Seema Singh
Seema Singh
I write about sci-tech and all things that lie at the intersection.

It’s that time of the year when most media outlets do a stock-taking – the best and the worst of news and news-makers of the year. This post is no such attempt. As the year comes to a close, I think one of the defining moments of 2013 in India has been the successful take-off of India’s Mars Orbiter Mission and the way it changed ISRO’s public communication: Nearly 300,000 followers on Facebook in less than three months of debuting on the social network! Hope it’s not restricted to MOM alone.

It certainly speaks of people’s innate desire to learn and care about science, particularly space science. People have watched Mars maneuvers and updates at 6 am, at midnight, even corrected the ISRO social media team when they merely said the task was ‘completed’, forcing them to add the word “successful”. (So successful was ISRO on social media that in no time several fakes sprung up, forcing ISRO to issue a statement on fake ISRO identities.)

Not many Indian scientific institutions can afford to have such mega projects that also catch the public imagination but at least they can make a beginning, in their own way, in reaching out to the people. They are obliged to do that; after all, nearly 80 percent of science in this country is done with taxpayers’ money. (More on that in some other post.)

This year has been good for ISRO, particularly if seen in the light of late 2010 and most of 2011 when the space agency was bogged down by Devas controversy which hurt most of its programmes. By that measure, 2013 saw some serious milestones being covered. (You can read about some of the technical gains from this mission in Forbes India year-end special which hits the stands on Dec 27.)

With the February launch of Saral, an oceanographic satellite which carries payloads made by the French agency CNES, ISRO also put six other satellites from four countries into the orbit. In July, it launched IRNSS-IA, the first in the series of seven satellites that will constitute India’s own navigation system, a limited version of GPS (global positioning system), so to say. Called Indian Regional Navigation Satellite System (IRNSS), its second satellite IRNSS-1B is getting ready for launch in the first quarter of 2014, says ISRO chairman K Radhakrishnan.

However, it was the Mars Orbiter launch of 5 November 2013 that evoked images of the awesome Martian landscape and united most space loving people in the country. Quite a feat it was to launch MOM using Polar Satellite Launch Vehicle, India’s trusted and versatile rocket, which hurled the spacecraft in a low earth orbit just when NASA launched MAVEN directly into the Mars orbit. Some critics have argued that ISRO showed hurry in choosing PSLV instead of waiting for GSLV to get ready for a Martian mission. That not only would have launched the satellite in an orbit closer to Mars but perhaps would also carry more instruments. But the fact that a Mars mission opportunity comes only every 26 months, if ISRO had missed the November 2013 chance, it’d have had to wait until 2016 for the next mission because the GSLV is not ready yet.

ISRO chairman says there’s a subtle technical point here which people are missing. It’s true that GSLV would give a higher apogee, say 40,000 km as opposed to 23,000 km which was achieved by the PLSV but it’s the attainment of the Argument of Perigee where GSLV is unsuitable. For this mission, the Argument of Perigee had to be 280 degrees but GSLV could achieve only about 180, rendering it unsuitable as the launch vehicle. (While Perigee is the point of the orbit closest to the centre of the earth, Argument of Perigee is the angle from south to north equator to the point of perigee and helps determine the orbital ellipse in which the spacecraft moves). As for the instruments, ISRO says there has been no compromise. When the Mission was announced, they started with 33 instruments, narrowed it down to 11, then 9, and finally zeroed in on 5 instruments. The chairman says whatever was built and qualified for flying has been carried on the spacecraft.

It’d have been a cracker of a year for ISRO if the GSLV–D5 — a vehicle that in the proverbial sense is proving to be rocket science for ISRO – was launched on August 19 as planned but it got called off at the last minute. A leak was detected in the fuel system of the liquid second stage of the engine. Radhakrishnan says he’s satisfied with the way the leak was detected and then managed. Nearly 350 tons of propellant was loaded in the vehicle which could have led to any kind of mishap. A review meeting is planned for December 27 which will decide the date of launch but in all likelihood GSLV will be launched on January 5.

Photo Courtesy NASA’s Curiosity

Photo Courtesy NASA’s Curiosity: These rocks record superimposed ancient lake and stream deposits that offered past environmental conditions favorable for microbial life. Rocks here were exposed about 70 million years ago by removal of overlying layers due to erosion by the wind.

In short, with GLSV launch in January, the MOM entry into Mars orbit in September, with a smattering of other launched interspersed throughout the year, ISRO will, hopefully, keep space buffs connected to its Facebook site which it is updating with discipline and enthusiasm. The Red Planet will continue to fascinate us. A fortnight ago, Science published findings from Curiosity Rover which shows that all the elements of life (oxygen, hydrogen, phosphorus, nitrogen, carbon and sulphur—which are considered by biologists to be fundamental to life) were present in one place, a dried lake bed, towards the south of the Martian equator. The nearby geology also supports the evidence of river channels.

More such findings may surface in 2014. Can ISRO’s MOM then tweak its payloads to add to the knowledge that Curiosity, MAVEN or other missions may throw up in the next several months? ISRO says it is tracking and talking to other mission heads but the capability of its instruments is fixed. What can indeed be maneuvered is the amount and quality of observations that these instruments can make.

MOM or MAVEN, Curiosity or Opportunity, the year 2014 certainly holds great promise for space science.

The year also ends on a promising note for the space start-ups, not necessarily in India though. Russian billionaire Yuri Milner, who was an early investor in blockbusters like Facebook, Twitter and Chinese e-commerce company Alibaba, last week pumped in several millions in a space start-up, PlanetLabs. Founded by NASA scientists, PlanetLabs, with its bunch of satellites, hopes to have the largest network of imagery satellites in space.

The next “launch” for ISRO should be to encourage and help fund a few Indian start-ups to take similar Moonshots! There’s nothing like space to fire a generation’s imagination. Nasa’s Apollo programme proved that beyond doubt.

PS: This is my last post for Forbes India. The year comes to an end, so does my tenure at the magazine as I choose to move on. Far from the madding world of viral content and (web)traffic wars, this blog has dealt with sober topics, topics that might not have got boatloads of unique visitors (the metric that matters in the digital world) like Bollywood or cricket posts get, but it got some involved readers. Thank you all for that. Wish you a Prosperous and Productive 2014. 

Barring a few lucky or enlightened ones who’ve learnt to slay this dragon, stress affects virtually everyone, in acute or chronic way, at some point in life. In this process, as the last 30 years of research shows, our brain is affected in many ways. One of the fascinating and evolving stories of stress is the contrasting effect it has in the two neighbouring parts of the brain —the hippocampus and the amygdala. It’s a story that is also, albeit very slowly, throwing crucial light on why most anti-depressants are not effective and why the world today is staring at a mental illness epidemic.

