Deciphering the Genes for Resilience

Jeffrey Bland PhD

Chairman Emeritus The Institute for Functional Medicine

Founder amp President

The Personalized Lifestyle Medicine Institute

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

Health is personal

Wellness versus Health

bull ldquoDisease is incompatible with health but not with wellnessrdquo

bull ldquoLess is known about what contributes to wellness than what causes diseaserdquo

bull The time is ripe for engaging people in the promotion of their own wellness

JAMA 2015 314 121-22

Statistical Humans are of Little Interestrdquo

5

ldquoMedicine is for Real People

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

Health is personal

Wellness versus Health

bull ldquoDisease is incompatible with health but not with wellnessrdquo

bull ldquoLess is known about what contributes to wellness than what causes diseaserdquo

bull The time is ripe for engaging people in the promotion of their own wellness

JAMA 2015 314 121-22

Statistical Humans are of Little Interestrdquo

5

ldquoMedicine is for Real People

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Health is personal

Wellness versus Health

bull ldquoDisease is incompatible with health but not with wellnessrdquo

bull ldquoLess is known about what contributes to wellness than what causes diseaserdquo

bull The time is ripe for engaging people in the promotion of their own wellness

JAMA 2015 314 121-22

Statistical Humans are of Little Interestrdquo

5

ldquoMedicine is for Real People

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Wellness versus Health

bull ldquoDisease is incompatible with health but not with wellnessrdquo

bull ldquoLess is known about what contributes to wellness than what causes diseaserdquo

bull The time is ripe for engaging people in the promotion of their own wellness

JAMA 2015 314 121-22

Statistical Humans are of Little Interestrdquo

5

ldquoMedicine is for Real People

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Statistical Humans are of Little Interestrdquo

5

ldquoMedicine is for Real People

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

The Gene-Environment Age

bull Much more genetic variation among ldquohealthy peoplerdquo than expected

bull More than 3 million single nucleotide polymorphisms discovered

bull Not sure how many have significant influence on how lifestyle and environment influence phenotype

NEJM 2014 371 503-05

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

May 27 2013hellipGenes and Disease

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Mary Claire King and BRCA 1 and 2

ldquoThe lifetime risk of breast cancer among female mutation carriers is presently 82 Risks appear to be increasing with time Before 1940 it was 24 Lack of physical exercise and obesity in adolescence may be important modulating factors for risk in carriersrdquo Science 2003 302 643-50

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Incidence of Breast Cancer in Women with BRCA12 mutations

Age

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Cell 2015 162 391-401

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Human Genome Project Reality

Single Nucleotide Polymorphisms (SNPs) are not the whole story (insertionsdeletions copy number variants mosaicism)

bull What we have learned from GWAS studies

Exome only 15 of whole genome

gt80 of traits in non-coding regions of genome

Cell specificity (more than 200 different cell types)

bull How epigeneticspost-translation shapes our phenotype

Methylation

Acetylation

Phosphorylation (kinases)

Small inhibitory RNAs (siRNA) Oral oligonucleotide SMAD7 inhibitor (Mongersen) and Crohnrsquos DiseaseUlcerative Colitis

Oxidation Glycation and Amino Acid Conjugation

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

bull Patient-Focused Drug Development

bull Biomarker Development

bull Accelerated Approval

bull Precision Medicine ndash Genetically Targeted

bull Clinical Trials ndash Innovative Statistical Methods

bull Expedited Patient Access and Input

Lancet 2015 385 2137-38

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

bull Treatments based upon the genetic biomarker phenotype and psychosocial characteristics

bull Differentiation of a given patient from other patients with similar diagnosis or clinical presentation

bull Minimizing adverse side-effects and maximizing clinical outcome

NEJM 2015 372 2229-34

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

NEJM 2015 3732235-42

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

bull gt 2 million annual adverse drug reactions bull gt 100000 deaths in the USA annually bull Individual response to drugs strongly related

to pharmacogenomic uniqueness

N Engl J Medicine 2008 359 856-58

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Personalized Cancer Care

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Cell 2015 162 33-44

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

My 23andMe Statin Response Genotype

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

N Engl J Med 2008 359 789-99

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

N Engl J Med 2011 365 285-87

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Am J Cardiovasc Drugs 2008 8 373-418

