2018 NOBEL PRIZE FOR MEDICINE – MY THOUGHTS ON THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE

American James Allison and Japan’s Tasuku Honjo have won the 2018 Nobel Prize in Medicine for a pioneering approach to cancer treatment.

The Nobel committee said the pair’s research — which harnesses the body’s immune system to attack cancer cells — amounted to a “landmark in our fight against cancer.” The approach, known as immune checkpoint theory, had “revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed,” the committee said.

NOBEL PRIZE FOR MEDICINE GOES TO CANCER THERAPY

Clipped from: https://www.bbc.com/news/health-45704322

Image copyright SPL

Two scientists who discovered how to fight cancer using the body’s immune system have won the 2018 Nobel Prize for physiology or medicine.

The work, by Professor James P Allison from the US and Professor Tasuku Honjo from Japan, has led to treatments for advanced, deadly skin cancer.

Immune checkpoint therapy has revolutionized cancer treatment, said the prize-giving Swedish Academy.

Experts say it has proved to be “strikingly effective”.

Prof Allison, of the University of Texas, and Prof Honjo, of Kyoto University, will share the Nobel prize sum of nine million Swedish kronor – about $1.01 million or 870,000 euros.

Accepting the prize, Tasuku Honjo told reporters: “I want to continue my research … so that this immune therapy will save more cancer patients than ever.”

Prof Allison said: “It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade. They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”

Treating the untreatable

Our immune system protects us from disease, but it has built-in safeguards to stop it from attacking our own tissue.

Image copyright. Kyoto University. Image caption. Professor Tasuku Honjo and his team at Kyoto University

Some cancers can take advantage of those “brakes” and dodge the attack too.

Allison and Honjo, now both in their 70s, discovered a way to unleash our immune cells to attack tumors by turning off proteins that put the brakes on.

And that led to the development of new drugs which now offer hope to patients with advanced and previously untreatable cancer.

Immune checkpoint therapy is being used by the NHS to treat people with the most serious form of skin cancer, melanoma.

It doesn’t work for everyone, but for some patients it appears to have worked incredibly well, getting rid of the tumor entirely, even after it had started to spread around the body.

Such remarkable results had never been seen before for patients like these.

Image copyright. Getty Images. Image caption. Professor James P Allison

Doctors have also been using the treatment to help some people with advanced lung cancer.

Prof Charles Swanton, from Cancer Research UK, congratulated the prize winners, saying: “Thanks to this groundbreaking work, our own immune system’s innate power against cancer has been realized and harnessed into treatments that continue to save the lives of patients. For cancers such as advanced melanoma, lung, and kidney, these immune-boosting drugs have transformed the outlook for many patients who had run out of options.

“The booming field of immunotherapy that these discoveries have precipitated is still relatively in its infancy, so it’s exciting to consider how this research will progress in the future and what new opportunities will arise.”

Medicine is the first of the Nobel Prizes awarded each year.

Previous winners

2017- Jeffrey Hall, Michael Rosbash and Michael Young for unravelling how bodies keep a circadian rhythm or body clock

2016 – Yoshinori Ohsumi for discovering how cells remain healthy by recycling waste.

2015 – William C Campbell, Satoshi mura and Youyou Tu for anti-parasite drug discoveries.

2014 – John O’Keeffe, May-Britt Moser and Edvard Moser for discovering the brain’s navigating system.

2013 – James Rothman, Randy Schekman, and Thomas Sudhof for their discovery of how cells precisely transport material.

2012 – Two pioneers of stem cell research – John Gurdon and Shinya Yamanaka – were awarded the Nobel after changing adult cells into stem cells.

2011 – Bruce Butler, Jules Hoffmann and Ralph Steinman shared the prize after revolutionizing the understanding of how the body fights infection.

2010 – Robert Edwards for devising the fertility treatment IVF which led to the first “test tube baby” in July 1978.

2009 – Elizabeth Blackburn, Carol Greider and Jack Szostak for finding the telomeres at the ends of chromosomes.

MY THOUGHTS ON THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE

The Molecular Basis for the Defense of Human Existence. Man’s Unity with LORD God Creator can be learned from the study of Immunology. Each Antibody molecule bears two identical binding sites consisting of six b-Loops.

