Indian team was close to Nobel in medicine

BANGALORE: An Indian researcher at the Centre for Cellular and Molecular Biology (CCMB) in Hyderabad believes that he and members of his former group "narrowly missed" this year's Nobel Prize for medicine.

The prize, announced Monday at Stockholm, is shared by Americans Andrew Fire and Craig Mello for their discovery of silencing genes by a method known as "RNA interference" or RNAi. The technique has opened new paths to treating and even preventing a disease by switching off the gene responsible for it by introducing small strands of custom-made RNA molecules.

CCMB scientist Utpal Bhadra said his group - which included his wife Monika and James Birchler at the University of Missouri in the US - was one of the first to work on gene silencing but narrowly missed the Nobel race.

Bhadra said that while working at the University of Missouri his group showed how to silence genes in fruit flies for the first time. He joined CCMB in 2001.

"We made the discovery by accident," Bhadra told IANS in a telephonic interview, adding that the finding laid one of the foundations for RNAi. They published their findings in 1997 in Cell, a prestigious journal.

Fire and Mello, selected for this year's Nobel Prize, demonstrated gene silencing in nematode worms called 'C.elegans'. They pushed their findings in 1998, a year after the publication by Bhadra's team.

"I think Bhadra's team missed it narrowly," CCMB director Lalji Singh said.

Fire has himself acknowledged the Bhadra group's contribution in a message that says: "While we got the Nobel Prize, there are a lot of giant discoveries and you are part of that."

Bhadra, who had a long chat on Monday with his collaborator Birchler at the University of Missouri, said his group was initially in the panel under consideration by the Nobel committee but was eventually dropped "as there were too many players".

While claiming it was a narrow miss, Bhadra said he was delighted that this year's Nobel gave recognition to the field of research he and his wife - both Wellcome Trust Fellows - are working on.

While he is working on how to use the gene silencing technique to prevent AIDS and Japanese encephalitis, his wife Monika at the Indian Institute of Chemical Technology, also in Hyderabad, is focusing on using this method to prevent cancer. Bhadra's group has used this technique, with funding from the silk board, to create transgenic silkworms resistant to viral diseases.

Lalji Singh said that Bhadra's work on HIV and other viral diseases would speed up once his institute completes construction of the special containment facility for handling infectious organisms in the next two months.

The institute has also requested the parent body, the Council of Scientific and Industrial Research, for a Rs.1.89 billion grant to set up a dedicated centre on gene silencing "for development of novel drug and novel therapy not only for humans but also for animals and plants", he said.

While CCMB is where the applications of gene silencing are seriously pursued, several laboratories in India are routinely using the technique for knocking out genes, says Govindarajan Padmanabhan, a biochemist at the Indian Institute of Science, Bangalore.

According to Padmanabhan, infectious diseases and cancer are the prime targets for gene silencing. In many types of cancer, the genes which over-express can be blocked by silencing them, he said.

"Unfortunately, the malaria parasite does not have the machinery for gene silencing and so this method is not useful to tackle India's major health problem - malaria," he said.

While RNAi based drugs are now racing towards the clinic, Padmanabhan said the real hurdle is delivery of the gene silencing molecules to the targeted organs.

"You can inject these molecules directly into solid tumours, but for treating other diseases one must develop a reliable delivery mechanism. Scientists are studying the possible use of nanoparticles for this purpose. It will take time." —IANS