It’s been established that stress not only shrinks the hippocampus, the seat of factual memory and learning in the brain, in volume but even reduces synaptic plasticity, or long term potentiation (LTP). A synapse is a junction that allows a neuron to pass electrical signal to another neuron or any other cell. When there’s a rapid and long-lasting enhancement of the response of a synapse to one of its inputs, it is called LTP which allows spatial memories to be formed in the hippocampus.

Decreased hippocampal volume has been linked to cognitive deficits, which are common in post-traumatic stress disorders. In fact, a shrinking hippocampus is also a risk factor for the development of such disorders.

In all these years stress has been extensively studied to show that it impairs LTP in the hippocampus. Neurons themselves lose dendrites, synapses, and their capacity for LTP. Together these explain why following chronic stress factual memory and cognition decline.

But all these studies fail to explain why when everything (volume and synaptic plasticity) is going down in the hippocampus; emotional response and anxiety are going up in the neighbouring part of the brain, that is, the amygdala. While scientists understand the former, they have little clue about the latter. Now, in the 40th year of the publication of the landmark paper on LTP that transformed the understanding of memory and stress, neuroscientist Sumantra Chatterji and his colleagues at the National Centre for Biological Sciences in Bangalore provide some scientific evidence. The mystery of exaggerated emotional response in stress disorders rests in the electrical activity of amygdala, part of the brain which is responsible for anxiety, fear and aggression.

Sumantra Chattarji

Sumantra Chattarji

We have shown that the same LTP which reduces memory in the hippocampus gives rise to enhanced fear and anxiety in amygdala, says Chattarji. “The same plasticity mechanism that is shown to decrease in the hippocampus is seen to be going up in amygdala. We know that LTP is pivotal for forming fear memories and we show that LTP goes up in amygdala during stress.”

Looking at the basic cellular mechanism, the NMDA receptors — the molecular substrate that is responsible for LTP to happen — are seen to pass double the current in the amygdala. In their earlier work Chattarji and his colleagues have shown that stress creates new synapses in this part of the brain. This, again, is in contrast to the hippocampus where synapses are lost during stress. In experiments on animal models, Chattarji has showed that it’s the new synapses – formed during stress—that pass extra electrical current, not the old synapses.

It turns out the new synapses, or the silent synapses as they are called, are loaded with memory-making molecules or the NMDA receptors. If you look at the cells at rest, says Chattarji, you can’t tell any difference. But if the cells get activated, such as during the formation of fear memory, then the silent synapses open up and create stronger memories.

This explains why stress, which in most cases makes us forget facts of life, elicits strong, many times exaggerated, emotional response in us.

Chattarji is reporting his finding at a stellar Royal Society gathering in London on Dec 2-3. Scientists have gathered to celebrate, as it were, the 40th anniversary of the unraveling of the LTP. It is convened by Timothy Bliss, the scientist who discovered in the 1970s how a few seconds of high frequency electrical stimulation can increase synaptic transmission in the rabbit hippocampus for days. He published his landmark paper in 1973 in the Journal of Physiology.

It’d be fair to say Chattarji’s work turns the entire hippocampus-stress-memory framework on its head.

Much as neuroscience has advanced, the correlation of mice model to humans remains as relevant as it was decades ago, except of course that the models are getting more sophisticated. Nearly 95 percent of neurobiology research even today is based on rats and mice, he says. Even if you consider the current LTP contrast in hippocampus and amygdala, animal and human studies complement each other beautifully.

For the last 5-10 years, clinicians have seen through brain imaging that in stress disorder patients, while hippocampus becomes less active amygdala becomes hyperactive. But they did not have a molecular basis for that. “What they’ve seen in humans actually bears out in animals now. And the fact that nothing invasive can be done in humans, the two together can now explain the mystery,” says Chattarji.

Fascinating as this aspect of brain may be, the findings raise a very common sense challenge. How do you design a drug that does opposite things in two adjacent parts of the brain. The reality is most anti-depressants are developed with just one model—of the hippocampus—in mind. This also explains why in recent times the US and UK carry warning labels on the most popular anti-depressant drugs (the selective serotonin reuptake inhibitors or SSRIs) like Prozac, Zoloft or Paxil because they create enhanced anxiety and suicidal tendencies in young patients, at least in the first few weeks of the treatment..

Chattarji, who in the last few years has made a systematic effort to bring psychiatrists closer to neuroscience by conducting week-end sessions at NCBS, says practitioners rarely care for the mounting scientific data and its implication in everyday practice. He says most clinicians are concerned about prescribing a drug and assuaging the symptoms of their patients rather than understanding how brain works and why their treatment may not be effective in the medium to long term.

It’ll take some time before the drug design community begins to take the double model—hippocampus and amygdala — into consideration. The world of psychiatric drugs has long rested on serendipity and marketing tactics, but this time the science looks convincing.

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.)

DNA sequencing gel, close up

DNA sequencing gel, close up

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?

The conference room at Strand Life Sciences looked welcoming, yet formidable. After all, four professionals had gathered to discuss what my Exome sequences were revealing.

Senior scientist Smita Agarwal had the power point slides on: “Personal Exome Screening: A Case Study”

That’s the paradox of genomics: it’s intimate and abstract at the same time. For geneticists and computational biologists my DNA sequences amounted to a mere case; for me, genomics was never more personal.

Before Agarwal could begin, chief technology officer Ramesh Hariharan set the tone and put me at ease. “There’s nothing dramatic [in the DNA],” he assured. Apart from a host of good and bad mutations, I was “the proud owner” of four novel genetic mutations. Unlike many tests being offered in the market today, Strand does not provide disease predisposition reports, except in rare cases where the science is more definitive. In other words, they’d not tell me what my risks for common chronic disorders such as type II diabetes, CVD, arthritis, etc were. It’s hard to predict with a high degree of accuracy anyway because these are multigenic diseases where the science is not well understood.

I was fine with it. In any case I am not interested in knowing how I’d look or behave based on my genetic makeup.

(To digress a bit, there’s difference in technology between what Strand uses and what most other genetic testing companies today use. While the former uses exome sequencing (as I explained in the first part), others use array based genotyping, which is a process to determine the genetic variants of an individual. Array- or chip-based genotyping requires prior knowledge of the variants or mutations one wants to analyze. Therefore most wellness or preventive tests choose a list of diseases or traits against which they analyse an individual’s predisposition. The service providers, say 23andMe in the US, Xcode and MapMyGenome in India use genotyping. Sequencing on the other hand, apart from being more time and money consuming, gives the exact nucleotide order. Genotyping looks at point mutations and picks up things which are commonly found; sequencing looks for mutations known in the population as well as for those unique to the individual.)

Agarwal started off systematically, with a primer on what to expect: How I fared as a carrier of genetic diseases, what are my risk factors for some diseases, and how will I respond to certain drugs given my genetic constitution.

Pretty much everyone is a carrier for some genetic disorder or the other. The data shows one in 1000 is affected. “Healthy individuals can carry many disadvantageous variants without showing any ill-effects and that’s because you only have one bad copy of the gene. Some are late onset diseases which can get triggered by environment or other factors and are categorized as risk factors,” Agarwal added.

