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ADVANCES IN AGRONOMY
Advisory Board
PAUL M. BERTSCH RONALD L. PHILLIPS
University of Kentucky University of Minnesota

KATE M. SCOW LARRY P. WILDING

University of California, Texas A&M University
Davis

Emeritus Advisory Board Members

JOHN S. BOYER KENNETH J. FREY
University of Delaware Iowa State University

EUGENE J. KAMPRATH MARTIN ALEXANDER

North Carolina State Cornell University
University

Prepared in cooperation with the

American Society of Agronomy, Crop Science Society of America, and Soil
Science Society of America Book and Multimedia Publishing Committee

DAVID D. BALTENSPERGER, CHAIR

LISA K. AL-AMOODI CRAIG A. ROBERTS
WARREN A. DICK MARY C. SAVIN
HARI B. KRISHNAN APRIL L. ULERY
SALLY D. LOGSDON
Academic Press is an imprint of Elsevier
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First edition 2009

Copyright # 2009 Elsevier Inc. All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted

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otherwise without the prior written permission of the publisher

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Obtaining permission to use Elsevier material

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No responsibility is assumed by the publisher for any injury and/or damage to persons or
property as a matter of products liability, negligence or otherwise, or from any use or
operation of any methods, products, instructions or ideas contained in the material
herein. Because of rapid advances in the medical sciences, in particular, independent
verification of diagnoses and drug dosages should be made

ISBN: 978-0-12-374818-8
ISSN: 0065-2113 (series)

For information on all Academic Press publications

visit our website at elsevierdirect.com

Printed and bound in USA

09 10 11 12 10 9 8 7 6 5 4 3 2 1
CONTRIBUTORS

Numbers in Parentheses indicate the pages on which the authors’ contributions begin

Muhammad Arshad (159)

Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad,
Pakistan
Marco van den Berg (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Richard M. Bruskiewich (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
H. Cantarella (267)
Instituto Agronômico, Campinas, SP, Brazil
S. H. Chien$ (267)
Formerly with International Fertilizer Development Center (IFDC), Muscle
Shoals, Alabama, USA
Jørgen Eriksen (55)
Department of Agroecology and Environment, Faculty of Agricultural Sciences,
Aarhus University, Tjele, Denmark
Ya-Jun Gao (223)
College of Resources and Environmental Sciences, Northwest Science and
Technology University of Agriculture and Forestry, Yangling, Shaanxi, People’s
Republic of China
Yong Gu (201)
USDA-ARS, Western Regional Research Center, Albany, California, USA
S. Heuer (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Khwaja Hossain (201)
Division of Science and Mathematics, Mayville State University, Mayville, North
Dakota, USA
G. Howell (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines

$
Present address: 1905 Beechwood Circle, Florence, Alabama, USA

ix
x Contributors

Sarfraz Hussain (159)

Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad,
Pakistan
A. Ismail (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
S. V. K. Jagadish (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Venu Kalavacharla (201)
Department of Agriculture and Natural Resources, Delaware State University,
Dover, Delaware, USA
Azeem Khalid (159)
Department of Environmental Sciences, PMAS Arid Agriculture University,
Rawalpindi, Pakistan
Shahryar F. Kianian (201)
Department of Plant Sciences, North Dakota State University, Fargo, North
Dakota, USA
Shi-Qing Li (223)
College of Resources and Environmental Sciences, Northwest Science and
Technology University of Agriculture and Forestry, Yangling, Shaanxi, People’s
Republic of China
Sheng-Xiu Li (223)
College of Resources and Environmental Sciences, Northwest Science and
Technology University of Agriculture and Forestry, Yangling, Shaanxi, People’s
Republic of China
Shivcharan S. Maan (201)
Department of Plant Sciences, North Dakota State University, Fargo, North
Dakota, USA
Noel P. Magor (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
S. S. Malhi (223)
Agriculture and Agri-Food Canada, Research Farm, Melfort, Saskatchewan, Canada
C. Graham McLaren (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Thomas Metz (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
H. Pathak (91)
International Rice Research Institute (IRRI), New Delhi, India
Contributors xi

L. I. Prochnow (267)
International Plant Nutrition Institute (IPNI), Piracicaba, SP, Brazil
E. Redona (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Oscar Riera-Lizarazu (201)
Department of Crop and Soil Science, Oregon State University, Corvallis,
Oregon, USA
Muhammad Saleem (159)
Department of Environmental Microbiology, UFZ Helmholtz Centre for
Environmental Research, Leipzig, Germany
R. Serraj (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
David Shires (135)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Tariq Siddique (159)
Department of Renewable Resources, University of Alberta, Edmonton, AB,
Canada
R. K. Singh (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
K. Sumfleth (91)
International Rice Research Institute (IRRI), Metro Manila, Philippines
Matthew D. Thompson (1)
Cancer Prevention Laboratory, Department of Horticulture and Landscape
Architecture, Colorado State University, Fort Collins, Colorado, USA
Henry J. Thompson (1)
Cancer Prevention Laboratory, Department of Horticulture and Landscape
Architecture, Colorado State University, Fort Collins, Colorado, USA
Xiao-Hong Tian (223)
College of Resources and Environmental Sciences, Northwest Science and
Technology University of Agriculture and Forestry, Yangling, Shaanxi, People’s
Republic of China
Zhao-Hui Wang (223)
College of Resources and Environmental Sciences, Northwest Science and
Technology University of Agriculture and Forestry, Yangling, Shaanxi, People’s
Republic of China
R. Wassmann (91)
Research Center Karlsruhe (IMK-IFU), Karlsruhe, Germany, and International
Rice Research Institute (IRRI), Metro Manila, Philippines
PREFACE

Volume 102 contains eight reviews addressing contemporary topics in the

crop and soil sciences. Chapter 1 is a timely review on biomedical agricul-
ture whose goal is to ‘‘identify specific genotypes of a food crop which,
alone and when combined with other food crops, form a dietary pattern that
reduces chronic disease risks.’’ Chapter 2 deals with sulfur cycling in
temperate agricultural systems. Chapter 3 covers an important topic –
climate change impacts on Asian rice production. Chapter 4 deals with
informatics in agricultural research. Chapter 5 discusses the impact of
pesticides on soil microbial diversity, enzymes, and biochemical reactions.
Chapter 6 is a comprehensive review on radiation hybrid mapping in crop
plants. Chapter 7 is concerned with nutrient and water management effects
on crop production and nutrient and water use efficiency in dryland areas of
China. Chapter 8 is a timely review on developments in fertilizer produc-
tion and use to enhance nutrient efficiency and minimize environmental
impacts.
I appreciate the excellent contributions of the authors.
DONALD L. SPARKS
Newark, Delaware, USA

xiii
 C H A P T E R O N E

Biomedical Agriculture: A Systematic

Approach to Food Crop Improvement
for Chronic Disease Prevention
Matthew D. Thompson and Henry J. Thompson

Contents
1. Biomedical Agriculture: A Twenty-First-Century Response to an
Emerging Global Problem 2
2. The Biomedical Landscape 8
2.1. Terminology 8
2.2. Chronic disease prevention 10
3. Agricultural Landscape 18
3.1. Genotypic diversity in crops 18
3.2. Chemical basis for CDP 18
3.3. Assembling a test collection of a crop’s genotypes 19
3.4. Extending chemical profiling to food crop combinations 22
3.5. Other considerations 23
4. Evaluating Crops 24
4.1. Animal-based approaches 25
4.2. Nonanimal approaches 26
4.3. Evaluation of crop genotypes and food combinations in human
participants 28
5. Biomedical Agriculture in Practice: A Developing Program in Crop
Improvement 30
5.1. Crops for HealthTM 30
5.2. The plant food–cancer risk conundrum 31
5.3. Biomedical agriculture: A transdisciplinary effort 32
5.4. The vanguard project: Determining the health benefits
of dry beans 33
6. Building the Infrastructure to Sustain the Effort 37
6.1. Transdisciplinary conceptualization 39
6.2. Land grant tradition 39

Cancer Prevention Laboratory, Department of Horticulture and Landscape Architecture, Colorado State
University, Fort Collins, Colorado, USA

Advances in Agronomy, Volume 102 # 2009 Elsevier Inc.

ISSN 0065-2113, DOI: 10.1016/S0065-2113(09)01001-3 All rights reserved.

1
2 Matthew D. Thompson and Henry J. Thompson

7. Summary and Future Prospects 41

Acknowledgments 44
References 44

Abstract
Biomedical agriculture (BMA) is a transdisciplinary approach and emerging field
that engages agronomists and biomedical scientists in a program of discovery,
dissemination, and training. The ultimate goal of BMA is to identify specific
genotypes of a food crop which, alone and when combined with other food
crops, form a dietary pattern that reduces chronic disease risk, that is, risk for
cancer, cardiovascular disease, type II diabetes, and obesity. To achieve this
goal, a systematic approach is required that investigates staple and specialty
crop genotypes for bioactivity that translates into improved chronic disease
biomarkers, alterations of which are associated with reduced disease risk. The
primary mechanisms targeted for food-mediated disease risk reduction are
altered glucose metabolism, chronic inflammation, excessive cellular oxidation,
and/or chronic endotoxemia. The crop improvement process via BMA is tiered,
establishing efficacy for chronic disease prevention in molecular, cellular, and
animal investigations of crop genotypes and food combinations before evalua-
tion in cohorts of human participants. Ultimately, specific dietary plans will be
tailored for individuals at risk for one or more chronic diseases. Informatics and
omics technologies enable transdisciplinary collaborations, giving the agricul-
tural and biomedical sciences a common research setting that sustains and
translates progress into the community.

