PureInsight | April 11, 2002
The biological research in the last century has taken the approach of reducing the organism into the smallest parts. For example, to understand the biology of bone, bone as an organ is first reduced to the level of tissues, which can be examined under a microscope. Different bones can be grouped based upon the differences at the tissue level. To understand how bone is formed, the study of bone even at the tissue level is inadequate. So bone tissues are further studied by examining the different types of cells, such as the bone-forming osteoblasts and the bone-absorbing osteoclasts. To study these cells, the osteoblasts and osteoclasts are then isolated from the bones, placed into Petri dishes that contain defined concentrations of inorganic and organic compounds. Then, the properties of these cells in such a defined artificial environment are studied. The studies at the cellular level are also driven by defined hypotheses. For example, a researcher first raises a hypothesis such as compound A can alter the ability of osteoblasts to make bone matrix. Then, the studies are carried out to specifically test the ability of the compound to alter the amount of bone matrix, in a defined setting with specific concentrations of chemical compounds. In such a defined setting, researchers further study the way the osteoblasts receive the instruction from compound A from outside of the cell and then relay such a signal from compound A to the cell to tell the cell to make new bone matrix. To understand this, the researchers then study the composition of cells. By breaking open the cells, researchers then find that cells are made of lots of molecules, which form different micro-systems (organelles). Each organelle consists of a distinct structure, composition and function. The make-up of each micro-system, the organization of each system and the rules of the operation of each system are approached again by breaking apart these systems and studying each system in a defined setting. For example, to study how osteoblasts can respond to compound A to make a bone matrix component, cells are broken apart and then proteins that can bind compound A are isolated. Once a "receptor" for compound A is found, then the next step is to discover how the receptor functions to communicate with the rest of the proteins in the cell. Such studies belong to a new field called signal transduction. Since cells are immersed in a "protein soup," each of which can initiate signal transduction, different research labs generally focus upon one extracellular signal molecule. The current state of biological research can be described as different research stations working on different molecules and different pathways. Each molecule works by communicating with several other proteins, via protein-protein interactions, which are dictated by their intrinsic affinity based on their chemical compositions. Such interactions, either transient or permanent, occur in a highly ordered fashion over a period of time and within a defined space. Any pair of protein-protein interactions leads to some degree of transient or permanent imprint and becomes the basis for subsequent signals. For example, some protein-protein interactions induce quite significant changes in the shape of a protein (conformational change). This changed protein can then bind to other proteins. Before the change, the protein could not interact with other proteins. Such an "imprint" would be very transient if the dissociation of the initial interaction allowed recovery of the original conformation of the protein. It would be less transient if the interaction of the third protein stabilized the new conformation. In another case, the interaction of one protein (A) with a second protein (B) could lead to a chemical reaction that adds a phosphate group to (or takes off a phosphate group from) the protein (A). The change can be again more or less transient, dependent upon the availability of the enzymes that can reverse the original modifications. In a third case, the interaction of one protein (A) with a second protein (B) could lead to a chemical reaction that produces another protein, such as the well known ubiquitin protein, which is a small protein that is made abundantly. Such a modification, called ubiquitination, can lead to alteration of the ability of the protein A to interact with other proteins, the alteration of the localization of the protein, or the ultimate destruction of the protein, depending upon several different ways the ubiquitin protein is added onto protein A. The change can be again more or less transient (except the destruction of protein A, which is final), depending on the availability of the enzymes that can reverse the original modifications. So, for any given protein, the following states exist: 1) newly made, original state, 2) participation in interaction with another protein but left unmodified, 3) modified and 4) degraded. In an interesting way, these stages are very similar to the life stages of a human being. A specific protein can interact with many different proteins. Such an interaction is dependent on many extracellular and intracellular factors. Any protein can be modified in many different ways, and these are also determined by many different