I n April 1997 Dr. Frank Baker, an emerg e n c ymedicine specialist from the Chicago area, tookp a rt in a clinical trial to test a form of art i f i c i a l

skin for treating insulin-dependent diabetics whose tissuehad been degraded by the secondary effects of chronic highblood sugar. Baker, who has had diabetes for more thanfour decades, was in danger of losing a foot because ofh a rd-to-heal skin ulcers. For him the trial results wereclose to miraculous: the laboratory - g rown skin didn’tjust cover and protect his wound, it released chemicalsthat caused his own tissue to grow back much faster. As Baker put it, the artificial skin “saved my foot.”

The material that worked this medical wonder wassynthesized from polymers, long molecular chains form e dby the chemical bonding of many small molecules of oneor more types. Most people are probably more familiarwith polymers in the form of the plastics that make upsuch everyday products as plastic food containers, bubblewrap packing, and videotape. But polymers also arefound every w h e re in nature. Wood, animal and veg-etable fibers, bone, and horn are polymers, for example,as is the deoxyribonucleic acid (DNA) inside the cellnucleus and the membrane that separates one cell fro ma n o t h e r. Indeed, when thepolymer industry began in thenineteenth century, it madematerials that w e re derivedf rom natural p o l y m e r s —a rtificial celluloid from plant cellulose, for instance.Eventually the industry begansynthesizing new materials,such as nylon, that re p l a c e dnatural materials and weremade without natural pre-cursors. Today products that

straddle the boundary between living and nonliving—like Frank Baker’s artificial skin—are beginning to sug-gest exciting possibilities for improving human health.

Behind these developments lies more than 150 years of pro g ress in polymer re s e a rch by hundreds of scientists as well as more than a century of re s e a rch in cell biology and o rgan transplants. As described in the followinga rticle, which highlights the work of only a few of manyre s e a rchers, the path to recent advances in modern med-ical treatment began with the investigations of scientistsi n t e rested in a better basic understanding of chemistryand biology.

Sorting Out Nature

Humanity has a long history of trying to under-stand the substance and structure of the physicalworld around us, whether by simple observation orexperimental manipulation. In ancient Greece, forexample, Aristotle concluded that all materials weremade up of combinations of only four elements: air,earth, fire, and water. During the Middle Ages,

alchemists tried in vain toconvert common metals intogold. By the late eighteenthcentury, chemists had begun

P O LYMERS AND PEOPLE

THE PATH FROM RESEARCH TO HUMAN B E N E F I T

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BEYOND DISCOVERYBEYOND DISCOVERYT M

Artificial skin grown in thelaboratory on scaffolding madeof long chain molecules calledpolymers can help heal thewounds of patients with ulcerscaused by poor blood circula-tion. (Photo courtesy ofOrganogenesis Inc.)

synthesizing and breaking down chemicals in an effortto determine their fundamental components. Early inthe nineteenth centur y, English chemist John Dalton,observing that chemicals would combine only in specific ratios, concluded that matter was made ofindivisible “atoms” (a concept first proposed by theGreek philosopher Democritus in about 400 BC).Nineteenth-century chemists also determined that it was possible to synthesize so-called organic com-pounds, once believed to be made only in living org a n-i s m s , from inorganic chemicals.

Even as chemists pursued their investigations intothe nature of nature, inventors were creating newmaterials by treating natural substances with variouschemicals at elevated temperatures and pressures. In 1839, American inventor Charles Goodyear discov-ered a technique, which he called vulcanization, formanipulating the properties of the sap from rubbertrees by treating it with heat and sulfur. The processconverted a gummy, springy material used mainly toerase (“rub out”) into a dry, tough, elastic materialthat would make automobile tires possible—and eventually a transportation revolution.

Investigators working at the theoretical level wereequally productive, arriving at a series of independentrealizations that would eventually lay the foundation for the polymer industry. In 1858, German chemistFriedrich Kekulé developed the framework for under-standing the stru c t u re of organic molecules when heshowed that a carbon atom can form chemical bondswith up to four other atoms and that multiple carbonatoms can join together to create long chains—a dis-c o ve ry also made at about the same time by Scottishchemist Archibald S. Couper. Then, in 1874, Jacobusvan’t Hoff of the Netherlands and Joseph Le Bel ofFrance independently suggested that the carbon atom’sfour bonds are arranged so that they point at the cor-ners of a tetrahedron, or pyramid. Since carbon atomsa re the framework for natural and artificial polymers, thetwo discoveries would in time furnish a thre e - d i m e n-sional p i c t u re of the molecular stru c t u re of polymers.