1. Biomedical Agriculture: A Twenty-

First-Century Response to an Emerging
Global Problem
The human experience has been continually redefined through agri-
culture. The domestication of modern crops enabled the development of
civilizations, and since then, we have continued to reap the benefits of more
modern agricultural revolutions: as examples, Mendelian and molecular
genetics applied to selection and breeding (Dwivedi et al., 2007; Pickersgill,
2007), mechanization and precision agriculture (Glancey et al., 2005), and
genomics (Burke et al., 2007; Varshney et al., 2006). As technology has
advanced, those in agriculture have always leveraged the new tools made
available through scientific enterprise to meet the changing demands of
society. Looking ahead, the agricultural sciences are once again poised to
improve the human experience, in part because of the omics revolution
(Brown and van der Ouderaa, 2007; Kaput, 2004, 2007; Kaput et al., 2005;
Watkins and German, 2002a,b; Watkins et al., 2001). In this chapter,
Biomedical Agriculture 3

approaches are discussed that deal with problems at the interface of agricul-
ture and human health, with emphasis on chronic disease prevention (CDP).
In the past decade, numerous approaches have been suggested to inves-
tigate food-based health improvement. Clearly, the magnitude of food-
related problems is enormous. Malnourishment and essential nutrient defi-
ciency continue to affect more than half of the world’s population (Mayer
et al., 2008), and concomitantly, a surge in chronic disease is being driven by
the obesity epidemic (Must et al., 1999; Rippe et al., 1998; World Health
Organization, 2003). While some agronomists work within their respective
specialties to combat plant pests and environmental constraints on yield with
omics approaches (Keon et al., 2003; Weller et al., 2001), others are applying
similar methods to find solutions to food and nutrition problems, such as in
biofortification (Nestel et al., 2006; Welch, 2005; Welch and Graham,
2005). Through highly integrative research, some have suggested agrono-
mists should work closely with nutritionists and those in the biomedical
community. In 1997, Combs, Duxbury, and Welch wrote:
The paradigms of agricultural institutions, public health departments, and
human nutritionists must be changed from current linear approaches to
integrated and interactive approaches. If effective, food-based solutions to
micronutrient deficiencies and other human health issues are to be forth-
coming. [The program] is forging explicit linkages across a wide array of
disciplines and is supporting interdisciplinary research, teaching and exten-
sion activities concerned with the development and use of food systems
technologies for improved human nutrition and health. By better linking
agricultural production to nutritional goals and human needs, food systems
that make sustainable improvements in human nutrition and health can be
formed. (Combs et al., 1997)
In the 11 years since this visionary thinking was introduced, progress has
been made in biofortification programs (Gilani and Nasim, 2007; Pfeiffer
and McClafferty, 2007) and the development of the field of nutrigenomics,
where diet–gene–disease interactions are studied (DellaPenna, 1999; Kaput,
2007; vanOmmen, 2004). In these settings, relationships between agricul-
ture and the biomedical sciences have continued to be encouraged (Hawkes
and Ruel, 2006; Kochian and Garvin, 1999; Metzlaff, 2005; Watkins et al.,
2001; Welch and Graham, 2005). Yet beyond efforts to improve micronu-
trient content of crops, little work has been done to establish a framework
for food-based approaches to prevent chronic diseases such as cancer,
cardiovascular disease, type II diabetes, and obesity. These complex diseases
are not based on a definable nutrient deficiency; therefore, greater difficul-
ties arise in developing strategies for crop improvement to combat their
occurrence and consequences.
Epidemiological evidence from prospective studies conducted in the
United States and Europe are consistent with the idea that dietary patterns
emphasizing plant foods are associated with lower prevalence of chronic
4 Matthew D. Thompson and Henry J. Thompson

diseases (Bamia et al., 2007; Hung et al., 2004; WCRF/AICR, 2007; World
Health Organization, 2003, 2007; Yusuf et al., 2001). However, efforts to
identify the specific foods and/or food components that account for the
reduction in disease risk have been mixed (Hung et al., 2004; McCullough
and Willett, 2006; McCullough et al., 2000; Riboli and Norat, 2003). This
situation underscores the current lack of knowledge about how foods affect
long-term human health. As a consequence, there is a lack of recognition
that food crop genotypes, that is, any genetic variation, whether evolved,
selected, or bred, in any particular food crop, can differ when evaluated for
health benefit. The absence of information about crop genotypes on ques-
tionnaires used to collect dietary information in human population studies
clearly illustrates this insufficiency ( Johansson et al., 2002; Willett and Hu,
2007; Willett et al., 1987). Similarly, there is currently no scientific rationale
for how to combine plant foods for maximal ability to reduce chronic
disease risk, although the need for a different approach has been voiced
(Chiuve and Willett, 2007; Thompson et al., 2006). Rather, the predomi-
nant focus of established dietary guidelines is on the provision of adequate
levels of essential nutrients (Aggett et al., 1997; Harris, 2000). Despite the
limitations in our knowledge, chronic disease risk and its associated comor-
bidities and mortality are reduced by plant food-rich dietary patterns
(Craddick et al., 2003; Fung et al., 2008; Hung et al., 2004), and this is
consistent with the hypothesis that specific food crops and genotypes within
each food crop will be identified that uniquely impact human health.
The literature is rich in studies that approach plant improvement from
the single trait perspective (Grusak, 1999; Kinney, 2006). Regrettably
though, populations around the world are experiencing mortality from
chronic diseases that reflect broader issues than mono- or binutrient defi-
ciency syndromes, a situation reflected in a recent meta-analysis that
reported that supplement-based nutrient interventions failed to prevent
chronic disease occurrence and in some cases actually increased mortality
(Bjelakovic et al., 2007). In seeking to define health-promoting traits of
crops, biomedical agriculture (BMA) looks at food as the primary vehicle by
which chemicals are delivered to the human body on a daily basis. The
premise of this approach is that there will be no single ‘‘magic bullet’’
chemical solution for CDP. This is a concept that is often met with
resistance, and so, it is a feature that distinguishes BMA from other
approaches to health promotion and disease prevention that are based on
single agent chemical strategies. Accordingly, for a food-based intervention,
there must be an identifiable pattern of biosynthesis in a crop that is
associated with CDP. Identifying the profile of chemical constituents of
crop and/or food combinations will provide the critical knowledge base
required to understand how crops can be ingested to maintain health,
reduce disease risk, and maximize effectiveness of treatment regimes for
established disease states. BMA aims to shape the health preventive nature of
Biomedical Agriculture 5

the diet by identifying food crop traits that agricultural practice can and
should improve.
BMA was conceptualized in response to a litany of issues that are
encountered by agronomists, biomedical scientists, and health care profes-
sionals interested in food-based approaches to disease prevention. Some of
those issues are summarized in Table 1. To clarify, BMA is not the science
of the Green Revolution and its biofortification extension that has as its goal
the eradication of starvation and malnutrition in the global community.
BMA also does not deal with therapeutic uses of foods that seek to comple-
ment the standards of medical care, nor does BMA deal with the use of food
as a substitute for pharmaceutical interventions in disease treatment,
although what is learned from BMA will certainly affect these fields. Rather,
BMA targets the plant food component of the human diet, since that
component is least understood relative to its potential to contribute to
health promotion and disease prevention. The primary focus of BMA is
on staple food crops of the world, specifically dry beans, corn, rice, wheat,
and potatoes. This approach capitalizes on the regular daily intake of a
consistent and large amount of food staples by all family members, and in
so doing, addresses a major public health concern about whether the foods
developed are likely to be consumed. Because staple foods predominate in
the diets of the poor, this strategy implicitly targets lower-income house-
holds. When this approach is combined with the use of adapted crop
genotypes with both agronomic and cultural food characteristics essential
to profitable and consistent production, and the culinary customs of the
target population, successful dissemination and consumption of foods with
CDP activity can occur.
The overall goal of BMA is to identify specific genotypes of a food crop
that alone and when combined with other food crops, form a dietary pattern
(food combination) that reduces chronic disease risk, that is, risk for cancer,
cardiovascular disease, type II diabetes, and obesity. To achieve this goal, a
systematic approach is required that investigates both staple and specialty
crops (i.e., a wide array of vegetables and fruits) for genotypes with bioac-
tivity against a set of chronic disease biomarkers, the alterations of which are
associated with reduced disease burden. The primary mechanisms common
to these chronic diseases and targeted for food-mediated disease risk reduc-
tion are altered glucose metabolism, chronic inflammation, excessive cellu-
lar oxidation, and chronic endotoxemia (Fig. 1). The crop improvement
process is tiered, involving molecular, cellular, and animal investigations of
crop genotypes and food combinations, as well as clinical studies.
Ultimately, specific dietary plans will be tailored for individuals at risk for
one or more chronic diseases.
We have been gratified over the last 3 years with the extent to which
agronomists, and particularly plant breeders around the country, have
responded to the content outlined herein, and this chapter is structured to
6 Matthew D. Thompson and Henry J. Thompson

Table 1 Issues encountered in biomedical agriculture

Category Examples
Plant/ Defining diversity for a crop
agronomy Ability to determine how commercial crop genotypes
relate to the crop’s domestication and extant diversity
Identifying germplasm resources for a crop
Obtaining crop genotype collection with adequate genetic
or chemical diversity
Gene versus environment interactions: relative importance
Plant physiology as a surrogate for bioactivity
Balancing agronomic traits (yield, disease resistance)
Appropriate time to develop a RIL population
Material accessibility, availability
Source of material, crediting donors
Material storage (space, temperature, amount)
Material traceability
Screening Hundreds to thousands of crop genotypes
Crop genotype grouping and selection
Assay selection, translation of effects (e.g., in vitro
antioxidant to in vivo antioxidant)
Cost of the assay versus throughput
Preclinical/ Tiered approach: what are the logical steps; what should be
animal measured
Animal physiology versus cells in culture
Complexity of food versus a single chemical
Drawing conclusions before working with biologically
diverse collections of crop genotypes
Gut microflora assessment and metabolism
Method of preparation of crop as a food
Amount of crop incorporated into diet
Nature of the control group; a reference diet; a reference
genotype
Quality control
Clinical Expense
Working with doctors and patients
Practicality and feasibility
Grower/ Profitability/cost
consumer Identifying exactly what accounts for protection
Public concern over GMO
Moving food to the market
Funding/ Motivation to collaborate, dealing with negative findings
collaboration Funding sources, nontraditional
Publication: work is out of scope, not mechanistic
Biomedical Agriculture 7

Figure 1 Chronic disease and pathogenesis. Major chronic diseases account for 60% of
all deaths worldwide. In BMA, the focus is on cancer, cardiovascular disease, type II
diabetes, and obesity. Common to the pathogenesis of these diseases are altered glucose
metabolism, chronic inflammation, increased cellular oxidation, and chronic
endotoxemia.

provide a vision for the integral role that those in agriculture need to play for
efforts in CDP to be successful. The chapter addresses the following topics.
A summary of commonly encountered terminology in the field of food,
nutrition, and health is found in Section 2.1. The rationale for selection of
biomarkers that will serve as targets for crop screening and improvement is
discussed in the remainder of Section 2. A series of recommendations for
selecting genotypes of a crop for evaluation is presented in Section 3 and the
integration of this selection process with preclinical testing in animal models for
human disease is discussed in Section 4. Extension of the evaluation process to
the clinic is outlined in Section 4.3. Examples from our own work in BMA that
illustrate the implementation of the principles presented in various sections are
provided in Section 5. An approach for sustaining the BMA initiative is the
topic of Section 6, and Section 7 is a summary with future directions.
8 Matthew D. Thompson and Henry J. Thompson

2. The Biomedical Landscape

2.1. Terminology
For those who work in fields related to food, nutrition, and health, and for
all consumers who make a concerted effort to benefit from foods at the
market to promote their health and prevent chronic disease, the area is well
known to be rife with claims, counter claims, half-truths, and ever-
changing recommendations and guidelines. To layout a framework for
investigating crop improvement for CDP, terminology commonly encoun-
tered in the area is briefly reviewed.