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Human Mol Genet 2007 16 1091-97

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

bull ldquoWe found that the majority of variations among the way people respond to various stimuli goes well beyond genetic variation the regulation of genetic expression may arise from epigenetic differences due to environmental factors such as lifestyle diet the microbiome drugs and toxic exposuresrdquo

Cell Systems 2015 1 51-61

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

Personalized Nutritional Pharmacology Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical a nutrigenetics proof of concept

bull Nutrition 200723844-52

bull Kornman K1 et al

bull At 12 wk of dosing with the botanical formulation IL-1beta gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1(Pos) and IL1(Neg) subjects Mean IL-1beta gene expression treatment effect over the 12-wk period was greater in IL1(Pos) than in IL1(Neg) subjects At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels However in IL1(Pos) subjects significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo No CRP effect was observed in the IL1(Neg) subjects

bull This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes

OMICS P4 Precision and Personalized Medicine

The Functional Medicine Revolution

bull Harnessing the ldquoomics revolutionrdquo requires a systems biology operating system

bull Functional Medicine is the systems biology operating system for all the ldquoomicsrdquo related technologies

Pioneer 100 Data

1 Full genome sequence 2 Microbiome 3 Quantified Self

(biometrics) 4 Phenotypic Data

(Functional Medicine Lab Tests)

Functional Medicine Core Physiological Processes

1 Assimilation and Elimination

2 Detoxification 3 Defense 4 Cellular Communications 5 Cellular Transport 6 Energy 7 Structure

P4 Medicine

bull Predictive bull Personalized bull Preventive bull Participatory

Objective To personalize healthcare from a systems biology perspective

The Era of Predictive Analytics

bull ldquoPredictive analytics incorporates complex information about the patient into prognostic models that estimate the likely hood of a particular eventrdquo

bull ldquoPhysicians must understand the limitations of the information that result in predicting risks or benefits of specific therapiesrdquo

JAMA 2015 314 25-26

Resilience versus Disease Risk

Eric Schadt PhD Stephen Friend MD PhD

Converting the At Risk Patient to the Resilient Human

bull 127 classical Mendelian single gene diseases

bull Over 5000 non-Mendelian diseases with different susceptibilities

bull Converting ldquoat riskrdquo to ldquoresilientrdquo is related to epigenetic effects

bull Epigene is modified by lifestyle and environment exposure

E Schadt and S Friend Science May 30 2014 344 970-72

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Pioneer 100 Data

1 Full genome sequence 2 Microbiome 3 Quantified Self

(biometrics) 4 Phenotypic Data

(Functional Medicine Lab Tests)

Functional Medicine Core Physiological Processes

1 Assimilation and Elimination

2 Detoxification 3 Defense 4 Cellular Communications 5 Cellular Transport 6 Energy 7 Structure

P4 Medicine

bull Predictive bull Personalized bull Preventive bull Participatory

Objective To personalize healthcare from a systems biology perspective

The Era of Predictive Analytics

bull ldquoPredictive analytics incorporates complex information about the patient into prognostic models that estimate the likely hood of a particular eventrdquo

bull ldquoPhysicians must understand the limitations of the information that result in predicting risks or benefits of specific therapiesrdquo

JAMA 2015 314 25-26

Resilience versus Disease Risk

Eric Schadt PhD Stephen Friend MD PhD

Converting the At Risk Patient to the Resilient Human

bull 127 classical Mendelian single gene diseases

bull Over 5000 non-Mendelian diseases with different susceptibilities

bull Converting ldquoat riskrdquo to ldquoresilientrdquo is related to epigenetic effects

bull Epigene is modified by lifestyle and environment exposure

E Schadt and S Friend Science May 30 2014 344 970-72

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

The Era of Predictive Analytics

bull ldquoPredictive analytics incorporates complex information about the patient into prognostic models that estimate the likely hood of a particular eventrdquo

bull ldquoPhysicians must understand the limitations of the information that result in predicting risks or benefits of specific therapiesrdquo

