This paper explores the nature of food and plants and their meanings in a British Bengali urban context. It focuses on the nature of plants and food in terms of their role in home making, transnational connections, generational change and concepts of health.An ethnographic approach to the research was taken, specific methods included participant observation, focus group discussions and semi-structured interviews. Thirty women of Bengali origin were mostly composed of “mother” and “daughter” pairs. The mothers were over 45 years old and had migrated from Bangladesh as adults and their grown-up daughters grew up in the UK.Food and plants play an important role in the construction of home “here” (London) while continuing to connect people to home “there” (Sylhet). This role, however, changes and is re-defined across generations. Looking at perceptions of “healthy” and “unhealthy” food, particularly in the context of Bengali food, multiple views of what constitutes “healthy” food exist. However, there appeared to be little two-way dialogue about this concept between the research participants and health professionals. This seems to be based on “cultural” and power differences that need to be addressed for a meaningful dialogue to occur.In summary, this paper argues that while food is critical to the familial spaces of home , it is defined by a complex interplay of actors and wider meanings as illustrated by concepts of health and what constitutes Bengali food. Therefore, we call for greater dialogue between health professionals and those they interact with, to allow for an enhanced appreciation of the dynamic nature of food and plants and the diverse perceptions of the role that they play in promoting health. The issues raised by her story are key themes explored in this paper. Lili’s relationship with the garden and food illustrate how the mediums of plants and foods are important to the home and home-making, as well as serving to create linkages with family and communities both locally and transnationally.The account below is a brief overview of the first author’s encounter with LiliI first met Lili in East London tending to vegetables on her allotment plot. Surprised by my ability to communicate with her in Bangla and my interest in her gardening, she was eager to show me what she was growing and share the fruits  of her labour. Lili soon invited me to her home where I spent several enjoyable afternoons being fed rice and curry and chatting to her two daughters. Lili’s daughters do not share their mother’s same interest in gardening. They do enjoy her food though; the oldest daughter, now married and moved out of home, says her cooking is different to her mum’s “a bit of everything really, a variety of Bengali….English and other dishes…today I’ve brought over some jolof rice (a West African rice dish) and Moroccan eggs I cooked”. Lili tells me that the food she cooks with her home-grown vegetables is good for me as the vegetables are “fresh” and “full of vitamins”. Many of the seeds for the vegetables she grows are sent from Bangladesh. Relatives also send her snacks and shutki (dried fish) when possible. Although she has only visited Bangladesh twice since moving to the UK in the 1980s, Lili maintains contact with her family through telephone calls and the exchange of gifts. Though London is now her “home” and the place she raised her four children, the continued presence of her “home” in Bangladesh is evident not least through her food and plants.desh  play a crucial role both in home-making in the UK for two generations of British Bengalib women and their role in maintaining on-going links with “home” in Bangladesh . The paper subsequently examines how and why diets change over time and post-migration to the UK, specifically focusing on the changing nature of diets due to the impact of health messages and perceptions of what constitutes “healthy food”. The paper then examines perceptions of food, particularly “Bengali” food, in terms of health. While the findings illustrate consistencies between the research participants’ and professional views of “healthy” food, they also highlight a power imbalance between research participants and community workers/health professionals and the labelling of “Bengali” food as “unhealthy”. We therefore suggest a need for greater two-way dialogue, with multiple understandings of food and health being appreciated, understood and expressed. Finally, the paper explores lay perceptions of health among British Bengali participants before drawing conclusions. As an introduction, we first highlight background literature and an overview of the methodology used.Drawing on ethnographic, qualitative research this paper explores how plants and food from lascars (sailors) and therefore travelling to and occasionally settling in the UK [The flow of people from largely rural Sylhet, North-eastern Bangladesh, to urban Britain is connected to the expansion of the British Raj and trade; it was maintained through a process of “chain migration”. Travel between Sylhet and the UK can be traced to the 19th century, with many Sylhetis working as n the UK ,3. Throun the UK , the 198n the UK ,6. Less n the UK . AccordiSocial and ethnographic research provides important insights into the Bengali community regarding identity ,10,11 anc. However, we did find over the course of the research that women were primarily responsible for the cooking and preparation of food in the home. All participants were of Sylheti origin. Research participants were recruited through community centres and a city farm . Snowballing techniques were used, as snowball sampling is an effective way of selecting cases within a network [This paper is based on ethnographic fieldwork conducted by the first author (referred to as the researcher) as part of her PhD research examining the therapeutic uses of food-plants and the transmission of knowledge among women of Bengali origin in London, Cardiff and Sylhet. For the purpose of this paper, we concentrate on the findings from fieldwork conducted in London specifically related to food. Research in London took place in two stints: January-December 2010 and June-December 2011. A range of methods were employed including focus group discussions, detailed open ended discussions, semi-structured interviews and participant observation. The research in London was conducted primarily among 30 women. The research focuses exclusively on women due to practical reasons and the nature of the project network . As the In order to gain access to Bengali women, the researcher initially volunteered at two community centres (referred to as the Shapla and Asha centres). Early on in the research period (February-March 2010) three focus group discussions were conducted at the Asha centre. The purpose of a focus group discussion is to explore attitudes, perceptions, feelings and ideas about a topic . IdeallyAt the community centres and the city farm the researcher acted as a participant observer. Participant observation is the process of immersing oneself in a “culture” through observing and participating in everyday activities of people in their natural setting and intellectualising what has been seen and heard . EstabliFrom the community centres and networks in Bangladesh, eight women  were formally interviewed at home using a semi-structured interview guide, developed following initial research at the community centres. Semi-structured interviews take less time and are more focused than unstructured interviews . They foEthical approval for the research was granted by the London School of Pharmacy and informed verbal consent was given by the research participants. Focus groups and interviews were audio recorded and transcribed verbatim and during more informal interactions, detailed field-notes were taken. The findings were analysed using a thematic approach and with the assistance of the computer software HyperRESEARCH . The researcher “immersed” herself in the data before identifying themes which were categorised and coded, the data were analysed through the development of concepts and linking themes and finding patterns . HyperREResearch that is valid means that the instruments of research, the data generated and the subsequent findings are both accurate and trustworthy . In ordeThe findings presented in this paper focus on several key themes. The first theme examined is the role of food, particularly Bengali food, in connecting the participants to “home” in Bangladesh. Changes in food consumption are also examined. The second theme is the role of garden plants regarding on-going connections to Bangladesh. Subsequently, the third theme the paper examines is perceptions of Bengali food in terms of health. The final theme explored is lay perceptions of healthy food according to the participants of the study.The food explored in this paper is food found in the “home”. “Home” refers to both the physical structure of a home and a symbolic site of belonging, embedded in historical and geographical relations and meanings ,29. The baji (vegetables fried in different spices), a meat and/or fish curry and daal (lentils). Salads would occasionally be served. “These are routine; curry, fish and vegetables” explained one participant (CD1). Home and “Bengali” food were spoken about interchangeably. There were similar views as to what Bengali food consisted of; “rice and fish” were considered quintessentially Bengali. Spices, lentils, certain vegetables, vegetables fried as baji with spices and various mishtis (sweets) were described as “Bengali”. Despite the apparent similarities in views as to what consists of Bengali food, there was plenty of room for negotiation. For the younger participants Bengali food was primarily connected to home and mothers. However, for the older participants Bengali food also connected them to “back home” in Bangladesh, not least through the active on-going exchange of food products between the UK and Bangladesh.Throughout the course of the research it was evident that food was an important aspect of people’s homes and lives. For example, food was an essential part of all visits, and the researcher would regularly be asked numerous questions about food: What food do you like? Do you like Bengali food? What type of Bengali food? Do you eat fish with bones? Can you eat spicy food? When visiting research participants at home, food was always served; preferably a rice meal, failing that tea and snacks were a minimum (serving no food was not an option). The rice meal that was offered, usually by older participants, would consist of white rice, at least one ilish (Hilsa fish), shutki (dried fish) and deshi (from Bangladesh) chicken. Despite