2.1.1. Food and health terms

Communication in this field can sometimes be unclear because the terms
are numerous, have both similar and sometimes vague definitions, and are
therefore often used interchangeably. Some of these terms will not appear
anywhere else in the chapter but are included to demonstrate that language
in nutrition and health has a powerful role in influencing the science and
public opinion:
(a) Essential nutrients are those substances that cannot be made in the human
body but that are required for normal cellular function. The absence of
essential dietary nutrients results in defined disease syndromes.
(b) Nonessential nutrients are not required for life, but they may promote
health. As discussed by Burlingame, the definition of a nutrient is up for
debate (Burlingame, 2001). Many chemical constituents of plant foods
are termed nonessential nutrients since they may positively impact
health; such chemicals are sometimes also referred to as phytonutrients.
(c) Phytochemical is a term that connotes health benefit based on colloquial
usage; however, in this chapter it will simply refer to plant chemicals.
Often the term phytochemical is associated with an antioxidant function,
but this practice is misleading.
(d) Dietary supplement is a term that infers a need to add a component to the
diet that is lacking. At one time, supplements were primarily comprised
of only essential nutrients such as vitamins and minerals. Currently, a
wide array of essential and nonessential nutrients can be purchased as
dietary supplements. The U.S. Food and Drug Administration regu-
lates dietary supplements as foods, not drugs, and therefore, there is
limited regulation of the dietary supplement industry (Sadovsky et al.,
2008). Of note, assumptions and claims regarding the positive health
impact of antioxidant supplements are being challenged. Studies have
shown supplements can be associated with increased risk of mortality
(Bjelakovic et al., 2007).
Biomedical Agriculture 9

(e) Functional food is a term lacking a standard definition but generally

implies a food or food product containing components that promote
health. The term was established in Japan in the 1980s and has since
become embraced by the health sciences community (Hasler, 2002).
The term is primarily intended to (1) raise awareness of food’s role in
promoting health and (2) define markets for products to be sold (Hasler,
2000). However, the use of the word ‘‘functional’’ implies any food
with health benefit is a functional food. This creates problems in
differentiating functional and nonfunctional foods given that most
foods have some health-related nutrient content (Scrinis, 2008). Func-
tional food and the related term nutraceutical both imply some level of
enhanced, beneficial biological activity.
(f ) Nutraceutical was coined by DeFelice in 1989 (Kalra, 2003). While it
connotes the properties of a food having health benefit to prevent or
treat disease, it has no strict regulatory definition, as opposed to the term
pharmaceutical (Mollet and Rowland, 2002).
(g) Medicinal food is yet another term denoting biological activity associated
with health benefit; however, like the nutraceutical and functional food
areas, it is not well regulated. Of note, overt medicalization of the food
supply is not desirable, as this would imply foods have drug-like effects
(Lawrence and Rayner, 1998).
(h) Bioactive food components (BAFC) do not imply health benefit or
embrace a medical platform. The term simply denotes that a food
possesses a component, that when consumed, influences a particular
biological system. As such, any given food has numerous BAFC
(Kris-Etherton et al., 2004).

2.1.2. Examples of the need to clarify terminology

In general, terms associated with health benefits of foods were developed to
avoid the strict regulatory oversight which pharmaceuticals receive; how-
ever, efforts are underway to standardize health claims (Hasler, 2008).
Nonetheless, examples of confusion regarding terminology abound, but
three that are commonly encountered illustrate the importance of under-
standing terminology. Dietary fiber is plant matter that is resistant to digestion
in the intestinal tract and that is known to improve gut function and reduce
the risk for certain types of cancer (Qu et al., 2005). Dietary fiber has also
been shown to beneficially reduce blood lipid profiles associated with
atherosclerosis (Berg et al., 2008). Fiber is a good example of a food
component that fits the majority of definitions outlined above (Prosky,
2000). The use of multiple, vaguely defined terms can lead to the perception
that a fiber-containing product has effects that cannot be achieved through a
balanced diet (Mayo Clinic, 2007). Vitamin C (ascorbic acid) is a well-known
essential nutrient and enzyme cofactor. Additionally, vitamin C plays an
important role as an exogenous antioxidant. However, in some cases,
10 Matthew D. Thompson and Henry J. Thompson

consumers use vitamin C for medicinal purposes. This can distort the
understanding of scientists and consumers alike about the role of vitamin C
in health promotion and disease prevention, and of what vitamin C is
capable of doing when ingested in the diet as an essential nutrient (Naidu,
2003). Antioxidants have many established health benefits resulting from
their ability to act as reducing agents in biological systems. The damage
accumulated by free radical species has been associated with ageing and
many chronic diseases such as cancer and heart disease (Ames et al., 1993).
However, the mechanisms of bioactivity of many phytochemicals with
antioxidant activity is likely to be via their function as cell signaling agents
(Williams et al., 2004), not their activity as reducing agents. Yet this aspect
of chemical functionality, that is, the ability to regulate critical cell signaling
pathways, is frequently overlooked, in part because of misused or inade-
quate terminology. Unfortunately, terminology in the marketplace more
often has been used as a means to avoid regulatory issues and to market
products. As is evident from this review of terminology and brief commen-
tary, crop improvement for CDP will benefit most from clearly stated
objectives and known target endpoints where these aspects of the work
are defined using carefully chosen terminology.

2.2. Chronic disease prevention

2.2.1. Background
Human diseases can be broadly categorized into infectious diseases and
noninfectious diseases. In general, chronic diseases are noninfectious dis-
eases. As defined by the U.S. Center for National Health Statistics, a chronic
disease is one lasting for a duration in excess of 3 months (Centers for
Disease Control, 2008). According to the World Health Organization
(WHO), chronic diseases progress slowly and are of long duration. Chronic
diseases, such as cardiovascular disease, cancer, and diabetes, are the leading
causes of mortality both in the United States and around the world (Centers
for Disease Control, 2007; World Health Organization Global Report,
2008). As reported by the U.S. Centers for Disease Control, data collected
in 2007 indicated that chronic diseases, specifically diseases of the heart,
malignant neoplasms, cerebrovascular diseases, and diabetes mellitus
accounted for over 60% of all deaths in the US (Centers for Disease
Control, 2007). These same diseases, as well as chronic respiratory disease,
were also reported by WHO to account for 60% of all deaths worldwide
(World Health Organization Global Report, 2008). Globally, as summar-
ized in Table 2, 80% of chronic disease deaths occur in low and middle
income countries, almost half of chronic disease deaths occur in people
under the age of 70, and without intervention, 17 million people will die
prematurely this year from a chronic disease (World Health Organization,
2008). The economic burden associated with prevalent chronic diseases,
Biomedical Agriculture 11

Table 2 Chronic disease statistics from the World Health Organization

Chronic disease is responsible for 60% of all deaths worldwide

80% of chronic disease deaths occur in low and middle income countries
Almost half of chronic disease deaths occur in people under the age of 70
Around the world, chronic disease affects women and men almost equally
The major risk factors for chronic disease are an unhealthy diet, physical
inactivity, and tobacco use
Without action, 17 million people will die prematurely this year from a
chronic disease
One billion adults are overweight—without action, this figure will surpass
1.5 billion by 2015
22 million children under 5 years old are overweight
Tobacco use causes at least five million deaths each year
If the major risk factors for chronic disease were eliminated, at least 80%
of heart disease, stroke, and type II diabetes would be prevented; 40% of
cancer would be prevented
Source: World Health Organization, http://www.who.int/topics/chronic_diseases/en/.

that is, obesity, diabetes, cardiovascular diseases, and cancer, is enormous,

approaching a trillion dollars per annum in the US and growing at a rapid
rate (Eyre et al., 2004; World Health Organization, 2007; World Health
Organization Global Report, 2008). If the major risk factors, of which diet
plays a central role, were eliminated, at least 80% of heart disease, stroke, and
type II diabetes, and greater than 40% of cancers would be prevented
(World Health Organization Global Report, 2008). The prevalence of
these diseases is being driven by the global obesity epidemic, with obesity
acting as a gateway disease, that itself is associated with decreased longevity
(Centers for Disease Control, 2008; World Health Organization, 2007). In
general, chronic diseases cannot be prevented by vaccines and are not
completely reversed by medication (World Health Organization, 2003).
Health damaging behaviors, such as poor eating habits, physical inactivity,
and tobacco use, are major contributors to these highly prevalent chronic
diseases. As a result, chronic diseases are largely preventable since causality is
linked to environmental exposures that can be controlled by the individual
(Eyre et al., 2004; World Health Organization Global Report, 2008).
Excess body weight for height is the single most prevalent chronic
disease in the world. Not only is life expectancy reduced by obesity, but
also the risk for chronic diseases and their associated morbidities and mor-
tality is increased (Eyre et al., 2004; Kahn et al., 2005). It is quantified by
determining an individual’s body mass index (BMI), that is, weight (in kg)
divided by height (in m2). A BMI between 18.5 and 24.9 is considered
12 Matthew D. Thompson and Henry J. Thompson

within normal limits; a BMI between 25.0 and 29.9 is categorized as

overweight; a BMI between 30.0 and 34.9 is considered obese; and a
BMI greater than or equal to 35.0 is considered morbidly obese (IARC,
2002). Based on this system, obesity is easily determined and can be
monitored over time via the measurement of BMI. For simplicity, we
will refer to excess body weight for height as obesity for the remainder of
this chapter. In BMA, obesity is viewed as the most important chronic
disease to prevent because it impacts the development of the others so
profoundly. If food crop genotypes and food combinations can be identified
that assist individuals in preventing excess weight gain, then a significant
amount of the world’s chronic disease burden would be relieved. A list of
candidate crop-related weight prevention strategies is provided in Table 3.
Crops clearly have the potential to reduce obesity and its consequences,
including the risk for cardiovascular diseases, cancer, and type II diabetes,
through weight regulation alone. However, other mechanisms are normally
involved in the progression of chronic diseases.

2.2.2. The basis of biomarker-assisted screening for CDP:

Mechanisms and markers
One of the goals for the biomedical research community, in support of
BMA, is to provide agronomists with a set of tools that can be used to screen
crop genotypes and food combinations for CDP activity. To achieve this
goal, chronic disease risk must be reduced to a simplified, representative set
of biological features in animal and human pathophysiology that can be
assessed using chemical analyses and that are causally associated with disease
occurrence. The tools that result from this effort are referred to as biomar-
kers. The characteristics of useful biomarkers include (1) causal linkage to
the initiation or progression of the disease process, (2) concentrations

Table 3 Potential modes of action for food crops to reduce body weight and
risk of obesity

Mode of action References

Reducing levels of digestible energy Englyst and Englyst (2005)
High fiber content that adds bulk to the Burton-Freeman (2000)
diet and accelerates and sustains onset of
satiety
Reestablishing normal function of cellular Marshall (2006)
energy sensors
Altering gut microflora to promote Turnbaugh et al. (2006)
negative energy balance
Increasing nutrient density, maximizing Drewnowski (2005)
the nutrient to energy ratio
Biomedical Agriculture 13

change in response to changes in disease risk, (3) concentrations respond to

changes in the foods consumed, (4) easily assessed using validated chemical
assays, and (5) similarly affected in preclinical models for human diseases and
in the human disease itself. Identifying a panel of biomarkers that have
shared associations with the risk for cardiovascular disease, cancer, type II
diabetes, and obesity is based on the common mechanisms that underlie the
pathogenesis of these diseases (Biddinger and Kahn, 2006; Eyre et al., 2004;
Holmes et al., 2008; Marshall, 2006).

