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 group2 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