Launching the PolymerIndustry

In 1870, four years before the structure of the carbon atom was elucidated, American inventor JohnWesley Hyatt won a contest to find a material for billiard balls to replace ivory—then as now in shortsupply. Hyatt’s prize-winning contribution was cellu-loid, based on cellulose, a polymer that is the basicstructural material of plant cell walls. It was the startof the polymer industr y. Hyatt treated cellulosenitrate, or guncotton—an explosive material made by exposing cotton plant fibers to nitric and sulfuricacids—with alcohol and camphor. What he got was ahard, shiny material that could be molded when hot.Cheap and uniform in consistency, this new materialdid indeed replace ivory in billiard balls. Occasionallythough, when the celluloid billiard balls collided, theycreated a small detonation like a firecracker because of the explosive nature of cellulose nitrate, which is related to trinitrotoluene (TNT) in composition.Celluloid also replaced horn in combs, found wideuse in housewares, and was made into the first flexible photographic film. In 1887, Count Hilaire deChardonnet created a related product when helearned to spin cellulose nitrate into Chardonnet silk,the first synthetic fiber to enter production and aforerunner of rayon, nylon, and Dacron.

Both celluloid and Chardonnet silk were polymersc reated by altering natural polymers. The first tru l ysynthetic polymer did not come along until 1909,when American inventor Leo Baekeland treated phe-nol, or carbolic acid, another derivative of coal tar,with the pre s e rvative formaldehyde under heat andp re s s u re. His product, Bakelite, was hard, immuneto harsh chemicals, electrically insulating, and heatresistant—characteristics that made it useful for amyriad of household goods and electrical part s .Soon Bakelite was being used to make tools,machines, and cookingware.

Science Explains Polymers

The rapid success of Bakelite sparked a flurryof synthesis investigations and innovations in bothAmerica and Europe. As the financial stakes rose, the hit-or-miss garage inventor’s approach that had dominated the industry gave way to more systematic

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A key discovery in the late19th century was that thecarbon atom can formbonds with up to fourother atoms, each markingone corner of a tetrahe -dron, or pyramid. Manycarbon atoms can bond,forming long molecularchains, or polymers, in possible combinations thatnumber in the billions.

efforts. No longer content simply to tinker with rawmaterials and various processing conditions, scientistsbegan basic research designed to understand the mol-ecular structure of polymers.

In 1920, the German chemist Hermann Staudinger,fascinated by the seemingly unique properties of poly-mers, began investigating their behavior and chemicalcharacteristics. Staudinger’s research suggested thatpolymers are composed of long chain molecules of many identical or closely related chemical units.Moreover, he suggested that their unusual tensilestrength and elasticity are a result of that great lengthor, in chemical terms, of their high molecular weight.Staudinger’s ideas may not sound especially radicaltoday, but at the time he was ridiculed by his col-leagues in organic chemistry, and his theories had little impact on the scientific community. Indeed, the existence of polymeric chain molecules was notaccepted until 1928, when Kurt Meyer and HermanMark, working for the German chemical trust I. G.Farben Industrie in Ludwigshafen, demonstrated theirexistence by examining the crystalline structure ofpolymers with x-rays. Many years later Staudingerwas recognized for his efforts and persistence, whenin 1953 he became the first polymer chemist toreceive a Nobel Prize.

Staudinger’s key insights—that polymers are longchains of many small chemical units and that chainlength plays a crucial role in determining physicalp ro p e rties and behavior—pointed up the need fortools to assess molecular weight and thus chain length.One of the first tools was the ultracentrifuge, inventedby the Swedish chemist Theodor Svedberg. The ultra-centrifuge spins samples at very high speeds and canseparate molecules according to their size. It can beused to estimate both the size of the molecules andthe distribution of sizes in a given polymer sample.