My ‘Theory of Man’ describes the Man as a Created Being. Man’s physical existence in the natural world in good health or ill-health always demands Man’s Unity (Sanskrit. ASMI) with LORD God Creator (Sanskrit. Brahman) for Man is constituted as a Spiritual Being. Man, the Rational Being is inclined to investigate the basis for the reality of his own existence. The reasoning for my statements is derived from the study of Immunology.

THE DEFENSE OF HUMAN EXISTENCE

THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE. NATURE OF HUMAN IDENTITY AND INDIVIDUALITY IS REVEALED BY HUMAN DEFENSE MECHANISMS.

An individual exists in the natural world by his biological abilities to defend his continued existence as an independent entity. This essay explores the physiological aspects of human existence and the defensive mechanisms that sustain this existence and the molecules which define and shape our INDIVIDUALISM. I had earlier described the Cultural aspects of INDIVIDUALISM while describing the Indian Identity. The term immunity describes the natural defensive mechanisms that give an individual the ability to recognize foreign proteins and foreign substances and neutralize or degrade them with or without injury to the individual’s own tissues. Immunology is the branch of science concerned with the body’s response to foreign agents and substances.

FUNCTIONS OF THE IMMUNE SYSTEM

THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE. ORGANS, CELLS, AND PROTEIN MOLECULES OF IMMUNE SYSTEM REPRESENT A CREATIVE MECHANISM TO OPPOSE, NEUTRALIZE, AND DESTROY FOREIGN INVADERS.

The immune system responds to invasion by the foreign organisms and their toxic products. This immune response is also described as active immunity. In the natural world, an infant is defended by molecules transferred passively across the placenta from the mother’s circulation during the fetal stage of development. The infant after birth may also receive passively protein molecules from mother when breastfed. This passive immunity defends the baby for several months and the baby further survives by developing its own immune system. Another major function of the immune system is the removal of damaged or dying cells. The immune system is also able to recognize and eliminate abnormal or mutant cells that frequently arise within the body. Using a system that is described as immune surveillance, the body recognizes and disposes of such abnormal cells which could result in the incidence of certain types of cancer. The immune system plays a vital role in protecting the body from bacteria, viruses, fungi, and parasites and helps to prevent certain types of cancer.

The immune system is very important and it is also very sensitive. The system’s very ability to recognize foreign substances may often result in undesirable reactions. Millions of people suffer on account of hypersensitivity or allergic reactions to fairly harmless substances present in the environment. Many individuals suffer on account of their sensitivity to proteins found in the foods such as milk, eggs, fish, wheat(gluten), and nuts that we consume. Sometimes, the immune system is misdirected and initiates an immune response against the body’s own cells or tissues producing a condition known as an autoimmune disease. While an immune system could cause some problems, we take full advantage of the system to defend ourselves from serious infectious diseases such as smallpox,polio,rabies, diphtheria, whooping-cough, measles, rubella, mumps, tetanus, typhoid, cholera, tuberculosis, hepatitis B, influenza and others by using vaccines and inoculations. Millions of lives are protected by routine use of vaccines and inoculations which help the body to become resistant to these infectious agents. We also use foreign proteins to protect the lives of people in times of a severe life-threatening crisis. We use blood, plasma, and sera( containing immunoglobulins secreted by animals) with utmost care to tide over an emergency. I used foreign immunoglobulins to treat snakebite victims and tetanus cases. The foreign proteins elicit a minor immune response and the situation is carefully monitored.

By being careless and reckless, and by polluting our food, water, air, and soil with dangerous chemicals, we damage our very sensitive immune system and this is contributing to a higher incidence of immune-related health problems in the population.

TYPES OF IMMUNE RESPONSE

The Molecular Basis for the Defense of Human Existence. The Fundamental Basis of Human Existence is not that of Man’s Intelligence, Mental Memory and Mental Functions.

The immune system defends human existence with a variety of cells and by the protein molecules known as immunoglobulins or antibodies produced by the immune function capable cells. The ability to recognize foreignness, specificity of the response, and the memory of the prior immune response are the key characteristics of immune defense. The immune system must be able to recognize the foreign agents and foreign materials in order to locate and destroy them. Specificity means that immunity to one foreign substance or organism does not provide resistance to another type of organism. Memory is the ability of the individual to develop an accelerated, enhanced, and long-lasting immunity after the initial attack by an infectious disease. The memory function described in Immunology should not be confused with the mental faculty called Memory. The body defends itself through two types of mechanisms which work together to protect our existence. 1. Humoral Immunity:- this involves the production of protein molecules described as immunoglobulins or antibodies.2. Cell-mediated Immunity:- It does not involve secretion of antibodies but requires direct physical contact with the foreign substance or agent. It also involves the use of other protein molecules which assist in the defense mechanisms.

