Monday, August 1, 2011

Biomedical Research Needs a Paradigm Shift

Without a major shift in how the medical establishment defines the nature of reality and its relation to human physiology, we are nearing the limit of what we can accomplish in biomedical research and its treatment of disease. The best example of this is cancer. In 1984, the National Cancer Institute (NCI) launched a program it claimed would halve the 1980 cancer mortality rate by the year 2000. Despite the fact that the NCI budget increased twentyfold between 1971 and 2003 (to about $4.6 billion), progress with cancer mortality rates during that period was modest. A review of the rates between 1980 and 2000 reveals that incidence rates in women for all cancers combined actually increased.1 For men there was more fluctuation: first an increase, then a decrease, then a stabilization.2 The overall net result, however, is that between 1990 and 2000 cancer mortality rates decreased in numbers ranging only from .08 percent a year to 1.8 percent a year.3 Given the major public health impact of cancer and the huge expenditures of research dollars, this disappointing result should raise some serious questions.
I believe the problem lies in two fundamental principles currently dominating biomedical research, both of which are based on outdated assumptions. The first is reductionism, the belief that complex diseases can be understood by dissecting them into their individual subcomponents (for example, genes, receptors, transcription factors, and signaling pathways). The second is materialism, the belief that matter is the primary cause of all physiological functioning, diseases, cognitions, and thought processes.
Reductionism – The Parts Are Greater Than the Whole
The greatest problem with reductionism is that it ignores the concept of emergent properties, the characteristics that emerge from the synergistic interactions of multiple units (such as genes and cells) that are not present in the individual components. An illustration of an emergent property is temperature.4 The temperature of a liquid, solid, or gas is defined as the average velocity (rapidity of motion) of all the atoms or molecules of the substance being measured. Knowing the velocity of a single atom, for example, gives no information about the temperature of the total substance, because increasing the velocity of one or even several atoms may not cause any temperature change since other atoms may simultaneously decrease in velocity. In fact, this is the case when temperature remains constant. The emergent characteristics of the collective particles (temperature resulting from movement) cannot be predicted or understood even by knowing everything there is to know about, for example, water’s individual atoms of hydrogen and oxygen.
In human physiology, organ systems are examples of emergent properties. Knowing everything there is to know about a cell in the heart (for example, a muscle cell) does not provide enough information to predict the function of the heart, nor does knowing the sequence of DNA base pairs that make up a single amino acid provide enough information to predict the characteristics of a transcription protein composed of many amino acids. In other words, the whole is more than the sum of its parts. The same principle applies to complex diseases, which evolve from the interaction of multiple genes and environmental factors occurring at single points in time and in other ways during the progression of the disease. What is more, we know that gene function varies and that one gene can have multiple functions based on environmental triggers that turn it “off” or “on” and regulate the extent of its activity. One of the consequences of these complex interactions is that gene expression varies greatly based on the cellular environment.5 If the gene isn’t consistently functioning the same way, it will not always be associated with the same phenotype or disease outcome, even if its function is important for that particular disease. This is one of the reasons that genome-wide association studies that investigate single genes are so difficult to replicate.
Thus, while investigating individual genes or signaling pathways is important, it doesn’t provide a complete picture of disease causality unless used in conjunction with research on multiple interacting systems – with cancer, this would mean those that fight against cancer by killing or repairing mutated cells. When experiments on single pathways are interpreted alone, they can lead to inaccurate conclusions. The analogy of blind men experiencing an elephant for the first time is appropriate here. The man feeling the tail says that elephants are like snakes, skinny and flexible. The man feeling the leg says that elephants are big and round like trees. The man feeling the tusk says that both of these descriptions are wrong because elephants are hard, smooth, and curved. Needless to say, all are partially correct, but none is even close to describing the essence of the elephant. Similarly, a detailed description of the well-known breast cancer genes BRCA1 and BRCA2 does not provide nearly enough information to understand the etiology (cause) and progression of breast cancer. Many women who have these genes don’t get cancer, and many women who get breast cancer don’t have these genes.
