《学术英语（医学）》拓展阅读资料：Personalized medicine something old, something new

EDITORIAL Personalized medicine: something old, something new At the level of clinical practice, personalized medicine is in fact nearly as old as recorded history That which has been is that which will be. And In a wonderful manuscript published in 2005 that which has been done is that which will be Sykiotis et al. argue that the pharmacogenetics So there is nothing new under the rinciples underlying our current understandi Ecclesiastes 1: 9 of personalized medicine are in fact traceable to the writings of Hippocrates, the 5th century Qohelet', the author of the biblical book BCE "father of western medicine[2]. Although Ecclesiastes [u], was a kill-joy of the first degree. the authors push the comparison a bit, the article He, or perhaps(though unlikely)she, argued does raise questions about our use of personal hat basically all human activity was futile and ized medicine as the phrase to capture what Fintan r steele repetitive, that 'progress was an apparition, and happening in our time Broad Institute of MIT all that mattered was what came after the wel- Hippocrates worked with the philosophical Harvard, 7 Cambridge Center come embrace of death. Hardly the first person and scientific language of his time, provided by Cambridge, MA 02142, USA that comes to mind for a quote in an editorial the pre-Socratic philosopher Empedocles Tel.+16173243872 on personalized medicine. define sickness as dyscrasia, or an imbalance of STeele@broad. mit. edu Yet there is something about Qohelet's obser- the four humors. The goal of the physician ation that we should take to heart before we to restore the patient to eucrasia or good bal- trumpet the matins of a new medical revolution. ance(i. e, wellness)by addressing the cause of In fact, when we step back from the attendant the disease as revealed by the phenotype hype, it becomes clear that at least part of what Let me offer a theoretical case study. Pythagoras is commonly called personalized medicine' comes to Hippocrates' clinic complaining of sad- is fundamentally nothing new?. Rather, what ness and low energy, his usual excitement about seems to me to be the primary 'newness of per- his mathematical pursuits overcome by a terrible sonalized medicine resides in the new language depression. Hippocrates determines, both from that is emerging. This new language attempts to Pythagoras self description and by visual inspec- ve us the ability to speak more authoritatively tion of the patient's presenting phenotype, that bout the phenotype of disease based on our Pythagoras is suffering from an overabundance growing knowledge of biology. Furthermore, of black bile, or melancholia. The this new language is very much in its infancy, doled out is precise to Pythagoras, including and the phrases and words that we manufacture changing his dietary habits, a temporary spate to mean one thing today will inevitably change of abstinence, and a harsh purging of his bow as the language is eventually codified by clini- els. Following treatment, Pythagoras is better, cal practice. But at the level of clinical practice, though whether that is due to the efficacy of the personalized medicine is in fact nearly as old as treatment or his relief that it is over is unclear. recorded history What has happened? From one perspective, the right treatment was given to the right pater That which has been is that which at the right time. Again, the notion of right'is will be" within the context of the knowledge of the time Personalized medicine-in the sense of the right (the humors), but the treatment was certainly treatment for the right patient at the right time- personalized and even effective has been practiced for millennia. One has to take The four humors as the basis of medical pra the term right in this context with a grain of salt. tice continued to reign for two millennia, an However, within the limitations of the knowledge bit beyond. It grew increasingly ember- uture certa appeared right to both physician and patient. bodily fuid became fair game for testing in ways medicine fsg 102217/17410541.6.1.102009 Future medicine ltd Personalized Medicine (2009)6(1), 1-5 ssN1741-0541

10.2217/17410541.6.1.1 © 2009 Future Medicine Ltd Personalized Medicine (2009) 6(1), 1–5 ISSN 1741-0541 1 Editorial “At the level of clinical practice, personalized medicine is in fact nearly as old as recorded history.” Fintan R Steele Broad Institute of MIT & Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA Tel.: +1 617 324 3872 fsteele@broad.mit.edu Personalized medicine: something old, something new “That which has been is that which will be. And that which has been done is that which will be done. So there is nothing new under the sun.” – Ecclesiastes 1:9 ‘Qohelet’, the author of the biblical book Ecclesiastes [1], was a kill-joy of the first degree. He, or perhaps (though unlikely) she, argued that basically all human activity was futile and repetitive, that ‘progress’ was an apparition, and all that mattered was what came after the wel￾come embrace of death. Hardly the first person that comes to mind for a quote in an editorial