accessibility to an industry catering to Bengali food, all of the participants reported themselves and/or members of their families bringing over foodstuff from Bangladesh. Vegetables, fruit, paan (Piper betle L.) and its accompanying shupori/goa , sweets, snacks such as pittas , mouri (puffed rice), chanachur  and certain spices were all reported to be brought over from Bangladesh. The items sent back are not depended upon as a regular food supply, but rather are sent as and when it is possible. The reasons for these regular exchanges vary across individuals and families.Spices, vegetables and fish are found in shops and supermarkets throughout London. In East London particularly there are several shops catering specifically to Bengali tastes, selling food items such as shutki (dried fish), prepared and fermented differently in Bangladesh. As illustrated, food is important to the home and food brought from Bangladesh enriches the food at home. Food from desh (homeland) as the source of Bengali food was considered by participants to be more “fresh” and tastier than food in the UK. While the exchange of these foodstuffs is valued in terms of its taste and “freshness”, another dimension the exchange is that connectedness between the two homes is maintained and strengthened. Gifts such as homemade pittas and the snacks chanchur and mishtis indicate food is sent with emotion rather than only for practical reasons as explained by a participant “they send us things that we like, homemade things, that’s the differences” (IM4). “They send us these things because they love us” another participant (IM3) succinctly explained. Sutton [Some of the items sent from Bangladesh are more difficult and expensive to acquire in the UK, such as seasonal fruit. For example, one older participant (IM2) said she has coconuts and bananas sent from Bangladesh when the opportunity arises. While these are available in the UK, she explained that they are more expensive and not as fresh as those in Bangladesh. Mangos, certain chillies and vegetables not as readily available in the UK are also brought back from Bangladesh. There is also more variety in Bangladesh; for instance, there are various types of . Sutton , in his . Sutton , in his Before moving onto an examination of garden vegetables, it should be noted that food, particularly food consumed outside the home, was subject to change. During the research younger participants in particular described changes in their diets over the course of their lifespan. Most older participants also described changes in their diet, however they tended to eat less “outside” food than their daughters. While food cooked and consumed at home included Bengali food, cereals, pasta and breads (described as “English” or more frequently described as “Western”) were also eaten at home. Foods eaten outside the home include fast foods such as hamburgers, pizzas and fried chicken. Also observed and described was the consumption of Indian, Middle Eastern and Nigerian food. The incorporation of “outside” food as well as continuing to eat food of one’s parents’ country is consistent with other studies looking at the eating patterns of migrants ,26,28. WFood is important to the home, more specifically Bengali food is important to home “here” in the UK. It is also important to maintaining a connectedness to home “there” for older participants. Food and its associated meanings are re-imagined and changed through migrations and generations; this is both reflected in and serves to define the home. Another type of food that is of critical importance to home making and maintaining links to ‘back home’ is food that is grown by the participants themselves.lau , lal shak (Amaranthus.) and other shaks (leafy vegetables) and kochu , in addition to those found more commonly in the UK such as tomatoes, potatoes, onions, coriander and, occasionally, strawberries. , older participants invested time, effort and money into growing plants and food. They would grow plants on windowsills, in gardens, allotments and community gardens. “Bengali” vegetables grown include , older psonar mathi” (golden earth) of Bangladesh, where plants grew freely with ease. The sangalis (wooden pergolas that vegetables grow up) that can be found all over Bangladesh have been replicated, space permitting, by Bengali gardeners in the UK. While practical, they are also a visually powerful reminder of Bangladesh. The fresh produce, particularly the Bengali vegetables grown, were reported by participants as being “tasty” and “fresh” and much better than any vegetables found in UK shops. The garden is a site where memory can be visualised and drawn on through practical action, fulfilling the everyday needs of food. Furthermore, like food, seeds from desh were frequently reported to be sent to the UK . This again serves to connect people now living in the UK to Bangladesh. Interestingly, upon further investigation in Sylhet, these seeds were often not from Sylhet but from other countries–India, Thailand, China and Malaysia. However, the fact that they were brought to the UK via Bangladesh was clearly important and were said to be better, with more availability than ones found in the UK.Previous research into gardening highlights gardens as social, personal and symbolic spaces ,44,45. Rlou (gourd). While each allotment plot was assigned to an individual, relatives would frequently share a plot and work on the land together or separately . Adult children would occasionally accompany their older parents, however it was more common for grandchildren to be brought to the plots where they could run around and play. In people’s homes seeds and plants would also be exchanged frequently and shared. Interactions were not always positive, however. For example on the city farm there were often tensions between plot holders, with reports of people stealing vegetables from neighbouring plots. Echoing previous studies on gardens, interactions between people (positive and negative) stress that the garden is a social space and that they facilitate links to “home here” [When looking at conceptions of “home” and the garden, the growing of vegetables was important to maintaining and creating social connectedness to “home here” as well as “home past” in Bangladesh. At community gardens and allotments it was not uncommon for whole families to visit, often interacting with other gardeners. The produce from these spaces was valued, as people fed their families the harvested foods and gave friends and neighbours their vegetables as gifts. On one of the researcher’s first meetings with Lili (FM1), she showed her around the allotment plots on the farm pointing out who had managed to grow the biggest me here” .While gardening is primarily an act of older participants, it was by no means exclusive to them. When examining younger participants’ gardening habits it is possible to see how concepts of gardening are re-imagined through interaction with society and “home here”. Among the three daughters interviewed, only one (ID3) expressed interest in gardening. However, daughters of the older Bengali women at both the farm expressed an interest in gardening. This conversation with a younger interviewee provides some insight into what may influence younger participants to be interested in gardening:So why…do you enjoy or do you like the taste of home grown food or?Researcher: I think it’s to do with um, I think in our culture, particularly in like Islam as well there’s that emphasis on like kind of pure living, like eating healthy food. You know you’ve got to look at where your food comes from, who made it and things like that…I don’t know what they call it but it’s just that sense of you know, you’ve prepared your own food and you’ve grown your own food, so I think in that sense there’s something special about itID3: Ok, so would that be a more Islamic thing or a Bengali thing? Or both maybe?Researcher: Um, it might be a bit of both. I think it’s just that natural living, trying to live a natural way of life…um part of it is from Islam as well, that influence, and part of it is from mum because she’s always been growing her own vegetables and things… and then there’s the uh, I think it has become quite big now, even in the media, they’re promoting all of this stuff, like ‘make your own produce’……….ID3: Yeah, yeah, all this stuff is good…and organic as well like growing your own food and trying to use organic soil.In her narrative, the younger participant combines beliefs about her “culture” and Islam as well as recognising her mother’s influence while linking in with wider narratives of the benefits of home-grown produce and organic food. For the younger participants that did engage with gardening, they spoke about observing their mothers or accompanying them; however, it is also compatible with narratives of “growing your own vegetables” and organic food production promoted in sections of the media and popular among differing groups. While the link to “home” may be less evident among younger participants, it does illustrates how the different aspects of “home”  as well as the wider society play out through gardens. Although highly valued at home, it is the interaction with wider society where the value of Bengali food and plants are often devalued, which is now discussed.ghee (clarified butter) and salt should be limited. Two of the interviewees stated that fast food should be avoided. Despite the importance of rice, the participants stated that it was important to reduce rice consumption by having smaller portions and/or having only one rice meal a day. Occasionally there was some confusion over messages; for example during a health session at the Shapla centre there was a debate as to whether red meat should be eaten and how much.Public health messages regarding diet penetrate women’s lives via the media, schools, community centres and GP surgeries. Participants and workers at the community centres reiterated these messages. Dietary advice from health professionals was highly valued and rarely questioned by participants. Furthermore there was generally a consistency between the participants’ views and diet-focused public health messages. Participants classified foods in terms of specific nutrients and food groups . Participants generally agreed that one’s diet should include plenty of vegetables and some fruit. They reiterated that oil, Despite a basic level of knowledge regarding standard nutritional advice, not all participants reported taking health advice, or the extent to which it was taken varied. Food and change to eating habits was frequently spoken about in the context of health conditions. For example, a participant Amira (IM3) reported