Research by the Harvard Medical School and others has demonstrated that the practice of Qigong positively affects gene expression, the immune system, nervous system, and cellular function allowing cells to live longer -- true "anti-aging" and the legendary "fountain of youth". Qigong promotes gene transcription for stress reduction and improvement of immune function. The scientific basis of Qigong is explained in part through the convergence of epigenetics (cellular biology) and psychoneuroimmunology (neuroscience).
Psychoneuroimmunology is the study of the relationship between the mind, or psychological processes, and the nervous and immune systems. The meditation component of Qigong is an example of a "psychological process" that affects physical health and well-being. The moving meditation of Qigong lowers stress, strengthens the immune system, reduces chronic inflammation, and improves cellular metabolism and aging.
Qigong can be considered a "mind-body" practice or "mind-body medicine." Dr. Herbert Benson of the Harvard Medical School and Founder of the Benson-Henry Institute for Mind Body Medicine describes the profound affects of the mind on the body and health based on his lifetime work as a cardiologist and researcher. Dr. Benson compares health and well-being to a three legged stool. The legs are pharmaceuticals, surgery, and self-care. Self-care includes nutrition, exercise, the relaxation response (practices to achieve the relaxation response include Qigong), and belief or faith.
Benson is quick to clarify that faith as a psychological state is healing, regardless of its origin.
"There's a rush towards Alternative Medicine which I essentially believe is remembered wellness". Dr. Herbert Benson.
The idea that the mind can heal is not new. In the early 1950's Norman Vincent Peale wrote The Power of Positive Thinkingwhich became a cultural phenomena. Peale's basic message was that individuals have the power to make themselves sick or well by their thoughts. By the 1960's the power of positive thinking was well accepted by the general population, but not the medical community. A major catalyst for a change of heart came from journalist and author Norman Cousins. Cousins was informed by his doctor that he was unlikely to survive a condition thought to be an autoimmune disorder. He not only embraced the power of positive thinking by refusing to believe his doctor's prognosis, but he also developed a radical new therapy: laughter. Cousins is credited with literally laughing his way back to health against all odds. In 1976 he wrote an article on his experience that was published in the New England Journal of Medicine. This article was positively received by thousands of M.D.s. He later expanded this article on the benefits of laughter and humor in the healing process to his memoir Anatomy of an Illness, published in 1979. Inspired partly by this high-profile case of healing through laughter, the medical community finally started taking notice of the effect of the mind on health in the early 1980's. The neuroscience sub-field of psychoneuroimmunology was one result, and mind-body healing through laughter became the object of serious scientific inquiry. Laughter therapy is widely accepted today even though it's mechanism of action is not fully understood.For example, see Laughter prescription and Laughter Remains Good Medicine.
Mind-Body Wellness. Blue Shield of California Health Library Article. Research shows that what your brain produces depends in part on your thoughts, feelings, and expectations. If you're sick but you have hope and a positive attitude and you believe that you'll get better, your brain is likely to produce chemicals that will boost your body's healing power. Negative thoughts and emotions can keep your brain from producing some of the chemicals that help your body heal.
Psychoneuroimmunology: the experiential dimension. "Experience makes an impact on all adaptive systems, including the endocrine, immune, and nerve systems, and is of the essence, not only for the unfolding of an organisms' healthy status, but also for the development of malfunctional traits."
The phrase "mind over matter" can be summarized in one word: "autogenic." Autogenic means conscious regulation of body function. In the case of Qigong, the mind is regulating the function of the autonomic nervous system through the combination of meditation and breathing. For more information see Autogenic Training.
It's a Gut Feeling - how the gut microbiota affects the state of mind.
The gut microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship with the host. This research describes the components of the gut microbiota and mechanisms by which it can influence neural development, complex behaviours and nociception. Furthermore, the authors propose the novel concept of a "state of gut" rather than a state of mind.
Fake Knee Surgery as Good as Real Procedure, Study Finds. A fake surgical procedure is just as good as real surgery at reducing pain and other symptoms in some patients suffering from torn knee cartilage, according to a new study that is likely to fuel debate over one of the most common orthopedic operations.
