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Physiome

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integr med res 5 ( 2 0 1 6 ) 37–40

Available online at www.sciencedirect.com

Integrative Medicine Research

journal homepage: www.imr-journal.com

Perspective

Perspectives of physiome research

Chae Hun Leem ∗


Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea

a r t i c l e i n f o a b s t r a c t

Article history: Physiome is an area of physiology to generate a whole system by analyzing and integrat-
Received 11 December 2015 ing scattered and discrete information. The term “physiome” was first introduced by James
Received in revised form B. Bassingthwaight in 1993, and officially announced by the International Union of Physi-
28 December 2015 ological Societies as the new field to be accomplished in the 21st century. In this review, I
Accepted 29 December 2015 introduce the concepts of physiome, why physiome should be pursued, what kind of strategy
Available online 5 January 2016 is necessary to form physiome, and how physiome can be used.
© 2016 Korea Institute of Oriental Medicine. Published by Elsevier. This is an open access
Keywords: article under the CC BY-NC-ND license
model simulation (http://creativecommons.org/licenses/by-nc-nd/4.0/).
oriental medicine
physiome

in order to understand life in an integrative way. When the


1. History and concepts of physiome total amount of knowledge was smaller, such reductionism-
based approaches were inevitable. In parallel, after the
The study of paradigms of life has been moved from the structure of the genome was identified, molecular biology
macroscopic view, such as the organism or organ/tissue, to the techniques were developed extensively over recent decades,
microscopic view, such as cell/protein/genome. This shift was and vast amounts of knowledge related to the genome and
caused by the reductionism in scientific fields; if we know the proteome have accumulated. However, the linkage between
elements, we can understand the systems. The vast amount structural components, such as the genome and proteome,
of data in life science related to the elements has accumu- and functional knowledge were not formed properly. Physio-
lated in recent decades; however, the efforts to integrate such logical scientists have great interest in how to link both sets
results and understand the life of the organism has not been of knowledge to understand life. Additionally, physiological
properly performed. Life sciences failed to show the tree and experimental techniques were developed, and the speed of
the forest together, especially in functional aspects. From this information accumulation increased, with scientists unable
reflection, new scientific approaches became acquainted for to catch up with such speed to integrate the data into life
integrating the information to understand the life system. systems. The information became scattered and discreet, and
Physiological scientists have been interested in functional microscopic categorical research prevailed. To overcome such
aspects of life and put substantial efforts toward finding the obstacles in physiological science, physiome was introduced.
mechanisms associated with life systems. The focus of the Physiome is a combinatory word from “physio” and “ome”
research has moved from the organism to the subcellular level for “life” and “as a whole”, respectively. The first introduction


Corresponding author. Department of Physiology, University of Ulsan College of Medicine/Asan Medical Centre, 88 Olympic-ro, 43-gil,
Songpa-gu, Seoul, Korea.
E-mail address: leemch@amc.seoul.kr
http://dx.doi.org/10.1016/j.imr.2015.12.004
2213-4220/© 2016 Korea Institute of Oriental Medicine. Published by Elsevier. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
38 Integr Med Res ( 2 0 1 6 ) 37–40

of physiome appeared in a report from the Commission This model will show the electrical activity of the whole
on Bioengineering in Physiology to the International Union heart; however, it cannot directly reflect neuronal or hor-
of Physiological Sciences (IUPS) Council at the 32nd World monal effects. For linking those effects, a cellular model needs
Congress in Glasgow, UK, in 1993. The aim of the project to be created. Each cell has common or different elements
was to provide a comprehensive framework for modeling the that respond to neuronal or hormonal effects. The cell model
human body using computational methods, which can incor- needs the same unit, structure, and function. Structure can
porate the biochemistry, biophysics, and anatomy of cells, be composed of cell dimension, ion channels, ligand recep-
tissues, and organs. The project was officially launched at the tors, intracellular organelles, each ion concentration inside
33rd World Congress of IUPS (St Petersburg, Russia, 1997) and and outside of cells, and temperature. Part of the function
was, at the 34th World Congress (Christchurch, New Zealand, can include ion-channel kinetics reflecting environmental
2001), designated as a major focus for the next millennium.1 changes, such as voltage, phosphorylation, and ion concen-
The physiome is the quantitative and integrated descrip- trations. Additionally, the functions of intracellular organelles
tion of the functional behavior of the physiological state of that control intracellular ion concentration or mechanistic
an individual or species. The physiome describes the phys- descriptions of the signal transduction pathways on receptor
iological dynamics of the normal intact organism and is activation need to be composed. If a model is to incorporate
built upon information and structure (genome, proteome, the genetic transcription or molecular mechanisms of pro-
and morphome). In its broadest sense, the physiome should teins, such a model can also be made. Therefore, the model
define relationships from genome to organism and from func- domain can be extended from the molecular level to whole
tional behavior to gene regulation. In context of the Physiome planet population. The domain of physiome was introduced
Project, it includes integrated models of components of orga- as shown in Fig. 1. If there are unknown mechanisms, they can
nisms, such as particular organs or cell systems, biochemical, be treated as a black box and can be incorporated into models
or endocrine systems (www.physiome.org). in a descriptive way.
The predictability of the model is the important reason why
the model needs to be developed; however, creating biologi-
2. Model simulation is a central tool for cal models like physiome capable of making predictions is a
physiome very difficult task due to its complex structure and functions.
Additionally, obtaining good data is another obstacle. Since
The development of computer-based quantitative models in most scientists have not done their research to create a good
physiome is inevitable to integrate the information in a quan- model, the majority of experimental results were not compa-
titative way. Quantitative models in physiome differ most rable and were difficult to use in model construction. There
significantly from other database-driven research areas, such was also a strong tendency for the experimentalist to regard
as bioinformatics, network biology, or big-data analysis. The the model as a decoration for their research. For the reposi-
physiomic model is a repository of the previous data and also tory role of the model, the developed model should be tested
a tool to test or predict the results by varying factors. Other by the experimentalists. If there are discrepancies, the reasons
data-driven research can show the linkage between compo- must be discovered and the model improved. If a model can
nents, however, they only see the strength of the linkage of explain and reproduce the previous data more and more, the
the data itself, and the interpretation tends to be subjective. predictability of the model can be continually improved. The
The data repository role of the model is very important for the cooperation between the experimentalist and model devel-
researchers, and it greatly reduces the burden to search the opers is essential to succeed in physiome. As a model is
appropriate results from the sea of references. developed in this way, eventually it can perform better than
To perform data repository roles, models need two kinds of most experiments. To see the tree and the forest together
data: structure and function. Model structure is very impor- clearly in the future, it is essential to pursue physiome.
tant, because it is a backbone of the model. Therefore, the
appropriate identification of the structure is essential to com-
pose the model. If the structure is set, the functions of the 3. How physiome can be used
structural element need to be known. Structure is the static
component of the system and function is the mechanistic The most important application of physiome is to develop a
description of the dynamic change. The model domain deter- new drug. The failure rate of new drug development is > 99.9%.
mines the necessary structure and function. For example, if The investment for new drugs is huge, with major pharma-
a heart model is created to generate the electrical activity of ceutical companies merging to cover the expense of new drug
the heart, first, the anatomical structure component of the development. Target identification for curing disease is the
heart, such as a shape, location, and direction of different cells, most important aspect of new drug development. If a phys-
interstitial space, etc., need to be known. Second, functional iome model can reproduce human biology in an appropriate
components of the heart, such as the electrical activities of way, it can be used to simulate disease states and for discov-
the cardiac myocytes in different locations (sinoatrial node, ery of the most effective targets curing disease. Furthermore,
atrium, atrio-ventricular node, Purkinje fiber, and ventricle) since physiome models already regenerate human responses,
and cell-to-cell electrical connectivity through gap-junction the burden of clinical testing and development time for the
channels, need to be known. Finally, both structure and func- new drug can be reduced substantially.2,3 Another benefit
tion need to be combined using mathematical methods, which includes reduction of ethical issues involved with using ani-
are usually used in mechanical and electrical engineering. mal or human subjects through the use of simulations.
C.H. Leem/Physiome research perspectives 39

