Ben Locwin09.06.17
With great scientific advancement comes great responsibility. Think nuclear weapons and fissile fuel, biohazardous materials, worldwide social media and whether internet censorship is needed, gene therapies, and genetic modifications. There are of course many, many more, but these are a selection of some of the topics that top the list of social consciousness concerns at the moment.
We think we’re getting smarter, and we are indeed exposed to more information than ever before in history, but we’re still the same species that we’ve been for dozens-to-hundreds of millennia. This makes us fall prey to the same sorts of logical fallacies and cognitive biases of the human condition that we’ve fallen to many, many times in the past.
Amidst all of the advancements currently ongoing, one of the particular technological and theoretical themes that seems to make a lot of sense to the general public is that of pharmacogenomics.
What is Pharmacogenomics?
Indeed, we can’t delve into the next level of thinking without first defining what it is we intend to dissect: Pharmacogenomics is the research behind how diverse and disparate genomes of individuals respond differentially to drug therapies—pharmacological function and therapeutic response. In other words, which drug treatments work for which individuals’ genetic composition. There is a fertile field on this topic just barely having its surface scratched at the moment. We know, for example, that drugs like naproxen sodium work for some people, and don’t work for others—and/or cause serious side effects. Or that the anxiolytic benzodiazepines have a positive effect in certain populations, but a paradoxical effect in others due putatively to a number of genetic variations in the GABA-A receptor and its subunits.1 This is based on downstream effects from individual genetic differences in ADME for a particular drug (absorption, distribution, metabolism, and excretion). Targeting drugs to certain individuals and/or conditions—what could be better?
While social media has recently begun to drum up similarities between current global politics and, for example, dystopian literature like 1984, there are similar parallels and cautions we can draw now with what’s occurring in the scientific medicine field, and how the public will perceive it. For example, in a relatively near future scenario, if we had the capability to precisely catalog every person’s genetic code on Earth, we could begin to draw correlations between each gene map and their overall susceptibility to certain diseases and disorders, which we know in large part are associated with genes. Of course, as with internet marketing, which at times borders on abusive, past performance may indicate future behavior: Once a certain proportion of the population have had their genetic code stored in a reference library, there may be large-scale rejection of the technology to where genetic privacy becomes the aspired-to status quo. 50 years ago, if you were to tell an audiophile that all of his/her favorite songs could one day be stored virtually on an impossibly small device, they would not have believed you. After all, only a handful of decades ago, single-digit-megabyte storage devices were the size of small rooms. What does society do to return homeostasis to rapidly scaling technological infrastructure? It buys records. On vinyl.
Nobody from our trip-back-in-time meeting would have wanted to keep vinyl records knowing that their future-selves, or progeny, could have access to nearly limitless music taking up what is ostensibly no physical space whatsoever—relatively speaking, absolutely insignificant amounts of spatial volume. But there’s a psychological backlash, related to 20- and 30-year “retro-cycles,” where ‘what’s old is new again.’ World getting too advanced? Return a modicum of control by appreciating the physicality of retro materials. This gives people the seeming ability to ‘slow down’ the pace of advancement in their immediate sphere of influence.
So how does this link to the populations’ connection with, or rejection of, pharmacogenomics? If a certain tipping point of the population has undergone gene testing, there will be tremendously significant social pockets of gene-testing resisters. Especially so if cataloging genes becomes a government mandate. So let’s extrapolate this to pharmacogenomics and how PG can help with existential social crises and worryingly perhaps, how we’ll thwart our own best intentions on a population-level.
If we wanted to look into the approximately 11% (~5-15%, SD ~2%) of the population who are estimated to be at high risk for developing abject addiction to opioid medications, and we develop protocols so that they are given alternative therapies and cannot get access to such a class of medications because of their underlying genetic profile, this brings us to a point in civilization’s development that seems almost like a Hippocratic panacea.
To be able to assess who will, and won’t, respond to certain medications, or if they’re responders they may be ‘hyper-responders’ (to detrimental effect), and so to therefore personalize treatment to what their genes suggest sounds philosophically like almost the pinnacle of medicine. Better targeted, personalized precision medicine, fewer adverse events and unwanted side effects. But here’s where ethics and the ‘people’ side of the equation come in.
The public at large may not want to have a smart, ‘profiled’ way of treating them. Imagine if you were one of the high-risk opioid patients—as determined through your genetic testing—and you fell into a class of individuals who could not get treated with an opioid. Assuming we develop similarly effective pain management treatments for this group, it won’t be satisfying enough. They’ve been ‘binned’ or classified in such a way that they can’t get the same treatment as everyone else.
While the alternative treatment offering may objectively be equivalently effective, there is an incredible psychological barrier one finds him or herself in when told that they ‘can’t’ get access to something. Then the ‘something’ becomes the only thing that they want to access. In this example, you may be told you’re at high-risk for addiction, but may have an internal dialog that goes something like, “I want to feel what this person over here feels, I don’t want anyone mandating how I can feel.” The moral and ethical implications of this are huge. Deciding what level of genetic risk of an adverse outcome then denies someone access to a particular medical therapy isn’t as objectively quantifiable as it initially may seem.
There’s no way to subvert the many ways in which we’re human, and how that shapes behavioral economics and our often irrational personal choices, but we also need to be sensitive that we’re involved in shaping policy and treatments for the global patient population. And that population may not be, and likely isn’t, as far along this mental journey of what healthcare ‘should’ look like in the future—and that in itself is a tremendous responsibility that we have to be instructional and compassionate in with regard to responding to a diversity of public opinions on the topic.
A war waged with objective data won’t work in changing the emotional reactions of a large percentage of the people. Instead, it needs to be a dialog with evidence-based recommendations.
Ben Locwin
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA).