The Molecular Basis of Emotions and Health
Dr. Candace Pert's (1946-2013) pioneering work in neuroscience uncovered the primary mechanisms for how mind-body medicine works at the molecular level. A bodywide network of peptides and receptors are the molecular (i.e. biochemical) basis of emotions, wellness, and life itself.
"Every cell in our body has a characteristic vibration. When these cells vibrate at a certain rate and in a certain pattern, the body functions well and the person feels good. When they vibrate at a different rate and pattern, the body functions less well and the person feels not so good … every thought is a pattern of energy characterized by a certain vibratory rate and pattern … the vibratory pattern of the thought and its consequent emotion are experienced throughout the entire body, by each cell, and this vibratory influence triggers the release of certain kinds of neuropeptides which flood through the body … thus thoughts are patterns of energy which influence the functions of the whole body." Dr. Candace Pert in Molecules Of Emotion: The Science Behind Mind-Body Medicine
PBS Special 'Healing and the Mind' with an excerpt of Candace Pert discussing her work (4:14)
Dr. Candace Pert wrote a popular book on her research called the Molecules of Emotion. The following are excerpts from this book:
The nervous system is a network based on neurotransmitters (chemical proteins which consist of peptides).
A "second" nervous system based on ligands and receptors (vibrating molecules/peptides) coordinates the activities of cells throughout the body. This includes the endocrine, neurological, gastrointestinal, and immune systems. Peptides are created throughout the body. Peptides that affect the brain are called neuropeptides. Brain function is moderated by both neurotransmitters and neuropeptides. A "gut feeling" is related to the density of receptors in the intestines.
Emotions are physically instantiated as neuropeptides and their receptors, both of which can be found throughout the body. Physiology and emotions are inseparable. There's a wonderful section in the movie What the Bleep which depicts this process.
Cells are constantly signaling other cells via neuropeptides, which bind with receptors. The signaled cells respond by making physiologic changes. These changes create a feedback loop to the signaling cell, providing a mechanism to moderate the production of the neuropeptides.
Virtually any peptide found anywhere in the body can be found in the respiratory center. This may provide the substrate for the powerful healing effects of consciously controlled breathing.
Psychoneuroimmunology is the study of the functional integration via peptides of the nervous, endocrine, and immune systems. Neuropeptides and their receptors join the brain, glands, the spleen, bone marrow, and immune system in a multi-directional network of communication between the brain and body. At the molecular level, there is no difference between the mind and the body.
Conscious breathing modulates peptide production and activity which in turn creates the healing effects associated with Qigong breathing practices.
Epigenetics (literally, control beyond genetics) is a new field of biology that is exploring the effect of the environment on cellular behavior. The "environment" includes one's physical, social, and electromagnetic environment as well as beliefs, perceptions, lifestyle, habits, behaviors, and mind-body practices such as Qigong. Gene expression is the process by which proteins are manufactured from instructions stored in the DNA. Humans have about the same number of genes as rats, mice, and other mammals (~30000) and roughly 4500 more genes than plants, 10900 more genes than roundworms, and 16400 more genes than fruit flies. There simply aren't enough genes to account for the complexity of human biological processes and behavior. The complexity is made possible by several factors. One is regulatory proteins which direct the activity of the genes. A cell's nucleus contains regulatory proteins and DNA. Environmental signals affect the binding of the regulatory proteins to the DNA within the nucleus as well as the function of the cell through interaction with proteins in the cell cytoplasm, cytoskeleton, and the cell membrane. The environment turns genes on or off through three main processes: phosphorylation of proteins and methylation and histone modification of genes and DNA. In addition, research indicates that "junk DNA" plays an important role in gene expression and is another proposed pathway for environmental signals to affect gene expression.
According to some epigenetics researchers, the true "brain" of every cell is not the nucleus but the cell's membrane which interacts with and responds to environmental signals. A broader view sees the environmental signals affecting proteins both inside and outside the cell, as well as on the membrane. Epigenetics gives a mechanism for a bridge between the energetic basis and the biomolecular/chemical physiological basis of our existence. The "energetic basis" is our fundamental bioenergetic structure and being interacting directly with environmental signals which are different forms of energy, such as light, electromagnetism, sound, heat, vibration, emotions, thought, and the practice of Qigong. See also Bioenergetic Basis of Life.