Her revelations on my carrier status blew me away: I am a carrier for seven disorders, some of whom like Buck or Fraser Syndrome I had not even heard of. (Later on, in post-sequencing genetic counseling, Dr Kavita Reddy informed that on average we are carriers for six to seven genetic disorders.)

But it was a slew of eye-related mutations that spooked me. I’ve had myopia since childhood and I got Lasik done eight years ago. But of late the eyesight has been weak. Three years ago the doctors diagnosed it as ‘computer vision syndrome” and recommended restricted screen time. But that’s a misnomer, we all know.

I learnt I carry carrier mutations for night blindness and retinitis pigmentosa. That means there are chances of my ‘offspring’ getting the disease. I also have a certain mutation linked to the protein expressed in the photoreceptor cells in the retina which is associated with occult macular dystrophy (OMD). My mind was racing to connect the dots as Agarwal explained how OMD was associated with “decreased visual acuity without any visible abnormalities that can be detected by a routine eye exam”. As I strained to see the slides (I really had problems seeing the slides), I told myself ‘it has to be OMD and not some exotic computer vision syndrome’ that was ruining my eye.

Hardwired that our brain is for stories, sometimes we go overboard.

Agarwal’s presentation clearly said OMD is “autosomal dominant with partial penetrance’. That is, not all individuals harboring the mutation will be affected. But I chose to see a retina expert.

Dr Rajani Battu at Narayana Nethralaya in Bangalore is not used to seeing a patient who is retrofitted to a possible diagnosis, more so in a disease like OMD, which, true to its name, is hidden. Surprised why somebody would get her genes sequenced just like that, the doctor took a few minutes to appreciate that it was more a journalistic adventure on my part than a medical misadventure.

A flurry of scans followed over the next few days. The final diagnosis: I don’t have OMD but it remains a risk factor for me and I pass it on to the offspring as well. Since the onset age for OMD can vary from 10 to 80 years, what are my chances of getting the disease later on?

A chemical engineer by training, Agarwal is now involved in the biological analysis and interpretation of most clinical cases at Strand. She says the literature shows some of the patients had the disease at 65 years. It’s very hard to predict the probability of developing the disease if I don’t have it now but the possibility of it striking me later can’t be ruled out.

Since I was the first ‘formal’ healthy subject, Strand did not ask me to fill any medical or family history record. So I was curious how and what did they look for. Agarwal says she mostly focused her analysis on a list of about 6500 genes that are known to be associated with some human disease. Within these genes she focused on mutations that cause a severe change in the protein and these include both known and novel mutations. The eye mutations mostly emerged from this analysis, she says, as she did not have any indication to guide her to focus on one system or the other.

In short, apart from seven carrier mutations and my risk for OMD, I am at a slightly higher risk for fungal nail infections (which haven’t manifested until now). Mercifully, I don’t have the dreaded breast cancer (BRCA1 and BRCA2) and some age-related macular degeneration (AMD) mutations.

I think one of the most useful information that came out of it was with respect to drug responses. I will respond poorly to the popular blood thinner clopidogrel (brand name Plavix) and my ability to metabolize certain anti-biotics is low.

The discussion summed it all tidily by disclosing that I have two good mutations that confer reduced risk of AMD and 4-5 years younger kidney function. (Of all age related diseases, AMD has the highest genetic component. So to learn that I have a protective mutation was fleetingly assuring.)

In future, if my physicians ever need to know the right blood thinner or the right chemotherapy drug, and in the right dose, they could peek into my exome sequences.

So what did I get here?  A list of good and bad genes! And a fresh pair of glasses for the newly detected cylindrical defect. Even the entire genome sequences — Whole Genome Sequences as they are called and are proving useful in understanding diseases and inventing new treatments — won’t predict, for most of us, our medical future.

In wellness/preventive tests I’d have gotten a list of disease predispositions. But their predictive power is limited. And that’s because people are applying population study data to individuals. (Last year a major study showed this limitation.) Most diseases involve interplay of behaviour, environment and random events which are hard to predict. For instance, in type II diabetes, the mutation that makes the greatest contribution can put you at 20 percent higher risk. So, if diabetes risk is 1 in 5 in India, this mutation could put you at risk of 1.2 in 5, says Hariharan.

Dna-SNPKnowing that may not change one’s life significantly but one could use it modify one’s lifestyle to delay the onset of such diseases. Companies like Xcode, which combine personal genomics with nutri-genomics and use a pre-selected set of markers that focus on lifestyle diseases and metabolism to also provide a comprehensive diet-plan, claim they maintain a feedback loop with their customers for improved outcomes. It uses a comprehensive panel to screen against diseases. For instance, says chief executive and founder Saleem Mohammed, “We use close to 80 SNPs to report the risk of diabetes. I don’t think anyone in the world is doing that.” (SNP, pronounced as snip, is Single Nucleotide Polymorphism, the most common form of genetic variation in humans and occurs when one letter of the DNA changes. There are about 10 million SNPs in the human genome.)

Many of these companies will improve their prediction engine as they gather more data. With 160 customers in India, Xcode is already discovering that some parts of the genome vary significantly when compared to Caucasians. Others have come to realize that the true potential of personal genomics lies in clinics, when applied to interventional diagnostics, or in drug responses to figure out which drug works on which patient.

Hyderabad-based MapMyGenome provides GenomePatri, a personalized genomics profile that covers 60 odd conditions, traits and drug correlations and claims to garnered 600 customers since its launch earlier this year. Founder and chief executive Anuradha Acharya says the growth is limited as at Rs 25,000-a-pop, these tests can only be taken by a certain class of people since it is not yet covered by insurance. So the company is now building smaller disease panels in cancer, gynecology, brain disorders, etc. It recently launched Cardiomap, a genetic test for cardiac health profile.

Looking at all this, it’s easy to say how more and more people are using genetics to pry open the black box of how disease works. Genes will not exactly be the fortune tellers but they’re certainly forcing us to move the ethics and regulations of genomic medicine from theory to practice, from the abstract to the physical.

Next: Part III will look at what basic regulations and standards need to be in place before spas and fitness centres start trivializing it and how ethics will play a part when sequencing becomes more common. What if people start getting discriminated on account of certain mutations?

Genes rarely hold the secrets to who we are, nor are they the final arbiter of some of the late onset chronic diseases the world is grappling with. But our genomes are something we can’t really negotiate with.

Late last month the US patent office granted a patent to 23andMe, a California direct-to-consumer genetic testing company, that would allow it to offer parents opting for in vitro fertilization to negotiate the genome of their child. That is, parents can choose to have a child with desired traits. The claim of the patent – Family Traits Inheritor Calculator — led to a few public debates about the ethics of ‘designer babies’. Keeping aside the ‘patentese’, the proprietary technology of this Internet start-up implies that prospective parents can select the donors of eggs and/or sperm to increase the likelihood of having a child with desired phenotype (i.e. physical features like light eyes, curly hair or fair/dusky complexion) and genotype (genetic makeup like long expected life span; reduced or no risk of certain disorders).