changing her diet after a diagnosis of diabetes and high cholesterol, she consequently reduced her rice, sugar and oil intake. Evidence suggests that people tend to be motivated to change dietary behaviours for health reasons, particularly once diagnosed with disease but less so for prevention or due to social influence or pressure from others . Howeverghee, salt and sweets were viewed as inherent to Bengali food and were identified as items that were particularly consumed by older participants. This concentration on the negative aspects of Bengali food contributes to a broad view that equates Bengali food with the concept of “unhealthy”. The quotes below illustrate how “Bengali” food is often perceived negatively,The researcher attended health education sessions at both the Shapla and Asha centre. While health and diet information was reported to be useful by attendees of the sessions, information was delivered by community workers or visiting health professionals in a very top-down manner, with little two-way dialogue. During group sessions, a worker would provide basic health messages and participants would be encouraged to ask questions at the end of the sessions. It was assumed that the worker had the “correct” answer and participants did not express opinions that may not fit in with standard medical advice. This often well-meaning but top down approach to providing health information extended to interactions with health professionals and community workers outside of the group sessions. Furthermore, during sessions the “unhealthy” aspects of Bengali food were often highlighted; participants reported these messages were frequently reiterated by doctors and other professionals they had contact with outside the centres. High levels of oil, “I know in other Bengali households they use a lot of oil, and they do cook a lot of red meat”“With my mother, and you will find with a lot of Bengalis, they are unwilling to change their habits. My mother eats a lot of rice, ghee and meat. The vegetables that are eaten are often overcooked.”“There is a lot of spice and oil in Indian and Bengali food. They need more salads, yoghurt and cucumber dishes.”(Community worker at the Shapla centre)biryani (white rice cooked in clarified butter with meat and spices) and mishtis (sweets) [ghee, salt etc.) “Bengali” food is not inherently unhealthy according to standard biomedical advice; it contains fish, plenty of vegetables and fruit, pulses, lentils and seasonings such as garlic and ginger, all of which are recommended by health professionals. Rarely was there mention of the “healthy” aspects of the “Bengali” diet. Furthermore the concept of a unified “Bengali diet” is misleading. While many foods are considered “Bengali”, the nature of “Bengali” food is not static but changing and fluid varying across individuals, families, age groups and across seas. The potential structural, practical and socioeconomic factors that affect one’s diet were not mentioned by health professionals, thereby placing the responsibility for diet on individuals and their “culture”. We suggest that people can place moral undertones on food, and urge caution when labelling food as “healthy” and “unhealthy” especially when attaching these labels to a particular group of people.Research into Bengali food habits in the UK to some extent agrees with these views. Chowdhury et al.  found an(sweets) . During (sweets) ’s findinWhen unpicking narratives of “good” and “bad”  food values, particularly in the context of ethnic identities, many issues are illuminated. They are indicative of key power imbalances between and within groups as well as a general lack of dialogue between professionals and the research participants. Moral judgements and disempowerment of individuals through the food they consume has been raised by academics. Foucault argued that power was inscribed on bodies through self-regulation of the body via diet and exercise . BuildinWe are thus caught in a dilemma. “Cultural” issues and links to home are important to understanding the different diets people consume and to providing inclusive public health services that cater to all members of the community. However by focusing negatively on the diets of other groups, there are very real risks of stigmatising and labelling not only the food people consume, but also the people themselves. Bhopal  suggestsjau (rice boiled to create a semi-liquid consistency), kitchuri (rice cooked with lentils and mild spices), milk, lentils and spinach. This food is literally soft in texture and is prepared with little or no spices. For very young children, it is “soft” foods that they are weaned on due to its attributed ease of digestion. For the sick, kitchuri is particularly given as it is considered nutritious  and easy to digest. In contrast, food that is classified as hard or “strong” is suitable for most (the well and not too old). “Strong” foods include rice cooked as pilou or biryani and meat (particularly beef). These foods are physically more “hard” and richer in oils and spices. Strong foods were rarely spoken about; one or two participants discussed them only when asked specifically about these foods, and they were described in contrast to the examples given for “soft” or digestible foods. Thus, the understandings of “Bengali” food groups expressed by participants in the current study did not match the detail of Chowdhary’s work. This could be because these categories and descriptions are theoretical in nature and are not necessarily how lay individuals discuss these groups of foods in their daily lives.In addition to notions of nutritional value, our research identified multiple expressions of dietary advice, goodness and health ascribed to food. Looking first at alternative food groups, we draw on Chowdhury et al’s  work on Azadirachta indica A. Juss) and korala . These vegetables were frequently described as “Bengali” and relate to those found in “traditional” medicinal remedies in Bangladesh.In regards to participants’ understandings of healthy food, the values of “freshness” and “balance” were expressed as particularly important. Participants spoke about “balance” in terms of having different types of food or “a bit of everything” as well as not eating in excess. This is consistent with Chowdhury et al. , as theyage kota” (“previous speak/knowledge”) and “ekone kota” (“present speak/knowledge”) in relation to the food that they previously ate and they now eat and know to be healthy. Both forms of knowledge are important and changing. Food, and healthy foods in particular, are embodiments of shared knowledge and various meanings influenced by emotions, family and personal histories.Among younger participants, the above values of health regarding food were less evident. For example, “soft” food was rarely spoken about and knowledge of food-medicines was less than that of older adults. With regards to “fresh” food, it was generally valued while taking on new meanings. Ruby , for example, said she had learnt about the importance of fresh food from her mother. She now equates it with foods that are “organic,” which is something she has learnt in the UK and feels is important to a healthy diet. Knowledge is dynamic and changing, and the body and self incorporate multiple knowledge sources as illustrated by Ruby and the multiple meanings of freshness when applied to garden vegetables. During a focus group discussion, women expressed the differing forms of knowledge they had acquired as they spoke about “Findings of differing and lay perceptions of food are consistent with research among other migrant groups. Park et al. , in theiFood and plants are the embodiment of multiple meanings; this paper illustrates how these meanings are fluid and changing over generations, across individuals, homes and groups. In the context of British Bengali women in London, our research found that “Bengali” food and plants are an important aspect of home “here” in the UK across different age groups. Bengali food is also important in connecting one to home “there” in Bangladesh through regular exchange of foodstuffs and seeds. The nature of the foods consumed is transformable, as we can see through differences between “inside” and “outside” food and changes within food at home. The influences on food by those outside of familial networks are illustrated though conceptions of “healthy” food. When looking at concepts of health and Bengali food we identify several crucial points. The first is that the existence of a power imbalance means that Bengali food is often devalued. The second is that there is a general lack of dialogue between health professionals and lay people which may be indicative of wider power structures as well as practical barriers such as a lack of time and interpreting services. Finally through examining lay understandings of healthy diets we find that there are multiple understandings of what healthy food means.While this paper does not explore the socioeconomic and structural factors influencing one’s diet and contributing towards power differences, it is important to be aware of their existence. In recognising an imbalance in power we urge for a greater dialogue between community workers, health professionals and those they cater to. Dialogue is different to advice, which tends to be a one-way flow of information from professional/worker to patient/participant. In contrast, dialogue, and even more importantly intercultural dialogue, is a mutual exchange of views encouraging expressions of lay understandings of health and recognising the meaningful nature of food. Food is ultimately the embodiment of multiple and fluid meanings-home here, home there, parents, children, local communities, global communities and health-to name a few. This embodiment needs to be taken into account in such dialogues aimed at groups like the Bengali community in Britain.aAll the names and places in the paper are pseudonyms.bThe term “Bengali” refers to people that trace origins back to Bangladesh, formally East Pakistan (1947–1971) and previously East Bengal in India. “Bengali”  is used as opposed to “Bangladeshi” as “Bengali” is the term used by the participants in this study.cThe PhD was part of a larger project, MINA , focusing on Bengali women in the UK and Bangladesh.We, the authors, declare we have no competing interests.HMJ was responsible for undertaking the fieldwork, interviews and analysing the data in the research presented in this paper. She wrote the first draft of the manuscript. MH, JT, JM and BB gave support and advice during the entire research process and contributed towards the writing and editing of the paper. All have approved the final version of this manuscript.