HUMORAL IMMUNITY

THE MOLECULAR BASIS FOR DEFENSE OF HUMAN EXISTENCE. HUMORAL IMMUNITY INVOLVES DEPLOYMENT OF UNIQUE PROTEIN MOLECULES TO COUNTERACT WITH FOREIGN PROTEIN MOLECULES.

The cells known as Lymphocytes or B cells are produced in the bone marrow and circulate in our blood and are distributed to the various lymphoid tissues in the body, such as the lymph nodes, spleen, tonsils, and Peyer’s Patches (Lymphoid Follicles) that line the small intestine. When stimulated by an infectious organism, production of lymphocytes increases and the lymphocytes are carried to the site of infection. Depending upon the site of infection, the lymph nodes of that region often swell up and are found packed with lymphocytes. The B cells produce chemical substances known as antibodies. These are protein molecules which are specifically generated against specific organisms. The foreign substance is described as antigen. The antibodies that are generated recognize their antigens with high affinity and extreme selectivity. The interaction of an antigen with its specific antibody involves only small areas on the antigen’s surface; these areas are known as antigenic determinants. Protein molecules are very potent antigens as they have several antigenic determinants. Many carbohydrates are also antigenic because they have antigenic determinants. The antibodies circulate in the blood. The simplest, most prevalent means by which the immune system defends the body against bacteria and viruses is by a combination of a specific antibody with the antigenic determinants on the surface of the invading organism. This interaction between antibodies and antigens produces an aggregate of cells called as an agglutination. The body has wandering scavenger cells known as Macrophages. The clumps of agglutinated cells are engulfed and digested by the macrophages. Antibodies also bind to toxic molecules given off by invading microorganisms and this reaction produces large, insoluble aggregates known as precipitates. These precipitates are also removed by macrophages. The virus after entering the body survives by its ability to invade or enter cells. Antibodies prevent the ability of the virus to infect cells by covering up and blocking the attachment sites of the virus.

CELL-MEDIATED IMMUNITY

THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE. INTERACTION OF CELLS AND UNIQUE PROTEIN MOLECULES OF IMMUNE SYSTEM DEFINES MAN’S IDENTITY ON MOLECULAR BASIS.

There is another distinct type of Lymphocytes known as T lymphocytes or T cells. T cells originate in the THYMUS and become localized in lymphoid organs. The immunity associated with T cells does not involve secretion of antibodies but through their direct contact with their targets or by the effects of secreted molecules known as lymphokines which help other cells to make the direct contact. There are four kinds of T cells. 1. The cytotoxic T cells
or Natural Killer cells or NK cells defend the body by destroying infected, foreign or cancerous cells. The other three kinds of T cells regulate immune responses by secreting messenger proteins known as lymphokines. 2. Helper T cells enable the other T cells and most B cells to perform their functions. The Helper T cells are destroyed by Human Immunodeficiency Virus (HIV) in Acquired Immune Deficiency Syndrome (AIDS) patients resulting in a depressed immune response that allows infection by a variety of microorganisms and the growth of some types of cancerous tumors. AIDS patients are very vulnerable to fatal infections. 3. Suppressor T cells dampen the immune response of the B and T cells. 4. The fourth kind of T cell is involved in certain kinds of hypersensitivity reactions. In a normal healthy individual, there is a balanced ratio of these four kinds of T cells to provide an efficient immune system for defense against all foreign substances. Macrophages and White blood cells known as neutrophils have the ability to engulf and digest particulate matter by the process of phagocytosis. They eliminate many foreign organisms and particulate materials that enter the body. The ability of NK cells to kill or destroy some cancerous or tumor cells is enhanced by two lymphokines known as gamma interferon and interleukin-1. Another lymphokine known as interleukin-2 activates the Lymphokine Activated Killer Cells or LAK cells which also have the ability to kill a variety of human tumor cells. Activated T cells also secrete a lymphokine known as Transfer Factor which is able to cause normal lymphocytes to release lymphokines or otherwise become activated and thus to destroy other cells. Transfer Factor stimulates the lymphocytes to develop normal immunity.