on personalized medicine. Yet there is something about Qohelet’s obser￾vation that we should take to heart before we trumpet the matins of a new medical revolution. In fact, when we step back from the attendant hype, it becomes clear that at least part of what is commonly called ‘personalized medicine’ is fundamentally ‘nothing new’. Rather, what seems to me to be the primary ‘newness’ of per￾sonalized medicine resides in the new language that is emerging. This new language attempts to give us the ability to speak more authoritatively about the phenotype of disease based on our growing knowledge of biology. Furthermore, this new language is very much in its infancy, and the phrases and words that we manufacture to mean one thing today will inevitably change as the language is eventually codified by clini￾cal practice. But at the level of clinical practice, personalized medicine is in fact nearly as old as recorded history. “That which has been is that which will be” Personalized medicine – in the sense of the ‘right treatment for the right patient at the right time’ – has been practiced for millennia. One has to take the term ‘right’ in this context with a grain of salt. However, within the limitations of the knowledge and language of the time, the therapy certainly appeared right to both physician and patient. In a wonderful manuscript published in 2005, Sykiotis et al. argue that the pharmacogenetics principles underlying our current understanding of personalized medicine are in fact traceable to the writings of Hippocrates, the 5th century BCE ‘father of western medicine’ [2]. Although the authors push the comparison a bit, the article does raise questions about our use of personal￾ized medicine as the phrase to capture what is happening in our time. Hippocrates worked with the philosophical and scientific language of his time, provided by the pre-Socratic philosopher Empedocles, to define sickness as dyscrasia, or an imbalance of the four humors. The goal of the physician was to restore the patient to ‘eucrasia’ or good bal￾ance (i.e., wellness) by addressing the cause of the disease as revealed by the phenotype. Let me offer a theoretical case study. Pythagoras comes to Hippocrates’ clinic complaining of sad￾ness and low energy, his usual excitement about his mathematical pursuits overcome by a terrible depression. Hippocrates determines, both from Pythagoras’ self description and by visual inspec￾tion of the patient’s presenting phenotype, that Pythagoras is suffering from an overabundance of black bile, or melancholia. The treatment doled out is precise to Pythagoras, including changing his dietary habits, a temporary spate of abstinence, and a harsh purging of his bow￾els. Following treatment, Pythagoras is better, though whether that is due to the efficacy of the treatment or his relief that it is over is unclear. What has happened? From one perspective, the right treatment was given to the right patient at the right time. Again, the notion of ‘right’ is within the context of the knowledge of the time (the humors), but the treatment was certainly personalized and even effective. The four humors as the basis of medical prac￾tice continued to reign for two millennia, and even a bit beyond. It grew increasingly embel￾lished with other phenotypic markers – every bodily fluid became fair game for testing in ways

EDITORIAL Steele that are best left undescribed here -and newer he carefully guarded (4l, opened up an entire world therapeutic interventions were employed to of external life, much of it living in frightening restore balance with mixed results(e. g, the over- and a bit disgusting proximity to the human eager blood-letting of George Washington may body. Suddenly there was external life everywhere have led to his untimely demise [31). Although beyond the naked eye's ability to take it in. And humors-based medicine as a way of phenotyp- some of it directly relevant to disease states, espe- ing individual patients was acknowledged to be cially certain types of bacteria. Subsequently, a incomplete, there was simply no other organiz- new language of phenotype fooded the medical ing principle at hand, apart from a resurgence of literature, at least for infectious diseases and other metaphysics-based beliefs and practices diseases that affected the human cells or tissues that could now be seen under the microscope Making the old new again: expanding "clinical knowledge may have been changing the language of phenotype Interestingly, some of those very metaphysical but clinical practice- in its most basic practices were the seed bed for the beginning incarnation of treating the right patient at the of the end of the humors as the medical para right time in the right way-was not digm. Parcelsus, nee Phillip von Hohenheim, grew up in Einsiedeln(near Zurich) in the Despite these amazing breakthroughs, the late 15th century CE and followed his father notion that the individual patient presenting in becoming a physician [101]. His particular in the clinic had an individual phenotype from familiarity with miners, the ores they mined, which to make a diagnosis and prescribe a treat- and the unique