The Fault, Dear Brutus, Lies in the Genes

Genetic testing for health risks holds plenty of promise in India, so long as enough people take to it
Diagnosis
Interest in ‘cancer genes’ has shot up, especially after Hollywood actress Angelina Jolie’s double mastectomy, which she had got done after a genetic test pinpointed a ‘faulty’ BRCA-1

As he peers over the diagram of a family tree, one among several he has drawn in the past five months, Dr Amit Verma runs his fingers along the arrows to trace cancer in his patient’s family. Two of the patient’s aunts were detected with breast cancer in their forties, and their father (her maternal grandfather) had died of prostate cancer. “[The patient] is now 34 years old and is worried that she might have inherited the ‘cancer gene’, as it were,” says Dr Verma, a molecular oncologist who has been studying genes and genetic mutations that cause cancer for ten years and set up a counselling centre for it this January at Max Hospital in Delhi. The patient in question, he observes, is at risk of developing ovarian or breast cancer, as both are caused by aberrations in the functioning of genes like BRCA-1 and BRCA-2. She is also worried that it might affect her son at the end of the family tree, who could be at risk of prostate cancer at some point in his life. The patient was referred to Dr Verma by Max’s Oncology Department, which is treating a member of her family. She is yet to decide on getting herself and her son tested. These would be genetic tests designed to pinpoint specific risks and may even call for precautionary medication.

“The cost and trauma of dealing with cancer, especially at a stage when there are no symptoms of it, is difficult to bear,” says Dr Verma, “It takes time.” He has at least half a dozen other cases of patients yet to take their tests, all of them advised to do so after a ‘pedigree analysis’ of cancer prevalence that involves tracing three generations of family history. However, interest in such ‘cancer genes’ has shot up lately, especially after Hollywood actress Angelina Jolie’s double mastectomy, which she had got done after a genetic test pinpointed a ‘faulty’ BRCA-1 and predicted an 87 per cent risk of her developing breast cancer and 50 per cent risk of ovarian cancer. The blaze of publicity generated by that event, Dr Verma hopes, will draw more people to have themselves screened for genetic risks of cancer. About 10 per cent of all cancers are directly hereditary, he says, passed along from parent to child, while about 15-20 per cent are familial in nature, which means that almost every member is at some risk if it runs in the family. “Since genes do have a considerable role to play,” he says, “genetic screenings are an important method of preventive diagnosis.”

The purpose is to ascertain the risk and take action early, before it reaches a stage that’s harder to treat (or worse). Not all patients at risk need surgery; Jolie’s was a rare case. “Patients can also be given chemotherapy for prevention or a dose of medication in case of suspected breast cancer,” says Dr Verma. He mentions the case of a teenaged girl in a family with a heavy record of breast and ovarian cancer who was put on a preventive regimen of oestrogen drugs.

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The test for BRCA-1 and BRCA-2 faces a chicken-and-egg problem in India. Since it can cost anything between Rs 50,000 and Rs 80,000, few people can afford it. “The cost is a deterrent in most cases,” says Dr Verma, “particularly if multiple members of a family have to take it.” But also, since so few people take the test, no company makes an effort to operate on a large scale and lower its cost; to complicate matters, doing so would require a company to challenge the controversial patent that US-based Myriad Genetics has on the genes BRCA-1 and BRCA-2. An Indian firm would do this only if it is assured of enough demand to justify the trouble. Right now, the test is conducted by local labs—at about a quarter of its cost in the US—on such a small scale that it escapes global attention.

There are several other genetic tests, however, that are available in India at prices that are within middle-class reach. Several private diagnostic clinics have sprung up in the past couple of years that offer tests to check for a predisposition towards lifestyle illnesses like hypertension, type-2 diabetes and cardiovascular disease, apart from DNA checks for metabolism rates and associated weight gain, even whether certain medicines suit a patient’s genetic make-up.

Most of these clinics operate in association with private research laboratories that have come up since 2009, when the Delhi-based Institute of Genomics and Integrative Biology (IGIB) successfully sequenced the Indian Human Genome (the body’s complete set of genes), just as it had been done in the US.

For packages that range from Rs 10,000 to Rs 15,000, many of these clinics offer genetic counselling, fitness plans and diet advice as well. For Rs 9,999, for example, Xcode Life Sciences in Chennai, launched in July last year, offers a package that includes predictive genetic tests for obesity, strokes, diabetes and cardiovascular diseases; it claims a clientele of over 100. For Rs 25,000, Hyderabad-based Mapmygenome, which started in January, offers its clients a so-called ‘genomepatri’ based on a set of tests; the company claims to have over 250 clients, including celebrities such as Congress Member of Parliament Shashi Tharoor.

Such tests can also be ordered online. A kit is sent to collect a sample of the customer’s saliva, which is then forwarded to a laboratory for testing. The results take about eight weeks, and are delivered along with medical advice. All of it by courier. Convenience is the seller here.

Often, people also have plenty of questions to ask. Delhi- based Nutragene, which operates with a network of private hospitals and doctors, offers a 45-minute counselling session over the phone before putting a patient under genetic tests. Some clinics even conduct anonymous tests recommended by doctors. “We just ask for the sex of the patient and conduct an analysis of the sample,” says Anu Acharya, founder of Mapmygenome. She claims that her company has conducted tests for several celebrities anonymously. “We also get requests from people looking at arranged marriages and getting tested to check for genetic predispositions,” she says.

