Jan van der Greef

“Transformation to a

Health-ecosysteem”

Connectivity

A systems view looks at the world in terms of

dynamic patterns of (non-linear) relationships

and organization

.

Van der Greef, Jan, 2011. All systems go. Article in Nature,

Perspective, Volume 480, p. 87.

Lao Tzu (604 BC - 531 BC)

If you do not change direction,

you may end up where you are heading.

Future of Health Care ???

Future driven by Health EconomicsFuture driven by Disease Economics

Time for a different

(Systems) View?

The Challenge in current Health Care: Medicine-related

> “One-size fits all” to Personalized Medicine

An Early Lesson

What a Genome Cannot Tell Us

What Cannot Be Learnt from a Genome

One Animal

One Genome

Two States

There is more to life

than DNA

Understanding

from

a Systems Perspective?

Biomarkers

Pathways

System

Knowledge

Info

rmati

cs

Transcripts

Proteins

Metabolites

Proteins

Metabolites

Systems Biology, towards personalized fingerprints

Systems

Analysis

Tissue

Cell Organism Measurement Interpretation

Systems cannot be understood by studying fundamental constituents,

the properties of the parts are not intrinsic but can be understood within the

context of the whole

Entire Correlation Network : Organized complexity

~3400 nodes

~17000 edges

abs R > 0.8

Patterns of self-organization are the key

Treatment a Treatment b Treatment c

Empirical Medicine

Biomarker-guided

therapy

Treatment aTreatment b

Treatment c

Biomarker-Guided Medicine

Personalized Health strategies based on drugs developed

via a reductionistic focus and the “golden-standard”

clinical trial design are limited !!

Van der Greef Jan; Hankemeier Thomas; McBurney Robert N, Metabolomics-based systems biology and personalized

medicine: moving towards n = 1 clinical trials?

Pharmacogenomics 2006;7(7):1087-94.

Towards biomarkers & Biomarker fingerprints

Nature Vol 520, p 609–611, 2015

What is Health ??

WHO 1948 :

“A state of complete physical, mental, and social well-

being and not merely the absence of disease, or infirmity.”

…………..Towards a new definition of health

Lancet 2009; vol.373, march 7: p.781

….ability to adapt and self-manage in

the face of social, physical and emotional challenges

…… towards a new definition of health

Homeostasis

AllostasisAdapted state

of the system

Disease

“Disease management”

Focus on single symptom

“Health promotion”

Focus on salutogenesis

Resilienceto different stimuli

physical, psychological, social, spiritual

Challenge

“Systems Thinking, natural products

and the future of Health Care”

• Smallest bird and animal with a backbone

• Has the largest brain of all birds (4.2% bw)

• Only bird that can fly backwards

• Heart rate up to 1260 beats/min

• Wing beat up to 200/sec

• Can lower metabolic rate to 1/15th and body

temperature by 20-50 degrees during torgor

• Can switch from nectar to insect diet

Resilience ??

In these “Blue Zones” they found that people reach age 100

at rates 10 times greater than in the United States.

Health Promotion By Reverse Engineering Longevity

Dan Buettner

“The dominant model of disease today is biomedical, and it

leaves no room within its framework for the social, psychological

and behavioral dimensions of illness.”

“How much longer must medicine’s science be bound by a 17th

century world view?”

>>> biopsychosocial model

George L Engel (1913-1999)

The need for a new medical model:

a challenge for biomedicine,

Science, 1977,196:129-132

New insights

Slide adapted after Ton Nicolai

Correlation Network : Organized complexity

How to find Phenotypic differencesIn the Health – Disease space ?

SYSTEM BIOLOGY : New insights, new options ?

Bioinformatics

“OMICS

”

Oltvai et al Science 298 (2002) 763

Life’s Complexity

Pyramid

Phenomenological

Systems perspective

Chinese Medicine

“ East is East and West is West and

never the Twain shall meet? ”

Science 19 December 2014:

Vol. 346 p. 1569

Symptom relations as bridge between

Chinese and Western medicine,

a step towards

Personalized Health/Medicine

DIAGNOSIS

is

KEY !!