sicknesses caused by the com- ment did not change Clinical knowledge may ing together of the two led him to question the have been changing, but clinical practice -in its reigning medical beliefs of his time, and his most basic incarnation of treating the right pater deep training in alchemy, at the time a highly at the right time in the right way-was not mystical enterprise, was steered by his observa- There are many other historical breakthroughs, tions away from its spiritual underpinnings to to be sure: my goal is not to write yet another his- a more rational foundation tory of medicine, but to help understand just how Paracelsus pronounced, much to the chagrin different-or not-things are today of the keepers of established medical wisdom, that human disease could be traced to the inter- The 21st century: evolution action of the individual with his/her individual versus revolution environment, and that chemical imbalance lay at In July 2000, announcing the relative comple the root. He also believed that chemicals given tion of the Human Genome Project, US President in a proper dose could most effectively treat William Clinton stated: With this profound new this imbalance, earning him the title of ' father knowledge, humankind is on the verge of gaining of toxicology, and ushering a new language of immense new power to heal. Genome science will chemistry into medical practice. The notion that have a real impact on all of our lives-and even external forces were as critical as internal ones more. on the lives of our children it will revolu in determining disease seems obvious to us, but ionize the diagnosis, prevention, and treatment was revolutionary at the time. Indeed, this is of most, if not all, human disease"s he explo- perhaps the first example of the ongoing debate about nature versus nurture, though it would sion in the past few years of genome-wide associ- not have been cast in such terms. Paracelsus also ation studies finding genetic linkages to a host of broke open the possibility that the phenotype human affictions seems to bear the President's of disease was far more complex than could be superlatives out. Yet what is really happening? accounted for by the humors, even in their most I believe that the new language of genomics, as nuanced understanding applied to medicine, is less a revolution than an But what were those external forces if not meta- evolution: the ability to more precisely describ physical? A bit more than a century later, a poten- phenotypes has allowed us to change the specif- tial answer came from the Netherlands by way of a ics, but not the fundamental practice of medicine hobby. Antoine van Leeuwenhoek, a haberdasher Thanks to our increased knowledge of genetic and chamberlain of the sheriffs of Dellf, decided and genomic vari i u seroma 00 Ce to over he could improve on the 3x magnifying glasses diagnosis of "blood dis sed by textile merchants to closely examine their 38 leukemia and 51 lymphoma subtypes(and stock in trade. His lens-crafting techniques, which more to come)in 2008 [6]. If you are suffering Personalized Medicine(2009)6(1) future science group

2 Personalized Medicine (2009) 6(1) future science group Editorial Steele that are best left undescribed here – and newer therapeutic interventions were employed to restore balance with mixed results (e.g., the over￾eager blood-letting of George Washington may have led to his untimely demise [3]). Although humors-based medicine as a way of phenotyp￾ing individual patients was acknowledged to be incomplete, there was simply no other organiz￾ing principle at hand, apart from a resurgence of metaphysics-based beliefs and practices. Making the old new again: expanding the language of phenotype Interestingly, some of those very metaphysical practices were the seed bed for the beginning of the end of the humors as the medical para￾digm. Parcelsus, nee Phillip von Hohenheim, grew up in Einsiedeln (near Zurich) in the late 15th century CE and followed his father in becoming a physician [101]. His particular familiarity with miners, the ores they mined, and the unique sicknesses caused by the com￾ing together of the two led him to question the reigning medical beliefs of his time, and his deep training in alchemy, at the time a highly mystical enterprise, was steered by his observa￾tions away from its spiritual underpinnings to a more rational foundation. Paracelsus pronounced, much to the chagrin of the keepers of established medical wisdom, that human disease could be traced to the inter￾action of the individual with his/her individual environment, and that chemical imbalance lay at the root. He also believed that chemicals given in a proper dose could most effectively treat this imbalance, earning him the title of ‘father of toxicology’, and ushering a new language of chemistry into medical practice. The notion that external forces were as critical as internal ones in determining disease seems obvious to us, but was revolutionary at the time. Indeed, this is perhaps the first example of the ongoing debate about nature versus nurture, though it would not have been cast in such terms. Paracelsus also broke open the