2.2.3. Common mechanisms and biomarkers

The goal of BMA is to reduce the risk of four seemingly unrelated chronic
diseases. The relationships between these diseases have become better
understood as data resulting from omics investigations has provided evi-
dence of a common pathogenic basis for their occurrence (Fig. 2) (Holmes
and Nicholson, 2007; Holmes et al., 2008; Li et al., 2008; Marshall, 2006;
Martin et al., 2007). Specifically, cardiovascular disease, cancer, type II
diabetes, and obesity are metabolic disorders with shared impairments in
both cellular processes and metabolism, although each disease also retains
unique characteristics. At the cellular level, the pathologies associated with
each disease display alterations in cell proliferation, blood vessel formation,
and cell death, that is, necrosis, apoptosis, and autophagy. Also common to
these diseases are alterations in glucose metabolism, chronic inflammation,
and cellular oxidation that is attributed to a common network of cell
signaling events that are misregulated in each of these disease states
(Marshall, 2006). In addition, emerging evidence indicates the modulation
of gut microflora predisposes an individual to each of the disease processes
(Li et al., 2008; Martin et al., 2007). Microflora appear to be able to exert
effects through either biosynthesis of new compounds or chemical trans-
formations of ingested ones, and as a consequence, influence exposure of
the host to gut microflora-associated endotoxins (Li et al., 2008; Martin
et al., 2007; Nicholson et al., 2008). Identification of a common set of
biomarkers for the shared pathogenic elements among these diseases is a
critical step in outlining a systematic approach to crop improvement.
A biomarker is objectively measured and evaluated as an indicator of
normal biological or pathogenic processes, or pharmacologic responses to a
therapeutic intervention (Packard and Libby, 2008). The substance is usu-
ally measured in blood or urine. The biomarkers relevant to BMA are
biological indicators of disease risk or disease presence (Table 4). The
information detailed in the following paragraphs provides a brief overview
of each biomarker class. Biomarker-assisted screening in animals on differ-
ent diets can be used to guide both crop genotype selection and the
identification of beneficial food combinations. Additionally, the same bio-
markers can be monitored clinically to determine efficacy of plant food-
based interventions in human subjects. Therefore, biomarker-assisted food
14 Matthew D. Thompson and Henry J. Thompson

Figure 2 Factors involved in chronic disease development. The pathogenesis of

cancer, cardiovascular disease (CVD), type II diabetes, and obesity have substantial
cellular and molecular interrelationships. As illustrated, consumption of a nutrient-
poor, energy-dense diet leads to altered glucose metabolism and insulin resistance. In
addition, Gram-negative bacteria in the gut flourish and die, leaving cell wall compo-
nents behind to enter the systemic circulation and result in a state of chronic inflamma-
tion. Glycation products are formed at increased rates due to elevated blood glucose and
may also lead to elevated levels of circulating inflammatory factors. Inflammatory
processes are one stimulus for increased production of free radical species in vivo.
Production of reactive species leads to oxidation of cellular components and can result
in DNA mutation and altered molecular function. In parallel, elevated levels of insulin
stimulate release of growth factors like IGF-1. Along with increases in available
glucose, this state of positive energy balance perturbs cellular energy sensing mechan-
isms. Dysfunction occurs as cells lose fine control of proliferation and death pathways.
Obesity results from a large number of known and unknown factors that elevate disease
risk. The cumulative and interdependent effects of many processes increase risk for the
development of chronic diseases. The aim of BMA is to develop crop genotypes that
have high chronic disease prevention (CDP) activity and high nutrient density. As
outlined, this may significantly reduce risk for disease.
Biomedical Agriculture 15

Table 4 Biomarkers associated with chronic disease risk

Biomarker class Chemical analyses

Glucose metabolism Fasting glucose
Fasting insulin
Hemoglobin A1c
Insulin-like growth factor-1, total and free
Inflammation C-reactive protein
Interleukin-6
Tumor necrosis factor-a
Oxidation 8-Hydroxy-2-deoxyguanosine
8-Isoprostane F2a
Oxygen radical absorbance capacity
Protein carbonyls
Endotoxemia Lipopolysaccharide, total and free

crop improvement has emerged as an essential component underlying the

development of the BMA framework:
(a) Glucose metabolism. Glucose is essential for life both as a primary source
of energy and as a building block that directly or indirectly supports the
biosynthetic processes required for growth and maintenance of cell
function. Consequently the supply of glucose to cells within the body
in mammalian species is tightly regulated. The pathogenic events that
occur in cardiovascular disease, cancer, type II diabetes, and obesity
involve alterations in glucose metabolism, a primary manifestation of
which is insulin resistance (Misciagna et al., 2005; Zieman and Kass,
2004). Insulin resistance causes increased circulating levels of glucose,
insulin, and insulin-like growth factors (Ezzat et al., 2008; Frasca et al.,
2008; O’Connor et al., 2008). Elevated levels of circulating glucose also
cause glycation of proteins, one of which is hemoglobin A1c (Giugliano
et al., 2008; Misciagna et al., 2007). Collectively, elevated levels of
fasting glucose and insulin and nonfasting levels of IGF-1 and hemo-
globin A1c are biomarkers for alterations in glucose metabolism asso-
ciated with chronic disease risk (Pirola et al., 2003; Soldatos et al., 2005;
Stumvoll et al., 2005).
(b) Inflammation. Inflammation is the body’s basic response to infection and
injury, but when the signals that regulate this process are continuously
activated, a chronic inflammatory process results. Chronic inflamma-
tion stimulates processes which underlie chronic disease development,
such as the increased oxidation of cellular macromolecules as reviewed
elsewhere (Schwartsburd, 2003). Obesity and insulin resistance are also
associated with chronic inflammation (Schenk et al., 2008). While the
16 Matthew D. Thompson and Henry J. Thompson

mechanisms are not completely elucidated, one hypothesis to explain the

association of insulin resistance with inflammation is that chronic hyper-
glycemia and insulin resistance lead to advanced glycation end products
that are able to bind to cell surface receptors that stimulate the production
of inflammatory cytokines (Lopez-Garcia et al., 2004). Three circulating
factors that are indicative of ongoing inflammation are interleukin-6,
C-reactive protein, and TNFa; they serve as biomarkers for chronic
disease risk (Casas et al., 2008; Coussens and Werb, 2002).
(c) Oxidative damage. Oxidative stress is caused by an imbalance between
the production of reactive oxygen species and a biological system’s
ability to readily detoxify the reactive intermediates or easily repair
the resulting damage. All forms of life maintain a reducing environment
within their cells which is largely preserved by enzymes and endoge-
nous reducing agents. Reactive oxygen species can be beneficial, as they
are used by the immune system as a way to attack and kill pathogens, as
well as participate in cell signaling (Martindale and Holbrook, 2002).
However, disturbances in the normal redox state can cause toxic effects
through the production of peroxides and free radicals such as hydroxyl
(OH
) and superoxide (O
2 ) radicals, hydrogen peroxide (H2O2), and
singlet oxygen (1O2) (Breimer, 1990; Cerutti, 1985; Halliwell and
Gutteridge, 1999), particularly in response to inflammation (Coussens
and Werb, 2002; Schenk et al., 2008). In humans, oxidative stress is
involved in the pathogenesis of a number of disorders including cardio-
vascular disease, cancer, type II diabetes, and obesity (Collins, 1998;
Cooper et al., 2007; Schleicher and Friess, 2007; Vincent et al., 2007).
Biomarkers of oxidative damage include 8-oxodG, a marker of DNA
damage (Cadet et al., 2002; Cooke et al., 2006), 8-isoprostane F2a, a
marker of lipid peroxidation (Milne et al., 2007), and protein carbonyls,
a marker of protein oxidation (Hwang and Kim, 2007; Shacter, 2000).
(d) Gut microflora. The human intestinal tract houses an ‘‘extended
genome’’ (Kinross et al., 2008), the microbiome. A complex symbiosis
influences human host metabolism, physiology, and gene expression
(Nicholson et al., 2008). Advances in microbiological analysis and
systems biology are now beginning to implicate the gut microbiome
in the etiology of cardiovascular disease, cancer, type II diabetes, and
obesity, in part by a process referred to as chronic (or metabolic)
endotoxemia (Cani et al., 2007). Endotoxemia is due to the absorption
of lipopolysaccharide (LPS) from the gut (Cani et al., 2008). This
endotoxin is continuously produced in the gut from cell wall compo-
nents of Gram-negative bacteria. Production and absorption of LPS can
be modulated via dietary effects on gut microflora composition and
inflammatory responses to LPS are influenced by obesity and insulin
resistance (Ley et al., 2006). The principal biomarkers for endotoxemia
are circulating levels of total and free LPS (Cani and Delzenne, 2007).
Biomedical Agriculture 17

In summary, for reasons not fully understood, chronic positive energy

balance and excess accumulation of body fat result in systemic changes in the
body such that the factors associated with physiological regulation of glu-
cose metabolism become dysfunctional; this is referred to as altered glucose
metabolism. As a component of altered glucose metabolism and fat accu-
mulation, the concentration of proinflammatory molecules in circulation
and in various organ sites begin to accumulate despite the lack of an external
inflammatory stimulus; this is referred to as chronic inflammation. Elevated
levels of reactive oxygen and nitrogen species can result, leading to the
oxidative damage of cellular macromolecules. A potential modulator of the
inflammatory condition is the presence or absence of populations of micro-
flora in the gut that can lead to increased systemic exposure to microbial cell
wall components that promote inflammation and cellular oxidation in the
body, a condition referred to as chronic endotoxemia. These four condi-
tions—altered glucose metabolism, chronic inflammation, increased cellular
oxidation, and chronic endotoxemia—are widely regarded as playing causal
roles in the initiation and progression of obesity, cardiovascular diseases,
cancer, and type II diabetes (Grundy et al., 2002).

2.2.4. Strategy for implementing biomarker-assisted crop

improvement for CDP
Biomarker-assisted crop improvement is envisioned as a dynamic process
that will evolve as the field of BMA matures. At the outset, three stages of
biomarker evaluation and use are envisioned. In the short term, one or more
biomarkers for each altered function associated with a disease condition
should be evaluated (Table 4). In the second phase, development of which is
ongoing, profiles of mammalian metabolites determined by high-
throughput LC or GC mass spectrometry platforms will be used for deter-
mining chronic disease risk (Nicholson et al., 2008). These profiles will
(1) have greater sensitivity to detect changes in disease risk; (2) have the
advantage of requiring a small sample of blood, urine, or tissue for analysis;
and (3) be available at a cost affordable for use in crop screening in animals as
well as for monitoring human populations. A third phase of biomarker-
assisted assessment is envisioned to include the use of genomics technologies
to categorize, more specifically, the nature of genetic predisposition of an
individual to chronic disease using functional polymorphisms (Ambrosone
et al., 1999; Kornman et al., 2004). The end goal is to determine crop
genotypes and food combinations that reduce chronic disease risk via
understanding how they affect pathogenic mechanisms involved in each
disease. Crop genetic and chemical diversity, as discussed in the next
section, are critical to understanding how to reduce disease risk by inhibit-
ing cellular and molecular mechanisms underlying chronic disease
processes.
18 Matthew D. Thompson and Henry J. Thompson

