Translational research: Medicine man

As director of the NIH's bold new translational research centre, Christopher Austin has to show that he can jump-start a tortuous drug-discovery process..

http://www.nature.com/news/translational-research-medicine-man-1.12380

A Benchmark for the Surgical Treatment of Congenital Heart Disease

http://www.okayama-u.ac.jp/user/kouhou/ebulletin/feature/vol2/feature_001.html

Rest in Peace Mother !

Since then, I have been feeling like I had no words to write any blog on cancer. I felt so helpless about this whole thing, was in complete shock, anger, and guilt of living so far apart from my mother especially for last 10 years while living in United States and working as a cancer biologist. However, I find it comforting that I was able to fly back and be with her in time while she was still alive, chatted with her intermittently for hours, right before the day she finally left us forever…….  

Deep down in my heart, I often think that had my mother been in United States where I live, she could have been saved as depending on the stage and spread of cancer, for localized cervical cancer, 5-year survival rates are 92% in the United States.  Unfortunately, she was in India, where 5-year survival rate is only 48.7%. She was only 64............................. It’s been more than 6 months, but I still feel lost ….helpless…….angered……and…. dispirited, especially after knowing that she could have been saved.

Anyways, I am trying my best to come back to my normal life where I could contribute whatever little it may be from my side to cancer research, a thing that I have been doing for last 15 years.

Mother, your battle against cancer strengthens my life’s goal to dedicate my career to cancer research.  I am sorry mother, recent developments in cancer research could not save your life, largely because you had no access to them, but I sincerely hope, that cancer care in third world countries will improve significantly soon and others will benefit. In the meantime, we will keep crusading against this disease in our laboratories…..amen….

DO’s and DON’Ts while dealing with Cancer Patients

Approximately half of all cancer patients and survivors suffer from poor mental health. Specifically, depression, anxiety, and adjustment disorders plague people with advanced or terminal cancer. While cancer treatment has improved significantly over the past decade and due to all these advancement in medical science it is not surprising to see many cancer survivors returning back to normal life especially in the west, yet mental health treatment has not been fully integrated into the treatment of cancer patients. Considering severe mental illnesses a cancer patient may have besides fighting against this dreadful disease, we can be more cautious and not add any further agony to a cancer patient/survivor while dealing with him/her.

When someone you know has cancer

What you SHOULD NOT DO:

·        

      Avoid talking about the illness–or talk about it constantly. The person might enjoy conversations that don’t involve cancer.

·         Comment on changes in the person’s appearance, such as weight loss, which may make her self-  conscious.

·         Offer advice the person hasn’t asked for.

·         Be afraid to hug or touch the person if doing so was part of your relationship before the illness.

·         Say, “I can imagine how you must feel.” In reality, you can’t.

Above steps indeed help patient feel part of the same society/family in which he/she has been living before being victimized by this dreadful disease and this way patient/survivor does not feel alienated because of his/her disease.

And what instead you SHOULD DO:

· 

             Listen without feeling compelled to respond. Sometimes a caring listener is what the person needs most.

·         Be open with your feelings, such as by saying, “I’m not sure what to say, but I want you to know I care.

·         Some people do not like talking about their illness while some others do. Therefore take your cues from the person with cancer and respect his/her need to share–or for privacy.

·         Respect his/her decisions about treatment, even if you disagree.

·         Offer to help in concrete, specific ways if you can or else just advising someone who is already so stressed out actually is more painful for him/her.

Abysmal State of Cancer Care in India

Cancer is known to have become one of the most dreadful diseases that have affected millions throughout the world. It is estimated that half of all men and one-third of all women in the US alone will develop cancer during their lifetimes. In another estimation by WHO, around 20 million people will develop cancer by 2020 worldwide with 70% in the developing countries, and out of those in developing countries only 5% will have access to any healthcare system.

