They are basic research prizes. But this year's Nobel Prize in physiology or medicine, which was announced yesterday, as well as the Lasker Prize for basic biomedical research announced Sept. 29, both have been harnessed for therapeutic use. Newly minted Nobelist Craig Mello pointed out that the therapeutic payoff cannot be had without the basic research payout.

The Nobel Prize was awarded to Mello, of the University of Massachusetts Medical School, together with Andrew Fire, from Stanford University, for their "discovery of RNA interference - gene silencing by double-stranded RNA."

RNAi essentially is a method of killing the messenger - messenger RNA, that is. Fire and Mello found that when they injected double-stranded RNA into a cell, not only did the cell destroy the double-stranded RNA, it also went after single-stranded RNA whose sequence matched the intruder RNA, enabling researchers to knock down messenger RNA with specific sequences.

I'm Too Young For This!

The prize follows by less than 10 years the publication of the discovery, which appeared in Nature in 1998 - unusually rapid by Nobel standards. While Alfred Nobel himself conceived of his prize as an award for a promising young scientist, over the years it has become more of a crowning glory for those with careers built on a long-ago seminal discovery. In fact, 45-year-old Mello told reporters at a press conference that the University had reminded him yesterday that the medicine Nobel was being announced today, but his response was that "it won't happen this year; I'm too young."

He also noted that his youth is unfortunately an exception to the trend in science, asserting that "we're not spending enough, as a nation, on basic science." Many researchers in their 40s, far from a Nobel, are just starting to get their own research grants, and Mello warned that this situation "is turning young minds away from science, because they see how tough it is to make a living" pursuing basic research.

University President Jack Wilson, who spoke at the press conference with Mello, warned that such a funding drought would ultimately trickle down into the medical area: "If you don't do the basic research, you won't have the applied research," he said.

Mello and Wilson get support from the business side for their assessment. The idea that basic science funding is necessary for applied research breakthroughs "is absolutely true and unbelievably important," said Barry Polinsky, chief scientific officer of San Francisco's Sirna Therapeutics.

Polinsky said that the prize itself does not make a big practical difference to companies like Sirna that exploit RNAi clinically: "Obviously, we're thrilled, and appreciate the great work that's been done by Craig and Andy and many others over the years," he told BioWorld Today. But "our course has been set for a number of years, and we've appreciated the power of this technology for a long time."

So while a Nobel Prize validates the technology to the public, Sirna's scientists will spend the week much like they spend every week: solving problems such as the best way to deliver RNAi.

But to even get to those problems, funding of basic research is critical. "It's how a nation and a society improves the health and welfare of its citizens," Polisky said, noting that the recombinant DNA technology, and hence essentially the entire biotechnology industry, resulted from government funding of basic research. "It's absolutely critical that government, and the public, see the connection."

The applied research resulting from RNAi is robust. A partial list shows Sirna Therapeutics has completed a Phase I trial for its lead compound, Sirna-027, in age-related macular degeneration in 2005, and expects to enter the clinic with a candidate for hepatitis C virus by the end of 2006. Competitor Alnylam Pharmaceuticals Inc., of Cambridge, Mass., has RNAi in the clinic to target viral infections, and is testing the technology in other preclinical indications. (See BioWorld Today, May 25, 2006, and Sept. 22, 2006.)

Telomerase: From Medically Irrelevant To Hot Topic

Telomerase, whose discoverers, Elizabeth Blackburn, Carol Greider and Jack Szostak, received the 2006 Albert Lasker Award for basic medical research last week, is another enzyme that receives attention from both the business and the basic science arena. One example is Geron Corp., of Menlo Park, Calif.

The company is trying to have it both ways with telomerase: The company is in clinical trials for solid tumors, as well as chronic lymphocytic leukemia with a telomerase inhibitor, while a joint venture between Geron and the Biotechnology Research Corp. of Hong Kong called TA Therapeutics Ltd. is exploring the use of telomerase activators to treat degenerative diseases including anemia, AIDS, macular degeneration and atherosclerosis.

In a commentary on the Lasker award published in the Sept. 22, 2006, issue of Cell, academic telomerase researcher Titia de Lange also made the case for basic research, writing that "its biomedical merits clearly warrant recognition of telomerase and its discoverers. [But the] enzyme did not emerge from research on cancer or aging, however. It was found as a solution to one of the most basic problems in cell biology" - the question of how cells replicate the last few nucleotides of their DNA sequence, which the cell's replication machinery cannot access.

For DeLange, telomerase epitomizes the sorts of unexpected findings that can come out of basic research. Originally, telomerase research was "basic research carried out in medically irrelevant organisms" whose possible medical relevance was not seen until 10 years after the enzyme was discovered, she told BioWorld Today.

Just as someone needs to pay for all those clinical trials to get the coveted blockbuster, "applied research follows up on existing discoveries" that basic research enables, she said. RNAi, which was discovered only in the 1990s, is a clear example that there are undiscovered pathways and processes with medical value; without funding basic research, "we'd be losing out on all those discoveries."

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