It is a controversial patent. The debate swings from one extreme to the other – From how ethical or morally correct it is for parents to play God to the defensive argument that this patent is merely a ‘deterrent’, preventing others from developing this technology, at least for a while.

But the horse has left the barn. And riders are trying to saddle it, with different services.

Around the same time last month that 23andMe was granted the patent (and soon announced that it wants to genotype at least 1 million people), I had my own moment of genomic reckoning. As I said earlier, a few months ago I volunteered as a ‘healthy subject’ to have my Exome sequenced. Exome constitutes nearly 1 percent of the entire human genome. If the latter contains 6 billion letters of DNA (or 3 billion base pairs of nucleotides) then the Exome is about 60 million letters, comprising 20,000 odd genes that code for various proteins.

Hardly any commercial health care organization is doing exome sequencing in India; it’s still restricted to researchers looking for genetic disorders. The Next-generation sequencing (NGS) that it entails, is just about taking off even in the developed countries and is still in infancy when it comes to clinical diagnostics. But the novelty of the technology was not quite the draw. I don’t have any chronic disease, yet. And my family doesn’t have any history of genetic disorders. I’m also not the type to lead a quantified life and tailor my life style to what my genes seem to predict. I think it was my conversation with Leroy Hood a few years ago in Hyderabad had sowed the seeds of participatory medicine. Hood, who automated DNA sequencing, and has been instrumental in setting up more than 15 biotech start-ups, including the giants like Amgen and Applied Biosystems, has added a new descriptor to personalized medicine – participatory. I decided to become a participant.

I had two other compelling reasons. As a journalist, it’s only when you get down to writing about a topic, that you put all energies in understanding it. As they say, writing is a concentrated form of thinking. Moreover, direct-to-consumer genetic testing has arrived in India. I wanted to explore what they have to offer and what should the consumers expect from these tests. (More on that later)

From the time the rough draft of the human genome was published in 2001 Nature (a for-profit journal publishing non-profit work of the International Human Genome Sequencing Consortium) and Science (a non-profit journal publishing for-profit company Celera’s sequencing work), we have come a long way. Pretty much in our lifetime, most of us could carry a copy of our DNA sequences in our pockets!

From the time the rough draft of the human genome was published in 2001 Nature (a for-profit journal publishing non-profit work of the International Human Genome Sequencing Consortium) and Science (a non-profit journal publishing for-profit company Celera’s sequencing work), we have come a long way. Pretty much in our lifetime, most of us could carry a copy of our DNA sequences in our pockets!

The second reason is more to do with science. I had the opportunity to see American scientists sequence, discuss — virtually live — genomes in 2000-2001. It was the time when genetics was publicly turning into genomics, a digital discipline. I was at the AAAS meeting in San Francisco in February 2001 when the two public figures of genomics – Francis Collins, leader of the Human Genome Project and Craig Venter, President of Celera Genomics, the private company which was then sequencing the human genome—with the respective rough drafts of the human genome published in Nature and Science, spun stories of health advances and public benefits. (I still have those editions of the journal, pix attached.) Some of those stories were oversold, prematurely. A decade later, in July 2012, at the European Science Forum in Dublin, as I sat through various talks and lectures of Craig Venter who spoke about some of the work he’s doing at Synthetic Genomics, it occurred to me that DNA sequencing will soon become affordable and pervasive like smartphones, though not all of the data being generated will be fully understood any time soon.

So earlier this year when I was writing a story on Strand Life Sciences, which has begun offering Exome sequencing, not directly to consumers but to patients and through their clinicians, I offered to be a healthy subject for their research programme.

I decided to go through the drill. And it started with a genetic counseling session with Dr Kavita S Reddy, a clinical geneticist at Strand and a former Kaiser Permanente veteran who’s relocated to India after 30 years in the US. (She is just getting down to training some genetic counselors in the country through an online programme.) Apart from helping me decide if I wanted the test, the consent form highlighted important information like the risks and benefits of the test, your rights as a patient, how the results from this test may or may not impact your medical care, how the results might be used in research, and how you may choose to participate.”

Dr Reddy said, “This is pre-test genetic counseling. Go back, think and then sign the form.”

It was fairly simple. I read the privacy protection part and checked all the boxes, except one which said: There are specific genes or diseases for which I DO NOT want to receive information (indicate them below or attached additional sheet).”

There was none. I wanted to know everything my DNA had to tell; whether it was related to any primary condition (in case of a known disease) or a secondary condition (adult onset of some diseases, treatable or untreatable).

I think I was pretty brave in un-checking that box. When Nobel laureate James Watson — who forms the famed Personal Genomics Trinity along with Craig Venter and George Church – got his genome sequenced, he didn’t want to know which version of APOE gene he had. Certain variants of this gene are known to confer high risk for Alzheimer’s or heart disease. Venter on the other hand is known to carry one high risk variant.

Perhaps what gave me confidence was my relative lack of knowledge of the complex and evolving science of genomics. The fact that the results would be reported through the healthcare professional, they’d be confidential and “will only be released to other medical professionals or other parties” with my written consent, was reassuring.  “All laboratory raw data are confidential and will not be released unless a valid court order is received.”

A few hospitals and direct-to-consumer genetic testing start-ups have been offering genetic tests even though the predictive power of most current genetics using common markers is very low. Some test whether a child has ACTN3 or sports gene that would make him or her super athlete; others give a disease predisposition report card, suggesting how high or low your risks of getting some diseases are and what lifestyle modifications are necessary. (More on that in the next blog post.)

There’s a consent form to be signed in these tests too. Uncheck the box if you don’t want your sample to be used for research. But remember that the promise of genomics rests in large numbers, really large numbers. It’s only by studying and analyzing data from hundreds and thousands of people can researchers detect meaningful genetic variants that affect complex conditions like diabetes and heart diseases.

“For research, very little genetic data exists, whether it is benign or pathogenic,” said Dr Reddy. And interpretation is not easy, nor a perfect one either.

I was cautiously briefed. People analyzing my data would look for “actionable” (genetic variations that can be acted upon) and “preventative” mutations.

It sounded like fun until late September when Strand CTO Ramesh Hariharan sent a mail: “We have gone through the first round of analysis on your genome. We can walk you through some of the findings if you can come by.”

Some of the initial courage I exhibited started melting. I wanted to know, but then I didn’t want to know. And there’s indeed such a thing as having too much information.

Do I have cancer mutations? (There’s now a map of genetic faults that lead to some cancers) What is my risk for Alzhemier’s, Parkinson’s, Age-related Macular Degeneration, (Eye has been my weak spot) – the list started swimming before my eyes.

Next: In Part II, what do my genome sequences tell me and what that tells us about genetic testing in general.

Is nuance dead? Do we live in the time of binary debates?