With recent advances in the field of cancer biology, while majority of the cancers are clinically manageable if not completely curable in developed countries with increase in survival years with quality of life, in poor countries such as India once cancer is diagnosed patients are often left to the mercy of God as there are hardly any dedicated cancer hospitals in India except few big cities such as Mumbai and Delhi. For significantly lower number of patients who are lucky enough to be diagnosed in early stages of cancers which is very uncommon owing to the lack of general health awareness among common people and lack of routine health check-up programs such as annual mammograms or endoscopy etc. Majority of the patients with cancers are diagnosed when cancer is inoperable (in patients with solid cancers) and due to the lack of a super specialty program namely Medical Oncology in most of the hospitals, these patients are left with only one choice, to go to the radiotherapists (even radiotherapy departments are quite uncommon in majority of hospitals even in bigger cities in India) who eventually become overwhelmed with number of patients they have to deal with using their limited resources including often nonfunctional old generation machines. It is not uncommon to end a radiotherapy session in the middle of it due to power outage, only God knows what might be happening to those patients who go through such radiotherapy sessions which are forced to be terminated by power outage because there is no such study which has ever been conducted anywhere in the world to determine whether or not power interrupted radiation beams (that are aimed to kill cancer cells)  do actually kill the cancer cells as effectively as they do without any such technical interruptions?  Well let us assume, nothing bad happens during such kind of technical hiatus as anyways we are not talking about effectiveness of cancer treatment in India. As I mentioned earlier, in spite of best intention a radiotherapist may have to treat a cancer patient, due to delay in start of radiation therapy because of long waiting line, old generation and often nonfunctional machines,  and so many different technical problems that may occur during a radiotherapy session, most of these patients end up having very short span of life ranging from few months to few years depending upon various factors including stage of the disease and type of cancer.

After chemotherapy and/or radiotherapy is over, while patient gets a sense of relief of having concurred the disease (which may or may not be true), another episode of suffering starts for a cancer survivor.  Most of these patients develop side effects of radiotherapy and chemotherapy which in most cases adversely affect day to day life of a cancer survivor.  Few examples of radiotherapy related side-effects are as follows:

Radiation therapy: side effects

        Radiation therapy treats cancer by using high energy to kill tumor cells. The goal is to kill or damage cancer cells without hurting healthy cells however, it is well known that most of the radiation therapy modalities available in India are not updated at par with international standards and end up killing normal healthy cells as well which often results in moderate to severe side effects. The specific side effects one may have depends on the type of radiation being used, the dose of radiation, the area of the body that's being targeted, and the state of patient’s health. There are actually two kinds of side effects from radiation therapy -- early and late. Early side effects, such as nausea or fatigue, are usually temporary. They develop during or right after treatment and last for several weeks after treatment ends, but then improve. Late side effects, such as lung or heart problems, may take years to develop and are often permanent when they do. The most common early side effects from radiation therapy are fatigue and skin problems. Other early side effects such as hair loss and nausea are typically specific to the site of the tumor being treated.

         Most cancer hospitals in western countries have counselors and/or do offer a class to help educate the patients about possible early and late side effects of radiation/chemo therapy and ways to conserve energy, reduce stress, and use distraction to not focus on the fatigue, pain and other problems, prioritize the regular activities so that patients do the ones that are most important to them first when they feel less fatigued. They also educate on importance of nutritious diet and exercise. Unfortunately, cancer patients in India going through chemo- or radiotherapy do not have such privilege of being educated about forthcoming problems intensities of which can be reduced with prior awareness if not completely avoided.  

One of the common side effects from radiotherapy is lymphedema. It is more common among women who have gone through radiotherapy for breast cancer or gynecologic cancers. Lymphedema is an accumulation of lymphatic fluid (lymph stasis) that causes an abnormal swelling of an extremity. Lymphedema affects 90 million to 150 million people worldwide each year. While for most patients, the mild swelling of a limb that may occur after lymph node removal during surgery resolves within a few weeks of surgery, in 10 to 30 percent of patients, however, the edema (swelling, or fluid accumulation) recurs, resulting in chronic lymphedema, which is associated with recurrent infections, pain, impaired limb mobility, and a decreased quality of life. It is a condition there is no good treatment for and no rational way of preventing.

In a recent personal experience, I shockingly learnt from a relative (located in a mid-size town in Northern India) who has developed radiation therapy induced lymphedema,  that most of the physicians in that town either are ignorant of this side effect of radiotherapy or do not have experience of managing lymphedema with this etiology as they treated the patient with high dose antibiotics which has no role in radiation induced and infection free lymphedema,  and those who acknowledged it to be lymphedema showed their unwillingness to treat this patient probably due to the fact that this condition is beyond their area of expertise. Or after realizing the fact that such conditions have very dismal prognosis these otherwise very able physicians considered to invest their time and resources in treating rather some other patient with manageable or curable disease.  And I do not blame them, it is not the job of a radiotherapist who is not specialized in managing side-effects (a radiotherapist is rather too busy making treatment strategies for newly diagnosed and/or old patients who are in immediate need to receive radiotherapy/chemotherapy.  It is rather a medical oncologist (a rare super-specialty which hardly exists in most of the academic university hospitals in India), or a palliative care specialist (who don’t exist at all in India) who should take care of such debilitating conditions.  