Fig. 1 – Illustration of the relationship between the physiome and other areas of biological organization.
Note. From Hunter PJ, Borg TK. Integration from proteins to organs: the Physiome Project. Nat Rev Mol Cell Biol 2003;4:237-43.
Copyright 2003, Nature Publishing Group. Reprinted with permission.

Another place is academic research. As mentioned, an in the form of systems biology is at an early stage of develop-
important role of physiome is as a data repository and a kind ment as a fully quantitative and computational discipline, it
of preliminary test bed for research ideas. If model results and remains unclear what kind of higher level concepts might map
experimental results contradict each other, it is worth pur- well to traditional oriental medical concepts. From the West-
suing the reason. If the model is the center for the research, ern point of view for physiome, the knowledge structure of
the speed of understanding life processes accelerates. Exam- oriental medicine is too weak and fragile. Since physiome and
ples of this have been shown in physics. Currently, virtually all oriental medicine like Sasang constitutional medicine direct
physics research is based on models. Model prediction, e.g., similar goals, e.g., a holistic approach, the development of
the Higgs boson, is to be proven by using cyclotron. Biolog- the proper higher level of physiome in the future may open
ical complexity retards development of physiome; however, the way to understanding oriental medicine mechanistically.
physiome will eventually be accomplished and used. In the Meanwhile, both approaches can contribute clinical data sup-
field of heart research, physiome is created and ready to be porting holistic models for physiome.4,5
used in clinical fields. Numerous trials using cardiac-related
physiome from the molecular to the organ level have been
accomplished and displayed significant improvements in new Conflicts of interest
drug development, academic research, and education.
The author declares no conflicts of interest.

4. Physiome and oriental medicine


Acknowledgments
Oriental medicine is basically holistic medicine; however, even
though oriental medicine is intended toward holism, there This work was supported by the Bio & Medical Technology
have been many trials to obtain mechanistic explanations, Development Program of the National Research Foundation
including five-chi or Sasang constitution. Because of these funded by the Ministry of Science, ICT & Future Planning
conceptual approaches, the knowledge associated with orien- (Fund receiver Chae Hun Leem, No. 2015M3A9B6028310 and
tal medicine is difficult to grasp in a systematic way. These No. 2014M3A9D7034366).
kinds of difficulties were described by Noble.4 To obtain a
model system like physiome, it should contain the structure
and the clear function. Oriental medicine has vast amounts of references
functional knowledge, but very vague and conceptual struc-
tures to assemble. As Noble4 mentioned, since the physiome
40 Integr Med Res ( 2 0 1 6 ) 37–40

1. Garny A, Cooper J, Hunter PJ. Toward a VPH/physiome toolKit. 4. Noble D. Systems biology, the Physiome Project, and oriental
Wiley Interdiscip Rev Syst Biol Med 2010;2:134–47. medicine. J Physiol Sci 2009;59:249–51.
2. Uehling M. Model Patient. Bio-IT World 2003;12:1–4. 5. Shim EB, Lee S, Kim JY, Earm YE. Physiome and Sasang
3. Food and Drug Administration. Innovation or stagnation: constitutional medicine. J Physiol Sci 2008;58:433–40,
challenge and opportunity on the critical path to new medical http://dx.doi.org/10.2170/physiolsci.RV004208.
products. Washington DC: U.S. Department of Health and
Human Services; 2004.

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