Mild Cognitive Impairment (MCI) is a diagnosis proposed to describe an intermediate state between normal cognitive aging and dementia. MCI has been criticised for its conceptual fuzziness, its ambiguous relationship to dementia, and the tension it creates between medical and sociological understandings of “normal aging”.We examined the published qualitative literature on experiences of being diagnosed and living with MCI using metasynthesis as the methodological framework.Two overarching conceptual themes were developed. The first, MCI and myself-in-time, showed that a diagnosis of MCI could profoundly affect a person’s understanding of their place in the world. This impact appears to be mediated by multiple factors including a person’s social support networks, which daily activities are affected, and subjective interpretations of the meaning of MCI. The second theme, Living with Ambiguity, describes the difficulties people experienced in making sense of their diagnosis. Uncertainty arose, in part, from lack of clarity and consistency in the information received by people with MCI, including whether they are even told MCI is the diagnosis.We conclude by suggesting an ethical tension is always at play when a MCI diagnosis is made. Specifically, earlier support and services afforded by a diagnosis may come at the expense of a person’s anxiety about the future, with continued uncertainty about how his or her concerns and needs can be addressed. Mild cognitive impairment (MCI) is a relatively new diagnostic category that first appeared in the medical literature in the 1990s . MCI wasIn attempt to resolve this uncertainty, the U.S. National Institute on Aging and the Alzheimer’s Association convened a working group to develop criteria for identifying “the symptomatic predementia phase of Alzheimer’s disease” p1, . This woGiven these inconsistencies, it is challenging to clarify how many people may be living with MCI. A recent systematic review  found a Whether from a clinical or patient perspective, the significance of a physician’s choice of label can hardly be overstated. The act of diagnosis has far-reaching implications for a person’s sense of self, especially if the diagnosis relates to mental health . HoweverSearches were undertaken across four key bibliographic databases: PsycINFO, CINAHL, MEDLINE, and Web of Science. As MCI is a recent category, searches were limited from the year 1998  original studies” , p. 366.In the next stage, themes were examined across studies, in an attempt to establish a “dialogue” between them . Paper cA total of 2,131 records were retrieved after duplicates were removed. Most  were excluded at title or abstract stage. Twenty-four full-text articles were removed, leaving a total of 17 for inclusion in the metasynthesis. The study selection process is summarised in Studies were conducted in a variety of countries: the United States (10 studies), United Kingdom (3 studies), Sweden (2 studies), and the Netherlands, Canada, and Taiwan (1 study each). Generally, participants were recruited from specialist AD or memory clinics. Data collection methods predominantly comprised semistructured interviews, or focus groups. Two studies also incorporated “real-time” participant observations: Two overarching conceptual themes were developed. The first, MCI and myself-in-time, examines the changes a MCI diagnosis brings with respect to the relationship between the self and the experience of time. Drawing on research from social psychology and phenomenological philosophy, the self is understood here as the locus of meaningful human agency and action . We emphIt is well-known that the onset of neurocognitive illness can mark a profound re-evaluation of one’s past. As a person comes to terms with a new position in the world, their biography needs rethinking, and many participants throughout the literature spoke of how they had changed relative to the past e.g., . DamianaThese are all people that I cared about, and they are no longer in existence … even if there’s some laughs in the movie I’m left with a little feeling of loss but it’s balanced to some extent by having a chance to see them again (pp. 29–30)Nostalgia for past relationships, roles, and experiences was widespread through the literature, and the only study in which this phenomenon was absent was Participant narratives of lost capabilities were heterogeneous, but widespread. Some spoke of giving up work or similar responsibilities Anxiety and worries about the future were ubiquitous through the literature. Many participants perceived MCI as an early or mild form of dementia, anticipating an inevitable decline in agency and selfhood: “We’ve just been turned upside down by it…. You picture these people who are vegetables … it’s horrific” , p. 8. “It was not only the perception of MCI as a prodromal form of dementia that led to future-oriented anxiety; concerns were also raised around the uncertainty of the label  you know, I have had a great life, I have a good job and kids and… all that is behind me you know. I just hope I will have some good and healthy years now” , p. 297.Uncertainty in diagnosis and information. Although a considerable body of research is beginning to investigate ways to reliably identify MCI using neurological, psychological, and even genetic tests, the extent to which MCI can be distinguished in routine practice is uncertain. Indeed, the literature showed some people with MCI explicitly questioning the clinical utility of the label. As one reflected: “My feeling is there is a lot of guesswork involved and that people don’t really know. Do you have early-stage Alzheimer’s? Do you have MCI? Is there a difference? […] It’s like trying to make sense of nonsense” , p. 138.Perhaps one reason for this uncertainty was heterogeneity in the way participants were diagnosed. In However, what actually happened in encounters between clinicians and people with MCI was unclear. As Linked with the uncertain status of MCI as a diagnostic entity, many research participants had questions concerning the extent to which MCI represented a “real” problem. As hinted by these varied accounts, the term “normal” carries two distinct but linked meanings: normative, and nonpathological. From a social constructionist perspective, Well, to be quite honest, I think I was relieved […] I was concerned probably like everyone else would [be], that I had Alzheimer’s, and then he said, ‘you don’t have Alzheimer’s,’ and you know that’s like taking a cloud off your shoulder […] so giving it a title, you can call it anything you want, but it’s not Alzheimer’s, so I can live with it  and medical  meanings  “normal,” (b) “non-normal,” or (c) “pathological.” These three interpretations, in turn, each bear a distinct set of implications for the temporal being of the self. We are not suggesting these interpretations act upon the self in a deterministic way; but rather that they help circumscribe the range of possibilities a person can envisage for herself. Indeed, our findings were suggestive that other mediating factors, including coping styles, level of social support, the experience of clinical assessment and diagnosis, and severity of cognitive difficulties, also appear to play into the relationship between MCI and the temporal situatedness of the self. It would perhaps be productive to examine the relationships between such constructs more systematically in future qualitative and quantitative studies.There are several limitations to our findings. Perhaps most importantly, the ambiguity in MCI fed into the metasynthesis, such that we could not tell if we were comparing accounts from people with similar cognitive issues. Some studies included participants with AD e.g., , and sliSecond, it is important to recognise the “third-order” interpretations on which our analysis was based —it is neTo conclude, we offer brief reflections on key ethical and psychosocial issues in MCI diagnosis, along with some implications for practice. First, disclosing a MCI diagnosis appears to be a double-edged sword. Benefits to patients might include intervening early, promoting self-management, and enabling the use of a medical label to make sense of one’s issues. By contrast, the ambiguity surrounding MCI may complicate such sense-making, and some have argued that the term may be stigmatising. This is an issue to which practitioners should remain sensitive. Second, the potential trade-off between early support and stigmatization suggests an imperative to develop and evaluate services and technologies of specific relevance to MCI. There may be an opening, when a person is diagnosed, to develop early support and preventive practice to avoid unnecessary disability and ill-being caused by MCI. One possibility we are currently exploring, for example, concerns digital technology. Many digital devices are currently being developed to assist people with MCI in activities of daily living such as navigation, remembering appointments, and maintaining cognitive abilities. In addition to such disability mitigating tools, a small body of evidence is emerging to suggest using novel digital technology can enhance cognitive function e.g., , improvewww.all-well.org) within which this review was undertaken.We are grateful to the Canadian Institutes of Health Research, the Economic and Social Research Council (UK), and the Swedish Council for Working Life and Social Research, for funding the Ambient Assisted Living for Wellness and Engagement in Later Life project (