The Cytotoxic T cells destroy other cells by interacting with antigens present on the surfaces of the cell. They are involved in the attacks on tissues and organs grafted or introduced into the body, viral antigens found on infected cells and on chemicals that have entered the body and found attached to cells. T cells are involved in skin reactions resulting from contact with molecules found in poisonous plants like Poison Ivy, Poison Sumac, and Poison Oak.

ORGAN TRANSPLANTATION AND CELL-MEDIATED IMMUNITY

THE MOLECULAR BASIS FOR THE DEFENSE OF HUMAN EXISTENCE. ORGAN TRANSPLANTATION AND IMMUNOLOGY. MOLECULES OF HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN (HLA) SYSTEM

T cells are involved in the rejection of transplanted tissues and organs. The chances of successful organ transplantation are improved by carefully matching the tissue or Histocompatibility Leukocyte Antigens known as the HLA system of the donor with those of the recipient. The protein molecules of the HLA Complex establish the identity of our body, its tissues, and various organs. They work to preserve the identity of the individual and to exclude the introduction or grafting of foreign material into the body. Even after careful matching, and selection of suitable donors, transplanted tissues or organs are usually maintained by using drugs that cause immunosuppression by which the normal immune response of the recipient against the donated organ is prevented.

BIOLOGICAL EXISTENCE

A normal, healthy immune system is vital to defend our biological existence. Immunodeficiency diseases, depressed or compromised immune system conditions such as associated with corticosteroid therapy, chemotherapy, radiation therapy, or exposure to certain types of toxic chemicals, and autoimmune diseases impose a heavy burden and threaten our existence. Medical interventions and treatment may help us but the quality of life is invariably compromised. A functioning immune system is important to defend our existence.

MOLECULAR INDIVIDUALISM

The Molecular Basis for the Defense of Human Existence. Man exists as Individual with Individuality as his existence involves defensive mechanisms operated by independent, individual cells, and protein molecules which exhibit Cellular Autonomy. The cell is the lowest common denominator of all life. While the cell is functionally independent or autonomous or self-governing, it displays the abilities characterized by Mutal Assistance, Cooperation, Tolerance, and Functional Subservience to provide some benefit to the Individual who lives in the physical world.

The unique protein molecules that we deploy to establish our identity, and to defend our existence exhibit individualism at a molecular level. Molecules can exhibit a surprising degree of individuality. In experiments that examine the physical behavior of single molecules, researchers at Stanford University have discovered that when identical polymers, long, flexible, spaghetti-like molecules that are found in everything from plastics to living cells( the strands of DNA and other protein molecules)- they UNFOLD in a variety of ways even when exposed to the same conditions. Nobel Laureate Dr Steven Chu, former Professor of Physics, and Applied Physics at Stanford( former United States Secretary of Energy) has stated that: We discovered it because we have developed the ability to visualize and manipulate single molecules. ONLY BY LOOKING AT INDIVIDUAL ANIMALS CAN YOU GET A TRUE SENSE OF THE DIVERSITY OF SPECIES. He had researched biological Physics and Polymer Physics at single molecular level. He made use of individual molecules of DNA to study Polymer Dynamics.

The Theory of Evolution fails to account for our Molecular Individualism. Our body is unique and does not display any affinity for foreign substances and proteins and is actually involved in degrading or destroying such invasion by foreign agents and their products. The body has no evolutionary preferences and the vigorous response of the immune system has no bearing upon any presumed evolutionary connections between species. We need to look at each human individual to truly understand the nature of our Human Diversity. When we look at the genetic code, the DNA molecules that operate this code, we can understand the nature of our Molecular Individualism. A man comes into existence as an Individual and he exists an individual according to the Law of Individuality.

2018 Nobel Prize for Medicine will help us to develop a ‘Theory of Man’ by the study of unique protein molecules that play an important role in the defense of human survival. The Physical Being called Man needs the support of Spirit, Soul, or a Divine Agency to bring Unity between the cells, tissues, organs, and organ systems providing the structural and functional basis for Man’s existence.