JAMA 2015 314 25-26

Resilience versus Disease Risk

Eric Schadt PhD Stephen Friend MD PhD

Converting the At Risk Patient to the Resilient Human

bull 127 classical Mendelian single gene diseases

bull Over 5000 non-Mendelian diseases with different susceptibilities

bull Converting ldquoat riskrdquo to ldquoresilientrdquo is related to epigenetic effects

bull Epigene is modified by lifestyle and environment exposure

E Schadt and S Friend Science May 30 2014 344 970-72

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Resilience versus Disease Risk

Eric Schadt PhD Stephen Friend MD PhD

Converting the At Risk Patient to the Resilient Human

bull 127 classical Mendelian single gene diseases

bull Over 5000 non-Mendelian diseases with different susceptibilities

bull Converting ldquoat riskrdquo to ldquoresilientrdquo is related to epigenetic effects

bull Epigene is modified by lifestyle and environment exposure

E Schadt and S Friend Science May 30 2014 344 970-72

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Converting the At Risk Patient to the Resilient Human

bull 127 classical Mendelian single gene diseases

bull Over 5000 non-Mendelian diseases with different susceptibilities

bull Converting ldquoat riskrdquo to ldquoresilientrdquo is related to epigenetic effects

bull Epigene is modified by lifestyle and environment exposure

E Schadt and S Friend Science May 30 2014 344 970-72

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Quantifying Wellness and Resilience

P4 Medicine bull Predictive bull Preventive bull Personalized bull Participatory

Leroy Hood MD PhD

Learn more

wwwsystemsbiologyorg

wwwp4miorg

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

The Institute for Systems Biology Pioneer 100 Wellness Project

Source Institute for Systems Biology

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

The First ldquoQuantified Humanrdquo

Source medstanfordedunews

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

What is a ldquoComorbidityrdquo or ldquoDisease Adjacencyrdquo in the Age of Systems Medicine

A Few Representative

Clinical Examples

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

J Am Med Assoc 2004 292 490-95

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Nature 2014

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Thorax 2012 67 456-63

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

GPCR41 Activation by Dietary Fiber Induces Lung Antiinflammation through GI Microbiota Short Chain Fatty Acid Production

Nature Medicine 2014 20 139-163

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Dietary Fiber Microbiome Gut Immune Response and Pulmonary Antiinflammation

Nature Medicine 2014 20 120-121

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

N Engl J Medcine 2013 368 1647

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Science 2015 348 80-87

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Nature Medicine 2015 21 839-41

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Nature Medicine 2015 21 895-905

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

bull Fecal Transplant- 1639 PubMed abstracts bull Helminth Therapy- 20448 PubMed abstracts

Phil Trans R Soc 2014 370 296-304

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

J Am Med Assoc 2015 314 895-84

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Dale Bredesen MD UCLA Department of Neurology

Director Mary Easton Center Alzheimerrsquos Disease Research

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Beyond the Pathology to the Functional Origin of the Disease

Epigenetics bull Trauma

bull Stress

bull Fear

bull Anxiety

bull Absence of ldquoLocus of Controlrdquo

bull Lack of attribution and love

bull Poverty- Being ldquoimpoverishedrdquo

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Nature Reviews Genetics 2007 8 253-262

Randy Jirtle PhD

Michael Skinner PhD

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Lancet 2015 386 388-97

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Moshe Szyf PhD

bull Professor of Pharmacology and Therapeutics

bull McGill University Montreal bull The Szyf lab proposed two

decades ago that epigenetic changes in DNA are a target in cancer and other diseases and has provided the first set of evidence that the ldquosocial environmentrdquo early in life can alter DNA epigenetics changing functional expression of the genes and launching the emerging field of ldquosocial epigeneticsrdquo

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Biological Psychiatry August 2015

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

ldquoUnderstanding of the biochemical individuality of

each human being based on the concepts of

genetic and environmental uniqueness seems

custom-made to cater to the belief among some

of the woo-prone that they are special

snowflakes so utterly unique that treatment must

be tailored to their finest uniquenessrdquo

David GorskiMD

Science-based Medicine Blog

Third most viewed medical blog

So Where Is the Future

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics

Treating the ldquoSnowflakerdquo in 21st Century Postgenomic Medicine

bull Focus on the gene-environment connection

bull Celebrating individuality bull Developing an

integrative systems approach

bull Unlocking resilience bull Quantifying wellness bull Redefining patient

engagement bull Pharmacogenomics bull Recognizing the

importance of epigenetics