The US Senate Appropriations Committee tonight approved a 2012 spending bill that cuts 0.6% from the budget of the National Institutes of Health (NIH) — and offers a starting point for negotiations with the Republican-led House of Representatives in the coming weeks. Significantly, the bill, which cuts the NIH budget by US$190 million to $30.5 billion, also includes money for a proposed translational medicine center whose establishment has become a key priority of NIH director Francis Collins.

But in an uncharacteristic turn, Democrats on the committee defeated, in a party-line vote, an amendment by freshman Republican senator Jerry Moran of Kansas (pictured), that would have restored the $190 million to the biomedical agency by implementing an across-the-board cut to all other programs in the massive bill, which funds the Departments of Labor, Education, Health and Human Services and related agencies.

Moran, who in his short time on Capitol Hill has become an outspoken booster of NIH, proposed the amendment, he said, because he wanted “to send a clear signal …that this Congress is not going to do anything but support and continue to support medical research.”

Richard Shelby (Republican, Alabama) a senior committee Republican, applauded the amendment before the vote: “NIH has been caught in the budget crossfire,” he complained. “The 190-million reduction was not based on committee concerns or [agency] performance.”

Every one of the 14 Republicans on the committee voted for the amendment, but every one of the committee’s 16 Democrats opposed it.

Just before the vote, Senator Tom Harkin (Democrat, Iowa), who chairs the subcommittee that drafted the bill and is also an ardent NIH supporter, was put in the uncomfortable position of arguing against protecting the agency.

“It sounds easy to do an across-the-board cut,” he told Moran. “But you take something like special education. This across-the-board cut would be a $200,000 cut to special education in the state of Kansas. That’s pretty tough." He added that "nationally, Head Start would be cut by 3,800 children”.

Harkin also said: "Cutting NIH is not a choice I wanted to make. [But] a [.6% ] cut to NIH is just something that I think that they can live with.”

“We’re grateful that the cut for NIH wasn’t worse,” said Jennifer Zeitzer, director of legislative relations at the Federation of American Societies for Experimental Biology in Bethesda, Maryland. Still, while her group appreciates the fiscal constraints the government is operating under, she says, “The bottom line is that we’re just really going in the wrong direction when it comes to funding medical research in this country.”

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It’s definitely a 21st-century ambition: a chip inlaid with human cells representing physiological systems from heart to brain to gut. A chip that would separate the wheat from the chaff among myriad potential new drugs, dispensing with those toxic to humans before they ever enter a human body. And doing so quickly and cheaply.

Today, the US military and the National Institutes of Health (NIH) proposed developing just such a chip in a US$140 million effort over the next five years. The Pentagon’s storied Defense Advanced Research Projects Agency (DARPA) is teaming with NIH — a first — to execute the project, with each agency committing $70 million. The NIH contribution would come from its director’s discretionary ‘Common Fund’, but be administered through a proposed new translational medicine centre at the biomedical agency. The Food and Drug Administration will also play a part, advising the agencies on how to meet its requirements for safety and effectiveness.

NIH director Francis Collins, reached by phone today after attending the ceremony where President Barack Obama signed a new patent law, waxed enthusiastic about the shared research project. “I will admit this is pretty ambitious but the time is right,” he said.

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President Barack Obama received from his bioethics commission today the exhaustive report that investigates US-funded experiments conducted in Guatemala between 1946 and 1948, in which nearly 700 Guatemalan prisoners, soldiers and mental patients were intentionally infected with syphilis without their knowledge or consent. Additional experiments involved orphans and prostitutes and other sexually-transmitted diseases; children as young as ten years old were infected.

In the 201-page report, entitled “Ethically Impossible,” the bioethics commission comes to a blunt conclusion about John Cutler and other US researchers who conducted the experiments with National Institutes of Health funding: “Their failure to exercise moral leadership cannot be excused, and their failure led to practices that were so wrong as to be fairly characterized as heinous.”

It continues: “Those who committed these actions were not under any unusual pressure to do so. They thought that they were above the rules, and went to some lengths to shield themselves from normal institutionally imposed scrutiny.”

The report includes previously unreleased details gleaned by the commission from 125,000 pages of documents, along with photos of patients with psychiatric disorders who were intentionally infected with syphilis. One such patient, a 16-year-old who was twice infected, “was uncooperative”, according to the report.