Why Your DNA May Not Be Your Destiny. Epigenetic changes are biological markers on DNA that modify gene expression without altering the underlying sequence. Researchers have found that environmental and lifestyle factors — such as trauma, stress and even diet — can activate epigenetic changes. Epigenetic traits can be passed down from generation to generation.
Bits of Mystery DNA, Far From ‘Junk,’ Play Crucial Role.
"The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches." NYTimes, Sep. 2012.
The following video gives a short introduction to epigenetics and explains how what you think directly affects cells. A longer, more complete version of the interview can be found in Bruce Lipton 'The Power of Consciousness'.
"Specific frequencies and patterns of electromagnetic radiation regulate and control gene regulation, cell division, cell differentiation, morphogenesis (the process by which cells assemble into organs and tissues), hormone secretion, nerve growth and function....Though these research studies have been published in some of the most respected mainstream biomedical journals, their revolutionary findings have not been incorporated into the medical school curriculum." Bruce Lipton: Biology of Belief
"At its most basic, epigenetics is the study of changes in gene activity that do not involve alterations to the genetic code but still get passed down to at least one successive generation. These patterns of gene expression are governed by the cellular material — the epigenome — that sits on top of the genome, just outside it (hence the prefix epi-, which means above). It is these epigenetic "marks" that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next."
Cancer is a Preventable Disease that Requires Major Lifestyle Changes. According to researchers at The University of Texas Anderson Cancer Center, only 5–10% of all cancer cases can be attributed to genetic defects, whereas our lifestyle and environment account for 90-95% of chronic illnesses such as cancer, the second most common cause of death after heart disease.
After sequencing his own genome, pioneer genomic researcher Craig Venter remarked at a leadership for the twenty-first century conference, “Human biology is actually far more complicated than we imagine. Everybody talks about the genes that they received from their mother and father, for this trait or the other. But in reality, those genes have very little impact on life outcomes. Our biology is way too complicated for that and deals with hundreds of thousands of independent factors. Genes are absolutely not our fate. They can give us useful information about the increased risk of a disease, but in most cases they will not determine the actual cause of the disease, or the actual incidence of somebody getting it. Most biology will come from the complex interaction of all the proteins and cells working with environmental factors, not driven directly by the genetic code”
How the Environment Affects Cellular Function at the Molecular Level -- The Details
Dr. Lipton explains how thoughts, emotions, and the environment affect cells at the molecular level. Genes do not control biology. Genes cause nothing. They are simply blueprints for how to build proteins. Proteins are the primal element of life. Proteins and genes are directly affected by the environment. The popular media has still not really discovered this fact. Lipton demonstrates how the new science of Epigenetics is revolutionizing our understanding of the link between mind and matter and the profound effects it has on our personal lives. The profound health effects of Qigong at the cellular level are due in large part to epigenetics. Lipton clearly explains why the accepted genome and gene functional paradigm is simply incorrect and out of date. Epigenetics is the most important revolutionary discovery in biology tantamount to the discovery of quantum physics as opposed to classic physics.
"The notion that only physical molecules can impact cell physiology is outmoded. Biological behavior can be controlled by invisible forces, including thought, as well as it can be controlled by physical molecules like penicillin, a fact that provides the scientific underpinning for pharmaceutical-free, energy medicine." Dr. Bruce Lipton.
Bruce Lipton basically "wrote the book" on epigenetics, and it's called Biology of Belief. Here are some of his insights from that book:
The function of the nervous system is to perceive the environment and coordinate the response/behavior of all cells in the body
Environmental influences, including nutrition, stress, and emotions can modify genes without changing their basic blueprint
Information that controls biology starts with environmental signals that in turn, control the binding of regulatory proteins to the DNA. The regulatory proteins direct the activity of the genes.
The malignancies in 95 percent of breast cancers are derived from environmentally-induced epigenetic alterations and not defective genes.