While reporting for the UIDAI story in Forbes India less than a fortnight ago and now looking at the reactions to the story, mostly on Twitter, it seems as a society we are fast losing our taste for nuances. In general, people look at Aadhaar with a black or white lens. As in climate change, GM crops, or as my colleague Rohin Dharmakumar says the birth control debate in the US, issues where people make up their mind about which side of the debate they want to be in and then process information to perpetuate that point of view, Aadhaar has fallen into that category.

When the story How Nandan Nilekani took Aadhaar past the Tipping Point went live on the website, some readers even accused us of “propaganda”.

Propaganda, really? Our editor tweeted on Tuesday: “Am not a fan of Aadhaar, but the Forbes India article shows how Nandan Nilekani overcame the system to get his way on UID.” Then there were four of us reporting on it. What propaganda are people talking about? We went looking for truth and we’ve written what we found.

Just like most innovations, Aadhaar implementation is messy on the ground. To cite just one example, as of August 2013, in one of the pilot districts in Rajasthan, less than 20-25 percent of direct bank transfers for various programmes were happening through Aadhaar seeding. If in some places scanning devices are not present, in others existing devices don’t work. Limited access to bank is a pullback too. In the bargain, a lot of people are given a run around. “The system will be dumped as far as cash transfers are concerned; it might work to track train and airline travelers and bank transactions etc,” says Nikhil Dey of NCPRI, a vocal critic of Aadhaar.

What services will Aadhaar be used for is the real thing, now as well as in future. Yet people are confusing the platform for the end product/service. Ashish Rajadhyaksha, a fellow at the Centre for the Study of Culture and Society in Bangalore, who has recently published a book In the Wake of Aadhaar after extensive research in eight Indian states, says there’s lot of confusion in the minds of people. Some think it’ll get them ration; others think it’ll grant them some kind of protection if they get caught in a legal suit.

His book argues that Aadhaar is just a cog, at best a huge cog, in the giant wheel of digital governance in India. He thinks the benevolent, democratic idea of Aadhaar will eventually be shaped by the service (and the ideology of its provider) that is mounted on it. And there lies the caveat. He cites the example of microfinance crisis in Andhra Pradesh. After the MFI Bill of 2010, when the state government cracked down on MFIs in the state, it is now working to establish banking correspondents by primarily using Aadhaar. “It is by no means clear that this will lead to any change in the sort of chronic indebtedness that the MFI explosion had created across several regions of the state,” says Rajadhyaksha.

He raises a valid point but Aadhaar was never meant to be the message; it is the messenger and, as wisdom says, you don’t shoot the messenger if you don’t like the message. Even the cash transfer debate has taken the tone that it has because politicians started to take credit for it even before it was sufficiently widely rolled out and its implementation adequately evaluated.

But going beyond the vote bank politics, there’s one use-case in healthcare which nobody is talking about publicly. (It’s understandable. When time is short and maximum bang for the buck has to be made, why waste time in healthcare where results will show only over time.)

Assuming that the data protection policy comes into effect soon, by linking each UID number to a person’s electronic health record (EHR), India can leapfrog health management. Nobody in India maintains EHR worth its name. However, two months ago the Union health ministry approved the national EHR standards. The idea is to have a country-wide rollout of EHR for all government hospitals. Private hospitals follow some minimal record keeping but most of them don’t lodge patients’ medical records and none provides an EHR which a patient can access remotely. With UID database residing in the cloud, even a rudimentary EHR linked to it and stored in the cloud along with critical information, say, about blood group, allergies, chronic illness, long term medication, etc, can go a long way not only in better healthcare delivery but even gathering epidemiological data.

The Centre for Development of Advanced Computing (C-DAC) in Noida has built a hospital information management system which can be seamlessly linked to UID. In states like Rajasthan and Maharashtra, where the state govt is rolling C-DAC’s HMIS, it is already linked to the UID database. Even if the UID number is not available (forgotten or lost), the HMIS can retrieve the UID number using the patients’ biometrics. Keeping privacy concerns in mind, says executive director BK Murthy, the management system is designed to give roll-based access at every level and no data can be shared without the patient’s and doctor’s consent.

Once the data protection policy is in place, which qualifies what patient rights are, more private companies in healthcare and IT will come forward to implement EHR. Vijaya Verma, founder and chief executive of Yos Technologies, which among other things provides IT solutions connecting care providers and patients, says “privacy is not a big deal” for patients today. Patients don’t get it and they sign the consent form even without reading it which ensures that we have the consent but it’s not informed consent, she says. Yos provides electronic medical records to hospitals (to be kept within the hospital) and electronic health records to patients (to be accessible over the cloud) which includes discharge summaries and prescription data.

Verma believes once the National Identification Bill is passed and the data policy comes into effect, UIDAI should use its permanent enrollment centres to update Aadhaar by adding some basic health data about individuals.

But that maybe too ambitious, both in terms of saddling UIDAI with additional work and exacerbating privacy concerns.

I’ve argued earlier why healthcare is not on the election agenda of Indian politicians but I hope the UIDAI and the rest of the bureaucracy find a compelling use-case in EHR.

Ever since the Food Security Bill was passed by the government last month, it has been widely debated whether this also secures nutrition. It doesn’t; neither in terms of overall calories nor in specific nutrients. The bill entitles 165 gm grains to each person that would provide 500 calories, just about 20 percent of the daily calories. With such a shortfall, addressing India’s chronic malnutrition where nearly half the children under five and one third of women are malnourished is a challenge of epic proportions.

Add to this the emerging complex scenarios that the Food and Agriculture Organization is stressing: rising problems of over-nutrition and continuing high prevalence of micronutrient deficiencies.

Since the spotlight is already on nutrition, I’d like to plug a thought in public consciousness: How about looking at micronutrient-rich seaweeds as an affordable source of nutrition?

In recent years, seaweeds, which contain a wide array of bioactive compounds that range from anti-oxidants to minerals, have proved to be a bonanza for pharmaceutical and agri-food processing industries. Several studies have showed that having seaweeds as part of the diet is one of the prime reasons for low incidence of breast and prostrate cancer in Japan and China as compared to North America and Europe.

Globally, nearly 15.8 million tons (in dry weight) of seaweeds are grown and the estimated market is $7.4 billion.

India has water on three sides but like a landlocked nation we’ve been oblivious to seaweeds. In the last decade or so one seaweed — Kappaphycus alvarezii – has been commercialized in India. This red alga has been the most important source of carrageenans, a gel-forming material that is now widely used in frozen desserts, cottage cheese, sauces, jellies, etc.

More recently, Central Salt Marine and Chemicals Research Institute (CSMCRI), a CSIR centre in Bhavnagar, Gujarat, has developed a new technology to make liquid seaweed fertilizer from Kappaphycus sap. It is protected by patents in the developed as well as Indian markets and initial commercialization led to 2 million litres being sold in 2012-13. A multi-crop project coordinated by CSMCRI in collaboration with 43 agricultural institutions across 20 states is underway and shows encouraging results.