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The US Senate’s leading advocate for government transparency wrote today to the White House’s budget office, demanding that it protect a proposed rule that would obligate universities to post their publicly-funded biomedical researchers’ financial conflicts on a publicly accessible website.

“The public’s business should be public… I urge OMB to follow through and approve a rule that includes a publicly available website,” Senator Charles Grassley, Republican of Iowa (pictured), wrote in in this letter to Jacob Lew, the director of the White House’s Office of Management and Budget (OMB).

Grassley also demanded copies of “all records, including calendar entries,” of meetings on the rule attending by Cass Sunstein, the leading OMB official negotiating the rule with the National Institutes of Health (NIH). He asked for such records since May, 2010, when the Department of Health and Human Services, NIH’s parent agency, published its proposed rule, “in order to understand why OMB appears to have concluded that weakening the HHS proposed conflict of interest rule is appropriate.”

Grassley was responding to this story in Nature today. It reported that, in closed-door negotiations, the OMB, motivated by a January, 2011 executive order from President Barack Obama, has insisted that NIH backtrack on a proposed requirement that universities and medical schools create websites that would post on-line the details of the financial conflicts of their NIH-funded researchers.

The requirement that institutions make such details public is still in place, according to a government official familiar with the negotiations between NIH and OMB, but universities and medical schools can choose the method they use to make the conflicts public.

The change, Grassley wrote, “flies in the face of President Obama’s call for more transparency in the government.”

When it first proposed the rule, the department called the website requirement “an important and significant new requirement to help the biomedical and behavioral research community monitor the integrity and credibility of [publicly] funded research and underscore our commitment to fostering transparency, accountability, and public trust.”

Grassley’s accompanying press release is here. In the letter, he asked for a response from OMB by August 25.

In a victory for supporters of human embryonic stem cell (hESC) research, a US district judge ruled today that government funding of the research is legal, despite an existing law that prohibits US funding of research in which an embryo is destroyed.

The 38-page summary judgment by Royce Lamberth (right), the chief judge of the US District Court for the District of Columbia, may not be the final word in the case of Sherley et al. v. Sebelius, the lawsuit that ground US stem cell research to a halt for 17 days last August and September. But it puts the plaintiffs, adult stem cell researchers James Sherley and Theresa Deisher, on a challenging course should they choose to appeal today’s decision to the US Court of Appeals for the District of Columbia Circuit or, ultimately, the Supreme Court.

Their lawyers said in this statement today that they “are weighing all of their options for appeal.”

Lamberth is the same judge who issued a preliminary injunction 11 months ago that temporarily suspended US funding for the research on the grounds that it was “unambiguously” prohibited by existing law. He noted in today’s opinion that an intervening decision in April from the Court of Appeals for the District of Columbia Circuit “constrains this Court” and obliges him to find that the law, the Dickey-Wicker amendment, is ambiguous enough to allow for National Institutes of Health (NIH) funding for hESC research.

The amendment prohibits government funding for “research in which a human embryo or embryos are destroyed.” The appeals court said in April that, given the ambiguity of the word “research” in that text, the NIH was “reasonable” in concluding that it could fund research using cell lines derived from embryos (which are destroyed in the process) as long as it does not fund the derivation itself.

Today, Lamberth wrote: “While it may be true that by following the Court of Appeals’ conclusion as to the ambiguity of “research,” this Court has become a grudging partner in a bout of “linguistic jujitsu”, such is life for a [lower] court.”

He added that, in briefs filed with him and with the appeals court since last August, the plaintiffs failed to present any convincing new arguments. “The only thing that has changed since this Court first considered the question of whether “research” in the statute is ambiguous is that the [appeals court] has made it abundantly clear that the term is ambiguous as a matter of law.”

Lamberth also pointedly dispensed with another argument made by the plaintiffs, that the NIH violated the Administrative Procedures Act (APA) in the spring and summer of 2009, as it drafted guidelines to implement President Barack Obama’s March 2009 executive order loosening constraints on government funding for the research. In those guidelines, it was up to NIH to specify exactly how that would be achieved, and to collect public comments on the guidelines. The plaintiffs had alleged that, by ignoring tens of thousands of public comments opposing any government funding of the research, NIH violated the APA.

