Only NIH escapes House cuts in nondefense R&D budget % change 3 10 5
Total nondefense R&D
ι Μ 11 Μ ι ym -10
III
L_I_CE^^H * Energy0
-15 -20 -25 I Transportation
-30 -35
•Commerce
a Percent change in fiscal 1996 budget from fiscal 1995, after 1995 rescissions, b Energy Department nondefense R&D. Source: American Association for the Advancement of Science
It is hard to gauge the impact of such large funding cuts. The cuts still seem far away at research universities and hightech corporations. William E. Kirwan, president of the University of Maryland, College Park—which received about $159 million in competitively funded re search grants this year—notes, " W e have . . . a brief grace period to begin ab sorbing cuts and to prepare for a sea change down the road in the nature of the sponsored research w e undertake and the manner in which that research is conducted/' U.S. industry will have to do some rethinking, as well. At a recent Wash ington, D.C., meeting of the Industrial Research Institute (IRI), corporate R&D directors discussed the effects of feder al cuts on industrial R&D. The shortterm impact would be small, says IRI Executive Director Charles F. Larson, but the longer term impact might be quite serious. Larson says the risk-sharing that the research industry n o w does with the government definitely would be missed. Cancellation of programs such as the Commerce D e p a r t m e n t ' s A d v a n c e d Technology P r o g r a m w o u l d b a d l y shake industry's confidence in the gov ernment as a partner. And, he stresses, despite what some members of Con gress claim, industry will not come for ward to replace federal funds. Overall, the proposed cuts would turn back the clock on R&D progress 10 to 15 years, he adds. David Hanson
Blocking telomerase RNA halts cell proliferation A team of researchers has cloned the ribonucleic acid component of h u m a n telomerase, an enzyme that directs the synthesis of structures called telomeres at the ends of chromosomes. The team finds that in cell cultures, inhibiting the telomerase R N A w i t h a n antisense RNA resulted in telomere shortening and cell death—supporting the idea that telomerase is a promising target for anticancer therapies. Telomeres, which in humans consist of a sequence of six nucleotides repeated hundreds of times, have long been known to play a role in maintaining the structur al integrity of chromosomes during cell division. A variety of research has led to the concept that the progressive shorten ing of telomeres that accompanies nor mal cell division contributes to cellular aging. The prior research also has led to the hypothesis that telomerase, which isn't normally expressed in cells other than reproductive cells, is required for the long-term growth of cancer cells. But testing that hypothesis has prov en difficult, because telomerase is an elusive enzyme. It contains an RNA component and a protein component. The telomerase RNA provides the tem plate for the repeating sequence of telo mere DNA and may participate in the catalytic reaction that forms telomeres. Very little is known about the protein component of telomerase. Researchers led by Bryant Villeponteau and Calvin B. Harley of Geron Corp., Menlo Park, Calif., and Carol W. Greider of Cold Spring Harbor Labora tory in New York have fished the RNA component of h u m a n telomerase (hTR) out of a library of RNAs prepared from cells known to be producing telomer ase [Science, 269, 1236 (1995)]. They have shown that mature hTR is about 450 nucleotides long and distinct from telomerase from ciliates or yeast. The team also created antisense hTR constructs—which encode RNA se quences complementary to hTR—and introduced them into h u m a n cancer cells growing in culture. At first, the cells expressing antisense hTR grew normally. However, after repeated cell divisions, 33 of 41 antisense-expressing cultures began to die. The team's data suggest telomeres in the dying cells were shortened due to inhibition of telo merase activity.
"These results indicate the human telo merase is a critical enzyme for the growth and proliferation of immortal tu mor cells," says Harley, w h o is vice president of research at Geron. "Further, we now have demonstrated that an in hibitor of telomerase has potential as a specific and effective therapeutic against human cancer." A scientist familiar with the team's work says it was a "tremendously diffi cult task to clone" hTR. The scientist calls the antisense experiment particularly im portant because it showed that, in tumor cells, "even partial inhibition of telomer ase can lead to arrest of cell growth." In a companion paper in the same is sue of Science [269,1267 (1995)], Greider, Villeponteau, and coworkers also re port cloning the RNA component of m o u s e telomerase. They show that about 65% of its sequence is identical to that of hTR. Access to the RNA compo nent of mouse telomerase will facilitate investigation of the mechanism and reg ulation of mammalian telomerases, the researchers suggest. Rudy Baum
Iraq was poised to use biological arms in 1991 Iraq finally has admitted to the United Nations that it ran an active biological weapons program that produced huge stocks of armaments that it could have used against U.S. and allied forces in the 1991 Persian Gulf War. Iraqi Deputy Prime Minister Tariq Aziz told Rolf Ekeus, executive director of the UN Special Commission (UNSCOM) on Iraq, that in December 1990—a month be fore the war began—Iraq filled 191 bombs and missile warheads with anthrax, botulinum toxin, and aflatoxin. Fifty bombs were filled with anthrax bacteria, 100 with botulinum toxins, and 16 with aflatoxin. Iraq also filled 10 Alhussein missile war heads with anthrax and another 15 with b o t u l i n u m toxin. Alhussein missiles were long-range modifications of Rus sian Scud missiles. However, Iraqi officials told Ekeus, they didn't use biological or chemical weapons because they feared U.S. nucle ar retaliation. This is the first official ex planation of w h y Iraq never deployed SEPTEMBER 4,1995 C&EN 7