As Arup Ghosh shows the crops in the green house at Bhavnagar, it is evident that those sprayed with the liquid fertilizer are far healthier than the control group (i.e. plants given the recommended dose of fertilizers.) Ghosh carries a big bulky folder and is visibly excited about its contents. Justifiably so; it contains field data from 100 trials which shows that the liquid fertilizer — used as a spray — increases yields on average by at least 20 percent, and in a variety of crops including rice, maize, potato, and blackgram.

But there’s another aspect of seaweeds which senior scientist CRK Reddy is obsessed with: using edible seaweeds as a nutritional supplement in Indian diet. He is convinced that Enteromorpha - leafy, paper-like seaweed that grows along the coast of Gujarat – can be used as a garnishing agent that can provide a host of micronutrients. By consuming as little as 1 gm/day/person, this seaweed can provide iodine, iron, magnesium, selenium and many other micronutrients which regular foods in the Indian diet do not provide.

Researchers at CSMCRI have profiled more than 100 seaweeds, out of 250 that grow along the Gujarat coast. Reddy and his team zeroed in on Enteromorpha. “We have showed that after solar-drying and pulverizing it can be used as a garnishing agent. We tested it on wafers and it tastes pretty good,” says Reddy. People shouldn’t confuse it with any ‘fishy flavour’, he adds. Reddy thinks this seaweed can be easily used as a constituent in Pizza seasoning, in spice sachets in noodle packets or as a flavouring agent in other instant snacks that children and adults like.



While Reddy has been slaving in the labs, it’s the commercial scale production issues that pose the challenge now. “We don’t know how to cultivate this seaweed on a large scale,” he says. His group has a small grant from the Department of Biotechnology to pursue this but he believes this needs sustained support for five to six years before a cultivation technology is developed and its business viability is demonstrated.

One concern other than scalability of cultivation, says Pushpito Ghosh, director of CSMCRI, is that edible seaweeds need to be grown in clean environment and unpolluted waters but our coastal waters are far from it.

seaweed-Enteromorpha-people-1These are serious challenges but certainly not insurmountable. After all, of the 250 macroalgal species commercially utilized worldwide, 150 are consumed as human food. Since seaweeds are rich in PUFAs (poly unsaturated fatty acids), which are not synthesized by humans and can be obtained only through dietary sources, a long-term, coordinated effort is needed towards commercializing edible seaweeds in India.

It may well reduce dependability on traditional foods and, who knows, add a new flavour to the assortment of Indian spices that we already enjoy. “It is a beautiful vehicle to take nutrition to children who’ll get it without knowing about it,” says Reddy.

For someone who found his first seaweed meal in Japan in 1989 to be “horrible”, Reddy today enjoys cooking Sushi and his Japanese colleagues bring him seaweeds as gifts. He regrets that even though he tested his concept of garnishing agent on wafers in India before the Japanese, latter succeeded in getting similar products to the market while he is struggling. Still, he says, “I’m determined to do it.”

A former professor of computer science from the Indian Institute of Science, Swami Manohar is the co-founder of LimberLink Technologies, which, among things, runs the annual engineering design challenge Jed-i. He and I have often discussed why we don’t have blockbuster technology products from India. His own first attempt, along with some colleagues at IISc, at building a low-cost handheld device Simputer, back in the early 2000s, proves the point he is making below. This is a guest post by him.

By Swami Manohar


Swami Manohar

I’m often asked, “When is the next Google or Twitter going to come out of India?”  I presume, the real question is, “When will there be a company out of India that dominates the marketplace like Google or Twitter?” It is also assumed correctly that such a marker leader has to be an internet technology company. In an age where the formerly lucrative telecom and bandwidth business have become commoditized like salt and pepper, internet tech companies are able to reach the masses.  Amazon aggregates consumer goods, Facebook aggregates people and relationships. In this age, the winner takes all, there is no second player; who remembers social networking site Orkut anymore?

In this environment of competition, companies around the country are on a quest to innovate and become the next market leader.The government has set up a national innovation council with a mandate to encourage innovation. Every corporate house is on an innovation mission, conducting workshops and seminars, and announcing incentive schemes for encouraging innovation among its workforce. The startup ecosystem is also abuzz with young entrepreneurs, angel investors and venture companies busily innovating to create the next Google and Twitter. Innovation, innovation, and innovation.

This one-sided emphasis on innovation is misplaced and based on an incomplete understanding of what makes market leaders.

Making it to the top of the technology market is both easier and harder today than it has been before. Ten years ago, when my colleagues and I built the Simputer, constructing a handheld Linux machine was an engineering challenge. Today anyone can build one. Ten years ago, creating a Google or an Amazon required one to build and manage a very large farm of machines. Today anyone can create an application that requires thousands of machines by buying time and resources from any one of many cloud providers.  Even five years ago, building an app for mobile phones required a mastery of several complex development systems and an understanding of the variations among different phones. Today Android has made it easy for anyone to create applications. On the marketing side, the Appstore concept means that anyone can sell an app to anyone else in the world by simply sending an email. The contradiction is that its easier today to build a technology company because the process is easier and its harder than ever before because everybody’s in the game trying to out-compete everybody else.

So what sets the market leaders apart?  It appears that everyone has concluded that it must be innovation. But if we look at it more carefully, that is an incomplete representation of the whole picture. Innovation cannot be created in a vacuum; the need for it arises when there is a problem to be solved, and is generated to deliver the best possible solution, using solid engineering and intelligent design. It must be noted that not all innovation is executed successfully. The ultimate measure of the success of an innovation is its direct or indirect impact on end user experience.

When Google first started, there were many competing search engines. Google’s simple interface and pioneering ad-based business model moved it ahead of the competition.  Google’s successful user experience was achieved by good engineering and design. Similarly, Twitter’s innovation, without the backing of engineering and design, would have rendered the limiting of communication to 146 characters at a time as just another novelty.

Market leaders deliver compelling user experience using their engineering and design competence. Innovation is a series of steps to deliver the best possible product, the magic ingredient that gives them the leadership. Success is not about innovation, it’s about the user experience.

Let us for a change look at a recent success story out of India: Redbus. Though it is limited to the Indian market at this time it has been acquired at a tremendous valuation for an Indian company.

The key to the success of Redbus is the focus on delivery of a fantastic user experience. Redbus has two user communities, the traveling public and the bus operators. For the traveler, the user experience covers the entire journey — from the start of using the website till the time the actual bus journey is completed  with the traveler arriving at the intended destination. For the bus operators, it is the experience of being able to fill seats in their buses through Redbus and collecting the revenue minus the commission. The delivery of such satisfactory user experiences depends very much on the engineering of the website, the payment and security systems, the back-end, and so on. It also depends on the design of many aspects of the entire system. However, for the end users, these details are irrelevant.

