NEWS OF THE WEEK
DOUBTFUL FUTURE FOR ENERGY BILL POLITICS: Senators meet with
President, but show little interest in climate legislation
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RESIDENT BARACK OBAMA continued press-
ing reluctant senators to pass climate and energy legislation this year during a 90-minute meeting last week with some two dozen of them. The President remains committed to provisions “putting a price on pollution,” he said in a statement after the closed-door meeting. But the statement noted that “not all of the senators agreed with this approach” and that the President welcomes other ideas to cut “dependence on oil, create jobs, strengthen national security, and reduce atmospheric pollution.” The fate of energy and climate legislation in the Senate is likely to turn on several draft bills under conAFP/SAUL LOEB/N EWSCO M
Kerry (center) and Lieberman talk to reporters outside the White House after meeting with the President.
TARGETING DISEASE DRUG DISCOVERY: Natural products may
not be the best place to look for small molecules to treat human ailments
HIGHLY CONNECTED The natural product ingenol (shown) targets a protein that interacts with at least 86 other proteins.
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MALL-MOLECULE natural products target es-
sential proteins rather than those involved in disease, according to a new study (J. Am. Chem. Soc., DOI: 10.1021/ja102798t). Stuart L. Schreiber of the Broad Institute of Harvard and MIT says his team’s findings suggest that drug designers hoping to hit disease proteins will have to look beyond nature for inspiration. Using network analysis, Schreiber, Paul A. Clemons, and coworkers show that natural products bind to proteins that interact with many other proteins, a hallmark of gene products encoded by essential genes. In contrast, proteins encoded by disease genes tend to have fewer interactions. In addition, the researchers find, approved synthetic drugs tend to strike proteins with network connectivity that more closely resembles that of disease proteins than that of natural-product targets. “Clearly, natural products can become drugs because many of them are drugs,” Schreiber says. But his team set out to determine whether natural products WWW.CEN-ONLINE.ORG
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sideration and the ability of Majority Leader Harry Reid (D-Nev.) to meld provisions that are popular enough to draw the support needed to reach a 60-vote majority and bring a bill to the floor. Reid says he hopes to produce such a bill this summer, but floor action may have to wait until after the November elections. So far, Senate attention has been fixed on a draft carbon dioxide cap-and-trade bill authored by Sens. John F. Kerry (D-Mass.) and Joseph I. Lieberman (I-Conn.). A somewhat similar bill placing a price on carbon emissions cleared the House a year ago. Also, Sens. Maria E. Cantwell (D-Wash.) and Susan M. Collins (R-Maine) have introduced a bill putting a price on oil and coal at their sources and returning 75% of that carbon tax directly to consumers. Nearly all Senate Republicans have made it clear that they would not support any carbon pricing or cap-andtrade approach, as have several Democrats. Hence a search is under way to find a compromise. Several senators have proposed legislation encouraging expansion of renewable energy through financial support and targets, but without a price on carbon emissions. Another option that has recently garnered interest is putting a price only on greenhouse gas emissions from electric utilities. Sen. Jeff Bingaman (DN.M.) has discussed this alternative, but last week he said he was unsure of when he might actually propose such a bill. At least one Republican senator, Olympia J. Snowe (Maine), is backing the power-sector-only approach.—JEFF JOHNSON
are optimal compounds for targeting disease proteins. “Our data suggest they are not,” he says. “This is a great challenge for synthetic organic chemistry: How do we turn our attention to new classes of compounds that target disease gene products?” The fact that natural products aim at proteins encoded by essential genes is not surprising, Schreiber says. Many of them evolved as weapons in microbial warfare, he explains, and “they will target the most essential genes possible.” “The idea that natural products might be less suited as drugs for human diseases due to evolutionary direction toward highly connected and essential biological processes is significant,” says John A. Porco Jr. of Boston University. “Such fundamental observations are an excellent step toward understanding how we should consider development of new drugs for human disease.” “Alas, as would have been expected from professor Schreiber and from the Broad Institute, the paper makes a strong case for the idea that the diversity required for pharma-level success is not likely to be provided by strictly small-molecule natural products,” says Samuel J. Danishefsky of Columbia University. But the “paper admirably serves to refocus reader interest on small-molecule natural products as well as synthesis. That’s all to the good.”—CELIA ARNAUD
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