possibility that the phenotype of disease was far more complex than could be accounted for by the humors, even in their most nuanced understanding. But what were those external forces if not meta￾physical? A bit more than a century later, a poten￾tial answer came from the Netherlands by way of a hobby. Antoine van Leeuwenhoek, a haberdasher and chamberlain of the sheriffs of Dellf, decided he could improve on the 3× magnifying glasses used by textile merchants to closely examine their stock in trade. His lens-crafting techniques, which he carefully guarded [4], opened up an entire world of external life, much of it living in frightening and a bit disgusting proximity to the human body. Suddenly there was external life everywhere beyond the naked eye’s ability to take it in. And some of it directly relevant to disease states, espe￾cially certain types of bacteria. Subsequently, a new language of phenotype flooded the medical literature, at least for infectious diseases and other diseases that affected the human cells or tissues that could now be seen under the microscope. “Clinical knowledge may have been changing, but clinical practice – in its most basic incarnation of treating the right patient at the right time in the right way – was not.” Despite these amazing breakthroughs, the notion that the individual patient presenting in the clinic had an individual phenotype from which to make a diagnosis and prescribe a treat￾ment did not change. Clinical knowledge may have been changing, but clinical practice – in its most basic incarnation of treating the right patient at the right time in the right way – was not. There are many other historical breakthroughs, to be sure: my goal is not to write yet another his￾tory of medicine, but to help understand just how different – or not – things are today. The 21st century: evolution versus revolution In July 2000, announcing the relative comple￾tion of the Human Genome Project, US President William Clinton stated: “With this profound new knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on all of our lives — and even more, on the lives of our children. It will revolu￾tionize the diagnosis, prevention, and treatment of most, if not all, human disease” [5]. Revolutionary stuff, indeed. And the explo￾sion in the past few years of genome-wide associ￾ation studies finding genetic linkages to a host of human afflictions seems to bear the President’s superlatives out. Yet what is really happening? I believe that the new language of genomics, as applied to medicine, is less a revolution than an evolution: the ability to more precisely describe phenotypes has allowed us to change the specif￾ics, but not the fundamental practice of medicine. Thanks to our increased knowledge of genetic and genomic variation, we have gone from a diagnosis of ‘blood disease’ in 1900 CE to over 38 leukemia and 51 lymphoma subtypes (and more to come) in 2008 [6]. If you are suffering

personalized medicine: something old, something new EDITORIA from chronic myelogenous leukemia as a result of and a lot of genome-wide association studies. As the rare Philadelphia chromosome translocation, heady as that information is, it is a long way from we have a drug that addresses that phenotype, at being completely or even adequately descriptive least temporarily. If your form of breast cancer is for diagnostic, much less therapeutic purposes overexpressing a specific gene, we have a drug that One need look no farther than the uproar that may work better for you than for others without followed the founding of genomic information that genetic variation. And so forth. However, companies such as Navigenics and 23andMe for most of the diseases for which we are gaining although questions were loudly raised about insight, we are still struggling with therapeutic privacy and ownership of genomic information, options. But there is real hope, buried within the the real question is whether this information in confusing new genomics-based language emerg- its current woefully incomplete form is worth ing from the lab bench into the clinic, that we anything from a medical perspective. I suspect ay find more effective new treatments. This not, or at best its worth is minimal and is largely evolutionary change, perhaps a period of punc- misunderstood by patients and their doctors tuated equilibrium, is still in line with all that 17-9]. Perhaps most telling is the blind faith of has gone before some customers of these companies, who have, essence, replaced rational knowledge with an odd The ability to more precisely describe kind of genetic determinism metaphysics, mir- phenotypes has allowed us to change the roring the surge of spiritual and mystical prac specifics, but not the fundamental practice tices that arose in response to the incompleteness of the humors paradigm By no means am I trying to belittle the progress"We particularly need to be cautious about made. Like the early rise of toxicology and drug what our current state of genomic knowledge treatments in the 15th and 16th centuries, and tells us-and does not tell us-about human he ability to see beyond the limitations of the disease and its treatment