factors from within and outside the cell. The protein levels and localizations are also dynamically regulated by these factors. As a result, the communication between different proteins is dynamically regulated and ever changing. For example, protein A, at concentration 1 can interact with protein B when signal 1 is present. However, at concentration 2, it can interact with B and C when signal 1 is present. At concentration 3, it can interact with only C and D when signal 2 is present. At concentration 4, it can interact with B and D if signal 1 is present. All these will again be different when signal 2 is present. All these again will be altered when signal 3 is present. All these will again be different when signal 1 and 2 are present together. All these will be different if signal 1 occurs before signal 2. All these will again be different in a different cell type since the interaction partners for protein A are different in the different cell types. Imagine that a cell is immersed in one hundred different signals, whose levels are constantly changing, with more than 100 receptors on the cell, which are also subjected to changes. The receptors are connected with immediate interaction partners, whose levels and interactions are also subjected to dynamic regulations. These immediate interactors again interact with secondary interactors, which again interact with tertiary interactors. There is another factor that escalates the complexity to a new level. Due to the involvement of a single protein in multiple regulations, the change in one molecule will lead to the simultaneous change in a network of molecules. This rapidly cascades into changes in many different molecular events of the entire cell. If we place such a complex picture of a cell back into a tissue, which involves the communication between a large group of different cell types, and then place the tissue back into an organ, which involves the coordinated communication between different tissues, and then place the organ back into the body, which involves the communications between each organ, then we should have a sense of the immense and almost infinite complexity of the biological system at the level of an organism.
In the human body, the complexity is enhanced. At the level of a human body, the communication signals are no longer easily detectable by physical means. These human communication signals, such as speech, music, painting and number, are sent and received in various ways. Human beings have a set of uniquely high organs that can decipher meaning from symbols. The perception of these symbols triggers a cascade of events that quickly manifest at all levels, from organ, to tissue, to cell and to intracellular molecular events. The "readouts" of these events are only known to the individual human being who experiences the process. They are then described by the human being in abstract concepts, such as love, hatred, fear, anger, sadness and happiness. The "signal transduction" at the human body level is extremely powerful and complex, but the studies of the nature of the "signals" and "readouts" currently belong to many different fields in a fragmented way and are almost totally placed outside of the field of biology. Most of our current knowledge in the field of biology is derived from studies of non-human subjects using artificial man-made systems. This then raises an important question about what approach we shall take to study human biology and the directly relevant field of human medicine.
With the completion of the human genome project, which accomplishes the identification of the DNA sequence of the human genome, biologists, with the help of advanced detection and computational technology, hope to decipher the functions of all genes. How can such a monumental task be accomplished? If the function of a gene is fixed, then there is no question that we will be able to eventually identify the functions of all genes. However, if the functions of each protein vary in different cells, at different times and under different conditions, then the hope to unravel the functions of 500,000 proteins at any given time, in any given cell and under any given condition is certainly not a human task. Even if we can map out all these details for one human being, can we assume that the same will apply to all other human beings? We have observed that proteins can behave very differently under different extracellular and intracellular conditions. The conditions that alter a human body include the most complex signals, both in physical and non-physical forms, all of which are constantly communicating with a sophisticated reception system and expressed in both physical and non-physical ways. The growth and differentiation of a cell and its responsiveness to any extracellular signal at a given time are determined by the history of the combined signals a cell has received. If we view a human body as a giant cell, the responsiveness of a human body to physical and non-physical signals from the environment is certainly also determined by the combined signals one has received during his or her life. The evidence for the different responses of different human being to the same signal is all too apparent, but so far such differences are not interpreted at the biological level.