Our beliefs about etiology are important because they influence how we design experiments and which variables we choose to investigate. If we believe that cancer can be reduced to a single gene mutation or signaling pathway, for example, the study design will reflect that, and we may ignore relevant factors that don’t fit this concept. A receptor in a chemical preparation outside the body will react differently to a stimulus than the same receptor in its natural environment in a living system, because the receptor outside the body is in an unchanging chemical environment. Genes and receptors in living systems are constrained or stimulated by a surrounding environment (for example, transmitter substances, immune parameters, hormones, etc.) that changes dynamically to meet the body’s needs. Genes can be functionally turned off and on by ambient factors that are influenced by our environment, such as nutrients, stress hormones, toxicants, and so on. In addition, many genes have multiple functions that adapt to meet the demands of the surrounding environment. Most animal models used in cancer research are genetically modified because it is difficult to get a tumor to grow in an “intact” animal. The reason is that the body’s natural defenses against tumor growth (such as DNA repair, programmed cell death, and immune function) respond by destroying the tumor cells. So the way that a study is designed plays a key role in determining the results as well as their generalizability to real-life situations.
Fortunately, a number of medical scientists have begun to grasp this fact, and they are beginning to use approaches that have been collectively termed “systems biology” to try to investigate the simultaneous interaction of multiple complex systems. Though still in its infancy, systems biology accompanied by new mathematical approaches has great potential for improving our understanding of disease causality.
Materialism – Matter Is Primary
Unfortunately, the same progress has not been made with the second faulty assumption – the belief that matter is the primary cause of all physiological functioning, diseases, cognitions, and thought processes – which currently dominates and limits biomedical research. Because this assumption has not yet been recognized, no attempts have been made to resolve it. The consequence is a fundamental divergence between the ways modern physics and modern medicine define the nature of reality, which hinges upon the fact that biomedical research has not incorporated the implications of quantum theory into its hypotheses. Biomedical research still focuses solely on particulate matter, refusing to investigate or acknowledge the functional importance of the intrinsic energetic aspects of living systems. In essence, medicine is only examining one side of Einstein’s equation. Without the inclusion of both sides, we will continue to be like the blind men describing the elephant, describing bits and pieces without understanding the fundamental essence of humanness or complex diseases such as cancer.
Einstein long ago showed us that matter and energy are interchangeable. This means that energy can be created from matter and that matter can be created from energy. We can all think of examples where matter is converted to energy, such as a fire that converts wood to heat energy. But Einstein’s equation, E=MC2, means that energy can also be converted to matter. This was verified as early as the 1950s, when it was demonstrated in a cyclotron that matter could be created from fast-spinning energy.
Quantum theory went a step further by showing that at a subatomic level, distinctions between matter and energy blur. One of the most well-known quantum physical experiments showed that whether light consisted of particles or waves (matter or energy) depended solely on how the experiment was set up. This completely contradicted the world of Newtonian physics, which defined reality as an objective state totally independent of the observer. The problem that quantum theoretical experiments present is that at a subatomic level, the little building blocks of matter disappear so that energy and matter become two aspects of one and the same reality. This is not some abstract theory but has been experimentally verified over and over again and is the basis of many of the electronic components in use today.
Quantum theoretical experiments have also shown that whether light appears as particles or waves depends on how the measurements are made. Despite the fervent wishes of some of the discoverers of quantum mechanics, this is not a function of measurement error but a statement about the nature of reality – it cannot be reduced to little building blocks of matter. We influence the outcome of our experiments by the way we measure, which has enormous implications for biomedical research.
The fact that matter and energy are interchangeable at a subatomic level means it is difficult to say which of them is primary. What quantum theory leaves open is the distinct possibility that energy may actually be primary and matter secondary – that energy “congeals” (for lack of a better word) into matter at a lower vibrational level. Another interpretation is that matter and energy are always coexistent. Either way, both of these concepts contradict the fundamental assumption of biomedical research that all causality can be found in particulate matter. Materialism has been disproved but not discarded, and it is time to examine the consequences that this bias has for scientific inquiry.
Consider the implications of common diagnostic methods. Hospitals regularly use ECGs (electrocardiograms) to assess heart function and to diagnose heart disease, as well as EEGs (electroencephalograms) to assess brain function and to diagnose diseases such as epilepsy. These instruments measure energy fields on the surface of the body, which are emanating from inside the body. But based on the belief that disease causality can only be found in matter, we assume these energies have no function – they can accurately diagnose function but are not causally related to it. This relegates them to the category of epiphenomena (secondary outcomes), although in some cases they are the most reliable measure of disease status that we have.
This type of assumption is important because it influences what we choose to investigate and can inadvertently introduce bias. If we only investigate the elephant’s tail, we may conclude that elephants are skinny and move like a snake.  If we only investigate particulate matter, we will definitely find significant correlations, but will it help us understand causality and provide enough information for effective treatments? Physics is the essence of biochemical processes in the body because chemical bonds consist of electromagnetic or electrostatic attraction between atoms. Examples are a covalent bond, which occurs when two atoms share an electron, or the creation of an ion, when one atom takes an electron from another and creates an unbalanced charge in the electron-depleted atom. These bonds are energetic forces that are needed to create molecules, so energy is fundamental to chemistry. Since chemistry is the basis of all processes in the body, whether it is the creation of hormones, neurotransmitters, cell metabolism, or any other process, energy plays a very prominent role in function. What is not well known is how relevant energy is for genetics.
