Gallantly fighting windmills? Complexity of a 21st century challenge

Abstract

Aptly titled, The Alzheimer Conundrum presents an intriguing picture of the state of Alzheimer's research and its abundant uncertainties. Through a series of interviews, observations, and informal conversations, medical anthropologist, Margaret Lock traverses the worlds of the laboratory, clinic, and lay public to produce a timely and insightful examination of the research effort aimed at one of the greatest challenges of the 21st century. But even this characterisation presents a conundrum, as Lock asserts that the entanglement of Alzheimer's disease and ageing has not been adequately addressed and questions whether disentanglement is even possible. Her message is partly that although the existence of an underlying neuropathological change is not in dispute, little can be said with certainty about what this finding means or what we should do about it.Lock poses the question of “what is normal?”, effectively setting the stage for a host of epistemological challenges. With the eye of a social scientist, Lock prompts us to consider how unrecognised assumptions about what is normal, both statistically derived and intuitive, impair the ability to devise an accurate starting point. Moreover, she takes on some of the dominant views in the research community. In a book that might easily have been called, The Amyloid Conundrum, Lock unveils the complex world of the amyloid hypothesis, possibly the biggest theoretical driver in Alzheimer research. This hypothesis posits that the presence of amyloid plaques inevitably found in patients with Alzheimer's disease plays a causal part in disease onset and progression, and that finding a mechanism that reduces or prevents amyloid burden would essentially amount to cure. Lock points out that trials targeting amyloid consistently show little or no effect, with no compelling evidence that this pathway is curative. Consequently, for Lock and others the persistence of this model as the dominant one is puzzling.Lock's inquiry into the “constructivist” nature of Alzheimer's disease is intriguing, referencing the various configurations of diagnostic criteria and varied application of the same criteria. Neither does she shy away from the politics of disease research. The subtitle, “The amyloid mafia and the prevailing paradigm of alzheimer disease” is telling; a hypothesis that presents pharmaceutical targets and is supported by powerful technologies (eg, Carbon-11-labelled Pittsburgh compound B [11C-PiB]/PET) and has garnered huge investments is surely difficult to displace, even if signs of success remain elusive. Lock ultimately succeeds in placing even this scenario in its broader social context nudging us to confront the convergence of scientific and political worlds.Lock has taken on an ambitious project. Key to this achievement is Lock's skill in integrating the voices of participants in the Alzheimer research enterprise, perhaps most notably when she allows the contrasting voices of researchers to paint a picture of an uncertain scientific community. Not surprisingly, her portrayal and presentation of patient voices comes across as an essential element of the research effort, poignantly situated in its combined scientific and social context. Her treatment of the long anticipated research trial with families with dominantly inherited Alzheimer's disease in Colombia in the chapter on Alzheimer genes is balanced and reflective, directly confronting the issue of possible benefits, against the realities of undertaking such a trial in the absence of sufficient health-care infrastructure. Her general exploration of embodied risk is an important contribution to the discourse on Alzheimer's research in view of the increasing attention to prevention.Such an ambitious project is bound to leave some areas less well attended. More could have been said about the role of differential diagnosis and the merits of other research strategies, such as tau and inflammation. To write such a book as this one is a daunting organisational undertaking. In attempting to address such topics as pre-clinical Alzheimer's disease, the amyloid hypothesis, Alzheimer genetics, and genome-wide association studies in separate chapters, it quickly becomes apparent that these topics are inseparable. The story of Alzheimer's research is not linear and Lock notes this fact in a robustly triangulated and non-linear look at its constitutive social and scientific worlds.The breadth and depth of research that has gone into this work is remarkable. This book needed to be written. Eagerness for a cure is not cause to abandon discernment. Yet, for all the uncertainty and multiplicity of causal suspects, The Alzheimer Conundrum is not a whodunit. In fact, this book left me thinking that we may not even be sure what the “it” is. Aptly titled, The Alzheimer Conundrum presents an intriguing picture of the state of Alzheimer's research and its abundant uncertainties. Through a series of interviews, observations, and informal conversations, medical anthropologist, Margaret Lock traverses the worlds of the laboratory, clinic, and lay public to produce a timely and insightful examination of the research effort aimed at one of the greatest challenges of the 21st century. But even this characterisation presents a conundrum, as Lock asserts that the entanglement of Alzheimer's disease and ageing has not been adequately addressed and questions whether disentanglement is even possible. Her message is partly that although the existence of an underlying neuropathological change is not in dispute, little can be said with certainty about what this finding means or what we should do about it. Lock poses the question of “what is normal?”, effectively setting the stage for a host of epistemological challenges. With the eye of a social scientist, Lock prompts us to consider how unrecognised assumptions about what is normal, both statistically derived and intuitive, impair the ability to devise an accurate starting point. Moreover, she takes on some of the dominant views in the research community. In a book that might easily have been called, The Amyloid Conundrum, Lock unveils the complex world of the amyloid hypothesis, possibly the biggest theoretical driver in Alzheimer research. This hypothesis posits that the presence of amyloid plaques inevitably found in patients with Alzheimer's disease plays a causal part in disease onset and progression, and that finding a mechanism that reduces or prevents amyloid burden would essentially amount to cure. Lock points out that trials targeting amyloid consistently show little or no effect, with no compelling evidence that this pathway is curative. Consequently, for Lock and others the persistence of this model as the dominant one is puzzling. Lock's inquiry into the “constructivist” nature of Alzheimer's disease is intriguing, referencing the various configurations of diagnostic criteria and varied application of the same criteria. Neither does she shy away from the politics of disease research. The subtitle, “The amyloid mafia and the prevailing paradigm of alzheimer disease” is telling; a hypothesis that presents pharmaceutical targets and is supported by powerful technologies (eg, Carbon-11-labelled Pittsburgh compound B [11C-PiB]/PET) and has garnered huge investments is surely difficult to displace, even if signs of success remain elusive. Lock ultimately succeeds in placing even this scenario in its broader social context nudging us to confront the convergence of scientific and political worlds. Lock has taken on an ambitious project. Key to this achievement is Lock's skill in integrating the voices of participants in the Alzheimer research enterprise, perhaps most notably when she allows the contrasting voices of researchers to paint a picture of an uncertain scientific community. Not surprisingly, her portrayal and presentation of patient voices comes across as an essential element of the research effort, poignantly situated in its combined scientific and social context. Her treatment of the long anticipated research trial with families with dominantly inherited Alzheimer's disease in Colombia in the chapter on Alzheimer genes is balanced and reflective, directly confronting the issue of possible benefits, against the realities of undertaking such a trial in the absence of sufficient health-care infrastructure. Her general exploration of embodied risk is an important contribution to the discourse on Alzheimer's research in view of the increasing attention to prevention. Such an ambitious project is bound to leave some areas less well attended. More could have been said about the role of differential diagnosis and the merits of other research strategies, such as tau and inflammation. To write such a book as this one is a daunting organisational undertaking. In attempting to address such topics as pre-clinical Alzheimer's disease, the amyloid hypothesis, Alzheimer genetics, and genome-wide association studies in separate chapters, it quickly becomes apparent that these topics are inseparable. The story of Alzheimer's research is not linear and Lock notes this fact in a robustly triangulated and non-linear look at its constitutive social and scientific worlds. The breadth and depth of research that has gone into this work is remarkable. This book needed to be written. Eagerness for a cure is not cause to abandon discernment. Yet, for all the uncertainty and multiplicity of causal suspects, The Alzheimer Conundrum is not a whodunit. In fact, this book left me thinking that we may not even be sure what the “it” is.