Crucial breakthroughs in the treatment of many common diseases such as diabetes and Parkinson's could be achieved by harnessing systems biology, according to scientists from across Europe. In a Science Policy Briefing released today by the European Science Foundation, they provide a detailed strategy for the application of systems biology to medical research over the coming years.
Systems biology is a rapidly advancing field that combines empirical, mathematical and computational techniques to gain understanding of complex biological and physiological phenomena. For example, dozens, or even hundreds, of proteins can be involved in signalling processes that ensure the proper functioning of a cell. If such a signalling network is disturbed in any way, diseases such as cancer and diabetes can result.
Conventional approaches of biology do not have the capacity to unravel these elaborate webs of interactions, which is why drug design often fails. Simply knocking out one target molecule in a biochemical pathway is turning out to be a flawed strategy for drug design, because cells are able to find alternative routes. It is a similar scenario to setting up a roadblock: traffic will grind to a standstill for a short time, but soon motorists will start turning around and using side-roads to get to their destination. Just as the network of roads allows alternative routes to be used, the network of biochemical pathways can enable a disease to by-pass a drug.
Systems biology is now shedding light on these complex phenomena by producing detailed route maps of the subcellular networks. These will make it possible for scientists to develop smarter therapeutic strategies - for example by disrupting two or three key intersections on a biochemical network. This could lead to significant advances in the treatment of disease and help with the shrinking pipeline of pharmaceutical companies using traditional reductionist approaches to drug discovery.
The new policy document, produced by the Life Sciences and Medical Sciences units of the Strasbourg-based European Science Foundation (ESF) calls for a co-ordinated strategy towards systems biology across Europe. The scientists have pinpointed several key disease areas that are ripe for a systems biology approach. These include cancer and diabetes, inflammatory diseases and disorders of the central nervous system.
The report's authors state that the recommendations outlined in the Science Policy Briefing provide a more specific, practical guide towards achieving major breakthroughs in biomedical systems biology, thereby covering issues that had not been previously addressed in sufficient detail. In particular we identify and outline the necessary steps of promoting the creation of pivotal biomedical systems biology tools and facilitating their translation into crucial therapeutic advances.
The report highlights some recent successes where mathematical modelling has played a key role. The conclusions from these examples are that success was achieved when quantitative data became available; that even simple mathematical models can be of practical use and that the interdisciplinary process leading to the formulation of a model is in itself of intrinsic value.
The report's authors believe that, if this document succeeds in prodding European institutions into supporting systems biology, the implementation of the recommendations presented will propel Europe to the forefront of research in systems biology and, in particular, help this interdisciplinary field to fulfil its promise of making a reality of personalised medicine, combinatorial therapy, shortened drug discovery and development, better targeted clinical trials and reduced animal testing.
This Science Policy Briefing is the contribution of the ESF to the EC funded Specific Support Action entitled "Advancing Systems Biology for Medical Applications" (SSA LSSG-CT-2006-037673). The recommendations resulted from ten workshops, in which more than 110 acknowledged experts from across Europe participated.
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Let me give you an example of what I mean. Take this insight - "Simply knocking out one target molecule in a biochemical pathway is turning out to be a flawed strategy for drug design, because cells are able to find alternative routes.". This is a clear sign that what is going on is that there is a larger causal factor in the background driving the disease process that hasn't been acknowledged or identified. I don't know if these scientists have been smart enough to work this out but their approach suggests not.
The scientific response is to use the same approach of suppression but at a more subtle level - it is still a "block the highway approach" as opposed to eliminating the reason for the need of cars to come down the highway in the first place.
Here is what i mean - "Systems biology is now shedding light on these complex phenomena by producing detailed route maps of the sub-cellular networks. These will make it possible for scientists to develop smarter therapeutic strategies - for example by disrupting two or three key intersections on a biochemical network."
The systems approach to health is the basis of Ayurveda and Chinese medicine. It is nothing new. The difference between the systems theory embodied in systems biology and these more mature systems appears to be their definition of what comprises a system. Systems biology is still caught in reductionist land but can't see it.
The Chinese and Indians take a cosmological view of systems. The Earth is a body just as the human is a body. Both are subject to the cycles of birth, maintenance and decline, the seasons etc. Both are predicated on stability but live in an environment of constant change. In order to maintain stability theses systems need to be able to constantly adapt. But these systems are subsumed in each other. At a larger level the human body and the earth body are part of a larger universal system.
Given the interdependent nature of the earth and human bodies and the fact that the earth body is the larger environment in which the human body is located and is its source of support and nourishment, we should be able to make the assumption that changes in the earth body will be reflected in the human body. So is this true?
The big picture is that 99.9% of species that have lived on this planet are extinct. This extinction was caused by changes to environmental conditions. Species are adapted to and evolutes of specific environmental conditions. When these conditions move out of a specific range the species die. There have been at least 5 extinctions in the past and we are in the middle of a sixth at the moment. The difference between this sixth extinction and the past 5 is that this extinction is being caused by us humans. We are changing the environment.
