From the Hill
New limits on funding of stem cell research questioned
In the wake of President Bush's decision to allow federal funding of human embryonic stem cell research, although only on the 64 stem cell lines that existed before August 9, 2001, many scientists and policymakers are questioning the adequacy of those lines for achieving medical breakthroughs. And a September 11, 2001 report by a National Research Council/ Institute of Medicine (NRC/IOM) committee states that, for a number of important reasons, new stem cell lines will be needed in the future.
"We . . . believe that new embryonic stem cell lines will need to be developed in the long run to replace existing lines that become compromised with age and to address concerns about culture with animal cells and serum that could result in health risks for humans," said Bert Vogelstein, head of the NRC/IOM committee, in a statement.
Stem cells are unspecialized cells that can renew themselves indefinitely and, under the right conditions, can develop into more mature cells with specialized functions. They are found in embryos at early stages of development, in some fetal tissue, and in some adult organs, although isolating adult stem cells is very difficult, and multiplying them outside the body is not yet possible in most cases. In addition, there is only preliminary evidence that cells obtained from an adult organ can be coaxed into becoming tissue types other than those characteristic of the original organ. In contrast, embryonic stem cells can be grown in the laboratory and appear to be capable of becoming or "differentiating" into virtually any cell type.
Although stem cell research is on the cutting edge of biological science, it is still in its infancy, and an enormous amount of basic research remains to be done before it can result in medical treatments. Because private industry is often reluctant to invest in such early-stage research, progress toward medical therapies is likely to be hindered without government funding.
The Bush policy bans not only the creation of new lines that involve the destruction of existing embryos but also the creation of lines in the laboratory through a technique called somatic cell nuclear transfer, sometimes referred to as "therapeutic cloning." The NRC/IOM report said that use of this technique to create new stem cell lines was essential for dealing with issues of human immune system rejection of new tissues.
Because the Bush decision was essentially a compromise, the resulting policy predictably produced mixed reactions from both supporters and opponents of stem cell research. On the one hand, both sides have expressed relief: supporters because the research was not banned completely and opponents because strict limits have been imposed. But both sides have also expressed displeasure. Many supporters have questioned whether the research that will be allowed to go forward will be enough to produce any progress, whereas many opponents believe that all research on stem cells derived from human embryos is immoral.
The National Institutes of Health (NIH) initially identified 64 existing cell lines that federally funded researchers can use. Previously, most scientists had thought the number to be much lower, and many have expressed doubts about how many of the 64 cell lines will be truly useful to researchers and meet the stringent ethical requirements set out by President Bush and imposed by many universities.
Concerns about the cell lines center on five questions: whether the cell lines are indeed robust enough, whether the procedures used to create the cells are consistent with high ethical standards, whether the different cell lines have sufficient genetic diversity, whether cells produced from the cell lines would be safe for implantation in humans, and whether the owners of the cell lines will make them available to researchers in a timely fashion and at a reasonable cost.
An August 27 NIH statement listing the owners of the 64 cell lines claimed that 19 stem cell lines have been created at Göteborg University in Sweden. However, the New York Times reported on August 29 that of these 19 lines, 12 are "still in early stages," 4 are "being studied and described," and just 3 are "established." Referring to the cells in early stages, Lars Hamberger, a scientist at the Göteborg lab, told the Times that "those 12 perhaps ought to be called potential cell lines. If we get three good lines out of them, we'll be satisfied."
In an appearance before the Senate's Health, Education, Labor and Pensions (HELP) Committee on September 5, Secretary of Health and Human Services Tommy Thompson acknowledged that just 24 to 25 of the 64 cell lines President Bush referred to in his address are in fact established lines. He referred to the 64 lines as "derivations" and emphasized that although some are in early stages of development, all were derived before August 9 from surplus embryos created by fertility clinics and are therefore eligible for use by federally funded researchers.
Regarding ethical requirements, the August 27 NIH statement says that all of the 64 cell lines "meet the President's criteria." In other words, they "must have been derived from an embryo that was created for reproductive purposes and was no longer needed," and "informed consent must have been obtained for the donation of the embryo and that donation must not have involved financial inducements." The statement did not indicate, however, whether the more detailed guidelines NIH developed under President Clinton would be followed, or whether the cells are likely to meet the strict ethical standards enforced by many universities.
