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RNA molecules evolve on their own Test-tube models of biochemical evolution have taken a substantial step closer to the way the process occurs in nature. A system in which catalytic RNA molecules are continuously replicated without any intervention from the researchers has been devised by postdoctoral associate Martin C. Wright and professor Gerald F. Joyce in the departments of chemistry and molecular biology at Scripps Research Institute, La Jolla, Calif. In the process, the molecules get better and better at their catalytic function [Science, 276,614 (1997)]. Since the early 1990s, several laboratories, including Joyce's, have been experimenting with directed evolution of DNA and RNA molecules in the test tube. In such experiments, a nucleic acid molecule with catalytic function is identified, separated from others that are poorer catalysts, amplified, and deliberately mutated. Improved catalysts are identified from the mutants, and the process is repeated over and over again. After many such cycles, the resulting molecules have "evolved" into better catalysts than the starting molecules. The new system bypasses the identification and separation steps of directed evolution by putting everything that's needed for the system to cycle in one reaction vessel and choosing a catalytic step that must take place for replication to occur. The researchers use an RNA whose catalytic function is to attach a piece of nucleic acid to the RNA. Polymerases in the reaction vessel specifically target the added segment, so they copy RNAs that have catalytic function and ignore those that don't. "Nothing gets reproduced in this system until it first exhibits catalytic function," Joyce points out. "Those that do the reaction best, of course, get to reproduce sooner and more often. The system has more of the look and feel of natural evolution because it's not an operator-manipulated process." From the experimenter's point of view, resembling natural evolution more closely has both advantages and disadvantages. A big advantage is speed. In one day, this system can complete as many replication cycles as any lab has ever done before, Joyce says. The previous record—63 cycles—took several years to accomplish; this system can do that in less than six hours. Each "generation" takes about five minutes, Joyce notes, "so you can see evolution in real time. You can actually get somewhere in a couple of days." 10 APRIL 28, 1997 C&EN
The disadvantage, at least for some applications, is that the system itself, and not the scientist, selects what mutations are advantageous, and so it evolves along its own rules of "fitness." But natural evolution also takes unexpected twists. "In vitro biochemical systems such as [the ones developed in the Joyce laboratory] may provide a new dimension to studies of classic problems in
organismal ecology and evolution," suggest chemists Andrew D. Ellington and Michael P. Robertson of Indiana University, Bloomington, and molecular biologist Jim Bull of the University of Texas, Austin, in an accompanying commentary in Science. The very unpredictability of outcome may make it a useful model for studying how natural selection works in nature. Rebecca Rawls
Raw material costs hit chemical earnings The initial rush of quarterlyfinancialreports shows a wide divergence among chemical company earnings forfirstquarter1997. At the extremes, Arco Chemical's earnings dropped 55% and Monsanto's rose 32% compared with last year'sfirstquarter. The main reason for the wide spread is that chemical companies that are highly dependent on petrochemical feedstocks had problems during the quarter. As Alan R. Hirsig, Arco Chemical's president and chief executive officer, points out, "During the first quarter, high raw material costs, coupled with weak product pricing, compressed margins in virtually all of our businesses." Monsanto, on the other hand, had strong increases in two of its four operating units: chemicals, driven by Saflex plastic interlayer and performance materials,
and food ingredients, through cost reductions. Operating profits at the company's agricultural products unit were also up sharply when nonrecurring charges are eliminated, leaving only the company's Searle pharmaceuticals unit with a decline. Many companies' sales volumes did increase during the quarter, but prices remained soft. Eastman Chemical Chairman and Chief Executive Officer Earnest W. Deavenport Jr. explained his company's 36% earnings decline from the yearearlier quarter: "The chemical intermediates segment had solid volume growth. However, earnings for the segment were slightly lower than thefirst-quarter1996 because of lower selling prices and higher raw material costs." He also pointed out that "worldwide increases in industry capacity, along with near-term addi-
Chemical company earnings: Declines, gains evenly split FIRST QUARTER Sales
Earnings8
Change from 1996 Sales
($ millions)
Profit marginb 1997
1996
12% -5 -55 -31 9
9.2% 10.2 4.7 6.8 8
9.3% 7.8 10.8 8.7 7.4
Earnings
$ 1,153.1 198.4 1,029.0 432.0 306.5
$ 106.0 20.2 48.0 29.4 24.6
14% -27 5 -12 1
4,992.0 11,211.0 1,171.0 239.2 493.5
452.0 1,020.0 72.0 12.1 52.9
0 4 -7 15 -8
-5 13 -36 -23 -20
9.1 9.1 6.1 5.1 10.7
9.6 8.3 8.9 7.6 12.3
Monsanto Morton International Nalco Chemical Olin Rohm and Haas
2,574.0 1,027.0 334.6 591.2 986.0
343.0 109.3 35.8 41.8 104.0
12 3 11 -15 -1
32 18 19 -18 4
13.3 10.6 10.7 7.1 10.5
11.3 9.3 9.9 7.3 10.1
Stepan Union Carbide Witco
139.7 1,638.0 568.5
4.5 157.0 24.6
7 9 -4
-21 0 4
3.2 9.6 4.3
4.3 10.5 4
Air Products Albemarle Arco Chemical Cabot Cytec Dow Chemical DuPont Eastman Chemical Georgia Gulf Great Lakes Chemical
a After-tax earnings from continuing operations excluding significant extraordinary and nonrecurring items, b After-tax earnings as a percentage of sales.