What is Palliative Care?

           Palliative care is an area of healthcare that focuses on relieving and preventing the suffering of patients. Unlike hospice care which is often confused with palliative care, palliative medicine is appropriate for patients in all disease stages, including those undergoing treatment for curable illnesses and those living with chronic diseases, as well as patients who are nearing the end of life. Palliative medicine utilizes a multidisciplinary approach to patient care, relying on input from physicians, pharmacists, nurses, chaplains, social workers, psychologists, and other allied health professionals in formulating a plan of care to relieve suffering in all areas of a patient's life. This multidisciplinary approach allows the palliative care team to address physical, emotional, spiritual, and social concerns that arise with advanced illness.

  Medications and treatments are said to have a palliative effect if they relieve symptoms without having a curative effect on the underlying disease or cause. This can include treating nausea related to chemotherapy or something as simple as morphine to treat a broken leg or ibuprofen to treat aching related to a flu infection.

Palliative care for cancer patients in India: a realistic dream

         The focus on a patient's quality of life has increased greatly during the past twenty years. In the United States alone, 55% of hospitals with more than 100 beds offer a palliative-care program, and nearly one-fifth of community hospitals have palliative-care programs. Some European countries have even better palliative care availability. A relatively recent development is the concept of a dedicated health care team that is entirely geared toward palliative treatment: a palliative-care team. As we all are aware of high mortality rate and almost all of cancer patients (in Indian context) dying in pain accompanied by so many other physiological complications, one can easily appreciate the need of a palliative care center in hospitals in India.  

 In my opinion, while advocating for state-of-art cancer hospitals in every small and big cities is still unrealistic and probably unfair demand from Indian government who has much bigger challenges in health sector such as to fight against malaria, tuberculosis and, Japanese Encephalitis which alone kills thousands of children each year in one small town namely Gorakhpur, UP, located in northern part India, I believe it would not be too much to ask if government could establish independent /autonomous departments of Palliative Medicine in every university hospitals that could take care of dying patients from cancers and many other debilitating diseases. In west, almost every hospital has an independent unit of palliative medicine. I think it is right of every human being on this earth to die gracefully, without pain, and without other complications which could have otherwise been avoided if we had these palliative care specialists in every hospital premises in India.

     However, in order to make it a reality, authorities who decide what to include in curriculum of medical education in India such as Medical Council of India, should consider about starting a new MD program which focuses on to train physicians to become specialists and leaders in the field of palliative medicine, especially those planning a career in an academic cancer center. The focus of training should be the development of expertise in:

•          Diagnosis and treatment of pain syndromes associated with cancer and cancer therapy
•          Diagnosis and treatment of non-pain symptoms associated with cancer and other life-limiting illness
•          Diagnosis and treatment of the neurological, psychiatric, and psychosocial complications of cancer and other life-limiting illness
•          Communication skills with patients, families, and professional colleagues
•          Clinical research methods used to address symptom control and quality of life
•          Basic principles and practical applications of the medical ethics and legal aspects of pain management and palliative care
•          Cultural, spiritual, religious, and existential aspects of palliative care
•          Care of the imminently dying patient including management of terminal symptoms
•          Assessment and management of patients in community settings, such as home and long-term care

I find it a typical example of deductive fallacy to open new institutions with promise of unrealistic dreams such as “Institute of Molecular Medicine” or “Institute of Regenerative Medicine” in cities like Lucknow, Jabalpur, Ranchi or Patna where they do not even have facilities to perform PET scans to diagnose some nuances of malignant cancers.  These are the places where a patient who has recently been diagnosed with cancer and immediately needs a session of radiotherapy to help prevent his cancer from spreading to other organs, has to wait for somewhat 3-6 months before his actual cancer therapy starts just because there a long waiting line of cancer patients and so few radiotherapy units (often 1-3 for a whole state) do exist in those places let alone a dedicated cancer center. Well, if you can’t provide them reasonable treatment for their cancer (it will certainly take at least few decades to have modern, state-of art treatment modalities and, specialists available in Indian hospitals at par with the west), at least help them die peacefully with dignity and without pain. And to do so, you need palliative medicine units in at least every university hospitals and this is a realistic goal that can be achieved with not much infrastructural investment. 