Humans have about the same number of genes as rodents; only 9000 more genes than fruit-flies; and only 1500 more genes than microscopic worms. How can we be so complex with so few genes?
The nucleus of a cell is simply a memory disk, a hard drive containing the DNA programs that encode the production of proteins - proteins are part of the endocrine system and they control the autonomic nervous system as well as all other bodily functions
Since each atom has its own specific energy signature (wobble or vibration), molecules radiate their own identifying energy patterns. Every material structure in the universe, including individual humans, radiates a unique energy signature.
Specific frequencies of electromagnetic radiation regulate DNA, RNA, and protein synthesis, alter protein shape and function and control gene regulation, cell division, cell differentiation, hormone secretion, nerve growth and function.
Protein synthesis, or folding, is where proteins (poly-peptide chains) are instantaneously transformed into their final three-dimensional state. The signaling speed required to make this happen is faster than is possible via a bio-chemical mechanism. In other words, the signaling seems to require electromagnetic (or faster) speeds.
Electromagnetic or acoustic vibrations can create a constructive interference or "harmonic resonance" in atoms. The atom absorbs energy and starts to vibrate faster as a result. Kidney stones have been treated by doctors with constructive interference mechanics. Focused energy waves interact with atoms.
Thoughts, the mind's energy, directly influence how the brain controls the body. Thoughts, a form of energy, can activate or inhibit the function of a cell's proteins via constructive or destructive interference.
Our conscious mind experiences the chemical communication signals between cells as emotions.
If positive thinking/emotions is good for you, imagine what negative thinking can do. See nocebo.
Epigenetics on PBS' NOVA
This video is from the Public Broadcasting System NOVA program. It is yet another explanation of epigenetics and the effects of the environment on gene expression. Genetically identical twins and mice have differentially expressed genes. The epigenome silences different genes to make cells different from one another. The epigenome regulates the genes.
Epigenetics and Pharmaceuticals
Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology. The term "Epigenetics" refers to DNA and chromatin modifications that persist from one cell division to the next, despite a lack of change in the underlying DNA sequence. The "epigenome" refers to the overall epigenetic state of a cell, and serves as an interface between the environment and the genome. The epigenome is dynamic and responsive to environmental signals not only during development, but also throughout life; and it is becoming increasingly apparent that chemicals can cause changes in gene expression that persist long after exposure has ceased. This paper presents the hypothesis that commonly-used pharmaceutical drugs can cause persistent epigenetic changes.
Qigong and Gene Expression
"For hundreds of years Western medicine has looked at mind and body as totally separate entities, to the point where saying something 'is all in your head' implied that it was imaginary. Now we've found how changing the activity of the mind can alter the way basic genetic instructions are implemented." Herbert Benson, MD, director emeritus of the Benson-Henry Institute
Genomics, Proteomics, Transcriptomics, and Metabolomics
Genomics is concerned with the structure and function of DNA. DNA is the parts list for the functioning components of the body, which are proteins. Knowing the details of one's DNA does not in most cases contribute to an understanding of function or disease. For example, knowing your DNA is not going to say whether you will get cancer except in possibly a small set of cases. On the other hand, DNA methylation and phosphorolation are more relevant, and they depend upon lifestyle, including thoughts, emotions, nutrition, life experience, and reactions to stress.
Even more relevant to health, wellness, disease, and function than genomics or DNA is proteomics, the study of proteins, including their structure and function. It is a new field of study whose name was coined in 1997. Recent research suggests that studying proteins might give a better understanding of the functional processes ongoing in cells than genomics because proteins are the molecules that directly regulate physiological processes. Proteins, in turn, are dependent upon RNA. Transcriptomics is the study of the function of RNA and the creation of proteins. Even more basic or fundamental is metabolomics, the study of human metabolism and metabolites, the building blocks of RNA and proteins. A thorough understanding of the structure, function, and control of human metabolism, function, and wellness requires an understanding of how electromagnetism relates to these four -omics. There is currently no theory for the relationship between electromagnetism and physiology, and yet this relationship is a fundamental fact of human existence.
