New Delhi: I.C. Verma, a senior consultant at the Center of Medical Genetics at New Delhi’s Ganga Ram Hospital, was approached by the parents of a child who suffered from epilepsy and whose whole body was covered with painful blisters.
After carrying out tests, doctors at the hospital determined that the blisters were the result of the child’s adverse reaction to the medicine he had been taking for epilepsy.
The child had a mutation in a gene called HLAB 1502 that caused the allergic reaction. “In India, this mutation is found in only 2% of the population,” said Verma. “We had to change his dosage to suit the mutation to avoid this adverse reaction.”
The Center for Genetics at Ganga Ram Hospital is currently studying the mutation in Indian genes that can cause adverse reactions to anticoagulant medicines such as Warfarin. “We have seen patients who take such medicines for heart diseases, but can have adverse reactions like haemorrhage, due to certain gene mutations,” Verma said.
In May, Hollywood actress Angelina Jolie wrote in a New York Times oped article that she underwent a preventive double mastectomy after she was told that a gene mutation made her much more vulnerable to breast and ovarian cancer compared to average women.
Jay Orringer, the surgeon who performed the breast reconstruction surgery on Jolie, said last week that by going public about her gene testing and the double mastectomy, Jolie had inspired countless women to undertake preventive gene testing.
In India, too, a growing number of women are taking such tests, said Verma.
“So many women come to the clinic to get themselves tested for their risk to breast cancer, as their mothers or sisters suffered from it,” he said.
Learning of one’s risk to disease is a useful application of gene testing, but scientists and doctors in India are more excited about the growing prospects of pharmacogenomics, which could usher in an era of personalized medicine in the future.
Pharmacogenomics is the study of how genetic make-up affects people’s response to drugs. All drugs that are taken orally are absorbed in the intestine, then metabolized in the liver and circulated for action. People react differently to drugs based on how they metabolize. The aim of pharmacogenetics is to assist in choosing the right medication for an individual.
According to Peter Goodfellow, head of the department of genetics at Cambridge University, if 10 patients are prescribed the same medicine, three will benefit, three will experience no appreciable effect, one will have an adverse reaction, and three will not take the medicine at all.
It was in 2009 that Vinod Scaria and Sridhar Sivasubbu from the Council of Scientific and Industrial Research’s (CSIR) Institute of Genomics and Integrative Biology successfully decoded the sequence of the genome of an anonymous, healthy Indian citizen.
The genome consists of around 3.1 billion base-pairs and 25,000 known genes. “In 2008-09, the cost of sequencing a genome was Rs.20-30 lakh (excluding equipment cost),” said Scaria. “By 2014, personal genomics could cost Rs.2-3 lakh as there will be a 50% drop in the cost every year.”
“This could become affordable for diagnosing many genetic disorders by 2015. Hospitals and patients will start using it for healthcare. When that happens, we will have to think about what kind of tools could be used,” the scientist said.
Scaria and Sivasubbu get cases with genetic disorders and they can find the mutation that caused it. In most cases, they look at a tiny 2% of the genome that codes for proteins and focus on variations—and assess which drugs the patient can take or not take.
The DNA is put up for sequencing using one of the next-generation approaches. The sequenced genome is assembled and analysed using large computers to decipher the genetic variations and analyse the genetic risk. “We take normal and diseased people to do genome sequencing; we collect data, curate and then create computational tools to interpret the data,” said Sivasubbu.
“The data is of more than 3.3 billion alphabets. With more technological advances, sequencing has to become cheaper,” he said. “We need more people and public awareness and price has to come down.”
They currently have 140 people who have shown an interest in getting their genomes sequenced through a website they have created called Meragenome.
Ganga Ram Hospital provides a range of laboratory tests in genetics to see how a person would react to drugs for diseases ranging from cancer, Gilbert’s syndrome, immunity disorders and rheumatic arthritis.
“For patients of depression or asthma, doctors use drugs by trial and error method. They keep changing the prescribed drug till something works. In cases like these, pharmacogenomics can be very helpful,” said Verma.
The US drug regulator, the Food and Drug Administration, has a list around 150 drugs that patients are advised to take only after genetic tests.
“In the Indian research setting, we have addressed the ethics issues; however, a stringent mechanism for oversight has to be evolved, especially in the commercial settings. This includes issues such as what and how a company can use the genome data for in the future” said Scaria.
He added that documentation of consent is a major policy requirement as there are several implications of sequencing a person’s genome.
The scientists from CSIR believe there could be many ethical dilemmas accompanying genome sequencing in India. For instance, anyone with the required knowledge can mine a person’s genome information to identify traits that could affect employment and insurance.
“Genome is a heritage and a collective resource. Your genome is not just your property, but your forefather’s and your progeny’s, too. One has to be careful about the implications of ethics in genomics,” said Sivasubbu.
“This field will evolve with regards to ethics, but according to me, insurance is the biggest implication,” he added.
In the US, there have been growing concerns that genetic information could be used by insurers and employers to deny, limit or cancel their health insurance and to discriminate against them in the workplace. The US Senate unanimously passed the Genetic Information Nondiscrimination Act of 2005 to lay the ground for the implementation of the policy recommendations on health insurance and to provide protection from such discrimination.