3. Agricultural Landscape
3.1. Genotypic diversity in crops
Progress in food crop improvement is driven by screening genotypes for
desired agronomic traits (Lenihan et al., 2004; Lindsay et al., 2004; Wu et al.,
2005). Worldwide, the total number of genotypes for a given food crop is
quite large, probably in excess of 1000 genotypes per species (Food and
Agriculture Organization, 1998). For some crops, core collections have
been or are being assembled from which to draw germplasm for evaluation
for traits of agronomic interest (Fowler and Hodgkin, 2004); rice is a model
crop in this regard (Londo et al., 2006; McNally et al., 2006; Monna et al.,
2006). However, there have been no systematic efforts to tap global crop
diversity for CDP. One only has to review the accomplishments of natural
products discovery programs to recognize the potential of this approach
(Guilford and Pezzuto, 2008; Kinghorn et al., 2004; Park and Pezzuto, 2002).
Crops have undergone a long process of selection for agronomic traits
during domestication and genetic improvement for commercial use (Stuber
and Hancock, 2008). The scientific basis for proposing to screen diverse
food crop germplasm for CDP activity derives from the bottleneck theory
of domestication that estimates as much as 95% of the variation in germ-
plasm for many traits was lost during that process (Ahn and Tanksley, 1993;
Frary et al., 2000; Gepts and Hancock, 2006; Gepts and Papa, 2003;
Lippman and Tanksley, 2001; Ross-Ibarra et al., 2007). Thus, one could
hypothesize that significant variation will be identified among genotypes
within a crop for CDP if sufficiently diverse germplasm resources are
evaluated. On the other hand, if only highly related commercial genotypes
are screened for CDP, it is likely that the genotypes tested will be found to
have limited variation for CDP. The prevailing practices for dietary assess-
ment in the biomedical sciences assume that different genotypes within a
food crop will have similar effects on CDP (discussed in Section 1).
Therefore, little has been done to engage agronomists to challenge this
assumption and take advantage of plant biodiversity (Keil, 2008). In view of
this, a critical step in successful implementation of BMA is that a diverse
collection of crop genotypes be evaluated; failure to do so will limit the
potential of crop-based research for CDP.

3.2. Chemical basis for CDP

The basis for CDP by a food crop is hypothesized to be through the crop’s
normalization of glucose metabolism and cellular oxidation and its inhibi-
tion of chronic inflammation and endotoxemia (Section 2). While dysre-
gulation of a common cell signaling network has been reported to underlie
Biomedical Agriculture 19

these metabolic alterations (Biddinger and Kahn, 2006; Marshall, 2006;

Schenk et al., 2008), that network has multiple regulatory inputs suggesting
that a single agent ‘‘magic bullet’’ is not likely to have the same impact on
CDP as multiple chemicals that target an array of relevant molecular targets
(Duthie et al., 2003; Karamouzis and Papavassiliou, 2004). This argument is
supported by the success of multiagent drug-based approaches to the man-
agement of chronic diseases like cardiovascular disease, cancer, and diabetes
where magic bullets alone failed but were found to be more therapeutically
effective when combined (Liby et al., 2007; Sporn, 2006). Since BMA is
based on food serving as the delivery vehicle for a milieu of health-
promoting chemicals, the goal is to identify a specific pattern of biosynthetic
activity associated with CDP for each crop investigated. The approach that
affords the richest opportunity to discover traits for CDP is unbiased
chemical profiling of a diverse population of crop genotypes.
As a starting point in this process, it is necessary to establish an initial
selection of genotypes of a crop for evaluation, whether that material has
been organized based on knowledge of the crops center(s) of domestication,
its genetic lineage, or other strategies that agronomists use to categorize a
crop’s available germplasm resources. From this selection, the chemical
diversity of the collection must be determined.

3.3. Assembling a test collection of a crop’s genotypes

The objective of the process described below is to obtain a limited number
of chemically diverse crop genotypes for initial screening in animal models
for human disease as illustrated in Fig. 3. By evaluating genotypes that are
the most chemically divergent, there will be a higher probability of identi-
fying chemical profiles that have large differences in CDP activity. The
following steps are recommended.

3.3.1. Collecting the crop genotypes

The ideal situation is to obtain genotypes from a core collection in which
one or more techniques have already been used to establish how the
available genotypes relate to one another. If a core collection is not avail-
able, then an effort should be made to obtain genotypes from distinct
geographical locations from around the globe and to include wild relatives
for the crop (Gepts and Papa, 2003; Keil, 2008). Chemical profiling can be
performed on as little as 10 g of material.

3.3.2. Deciding on method of preparation and extraction

Most food crops are consumed in more than one way. There is no correct
preparation/processing method, but there should be a strong rationale for
method selection. The method must be uniformly and reproducibly applied
to all samples of the crop that are evaluated. The reason for proposing to
20 Matthew D. Thompson and Henry J. Thompson

Figure 3 Crop selection. This figure is a depiction of the process proposed in Section 3
for identifying crop genotypes that differ in genetic and chemical composition. The
illustration is based on actual data on crop genotypes. Panel A illustrates genetic
relationships among 19 genotypes from a model food crop; genotypes are noted as
C1–C19. Panel B shows a subset of the crop genotypes shown in panel A that were
selected for metabolite analysis because they were in different genetically defined
clusters. The panel B crop genotypes were subjected to LC/MS-based chemical
profiling. Note that crop genotypes cluster based on chemical similarities; these clusters
Biomedical Agriculture 21

evaluate the crop as it is processed for human consumption is that once an

effective genotype is identified, there is more relevance in determining how
it works in the form prepared for human consumption. From there, one can
work backwards to determine if there are additional means of further
enhancing activity in all the steps involved in getting the crop from the
field to the table.
There are a large number of published methods on food crop extraction
(Robbins, 2003; Wu et al., 2004a); there is no single correct method.
However, the method must be well justified, practical, give uniform
extraction efficiencies, and be appropriate for unbiased chemical profiling
using a LC/MS or GS/MS analysis platform. Because unbiased chemical
profiling is desired, the analytical approach must be comprehensive, asses-
sing the 14 classes into which plant secondary metabolites are categorized
(Table 5). We recommend consideration of the modified Bligh–Dyer
extraction technique (Fischer and Sana, 2007).

Table 5 Major classes of plant secondary metabolites

Alkaloids
Triterpenes, Saponins, Steroids
Sesquiterpenes
Diterpenes
Flavonoids
Polyacetylenes
Phenylpropanes
Monoterpenes
Polyketides
Nonprotein amino acids
Tetraterpenes
Cyanogenic glycosides
Glucosinolates
Amines
Source: Wink (2003).

were determined by principal components analysis (PCA). Based on genetic and

chemical analysis, two of the three circled crop metabotypes, C1 and C10, would be
evaluated in an animal model for assessing effects of the crop on chronic disease risk
biomarkers because both were genetically and chemically distinct. The C16 genotype
from the group 3 genetic cluster in panel A was distinct from C18 but further chemical
analysis, shown in panel B, revealed C16 was not chemically distinct from C18.
Therefore the C16 genotype may not be as ideal for initial evaluation in animals.
(This is an original figure using our own data)
22 Matthew D. Thompson and Henry J. Thompson

3.3.3. Analysis
Because many analytical options are available, we strongly suggest the use of a
core facility that routinely profiles plant extracts. This enables working with
an analytical team that uses a standardized analysis platform, which can better
guarantee elution time and mass consistency. This then allows one to use a
library of compounds, validated for the standardized platform, to obtain
chemical compound identities from chromatographic features (Dixon et al.,
2006). Unsupervised multivariate analysis techniques are used to determine
the degree of relatedness of various genotypes. Multiple workflows are
available for this purpose depending on the instrumentation used to generate
chromatographic data and the bioinformatics support that is available. Gen-
eral steps include subjecting the chromatographic feature data to normaliza-
tion, filtration for the presence of multiple ions, calculating the magnitude of
fold differences and/or statistical significance of fold difference, and
subsequent principal components analysis.
If there is little or no separation among the genotypes selected for
analysis for chemical features (profiles), the process of genotype selection
should be repeated using more diverse germplasm with likely greater varia-
tion in presumptive chemical composition. If the decision is made to move
the work to the next step, then a well-justified process needs to be used by
which to select one or a few genotypes from each grouping of genotypes for
further analysis in animals.
The ultimate goal of this process is identification of biosynthetic profiles
that have CDP activity in preclinical models and the use of validated profiles
to (1) screen additional selections for greater CDP activity; (2) screen other
crops for CDP activity; and (3) evaluate food combinations for comple-
mentary, additive, and/or synergistic CDP activity. While there is no direct
way to screen germplasm for CDP activity at this time, the approach
described here has the potential to evolve into a high-throughput method-
ology, the principles for which are reviewed and discussed elsewhere
(Buxser and Chapman, 2007; Gagarin et al., 2006; Kevorkov and
Makarenkov, 2005; Walters and Namchuk, 2003).

3.4. Extending chemical profiling to food crop combinations

The occurrence of crop genetic diversity is suggestive of the presence of
different patterns of chemical biosynthesis within plants. For many years,
there has been interest in the potential value of chemical profiling of plants
to assist with plant taxonomy, a field referred to as chemotaxonomy. Wink
(2003, 2008) has provided excellent reviews of plant chemical diversity and
taxonomy. From such work has emerged an understanding that plants in
different botanical families can have more divergent profiles of chemical
constituents than those within a family. Further, plants within a botanical
family tend to utilize specific classes of chemicals for defense against diseases,
Biomedical Agriculture 23

pests, and other plants as solutions to support their survival. Plants produce an
array of antimicrobial chemicals and pesticides as well as chemicals that inhibit
the intrusion of other plants into their ecological niche (Bais et al., 2003;
Weir et al., 2004). The chemicals that mediate these responses undoubtedly
modulate the activity of cell signaling pathways in targeted organisms;
interestingly, many of these signaling pathways are conserved in mammalian
species (Prithiviraj et al., 2005). Consequently, one can reasonably hypo-
thesize that plant chemicals have the potential to impact human disease
mechanisms that share molecular pathways in common with naturally occur-
ring molecular targets for phytochemicals, that is, plant chemicals which offer
plant-related protection against microbes, pests, and other plants may also
have activity against chronic diseases in animals (Prithiviraj et al., 2005).
As such, an understanding of plant chemical diversity and the plant’s natural
molecular targets may be leveraged in a systematic manner to provide to
the consumer an entire array of diet-derived plant chemicals with proven
bioactivity in nature. Combinations of foods that offer complementary
chemical profiles may increase the capacity to protect against a spectrum of
chronic diseases. Thus, we recommend investigating different botanical
families to achieve BMA goals, and in so doing, identify and implement
new recommendations for dietary patterns (food combinations) for CDP.

