabetes.
Jeffrey Bland: 02:41 Remember, the early diagnosis diabetes, prior to the 20th century, was tasting the urine.
James Maskell: 02:49 Really?
Jeffrey Bland: 02:50 Yes, tasting if it was sweet. Now that wasn’t a big attraction for most clinical chemists in those days.
James Maskell: 02:55 They’d outsource that to the nurses, surely.
Jeffrey Bland: 02:57 Exactly. So, the advent of chemistry really was a step up in terms of both the specifics and the precision, but also getting away from having to taste urine for sugar, sweetness.
Jeffrey Bland: 03:08 So, the bottom line is that this concept of measuring things, chemicals, became a very important diagnostic determinant that underlies most people’s general health screening. When they go in, they’ll have their blood taken, and a whole family of different—what are called analytes—will be measured.
Jeffrey Bland: 03:27 Now, with that as a concept then, people started saying, “Well, what else can we measure?” Because, it turns out that we have 35,000 genes in our book of life, but those genes code for more than a million different proteins, which are found in our cells, tissues, and our blood. Each one of those proteins may have some diagnostic characteristic that would be of interest if we knew about them. So, this is a rich field of discovery and investigation. So, all sorts of people, clinical chemists, immunologists, all sorts of different fields of discovery, have been trying to understand what these things are that float around in our blood, what they mean in terms of how our body is functioning in terms of health and disease.
Jeffrey Bland: 04:11 With that as a kind of a background, then, people have said, “Wouldn’t it be wonderful if you could develop a technology where by just taking a finger stick of blood, in that single drop—so microliters of volume; a very small amount—that you could analyze an infinite number…that’s an exaggeration, but a large number of different things, and you would know what they meant.”
Jeffrey Bland: 04:36 Well, if you could do that, if that technology were to be developed as a breakaway, new age technology, you can imagine it would both reduce the trauma of having your blood taken, because you don’t have to puncture the vein then and take a bigger volume of blood. Secondly, it would make it accessible to be done in all sorts of places, because you don’t need a trained phlebotomist of a blood taker to puncture the skin of your finger and take one drop of blood, so it’d make it much more accessible. Third, it would make it much more convenient if you could measure many things in that one spot of blood, and therefore the cost should come down significantly, making it more accessible to all sorts of different less advantaged individuals, so that they could better get diagnostic care. So, there are all sorts of extraordinary values that could come from that technology.
Jeffrey Bland: 05:28 And then, lo and behold, this brilliant wunderkind of an individual, dropout from Stanford, Elizabeth Holmes, who has a personality second to none in terms of personal self-affirmation, decides that this technology can and will be developed under her reign, her rule, her watch, and that it will be a fingerstick technology. It’ll be accessible to everybody, it’ll be inexpensive, it will measure everything in one spot of blood, it will be done quickly, and in fact, we’ll produce a machine that can go in every home. It’ll be so inexpensive that everybody can become a diagnostician and follow serially their health throughout their life and become their own personal master of their health.
Jeffrey Bland: 06:09 Wow. This sounds like a company I’d want to invest in, right? And lo and behold, a lot of people did, raising not an inconsiderable hundreds of millions of dollars of investment capital.
Jeffrey Bland: 06:21 Now, what happened? Well, what happened is, we have to be very cautious sometimes between our aspirations, our dreams, and then the application of that in reality, and in delivery and execution. The challenge that you have when you’re trying to measure from any single bit of blood in one instrument all these different things that you want to measure, is that you have four different kinds of things you want to measure. And, just from a clinical chemistry point of view, let me just tell you what they are.
Jeffrey Bland: 06:50 You want to measure simple salts like potassium, magnesium, sodium, iron, so these inorganic elements. There’s something related to all of those, like iron with anemia, sodium and potassium relative to your kidney functions, so these are important to measure.
Jeffrey Bland: 07:06 Then you want to measure what are called organic chemicals, things like glucose, or things like uric acid, or things like urea, things that we know are associated with organ function—these chemicals of which there are literally thousands of different chemicals.
Jeffrey Bland: 07:26 Then there’s the third category, which are proteins, right? And think of all the kinds of proteins we have. These proteins are enzymes that regulate metabolic function. So, if you were to measure liver function, you might want to measure enzymes that are unique to the liver that if the liver is damaged, it would be released into the blood, and you’d measure as analytes like AST and… well, various enzymes that are liver specific.
Jeffrey Bland: 07:51 Then the fourth category are infectious organisms. You’d like to measure things like viruses or bacteria. Now, if you examine the technologies that are required to measure each of those different four categories, they’re very different technologies. They have different conditions upon which they’re measured, different pHs, different temperatures, different all sorts of things. So, to put them all in one test and to do it on one drop of blood? That’s no small challenge, maybe not impossible, but it’s extraordinarily challenging.