Today, Lamberth wrote that: “the NIH wasn’t obligated to respond to [public] comments on the topic of whether to fund human embryonic stem cell research…..The NIH rightly disregarded comments that provided no assistance regarding the task at hand: to create guidelines for funding embryonic stem cell research that would ensure that funded projects are ethically responsible and scientifically worthy.”

Supporters of the research were both jubilant and cautious. “Given the quality of the briefs, this is certainly what we expected and hoped for, and it’s the right ruling,” said Amy Comstock Rick, a lawyer who is chief executive officer of the Parkinson’s Action Network in Washington, DC.

“This is a great victory for patients and the researchers who are trying to help them,” added Tony Mazzaschi, the senior director of scientific affairs at the Association of American Medical Colleges in Washington, DC. “[But] obviously, it’s likely that the plaintiffs will appeal this decision.”

George Daley, a stem cell scientist at Children’s Hospital, Boston, said: “While I am relieved that this case was decided in favor of the NIH policy on stem cell research, I remain concerned that the opponents will press this issue further, perhaps to the Supreme Court.”

Francis Collins, the NIH director, said in a statement: "“We are pleased with today’s ruling. Responsible stem cell research has the potential to develop new treatments and ultimately save lives. This ruling will help ensure this groundbreaking research can continue to move forward.”

Plaintiffs’ attorney Stephen Aden of the Washington, D.C.-based Alliance Defense Fund, portrayed Lamberth as having his “hands tied” by the court of appeals’ April decision.

“Americans should not be forced to pay for experiments that destroy human life, have produced no real-world treatments, and violate federal law,” Aden said in a statement. “The law is clear, and we intend to review all of our options for appeal of this decision.”

For all of Nature’s coverage of the stem cell injunction, see our special collection.

Geron made medical history last October, when it treated subject number one in the first-ever trial of a human embryonic stem cell (hESC) therapy, for spinal cord injury.

Now, the second and third hESC trials have been launched. On July 12, in an operating room at the University of California, Los Angeles, the first subject in each of the trials — one for a rare form of blindness that usually begins in childhood, the other for a common cause of blindness in the elderly — was treated with retinal pigment epithelial (RPE) cells derived from hESCs. Details are available in this press release from the sponsoring company, Advanced Cell Technology, based in Santa Monica.

The surgery was performed by Steven Schwartz, the study’s principal investigator and retina division chief at UCLA’s Jules Stein Eye Institute, who is pictured above in the process of transplanting the cells into one of the patients on Tuesday.

The trials, each of which aims to enroll 12 patients, will assess over the course of one year the safety and tolerability of ascending dosages of the cells. The first two patients received what are considered small doses — 50,000 cells each — transplanted into the tissue directly under their retinas.

“Early indications are that the patients tolerated the surgical procedures well,” Schwartz said in the press release.

The company’s therapy uses hESCs to recreate RPE cells, which support the photoreceptors needed for vision. It has shown promise in rat and mouse models of degenerative disease of the macula, a three-to five millimeter area that is responsible for central (as opposed to peripheral) vision. It also contains the fovea, the high-acuity hot spot of the retina. Abstracts of the relevant papers are here and here.

One of the conditions being treated, Stargardt’s Macular Dystrophy, it is a degenerative disease of the retina that affects roughly 1 in 10,000 US youngsters. The other, a closely related cause of blindness, Age-related Macular Degeneration (AMD), affects millions of Americans. (The trial therapy is attacking “dry” AMD, which account for about 90% of all AMD.)

To date, the US Food and Drug Administration has approved only these three hESC trials. For a profile of the first subject in the Geron trial, an Alabama man in his early twenties, see this article from The Washington Post.

Scores of protestors, many of them women with breast cancer, demonstrated outside a pivotal meeting at the US Food and Drug Administration (FDA) earlier today.

They were demanding that the US drug regulator reverse a December decision to withdraw its approval for the use of Genentech’s Avastin (bevacizumab) in metastatic breast cancer – breast cancer which has spread to other parts of the body.

“We sent a message to the FDA today loud and clear: Keep your hands off our women and allow them to keep their Avastin,” said Terry Kalley, the founder and president of the group Freedom of Access to Medicines which organized the protest along with the Abigail Alliance for Better Access to Developmental Drugs. The protestors estimated their numbers at 75 to 100. (FDA challenged this figure: see the update below.)