3.5. Other considerations

3.5.1. Genetic modification of crops
Developments in producing genetically modified organisms (GMOs), where
introduction of specific genes into plants is done to achieve new functional-
ity, have dramatically increased the opportunities to improve crops (Chassy
et al., 2005; Food and Agriculture Organization, 2008). There are a host of
issues that have been raised about the potential impact of GMO and those
questions and concerns are embodied in a number of standards for GMO
introduction into a given environment and country (Chassy et al., 2005;
Food and Agriculture Organization, 2008). When GMOs are food crops,
consumers, in particular, have voiced concerns about potential health impact.
Regardless of the science supporting or refuting these concerns, there are
other reasons to pursue traditional breeding approaches within BMA at this
time (1) single gene, single chemical solutions are not likely to be efficacious
for CDP; (2) introduction of one gene is likely to alter the activity of other
genes, leading to changes in patterns of biosynthetic activity associated with
CDP, both positive and negative; (3) benefits from a GMO crop may be lost
when combined with other foods in a typical diet, hence negating the effort
that went into producing the GMO crop; and (4) altered agronomic char-
acteristics of the GMO may diminish the likelihood that it will be widely
grown. These issues have many parallels to those encountered in the field of
biofortification (Nestel et al., 2006).
Exploring the Variety of Random
Documents with Different Content
 2/6 THE SOUTHWICK GENEALOGT. 1275. Catharine Q?,
born Nov. 10, 1826; married Seth T. Aldrich. Nov. 16, 1850. 1276.
Hannaii Smith', born April 30, 1828; married William P. Holder, Apiil
16, 1850. 1277. Mary Martha', born Nov. 8, 1830; married, Aug. 10.
1864. Henry Babcock, died March 8, 1868. 127S. Lydia Anna', born
Feb. 19, 1836; married Dr. George Billiard. 313. Enoch SoUTHWICK^
(John', Jonathan', Daniel", Daniel, Lawrence'), son of John and Chloe
A. (Bartlett), born June 7, 1776, died Dec. 5, 1864. Married, Dec. 10,
1800, Wait Arnold, daughter of EHsha Arnold, of Leicester, Mass.,
born Nov. 12, 1780, died Sept. 16, 1859. He was a farmer at
Uxbridge, Mass. Children : I278«. Lydia', born Sept. 10, 1801, died
Nov. 27, 1S22. Unmarried. 1279. Elisha Arnold', born May 31, 1805;
married, July, 1831, Athaline Inman, at Smithfield monthly meeting,
R. I. He was a wheelwright, and settled at Uxbridge, Mass. 1280.
Israel Mowry', born Aug. 22, 1809; married Lucy H. Sayles, June3,
1840. He is a machinist, lives at Uxbridge. Mass. 1281. Thomas
Mussey', born March 9, 1812 : married Lavina Mowry. 1282. Joseph
Bartlett', Nov. 7, 1813, died Dec. 24. 1879. Unmarried. 497. George
SoUTHWICK^ (John', John\ John'', John'. Lawrence'), son of John 3d
and Eunice, born 1750, was killed at the battle of Lexington, April
19, 1775. Married Hephzibah Burrill, July 9, 1769. Children:
 I SIXTH GENERATION. 277 1283. Hephzibah', born Feb. 18,
1770. 1284. Lydia'. born June 5, 1771. 1285. George 4th^, born
June 3, 1773, died Jan. 7. 1846. 1256. Joseph', born April 21, 1775;
not mentioned in grandfather John's will, 1785. 310. Eber
Southwick", John', Jonathan*, Daniel', Daniel, Lawrence' ) , son of
John and Chloe A. ( Bartlett) , born Nov. 27, 1768, died Nov. 5,
1856. Married first, Marcy Cass, born 1772, died April 17, 18 14,
aged 42 years; second, Freelove Usher, born 1794, died Aug. 9,
1844. Children: 1257. Ebenezer Cass', born Dec. 3, 1803; married
Sarah Ann Luther. 1288. Eber Bartlett', born Oct. 15, 1806, died May
30, 1812. 1289. William Riley', born May 25, 1809, died April 22,
1814. 1290. George Stanford', born Feb. 28, 1813 ; married Maria
Morse. Second wife, Freelove Usher. One child : 1291. Diana', born
June 3. 1815, died Oct. 23, 1838. Married Emer Smith. ;?09. Lucy
S0UTHWICK^ (John', Jonathan*, DanieP, Daniel", Lawrence'),
daughter of John and Chloe A. (Bartlett), born April 22, 1767, died
Dec. 17, 1805. Married, Dec. 5, 1787, David Green, of Uxbridge,
Mass. Children : 1292. Mary', born 17S6. Married Joseph Holden, of
Bolton. Mass. 1293. Jabez', born Dec. 20, 1791, died Oct. 8, 1864.
Married first, Nancy Brown, 1815 ; second, Philadelphia Cook, Sept.
30. 1830.
 278 THE SOUTH WICK GENEALOGY. 1294. Hannah^, born
1798. 1295. James'', born April 15, 1800; married Lo\ici Barton, of
Chatham. N.Y. Thej had one child. Jannette. 307. Elijah
SoUTHWICK^ (Jonathan', Jonathan\ Daniel^. DanieP, Lawrence'),
son of Jonathan and Judith (Mussey), born Nov. 6, 1768, died April
6, 185 i, at Lenox, Madison Co., N.Y., aged 83 years, 8 months.
Married, about 1790, in Richmond, R.L, Ehzabcth Bentley, daughter
of Gideon Bentley, of Point Judith, Washington Co., R. L, born Feb. 6,
1770, died Aug. 6, 1843, at Oneida Lake Village, Madison Co., N.Y.
Children : 1296. Gideon Bentley^, born Sept. 8, 1791, died March
14. 1872. Married, Dec. 16. 1816, Hannah Ennis. born Dec. 22,
1789, died Jan. 14. 1868. 1297. Mary', born 1793, died on Great
Island in Salt Lake, South Kingston, R. I. Married Elias Carpenter.
129S. Nathan'', born 1795 ; married Mary Kenyon of Point Judith, R.
I., and settled at Newfield, Conn. 1299. Daniel Champlin', born 1797.
died of consumption at Point Judith, R. I. 1300. Lyman', born 1799;
married and settled in Florida. 1301. Remington", born Jan. 8, 1805,
at Richmond, R. I., died Oct. 31, 1862, at Newport, R. I., with
consumption. Married, April 14, 1827, Celinda Whitford, at South
Kingsford, R. 1. 1302. Hannah', born Aug. 22, 1S08, died July 18,
1844. Married, Sept. 20, 1827, Varnum Ennis. born Oct. 15, 1799,
died Oct. 20, 1853. 1303. Bradfoi'd', born 1812; married. 1836,
Catharine Antonio De Medicis, at St. Augustine, Florida, born Nov.
12, 1814. 818. Lavinia SoUTHWICK^ (John', Jonathan', Daniel",
DanieP, Lawrence'), daughter of John and Chloe A. (Bartlett), born
Jan. 26, 1786; married, Nov. 26,
MRS. ELLIS ALBEE.
 S/A'TH GENERATION. 279 1827, Ellis Albee, of Uxbridge,
Mass., was a farmer. Children: «304. Laura Southwick', born May 16.
1829, died Jan. 25, 1847. 3305. Ellis Albee, Jr.', born May. 1830;
married. Nov. 24, 1853. Sarah J. Southwick, a teacher. They had
three children, viz.: Louis Fremont, born Oct. 16. 1856; Percy
Sumner, born Feb. 18, 1859, died Nov. 2, 1877; Everett Ellis, born
Feb. 18, 1859: he and his brother Percy were twins. Lavinia
S()L'TH\VK■K^ daughter of John and Chloc A. (Bartlett) Southwick,
was born in Mendon, Mass., Jan. 26, 1786. She was noted for her
strong mind, excellent judgement and strict adherence to principles
of right. She learned the tailor's trade of her brother-in-law, David
Greene. After she completed her apprenticeship, she set up in
business for herself, cutting, making and furnishing goods,
emplo}ing man}' to work for her, havang taught twenty-seven girls
the trade. She was very thorough, conscientious and prompt in her
work. Her fame was not merely local, but extended through many
towns, people coming from a great distance to employ her instead of
those near by. Her peace principles were very firm ; when desired to
put a pocket in some garments to carry a weapon of war, she utterly
refused to do it. She succeeded in her business beyond her
expectations and continued in it until she was forty-one, when she
married. 312. John Southwick®, (John', Jonathan', DanieP, Daniel,
Lawrence'), son of John and Chloe A. (Bartlett), born Aug. 29, 177 1
, died July 12, 1857. Married
 2So THE SOUTHWICK GENEALOGT. first, Jan. 7, 1795,
Anna Callum, born April 5, 1774. died April 3, 1825; second, Mary M.
G. Bellmer. Children : 1306. Smith Southwick". born Oct. 7, 1796,
died Nov. 25, 1824. 1 307. William Arnold", born April 17, 1797 ;
married Betsey Gurney, 1817. 130S. Oliver Bartlett', born March 19,
1799; married Marj O. Smith, Nov. 22, 1832. 1309. Hannah Galium",
born March i. 1801 ; married first, Phineas Underwood ; second,
Jacob Aldrich, 1839. 1310. John', born Nov. 5, 1804; married first.
May 5, 1836, Harriet Walker, of Charlestown, Mass.. died 1840:
second, Louisa Richardson, Jan. 15, 1843. 131 1. Lucy Green', born
Nov. 11, 1807; married Cyrus Barker. 1312. Ann Galium', born March
16, 1810; married George F. Read, of Salem, Mass. 1313. Abigail
Bartlett', born Jan. 28, 1812 ; married, Jan. i, 1S35. Henry V. V.
Blanchard, of Gharlestown, Mass. John lived at Charlestown, Mass.,
and was in the employ of government at navy yard there, he bought
and sold much property at Charlestown, from 1 802 to 1 81 8, as per
records of deeds and mortgages there as per " Wymans-
Genealogies and estates of Charlestown, Mass.," he was also the
proprietor of the only woollen factory ever in Charlestown, and did a
prosperous business until the war of 181 2 when he was obliged to
abandon it on account of the war troubles. ;3i4. Amasa
S0UTHWICK^ (John", Jonathan', DanieP. DanieP, Lawrence'), son of
John and Chloe A. (Bartlett,) born March 5, 1778, died at Uxbridge,
Mass. Married, Nov. i, 1800, in Friend's Meeting House at
 SIXTH GENERATION. 28 1 Newport R.I.. Alice Chase,
daughter of Peter and Hepzibah (Mitchell) Chase.* of Newport, R. I.,
born May 19, 1781, died 1874, aged about 94. Sept. 13, 181 3, Alice
(Chase) Southwick and three children received a certificate to go to
Rhode Island monthl\' meeting. Children : 1314. Eliza Ann', born at
Uxbridge. Aug. S, iSoi ; married, Aug. 8, i8i8, in Friend's meeting
house. Osborn Mowrv. of Newpoi-t, R. I. 1315. James", born at
Uxbridge, March 19, 1S03. died Sept. 29. 1878, at Southington,
Ohio. 1316. Hepzabeth", born at Uxbridge. Julv 19, 1807; married.
Jan. 19, 1835, Charles U. Wood, of Hadlej. Mass. 1317. Amasa, Jr.'',
