JOIN USA walk through the bold new world of genetic research
It’s not often that I am thrilled to give my blood sample. But this time, as a technician draws my blood in a phlebotomy room, I tell him I am excited to see the results. My blood sample will now go through a battery of tests, starting with the extraction of DNA. Soon I will be told if I have an average, moderate or high risk of developing cardiovascular disease. The evolving nature of genetics research has always been alluring, and I opted to play guinea pig, out of curiosity but also overconfidence that I am healthy.
I am at the MedGenome Labs in the Electronics City in Bengaluru, and Abhijeet Shahi, who heads the Direct-to-Consumer (DTC) division, hands me a pamphlet on Kardiogen, the test I have just undertaken. The test is also available as a home kit and can be taken without a doctor’s referral to check one’s genetic predisposition to cardiovascular conditions.
Such tests allow people time to take appropriate measures and reduce the risks through lifestyle changes, he explains. This lab performs more than 500 genetic tests and is referred by doctors to check for inherited conditions such as cancers, metabolic disorders, thalassemia, among others. They process only
blood or saliva samples.
Dream comes true
Technicians in blue scrubs, spotless lab coats and squeaking sneakers strut past in a hurry. ‘Entry is restricted’ screams the main door. It begins to feel like a scene out of sci-fi movies like ‘Contagion’, but thanks to two years of the pandemic, the sight of lab assistants mummified in PPE kits is no longer unsettling.
Manjunath V, senior manager of lab operations and my guide for the day, soon arrives and motions me towards four big colour-coded dispensers, one each for shoe covers, PPE kits, hair covers and face masks. It takes me ten whole minutes to get equipped. I also squeeze my notebook full of scrawls into the PPE suit.
Well, in the days leading up to the lab tour, I scoured through my old biology textbooks and also Google to grasp the jargon (DNA, RNA and genome sequencing) and also big numbers (A human genome has around 3 billion base pairs). I am a writer and a journalism teacher but I was determined not to appear silly amid the scientists.
In college, I was one of those torn between a passion for liberal arts and a love for science, specifically biology. As a doctor’s daughter, I briefly contemplated giving in to nepotism. But studying maths was hard, and decoding genetics was harder. But the curiosity for genetics remained. Siddhartha Mukherjee’s book ‘The Gene: An Intimate History’ was devoured and visiting a gene lab became the stuff of my dreams. Until now.
Tour begins
Manjunath slathers his hands with sanitiser and nudges open the heavy steel door with his shoulders. We step on a sticky dust mat that absorbs all the grime from under our feet. The lab tour begins.
It’s teeming with people. Some sit hunched over their computers, processing the mounds of data on their screen. Others are operating whirring glass machines. All of them seem too busy to pay heed to the new visitor strolling through their workplace. A trolley of packets is wheeled in. These are samples that have just arrived from all over the country. The packets are opened, and the test tubes are arranged in an enclosed zone named ‘bio-safety cabinet’. A technician sits outside the glass cabinet with gloves protruding in and reviews the sample for damage or spillage. After the quality check, the processing of the sample begins.
Scientists and doctors have been studying genes and heredity for decades. When a test is done, the technician looks for changes in a specific gene or in the whole genome. When The Human Genome Project concluded with the complete sequencing of the human genome 13 years after it started in 1990, it opened new avenues in healthcare in the form of personalised medicine. This combines genomics with big data analytics to offer medical interventions targeted to a particular individual to yield better results. It was a significant departure from the 1980s and 90’s when only blood parameters were used for diagnosis. Manjunath shares the history with much jargon.
My heart pounds with excitement as we enter the DNA Extraction Room. Images of Watson, Crick, and the double helical model float before my eyes. However, I am disappointed to see that all rooms look the same — a maze of white and blue walls, glass and steel cabinets, an elaborate network of air vents, rows of machines and stacks of test tubes. Manjunath introduces me to the high-throughput machine with mild excitement in his voice. “These machines can sequence multiple parts of the genome at the same time, and extract DNA from 24 samples in 45 minutes,” he announces.
Hoping to see the helical structure, I ask if they can show the extracted DNA to me. The technician shows me a clear liquid instead. Hmm. Maybe I can see it under an advanced microscope, I wonder?
“Microscopes are used only at the cellular level to look at the nucleus and chromosomes. The DNA molecule is packaged into thread-like structures inside the nucleus. To view them, we now have advanced computers,” says Dr Venu Seenappa, senior scientist, dashing all my hopes.
Once the DNA passes the quality requirements, the lab starts testing the sample for any abnormalities. “We use two techniques. NGS (Next Generation Sequencing) is used to study single gene mutations like in cystic fibrosis. The non-NGS technique is used for testing larger genetic changes (like a completely/partially missing or duplicate chromosome), polygenic conditions, or mutations in multiple genes.”
Genomics in sports
Trivia time. After my tour, my doctor dad told me that genome sequencing tests are most common in the field of prenatal diagnostics, with prospective parents not wanting to inadvertently pass on genetic conditions to their offspring. Also in the field of sports, I add. In the early days of his career, tennis ace Novak Djokovic would often stumble at the finals, despite giving it his all. Rumour goes that a personal genomics study helped him to design his food and training. The rest, we know, his history — he has 21 grand slams in his kitty now. My father speculates the Indian cricket team has been also reaping the benefits of personal genomics. Trivia over.