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Proponents and opponents of US government funding for human embryonic stem cell (hESC) research have filed what may be their final arguments to the judge who shut down the research for 17 days last August and September.

Briefs were filed today by both sides in Sherley et al. v. Sebelius, the landmark lawsuit challenging the legality of government support for the controversial research.

Lawyers for the plaintiffs, adult stem cell reseachers James Sherley and Theresa Deisher, argued in this brief that government funding of the research “inevitably” creates an incentive for more embryos to be destroyed. They write:

“Each time grant-awarding officials and federally funded scientists support or engage in hESC research, they `knowingly subject’ human embryos `to risk of injury or death,’ in violation of [existing law.]. The federally sponsored hESC research…inevitably creates a substantial risk—indeed, a virtual certainty—that more human embryos will be destroyed in order to derive more hESCs for research purposes.”

Lawyers representing Kathleen Sebelius, the secretary of Health and Human Services, anticipated the plaintiffs’ argument in this brief. They write that, this spring, an appeals court

“held that [existing law] is ambiguous, and that [the National Institutes of Health] had reasonably read the statute to permit the funding of hESC research but to forbid funding for the derivation of hESCs. Plaintiffs, presumably, will now switch gears and advance an alternative theory that [existing law] forbids any actions that `incentivize’ the destruction of embryos.”

That argument is beside the point, the Sebelius brief continues, because the derivation of stem cell lines, which must be funded with private money, is legally distinct from actual research on those lines.

“Whether or not plaintiffs are correct to speculate that the [NIH] Guidelines or `media portrayals’ will encourage patients of IVF clinics to donate embryos, that donation is still not `research in which’ an embryo is knowingly subjected to a risk of injury or death.”

Both documents were filed with Chief Judge Royce Lamberth (pictured) of the U.S. District Court for the District of Columbia.

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<img alt=“woodcock.june 2011 002.jpg” src=“https://blogs.nature.com/news/woodcock.june%202011%20002.jpg” width=“260” height="176 " align+"right"/>The US Food and Drug Administration (FDA), often denigrated for being slow to approve new drugs for market, has recently been speedier than its European counterpart in approving new cancer drugs, according to a study in the journal Health Affairs released today.

Between 2003 and 2010, the US agency approved 32 new anti-cancer drugs while the European Medicines Agency (EMA), approved 26, the study says. More striking is the difference in times to approval: in the US, the median time between a company’s submission of a new drug application to the FDA and the agency’s marketing approval was 182 days. The analogous time in Europe was nearly twice as long: 350 days. Furthermore, all 23 of the drugs approved by both regulators made it to market in the United States before they became available in Europe.

“I’m pleased, but that doesn’t mean they [at FDA] get a free pass” said Ellen Sigal, one of the three authors of the study, and chair of the advocacy group Friends of Cancer Research. She couldn’t believe the results when she first saw them, she added. “It defied urban legend.”

Janet Woodcock the director of the Center for Drug Evaluation and Research at FDA, spoke with Sigal and others at a panel on Capitol Hill today. “We are not in a contest or a race with the European Union or any of our regulatory partners around the world,” she said.

Still, she added: “It isn’t just your cancer drugs” that FDA approves ahead ot its counterpart. The agency recently examined approvals of novel drugs in the US and Europe in all disease areas, between 2006 and 2010. Forty-three of 57 such drugs were first launched in the United States. “This trend is across all different indications,” Woodcock said. (Woodcock is pictured at left, above, speaking with co-panelist John Marshall, an oncologist at the Georgetown-Lombardi Comprehensive Cancer Center in Washington, D.C.)

Jonathan Leff, a panelist who is managing director ar Warburg Pincus, a private equity investment firm, noted that more than half of the 32 cancer drugs approved by FDA over the seven-year period in question were granted “accelerated approval” — a designation which allows the agency to approve a drug using surrogate endpoints expected to predict clinical benefits — rather than requiring a company to demonstrate the benefits themselves.

It appears, added Leff, that “Europe has not quite been able to apply that flexibility.”

Nonetheless, Leff said, a perception problem remains for FDA, which industry views as giving more weight to the risks of a drug than it does to its benefits. If he were to ask 50 venture capitalists, or the chief executives at 50 biotechnology companies, why investment in the area is diminishing compared to ten years ago, he said, “The answer invariably comes back….`It’s the FDA.’”