Also in doubt is the genetic diversity of the cells. In order to account for genetic differences in studying stem cells, researchers will need to carry out experiments on cells derived from a group of embryos that is genetically variable. However, although NIH has revealed the locations of the existing cell lines, their origins remain uncertain.
The safety of the existing cell lines for implantation is also emerging as a major concern. Most of the 64 cell lines have been grown in cultures with the help of mouse stem cells that potentially could introduce animal viruses dangerous to humans. Although scientists say that human clinical trials are years away, if stem cells are to produce the type of revolutionary medical benefits many hope for, they will need to be transplanted into humans, and this may be impossible or impractical with the currently available cells. Under Food and Drug Administration rules, such transplants with existing cells would be classified as "xenotransplants," or transplants of animal tissue, and would be subject to strict requirements for both researchers and patients.
In order to address concerns about the access researchers will have to existing cell lines, Thompson announced at the HELP Committee hearing that NIH had signed a memorandum of understanding with WiCell Research Institute, which according to NIH is the owner of five cell lines, including the first embryonic stem cell line ever created. The agreement allows NIH scientists to access these cells for their research and to freely publish their results, while guaranteeing that WiCell will retain commercial rights to its materials and receive a fee to cover handling and distribution expenses. In addition, WiCell has agreed to make its cells available for use by nonprofit institutions that receive NIH grants under the same terms as those available to NIH scientists.
This step, however, has not silenced the concerns of some critics about access to the stem cells. Several Democratic members of the HELP Committee, for example, questioned the wisdom of limiting research to cell lines that are controlled by just 10 different entities. "People complain about OPEC being a monopoly, but even they have 11 members," said Sen. Edward M. Kennedy (D-Mass.), the HELP Committee chairman.
Likewise, Sen. Arlen Specter (R-Penn.), testified that "we are just beginning to learn which researchers and companies throughout the world have ownership of existing stem cell lines, but we have little knowledge of their property rights, [and] their willingness to share or license the use of those lines to other researchers."
"Science should have the full range of opportunity," Specter said, referring both to embryonic stem cell lines not created before August 9 and to adult stem cells.
Scientists are anxiously awaiting further information about the existing cell lines, and NIH has promised to facilitate the dissemination of this information by creating the Human Embryonic Stem Cell Registry. Thompson promised at the September 5 hearing that the registry would be launched in 10 to 14 days.
As more becomes known about the 64 cell lines, the future of federally funded embryonic stem cell research will become clearer. Although some claim that a majority of Congress favors a policy less restrictive than the president's, it is unclear whether Congress will act. Even if it does, President Bush has vowed to veto any legislation that would loosen his restrictions. NIH, meanwhile, has encouraged researchers to submit research grant applications and requests to use existing funds for such research.
The president also announced during his August 9 speech the formation of a new President's Council on Bioethics, to be chaired by Leon Kass, a bioethicist at the University of Chicago. In addition to studying a range of ethical issues raised in the biomedical and behavioral sciences, the council will oversee all federally funded embryonic stem cell research.
House considers bill to strengthen science at EPA
In an effort to improve science at the Environmental Protection Agency (EPA), a House Science Committee panel has proposed the creation of a new deputy administrator who would coordinate science across the entire agency. The position would wield much greater influence than that of EPA's current highest-ranking scientist.
"Many people believe that the EPA does not always base its regulatory decisions on strong scientific evidence," said Rep. Vernon J. Ehlers (R-Mich.), the chairman of the Science Committee's Environment, Technology, and Standards Subcommittee, who has authored H.R. 64 to establish the new position. "I believe [H.R. 64] will help change this perception and ensure that science informs and infuses the regulatory work of the EPA."
Currently, the EPA administrator has one deputy administrator and nine assistant administrators. One of the assistant administrators heads the Office of Research and Development (ORD) and is typically the agency's highest-ranking scientist. However, many of the EPA's other offices also carry out scientific research, so the head of ORD does not have overarching authority over science and does not necessarily participate in regulatory decisionmaking.
