Monoclonal Antibodies – the Magic Bullets are Here

The pharmaceutical industry went through a major paradigm change in their product development strategy during the last decade, with the advent of biologics especially monoclonal antibodies. Until recently they were very much focused on small organic molecule based drug development. Things started changing when more and more protein based biologics got approvals and some became blockbuster drugs. Also poor success rate recently with small molecules have contributed to this change.

The global monoclonal antibody drug market, presently worth $30 billion, is probably the fastest growing segment in pharmaceutical industry recording 14% annual growth rate (versus 0.6% for small molecule). Over 50% of products in development currently are biologics that include monoclonal antibodies and recombinant proteins. It has seen a growth of 50% every year over the last 5 years.

Antibodies are proteins made by cells of immune system of most vertebrates to protect them mainly from infections. They do this by identifying and binding to chemical epitopes unique to the infectious agent or foreign to the host organism, called an antigen. Our genome has developed a vast complex of genes, which by combinatorial reorganization can generate millions of combinations of unique antibodies, one unique antibody per immune cell. When a cell, with its unique antibody, encounters its antigen present on a pathogen it will be triggered to multiply exponentially to generate a large clone of cells making one type of antibody, or monoclonal antibody, to destroy the pathogen.

In 1975 Milstein and Kohler developed a way to artificially generate a monoclonal antibody in the lab, for which they got Nobel Prize in 1984. Since this invention, it was said that the age of monoclonal antibodies as ‘magic bullets’ to cure diseases has arrived. The idea of a ‘Magic bullet’ was first proposed by Paul Ehrlich in 1900’s, that if a compound could be made that selectively targeted a disease causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. It took over 10 years for the first monoclonal antibody drug to get to the market in 1986. Since then monoclonal antibodies has become the most successful class of biotech drugs in history, with 26 approved therapies currently in market, of which many are blockbuster drugs (see table below). They have clinical utility ranging from molecular diagnostics, inflammatory and autoimmune diseases, oncology and infectious diseases.



As Paul Ehrlich envisioned, monoclonal antibodies as ‘magic bullets’ are now used to deliver a toxic payload to target pathogen or cancer cells to cure diseases. There are three types of antibody payloads namely drugs, bacterial protein toxins and radioactivity. Examples of drugs include taxol, doxorubicin, and DM1. Examples of toxins are Diphtheria toxin, Pseudomonas endotoxin, and Ricin. Radioactive payloads include 90Y, 131I, imaging isotopes, as well as radio phosphate (32P and 33P).

Toxic payload is not the only use of monoclonal antibodies as drugs. The major growth areas for monoclonal antibodies include therapeutics antibodies (including toxic payloads) and molecular diagnostics. The major therapeutic segments are Oncology (solid and liquid tumors), autoimmune and inflammatory diseases. Molecular diagnostics include in vivo radio imaging for clot proteins, pulmonary embolism, deep vein thrombosis and in vitro diagnostics such as emergency room drug testing for cocaine, heroin and amphetamine.

I see a bright future for monoclonal antibodies, with over 200 or so in various stages of development for varied indications. Advances in technology are also helping to reduce cost of production, improve efficacy and safety. The perceived bottle neck is in the large scale production needed to meet future market needs. Because monoclonal antibodies are made by live cells, production costs are still high. The rapid advancement in development of biopharmaceuticals and biologics recently has forced the industry to come up better solutions to some of these issues. Some of these drugs could be life saving to many patients around the world, but high cost may be keeping it from their reach. The challenge to the industry is to bring the cost down to be affordable to all.

Swine Flu – Are We Facing a Pandemic?

The world health organization (WHO) has already declared the current outbreak of ‘flu’ as a pandemic in June. So it has gotten much attention it deserves to contain it from countries across the world. It has already reported from many countries around the world.

Influenza virus has killed millions of people during the last century. The major pandemic of ‘Spanish flu’ in 1918 was estimated to have killed over 50 million people. Although the current outbreak has affected millions of people around the world and will affect millions more, my prediction is that it will not be as deadly as previous outbreaks, based to available data so far. It will definitely increase in the coming months, especially in many developing countries not affected so far. Number of cases will also shoot up in the ‘flu season’ with the climate favoring the disease.

An ‘epidemic’ is the spread of an infectious disease, usually localized in an area and called ‘endemic’. While the epidemic occurring on a world wide scale is a ‘pandemic’. Historically there have been many pandemics such as small pox, tuberculosis, flu, and HIV recently. With the increased travel across the world in modern times it is predicted that there is higher chance of spreading a disease quickly across the globe creating a pandemic.

Influenza is one of the common viral infections recurring every year, may be only next to common cold. This virus has the ability to change quickly and appear has new variant every so often. For example the current H1N1 variant, commonly called ‘Swine flu’, originated in Mexico early this year, is an assortment of an endemic human strain, an endemic avian (bird) strain and 2 swine flu virus strains. Our immune system is very good at identifying new and emerging virus and contains them most of the time. But once in a while they may have developed enough variation to escape immune surveillance to cause disease. In such circumstances they can quickly spread through the population.