Cystic Fibrosis and Cass4/HEPL

Cystic fibrosis (CF) is a disease which is usually inherited through families. In this disease, patients’ body especially lungs and digestive tract produce thick, sticky fluid, called mucus. Importantly, it is one of the most common chronic lung diseases in children and young adults which could be a life-threatening if not taken care of properly by an experienced physician, because collection of sticky mucus in airways, may lead to lung infections and serious digestion problems. The disease sometimes also affects the sweat glands and a man's reproductive system.

In order to develop CF, a person must inherit two defective CF genes - one from each parent, this is the reason that a majority of people carry the defective CF gene, but do not have any symptoms. An estimated 1 in 29 Caucasian Americans have the CF gene. While CF has primarily been considered as one of the most deadly inherited disorder among Caucasians (white people from West) recent reports suggest its presence in Indian subcontinent too, however, its precise magnitude is not known. Studies on migrant Indian population in United States and United Kingdom estimate that one out of each 10,000 Indians could be affected with CF. CF in Indian children is usually diagnosed late and in advanced stage. Children are more malnourished and may have clinically evident deficiency of fat soluble vitamins such as  A, D, E and K. Diagnostic facilities in form of sweat chloride estimation and genetic studies are not available readily. While in recent years Indian diagnostic laboratories have introduced several state-of-art molecular tests for various viral and genetic diseases, lack of ample amount of scientific data on complete genetic make-up of CF in India (as Indian patients harbor different mutations in their CF genes than their western counterparts) makes it even more difficult to diagnose this disease at molecular level.  

Symptoms

Symptoms in newborns may include:

Failure to gain weight normally during childhood which ultimately results in slow growth

No bowel movements in first 24 to 48 hours of life

Salty-tasting skin

Symptoms related to bowel function may include:

Belly pain from severe constipation

Increased gas, bloating, or a belly that appears swollen (distended)

Nausea and loss of appetite

Clay or pale colored stools with foul smelling, have mucus, or that float

Symptoms related to the lungs and sinuses may include:

Coughing or increased mucus in the sinuses or lungs

Fatigue

Nasal congestion caused by nasal polyps

Recurrent episodes of pneumonia.

Symptoms in someone with cystic fibrosis include:

Fever

Increased coughing

Increased shortness of breath

Loss of appetite

More sputum

Sinus pain or pressure caused by infection or polyps

Symptoms that may be noticed later in life:

Infertility (in men)

Repeated inflammation of the pancreas (pancreatitis)

Respiratory symptoms

Signs and tests

A blood test is available to help detect CF. The test looks for variations in a gene known to cause the disease. Other tests use to diagnose CF include:

Immunoreactive trypsinogen (IRT) test is a standard newborn screening test for CF. A high level of IRT suggests possible CF and requires further testing.

Sweat Chloride Test is the standard diagnostic test for CF. A high salt level in the patient's sweat is a sign of the disease.

Other tests that identify problems that can be related to cystic fibrosis include:

Chest x-ray or CT scan

Fecal fat test

Lung function tests

Measurement of pancreatic function

Secretin stimulation test

Trypsin and chymotrypsin in stool

Upper GI and small bowel series

Management of the disease

To educate masses especially those from India, I presented a very simple outline of  Cystic Fibrosis here, however, please keep in mind that this is one of those diseases with so complicated mechanism that there is no straightforward way to diagnose the disease. However, be assured that an early diagnosis of CF and a comprehensive treatment plan can improve both survival and quality of life. I will not discuss the treatment modalities here, so if you have any further questions/doubts, please discuss it with your physician/pediatrician.  However, I would like to mention that most children with cystic fibrosis are fairly healthy until they reach adulthood. They are able to participate in most activities and should be able to attend school. Many young adults with cystic fibrosis finish college or find employment.

Lung disease eventually worsens to the point where the person is disabled. Today, the average life span for people with CF who live to adulthood is approximately 37 years in western countries, a dramatic increase over the last three decades. Death is usually caused by lung complications.

