Every child born in the United States is today screened for diseases at birth, though the range of testing is not uniform, it varies from state to state. In India, we are very far from such screening but I believe, at individual levels, it will become commonplace soon. More than 70 percent of healthcare is in private sector and in the absence of universal coverage individual choices prevail, particularly when direct-to-consumer companies are getting aggressive.
Even if we take clinician-mediated genomic testing, Strand Life Sciences alone has expanded its exome sequencing services from one hospital at the beginning of the year to more than 20 as the year closes.
So what choices can individuals make when they get their genome (exome in the foreseeable future) sequenced? When the mutation is actionable, one needs to take action; but what if one has a mutation that increases the risk for Alzheimer’s? Forget about it?
But before we come to that, clinics and genetic testing labs must get basics right. They must arrive at some kind of standardized report – even a process laid down by genomic experts – that is useful for doctors who are not trained in understanding genomic analysis. (It was just chance that I happened to see a general physician at a large corporate hospital for a minor problem soon after I got my exome analysis. Out of curiosity when I asked if late onset breast cancer was common among her patients and what 1.3X increased risk, which I had, meant? The doctor did not even pretend to be interested. “You must consult an oncologist,” is all she’d say dryly, without moving her gaze from the keyboard which she was pounding to enter her regular consultation remarks.)
The genomics, clinical and regulatory community must also formulate guidelines for uniform reporting and analysis. Imagine how a person’s life would go out of gear if her diabetes or colon cancer risk varied widely from one lab to the other – 15 percent in one lab report and 40 percent in another? Anuradha Acharya, founder of MapmyGenome believes an NABL-like certification (which is administered by the Department of Science and Technology) should be is in place so that genomic testing falls within regular diagnostic tests. She thinks this would prevent random companies from setting up shops.
I’d go even a step further and suggest a consortium be set up which develops standards for nearly everything – consent forms for DNA donors to methods of collecting and analyzing DNA samples. This would allow the community to share and study multiple data sets.
Sequencing technologies are getting fairly close to plug and play and so the ability to set up a lab to run samples and get some data out is gradually becoming fairly commoditized. This is even more the case if you are running micro-arrays, says Vijay Chandru, founder and chairman of Strand Life Sciences. Getting good quality data requires deep bioinformatics expertise. Then comes the mother of all challenges: clinical interpretation of sequencing results which is a tricky problem even for the most advanced research institutions in genomics.
Since this is directly or indirectly taken as medical advice by the patients and attending physicians, it is essential that only experienced and certified medical geneticists and genetic counselors trained in interpretation of genomics communicate the results to the people and their physicians, says Chandru.
During my post analysis genetic counseling when I asked Dr Kavita S Reddy how much of the carrier mutation information should I share with my child; she said it was my call. Well, I still have time until the 11-year-old is mature enough and wants to know what his inherited genetic vulnerabilities are but the dilemma is really serious in the case of new-born screening? Won’t parental consent violate a child’s right to know or not know? On the other hand, if you wait for the child to become a major and consent, it may be too late for her to truly benefit from this knowledge.
It appears that the human race is at crossroads as well as at a frontier which is as much technological as moral and philosophical. The theory of evolution may tell us how humans got here, but we don’t think it’d tell us where we go from here. The possibilities are enormous.
“This is the biggest game changer in our life time and till the genome is understood completely variants are only a probable cause,” says Dr Reddy. Her biggest concerns are:
1) The genome may lead to discrimination for jobs and health coverage.
2) Matching personal genomes may be involved in choosing mates.
3) Assisted reproduction and designer babies will change the parent-foetus equation.
4) Who will keep the genome data in pace with the current knowledge and who will safely store it?
5) Medical practice will change forever; the genome may be the starting point for all decisions. And hence without barcode you will not be treatable.
6) Who controls your data while you are a minor and after your demise?
These are mind-boggling questions. I even shudder to think, given India’s social structure, if marriageable girls, or even guys, get their genome sequenced and some sort of discrimination creeps in. What if a young person is known to carry some mutations which are not fully understood by the medical community to be the definitive cause of a disease and the families or respective individuals take mating decisions based on incomplete knowledge?
For these and many other reasons, believes Chandru, that “it is really bad idea to communicate results and clinical interpretations directly to patients without an attending physicians and genetic counselors involved.” States like New York and Maryland in the US explicitly forbid direct-to-consumer genomics tests like 23andMe.
Still, given how valuable sequencing is for clinical conditions – to understand how a tumor is progressing or for patients whose diseases can’t be identified by the standard genetics tests or whose diseases don’t respond to conventional tests — at least Indian professionals should gun for a law that doesn’t deny health insurance to people. The US passed GINA—Genomic Information Non-Discrimination Act – 2009. That’s a good model for India to look at, says Chandru.
We don’t know if insurance coverage of clinical genomics test will become popular or acceptable any time soon. It is a complex value proposition even in the developed markets.
In India, says Chandru, the most likely insurance coverage of preventive tests may come in diabetes and cardiac conditions. We have only had a couple of preliminary conversations around tests for Gestational (diabetes during pregnancy) and MODY (maturity onset diabetes of the young which is more likely to be inherited than other types of diabetes) and there seems to be interest since the therapeutic intervention based on the tests can have long term health consequences, he says. The standard of care, which is reimbursed by insurance, in the West for individuals with serious family history of cardiac disease involves genomics testing for risk of cardiomyopathies etc. as lifestyle modifications and closer monitoring of the patients would be called for if the patient has the pathogenic inherited genomic variants. This standard has not come to India as yet although we are gradually getting some traction with younger cardiologists, he adds.
In a society ridden with all kinds of social discrimination, we are today at a risk of creating one more for of differentiation — one based on genetic health. Can we have the basics, the 101 of genomics awareness and regulation as it were, in place? What are you thinking?