By establishing the new position, Ehlers hopes to raise both the profile of scientific considerations in the agency's regulatory decisions and improve the quality of the agency's scientific research. In support of the latter goal, the bill would make the head of ORD a nonpolitical appointee, with a five-year term and the additional title of chief scientist. The Environment Subcommittee passed H.R. 64 by voice vote on May 17.
The creation of a new deputy administrator was recommended by a National Research Council (NRC) report released in June 2000 on strengthening science at the EPA. Last spring, committee chair Raymond C. Loehr told the subcommittee that: "Throughout EPA's history, no official below the level of administrator has had overall responsibility or authority for the scientific and technical foundations of agency decisions, and administrators of EPA have typically been trained in law, not science. In the committee's unanimous judgment, the lack of a top science official is a formula for weak scientific performance in the agency and poor scientific credibility outside the agency.
"The importance of science in EPA decisionmaking should be no less than that afforded to legal considerations," Loehr added. "Just as the advice of the agency's general counsel is relied upon by the administrator to determine whether a proposed action is legal, an appropriately qualified and adequately empowered science official is needed to attest to the administrator and the nation that the proposed action is scientific, that it is consistent, or at least not inconsistent, with available scientific knowledge."
William H. Glaze, chair of the EPA Science Advisory Board's executive committee, also testified in favor of the proposal. "The bill would send a strong signal that the Congress and this administration plan to make science a stronger and more integral part of the way EPA conducts its business," he said.
However, a third witness, Rick Blum of the nonprofit group OMB Watch, declined to endorse H.R. 64, citing questions about how the proposal would actually work and how it would relate to the EPA's existing Office of Environmental Information. "The establishment of a Deputy Administrator for Science and Technology," he said, "may send unintended signals that scientifically drawn conclusions should be given prime weight in any decision to establish environmental safeguards, that the lack of scientific certainty requires inaction."
Several other organizations have expressed support for the proposals in H.R. 64. The Business Roundtable endorsed the idea of a new deputy administrator in its Blueprint 2001, a report on environmental policymaking. The American Chemical Society endorsed the proposal as well, in a statement that called for giving ORD more prominence within EPA and increased funding.
FY 2002 R&D funding outcome unclear as budget surplus disappears
As of mid-September, the outlook for R&D spending in fiscal year (FY) 2002 was unclear, complicated by the political dilemma resulting from the disappearance of the non-Social Security budget surplus and by the need for Congress to focus on measures aimed at dealing with the September 11 terrorist attacks in New York and Washington.
Before the attacks, Republicans and Democrats in Congress, as well as the White House, had been gearing up for a major fight over responsibility for the disappearance of the non-Social Security budget surplus and over whether Congress should tap the Social Security trust fund to pay for increases in defense, education, and other areas. That debate will now be put off to another day. It was not clear when the appropriations process would be completed. The new fiscal year began October 1.
As of mid-September, the House and Senate had drafted 9 of the 13 appropriations bills. Both chambers have backed modest increases in overall R&D spending, in contrast to President Bush's budget, which called for cutting spending for nondefense, non-National Institutes of Health (NIH) R&D agencies. The House would appropriate $28 billion for R&D in its versions of the nine bills, 2.2 percent more than in FY 2001 and $1.2 billion above the level requested by the administration. The Senate has proposed $28.6 billion for the same programs, 4.1 percent more than last year and nearly $1.8 billion more than the president's request
In the House budget, R&D funding for the National Science Foundation (NSF) would rise 8.3 percent. R&D funding for the National Aeronautics and Space Administration (NASA) would increase 4.5 percent, compared to the flat funding proposed by the president. With the exception of the Department of Commerce, most other R&D funding agencies would see flat funding or small increases but still far more than the administration proposed. Commerce R&D would fall 9.4 percent in the House budget, because the House concurs with the administration plan to eliminate R&D in the Advanced Technology Program (ATP).