born at New Lebanon. N.Y.. Nov. 2^. 1810. died July 19, 1825, at
Pelham, Mass. 1318. Peter', born at Newport, R. I., July 23, 1813,
died Nov. 1. 1851. at Palmer. Mass. Married Mary Boynton. of Palmer.
Mass. 1319. Gilbert', born at Pelham, Mass., May 24, 1822; married.
Oct. 31, 1849, Alice M. Kellogg, at Amherst, Mass. 317. George
Southwick*, (John', Jonathan", Daniel^ DanieP, Lawrence'), son of
John and Chloe A. (Bartlett), born Feb. 28, 1784, died June 20,
1867. Married, Nov. 29, 1804, Sally Daniels, daughter of Moses and
Abigail (Aldrich) Daniels, born Nov. 27. 1784, died Sept. 6, 1842.
Children: 1320. Moses Daniels', born July 9, 1805, died June 9,
1875. Married first, Adeline Fisher; second, Lorana Farnum. He was
a doctor and highly esteemed at Millville. where he practised; he was
a member of the Massachusetts Legislature. * Peter Chase came
over from England in company with his brothers William and Aquilla.
Peter and Hepzibah (Mitchell) Chase had two children, James and
Alice. James died a bachelor.
 282 THE SOUTH WICK GENEALOGT. 1321. Baruch A.', born
March :;8, 1807, died July 16, 1871. Married. Nov. 6. 1S33. Marj
Fowler, of Northbridge. He left three children in Illinois. 1322. Mary
Ann', bom Feb. 10, rSii ; manned Christopher Daniels, 1S39. 1323.
George B.', born Oct. 27, 1S13; married first, Amanda M. Southwick,
Feb. 2, 1837; second, Marj Green, Aug. 7, 1842. 1324. Louisa", born
June 10, 1816, died Aug. 18. 1816. 1325. Andre', born Dec. 1,1817;
married, Feb. 26, 1843, Betsev W. Taft, born Nov. 28, 181 5. 1326.
Maria Louise', born Oct. 8, 1824: married Davis Bills. July 17. 1858.
No children. George Southwick, son of John and Chloe (Bartlett)
Southwick, was born July 6, 1784. He was a man of good intellectual
abilities, much above the average. He was fond of reading and
always selected books to read which were written by firstclass
writers, he was a great admirer of the best English poets and
classical literature and consequently became a good critic, although
very unpretentious. While a young man he taught school, he became
a farmer and was a very industrious, prudent and prosperous man,
and was very much esteemed by those who knew him ; he was an
honored member of the Society of Friends. Wait SoUTH\\TCK^
(John^ Jonathan\ Daniel"'. Daniel^, Lawrence'), daughter of John
and Chloe A. (Bartlett), born Jan. i, 1782, died July 13, 1841.
Married, Feb, 2, 1803, in Friend's Meeting, Savel Aldrich, a farmer, of
Uxbridge, Mass. Children:
 SIXTH GENERATION. 283 1327. Lavinia Southwick', born
Sept. 11, 1804, died Aug. 28. 1S74. Married, Nov. 17, 182S, John A.
Smith, a fanner of Uxbridge, Mass., they had three children, viz. :
Albert", born 1832, died young; Albert S.**, born May 28, 1S34,
died Dec. 5, 1854; Ellen S.®, born March 3, 1837, died Nov. 10.
1S70. Albert S. Smith*, married, June 17, 1865. Marcilia Richardson,
of Woonsocket, R. I., had three children, viz. : Elma C.^ born July
27, 1858; Katy ¥.», born May 2. i860; Mary C.^, born July 2, 1862.
Ellen S. Smith*, married. May 3, 1857, Levi S. Cook, of Mapleville, R.
I., had two children, viz. : Garton^, born Feb. 15, 1S58; Martha M.",
born Nov. 20, 1862. Garton Cook', married, March 3. 1877, Katy
Cooper, of Providence, R. I., had three children, viz. : Howard A. '°,
born July 29. 1S7S; Albert S."^, born Aug. 30. 1S79; Lulu S."^, born
May 12, iSio, died aged 3 days. 1328. Lucy Green', born Feb. 24,
1S06, died Aug. 30, 1856. Married Richard Henry. 1329. Alvira
Maria', born Sept. 16, 1S07, died Jan. 20, 1875. Married Josiah
Fisher, had two children, viz. : Eldora*. born Sept. 10, 1865 : Ernest
Savil*, born Oct. 24, 1S66. 389. George South WICK^ (DanieP,
Lawrence', Lawrence"*, DanieP, Lawrence'), son of Daniel and
Jemima (Bartlett), born Feb. 14, 1800; married, 1827, Louisa
Tenney, in Danby, Vt., deceased. He was a school teacher, at Collins,
Erie Co., N.Y. Children : 1330. Mary', born May 20, 1828; married
Aug. 20, 1845. 133 1. Aaron', born March 8, 1830. 1332. Melissa',
born Feb. 14, 1836. 1333. Jacob', born Feb. 4, 1839; deceased.
1334. Emma', born Feb. 21, 1S44; married Gilbert Mayo, Aug. 8.
1862. 1335. Sarah', born May 26, 1S51 ; married Coburn Blake, Aug.
29, 1869. 387. Sarah SoUTHWICK^ (Daniel', Lawrence', Law 
 284 THE SOUTHWICK GENEALOGY. rence^, Danie^^
Lawrence'), daughter of Daniel and Jemima (Bartlett), born 1795;
married, July 1814, Luther Colvin, deceased. Children : 1336. Caleb',
born probably in 1815; deceased. 1337. Prussa'', born probably in
1817; deceased. 1338. Benoni''', born probably in 1819; deceased.
1339. Mary', born probably in 1821 ; deceased. 1340. Henry', born
probably in 1823 ; deceased. 1341. Lydia', born probably in 1825.
1342. Moses', born probably in 1827. 390. Judith SouTHWICK^
(DanieP, Lawrence', Lawrence'\ DanieP, Lawrence'), daughter of
Daniel and Jemima (Bartlett), born 1801 ; married John Roberts.
Children : 1343Susan Anna". Deceased. 1344Ruth'. 1345Jemima'.
Deceased. 1346. Austin'. 1347Rachel'. 1348. Chloe'. Deceased
1349Sally'. 1350. William'. 393. Lydia SoUTHWICK^ (Daniel'
Lawrence', Lawrence^ DanieP, Lawrence'), daughter of Daniel and
Jemima (Bartlett), born 1807 ; married Calvin Hitchcock, of Brant, N.
Y. Children : 135 1. George'. 1352. Abigail'. Deceased. 1353. Helen'.
Deceased.
 SIXTH GENERATION. 285 395. Maria South WICK^
(DanieP, Lawrence*, Lawrence'\ DanieP, Lawrence'), daughter of
Daniel and Jemima (Bartlett), born Jan. 9, 1809; married Austin
Shaw. Children : 1354. Emily'. 1355- Harry'. 1356. Edgar'. 391.
Patience SouTHWICK^ ( Daniel', Lawrence*, Lawrence^, DanieP,
Lawrence'), daughter of Daniel and Jemima (Bartlett), born 1803;
deceased. Married Ebenezer Holton, of Dorset, Vt., died 1833.
Children : 1357- Elijah'. 1358. Plynn'. 1359. Eliza'. 1360. Lydia'.
1361. Rachael'. 388. Anna SouTHWICK^ (DanieP, Lawrence*,
Lawrence^, DanieP, Lawrence'), daughter of Daniel and Jemima
(Bartlett), born 1797; married David Clark; deceased. Children :
1362. Abigail'. 1363. Joseph'. Deceased. 1364. Maria'. 1365. Naomi'.
397. Daniel SouTHWICK^ (Daniel*, Lawrence*, Lawrence^, DanieF,
Lawrence'), son of Daniel and Jem 
 286 THE SOUTH WICK GENEALOGY. ima (Bartlett) ;
married first, Nov. i6, 1853, SallyAnn Fisk, and went to Brant N.Y. ;
second, Dec. 24, 1859, Lydia Sisson, of Oueensbury, Warren Co.,
N.Y. He was a farmer. One child : 1366. Jemima". 399. Jacob South
WICK^ (DanieP, Lawrence', Lawrence'\ DanieP, Lawrence'), son of
Daniel and Jemima (Bartlett), born May 20, 1820; married Mary A,
Wealthy, Jan. 11, 1857. He settled on his father's homestead in
Brant, N.Y. ; occupation, shoemaker, farmer, blacksmith and and
carpenter. Children : 1367. John D.'', born Dec. 3, 1857; deceased.
136S. Phebe', born Jan. 18, i860. 1369. George'', born Dec. 6, 1S62.
1370. Alice O.', born Aug. 10, 1866. 1371. Anna K.'', born Aug. i,
186S; deceased. 1372. Anna M.', born April 9, 1870. 1373- John D.'',
born Dec. 10, 1879. 392. Asa S0UTHWICK^ (DanieP, Lawrence',
Lawrence^ Daniel, Lawrence'), son of Daniel and Jemima (Bartlett),
born March 19, 1805; married, 1827, Sarah Tenney, of Danby, Vt.,
went to Brant, N. Y. He is a cheese manufacturer at Burbank, Wayne
Co., Ohio. Children : 1374. Artemas R.', born 1828; married Ann
Widafield, 1850. 1375. Clark S.', born 1831 ; not married, lives with
Naomi. 1376. Naomi^, born 1839; married Harrison Tajlor, 1862.
 SIXTH GENERATION. 287 394. Nathan South wick*,
(Daniel*, Lawrence*, Lawrence^ DanieP, Lawrence'), son of Daniel
and Jemima (Bartlett), born April 19, 1808, died Sept. 22, [867,
killed by a falling tree. Married, Feb. 22. 1832, Clarinda Hall. He was
a farmer. Children: 1377. Mercj Ann', born July 13, 1834. .1378.
Melissa', born July 19, 1849. 493. Mercy SoUTHWICK^ (George*,
John', John^, John". Lawrence'), daughter of George and Sarah
(Sitchell), born March 19, 1769, deceased. Married Joseph Brown.
Children : 1379. Betsej'. 1380. John'. 13S1. Daniel'. 1382. Joseph Jr.'
1383. George'. 1384. Sarah or Sallej'. 1385. Rebecca'. 1386. Mercy'.
496. Mary Southwick', (George", John', John-\ John", Lawrence'),
daughter of George and Sarah (Sitchell), born June I 5, 1777 ;
deceased. Married Robert Wilson. Children : 1387. Samuel'. 1388.
Mercy'.
 288 THE SOUTH WICK GENEALOGT. 462. Cassandra South
wick^, (Josiah', John\ DanieP, Danic^^ Lawrence*) daughter of
Josiah and Elizabeth, born March 2, i/Si.died Dec. 25, 1819. Married,
Oct. 29, 1812, Stephen Nichols,* son of John Nichols, born Aug. 15,
1770, died Dec. 17, 1846. Children: 1389. George", born Jan. 12,
1814; married Lydia Horton. 1390. Stephen', born Jan. 4, 1815, died
Feb. i, 1828. aged 13 years. 28 days. 1391. Abigail Moulton'. born
Oct. 9, 181 7. 570. Arn()L1) Southwick", (Lemuel", Jonathan',
SamueP, John^ Lawrence'), son of Lemuel and Mary (Spencer), born
June2,i8o2; married, Aug. 5, 1838, widow Sally Ellis, born Nov. 16,
181 7. He served -in the late war. They reside at East Valley, McKean
Co., Pa. Children : 1392. Philetus P.', born April 26, 1839; entered
the army in 1862 and was killed in the battle of the Wilderness,
1864. 1393. Samuel G.', born Aug. 30, 1842; married Emma Rice.
1866. 1394. John F.^born Oct. 8, 1858, died May 30, 1878. 564.
Lemuel Southwick*, (LemueP, Jonathan^ Sam* Stephen Nichols
man-ied for first wife, Jan. 28, 1798, Abigail Moulton, born Dec. 12,
1773, died Oct. 13, 1810. Children : John, born Nov. 25, 1798;
Samuel, born Dec. 6. 1800, died Oct. 17, 1856; Josiah Moulton, born
Sspt. 25, 1804; David, born Aug. 23, 1809. He married third wife,
April 19, 1821, Mary Buxton, daughter of Henry and Eleanor, born
Oct. 2. 1786. died Feb. 20. 1865, aged 88 years.
The text on this page is estimated to be only 0.00%
accurate