Now, back to our question at the start! The good news is that Indian companies are beginning to deliver on the possibility. The reality is that we need hundreds of high quality ventures to be initiated to result in a handful of global leaders. The good news again is that as mentioned earlier, the startup ecosystem has gained huge momentum in recent past.  So where is the catch? It is in the shortage of engineers with competence in engineering and design.

The average engineering graduate of today is saddled with three handicaps. First, they seriously lack depth in engineering: in the race to be seen as up to date and industry-ready, most curricula have crowded three years of  engineering with so many subjects that there is hardly any time for the student to engage in depth with any one. So the best of students are familiar with a large number of topics but lack mastery in any. Second, the engineering curriculum today is completely lacking in design and design thinking. Our curricula focus on analysis with very little scope for synthesis, primarily because the examination system can deal very well only with questions that have a single right answer. However, engineering synthesis or design by nature is an exploration of possibilities under constraints. Third, engineers are never trained to think about end users, to understand their needs, and to empathize with the human condition, the improvement of which is the end goal of all engineering. The combined effect of these three handicaps serially limits any scope for innovation. It is not that our students are not innovative, but four years of engineering education provides them with so little scope for understanding and experiencing innovation.

The good news once again is that several product and technology companies are taking the time and effort to enhance curricula in engineering colleges. It will be good if they bring in an emphasis on design, in the broadest sense, into the engineering curriculum. In particular, design, as in synthesis, needs to be brought in right from the first year of engineering, rather than relegating it as advanced topic. Further, there are no courses that deal with user experience design anywhere in the engineering curriculum. This lacuna has to be fixed at the earliest. Very few institutions in India have a strong design focus: examples include IIT-Mumbai, IIT-Guwahati and IISc’s CPDM.  Other institutions and universities should include multiple aspects of design in their  curriculum. This is definitely not a recommendation to include a sequence of two courses called Introduction to Design and Advanced Engineering Design, and saddling students with two more courses to be completed. There is already an overload of coursework.  What is needed is the restructuring of existing courses in engineering to weave in aspects of design.  If a fraction of the energy and resources spent in fostering innovation is reoriented to encourage engineering and design, innovation will follow.

Global success stories are scripted by passionate entrepreneurs with strong foundations in engineering and design by delivering compelling user experiences.  Innovation is simply the magic ingredient that binds it all.

For very long the venerated and coveted IITs and their entrance exams have been considered as the great leveller in India, a country where inequality and diversity are two sides of the coin. Students from villages, from uneducated backgrounds and low economic strata have qualified for these exams. But now this notion seems to be turned on its head.

A statistical analysis of the results of 2012 admission tests by scientists at Indian Statistical Institute (ISI) in Kolkata shows that certain Boards, students from high income families, and urban areas bag most of the IIT seats. In fact, among those who had registered, students from higher income group have four times higher success rate than those from lower income group.

As for the Boards, IITs picked over 57% of their selected students in 2012 from CBSE, a board that represents that 6% of their target group.

Isn’t that shrinking the supply base of these institutions to a disastrously narrow band? And if you’ve followed the rather messy process of “improving” the supply base of IITs — not to get just factory-produced students whose primary (and secondary) aim in life becomes to ‘crack’ the admission test and then lose steam when the actual learning starts at IITs — then you’d see below how even the new system that was adopted in 2013 beats the entire purpose of admissions revamp downright hollow. Predictably, the preliminary analysis of 2013 JEE-Advanced results shows that CBSE predominance continues.

The table below from ISI  shows IITS hardly select an inclusive group. As far as board affiliation is concerned, CBSE and ICSE accounted for less than 7% of all students appearing for Class XII Board examinations in 2012 in India.


Composition by parents’ income Composition by place of dwelling Composition by Class XII Board affiliation
More than Rs. 4.5 lakh






Between Rs. 1 lakh and 4.5 lakh






Less than Rs. 1 lakh




Other boards


All three groups


All three groups


All three groups



The success rates of different sections of candidates (number of qualified candidates divided by the number of registered candidates) tell a similar story:


Success rate by parents’ income Success rate by place of dwelling Success rate by Class XII Board
More than Rs. 4.5 lakh






Between Rs. 1 lakh and 4.5 lakh






Less than Rs. 1 lakh




Other boards


All three groups


All three groups


All three groups



While no reliable data on the effect of coaching is available, the unusually high success rates of candidates from the higher income group and city-dwellers suggest that access to coaching substantially increases the success rate, says ISI.

The cat-and-mouse game of ‘normalisation’

In an exemplary act of transparency (and in the interest of the people), ISI has made public the entire minutes of meetings and deliberations that took place over the last two years leading to the 2013 IIT revamped entrance test. A humongous task for a government agency, it explains “why there was a lag between the last meeting and the publication last week,” says Debasis Sengupta of ISI. “We just wanted to put forth everything before the public.” Beyond that he’d not say anything except lament that all good intention behind the revamp remains just that: an intention. IITs are still not selecting the brightest students; if anything, the reality distortion field for the Boards, other than the CBSE, looks more unfriendly.

Because there are dozens of Class XII Boards, a long-drawn process was adopted to arrive at a new admission process that gave weight to entrance exam scores and normalised class scores.

“When performances from multiple exams are to be combined, it is usually apples and oranges. So extensive simulations on past data has to be conducted to make sure the outcomes are fair. I very much doubt if any of this was done. More thought and simulation has gone into the Duckworth-Lewis system in cricket,” says V Vinay, chairman of LimberLink Technologies and President of the Indian Association for Research in Computing Science.

Debasis Sengupta says a lot of work went into the statistical inputs that ISI gave for the normalization process. But as the documents show, none of the suggestions was adhered to.

In short, the cut-off scores for IITs are too “weak” and not the best way to select really good students, especially students with analytical and problem solving skills.

However, it’s the NIT’s where the normalization formula takes the cake. It’s as bizarre as it can get in the world of statistics. You can see the full description in the link above but to summarise it in plain English: One group of experts (from ISI) believes that all Boards, whether central or State, have meritorious students and proposes a normalisation formula. Let’s call it A. The second group (from the Chair of CBSE) assumes that some Boards (read CBSE) students “are more able” than other boards and proposes another formula. Let’s call it B. The two groups don’t agree, the latter apparently don’t provide scientific answers and the logjam continues. The issue is resolved by taking the mean of both the formulae:  Add A and B and divide by 2.

“This is true scientific black comedy,” remarks a mathematician from Chennai.

To simplify it further, as one parent explained it to me in utter frustration: “See, this is a case where suppose you have five children with different shoe sizes. To find the common size, you find the average but at size 6¼ this shoe fits no one.”

Hopefully the anomaly will be corrected sooner rather than later. As one person close to the developments said, “Things are moving fast and a lot will happen before 2014 exams.”

Still, a few facts in this bunch of documents made public need attention: There was a huge effort to make sure the CBSE students did not suffer; there has been a serious conflict of interest with CBSE, which was supposed to be an implementing agency but turned out to be a decision-making body, even recruiting people for the decision-making committee; none of the other Boards were represented or even called for consultation; please read points 11 and 12 in this ISI letter to the Govt

A fortnight ago, the NIT admission test row reached the Supreme Court. Whatever the verdict of the apex court, the case is far from settled, in more ways than one.