Jeffrey Bland: 08:22 So with that then, what happened with the Theranos example is that this is really an example of over-promising and under-delivering. And, would it have been able to have been delivered in time? I think the answer is potentially yes, over time. But, the difficulty is that the compression of the commercial world to try to make a commercial product, and try to make it profitable, and try to return an investment to venture capitalists and other investors that felt that this was going to be a quick return to success, really put undue pressure on the company that should have been in a research mode for some longer period of time. And, they should have also qualified that they’re not going to be able to run every test on a few microliters of blood. If they would have then been able to qualify properly their results, it could have been a sustaining growth company, I believe. But, it exaggerated the opportunity and produced then its own death knell through its own activities.
Jeffrey Bland: 09:22 Now, the problem for all of us in this field is that there is a spreading effect when you have something that’s that prominent and that investment-worthy that disillusions so many shareholders, and gets the government involved, and major distribution systems like Walgreens that become disillusioned, and Safeway, that you then start to have a color about all other technologies, and people get very disillusioned. And they say, “I’ve heard that before, and I’m not going to be interested.” I think that’s a shame, because there are extraordinarily robust new technologies that are developing all the time that will help move us towards that goal, to make the testing much more inexpensive and readily available.
Jeffrey Bland: 10:05 Let me give you an example to show you the good side of the curve. The good side of the curve would be genetic testing. When I first got involved in the concept of deciphering the genome as a practical assessment tool or technology… You probably know the first human genomes that were deciphered, that led to the rose garden discovery with President Clinton at that point, saying that we’ve now deciphered the book of life. It was about $3,000,000,000 to decipher the first genome. Well, that’s not very commercially practical.
Jeffrey Bland: 10:42 Over time however, with the so-called Moore’s Law—which is found in computing—that you have an exponential increase in the power of technology over time. What we’ve seen that Moore’s Law can be applied to the genome testing, and so the cost per analysis has gone from a billion, to a million, to a hundred thousand, to ten thousand, to where now I’ve had my full genome deciphered, which includes both the coding and noncoding region. Meaning the dark matter of my genome, has been analyzed for under a $1000, and it’s going to come down, presumably, to be around $100 to get your genome deciphered.
Jeffrey Bland: 11:20 Now how is that being done? Well, the development of technologies that we never had the knowledge would even come about, with young, new minds that are evolving new ways of looking at how to decipher the human code, based upon methodologies that were not available even five years ago. So, that’s a very exciting example of what can happen if we have the patience and the stick-to-it-ness to allow these technologies to be developed and to have the proper proof of concept.
Jeffrey Bland: 11:47 So, will we get to the point in the lifetime of people living today where we can have a very robust, simple way of using blood spot analysis for determining all sorts of analytes? I think the answer is yes. Will it be everything that Theranos talked about? Probably not. It probably won’t analyze everything in the world from a single drop of blood, but we will be seeing, and are seeing already, technologies that allow us to interrogate not just the presence of disease, but the presence of health and function, which helps us to measure not our disease characteristics but our health span. Our health span, that’s where we’re going.
James Maskell: 12:26 Yeah, one of the things that sort of I think stopped the architecture of health creation from occurring is just the fact that there’s not as many numbers, right? There’s not as much quantification of these kind of things, and ultimately, I think quantification is something we’ve spoken about with the continuous glucose monitoring and that kind of thing. What do you feel is the quantification of health that is going to be necessary for this to stand by itself and say, “Hey, this is a legitimate way of understanding health?”
Jeffrey Bland: 13:01 Oh boy. That is a really fantastic question. You’ve been thinking about this, I can tell.
James Maskell: 13:06 I have.
Jeffrey Bland: 13:07 That’s really insightful. So, the way that we have used the diagnostic tool of measuring stuff in the blood, or in tissues of the body, or in saliva, or in urine is to look at the presence of things in those biological samples that are indicative of a damaged organ, I mean a disease. So, these become indicators of disease.
Jeffrey Bland: 13:27 The first analyte, the first substance, that was measured in the blood, that was generally accepted in medicine, that didn’t analyze the damage of an organ, i.e. a disease… Let me ask you, do you know what it is?
James Maskell: 13:40 Glucose?
Jeffrey Bland: 13:41 No, because glucose measures diabetes, right? So, I’ll help you, it is cholesterol. Think of cholesterol—Is there a single disease that is diagnosed by seeing elevated cholesterol in your blood? The answer to that is no. Cholesterol was the first substance that general medicine accepted as being important to evaluate that has nothing to do with the diagnosis of disease, it has to do with the prognosis of potential disease.
Jeffrey Bland: 14:10 Let me set that in for a moment. This is a very important demarcation in the way that we use this kind of testing. In the past, testing was always used to evaluate the presence of a disease. With the addition of cholesterol to a standard blood test, now suddenly it was to assess the risk to a disease, cardiovascular disease, right? There is no disease for which cholesterol elevated is diagnosed. It tells you about the potential of a disease.
Jeffrey Bland: 14:43 Now, why that’s important is that that leads us from diagnosis to prognosis, and that leads us from disease to health trajectory, and health production. So, what we are witnessing right now is a very interesting transformation in asking the question, “What other things do you want to measure in the body’s fluids that would help us to understand the trajectory towards dysfunction?” And, well before you get to disease, that’s a measurement of your health capacity, so that you can measure that serially, meaning over time, and you can be a benchmark as to how your engaged in a health creation program.