General Psychopathology, published by Karl Jaspers in 1913, is considered a groundbreaking work in psychiatric literature, having established psychopathology as a space of critical methodological self-reflection, and delineating a scientific methodology specific to psychiatry. With the advance of neurobiology and molecular neuroscience and its adoption in psychiatric research, however, a growing alienation between current research-oriented neuropsychiatry and the classical psychopathological literature is evident. Further, consensus-based international classification criteria, although useful for providing an internationally accepted system of reliable psychiatric diagnostic categories, further contribute to a neglect of genuinely autonomous thought on psychopathology. Nevertheless, many of the unsolved theoretical problems of psychiatry, including those in the areas of nosology, anthropology, ethics, epistemology and methodology, might be fruitfully addressed by a re-examination of classic texts, such as Jaspers’s General Psychopathology, and their further development and adaptation for 21st century psychiatry.Modern molecular psychiatry benefits immensely from the scientific and technological advances of general neuroscience . This “progress” of molecular psychiatry, however, will be to a degree “unbalanced” and “epiphytic” should the development of the corresponding theoretical frameworks and conceptualization tools that allow contextualization of the individual neuroscientific findings within the specific perspective of mental health care issues be neglected. The  General Psychopathology at a time when psychiatry had only recently been solidly established as a medical and scientific discipline, and ambitious research projects, such as that of Kraepelin, were inaugurated in order to uncover the fundamental bases of psychiatric conditions. The enthusiasm for purely biological approaches in psychiatry according to Griesinger’s dictum that all psychiatric disorders were brain disorders, however, was already meeting with increasing skepticism; Freud, for example, who had commenced his career as a neuropathologist, had already decided to proceed within a totally different theoretical framework, a psychological approach he termed psychoanalysis. Jaspers seemed to strongly feel the need to critically evaluate psychiatric methodology, and to develop a methodological system that would be based on “dynamic” principles, permitting continuous re-adjustment as the discipline of psychiatry generated increasing knowledge about the mind and the brain [The young Karl Jaspers (30 years of age) published the first edition of his he brain .Tractatus logico-philosophicus by Ludwig Wittgenstein, who similarly employed his labors to the advantage not only of philosophy, but also in order to earn his doctoral degree from Cambridge University. An acquaintance with the biography of Karl Jaspers will greatly enhance the ability to analyze and comprehend his work and to place it in its historical context.In parallel with these genuine scientific-philosophical considerations, Jaspers also composed his work in order to foster his academic career. It was submitted to the University of Heidelberg as his “habilitation” thesis, in order to obtain his license to teach psychology at the university; it also enabled him to move from the Medical Faculty to the Faculty of Philosophy. This practical aspect shares some similarities with the preparation of the General Psychopathology he began a career as philosopher, and never returned to practicing medicine or psychiatry. Instead, he became, together with Martin Heidegger, one of the most important representatives of German existentialism [Born in 1883 in Oldenburg (Germany), Karl Jaspers suffered poor health throughout his youth (hereditary bronchiectasis) which, according to his own testimony, shaped his character to a certain extent, as it rendered him physically fragile and thus required stringent discipline in order to overcome his weakness. Born into an upper middle-class family, he was able to study law for a few semesters in Heidelberg and Munich before beginning his medical training during 1902 in Berlin, Göttingen and Heidelberg. In 1908, he obtained his medical degree, and worked until 1914 as a junior physician with Franz Nissl, who was at this time Director of the University Psychiatric Hospital in Heidelberg [From 1945 to 1948, he actively supported the re-establishment of free academic life at Heidelberg University and other academic centers. He was disappointed by political developments in post-war Germany, however, and emigrated to Switzerland in 1948, where he obtained a professorship in philosophy at Basle University. He adopted Swiss citizenship, and died in Basle in 1969.General Pathology has appeared in no less than eight editions since its first publication in 1913 [The  in 1913  to the l in 1913 , togetheGeneral Psychopathology is generally considered one of the major works in psychiatric literature, it is interesting to notice that very few papers published over the past 20 years in Medline-listed psychiatric, medical and scientific journals have concerned themselves with his thought (0–3 articles per year). In the centenary year of 2013, on the other hand, around 25 articles can be retrieved if one searches for titles including “Jaspers” and “psychopathology”. This is clearly an indication that Jaspers’ work is remembered for historical reasons, but seems to play only a minor role in current scientific discourse in psychiatry. With the advance of molecular psychiatry, the reception and reflection of Jaspers’s psychopathology seems to be receding ever further.While the General Psychopathology.While the so-called biological psychiatry of the 1970s, 1980s and 1990s was mostly based upon quite reductionist (and retrospectively simplistic) hypotheses about psychiatric conditions , the introduction of more advanced molecular neuroscience methods , 7 makesIntegrating psychopathological thinking into modern molecular psychiatry might at least initially be difficult due to a number of significant differences. Formally, discoveries in molecular psychiatry are published in relatively short journal articles with a very short “half-life” of sometimes only a few months. In contrast, psychopathological thinking is – similar to philosophical thought – outlined in rather voluminous books whose content can remain relevant for more than a hundred years (such as Jaspers). Further, classic psychopathological work is not always published in the current lingua franca (English), and translations of appropriate quality are not always available, complicating the reception of such work.Methodologically, the philosophical method of developing ideas and arguments based upon logic, conjectures and refutations, as applied to psychopathology, is quite different from the empirical-experimental approach employed in molecular psychiatry . A tendeErhellung), a term often found in modern scientific texts.There nevertheless exists a common basis for trying to better understand the mind and brain, and to fundamentally comprehend practical psychiatry. In this context, Jaspers often used the word “elucidation” (Ausdruck) and facts (Tatbestände) of this condition need to be differentiated, and that these terms must not be confused with the mental (das Psychische), which cannot be investigated per se.Jaspers underscored the contrast between an individual patient with their personal history, and the experience of complex states or conditions that are independent of individuals. He postulated that the expression (innige Einheit) between the mind/psyche and the physical/somatic. Nonetheless, a 1:1 correspondence between the two is not possible, despite certain “parallelisms” and interdependencies. It rather is like a “continent observed from two sides”, an “ocean whose coastline is examined”. He therefore postulated that general psychopathology should be freed from the slavery (Knechtschaft) imposed by the dogma that psychiatric disorders are brain disorders.He also discussed the relation between general psychopathology and somatic medicine, and spoke of a deep unity , “mind” (Geist), and “human soul” (Menschenseele), and also give rise to the question whether animals can suffer from mental illnesses, which would be necessary, were animal models in psychiatry to be valid; this remains a highly contested question in current empirical molecular-psychiatric research. It also reminds one of Tim Crow’s dictum that “schizophrenia is the price that homo sapiens pays for language” [Jaspers attempted to derive a specific psychopathological terminology by discussing three central problem areas: comparison of human beings and animals in order to define their similarities and dissimilarities; objectification (and organization) of the soul; and the interaction between the inner and outer worlds of the individual. The first area provided a useful somatic terminology because of identified somatic similarities. The dissimilarities lead to terms such as “personhood” , including somatic (organic) data. The soul/mind itself remains the all-encompassing that cannot be objectified itself. This train of thought on the soul/mind (Seele) provided key psychopathological terms, such as consciousness (inwardness of experience: Innerlichkeit derErfahrung), representational consciousness (objektivesBewusstsein), self reflection (Selbstreflexion), existence in one's world (Sein in ihrer Welt), as well as becoming (Werden), development , and differentiation (Differenzierung), terms which also signify its non-finality (nicht engültig) and incompletion (nicht vollendet).Jaspers also stressed that the soul Innenwelt) and the environment (Umwelt) makes it necessary to interpret “life” from a psychopathological view as existence in its world , which again unlocks a thesaurus of terms that have, in part, become part of current molecular psychiatry .Finally, the interaction between the inner world  outlook. So-called neurophilosophy had, however, not yet been developed at the time when Jaspers was writing; this form of “empirical philosophy” aims at unifying theories of the mind and the brain  accordinSeelenleben) cannot be reduced (zurückgeführt werden) to a few universal principles. It would therefore be wrong to metaphorically compare the soul/mind to an ocean, with psychopathology discovering and describing more and more of its shores and islands.The theoretical prejudice sees psychopathology as a “unifying theory”, but Jaspers actually argued that the mental world (Hirnmythologie) [das Seelische und das Körperliche) are intertwined through parallelisms and interactions (Wechselwirkungen).The somatic prejudice identifies psychopathology with physiological, anatomical and/or general biological phenomena and processes. In this context, Jaspers states that identifying the methodology underlying Meynert’s and Wernicke’s work on aphasias and apraxias with genuine psychopathological practice would lead to “brain mythology” (hologie) . NeverthThe psychological-intellectualistic prejudice implies an interpretation of psychopathology that considers it as pure speculation without any basis in reality. Such a stance, however, has rendered it impossible for so-called ‘somaticists’ to accept phenomena such as hysteria.Bilder als “Seelengrundrisse”).The image prejudice is defined by a reduction of psychopathological phenomena to pure images  that are misinterpreted as the actual design of the soul/mind .Beherrschen der Methode). Secondly, openness and the ability to see and experience are required . Thirdly, all prejudices must be eliminated. Finally, one must possess the capacity for self-criticism (Selbstkritik).After delineating possible routes to the required psychopathological vocabulary and discussing possible stumbling blocks to the project (prejudices), Jaspers discussed the necessary prerequisites for successful engagement in psychopathology. Firstly, it is necessary to be thoroughly competent in its specific methodology and its application , statistics, and experiments.Auffassung von Einzeltatsachen), that is, phenomenology; the examination of contexts and relations (Erforschung von Zusammenhängen), leading Jaspers to his well-known differentiation between understanding  and explaining ; and the “embracement of the whole” (Ergreifen der Ganzheit).The logical methods include the apprehension of individual phenomena (Abwege), Jaspers anticipated several problems within the theoretical framework of current psychiatry that have still not been solved:By discussing possible errors which might lead psychopathological (and other) research astray (Überwältigungdurch die Endlosigkeit). In this context he cited the infinitude of case histories, the endless enumeration of the countable (Zählbares zählen), the infinitude of correlations and of elements, combinations and permutations. He further mentioned the infinitude of “auxiliary constructions” (Hilfskonstruktionen) and of “potentialities” (Endlosigkeit des Allesmöglichen). He further criticized the risk of “literary endlessness” (literarische Endlosigkeit), thereby anticipating the modern madness of “publish or perish”.According to Jaspers, the key problems are related to being overpowered by boundlessness (Festfahren in der Verabsolutierung), that is, the risk of doctrinism that is especially virulent in academic circles where psychopathology is taught as a “school of thought” (such as the Leonhard school [Scheineinsicht durch Terminologie), a problem that haunts commissions established to edit consensus-based “classification criteria”, the ever increasing number of new editions of which represents little more than faux progress and a deceptive advance of psychiatry.Two further errors to be avoided were “becoming bogged down by dogmatism” , as the principle of classification (Gliederung), and as isolation of the single methods as well as the whole picture (Gesamtbild). This is the central narrative of his work. It is accordingly a misunderstanding to identify his thought with phenomenology, biology or the difference between them (as has often been in the course of the reception of his work). Like early Socratic dialogues, the General Psychopathology appears to end aporetically regarding the issue of how firm results can be obtained within this definition of psychopathology. Jaspers, however, believes that at least an approach to (Annäherung) and an encircling (Einkreisen) of universal “truth” is, at least in principle, possible [offene Erkenntnisfragen) and an awareness of one’s own limits (Grenzen). The experience of limits or border situations (Grenzerfahrung) is a central term of Jaspers’s philosophy [For Jaspers, psychopathology consisted of methodology and methodological criticism. He defined methodology as the combination of methodological consciousness and methodological system . Natural sciences are for him not an alternative to psychopathology, but an integral component of it.Psychopathology as defined by Jaspers is thereby a chance for molecular psychiatry to look beyond its own biologistic borders and to overcome its solipsism, frustration, and lack of orientation. Psychopathology can assist finding answers to essential questions that cannot be addressed by neurobiological means alone, but are fundamental to psychiatry.


The yet-unrealized potential for more “personalized” Direct-to-Consumer (DTC) tests to fundamentally alter the practice and economics of healthcare is undeniable. However, there are also many challenges to be met, including the herculean task of ensuring that the information provided by such tests is scientifically sound and, ideally, medically actionable. We consider recent events in DTC testing and suggest a “thought experiment” of an approach that could ultimately meet the needs of patients, providers and regulatory authorities. The development and marketing of Direct-to-Consumer (DTC) diagnostic or “health information” tests are redefining the boundaries of the medical and consumer cultures, in ways that have only begun to be recognized ,2,3. Boti.e., DTC tests that would provide information of value in empowering individuals to better manage their health in the context of the current healthcare system in a manner that might be welcomed by those with regulatory concerns about safety and validity. The recent dust-up between one of the few remaining genomics-based DTC companies and the Food and Drug Administration helps focus attention on what is at stake. Here we consider some early lessons emerging from their clash, and suggest an approach to providing DTC tests in a way that benefits all stakeholders, The yet-unrealized potential for some form of more “personalized” DTC tests to fundamentally alter the practice and economics of healthcare is undeniable. However, it is also clear that there are serious issues—though perhaps not as many as feared—to be resolved if DTC testing is going to be successfully integrated into the current healthcare system.by patients for their own decision-making. Tests promoted to patients but ordered by physicians are not strictly DTC tests, at least for the purposes of what we are considering here. In addition, a DTC test should be affordable and easily done . It should also be accurate and actionable, even if the action suggested is as simple as a timely visit to a physician, who (it is hoped) has at his or her disposal enough biomedical knowledge to correlate the results of the test with appropriate disease management. We recognize that this may be a tall order in some cases, particularly as reflected in recent events related to certain genotype-based DTC testing.Although obvious, it is important to note that DTC tests are, by definition, a set of tests requested At least 27 “DTC” companies currently offer, or have done so in the past, genetic testing either “directly” to consumers or via a doctor’s order ,7. SeverInitially, DTC genetics companies grew out of the research findings from genome-wide association studies (GWAS). In essence, the research-based association of specific polymorphisms in the individual’s genome with common diseases and traits formed the basis for several companies’ initial test offerings. Larger GWAS studies in multiple populations have continued to refine both the correlations of specific genetic variations with disease, as well as the scope of DTC tests offered. Companies providing these tests run the gamut of types of information offered, from ancestry to “nutrigenetic” evaluations ,11. AlthThis growing awareness on the part of those who embrace genetics-based DTC tests and those who raise serious concerns about their value is further intensified by the astounding technological advances in genetic technology, particularly in whole genome or whole exome sequencing (WGS/WES). These advances have brought the cost of this higher level of genomic resolution closer to the cost of traditional GWAS studies. Although no company currently offers its WGS technology on a DTC basis, the FDA has recently approved the use of several of Illumina’s