human eye in the 17th, the toolbox of medicine btedly be changed Incorporation of new findings into regula in the 21st as well, thanks to our ability to ever medical practice requires that the language of the more precisely define phenotype with genomic omics be translated into clinically relevant and tools and insights. Personalized medicine, which meaningful terms, and be tied to some actionable has been around a long time, will be ever more outcome. Driven to date by molecular biologists exquisitely personalized based on better phe-( for the most part), there remains a significant gap notype definitions, though perhaps not as fast between genomic knowledge and clinical prac- as suggested in the President's words or by the tice. At its heart is the silence that meets the most various groups that have formed to promote this common question from practicing physicians newold field. I believe that the primary chal- what difference does this make in how I trear lenges we face are threefold, in decreasing order patient X? There are a few examples of answers urgenc for some diseases, but that fundamental medical Sorting out meaningful phenotypes from question is still unanswered in the vast major- ity of cases. This must be acknowledged, even as many academic centers are racing to focus on Incorporation of this knowledge and language the translational research needed to drive bench into medical ractice findings to the bedside, making genomic knowl Incorporation of this refined diagnostic ability edge relevant to practicing physicians and their into healthcare and regulatory systems built patients. And by relevant, I mean that it has to be around older medical paradigms more than a statement of molecular phenotyp in other words, it has to be accompanied with ar Previous(r)evolutions went through similar option for addressing the problem. steps,and there is no reason to believe the current One particularly interesting potential effect of one is any different. his new knowledge in driving clinical practice We particularly need to be cautious about what may be the shift of focus away from traditional our current state of genomic knowledge edical divisions based on organs and organ and does not tell us -about human pathology towards a more mechanistic disease and its treatment. Much of our current description based on cellular pathways [Iol edge is based largely on a few complete genomes is not too far a stretch to think about doctors www.futuremedicine.c

future science group www.futuremedicine.com 3 Personalized medicine: something old, something new Editorial from chronic myelogenous leukemia as a result of the rare Philadelphia chromosome translocation, we have a drug that addresses that phenotype, at least temporarily. If your form of breast cancer is overexpressing a specific gene, we have a drug that may work better for you than for others without that genetic variation. And so forth. However, for most of the diseases for which we are gaining insight, we are still struggling with therapeutic options. But there is real hope, buried within the confusing new genomics-based language emerg￾ing from the lab bench into the clinic, that we may find more effective new treatments. This evolutionary change, perhaps a period of punc￾tuated equilibrium, is still in line with all that has gone before. “The ability to more precisely describe phenotypes has allowed us to change the specifics, but not the fundamental practice of medicine.” By no means am I trying to belittle the progress made. Like the early rise of toxicology and drug treatments in the 15th and 16th centuries, and the ability to see beyond the limitations of the human eye in the 17th, the toolbox of medicine will undoubtedly be changed in profound ways in the 21st as well, thanks to our ability to ever more precisely define phenotype with genomic tools and insights. Personalized medicine, which has been around a long time, will be ever more exquisitely personalized based on better phe￾notype definitions, though perhaps not as fast as suggested in the President’s words or by the various groups that have formed to promote this ‘new’ old field. I believe that the primary chal￾lenges we face are threefold, in decreasing order of urgency: n Sorting out meaningful phenotypes from irrelevant ones; n Incorporation of this knowledge and language into medical practice itself; n Incorporation of this refined diagnostic ability into healthcare and regulatory systems built around older medical paradigms. Previous (r)evolutions went through similar steps, and there is no reason to believe the current one is any different. We particularly need to be cautious about what our current state of genomic knowledge tells us – and does not tell us – about human disease and its treatment. Much of our current knowl￾edge is based largely on a few complete genomes and a lot of genome-wide association studies. As heady as that information is, it is a long way from being completely or even adequately descriptive for diagnostic, much less therapeutic purposes. One need look no farther than the uproar that followed the founding of genomic information companies such as Navigenics