“As a non-IITian my view has been that the current IIT students barring may be the top 1000 JEE-rankers  are simply one-track horses, having spent about four years preparing just for the JEE at the cost of everything else. No amount of tinkering with the selection process is going to fix the core issue that very high career rewards are dependent on one or two numbers (in the current case, JEE advanced and Board normalised score),” says Swami Manohar, managing director of LimberLink Technologies, a start-up that is attempting to re-engineer education in professional engineering colleges.

Unfortunately, after the two-year ‘pilgrimage’ of IIT admission tests revamp, perhaps everyone is still standing in purgatory.

Throughout last week we were treated to some kind of media circus that pitched Nobel laureate Amartya Sen against Columbia University professor Jagdish Bhagwati. A lot of it was unseemly; but the good thing that came out of it was that even those readers who’d normally not pay attention to such topics, ended up reading it and came away better informed. (After some initial wading, I figured if you had read just this piece by Mihir Sharma, you’d have got all that you needed to know about this debate.)

Unfortunately in this verbal duel we forgot to read and debate this news: The Technical Expert Committee (TEC) constituted by the Supreme Court, which is hearing the public interest litigation seeking moratorium on public field trials of Genetically Modified (GM) crops, came out with its report. In this report the panel is seeking a freeze on open field trials of GMOs (genetically modified organisms). The report says, the “system has major gaps and these will require rethinking and relearning to fix.”

The court will now seek a response from the government and if the apex court accepts this report with its current recommendations, then, many scientists say, it could prove detrimental to all genetic modification in agricultural research in India.

Enormously serious as this news was, it could have equally benefited one and all if we had a “scientific” debate on the subject by some senior scientists. How about the most respectable pro-GM scientist G Padmanaban, professor emeritus and former director of IISc pitched against one of the founding fathers of biotechnology in India, Pushpa M Bhargava who is now one of the most ardent critics of the use of GM technology for solving some agri issues. Incidentally, the American journal Science organized a debate between the two a few months ago, conducted by editor Bruce Alberts. Alas, such debates don’t carry much charm  for mainstream Indian media, both newspapers and magazines.

Prof G Padmanaban

Prof G Padmanaban

I asked both senior scientists why we don’t we have debates on this issue and if they’d want to participate someone were to organize one. Unsurprisingly both seem very willing and keen to have such open debates as long as the rules are defined; it doesn’t get personal and statements are backed by scientific evidence.

To get the facts first, I’ll state their positions upfront. Both are distinguished biochemists but have now taken up the role of being the public face of pro- and anti-GM technology.

Prof Padmanaban believes that the TEC report is very “disappointing” though it was a foregone

PM Bhargava

PM Bhargava

conclusion. “If you saw the four out of five names in the committee, and knew their stated positions on this, it was known that they’d give a report like this, one that’d curb GM research. There’s just one dissenting voice in the committee.” The position that Padmanaban has taken is that the biodiversity fear created by the anti-GM community is magnified several times over and that as long as the particular gene that is being introduced in the crop, in this case Bt, is tested for safety, there’s no danger to the biodiversity. As for harm to the humans, he says people have consumed Bt corn for over 15 years in at least six countries and there’s no scientifically validated study that shows any harm to human health or environment. In short, GM technology is as safe or not as safe as any other breeding technique in agriculture.

Prof Bhargava’s stated position is: we need more testing, given that GM crops are grown by just a handful of countries (90 UN member countries do not grow GM crops) and the growing public opinion (of which he is a very prominent voice) warrants that more tests need be done. In the Science debate, Prof Bhargava cites an example that is not quite scientifically validated: He says if the increase in incidence of gastrointestinal disorders among Americans and the use of GM crops were to be plotted, there’d be an “overlap in the curves”. He even mentions high incidence of autism, and other health problems.

Well, as far as I know (and can search the literature) there’s no published scientific evidence to prove this correlation between GM food consumption and various health problems. (In fact, I remember asking Mriganka Sur, who heads the Simons Center of Autism at MIT, Mass., last year if scientists had any handle on the increasing cases of autism in the US and he said they didn’t have a clue, it could even be the increasing use of plastics, environmental pollution, etc. In this video, Sur talks about the challenge of autism spectrum disorder and how he’s gearing up to solve it, one mutation at a time.

So as the GM issue gets muddled — yes, that’s the word to describe it when it comes to its perception and understanding in India — if we had a sustained public debate that relied on science rather than dogma or hearsay, we’d all come away more informed. Today, with every Supreme Court move, the subject gets harder to grasp.

Things have come to such a state that most newspapers don’t even accept opinion pieces from scientists that aim at explaining the technology, says Prof Padmanaban. Citing the example of a respectable, large newspaper (whose name I have promised him I will not disclose), he says he’s had many instances where the editorial team just keeps mum on such articles, once even admitting that the “editor did not want pro-GM articles”.

The science Academies in India could have at least arranged a few discussions among the editors of the country but they put their foot in their mouth when in 2010, at the time of being called upon to prepare a scientific report, they messed it by “plagiarizing” and doing a shoddy job of it. “Science is a big casualty in all this and it’s highly misinterpreted,” laments Padmanaban.

Prof Bhargava too agrees that more intellectual public debates would help. “I’d love to do such debates. I’ve said umpteen times let’s have a scientific discussion; let it be moderated by someone we trust.” He gets nostalgic about some debates in the past, notably one that was held on the “scientific temper” at the Nehru Centre in Mumbai, where every seat in the Discovery of India Hall was occupied during the three-day public debates.

He says the TEC report is very well produced with exhaustive references, whereas the industry body, ABLE, gives only sound bites or quotes to the media.

Now, that’s a serious provocation. How about ABLE taking the TEC report and producing a scientific rebuttal, at least to points that need a scientific rebuttal? (Policy issues of course rest with the govt.)

I’d also agree with Prof Bhargava when he says that it upsets him that at 85 he has to come out and speak while others don’t come forward. Ideally, it should be the practicing scientists who should come out and debate in the open. Both Bhargava and Padmanaban, 75, have lived their active laboratory years, if they get into any such slugfest, it’s due to their commitment to science and society! Why are other scientists, pro or anti-GM, socially insensitive?

Seema Singh
Until Dec 31,2013, I was a Senior Editor at Forbes India and I usually wrote about science and technology on this blog. I believe while we may have settled into consuming the nicely packaged final products of science - technology being a hand maiden of science - we are distancing ourselves from all the effort that goes into it. This blog was an attempt to bring occasional peek into those efforts and ideas.
I've been a journalist for 17 years and have written for The Asian Age, The Times of India, Mint, Red Herring, IEEE-Spectrum, Cell, New Scientist and others.
I'm now available at

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