Interesting question and a dilemma that modelers have to grapple with. One of the main problems is the scaling up feature from the cellular to the physiological dimensions. There is a threshold that needs to be crossed after which the model loses its continuity. I think the same can be said of models and theory that attempts to unify a system. And you are right to say that the predictive power may be reduced if we adopt a mix-and-match approach to integration of the various modeling platforms. Problems of reliability and validity start to offset the effort invested. Hence the focus tend to be on what is pertinent. Especially nowadays where the focus is on bioinformatics, the cellular and genetic levels become the primary focus. Unfortunately things start to get a bit abstract once we go down that lane. Also there is a counterargument that physiological dimensions are just a manifestation of the more fundamental units- cells and genetics. Interesting that intelligence has been found to be located in cells outside of the brain- distributed intelligence in humans (i.e. neurons that exist in other parts of the body beside the brain)

First, I strongly believe that "physiological dimensions are just a manifestation of the more fundamental units- cells and genetics". And this is in fact should be a motivation to develop physiological models. Modeling can help us show 'constructively' that the intelligence at cellular level can generate physiological system. Through many models have shows the development of higher order structure from lower structure, these higher order structures are generally not physiological systems.

Second, about the statement "One of the main problems is the scaling up feature from the cellular to the physiological dimensions." Could you be more specific please?

Third, regarding bioinformatics and related things, how important it is to consider the exact gene functioning? We eitherway not have full knowledge about any of the pathways, so what about working a higher level of abstract? I see a drawback this approach that it may be useful to find a exact drug target, but, it can help in understanding the life from different perspective. This definitely not the alternative to bioinformatics-based approach but I think can significantly add to that.

A good and difficult question. You say, Sandeep, that : I strongly believe that "physiological dimensions are just a manifestation of the more fundamental units- cells and genetics". Here is your contradiction - you want to adress the WHOLE with an elementaristic approach. Although elementarism is a trend of current biology, likely the people somehow recognise that organisms act on their own. Evolution of species gives a lot of food to think over.

@Dr Jekaterina: Thanks for your opinion. My believe that "physiological dimensions are just a manifestation of the more fundamental units- cells and genetics" is based on  the fact that even the evolution can be broken into two elementary process named 'mutation' and 'selection'. Both of these are significantly lower scale (both in time and space) phenomena but have been proposed to derive the process of evolution. And this idea of 'mutation' and 'selection' is reasonable old.

Thoughts??

Thanks Dr Scheler for your opinion. Yes I agree there are models for multicellular systems, however most of these models do not take physiological aspects (e.g., blood flow, tissue geometry, O2 flow etc.) into consideration. Yes, some of the heart models are exception to this.

Though the components of the model depends on the exact problem of interests and research questions, I am just wondering that is it possible to go for drug development without considering these physiological aspects? Alternately, if I draw a parallel from the field of aerospace engineering, we have flight simulators which one can use to simulate the flight journey before actually starting the journey. However, we do not have simulators for organ which can be used to study the drug efficiency/efficacy. If developed, will such models help in cutting the drug development time? and, what are the challenges to that? 

Dear Sandeep, you say that; " even the evolution can be broken into two elementary process named 'mutation' and 'selection'. Also this, although popular, may be not the only way of evolution. There exist parallel views on the instancy of creation of the complexity and I rather believe in this. I would recommend the books by Alexander Markov https://en.wikipedia.org/wiki/Alexander_V._Markov

I do not know if he wrote not in Russian but there are similar views by other people. Excuse, dear Sandeep that I do not have time to provide you with more references but you will certainly find them. And first of all, read on thermodynamics of dissipative systems. It gives much more realistic view on biological systems. With best wishes, Katrina

Thank you very much Dr Jekaterina. I just just about the hyperbolic model by A Markov. This is indeed very interesting. 

I will dig out further reference about this line of thought and will read about the thermodynamics of dissipative systems. I think this will be even interesting. 

Back to the original questions.

@Dr Jekaterina and Dr Scheler: So, is it the complexity of evolutionary process, atleast one of the reasons, which make is difficult to develop physiologically relevant mathematical models?

My answer is "yes".

But this can be modelled with some aproximations. Allow more physics into biology! Physics makes the things simpler. You have much ahead. Good luck!

Katrina

I actually disagree. I think there have been more successull whole organ or whole system models than cellular models.  Whole organ models such as kidneys and liver are becoming a reality. We have even grown to the extent where we can make engineered kidneys and livers using MEMS technology.  This can only be done if we have an appropiate model of the whole organ.  The only organ that is next to impossible  to model is the brain because it includes not just physics but also  a lot of information processing which is outside the realm of physics.

I think cell level models are possible to certain extent such as if we consider the ion channel pathways or some individual pathways.