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Bala M, a marketing professional in Chennai, has been watching his diet very closely over the past few months. Bedridden for a long time with a leg fractured in an accident eight years ago, he had piled on a lot of weight and was struggling to slim down. His diet plans and gym efforts were not doing him much good. “During an informal conversation, a friend remarked that maybe it was genetic,” says the 40-year-old, “So I started reading up on the internet and found that one could have a propensity to acquire lifestyle diseases because of one’s genes.” He signed up with XCode Life Sciences to have himself tested.

Bala ordered a kit from XCode, sent his saliva sample by mail, and waited eight weeks for his test results and lifestyle recommendations. As it turned out, he was not predisposed to obesity, but his genetic scan revealed a risk of hypertension traceable to genes acquired from his mother’s side of the family. “I was advised to reduce my intake of carbohydrates.” While he admits that he has not done this too ‘seriously’, he says he feels lighter. And since the test cost him only Rs 10,000, he had his wife undergo one as well. “It’s not very expensive,” says Bala, “and if nothing else, it helps prevention.”

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Genetic testing involves the molecular level study of DNA for genetic disorders. Passed on from parents to their offspring, DNA encodes the genetic information that determines a variety of functions and outcomes in a human body. Since parents give children their DNA, they pass on genetic risks alongwith their physical and other traits to the next generation. The ideal way to study a person’s genetic makeup in its entirety is to sequence his or her genome, a process called genotyping. The genotype so obtained is then compared with genetic information collected from a large population for the identification of aberrations or mutations. Called ‘personal genomics’, this is what most tests offered by the abovementioned clinics entail (these are distinct from classic paternity tests, prenatal tests for Down’s Syndrome and the like).

Personal genomics has been a global endeavour since 2003, when the entire Human Genome was sequenced for the first time after a 13-year effort by the US Department of Energy and National Institutes of Health (NIH), with the help of Japan, France, Germany, Spain and the UK—and speeded up by Craig Venter’s ‘shotgun’ method.

In India, the IGIB achieved the same with its Indian Human Genome Project six years later. The sequencing done by the IGIB could be of special value to gene testers in India because the project drew its data from an Indian population that has an enormously wide range of genetic diversity. Scientists hope that this special focus will help spot key genetic markers that are prevalent in this part of the world.The project discovered a community in Himachal Pradesh, for example, that was found to display a genetic resistance to the HIV virus.

Gene tests in India, many say, need to be sensitised to local variations to the extent possible. Saliva works well for such tests because it lets labs study genome contrasts through variations called Single Nucleotide Polymorphisms (SNP), which vary so much from one person’s genome to the next that they permit the observation of fine differences.

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While health enthusiasts and wellness experts are excited about genetic tests, the medical establishment is keen to see that expectations do not exceed their potential. Many doctors have reservations about how these tests can aid healthcare. According to Dr PK Jhulka, who heads the Oncology Department at All India Institute of Medical Sciences (AIIMS), genetic testing is still at an evolving stage in India and should be used with caution. “Genetic test results can predict [some future illnesses] with a 70-80 per cent accuracy rate,” he says, “but it is still only a prediction and should be used with great care as it can have a huge psychological impact on the patient.” According to an IGIB scientist, the benefits of some of these tests do not justify their high cost in terms of money and effort. To her mind, tests for cancer and ailments like Parkinson’s or Alzheimer’s are worth opting for, but those for diabetes and cardiovascular ailments have cheaper alternatives that are reliable. “Even then, these ailments are not caused by a single gene mutation that is easily identifiable as in the case of breast cancer, so it is far more complicated,” the IGIB scientist says.

Biotechnologists and entrepreneurs, however, see a great future for genetic tests and preventive healthcare. Such tests, they say, pinpoint the exact nature of several ailments and provide an opening for breakthroughs in cures for ailments. “We are collecting data and studying it in our labs, hoping that through these varied samples and comparisons, one may find something new that is not known in the human genome,” says Acharya of Mapmygenome.

Globally, many researchers consider genetic diagnosis the first step towards gene-customised healthcare, which would be a big leap over the current one-pill-cures-all approach.

In India, much work is being concentrated on diseases that Indians are especially vulnerable to. Such as diabetes, both type I and II, the genetic risk of which Acharya places at about 26-30 per cent. “So, if you have a high genetic disposition towards this ailment, you can make changes to alter the assessment instead of waiting to develop the disease and then testing for it,” she says, “That is the beauty of it.”

The key question at the end, though, is of test accessibility. Prices could come down sharply if more and more people opt for these tests, since there would be a much larger number of customers to cover the huge set-up costs of these businesses. According to Anubhav Anusha, proprietor of Nutragene, the market for genetic testing today is like that for telecom more than a decade ago. “The cost of a cellphone at one point was Rs 40,000, but is now accessible to everyone even in low-income groups,” he says, “The business is in volumes. It has to get cheaper—patents notwithstanding, of course.”

Indeed, volumes make a big difference. If the test for BRCA-1 and BRCA-2 catches on, an Indian firm might be tempted to challenge Myriad’s patent and crack India’s chicken-and-egg problem.