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1 The New Biology Brightly colored cells can be followed as they move, their structural changes can be monitored, and even their internal chemistry is visible with advanced imaging techniques. Such a wide variety of features is now readily observed with specific fluorescent probes and a fluorescence microscope and with computer- imaging methods. This new ability is illustrated on the cover of this report, where cells migrating into a wound are shown. The biochemical, physical, and data- processing techniques that allow such pictures represent just some of the many new research tools that have revolutionized biology and allowed us to observe and begin to understand what is happening inside living organisms and their cells. This report attempts to elucidate the present state of biology and to predict some of this science's goals and research opportunities. Such an attempt is filled with uncertainties, for biological research is dynamic and scientific breakthroughs unpredictable. Our primary objectives are to show the currently exciting activity in biology and to explore foreseeable research opportunities; we fully appreciate the explosive nature of biological research and the near impossibility of anticipat- ing the many directions that may assume central importance in the immediate future. We are afforded some help in anticipating the future by our recognition of the unity of biology. Valuable information on intractable research systems can be gained by drawing direct parallels from more tractable research systems. For example, although substantial differences exist among yeasts, plants, and animals, their mechanisms of gene expression at the molecular level are strikingly similar. As a result, each new bit of information obtained by studying yeasts and other model organisms has a good chance of being useful for understanding many other experimental systems. The principles of physics, chemistry, and biology that apply to living systems, be they entire ecosystems, unicellular organisms, or 15

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16 OPPORTUNITIES IN BIOLOGY individual organelles, operate at the core of biological function. The main role for biologists today is to elucidate these basic principles and determine how they are modified to produce the diverse world we inhabit. Divisions Between Traditional Disciplines Are Being Removed Over the past two decades, contemporary biology research has been launched into an era in which many new biological principles can be determined and studied experimentally. Quantum leaps in understanding have been made in such areas as enzyme catalysis, molecular recognition, transmembrane signaling, ge- netics, and organismal relationships. With these advances, disciplines such as molecular, cellular, and developmental biology have become impossible to sepa- rate, so that the borders between traditional fields of study have become largely artificial. Similarly, the organismal sciences, such as ecology, are now closely linked to physiology, behavior, and molecular biology. These developments reflect a synergism among disciplines that is unprecedented in the history of biological research. An example is the discovery and characterization of an important new class of antibiotics from the skin of the clawed African frog, Xenopus laevis. Here, the observation that these frogs resist infection led rapidly to the isolation of the protein antibiotic, the sequencing of this protein and its complementary DNA (cDNA), and now to the possibility of controlling infec- tions by using the antibiotic. Spectacular advances are being made in determining the molecular structure of proteins and nucleic acids by physical methods such as x-ray crystallography and nuclear magnetic resonance spectroscopy. Here too, techniques of molecular biology are being used, allowing scientists to analyze the effects of designed changes in the amino acid sequence of enzymes on structure and catalytic func- tion. In the future, the results from these studies will have direct application to the development of improved agriculture and health care by guiding the production of modified preexisting enzymes as well as the production of other new molecules that can be used as therapeutic drugs. Advances made in determining ways in which organisms interact have revolu- tionized the study of ecology. For example, the pheromones, or chemical signals, of insects and mammals have been shown to play crucial roles in the organisms' biology. Pheromones influence the attraction of mates, the recognition of specific mating groups, and the synchronization of biological cycles. Recently, phero- mones have been exploited to alter the behavior of pest organisms in agroecosys- tems to bring about their control without the use of synthetic chemical insecti- cides. A recent application of the techniques of molecular biology has made it possible to monitor the fate of microorganisms released into the environment and has thus contributed to our understanding of ecological principles. Molecular markers produced by recombinant DNA techniques are being developed to facili