tional capacity under construction, have created the conditions for the significant price erosion that has occurred for [polyethylene terephthalate] bottle resin." The one company that had it both ways was DuPont. Earnings declines in some of its chemical operations were buffered by increases in oil prices for its energy subsidiary, Conoco. Earnings, excluding special items, rose 13% for the quarter to $1.02 billion. But this included a 55% increase in after-tax earnings from petroleum operations. Excluding petroleum, combined earnings from other operations were essentially unchanged, despite a very healthy 30% increase in earningsfromfiberoperations. William Storck
covered industries, particularly trade associations representing companies that buy, store, and sell chemicals and petroleum products. Their concerns were reflected in comments made during the rule's development and in a lengthy debate within the Administration during the Office of Management & Budget's (OMB)reviewof the proposal, which began last November. "This was a rush to judgment," says John Huber, vice president of the Petroleum Marketers Association of America. "Although the rule was being substantively evaluated by OMB, [the Clinton Administration] needed a press release for Earth Day, and so all our negotiations to lessen the impact on our businesses were imme-
Toxic chemical release reporting expanded An additional 6,100 facilities now will report toxic chemicals released to the environment, President Clinton told reporters on Earth Day, April 22. The new rule brings to more than 31,000 the number of facilities required to report emissions for the Toxics Release Inventory (TRI). The rule covers seven industry sectors that previously had avoided the act's reporting requirements: metal mining, coal mining, electric utilities, commercial hazardous waste treatment facilities, chemical and allied product wholesalers, bulk petroleum terminals, and solvent recovery services. Theregulationalsorequireschemical manufacturers toreportemissionsfromcertain hazardous waste treatment activities, but a Chemical Manufacturers Association spokesman says the addition will have little impact because most chemical companies alreadyreportthose releases. In announcing theregulation,the president noted that manufacturers have cut emissions 43% since thereportingact became law a decade ago. He attributed this decline to the act's provisions giving communities "the power to protect themselves" through knowledge about "exactly what substances are being released into their neighborhoods." "The measure probably has more support across all lines in America than any other thing that we can do," added Vice President Al Gore. Both men pledged to continue the Administration's efforts to expand the reporting requirements. Although applauded by environmental groups and community organizations, the additions were criticized by the newly
Clinton and Gore pledge further expansion toxic reporting requirements.
diately dispatched as unimportant. We're furious; that's the bottom line. "We hope they made some mistakes in preparing the rule because we will sue them under anything we can find in the Regulatory Flexibility Act. Even if we have to hang our hat on some nit-picking procedure, we'll find it and use it." Officials of the National Association of Chemical Distributors and the Petroleum Transportation & Storage Association also expressed disappointment and anger at the Administration's decision. They say the rule will be particularly burdensome and expensive for small businesses that, despite small profits and few employees, handle chemicals in amounts large enough to exceedreportingthresholds. Huber acknowledges that emissions do occur but asserts that they are small. "These are not wastes to us; we don't want to throw them away." But according to Maria J. Doa, chief of EPA's TRI branch in the Office of Pollution Prevention & Toxics, the regulation simply closes a loophole in reporting requirements.
"Only through TRI do you get specific information on the exact release of chemicals," she said. "What if you live in a community with many small facilities all with medium-sized releases? Well, they add up. So when we examined [the possibility of| including these industries, we felt their inclusion would provide valuable information." Doa also notes that the final rule contains a provision committing EPA to hold stakeholder meetings intended to develop a new system that will make reporting less burdensome and more costeffective. The guidance document must be produced by November 1997. The first reports under the new regulation are due July 1999. The associations are not encouraged. "This is an attempt to sugarcoat the rule for small business," says Mark S. Morgan of the Petroleum Transportation & Storage Association. "Stakeholder meetings are fine, but if EPA didn't listen to us up front, which they didn't, I don't have a lot of hope that they will listen to us this time. But we'll take part." "Everybody's willing to study things," adds Huber, "and create stakeholder groups with citizens, public-interest organizations, and others. But we don't need the Sierra Club and citizens sitting at the table with us. They're not interested in alleviating our burden." Jeffjohnson
House endorses patent law changes After two years of rancorous debate, the House of Representatives has given its stamp of approval to legislation revamping the nation's 200-year-old patent system. If, as is likely, H.R. 400 becomes law, it will fundamentally change patent practice, bringing U.S. law into step with international norms and changing the operations of the Patent & Trademark Office (PTO). To a great extent, the bill harmonizes U.S. law with those of Europe and Japan. It requires publication of most patent applications 18 months after they are filed and provides a defense against infringement for prior domestic users of a patented technology. The bill also converts PTO into afreestandinggovernment corporation and allows it to keep all the APRIL 28, 1997 C&EN 11