James Maskell: 15:22 It seems to me that you have to start with the end in mind. So, with Theranos, the thing that jumped out to me from the book was that she started with the end in mind, which is first of all the big vision, right? Being able to get everything from one drop of blood, and the second thing was just how sort of comical it was that it had to fit, it had to be this size, right? That was like the focus of it. It seems to me that projects that start with the intention to be able to measure what has previously not been measured with a vision towards understanding the complexity of prognosis and health, is a starting point for a project that could yield the kind of results that you’re probably talking about, is going to be necessary for this next era.
Jeffrey Bland: 16:02 Yeah. Again, you’re speaking about this book, The Bad Blood, which really is a history of the Theranos rise and fall, and again, I think you chose a good example with that story, because the Theranos example was really trying to talk about early diagnosis, making earlier diagnosis, like earlier recognition of when you might have cancer, or heart disease, or diabetes. That’s all meritorious and valuable, but that doesn’t really tell you about health.
Jeffrey Bland: 16:31 The next stage, which is the stage we’re involved in right now, and is the focus of the Big Bold Health Podcast is, what do you really need to measure to understand the presence of health in the individual? Meaning their function. And as we said, the function is really broken down into four categories, their physical, their physiological or metabolic, their cognitive, and their behavioral, psychological function.
James Maskell: 16:54 So, for people who are listening at home who want to get a sort of a heads-up on this and ahead of the game, maybe they’re a biohacker, maybe they’re people who have been faced with some disease, have come out the other side of it and are now ready to think in this new way, what are some of the sort-of basic things that fit into that category right now today?
Jeffrey Bland: 17:12 Yeah, so let’s start with physical functioning quickly. Physical functioning is strength, flexibility, and endurance. Are there simple ways to assess those that you don’t have to go to a doctor’s office and don’t have to do a sophisticated kind of machine testing? And the answer is yes.
James Maskell: 17:25 Can you do 40 pushups?
Jeffrey Bland: 17:27 That’s right. There’s the step test. There are different ways of examining, very easily, your cardiorespiratory function with minimum exercise. There are ways of examining your flexibility, like reach testing. There are ways of looking at your strength, as you said, like pushups or pull-ups. So, that’s one way that we can start assessing that, and we can track it over time to see if we’re improving.
Jeffrey Bland: 17:51 The second would be metabolic. Are there ways that you can examine your metabolic function? And, the answer is yes. Now there are many direct to consumer labs that are providing very inexpensive panels of tests that allow you to examine things that would show whether you have insulin resistance, or a risk towards poor insulin signaling, or you have inflammation, central features that give rise to understanding your health inventory.
Jeffrey Bland: 18:15 Third of which is cognitive. There are cognitive tests now on the internet that you can test your short-term memory and your ability to do pattern recognition. And, lastly is behavioral and psychological testing. Tests are available once again, pen and paper tests or computer algorithms, digital tests, that allow you to understand your behavior relative to certain opportunities for function and health.
Jeffrey Bland: 18:37 So, we are witnessing the emergence of a new big, bold health technology. Not a disease technology, a health technology. And, we’re going to be spending at Big Bold Health, in this podcast, going through and chronicling this revolution to make this accessible to our users, so that it will not just be some esoteric, conceptual thing out there in the blue sky, but actually delivered as a value to individuals so they’ll take charge of the most important thing we own, which is our health.
James Maskell: 19:04 Absolutely. I’m really excited to get into some of this, because I feel like at this moment in history there’s almost something unusual that has to happen to propel people to want to participate in it. But ultimately, what we’re looking for is a moment where this is just the norm.
Jeffrey Bland: 19:21 That’s exactly right. And, I think that any shift of the general zeitgeist of a population undergoes those transition doesn’t… You have the early adopters. Then you’ve got a lot of naysayers. Then the naysayers start to say, “Well, hold on. Maybe that’s not as wrong as I thought.” And then later, they come and say, “No, I always believed in that. It’s always been part of my belief system.” And, I think we’re in the middle transition. We’re beyond the early adopters, the biohackers. We’re into the kind of how do you take these concepts that came out of these early adopters and translate it into the more general health-conscious consumer so that it ultimately becomes the standard of identity for all individuals, that people have access to independent of their socioeconomic status, or their ethnicity, or their cultural belief systems, that they have access to things that will revolutionize their ability to achieve good health.
James Maskell: 20:13 Beautiful. Well, that is something that is going to be available to more people. I’m excited to be chronicling this with you. We’re going to be talking about biohacking. There’s a number of other topics that will be coming soon on the Big Bold Health Podcast, but I hope that for everyone who’s listening, that the Theranos example can serve as a warning signal of how good ideas can sort of go a little bit wrong, but that ultimately those ideas are moving us in a direction that is going to be beneficial for all of us and mankind.
James Maskell: 20:44 So, this has been the Big Bold Health Podcast. Been great to be with you here. Dr. Jeffrey Bland, myself, James Maskell. Thanks so much for listening, and we’ll see you next time.