Proteomics and Personal Medicine
Scientific medicine is beginning to revert back to more ancient, ayurvedic lessons about healthcare. The approach is to treat the body as a system, where balance is the foundation for good health and disease and sickness are the externalities of imbalance. With advancements in proteomics and computing we can begin creating models of what a healthy bodily state looks like. In the same way we might use environmental models to analyze the global climate, we can isolate specific variables that can inform the larger picture. As the data piles up, preventative medicine will become a quantitative endeavour. A doctor visit of the future will be a simple blood test that measures proteins, lipids and some other key signals, which can then be plugged into a systematic database to help us treat diseases long before any symptoms arise. It is a huge upgrade in efficiency, one that could save millions of lives and alleviate the indebted healthcare system in the process.
C-Reactive Protein (CRP) is a biomarker of chronic inflammation. CRP can be measured in the blood, and higher amounts indicate inflammation somewhere in the body. In addition to inflammation, physical inactivity is associated with elevated C-peptide, IL-6, and CRP.
Mind-body practices that elicit the relaxation response (RR) such as Qigong and Tai Chi have been used worldwide for millennia to reverse the detrimental physiological effects of stress. Practices that trigger the relaxation response (a term pioneered by Dr. Benson), have been reported to be beneficial therapeutically (sometimes as an adjunct to medical treatment) in numerous conditions that are caused or intensified by stress.
Dr. Roger Jahnke has written a review of the Benson study and several others on gene expression that will fundamentally transform science, medicine and society. The implications for corporate wellness, integrative medicine and fitness are huge. Read Dr. Jahnke's Report [PDF].
Genomic counter-stress changes induced by the relaxation response
ABSTRACT: Mind-body practices that elicit the relaxation response (RR) have been used worldwide for millennia to prevent and treat disease. The RR is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. It is believed to be the counterpart of the stress response that exhibits a distinct pattern of physiology and transcriptional profile. We hypothesized that RR elicitation results in characteristic gene expression changes that can be used to measure physiological responses elicited by the RR in an unbiased fashion.
This study provides the first compelling evidence that the RR elicits specific gene expression changes in short-term and long-term practitioners. Our results suggest consistent and constitutive changes in gene expression resulting from RR may relate to long term physiological effects.
Dusek JA, Otu HH, Wohlhueter AL, Bhasin M, Zerbini LF, Joseph MG, Benson H, Libermann TA.,
Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital, Chestnut Hill, Massachusetts, United States of America, “Genomic counter-stress changes induced by the relaxation response.”, PLoS One. 2008 Jul 2;3(7):e2576.
Mindfulness Meditation Alters Gene Expression. A new study conducted by researchers working in Wisconsin, Spain, and France shows that mindfulness can even affect your genes. Specifically, the study shows that mindfulness can limit the "expression" of genes associated with inflammation. "The changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs," study co-author Dr. Perla Kaliman, a researcher at the Institute of Biomedical Research of Barcelona in Spain, said in a written statement. "Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions." Also see Scientists Finally Show How Your Thoughts Can Cause Specific Molecular Changes To Your Genes.
Study Reveals Gene Expression Changes with Meditation. The study investigated the effects of a day of intensive mindfulness practice in a group of experienced meditators, compared to a group of untrained control subjects who engaged in quiet non-meditative activities. After eight hours of mindfulness practice, the meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which in turn correlated with faster physical recovery from a stressful situation.
Bioelectromagnetic medicine: The role of resonance signaling. The discovery by Zhadin that ultrasmall magnetic intensities are biologically significant suggests that electromagnetic signaling is endogenous to cell regulation, and consequently that the remarkable effectiveness of EM resonance treatments reflects a fundamental aspect
of biological systems.
Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators. After an intensive one-day meditation intervention we detected reduced expression of histone deacetylase genes (HDAC 2, 3 and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with controls. The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions.
Relax - it's good for you. Researchers at Harvard Medical School completed a comprehensive scientific study showing that deep relaxation changes our bodies on a genetic level. What they discovered is that, in long-term practitioners of relaxation methods such as yoga and meditation, far more ''disease-fighting genes'' were active, compared to those who practised no form of relaxation. The research is pivotal because it shows how a person's state of mind affects the body on a physical and genetic level.
