Life vs death: Lab uses DNA to fight cancer

Malathy Iyer, TNN, Nov 13, 2010, 02.59am IST
Article

MUMBAI: The simplicity of Lab Surgpath's office in Mumbai Central gives no indication of the cutting-edge work being done there. The six i-Macs bunched up in a corner of the largely bare office, however, provide the answer when they are switched on: Hitherto unseen high-definition images of normal and cancer cells start flashing rapidly on the screen.

It's here that a part of the ambitious sequel to the Human Genome project — the sequencing of the complex human DNAs — is being played out. Called the Human Protein Atlas (HPA), the sequel's Mumbai chapter is being handled by surgical pathologist Dr Sanjay Navani and his 10-member team of doctors.

Headquartered in Sweden, the Atlas is envisaged as a natural progression to the Genome project. The effort is to map each protein's behaviour in normal and cancer tissues. Once the proteins and the genes on which they occur are correlated, it would be easier to spot an anomaly that causes a disease. Once the antibody for each protein is known, preparing medications would be easier — a concept gaining popularity through the term 'personalized medicine'.

On November 15, 2010, when the HPA team presents the half-mark of its project in Stockholm — the sequencing of half the human proteome — Lab Surgpath's team of pathologists will also take a bow. They have painstakingly validated and documented the profiles of over 10,000 antibodies that the Swedish team has so far produced.

''The validation is an online exercise, as India has stringent rules governing the transfer of biological samples,'' says Dr Navani, who is among the handful of pathologists in the country practising surgical pathology (the study of human tissues under a microscope) and immunohistochemistry (in which proteins in tissues are detected using antibodies). So, teams in Stockholm's Royal Institute of Technology Stockholm and Uppsala University prepare slides of normal and cancer tissues. They use various antibodies generated within the project to stain the tissue: A dark stain would mean the sample has a particular protein while a lighter one would mean poor concentration of that protein.

At the Lab Surgpath office, pathologists such as Dr Naila Khan and Dr Tushar Patil study the stained samples and grade the antibodies on high-definition computer screens — their efficacy as well as their usefulness in diagnosing a particular form of cancer such as cancer of the ovary, breast or others. ''The HPA has provided us an excellent way to educate ourselves,'' say Dr Khan and Dr Patil.

The team works in batches, and follows a system of counter-checking each other's work. ''So, a sample graded by Dr Naila could be further validated by Dr Patil or an international expert,'' says Dr Navani, who until the start of the project worked with Breach Candy Hospital.

At present, the Human Protein Atlas site (www.proteinatlas.org) hosts 11,274 antibodies and 9,103,793 images. The project leader, Prof Mathias Uhlen, has been quoted in various fora as saying, ''We are trying to map the building blocks of life.'' His colleague, Fredrik Ponten, in an email interview to TOI, points out three stages of work: Preparing antibodies, matching them with the proteins in various tissues, and utilising the information to develop diagnostic tools and therapies.

Why was an Indian team selected for the process? Ponten says, ''Our work can only be evaluated by skilled pathologists who understand the microscopical landscape.

Dr Sanjay Navani was selected, based on his knowledge of surgical pathology and immunohistochemistry, which is fundamental for interpretation of what cells and tissues actually do.''

Dr Navani admits there was scepticism initially. ''The field of immunohistochemistry expertise itself is small in India. Here, we were training pathologists for the first time in the field. Yet, in the first month itself, we more than met the standards and volumes expected of us.'' Ponten concurs: ''The volume of images that are being evaluated every day at the Indian site is unheard of in the rest of the world and, as such, adds to the uniqueness of this successful project.'' More than 8 million images have been evaluated at the Mumbai site — the largest effort made by a single group of surgical pathologists ever.

Incidentally, the Atlas has spawned a rush for research work as well. The Swedish team, on special requests from research scientists in India who work in tandem with Dr Navani, has sent several samples of validated antibodies. ''Such research in India is very expensive, but the Atlas team has been generous enough to share its samples with Indian students and researchers,'' Dr Navani adds


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