My connection with Cystic Fibrosis 

Anyways, the reason that prompted me to write this article is due to my indirect role in the understanding of the Cystic Fibrosis at mechanistic level.

Well, it is known that Cystic fibrosis is an autosomal recessive inher­ited disorder caused by alterations in a gene called CFTR, the cystic fibrosis transmembrane conductance regulator gene. CFTR gene encodes a transmem­brane protein present at the surface of most epithelial cells. It is proposed that abnormal electrolyte transport caused by defective CFTR gene causes altered mucus viscosity and decreased mucosal defense against infec­tion, which leads to airway plugging, chronic inflammation and progressive destruction of the lung. There are several types of mutations or variations in CFTR gene/protein that result in this disease. However, it is important to notice that the disease progression and its severity do not appear to correlate with the type of CFTR variant and seems to be largely dependent on secondary factors which means there could be more genes/proteins besides CFTR that could indirectly be contributing towards disease progression and could well affect disease prognosis and its clinical management.

In a recent paper published in a reputed journal, Nature Genetics, Dr. Garry Cutting, M.D., from a very prestigious medical school at John Hopkins University and his collaborators identified two new genetic loci on chromosome 11p13 and chromo­some 20q13 contributing to variation in lung function in patients with cystic fibrosis.  This group conducted a combined genome wide association and linkage study in 3,467 individuals with cystic fibrosis originating from three different study populations. Linkage analysis of 486 sibling pairs from the family based study they identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03).odds = 5.03). 

http://www.nature.com/ng/journal/v43/n6/full/ng.838.html#/affil-auth

While 3 out of all five genes within the chromosome 20 linkage region are not well characterized in the terms of their structure and function, two of them CASS4-HEPL and Aurora kinase A (encoded by AURKA) are the ones that I have been personally been interested in and involved in the past in a different context.  

Well, it was me who first identified and cloned this locus - Chr. 20 orf32, while working at Fox Chase Cancer Center, Philadelphia, in 2008  and designated it as HEPL (for HEF1-Efs-p130Cas-like) protein due to its structural similarity to Cas family proteins which are HEF1, Efs, and p130Cas. Later HUGO gene nomenclature committee gave it an official name CASS4 (Cas scaffolding protein family member 4) because it is now considered as 4th member of Cas family of adapter proteins which are well studied and implicated in many cellular functions including cell attachment, cell migration establishing polarity, invasion and phagocytosis of bacterial pathogens. 

http://www.ncbi.nlm.nih.gov/pubmed?term=singh%20MK%20and%20HEPL

Expression of HEPL in various tissues and cell types

I had observed that the human HEPL mRNA and protein are selectively expressed in specific primary tissues and cancer cell lines, and HEPL protein maintains Cas family function in localization to focal adhesions of the mammalian cells, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading.

Lung sections stained with Anti-HEPL antibody, which shows high expression levels of HEPL in lung tissues. 

When I saw Dr. Garry Cutting’s paper in Nature Genetics paper, it kind of reaffirmed my earlier hypothesis that HEPL could be involved in lung diseases, as in my own work with this protein while characterizing the molecular pathways pertaining to this protein, I had noticed an unusually high expression of HEPL protein in lung tissues (both normal and cancerous). However, due to my primary interest in Cancer Biology, I kept on working on other aspects of the same protein family. I hope Dr. Cutting who is an expert in the area of Cystic Fibrosis, and other investigators will continue working on the mechanistic connection between HEPL loci on Chromosome 20 and Cystic Fibrosis. Well, the good news is - HEPL being a scaffolding protein may well serve as molecular target because of its interactions with several important kinases such as FAK and Src etc. that I discussed in my 2008 publication.  I am very enthusiastic about these findings as they provide deep insight into the causes of variation in lung disease severity in cystic fibrosis and have a great potential for development of new therapeutic targets for this deadly disorder.

Study on “Snake oil” opens up doors for new drugs to treat heart diseases....

Most of us specially those coming from countries like China and India, where we have ago old tradition of using herbs and products from various animals to cure our ailments, may have heard of Snake oil which is a topical preparation most commonly made from the Chinese Water Snake , and other varieties of other species of snakes in other countries. Snake oil used to be known rather infamous for treatment of joint pain, and used as aphrodisiac in many ancient cultures. Medical Scientists have always seen it with skeptic eyes and it has become such a controversial research topic during 19th century, that they started using snake oil as a phrase/a derogatory term for quack medicine. The expression is also being used metaphorically to any product with questionable and/or unverifiable quality or benefit. However, after a publication recently appeared in a top notch journal Science, a collaborative effort of a reputed group of scientists from Universities of Colorado and  Alabama, USA, people have started thinking that there might be something really worth considering seriously to snake oil after all.

