Once the world’s gold standard, American scientific enterprise is in free fall. Short of government funds and strapped for cash, researchers across the country are abandoning promising avenues of scientific investigation and, increasingly, the profession of science itself.

The worry, say policy experts, is not just the curtailment of innovative research, but a reduction in potential treatments for hundreds of human diseases.

The 2008 congressional appropriations bill, which dramatically cut money to federal research institutions, already has had “a disastrous effect on science, causing irreparable harm to the nation’s science and technology enterprise,” according to the American Physical Society.

An emergency bill passed by Congress last week allocates an additional $275 million to be distributed among the National Institutes of Health, the Department of Energy’s Office of Science and the National Science Foundation, but it did little to stem the pessimism.

Rep. Rush Holt, D-N.J., called the emergency allocation a mere “down payment” on basic science research, adding in a statement, “We still have not lived up to our responsibility to fund fully these efforts.”

Nowhere is the crisis more evident than at the NIH, the major funder of biomedical research in the United States. Between 1998 and 2003, the federal government doubled the budget of the National Institutes of Health, allowing for the completion of the human genome project; new treatments that reduced mother-to-child HIV transmission from 25 percent to 1 percent in the United States; and the creation of the first clot-busting drug to prevent massive disability from stroke.

Since 2003, however, the budget increases have stopped and the NIH remains trapped in a five-year run of flat, or below-inflation, budgets. In 1999, one in five original grant applications to NIH was funded. Today, nine out of 10 are rejected.

“The funding cuts have slowed the progress of science demonstrably,” said Kevin Casey, associate vice president for government and public affairs at Harvard. “Older researchers are demoralized and a generation of young investigators now are leaving academia. Foreigners who were trained here are not staying; they’re going home. It’s a cascading effect … and there’s a perception of hopelessness.”

Federal research institutions also have been hard hit. The Fermi National Accelerator Laboratory in Batavia, Ill., had its funding cut by $52 million this year. The budget for the Argonne National Laboratory, near Chicago, was slashed by $21 million. And at the Lawrence Livermore National Laboratory in northern California, a $100 million shortfall led to the layoffs in May of 440 full-time employees, some of them scientists and engineers who had worked at the lab 20 years.

After the federal decreases in scientific funding were announced late last year, Nobel Prize-winning physicist Leon Lederman, a former director of the Fermi Lab, admitted to being in a state of shock.

“I’ve been around this lab since it was all farmland,” he told a reporter. “I can’t remember a crisis of this severity.”

Lederman’s sentiments were echoed by four science policy analysts who wrote in the New England Journal of Medicine in January, “The nation’s biomedical research enterprise has never experienced a recession of this magnitude or duration.”

Most scientists blame the federal funding woes on the war in Iraq, as well as congressional budgetary restraints and entitlement spending.

“There’s just less and less discretionary funding,” said Stephen Heinig, lead science policy analyst at the Association of American Medical Colleges in Washington. “I think we’re going to weaken a lot of institutions. The saddest thing for me is thinking about the missed opportunities with research that never gets started. It’s exceptionally frustrating.”

The frustration reaches deep into many colleges and universities where experimental scientists depend heavily on federal grants. Overall, original research grants were funded by the U.S. government at close to 30 percent in 1999. Today, that rate is just 12 percent, leaving many established scientists scrambling to continue their experiments, and newly minted scientists unable to gain a foothold.

Many scientists believe the government’s de-investment in scientific enterprise is disturbingly shortsighted at a time of significant economic woes. Continued flat-funding, they say, will only set the country up for monumental failure down the line. Since World War II, science and engineering have been responsible for close to half the growth in the U.S. economy, according to Ray Orbach, head of the government’s Office of Science.

Nor will it be easy to recover from the shut-off of federal funding for scientific enterprise. Without grants, there will be less research – and with less research to do, there will be far fewer scientists entering the profession. Already, Asian countries are graduating 10 times the number of scientists and engineers as the United States.

“Without effective national policies to recruit young scientists to the field,” wrote Elias Zerhouni, the NIH director, in March, “in 10 to 15 years, we’ll have more scientists older than 65 than those younger than 35. This is not a sustainable trend in biomedical research.”