To summarize, a human being can be viewed as a cell, which is constantly changing in response to different signals from the outside. In this case, the signals from the outside are physical and non-physical. These signals are sent and received by human beings via different vehicles. For instance, written language. Many of the artistic expressions of the human spirit can be viewed as vehicles of signals, such as music, painting and sculpture. These signals, like the cytokines in a human body, are regulated at a system level. In this case, the system is the entire human society, which can be viewed as the "tissue" for the "cell" (individual human being). The level above, which corresponds to the level of an "organ," is the Earth system with many different "tissues," such as those formed by microbes, plants and animals. The level above the Earth system is our galaxy. The level above the galaxy is what we might call a universe. So, if we truly take the system view all the way, human biology can only be properly studied in the system of our entire galaxy. From this, we see that human biology is an integrated field of study of the human being (cell level), human society (tissue level), the Earth Ecosystem (organ level) and the galaxy (body level).
So, we start by examining the complex web of communication between different molecules in the cell, to the recognition of the complex web of communication between different human beings in human society. When we ask the question, "If we map out and then input all the fine details of molecular composition and interconnections between the molecules in a cell, into a computer, can we understand the nature of the cell and predict the future of the cell?" The answer is, "No, since you cannot predict the signal inputs from outside of the cells and it is the total signal input that determines the function of a cell at any given moment." If we then ask, "If we map out and input all signals from outside of the cell in a given tissue, can we understand the nature of the cell and predict the future of a cell?" The answer is, "No, since you do not know the signal input at the organ level." Following this line of thought, the question we are really asking is, "Can we ask a computer to figure out how the universe works?" Even if we can put all information in the entire universe into a computer, the next question is, "What is signaling the universe?" Can a computer answer this question?
We use our intellectual mind to approach life phenomena and realize that they are far too complex for a human mind to decipher. So, we then think that a computer may be able to solve this problem. But a computer lacks many features of the human mind, so we reject it as a means to the solution.
We started by looking at molecules, the building blocks of cells, to try to understand how molecules work together. Then, we realized that the molecular activities of cells in a living human being are controlled by layers and layers of signals and therefore can only be understood by placing the cell in the complete system of the macrocosm if we wish to predict and understand the cell's behavior. If we ask, "What is the composition of a molecule?" Molecules can be broken down into atoms. Atoms can be broken down into electrons, protons and neutrons. Electrons spin around the protons and neutrons. Then, of what are these subatomic particles made? They are made of smaller and smaller particles, each in motion in a vast space. The particles are not solid balls, but are primarily a manifestation of space and motion. The phenomena observed at the subatomic level are reminiscent of the phenomena of the macrocosm. When our intellectual mind reaches out into the macrocosm or the microcosm, we feel their impenetrability.
So are we doomed to be ignorant? Or are we looking in the wrong direction? The phenomena are complex and beyond the comprehension of the human mind or a computer. The reason we look at phenomena is to understand the meaning of and the laws behind them. Is there a fundamental law behind all phenomena? Are all the phenomena only the manifestation of one law? Since there are no motionless particles in the entire universe, then what is the force behind the physical world? We call the force that drives a human being the human consciousness or the human spirit. Human consciousness cannot be measured and calculated, but is constantly working. Fortunately, it has the ability to be aware of itself! If the human spirit governs the activities of a human being, then the activities of all other forms in this physical universe are also likely to be governed by some form of non-physical force or spirit. The only reason we do not know of the existence of spirits behind all physical manifestations is that our consciousness is limited by the human body. However, there are some who do see spirits and others who recall their previous existences as animals, plants or even rocks.
Human biology needs to face some fundamental questions that have been raised in religion, metaphysics and cosmology. The fragmented human mind created different fields of study. If we wish to take a systems approach to human biology, we need to take a systems approach to life in general. The study of human biology cannot exist independently from the study of the human spirit. The ultimate understanding of health and illness of a human body can only come from the understanding of the laws that underlie the deeper connection between body and spirit. Such a goal, therefore, calls for the end of the old paradigm of the separation of matter and spirit. The field of human biology might be ideal for the unification of all scientific disciplines, which, only by working together as one "body", could make a great leap forward towards the understanding of the fundamental law of life itself.