next-generation sequencing technologies as devices for the diagnosis of cystic fibrosis .So where did 23andMe run afoul of the rules? Although 23andMe’s tests, like those of other companies currently or previously in this market space, are generally sold to consumers under the appealing idea of “empowerment” .However, 23andMe appears to have overreached by offering health-related interpretations of the raw genomic data directly to consumers, crossing an uncertain boundary between information and true “diagnostics”. That, more than anything else, appears to have captured the attention of the FDA. In addition, as the FDA’s 22 November letter indicates, 23andMe inexplicably “went silent” for months on the FDA’s requests for further information and validation studies, leading Forbes’ Matt Herper to wonder if the company is “guilty of the single dumbest regulatory strategy I have seen in 13 years of covering the Food and Drug Administration” .23andMe was building something of real value, we believe, analogous perhaps to the early days of basic human anatomy. They knew that to truly unravel the correlations of genomic variation with various disease processes they would need a massive database of genetic variation derived from potentially millions of people, with as much associated clinical data as possible. It would be a shame if those visionary efforts were stymied by a wrong-headed marketing strategy that proffered something to consumers that simply was not deliverable in these early days. The repercussions of the 23andMe/FDA dispute have yet to be measured, and yet we know that the health value of deep genetic analysis of human populations will be crucial.On the positive side, the 23andMe-FDA interactions have helped us crystallize a bit more our ongoing thoughts about how one could set up a DTC strategy that could ultimately have a positive impact on individuals’ health ownership, the effectiveness of health care providers, and the important concerns of the regulators.We should first note that we have spent the past 14 years focused on developing “phenotype-based” tests, in particular the measurement of protein changes in the body and the correlation of those changes with a variety of diseases and conditions ,23. We, etc.“…your doctor doesn’t check your cholesterol because they are primarily seeking predictive information. Your doctor checks your cholesterol because they can change your cholesterol. They aren’t doing it just so they can say, ‘Oh, you’re at increased risk for a heart attack. Have a good day.’ They are checking it because they can do something about it. And that puts it in an entirely different category than these direct-to-consumer genetic tests”.The difference between such phenotypic tests and ones based on assessing genotype is perhaps best summed up by Dr. James Evans at the University of North Carolina, in an interview with GeneWatch :“…your Although cholesterol may not be the best example, particularly in light of the new guidelines recently issued by the American College of Cardiology and American Heart Association , Dr. Evaetc.), measure most of the protein levels in your blood, and provide that information back to you. In a few cases, those findings might be interesting, a few maybe even clinically relevant . You wo testing .Suppose further that as many people do this kind of testing, the data from many people with many different health conditions is combined to generate a knowledge database of what those changes in the measurements might mean in the context of health and disease. In this context, these data are analyzed, published, and provided back to you (and your physician). This kind of regular testing, research analysis, and knowledge gain would continue to grow, particularly if there were a large number of public and private collaborators supporting this effort and sharing (de-identified) data openly. In essence, the individual would not only be gaining greater insight into his or her own biological status, he or she would be participating in a new kind of clinical trial that could lead, eventually, to real diagnostic tests of value that would pass regulatory muster  in the urine, or the recently approved first home test for HIV , which mWe also believe that this kind of DTC approach may be what 23andMe initially intended, although based more on honing risk prediction than measuring real-time phenotype. However, the marketing gloss they provided to bring in the kinds of customer numbers they needed to gain enough data to build meaningful interpretations unfortunately put the cart a good way ahead of the horse.Interestingly, several companies are gearing up to offer phenotype-based DTC clinical laboratory tests, either through pharmacy store chains (Theranos—) or by sThe emergence of DTC testing reveals the dynamically shifting boundaries between health care providers, consumers, and regulators. The fact that gene-based diagnostics, by and large, were the first entrants into this new world highlights the challenges faced, largely because of the inherent uncertainty around assigning relative risk of developing various diseases to uncovered genetic variants. Furthermore, genomics introduced a new lexicon into medical practice, one that is still foreign to most physicians and other health care providers. Throughout history, doctors have spoken the language of phenotype, not genotype, largely because phenotype describes “what is” in real time. One’s genetic makeup is, indeed, “personalized”, but whether that personalization translates into medicine in useful and actionable ways remains to be proven. It certainly is not good enough now, at least for regulatory purposes, as demonstrated by the recent FDA action against 23andMe.However, if phenotypes can be measured via proteomic analysis, perhaps even earlier than traditional symptoms appear, a DTC testing approach could help provide a deeper, integrated form of truly personalized medicine. Though there are many challenges still to be met, the recent advent of robust proteomic technologies  could he


Actually it has not quite happened yet, but almost imperceptibly, by degrees, we are learning to live with cancer. The “War on Cancer,” although generally successful in the pediatric population, has gradually been replaced with a kinder, gentler treatment paradigm that strives to contain and maintain with stalemate over checkmate, a strategy that may literally constitute the path to least resistance. The purpose of this review is (1) to critically examine the War on Cancer as a powerfully evocative metaphor that is directly responsible for a counterproductive and even potentially dangerous war-like cell-kill treatment paradigm, (2) to suggest that a reframing of this metaphor in less retaliatory and aggressive terms along with a shift in clinical practice from a maximalist to a minimalist strategy is more appropriate to the treatment of cancer, and (3) to draw on examples from the military sector as points of reference and comparison that closely parallel the three therapeutic “control and containment” strategies discussed in this review: (1) “Optimox-like” trial designs, (2) epigenetic modulation, and (3) metronomic dosing. Actually it has not quite happened yet, but almost imperceptibly, by degrees, we are learning to live with cancer.As improbable and counterintuitive as it sounds, the scorched earth, win-at-all-costs ethos from the “War on Cancer,” although generally successful in the pediatric population, has gradually been replaced with a kinder, gentler treatment paradigm that strives to contain and maintain with stalemate over checkmate, a strategy that may literally constitute the path to least resistance.The live-and-let-live handwriting is already on the wall with strategies that include “Optimox-like” trial designs, metronomic dosing, and epigenetic modulation, discussed in this review; the reality, largely unacknowledged though it may be, is that the war on cancer may not be winnable in the majority of cases, as currently waged.Chemotherapy and radiation are the ultimate stress test for cancer cells, leading to an unintended “survival of the fittest” response in which the most sensitive cells are culled from the treatment-resistant herd; inevitably the price of this selection pressure is the emergence of acquired resistance and therapeutic failure, making aggressive therapy a self-defeating process. Nature abhors a vacuum and fills it up with resistant tumor cells, which ultimately dooms the outcome to failure.This is not to sound a pessimistic or defeatist note; to the contrary, it may be finally possible to imagine a world in the not-too-distant future when cancer is a chronic disease like HIV, COPD, or diabetes: if total eradication is impossible, except in certain circumstances, due to the development of acquired resistance, then one alternative is simply to hold the line: to box-in the tumor cells with a discrete, focused strategy of containment, a path between the extremes of all-out assault and appeasement, thereby turning metastatic cancer from a death sentence into a chronic disease.The purpose of this review is (1) to critically examine the War on Cancer as a powerfully evocative metaphor that implies the promise of complete victory, motivates an overly strong desire to retaliate  and is directly responsible for a counterproductive and even potentially dangerous war-like cell-kill treatment paradigm, (2) to suggest that a reframing of this metaphor in less retaliatory and aggressive terms along with a shift