Nature India | Indigenus

Mapping the malady of cancer

The demonstrations we were so proud to have put together garnered forced applause and empty smiles. We had not addressed their main concern, the sense of finality associated with cancer.

Second runner-up, Nature India Essay Contest 2020

Aditi Ghose

Aditi Ghose explaning an exhibit on COVID-19 at the Birla Industrial and Technological Museum, Kolkata.

A group of cancer patients under palliative care, aged under 15, were scheduled for a guided visit to our Science Centre. As a science communicator I was desperate to make it special. Having lined up the choicest of our expositions, I was adamant on giving them an amazing experience. From decking the halls with cheerful banners, to ensuring that they could touch and see science-in-action – I believed that all would take part.

At the end of the day though, I realised I couldn’t have been more wrong. Moving along on wheelchairs through decorated alleys, the children wore desolate looks. The demonstrations we were so proud to have put together garnered forced applause and empty smiles. No amount of enthusiasm from our side could counter the children’s vibe of helplessness. The care-givers thanked us for our initiatives that day, but we knew we had failed. We had not addressed their main concern, the sense of finality associated with cancer.

With the World Health Organisation reporting that one in six deaths is caused by it, cancer is aptly called ‘the Emperor of All Maladies’.  The messages about cancer can be conflicting. ‘Cancer cannot be prevented.’ ‘It is a death sentence.’ ‘It’s contagious.’ ‘Everything causes cancer.’ ‘Over-the-counter remedies can cure cancer’. ‘Children don’t develop cancer.’  Trying to turn these children away from their fears and divert them to our regular demonstration routine had been a mistake. They could be best addressed only where they hurt most — we had to show them how cancer is being challenged today. We called in a few favours and asked the children to visit again. This time we wanted to tell them of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Project.

Featuring a cast of more than 1300 scientists and clinicians with 744 affiliations between them, across four continents, analyzing 2658 whole genomes for 38 types of cancer, the PCAWG Project had revealed, in a suite of six research papers, the most complete picture (yet) of how DNA glitches drive tumour cell growth. It had identified the driver mutations — limited between four of five in 95% of the samples —  that powered the typical shattering and rearrangement of cells in tumor growths. This implied that patients diagnosed with those hallmark mutations will, in principle, be matched to a drug that targets the protein made by that driver gene. Another paper revealed that these mutations cropped up years or decades before the actual cancers were diagnosed. Detecting such anomalies suggested that many could be detected and treated earlier now.

Processes such as defective DNA-repair mechanisms or exposure to environmental mutagens produce characteristic patterns of DNA aberrations. Expanding our knowledge of genomic data sets of these mutations, the current study had identified 97 such signatures, crucial to the refinement and extension our understanding. It introduced the idea of ‘molecular time’ to classify mutations in tumour cells – helping identify and perhaps monitor common mutational trajectories. Papers matching data to functionally link DNA and RNA alterations illustrated the power of their integrated analysis for cancer studies.

The efforts warranted hundreds of terabytes of data, spread across multiple data centres, exacting millions of processing hours, making this level of international collaboration a reality. Pinpointing 705 recurring mutations in cancer genomes, acquiring samples protecting patient privacy while generating terabytes of data for use by the researchers, the project was a milestone in cancer genomics, along with a marvel of cloud genomics. It was only fair that the findings and implications of this gargantuan scientific endeavor be put forward to those who hope and pray for such miracles day in and day out. All that was left to do was figure out how.

Poring over the original papers, I realised the research findings were basically a heat-map, identifying the causal regions responsible for the genetic aberrations. A similar heat-map, for an entirely different purpose, was devised in 1914. It was the First World War and the number of bomber-planes that made it home was central to deciding the outcome of the war. To turn the odds in their favour, researchers from the Center for Naval Analyses had devised a simple card containing the outline of the bomber-plane, to be handed over to the returning pilots, to mark out the areas where the plane had taken a hit. Stacking up such cards would lead to a heat-map indicating where the planes were receiving the most damage.

It turned out that these regions included the centre along the tail gunner and edges along the wings. These were the most resilient parts of the plane – they had managed to return home, hole and all. The parts that were left unscathed in the cardboard outline – the cockpit and the fuselage – warranted a layer of protective-cladding.  Planes that had been hit in those areas were lost forever. Taking the missing planes into account was seminal to the contemporary discipline of operational research. Similarly, identifying the driver mutations in each cancer cell is going to be decisive in developing precision medicine, tailored to understand cancer better. We decided to tell the data-intensive story of the latter while demonstrating the bomber plane heat-map on paper gliders.

Skeptical at first, the children were gradually drawn in to the floating gliders. By the end of the session, the room was resonant with their laughter while the floor was carpeted with their paper planes. We even saw their care-givers eyes sparkle. A few strategically reinforced bomber planes had not won the war for the Allies – but they certainly helped. The six PCAWG papers and global consortium of researchers are only perhaps the beginning – their collaborations, knowledge exchanges and insights are going to provide the air beneath the wings of all fighters who battle cancer — either for themselves or for someone they care about.

[Aditi Ghose is an Education Assistant at the Birla Industrial & Technological Museum, Kolkata. She can be reached at aditincsm@gmail.com.]

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