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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.