Public education is the major key to controlling the spread of disease, especially in third world countries. Proper hygiene and plans to isolate infected individuals should be done at city or state level. Anti-virals such as Tamiflu and Relenza effective against Influenza should be stock piled and made available to individuals already infected with the virus. Development of a vaccine is if often time consuming and may not be available at the time of urgent need, when the disease spreading.

A Case for Coconut Oil

At a recent party I was preview to a discussion about oils they are using for cooking. I was especially surprised to find negative impression many people have about coconut oil. Someone even commented that coconut oil is full of cholesterol (cholesterol is exclusively an animal derived product and not present in any vegetable oil). I hail from Kerala or the land of coconuts, where coconut oil is used for most cooking. This what prompted me to write this article.

What are the facts about coconut oil? Is it such a monster we make out to be? In reality we are not giving all the credit it deserves. Why and who is spreading these negative rumors?

Since 1950’s coronary heart disease (CHD) was becoming the primary cause of mortality in the adult population is US. In 1954, a researcher named David Kritchevsky published two research papers demonstrating that feeding cholesterol to rabbits lead to the formation of blocked arteries and thus contribute to potential heart disease. Subsequently he showed that consuming polyunsaturated fatty acids from other oils such as corn, soybean, safflower and sunflower seeds results in the lowering, at least temporarily, of cholesterol in the blood. This let to ‘lipid hypothesis’, that saturated fat and cholesterol raise cholesterol levels in the blood, leading to possible deposition of cholesterol and fatty acids as pathogenic plaques in the arteries. Although many other studies at the time had also shown data to the contrary, the well oiled marketing machinery funded by the soy bean and corn industry and supported by the American Heart Association was committed to change the American Diet.

During the no-fat craze of the past several decades, all fats were marked as bad, as something to be avoided. The substitution of saturated fats with polyunsaturates gained acceptance pushed by industries like the corn oil companies who profited immensely from doing so, overshadowing science. Coconut oil, far more nutritious and beneficial than corn, peanut, soy, safflower and many other oils out there got tossed into oblivion. Even now this conceptual change in the eating habits of Americans has negatively influenced and changed the dietary regimes of many societies all around the world, some that were not even affected by America's style food habits.

Today heart disease, diabetes and obesity is still on the rise worldwide. During 1960s, fats and oils supplied Americans with about 45 percent of their calories; with about 13 percent obese and only 1 percent had type-2 diabetes. Today, Americans take in less fat, getting about 33 percent of calories from fats and oils; yet obesity has ballooned to 34 percent of US population and about 8 percent have diabetes.

The discovery of hydrogenation process for vegetable oils in the early 1900’s solved many of the problems associated with unsaturated oils such as short shelf life due to rancidity, and improved consistency similar to butter. Hydrogenation process breaks the double bonds in unsaturated fat molecules and introduces hydrogen atoms in their place. One problem associated with partial hydrogenation process is that it creates high amounts of trans fatty acids, the ill health effects of which is only recently been documented. Transfats are not naturally occurring and are created during the high heat and pressure of hydrogenation process.

Coconut oil is about 92% saturated fat and rest mono or poly unsaturated. It does not contain any trans fatty acids and do not require hydrogenation. Unlike saturated fat in most other oils, coconut oil is made up of medium chain and short chain saturated fatty acids. Lauric acid a medium chain fatty acid account for about 50% coconut oil. Various studies are pointing to the health benefits of short and medium chain fatty acids. Coconut oil has antioxidant tissue protective properties.

There is no evidence that saturated fat increases heart disease. On the contrary there are lot of evidence that trans-fat increases LDL or the bad cholesterol and reduces HDL or the good cholesterol. Medium chain saturated fats, such as those in coconut oil are beneficial to human health.

General aging closely associated with oxidation and peroxidation of various macro molecules in the body. Various tissues accumulate such oxidated or peroxidated proteins and lipids over time, leading to the aging process. Recently it was shown that ultraviolet light induces peroxidation in unsaturated fats, but not saturated fats. Lipid oxidation is found to be involved aging of brain including in Alzheimer's disease. Oxidants damage the protein & lipid structure in cell membrane increasing their fluidity with aging.

Coconut oil is rich in short and medium chain fatty acids. So I believe that the benefits of coconut oil out weights its pitfalls. Or among a choice of oil Coconut oil may be one of the best you can choose. It helps you lose weight, lowers cholesterol, reduce your risk of heart disease and other diseases, helps those with diabetes, thyroid, chronic fatigue, improves Crohn's, IBS, and other digestive disorders, boosts your daily energy and rejuvenates your skin, prevents wrinkles.

I have been consistently using coconut oil since childhood I can remember, not only for cooking but also use on my skin and hair. I believe eating processed foods such as hydrogenated vegetable oil or refined sugar containing foods expose you to many of the illness associated with modern life. I like any one to comment on their experience with coconut oil, either good or bad.