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THE NEW BIOLOGY :~::: :.: :~ ~ : ~ If: ~:~Th^~ ~^r`^ra:t~;^n: Phi c hewn ~n"~rf~rm~:~ hi '~nd:~r=il~ ~:nf: ~ti:mn~=th:e~:rem~oval of The ~:~ ~ 17 :~::~ ~FROG~:~SK~I~N~ANTIBIOTIC:S~ Ail: ~:~ ::::: ~ ~ :::: ~:::nvariQ~:af~:th~e W~ncan~ clawed ~.~70Dus~fad~v'~:~Th~Q~'nc~s~o~n~:~ls ~sutured~ane~:~::~ ~ ~ ~ :~:::~::::th~e~:~frog ~:~is~:~r~btu~rned~to;:~:~an:~aq~:u~arium~, ~ widen charae~ensl~leally~;~eem~s~ won't Bias ~:~:div~erse~a~rr~ay of microorganisms.~ln~:1~ 987,~however,~a~b~o:logist:obser~r'~ng:~t~hat~ ~:~ these:~:f~rogs Seldom ~expe:rJence~ any:~postope~ti - ~:~i:~e~bn, ~eve~n~::t~houghtth~:~:~;:~:~:~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ , . ~ receive~:~:~no~:~ppstoperdtive~;~care~,~: began: :~to ~search~:~for:~th:e~ ~:reason:~:~tor~t Ear::: : ~:~res~istance.~:~: ~:~:~ ~ :~ ::: ~A~:~siandard ::~antibiotic ~:~assav~.~ Which ~:~inYo~:h~d::~ ~obse~winn~:~t~he~ ~ badericid~::~ . ~ , . ~ , I: I: ~ en eats: of ~::~s~ us 3st ances on fit: tie Taco mm o n ~ co o no: ~ ~ Came rum, ~ tsoner~cn~a~ Do: waste ~:~:~ u - ~t0 ~r~mine::~the:~locat'ion:~ in~:th~e fro9::6f t~hypoth~s:iz~ed~ antimicro~al~:::~:~ ::::: agent. :~Antl~mic:robla ~activ~ty::~:was~c :~m~onstrates ant As ~ow~n~;to ice ~ ll9 ,:e~st~:~ln~ ::;: Akin extracts. Winnow that~the~30catbn~6f th~e~antibiotic~was~determined,~its~char-~ acteriz~t~ion~cou~W~ b~gin.~Standard~b oGhemical~purification pr~cedures~were~ ~used~;to~lsolate~t~h~a~biotic.~lt~was~eventu~f ~shown~to:~be~a:~newl class~of~ in~ ~l~h~Q~uentiv~nam~ed~ ~maaainins.~ f~m~th6~ ~H~ebrew~woid~magain,~ ::: ~ m~:ean~in~g~::~:~sh:ie~id.:~:~:~:~: ~:~:~ ~ A: ~:~:~ ::::: ~:~::~:~ ~Th~-~amino~acid~sequ~ence~of~t~he~rnagainins~was~determined.~This~se-~ quence~was~than~used~to~synth~esize short ~DNA~prdbes~th~at~we~re~us~d~ :: ~ ::~ :~ ~ :~: : : ~ ~ : ~ :: ~ ::: : : : :: ~ : :: Scene I ibrary~of~Comple~mentary~D~JAclones~construct~frotm~m~ess~enger I :: ~ ~ ~ :~RNA~ishlated~from~th~e~frog s~skin.~ ~ThJs~experimerit was of:~;n~rest ;s~ince~the ~ isolate com~em~eritary~DNA clones could by us~d~to ~d~ete~rm~i~ne~t~he ~rnecha :~nism~ofm~againin~prod~uctlone~Specilccomp~le~menta~NA;~clones~weme~ ~ ~ ~ isolate and~their~ nucleic acid~seqluence determined a~analy~ed. :: : : : :: :lbus,~in~a~sin~gle year, a~scier'\ist~progressed~from~an~origin~al observation ~ ~ a~bio~logicai~phenomenon~to~the;~isolation and~6ha~racterization~W~wh~at~;might ::: :~ :~be via very important :anti~tic.: ~R~ap:id~p~rog~ress~:of tli~s~sort~:wo~u:ld:~;not :have~been~ ~ :: ~ ::: ~ ~:poss~ible~ ~without~:~t:he~:~coupling~:::of ~:organismal~biology~with~::microb~o:logy,~bio-~ ~: :~:~:c~he:m~strv.~:~and~:~ molecular booby ;: ~:~:~:::~ ~:~ ~:~ ~ ~ late the determination of organismal spread and survival. Such findings have both theoretical and practical applications. Great advances should be seen in health care, with the development of power- ful new therapeutic drugs and improved methods of diagnosis. Some of the world's greatest health problems will reach critical levels in the next two decades. The disease most discussed is acquired immune deficiency syndrome (AIDS), but other problems may be of equal importance, such as atherosclerosis, Alzheimer's disease, and many forms of cancer. We can expect significant advances through improved diagnosis and treatment. Recombinant DNA techniques will help

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18 OPPORTUNITIES IN BIOLOGY greatly in the development of improved vaccines and in the development of specific DNA probes that can be used for carrier detection. In addition, these techniques make possible the commercial production of powerful cell-regulating molecules such as growth factors. It is hoped that these compounds will have an important role to play in the therapy of many intractable diseases. The genomes of several different types of organisms, including human beings, should be mapped and sequenced by early in the next century. Advances cur- rently being made in the automation of DNA handling and sequencing should greatly facilitate this effort. The enormous amount of sequence information then available will provide an invaluable tool for the medical sciences, as well as for basic biology. Obstacles in program funding and organization are being dealt with and must be overcome before such a project can be camed out efficiently. The characterization and protection of the world's biological diversity will be an important issue during the next two decades. The destruction of the tropical forests, resulting in the loss of species habitat, is largely responsible for the accelerated rate of species extinction. Efforts are now being mounted to slow this extinction rate through improved land management and through such methods as the application of the principles of conservation biology and the formation of seed banks and other collections of living organisms. In addition, biologists are trying to understand more completely the interactions of the organisms that live in rain- forest ecosystems. International cooperation is vital for these efforts to succeed. It is crucial that the United States provide leadership and support in this area. Agriculture should experience many significant changes in the next two de- cades. There is an urgent need to make American agriculture more efficient through research. Good prospects exist to realize benefits from biotechnology in animal and crop agriculture. The production of transgenic agricultural organisms with desirable simple agronomic traits, such as herbicide resistance, has already been accomplished. Scientists are making considerable progress in the produc- tion of transgenic organisms with more complex traits, such as drought tolerance. Obstacles to the transfer of complex traits should be overcome with increased basic research on gene expression and regulation. This report identifies many of the research opportunities that currently exist in biology and attempts to predict some of those that may emerge in the near future. This task is difficult, since biological research is progressing so rapidly. The report takes the reader through the disciplines of biology from molecular structure and function to evolution and diversity, while stressing the interdisciplinary approach taken by most biologists today. After a discussion of basic research, the report then addresses the applications of biological research in medicine, agricul- ture, and other areas. The report concludes with recommendations on the infra- structure needs of future biological research.