and 23andMe: although questions were loudly raised about privacy and ownership of genomic information, the real question is whether this information in its current woefully incomplete form is worth anything from a medical perspective. I suspect not, or at best its worth is minimal and is largely misunderstood by patients and their doctors [7–9]. Perhaps most telling is the blind faith of some customers of these companies, who have, in essence, replaced rational knowledge with an odd kind of genetic determinism metaphysics, mir￾roring the surge of spiritual and mystical prac￾tices that arose in response to the incompleteness of the humors paradigm. “We particularly need to be cautious about what our current state of genomic knowledge tells us – and does not tell us – about human disease and its treatment.” Incorporation of new findings into regular medical practice requires that the language of the omics be translated into clinically relevant and meaningful terms, and be tied to some actionable outcome. Driven to date by molecular biologists (for the most part), there remains a significant gap between genomic knowledge and clinical prac￾tice. At its heart is the silence that meets the most common question from practicing physicians: what difference does this make in how I treat patient X? There are a few examples of answers for some diseases, but that fundamental medical question is still unanswered in the vast major￾ity of cases. This must be acknowledged, even as many academic centers are racing to focus on the translational research needed to drive bench findings to the bedside, making genomic knowl￾edge relevant to practicing physicians and their patients. And by relevant, I mean that it has to be more than a statement of molecular phenotype; in other words, it has to be accompanied with an option for addressing the problem. One particularly interesting potential effect of this new knowledge in driving clinical practice may be the shift of focus away from traditional medical divisions based on organs and organ pathology towards a more mechanistic disease description based on cellular pathways [10]. It is not too far a stretch to think about doctors

EDITORIAL Steele who specialize in, say the TGF-B pathway-asso- hand". Using the term personalized medicine ciated diseases rather than the organs or systems to cover the potential flowing from the post- affected. But such a shift will require a more genomic research world appeals to the gut and complete catalogue of the meaningful molecular the ear, but ultimately misleads. And I suspec phenotypes and their effects than we currently that physicians from Hippocrates to your cur- of medical practice; just the means by which that have not practiced personalized medicine. ave And it won't change the fundamenta rent gP would be appalled to learn that they goal is reached. 4. Finally, plenty of ink has been spilled about the"We have to acknowledge that personalized eful inadequacy of our current healthcare and medicine as a clinical approach is indeed regulatory systems to deal with the new infor nothing new under the sun nation Howing from postgenomic laboratories, and a lot of hand-wringing happens at a growing Yet it is hard to construct some other number of annual personalized medicine meet- terminology that works. Molecular medi- gs about how the current system may slow or cine or genomic medicine are perhaps more even prevent the advent of the new personalized accurate to the real novelty of what is hap medicine. There are undoubtedly some tough pening, but may not be as attention grabbing transitions ahead, but until the new language of Individualized medicine suggests more varia- phenotype is more complete, codified in mean- tion in the human species than evolution would gful ways and incorporated more integrally into actually allow. Thus, I suspect we are stuck, regular medical practice, substantial changes in at least for now, with the term personalized the regulatory or healthcare structures may prove medicine. But at least let us agree that we have ineffective at best and counterproductive at worst: to be clear about the meaning it carries: an is very hard to prepare a new system to handle a evolutionary growth in our medical lexicon of surge of new data that are not yet well-understood disease phenotype and treatment. And we have and a language that has not settled into a com- to acknowledge that personalized medicine as a Before we demand that the em clinical appr ng new unde accommodate us. we need to be sure we know the sun what it is we are asking the system to take on in as concrete a way as possible. Conclusion 'Personalized med as a term is attention So what 's new? grabbing, but may be incorrect. As long as it Despite the curmudgeonly admonitions of refers specifically to our increased molecular Qohelet, there is indeed something new under knowledge of human biology and its application the sun in medicine. But it is not personalized to diagnostics and therapeutics, it is acceptable, medicine per se. Rather, it is our ongoing eking if incomplete. If it is used to denote a change in out through the finer lenses of new postgenomic