DNA is packaged in the nucleus by being wrapped around a positively charged group of histone proteins, sort of like thread wrapped around a spool. What keeps the DNA in place is an attraction between the negatively charged DNA and the positively charged histone tails. This packaging not only helps the DNA fit inside the nucleus, it keeps the gene from being expressed until it is needed. In order to become functional, the DNA must be unwound from the spool so that factors that help to activate it can reach it. For this to happen, the electromagnetic charge between DNA and protein spool must be dissolved. In short, energetic forces are fundamental to every process in the body, starting with genes and moving to the level of organ systems. (See note #6 below to access a more detailed description of electromagnetic phenomena in biological systems.)
Bringing Physics and Biology Together
Despite the importance of energetic aspects to human physiology, we limit research on functional mechanisms and treatment modalities to particulate matter. This is not consistent with quantum theory and makes the primary theoretical framework of biomedicine more than ninety years out of date. As cancer statistics show, the true “essence of the elephant” is still eluding us. Cancer is currently the second leading cause of death in the United States, and it is expected to become the leading cause of death within the next decade.7 Estimated costs for cancer in 2010 totaled $263.8 billion, including $102.8 billion for direct medical costs, 20.9 billion for indirect costs of morbidity (for example, lost productivity from illness), and $140.1 billion for lost productivity due to premature death.8 Clearly, we have a long way to go in our understanding of this disease. After many years of increasing investment and diminishing returns, the question we must begin to ask ourselves is, Are we using the right paradigm? Given the experimentally verified validity of quantum mechanics, I believe it’s time to seriously consider the implications for biomedical research.
So, what kind of research do we need? Consider the following example. Acupuncture as a treatment is more than two thousand years old and is regularly used in China to treat a multiplicity of diseases. It is based on the theory that there are energy meridians in the body and that when they are out of balance, susceptibility to disease increases. Because this paradigm does not fit Western medical concepts of disease causality, it has essentially been dismissed. The medical community has limited acupuncture’s potential usefulness to pain relief and therapy for nausea from chemotherapy. Such limited use contradicts research reported at a 1997 Consensus Development Conference on Acupuncture held at the National Institutes of Health, which covered basic studies on mechanisms of action from acupuncture treatments, including the release of opioids and other peptides in the central nervous system as well as changes in neuroendocrine function.9 Studies found acupuncture also influenced other physiological systems including substances that constrict and dilate blood vessels, those that stimulate or calm the nervous system, and those that affect reproductive and immune function.
Close examination reveals that acupuncture needles are not inserted in places that would logically elicit these effects based on traditional anatomy. So what can explain them? It is interesting that many of the molecules in the body (water molecules, protein molecules, etc.) are dipoles. A dipole has both a positive and a negative charge, sort of like a magnet except the strength of the attraction isn’t constant. Theoretically, the structure of dipoles would allow them to align with other dipoles in “strings.” Is it possible that the acupuncture meridians are strings of dipoles held together by their electric charges? If that is the case, the structure of these meridians might be partially determined by the geometry of the body. If such meridians exist, the insertion of acupuncture needles might function to modulate their orientation by changing the vibration of atoms in nearby molecules, resulting in the propagation of an electromagnetic wave along the meridian.Since the chemical properties of atoms and molecules are determined by their electron configurations, which in turn determine the types of bonds they form with other molecules, a perturbation at a particular point in a meridian might be associated with a specific range of chemical changes (for example, neuroendocrine or immune changes).10
The concept of longitudinal electric modes based on the dipolar properties of cell membranes was introduced by Frohlich in 196811. From a technical perspective, and according to his theory, components with electric dipole oscillations interact through nonlinear long-range Coulomb forces and thus establish a branch or branches of longitudinal electric modes in a frequency range of 1011-1012 sec-1. If the rate of energy supply to the relevant components is sufficiently large, it gets channeled into a single mode which then presents a strongly excited coherent longitudinal electric vibration whose wavelength depends on details of the geometrical arrangement of the components.
This is only one example, and it illustrates that relevant and potentially fruitful avenues are not being pursued in biomedical research because of a dominant paradigm that is no longer valid. It is time for an open discussion in the biomedical community about the fundamental assumptions that influence its work, and quantum theorists should be part of that conversation.

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