C2)a'0''i^^ ^i
 SIXTH GENERATION. 289 ueP, John^ Lawrence'), son of
Lemuel and Man(Spencer), died Sept. 1857, in Upper Sandusky,
Ohio. Married Joanna Rice, died, 1863, at Big Island, Marion Co.,
Ohio. He served in the war of 181 2, his term of service altogether
was 9 months. Children : 1395. Alonzo', born June 7, 1S19; married
Jane Van Warner. 1396. Electa^, born Aug. 30, 1821 ; married Jones
Cram. Nov. i. 1846. 1397. Adaline', born Dec. 15, 1S22, died April
15. 1832. 1398. Mary', born July 29, 1824. 1399. Lemuel', born Aug.
9, 1826. 1400. Elizabeth', born Feb. 22. 1828. 1401. Lydia', born
Jan. 13, 1830, died April 20, 18351402. Arnold', born Feb. 7, 1S32,
died in the army. 1403. Russel', born Sept. 22, 1833. 1404. EzekieF,
born Feb. 28, 1835. 1405 David', born Sept. 29, 1836. 424. Mary
S0UTHWICK^ (Joseph^ Lawrence\ Lawrence^ DanieP, Lawrence'),
daughter of Joseph and Ailse (Sayles), born July 15, 1787, at
Mendon, died Aug. 26, 1872. Married, Feb. 28, 181 i, Daniel Farnum,
at Uxbridge, son of David and Ruth (Southwick) Farnum, born Nov.
22, 1784, died Dec. 10, 1879, aged 95 years, 18 days. He was a
farmer at Northbridge, Mass. Children : 1406. Jonathan Sayles', born
Oct. 15. 1812. at Uxbridge. died July 14, 1814. 1407. Joseph
Southwick', born Aug. 21. 1814, at Mendon, died Dec. 22, 1873, at
Worcester. Mass. Married Lois N. Stoddard, 1841. 1408. Luke
Southwick", born Jan. 20, 1817. at Mendon; married Chloe M. Taft,
1849.
 2 go THE SOUTHWICK GENEALOGl^.1409. Ruth Maria',
born Aug. 29, 1S19, at Northbridge. 1410. James Moore", born April,
11, 1822, at Northbridge; married Ophelia Stoddard, 1847. 1411.
Marj Alice', born Aug.4.i82S. at Northbridge, died Dec. 31, 1829. The
venerable DANIEL FarNUM of Northbridge, the oldest man in that
town or vicinity, departed this life Dec. 10, 1879, aged 95 years and
18 days. The deceased was of the fifth generation in descent from
John Farnum, an early settler at the ancient town seat in Mendon,
and a little later in the southerly part of Uxbridge. The lineage is
John, Moses, Moses, David. Daniel. His grandfather, Moses, was an
eminent minister in the Society of Friends, whose memory is still
fragrant in many bosoms. The deceased has dwelt through all the
mature part of his long life, in Northbridge, near the border of
Uxbridge. He was the oldest son of a large family, and is survived
only by his youngest brother, Samuel J. Farnum, formerly mayor of
Newburg, N.Y., now resident in or near Poughkeepsie, and past his
three score and ten. The wife of his youth preceded him into the
higher life about seven years ago. Two sons and a daughter with
their companions, and numerous grandchildren, were privileged to
soothe and cheer his old age, and to nourish him tenderly at his
bedside in his last sickness. He was born with a good constitution,
which he preserv'cd well by regular and temperate habits,
experiencing but little sickness, and retaining his faculties in
remarkable vigor till within the last year. His was emphatically a
sound mind in a sound body; he was
 SIXTH GENERATION. 29 1 characterized for sound common
sense, a strong sentiment of justice and honesty, insistence on his
own rights, and respect for those of others ; economy, simphcity,
and hospitahty in domestic affairs ; was provident, faithful, and kind
in the family circle ; a peaceable, prudent, and accommodating
neighbor ; a serviceable, judicious, and trustworthy townsman,
honored with the principal municipal offices, including those of
selectman and representative in the legislature; a reliable counselor
in financial matters; a lover of his country and its liberties ; a firm
opposer of slavery and oppression ; sparing in religious professions;
of broad tolerance towards all denominations ; liberal in theology,
and a steadfast hoper in the final triumph of good over evil. These
were qualities and characteristics which in the deceased
overshadowed the incidental imperfections common to human
nature. He was warmly attached to the interests of the town, and
was a constant attendant on town meetings, the last one he
attended being in 1878, when in his 94th year. Among the positions
of public financial trust he occupied, was that of director in the
Blackstone Bank of Uxbridge, over twenty years. He had been
expecting his departure for three years, expressed his entire
resignation to the Divine disposal, and passed away in the confident
assurance of the life everlasting. Appropriate funeral honors were
paid to his memory and remains, at his late residence, the 13th, with
ministrations by Rev. Geo. S. Ball of Upton, Rev. Adin Ballou of
Hopedale, and now his mortal part sleeps with the dust of his
ancestors in 38
 292 THE SOUTHWICK GENEALOGY. Friends' Cemetery at
South Uxbridge. All the numerous descendants of the deceased were
present at the funeral, except the four great grandchildren. A. B.
 SEVENTH GENERATION. 862. LovELL PULSIFER Southwick',
(Moses^ Joseph', Lawrence*, Lawrence', DanieP, Lawrence'), son of
Moses and Sarah (Pulsifer) Southwick, born Dec. 7, 1806; married
first, Dec. 13, 1830, Phebe Lougee, born Nov. 11, 1 8 1 1 , died Aug.
6, 1 85 i ; second, April 4, 1854, Lucinda Thayer, born July 15, 1827.
He is a millwright and carpenter, and has built several first class
houses in Uxbridge and vicinity and is an energetic and much
esteemed man. Children: 1412. Ira^, born Nov. 2, 1S32; married
Angenette F. Thayer. 1413. Wellington®, born June 21, 1835, died
Sept. 6, 1853 bj bursting a blood vessel. 1414. Mary®, born Sept. 4,
1837; married Addison J. Williams. 1415. Samuel Taylor®, born
Sept. 7, 1838, died July 17, 1840. 1416. Augustus®, born Oct. 25,
1840, died Dec. 8, 1841. 1417. George Lovell®, born Dec. 3, 1845;
married, June 2, 1869, Mary Adeline Morton, daughter of Alfred and
Mary (Abbott) Morton. Married second wife, April 4, 1854, Lucinda
Thayer. Children : 1418. John Slater®, born Dec. 26, 1854, died
March 1855. 1419. Manly®, born March i6, 1855, died Sept. 12,
1855. 1420. Edward Francis®, Oct. 3, 1857, died Aug. 23, 1858.
1421. Wellington®, born Oct. 15, 1859. He was a farmer. 1422.
Louisa®, born Aug. 22, 1864, died June 20, 1865. 1423. Adeline
May®, born Sept. 12, 1868; deceased. 865. Luke S0UTHWICK^
(Moses^ Joseph', Lawrence', 293
 294 THE SOUTHWICK GENEALOGT. Lawrence^, DanieP,
Lawrence") son of Moses and Sarah (Pulsifer), born Dec. 3, 1823;
married, Dec. 20, 1840, Sarah Smith Thayer, born Feb. 20, 1825. He
was a millwright. Children : 1424. Dirantha Augustus*, born April 13,
1S47, died Sept. 20, 1848. 1425. Elsie Maria*, born March 27, 1848;
married Jan. 19, 1867, Lyman F. Arnold, occupation, a blacksmith.
1426. Chloe Francis^, born March 31, 1850; married, Jan. i, 1873,
Leroj D. Morrill, occupation, engineer. 1427. Marvel Walter*, born
June 4, 1857, occupation, carpenter. 888. Edward Seth Southwick',
(David^ Edward', Lawrence'*, Lawrence^, DanieP, Lawrence'), son
of David and Mary (Sherman), born Oct. 3, 18 14; married Lucy
Ruany Fuller. He lives (1881), at Rutland, Vt. Children : 1428.
Edward Oscar*, born May 31, 1849, ^^ Ludlow Vt., died March 31,
1851. 1429. Austin Edward*, born Sept. 27, 1852, at Rutland, Vt.,
died Nov. 6, 1861. 1430. vVnna Jane*, born Sept. 16, 1858, at
Stoughton, Wis. ; married, Oct. 25, 1877, John Patterson, lives at
Rutland, Vt. 1431. Herbert*, born Aug. 31, 1866, at Rutland, Vt.,
died Aug. 4, 1867. 1432. Mattie May*, born March 2^, 1869, at
Rutland, Vt. 861. Lucy Southwick', (Moses^ Joseph^ Lawrence\
Lawrence^, DanieP, Lawrence"), daughter of Moses and Sarah
(Pulsifer), born July 7, 1805 ; married Leonard Lougee. Children :
1433. Sewell*. Married Maria Young, May 24, 1853. He was a
blacksmith. 1434. Margaret*. Married Young, Dec. 8, 1853.
 SEVENTH GENERATION. 295 1279. Elisha Southwick',
(Enoch"', John', Jonathans Daniel\ Daniel", Lawrence' ), son of
Enoch and Waity ((Arnold), born May 31, 1805; married, July 1828,
Athaline Inman, of Smithfield monthly meeting, R. 1. 'Children ;
-3435. Lvdia*, born Oct. 11, 1831 ; married, 1S52. Edward Shernian,
of Millbury, Mass. 0436. Wiilett^ born about 1848. ^437. Cornelia*,
died young. 1147. Masa Branch Southwick', (jonatl^an^ Samuel\
Daniel*, Samuef, John^, Lawrence'), son of Jonathan and Sarah
(Branch), born at Orwell, Rutland Co., Vermont, April 5, i8o{, died at
Mont St. Hilaire^ Canada, Oct. 16, 1879, in his seventy-eighth year.
Married, Feb. 5, 1827, Eliza Andres, daughter of Samuel Andres,
Esq., of Acadia, Canada. Children: 1438. Daughter*, born Dec. 9,
1S29, died Dec. 10, 1829, at Monl St. Hilaire, Canada. 1439.
Daughter*, born June 23, 1837, died March 24, 1838. at Mont St.
Hilaire, Canada. Masa Branch Southwick was the son of Jonathan
and Sarah (Branch) Southwick, of the town of Orwell, Rutland
County, Vermont, born April 5^ 1801, his mother died when he was
thirteen years of age> He was remarkably kind to his )'ounger
brothers and sisters, exercising an almost parental care over them,
his superiority of character enabled him to have a great influence
over them for their good. During his
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