Up next in my tour is the DNA sequencing lab. The biggest and most sterile room thus far thrums with a low-frequency vibration. Manjunath introduces me to the MiSeq machine. “It took 13 years to sequence the complete human genome, but this instrument does it in two days,” he says.
Dr Praveena L Samson in the Microarray Room is a picture of calm. She fishes out a silicon chip about 10 cm that gleams with rectangular bands. It contains ‘probes’ — it gets data from more than 6,00,000 genetic markers from the human genome and each DNA sample is screened to detect one’s genetic makeup.
The sequenced DNA yields reams of data, like an Excel sheet running into many pages. The Bioinformtics team analyses the data using software and the Interpretation team compiles the report. Genetic counsellors take over the task of breaking down the report to the patient. The entire process takes a fortnight.
What’s next
The lab tour ends with a discussion with scientists Dr Ram Murthy A and Dr Venu in the conference room. They mention they plan to offer DTC tests for diabetes and Parkinson’s soon.
I quiz Dr Venu on the viability of using genetics to pre-empt hereditary neurological conditions like schizophrenia. “The brain tissue is the only one we can’t take a biopsy of, and this is a severe limitation. Genetic research on neuro conditions is still nascent. Tests only indicate the probability of getting schizophrenia or Parkinson’s. But there are chances that one may not. And since one can’t pre-empt neuro conditions unlike a cardiovascular disease or diabetes, it is a huge concern,” he says.
The conversation steers towards using genomics to trace one’s ancestry and race, which 23andme is providing in the US and is quite popular among the young. It piqued my interest when a historian friend suggested that I get my ancestry mapped because he suspected I have a strong south-east Asian gene.
“We have the facility for such tests but we haven’t rolled them out. Ancestry mapping is usually done out of curiosity or fun but we feel genetic testing for diagnosing diseases is the need of the hour now. A lot of youngsters are falling prey to cardiovascular conditions and early detection can help,” says Abhijeet as I get ready to leave.
Results arrive
Fifteen days later after the lab tour, my phone blinks awake with a message that my Kardiogen report is ready. I open it with trepidation but the report looks cheery with a plethora of colourful graphs and corresponding explainers. It says I am in the low-risk cohort for developing cardiovascular disease. It also says that my sample was tested against six million genetic markers from the South Asian population. Does that mean I can eat more cake, skip exercise and sleep more instead? The scientists slogging away at MedGenome would probably disagree. But they have given me a timely heads-up. I better start jogging.
Nutrigenomics for personalised fitness
Dr Krupesh Nandeeshwara, Director of Intensive Care, HCG (Health Care Global),
Bengaluru, recalls how he dropped body fat from 15 per cent to 4 per cent in four months
I was working out five times a week at the gym. I was clocking 17,000 steps daily. My fat reduced from 19 per cent to 15 per cent. And soon, it plateaued. It was in 2007. Around the same time, in the same gym, I saw a colleague’s body transform dramatically and he wasn’t even taking protein supplements!
He introduced me to Manoj Mukunda, a physical trainer and dietician based in Australia, who introduced me to nutrigenomics — a genomics study that investigates the food groups one’s body is sensitive to and incompatible with.
The test in India was costing Rs 35,000 at that time as opposed to a lab I found in Australia that was charging 50 dollars (Rs 25,000 approx). I sent my hair sample abroad, and in three weeks, my genomic analysis showed that I was allergic to gluten and lactose.
I used to suffer from Irritable Bowel Syndrome (IBS) and it was a result of the gluten allergy, I realised.
So bad was my IBS that I would run marathons only around Lalbagh in Bengaluru because I knew where the restrooms were. To be doubly safe, I would also pop in a loperamide pill (to treat sudden diarrhoea).
With the new insights, I dropped wheat and milk from my diet and signed up for a personalised training programme. Within 16 weeks, my fat dropped from 15 per cent to 4 per cent.
Losing weight and staying fit is 80 per cent diet and 20 per cent exercise. The more natural the process, the better it is. Currently, my diet consists of salads, cashews, fruits, black peas, rajma, and rice in prescribed quantities.
I feel it’s best to eat the food closest to what our ancestors consumed. A lot of south Indians, including me, who are heredity rice eaters switch to chapatis or wheat-based diets to lose weight but our bodies are not accustomed to processing so much wheat.
More awareness about nutrigenomics in India is imperative but I suspect the supplements and whey protein industry in India is far too big and cheap right now.
Fact file
* Hollywood actor Angelina Jolie brought international attention to personal genomics when a test showed that she had a mutation on the BRCA gene, indicating a high risk for breast cancer. Jolie got her breasts surgically removed to avoid the risk.
* Octopus can edit its genes. Humans can’t. So scientists have developed a complex protein-based tool called CRISPR-Cas9, which has been used to successfully alter DNA in defective embryos to prevent inherited diseases.
* There is an immortality drive aboard the International Space Station that contains DNA of prominent people such as Stephen Hawking and Lance Armstrong.