in clinical practice from a maximalist to a minimalist strategy is more appropriate to the treatment of cancer, and (3) to draw on examples from the military sector as points of reference and comparison that closely parallel the three therapeutic “control and containment” strategies discussed in this review: (1) “Optimox-like” trial designs, (2) epigenetic modulation, and (3) metronomic dosing. This review is warranted if only because the central tenet of the War on Cancer, tumor eradication, has remained essentially invariant for over 40 years despite the fact that, by and large, it has not succeeded.In American strategic language, rollback is the doctrine that advocates regime change, by force if necessary . On the Ever since Nixon’s War on Cancer declaration in 1971  , as if cancer were an enemy to be defeated through a massive or overwhelming display of force. Based on the fervor with which it is conducted, the War on Cancer seems closer to a hyper-aggressive military campaign than a treatment trope. Slowly, however, with the recognition that the War on Cancer is less a war than a quagmire, having, by and large, failed to a deliver on its promise of a decisive victory , which refined the War on Cancer metaphor into a series of six unifying principles that control cell growth and metastasis and ushered in the era of targeted therapies challenged the medical community to take stock and recognize that the only way to defeat cancer was to better understand it. History’s timeless lesson from as far back as Sun Tzu, the Chinese general from the sixth century, is that the successful outcome of war critically depends on accurate intelligence and knowledge of the enemy. The H&W war doctrine describing the strengths and perhaps weaknesses of Mankind’s enemy (cancer) was updated and expanded in 2011 .Quagmires, defined as impasses or deadlocks, have occurred repeatedly in the context of military and evolutionary conflicts where one side is a much more pronounced orchestrator of pressure. This pressure forces or induces the other side to evolve countermeasures to resist it. Thus, in Vietnam, Iraq, and Afghanistan , it was Likewise, in the case of cancer, the lethal force of chemotherapy, designed to wipe out the tumor, may actually have the opposite effect: the chemosensitive cells, which normally keep the chemoresistant forms in check, by competing for scarce space and resources, are killed off. Cancerous tumors adapt in Darwinian fashion to their environment and evolve by clonal expansion and genetic diversification . As a reCancer is by no means monolithic; rather, it is a highly diverse and heterogeneous population of cells, with different degrees of overall fitness, even within a single tumor due to both genetic and environmental factors . In geneAccording to the Red Queen hypothesis, a widely used concept from evolutionary biology, in reference to the character from the Lewis Carroll novella, “Through The Looking Glass,” who comments to Alice that “it takes all the running you can do, to keep in the same place,” co-evolution drives continuous adaptation and counter-adaptation just to stay even . SimilarAnd so while the War on Cancer drags on officially without armistice or quarter unofficially signs of a tactical shift are already underway, with “Optimox-like” trial designs, epigenetic modulation, and metronomic dosing serving as the basis for discussion in this review.The Surge, as it was called, referred to a modest temporary increase in U.S. troops in 2007 in Iraq to quell an insurgency that was spiraling (surging) out of control, after which Bush’s plan was to return to pre-surge levels . An ObamThis surge strategy finds parallels in the “stop and go” Optimox 2 trial design  to managa complete break in treatment after induction therapy until the tumor begins to regrowthe modified “stop and go” of the Phase 3 Combined Oxaliplatin Neurotoxicity Prevention Trial (CONcePT) study in which patients were “on” oxaliplatin for a predefined interval of 4 months (FOLFOX and bevacizumab) and “off” oxaliplatin for a predefined interval 4 months (LV5FU2 plus bevacizumab). Despite early termination, CONcePT, which compared this intermittent oxaliplatin (IO) schedule to a conventional oxaliplatin (CO) “treat-to- failure” approach, demonstrated an impressive improvement in PFS from 7.3 months to 12.0 months with the stop-and-go strategy .Variations on this Optimox theme includeIn a recent review of stop-and-go clinical trials from 2000 to 2013 entitled, “Continuous versus Intermittent Chemotherapy Strategies in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis” by Berry et al. the authors concluded that compared to continuous chemotherapy, the intermittent strategies did not negatively impact on overall survival (OS) and “either maintained or improved quality of life (QOL)” .An additional Optimox-like variation, called adaptive therapy, developed by Gatenby et al.  through So pervasive and influential is the War on Cancer mindset especially in the U.S. that patients may refuse sporadic or intermittent therapy on the basis that it is preferable to hit the tumor hard and often – it may be for this reason that the Optimox trials were enrolled in Europe not U.S. – even though continuous treatment appears to result in pain without gain, i.e., increased toxicity to patients without improvement in overall survival, compared to a stop-and-go strategy.A shaping operation is an operation at any echelon that creates and preserves conditions for the success of the decisive operation. Shaping operations establish conditions for the decisive operation through effects on the enemy, population , and terrain… Shaping operations may occur throughout the operational area and involve any combination of forces and capabilities.”At times of war, the act of degrading and softening up an enemy in support of and in preparation for a decisive assault is called, in military parlance, a “shaping operation.” According to the Army Field Manual 3-0 , “A shapre-shaping operation” describes the tumor remodeling action of the epigenetic agents, through beneficial re-expression of methylated and abnormally silenced genes to degrade and reverse resistance to subsequent therapy.In many ways a “shaping operation” or, rather, a “of 4 years or more following progressive disease on azacitidine and entinostat , several patients demonstrated sustained and durable responses to their immediate next line of therapy tinostat , 22, leaThese observations are in agreement with another Phase 1 trial with the novel systemically non-toxic epigenetic agent, RRx-001, a double HDAC, and DMA methyltransferase inhibitor, where five colorectal cancer (CRC) patients were resensitized to previously failed FOLFIRI for 6 months or longer post-RRx-001 progression , 24, whiIn this way, epigenetic inhibition may represent a “kinder, gentler” approach in which the tumor is “reprogramed” during a preliminary “run-in” or priming period, similar to the shaping operation described in the Army Field Manual above, to respond to subsequent cytotoxic treatment, thereby increasing survival but not toxicity.As an alternative to armed conflict and all-out war, economic sanctions have played an important role in U.S. foreign policy throughout the twentieth and twenty-first centuries as a strategy to isolate, destabilize, and cripple “bad actors,” countries with inimical agendas like Russia, Cuba, Iran, North Korea, Sudan, and Syria .Metronomic chemotherapy involves regular, frequent systemic administration , i.e., wThe phrase, The War on Cancer, evokes the liberation of enemy-held territory and regime-change operations, a kind of C-Day or “Operation Overkill.” The problem with this image is that it misrepresents cancer as an enemy that is defeatable when, in fact, in the case of cancer cells, victory is only achievable with total eradication, which may not be readily possible. The very act of trying to drive the cancer cells to extinction only succeeds for the most part in removing the moderates, i.e., the chemosensitive cells, and leaving behind the extremists, i.e., the chemoresistant cells, which makes the situation that much more desperate.A middle course between appeasement and Armageddon is containment, which takes a long view, and eschews “rollback,” provided the tumor remains in its box. According to Gatenby et al. , drug-suDespite this apparent lose–lose, Catch-22 scenario , a third strategy, containment, presents itself as a solution to keep the “long peace” by turning cancer into a clinically manageable chronic disease like diabetes or hypertension, which is controlled but not cured with medication. Hopefully a state of balance is reached, in which the net result of tumor growth and destruction is zero or close to zero, resulting in stabilization or non-progression of disease.status quo and thereby turn a “hot” war into a cold one. Although it may chafe and go against the grain to play not to lose rather than to win, the strategies discussed herein suggests that with respect to cancer we have started to do just that, slowly.For this reason, a hard line strategy, which emphasizes cure over coexistence and an all-out war instead of a limited one, may only force cancer down its projected path to surpass heart disease as the leading cause of death by 2030  in a kinThe authors declare that the drug RRx-001, mentioned in this review, is manufactured by EpicentRx, Inc., and the majority of the research and clinical trials associated with drug RRx-001 have been funded by EpicentRx, Inc.