How Exercise Changes Fat and Muscle Cells. Exercise changes the expression of genes through a process called methylation. Methylation, analogous to a light-switch, turns on or off the expression (or behavior) of genes. Exercise and lifestyle (e.g. Qigong practice) directly influence methylation patterns. Epigenetics is the study of the effect of lifestyle and environment upon genetic activity.
Changing Your Lifestyle Can Change Your Genes
Genes are not Your Fate (video 3:11). Changing your lifestyle will change the expression of your genes. Proper nutrition, exercise, managing stress, loving more, your brain gets more blood flow and oxygen. The result is an increase in brain size through the creation of more neurons.
Changing Your Lifestyle Can Change Your Genes. Newsweek article by Ornish describing research which shows that improved diet, meditation and other non-medical interventions can actually "turn off" the disease-promoting process in men with prostate cancer.
Understanding cancer through proteomics (video 19:55). Danny Hills makes a case for the next frontier of cancer research: proteomics, the study of proteins in the body. As Hillis explains it, genomics is not a blueprint but merely shows us a list of the ingredients of the body -- while proteomics shows us what those ingredients produce. Understanding what's going on in your body at the protein level may lead to a new understanding of how cancer happens.
SERS Based Protein Assays. The goal of this project at University of California Davis Center for Biophotonics Science and Technology is to exploit the sensitivity offered by the SERS (surface enhanced Raman scattering) effect as applied to label-free detection of target biomolecules for medical and fundamental biological applications. Currently available assays and sensing techniques involve either tagging of the target molecules with fluorescent markers and/or incorporating a secondary tagged-molecule. These conventional approaches are subject to numerous limitations (i.e., sensitivity, specificity, complexity, expense, assay time, possible loss of activity, photobleaching, toxicity, etc). Present studies seek to develop assays for direct or indirect detection of biomolecules.
Proteins provide a measure of actual status, not just risk or disposition. Proteomics is the study of many proteins at once in a biological system using a given technical approach. The enormous diversity of proteins can be appreciated by considering that tens of thousands of genes give rise to hundreds of thousands of mRNAs which in turn give rise to potentially a million or more forms of proteins including post-translational modifications; a typical biological sample may contain tens of thousands of different protein forms. Proteins are a very valuable source of potential biomarkers: protein presence is driven by combined genetic and environmental factors, and thus proteins provide a measure of actual biological and disease status, not just risk or disposition. In addition, proteins are easily accessible in body fluids and tissues that collect from many of the body's systems.
Applied Proteomics, Co-Founded by Danny Hillis, Gets New CEO, $22.5M. API’s goal, Klemm says, is nothing less than to “elevate molecular diagnostics to another level beyond the genome” by measuring the proteins made by genes—a long-sought technology that is expected to help doctors improve medical care for individual patients. Because proteins carry out most cellular functions, the company says a snapshot of all the proteins circulating in the body at a given moment represents “the most powerful source of information” in terms of understanding a patient’s health status.
Metabolomics is the chemical fingerprint of your body. Your genome and genetic profile are simply a blueprint of the raw material or ingredients (proteins) of your body. The blueprint does not give an idea of how the (expressed) genes interact and how the environment affects the genes. Metabolomics is concerned with what is occurring in your body moment to moment as a result of factors such as nutrition and lifestyle with the ultimate goal of understanding how metabolism is regulated and identifying the metaboloic signatures of disease.
Enzyme Kinetics, Past and Present. Enzymes catalyze biochemical reactions, speeding up the conversion from substrate to product molecules. One hundred years ago, Leonor Michaelis and Maud Leonora Menten studied the equation characterizing enzymatic rates This landmark development in the quantitative description of enzymes has stood the test of time, and the Michaelis-Menten equation remains the fundamental equation in enzyme kinetics. Today, the quest for fundamental understanding of the working of enzymes continues with vigor at the single-molecule level as new experiments and theories emerge.