We think we’re getting smarter, and we are indeed exposed to more information than ever before in history, but we’re still the same species that we’ve been for dozens-to-hundreds of millennia. This makes us fall prey to the same sorts of logical fallacies and cognitive biases of the human condition that we’ve fallen to many, many times in the past.
Amidst all of the advancements currently ongoing, one of the particular technological and theoretical themes that seems to make a lot of sense to the general public is that of pharmacogenomics.
What is Pharmacogenomics?
Indeed, we can’t delve into the next level of thinking without first defining what it is we intend to dissect: Pharmacogenomics is the research behind how diverse and disparate genomes of individuals respond differentially to drug therapies—pharmacological function and therapeutic response. In other words, which drug treatments work for which individuals’ genetic composition. There is a fertile field on this topic just barely having its surface scratched at the moment. We know, for example, that drugs like naproxen sodium work for some people, and don’t work for others—and/or cause serious side effects. Or that the anxiolytic benzodiazepines have a positive effect in certain populations, but a paradoxical effect in others due putatively to a number of genetic variations in the GABA-A receptor and its subunits.1 This is based on downstream effects from individual genetic differences in ADME for a particular drug (absorption, distribution, metabolism, and excretion). Targeting drugs to certain individuals and/or conditions—what could be better?
While social media has recently begun to drum up similarities between current global politics and, for example, dystopian literature like 1984, there are similar parallels and cautions we can draw now with what’s occurring in the scientific medicine field, and how the public will perceive it. For example, in a relatively near future scenario, if we had the capability to precisely catalog every person’s genetic code on Earth, we could begin to draw correlations between each gene map and their overall susceptibility to certain diseases and disorders, which we know in large part are associated with genes. Of course, as with internet marketing, which at times borders on abusive, past performance may indicate future behavior: Once a certain proportion of the population have had their genetic code stored in a reference library, there may be large-scale rejection of the technology to where genetic privacy becomes the aspired-to status quo. 50 years ago, if you were to tell an audiophile that all of his/her favorite songs could one day be stored virtually on an impossibly small device, they would not have believed you. After all, only a handful of decades ago, single-digit-megabyte storage devices were the size of small rooms. What does society do to return homeostasis to rapidly scaling technological infrastructure? It buys records. On vinyl.
Nobody from our trip-back-in-time meeting would have wanted to keep vinyl records knowing that their future-selves, or progeny, could have access to nearly limitless music taking up what is ostensibly no physical space whatsoever—relatively speaking, absolutely insignificant amounts of spatial volume. But there’s a psychological backlash, related to 20- and 30-year “retro-cycles,” where ‘what’s old is new again.’ World getting too advanced? Return a modicum of control by appreciating the physicality of retro materials. This gives people the seeming ability to ‘slow down’ the pace of advancement in their immediate sphere of influence.
So how does this link to the populations’ connection with, or rejection of, pharmacogenomics? If a certain tipping point of the population has undergone gene testing, there will be tremendously significant social pockets of gene-testing resisters. Especially so if cataloging genes becomes a government mandate. So let’s extrapolate this to pharmacogenomics and how PG can help with existential social crises and worryingly perhaps, how we’ll thwart our own best intentions on a population-level.
If we wanted to look into the approximately 11% (~5-15%, SD ~2%) of the population who are estimated to be at high risk for developing abject addiction to opioid medications, and we develop protocols so that they are given alternative therapies and cannot get access to such a class of medications because of their underlying genetic profile, this brings us to a point in civilization’s development that seems almost like a Hippocratic panacea.
To be able to assess who will, and won’t, respond to certain medications, or if they’re responders they may be ‘hyper-responders’ (to detrimental effect), and so to therefore personalize treatment to what their genes suggest sounds philosophically like almost the pinnacle of medicine. Better targeted, personalized precision medicine, fewer adverse events and unwanted side effects. But here’s where ethics and the ‘people’ side of the equation come in.
The public at large may not want to have a smart, ‘profiled’ way of treating them. Imagine if you were one of the high-risk opioid patients—as determined through your genetic testing—and you fell into a class of individuals who could not get treated with an opioid. Assuming we develop similarly effective pain management treatments for this group, it won’t be satisfying enough. They’ve been ‘binned’ or classified in such a way that they can’t get the same treatment as everyone else.
While the alternative treatment offering may objectively be equivalently effective, there is an incredible psychological barrier one finds him or herself in when told that they ‘can’t’ get access to something. Then the ‘something’ becomes the only thing that they want to access. In this example, you may be told you’re at high-risk for addiction, but may have an internal dialog that goes something like, “I want to feel what this person over here feels, I don’t want anyone mandating how I can feel.” The moral and ethical implications of this are huge. Deciding what level of genetic risk of an adverse outcome then denies someone access to a particular medical therapy isn’t as objectively quantifiable as it initially may seem.
There’s no way to subvert the many ways in which we’re human, and how that shapes behavioral economics and our often irrational personal choices, but we also need to be sensitive that we’re involved in shaping policy and treatments for the global patient population. And that population may not be, and likely isn’t, as far along this mental journey of what healthcare ‘should’ look like in the future—and that in itself is a tremendous responsibility that we have to be instructional and compassionate in with regard to responding to a diversity of public opinions on the topic.
A war waged with objective data won’t work in changing the emotional reactions of a large percentage of the people. Instead, it needs to be a dialog with evidence-based recommendations.
Ben Locwin
Ben Locwin, PhD, MBA, MS writes the Clinically Speaking column for Contract Pharma and is an author of a wide variety of scientific articles for books and magazines, as well as an acclaimed speaker. He is an expert media contact for the American Association of Pharmaceutical Scientists (AAPS) and a committee member for the American Statistical Association (ASA).