Subtype B

Subtype A

Targeted care – disease phenotype focustheranostics related to efficacy and adverse effects

Stratified/Individualized Care

Symptom/Signs

Molecular pathology

@@

Disease - symptom management1 disease -1 target – 1 (block buster) drug

Patient Wellness focusIntegrated systems approach

Life style

Psychology/Consciousness

Environment, Nutrition

Medicine

One-size-fits-all

Personalized

Health Care Ecosystem

Symptom/Signs

Molecular pathology fingerprint

Diagnosis is key !!

Subtype B

Subtype A

disease phenotyping

Stratified/Individualized Care

Symptom/Signs

Molecular pathology

One-size-fits-all

Heng Wei

Sub-typing :

early Diabetes type 2

Herman van Wietmarschen

Sub-typing :

Rheumatoid Arthritis

J. Clinical Reumatology, 2009, 15 ,330-337

Mol. BioSyst., 2012, 8, 1482–1491

Diagnosis is key !!

New diagnostic tools available for System Diagnosis?

How to measure

coherence in

organization?

Life Complexity Pyramid

How to measure

interrelation with the

outside world?

Bioluminescence is directly related to

Dynamic Systems Organisation (Chronobiology)

Every organism (every cell) emits light ( bioluminescence) , which is unique

in wavelength, duration, timing and rhythms (information & communication)

1923 Alexander Gavrilovich Gurwitsch

Алекса ́ндр Гаври́лович Гу ́рвич

Roel en Eduard

Van Wijk

“The human body

literally glimmers”

The light intensity emitted by

the body is 1000 times lower

than the sensitivity of our

naked eyes.

Human biophoton emission is invisible to the naked eye but can be

detected by Ultra-weak Photon Emission (UPE)-TECHNOLOGY

UPE-technology measures light emission dynamics

L:palm R:dorsum

R:palm L:dorsum

Reactive Oxygen Species (ROS), free radical reactions and

excited chemiluminescence species >> sources of photon emission

Healthy (N=50)

pre-diabetes (N=50)

patient (N=50)

-0,05 0,00 0,05 0,10 0,15 0,20 0,25 0,300

5

10

15

20

25

30

35

No

of o

bs

The squeezing parameter r show

differences between groups of healthy, pre-

patient and patient subjects

(M. Orszag, Quantum optics 2000)

Quantum photon signal analysis in health and disease

4 parameters to describe the properties of

the signal, i.e., the magnitudes and phases of

the two complex parameters:

α = |α| exp (iΦ)

ξ = r exp (iθ)

Roel en Eduard van Wijk et al. – Sino-Dutch center for Preventive and Personalized Medicine

Paramecia are widespread in freshwater, brackish and marine environments

Observed mutual influence on population growth

is stopped with Visible Light filter

Fels D (2009) Cellular Communication through Light. PLoS ONE 4(4): e5086. doi:10.1371

Communication

by Light

Paramecia

in closed

container

Paramecia

in closed

container

Fil

ter

Human – Human intentional healing influences Algae bioluminescence

Biofield

Communication

Roel en Eduard van Wijk et al.

The music of Life :

System coherence :

biophoton dynamics of left and right hands

The Rhythm of Life is a collaboration between designers / artists Mike Thompson, Susana Cámara Leret and

Dave Young and the SD PPM / Netherlands Metabolomics Centre. The artists investigate the potential of sensory data experiences, through an ambiguous data collection process

Psychology Words (psychotherapy)

Body language

Nutrition

Medicine

Life Style advice

Health care provider

World view

Spirituality

Patient

Physiology

Fam

ily

Cu

ltu

re

So

cia

l n

etw

ork

Self-identity

Diagnosis & Treatment in a Personalized Health Care Ecosystem

Relationship between patient and Health Care provider is key

(compassion)

Patient-Physician relationships

Otto Scharmer, U-Theory

Mensgerichte

Zorg

……. towards a Human-oriented

Health Care Ecosystem

Production

oriented Care

Outcome

oriented Care

Human

(Compassion)

oriented Care

4P Health

Personalized

Preventive

Participatory

Predictive

2012 20202007

Participation

society

Integrated Medicine

Information

society

From reductionism

to systems biology

From disease

to personalized system wellness

Perspectives

“I”-llness <> “We”-llness