Although the Senate is proposing larger overall increases than is the House, it would provide smaller increases for NSF R&D (up 4 percent) and NASA R&D (up 0.4 percent). However, the Senate would provide larger increases for most other agencies. The Senate would boost Department of Energy (DOE) R&D by 8.3 percent, with increases for all three of DOE's missions in defense, energy, and science. In contrast to an administration-proposed cut of nearly 10 percent, the Senate would boost R&D at the Department of the Interior by 4.3 percent. And in contrast to the House and the administration's proposal to zero out ATP, the Senate has proposed substantial increases in not only ATP but also other Commerce R&D programs for an overall increase of 13.5 percent.
In the nine bills drafted thus far, both the House and the Senate would increase funding for basic and applied research. The House would increase basic research funding 2.9 percent to $9.4 billion, including a 9.2 percent increase for basic research at NSF, whereas the Senate has proposed a 3.6 percent boost to $9.5 billion, including large increases for NSF, DOE, and the U.S. Department of Agriculture. If applied research is included, total R&D spending would increase 3.2 percent to $17.8 billion in the House and 7 percent to $18.5 billion in Senate.
The future of the R&D budget, however, is overshadowed by the larger discretionary budget. In April, President Bush requested $661 billion for discretionary programs in FY 2002, a 4 percent increase, but this included only preliminary figures for the Department of Defense (DOD). In late June, the administration proposed a $27 billion increase in the DOD budget to $329 billion. This increased the discretionary request to $680 billion, all of which would go to defense, education, and NIH, with all other domestic discretionary programs receiving less money than in FY 2001.
The April budget projections showed that the president's discretionary proposals, the tax cut, and other budget proposals could be paid for while preserving Social Security surpluses for the next 10 years, allowing all Social Security surpluses to be used for paying down the national debt. In the May congressional budget resolution, Congress factored in the cost of the tax cut and agreed with the president's original $661 billion proposal.
By summer, however, it became increasingly clear that the April budget projections were far too optimistic. At the end of August, the Office of Management and Budget released its revised projections, reporting that the unified FY 2001 surplus projection had plunged from $281 billion to $158 billion. More important, the non-Social Security surplus in both FY 2001 and FY 2002 had narrowed to a projected $1 billion, with surpluses of just $2 billion in FY 2003 and $6 billion in FY 2004. Shortly thereafter, the Congressional Budget Office (CBO) released its own revised projections, which showed that because of the tax cut and the slowing economy, the non-Social Security surplus in FY 2001 would completely disappear. The CBO projects a $9 billion on-budget (excluding Social Security and the U.S. Postal Service fund) deficit in FY 2001 and further on-budget deficits in FY 2003 and FY 2004. In FY 2002, however, the CBO analysis projects a tiny $2 billion on-budget surplus because of projections that assume discretionary spending will grow at the level of inflation after FY 2001.
The dilemma facing lawmakers is simple: It is impossible to preserve the entire Social Security surplus in FY 2002 while at the same time increasing spending on defense, education, and other discretionary programs.
There will be too little time in September to approve all of the appropriations bills through the normal process, especially if there are vetoes. In the end, Congress may be forced to bundle several unfinished or vetoed bills together into an omnibus appropriations bill, negotiated behind closed doors by congressional leaders and administration officials. Only then will it become clear how lawmakers plan to deal with the Social Security trust fund issue: quietly, openly, or disguised in budgetary gimmicks.
Left hanging in the balance is the fate of federal R&D. Although DOD will almost certainly receive large increases no matter what happens, the appropriations outcomes for the nondefense agencies, including NIH, are still unclear. Although the House and Senate have so far offered modest increases for the majority of these programs, setting final funding levels will be difficult in this budget environment. It is uncertain whether the president will go along with the higher funding levels or whether he will insist on his requested levels in order to conserve funds for his priorities. For all the agencies, even DOD and NIH, it may be a long fall of waiting.
"From the Hill" is prepared by the Center for Science, Technology, and Congress at the American Association for the Advancement of Science (www.aaas.org/spp) in Washington, D.C., and is based on articles from the center's bulletin Science & Technology in Congress.