How are humans changing the environment? Let us assume that some version of the human species has been around for a million years. Now in the giant scale of the universe or the earth where time moves in billions of years this is like a nano second. Over these billions of years fossil fuels have been sequestered in the surface of the earth in the form of coal and oil.
History reveals that the complexity of society depends on its capacity to preserve and harness energy. The modern western society is less that 300 years old. And its beginnings can be identified with the discovery of the steam engine and the capacity to harness coal as an energy source to do work. Prior to this the human race relied upon food, fire, slaves, animals, water and wind for energy.
The next level of energy acquisition came with our capacity to harness oil as an energy source. We have used oil to increase crop yields at least 3 fold and this in turn has allowed the population to increase exponentially. It has also produced processed, energy dense, nutrient deficient foods. These refined foods are playing havoc with body feedback systems that evolved on a diet of complex unrefined foods.
At a larger level, the liberation of fossil fuels has, and is continuing to, liberated heat. This is manifesting itself as global warming or climate change. Planet earth is suffering from a systemic inflammatory condition. And this inflammation is manifesting as various symptoms such as increased storms, floods, droughts etc. You might like to think of these as "symptoms" of "systemic inflammation" that are manifesting as changes to local environmental conditions.
Given that the human body exists as a sub system of the earth body we should expect an increase in "system inflammation" in the human body and for this to manifest as changes in local body climates. And from an Ayurvedic understanding this is what we are seeing in the world today. Chronic disease may have names like diabetes, cancer, heart disease, arthritis etc. But these are simply symptoms of "systemic inflammation". They are the equivalent to the floods and droughts.
What has happened is that reductive science has forgotten that there is no absolute basis for calling something arthritis or diabetes. These are names that emerged out of a disease classification system that is predicated on a reductive world view that rejected anything "hidden" from objective measurement devices. From the Ayurvedic perspective chronic diseases are better seen as processes. Chronic diseases are the way that the body is responding to environmental changes. Just as some countries become drier and some wetter so some people will manifest "diabetic symptoms", others "arthritic symptoms" and yet others "heart disease symptoms".
Just as we can't stop systemic global warming and climate change by taking pharmaceuticals, we can't stop systemic inflammation in the human body by taking pharmaceuticals. The only way to resolve the problem is to resolve the cause.
Now sadly we won't have to wait to long for the causes to resolve themselves, especially if the peak of human thinking is represented by what is being called systems biology.
The energy source that has both powered our modern society and our inflammatory environment is finite and rapidly running out. It has at maximum a 400 year limit and we are well into the last quarter of that. At the same time the global population is still growing and we are addicted to a "growth economy". If you understand the realities of finite energy resources, the laws of thermodynamics / energy and exponential growth the only conclusion for the human race is abrupt decline and possible extinction. At the very least we will revert to a level of societal complexity commensurate with the per capita energy available to us.
Excuse the diversion. Lets get back to the original observation that classic biology was unable to comprehend true systems level thinking. It tried to block the highway to stop the symptoms. But because it never acknowledged or stopped the cause of the symptoms the cause persisted. In this case systemic inflammation remained. Because of this, the inflammation simply found another route and as in the case of COX-2 inhibitors the inflammation continued and manifest its symptomatic expression in the blood vessels. Arthritis had been transformed into heart disease.
So what exactly does "systems biology" propose to do? Are they looking for the cause of the system inflammation and working at that level? No. They are playing more of the suppression game. Only now they are planning to block more than just the main highway. They think that their new map which shows sub roads will allow them to stop the inflammation by blocking these routes too. This is madness - total delusion.
I can tell you what will happen right now if we go down this route of blocking symptoms. The inflammation will continue unless its cause is removed and more sophisticated blocking will simply result in more sophisticated adaptation in the body. This is like the arms race or terrorism. The more sophisticated we get the more sophisticated the opposition gets and the more subtle and dangerous the situation becomes.
True systems level thinking will recognise that systems biology - as it is defined here - is a delusional waste of energy as is any human level "arms race" level activity. Systems thinking requires an internal rewiring of the human world view that is able to include a larger and more complex web of life and longer time horizons. Humans can never win an evolutionary battle against bacteria and viruses. Because of their shorter lives they will always be able to adapt more over a give time span that humans - and we are mainly a collection of bacteria that lives symbiotically with human cells. Our human ecosystem probably has at 10 to 20 times as many bacteria as human cells.
Our only chance as a human species is to shift from a competition approach to co-operative approach. We need an expansion of consciousness that is accompanied by a change in our world view and what we value in life. We need to get a grip of the concept of limits to growth, of how exponential growth functions, of how complex systems interact and of the differences between causes and effect.
Our current disease are a reflection of a confluence between the human system that evolved in a low energy environment and a high refined energy, low exercise, high mental and emotional stress environment. The human body is reacting predictably to the changed environment. Yet because there is a delay between cause and effect and we don't have inbuilt "long term negative feedback" loops we fail to recognise the negative effects that our current behaviour is having. This is unsurprising given that we evolved in times where we lived day to day. If we are truly smart we will use our intelligence to create external negative feedback loops where they fail to exist - we wont waste our valuable limited energy playing more and more subtle arms races that fail to address the casual factors.