In their experiment, these investigators fed a group of mice (which have hearts quite similar to humans) with a chemical cocktail, which are chemically inspired by the fatty acids of Burmese pythons. After a particular time point, these mice found to have grown bigger hearts than control fed mice.

To understand the origin of the research, we must understand the physiology or functioning of the heart. When the situation demands it, the muscles of mammalian hearts grow larger and pump more vigorously. That's useful for pregnant women who need to pump for two, toddlers who need to fuel their rapid growth, or athletes who need to power their regularly exercise. But growing hearts can also be bad news if they're triggered by genetic disorders, high blood pressure or heart attacks. These situations can cause a condition called "hypertrophic cardiomyopathy", in which the heart's thickening walls force it to work harder to pump blood.

To understand how hearts get bigger, this group of scientists which include Cecilia A. Riquelme, Jason A. Magida, Brooke C. Harrison, Christopher E. Wall, Thomas G. Marr, Stephen M. Secor, and Leslie A. Leinwand who is group leader of this study, turned to an animal whose heart is known for swelling in size every time it eats – the Burmese python. As we all know Pythons can swallow extremely large prey like deer, and they remodel their organs to cope with their meals. Intestines and livers of these pythons nearly double in size and their hearts become 40% bigger in just two to three days in comparison to most mammalian hearts which become only 10–20% bigger after months of exercise.

http://mcdb.colorado.edu/mcdb/leinwand

After their swollen hearts these pythons change their heart functioning. Their bigger hearts’ vigorous pumping results into higher oxygen supply through the snake's bloodstream, leading to up its metabolism by 44 times. Its cells produce more proteins that strip electrons from food molecules and shunt them onto oxygen, producing water and liberating energy. Its blood vessels fill with 52 times the usual level of triglycerides, substances found in fats and oils. Such levels would clog mammal hearts with fat, but the pythons seem immune. These changes turn the snake into a long, supercharged energy-extracting machine.

FThese scientists discovered that there is something in the python's blood that triggers the transformation. They extracted plasma from the blood of pythons that had just been fed, and placed it on rat heart cells. They grew in size. They wondered if a protein could be responsible? Then they used either heat or digestive enzymes to destroy the proteins in the python plasma, but it still managed to engorge the rat cells. They concluded that it was not a protein as proteins would have been destroyed by heat or protein specific enzymes. Then what else it could be?

The miraculous ingredients in python blood turned out to be fats. The blood of fasted and fed pythons contained very different blends of fatty acids, and the team identified three that are particularly important – myristic acid, palmitic acid and palmitoleic acid. Well-fed pythons have lots of all three fats, balanced at a very specific ratio. When investigators mixed up this cocktail and injected it into a fasting python, the snake's heart grew as if it had just eaten a big meal.  Then they extended their study to a mouse model because they wanted to know if this phenomenon holds trues to mammalian hearts as well. Lo and behold the same fatty acid cocktail also increased the size of mouse hearts within a week. The effects were very specific – the cocktail didn't affect the size of the rodents' other muscles, but cardiac muscles. The enlarged hearts showed no signs of clumps of fat, or fibrosis – a condition that stiffens the heart and accompanies disease.

Wow……the implications are intriguing…is not it??. Might it one day be possible to give someone the heart of an athlete by administering the right combination of python-inspired fatty acids?  Dr. Leslie Leinwand herself hopes so, however, she warns  - "That is the hope, but we are not advocating that people take pills instead of exercising. We are hoping first to show that these fatty acids might be beneficial in the setting of heart disease and it is a long way off to humans from here."

On a lighter note, for the people in India, next time you see a snake charmer or a quack selling snake oil, just do not reject all his proclaims, he might well be selling something that can cure your ailing heart. And not to forget that every 4^th Indian is genetically susceptible to develop cardiac problem in his/her lifetime.  

For those who want to read the technical side of the story, here is the link:

http://stke.sciencemag.org/cgi/content/abstract/sci;334/6055/528