the fundamental practice of medicine, it is a poor technologies the molecular phenotypes that choice of words. contribute to or even directly cause a range of human diseases. It is exciting stuff, both intel- lectually and in its potential for better medical Financial competing interests disclosure are. However, the food of new data we have The author has no relevant affiliations or fnancial oduced in such a short time is really only a involvement with any organization or entity with afnan trickle compared to what we have yet to gener- cial interest in or fnancial conflict with the subject matter ate before we can speak about a revolution of or materials discussed in the manuscript. This includes medicine with any kind of authority beyond employment, consultancies, honoraria, stock ownership or ng genomic tea leaves options, expert testimony, grants or patents received or Lewis Thomas is credited with saying that pending, or royalties. the great thing about human language is that No writing assistance was utilized in the Production of it prevents us from sticking to the matter at this manuscript Personali dicine(2009)6(1) future science group

4 Personalized Medicine (2009) 6(1) future science group Editorial Steele who specialize in, say the TGF-β pathway-asso￾ciated diseases rather than the organs or systems affected. But such a shift will require a more complete catalogue of the meaningful molecular phenotypes and their effects than we currently have. And it won’t change the fundamental goal of medical practice; just the means by which that goal is reached. Finally, plenty of ink has been spilled about the woeful inadequacy of our current healthcare and regulatory systems to deal with the new infor￾mation flowing from postgenomic laboratories, and a lot of hand-wringing happens at a growing number of annual personalized medicine meet￾ings about how the current system may slow or even prevent the advent of the new personalized medicine. There are undoubtedly some tough transitions ahead, but until the new language of phenotype is more complete, codified in mean￾ingful ways and incorporated more integrally into regular medical practice, substantial changes in the regulatory or healthcare structures may prove ineffective at best and counterproductive at worst: it is very hard to prepare a new system to handle a surge of new data that are not yet well-understood and a language that has not settled into a com￾mon tongue. Before we demand that the system accommodate us, we need to be sure we know what it is we are asking the system to take on in as concrete a way as possible. So what’s new? Despite the curmudgeonly admonitions of Qohelet, there is indeed something new under the sun in medicine. But it is not personalized medicine per se. Rather, it is our ongoing eking out through the finer lenses of new postgenomic technologies the molecular phenotypes that contribute to or even directly cause a range of human diseases. It is exciting stuff, both intel￾lectually and in its potential for better medical care. However, the flood of new data we have produced in such a short time is really only a trickle compared to what we have yet to gener￾ate before we can speak about a revolution of medicine with any kind of authority beyond reading genomic tea leaves. Lewis Thomas is credited with saying that “the great thing about human language is that it prevents us from sticking to the matter at hand”. Using the term personalized medicine to cover the potential flowing from the post￾genomic research world appeals to the gut and the ear, but ultimately misleads. And I suspect that physicians from Hippocrates to your cur￾rent GP would be appalled to learn that they have not practiced personalized medicine. “We have to acknowledge that personalized medicine as a clinical approach is indeed nothing new under the sun.” Yet it is hard to construct some other terminology that works. ‘Molecular medi￾cine’ or ‘genomic medicine’ are perhaps more accurate to the real novelty of what is hap￾pening, but may not be as attention grabbing. ‘Individualized medicine’ suggests more varia￾tion in the human species than evolution would actually allow. Thus, I suspect we are stuck, at least for now, with the term personalized medicine. But at least let us agree that we have to be clear about the meaning it carries: an evolutionary growth in our medical lexicon of disease phenotype and treatment. And we have to acknowledge that personalized medicine as a clinical approach is indeed ‘nothing new under the sun’. Conclusion ‘Personalized medicine’ as a term is attention grabbing, but may be incorrect. As long as it refers specifically to our increased molecular knowledge of human biology and its application to diagnostics and therapeutics, it is acceptable, if incomplete. If it is used to denote a change in the fundamental practice of medicine, it is a poor choice of words. Financial & competing interests disclosure The author has no relevant affiliations or financial involvement with any organization or entity with a finan￾cial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript

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