NEWS OF THE WEEK the weapons—which, if used, would have had a devastating effect on poorly protected U.S. troops. Gas masks supplied to U.S. troops would have protected them from biological agent inhalation, the primary exposure route for such weapons. But the U.S. had no real-time biological agent detectors capable of warning troops when to don the masks. In addition, only oneseventh of the nearly 700,000 U.S. troops sent to the Gulf region received prophylactic vaccines against anthrax and botulinum toxin. And even troops so protected might have been overwhelmed by high bacteria or toxin levels. Anthrax and botulinum toxin are deadly agents that can kill at very low exposure levels. Aflatoxin is a carcinogenic mycotoxin produced by molds in corn, wheat, and other plants. However, says UNSCOM spokesman Tim Trevan, aflatoxin "causes short-term gastric effects" and thus can be used as an incapacitating agent. Trevan stresses that if killing is the aim, bombs are not the most effective way to deliver proteinaceous substances, because such agents are mostly destroyed by the heat of explosion. But the bombs can be effective in terrorizing enemy troops, he adds. Besides the three biological agents put into weapons, Iraq says it also developed a pathogen to destroy wheat and trichothecene (yellow rain) mycotoxins that were not placed in weapons. And it was researching—but had not yet developed—weapons-quality viral agents. Trevan expects more information about "how far Iraq got on the research and development of the plant pathogens and viruses" as UNSCOM studies the thousands of documents Iraq has turned over. UNSCOM now is selecting the highest priority documents for translation and analysis and will report its findings to the UN Security Council. At a recent press conference, Ekeus said UNSCOM's primary aim is to ensure that Iraq destroyed all its biological arms in July and August 1991, as it claims. The commission will focus on anthrax because botulinum is unstable and difficult to preserve. Until UNSCOM verifies that Iraq has destroyed all its weapons of mass destruction—chemical, biological, nuclear, and missile delivery systems—the Security Council is expected to maintain trade sanctions against Iraq. Lois Ember 8
SEPTEMBER 4,1995 C&EN
age alkanethiolate self-assembled monolayers that cover an etchable base. The new method has several advantages, the researchers say. Diffraction limits conventional photolithography A new microlithography technique resolution to around 100 nm. But neutral that uses atoms instead of light to cre- atom beams, because of their extremely ate patterns on an etchable substrate short wavelengths, show very little difhas the potential to create far tinier and fraction. Additionally, lithography techmore unusual structures than standard niques that use beams of electrons or ions suffer from electrostatic interactions photolithography. The new method—described in last that limit the extent to which the beam week's Science [269, 1255 (1995)] by sci- can be focused. Beams of neutral atoms, entists at Harvard University and the however, can theoretically be focused to National Institute of Standards & Tech- the size of the atom itself. Such control nology (NIST)—exploits the wavelike could lead to improved, more econominature of atoms to do tasks more com- cally manufactured chips and other microelectronic devices. monly thought of as suited for light. The team uses a substrate of thin gold Conventional lithography is performed by projecting a pattern onto a light- on a titanium-primed silicon wafer, coatsensitive surface to selectively remove ed with a 1.5-nm-thick self-assembled the surface layer, exposing a substrate monolayer of dodecanethiolate (DDT). beneath that can then be chemically The image is "developed" with a beam of argon atoms, a small percentage of etched. The Harvard/NIST team—led by which are metastable—that is, with Harvard chemistry professor George M. higher internal energies. This higher enWhitesides and Harvard physics profes- ergy is what causes damage to the sor Mara Prentiss—finds that metastable monolayer, whereas ground-state atoms neutral argon atoms can be used to dam- simply bounce off the surface, leaving it unscathed. And because argon is neutral, it is free from the pitfalls of other elements such Argon beam creates path as chromium or aluminum, which can in monolayer for etching end up plating out on the substrate, Prentiss notes. DDT The researchers experimented with monolayer two types of masking. In one case, they Gold layer Titanium layer placed a mechanical mask—a triangleSilicon wafer shaped aperture with an area of about 3 sq mm—over the wafer and then exposed the substrate to argon. The second type of masking employs the ability of the metastable atoms to be returned to the ground state, or quenched, by light. When the beam of argon atoms is crossed by a beam of light, the metastable argon atoms in the regions exposed to the light return to their harmless ground states and so do not damage the DDT layer. "The light acts like a mask by removing the argon's internal energy," Prentiss says, A self-assembled monolayer of dowhile unlighted areas of the beam redecanethiolate (DDT) on a thin gold tain their damaging properties. film supported on a titanium-primed The team is continuing to experiment silicon wafer is exposed to a beam with different light masks. Because of containing metastable argon atoms nonlinearities in the reaction of the atom (Ar*). Exposure to the Ar* beam rebeam with the light field, the scientists sults in disordered damage to the monolayer, creating a path to etch believe it may be possible to make feathe gold and titanium layers with an tures much smaller than the wavelength aqueous ferricyanide solution. of the light, Whitesides says.
Microlithography uses metastable argon atoms
Elizabeth Wilson