By the end of the 1920s, armed with better toolsand better theories, polymer scientists were makingdramatic breakthroughs. In 1928, the DuPontCorporation hired chemist Wallace Hume Carothersto build new kinds of polymers in a new laboratorydedicated to basic research. To test Staudinger’s still-controversial theory, Carothers carefully joined smallorganic compounds into long chains and examinedthe properties of his products. He found that collec-tions of very long chain molecules produced stiffer,stronger, and denser materials. By 1930, Carothers’ssystematic synthetic approach was bearing fruit as he came up with a new class of polymers calledpolyamides, or “nylons.” These polymers could bemelted and drawn into a remarkably strong fiber.

The Glory Years

When nylon was introduced as a substitute for silk in stockings in 1937, the new material—strong,cheap, and easy to work with—became an unqualifiedcommercial hit. The instant success of nylon fibersand neoprene, the first synthetic rubber, taught thepolymer industry an important lesson—that basicresearch can lead to products that can replace naturalmaterials. It can also eventually lead to Nobel prizes.Paul Flory of Stanford University received one for hiscareer contributions to polymer science while workingin both academic and industrial laboratories. Florywas instrumental in developing the theory of howpolymer molecules behave, especially through mathe-matical and statistical analysis of the shape and prop-erties of polymer chains.

The 1930s were the glory years for the develop-ment of new synthetic polymers, producing polyvinylchloride (PVC), polyurethane, polytetrafluoroethylene(Teflon), and polystyrene, which together would

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In 1920, German organic chemistHermann Staudinger proposedthat the unusual strength andelasticity of polymers was due totheir great length and high molec-ular weight. (Photo of HermannStaudinger courtesy of Institutefor Macromolecular Chemistry,Freiburg, Germany); (Diagramof a polymer, in this case, polyeth-ylene strands, courtesy of Biografx)

revolutionize the fabric, coating, houseware, packag-ing, and insulation industries. These new materialsbore no resemblance to their raw materials (whichw e re commonly oil or natural gas) and were celebratedfor their very artificiality. Because many of these polymers became malleable when heated, they cameto be called “plastics” from the Greek word meaning“able to be molded.”

Another important development beginning in thelate 1930s and 1940s was the large-scale production ofa rtificial ru b b e r, spurred by the booming automobilei n d u s t ry and the military demands of World War II.By 1930, two new forms of artificial rubber had beendeveloped in Germ a n y, both based on the petro l e u mb y p roduct butadiene. As tensions grew in Europe, theU.S. government recognized the vulnerability of thenation’s rubber supply and in 1941 established theRubber Reserve Company to produce 10,000 tons ofrubber annually. By the middle of 1942 the pro d u c-tion goal had soared to 850,000 tons annually inresponse to the Japanese occupation of the EastIndies, whose vast rubber tree plantations had suppliedthe world with the raw material for ru b b e r. Polymerscientists and engineers worked together to develop a variety of new processes to meet wartime demands.One of the most important was a light-scattering tech-nique developed by Peter Debye of Cornell University,who used it to determine the molecular weight and

sizes of very long polymers. Polymer scientists usedthis knowledge to analyze the artificial ru b b e r. Modernversions of his technique are invaluable to re s e a rc h e r scharacterizing complex molecules.

Polymers from Petroleum

Although both the science and technology ofpolymers had advanced remarkably by the early1950s, formidable challenges remained to be sur-mounted. Because of the abundant supply and lowcost of their component petroleum-derived buildingblocks or “monomers,” hydrocarbon polymers con-taining only carbon (C) and hydrogen (H) atoms represented a potentially highly useful class of sub-stances. Particularly attractive targets were polymersof the smallest and most abundant such monomers,ethylene and propylene (containing two and three carbon atoms, re s p e c t i v e l y ) . The general ability ofsuch molecules, containing pairs of carbon atoms connected by “double bonds,” to join together to f o rmlong chains (see figure opposite) had long been re c o g-nized (a familiar example being polystyrene). H o w e v e r,in the case of ethylene and propylene this presented aformidable challenge. The “polymerization” of ethyl-ene had been accomplished, but only at undesirably

1 8 3 9Charles Goodyearinvents the process ofvulcanization, whichmakes rubber into adry, tough, springymaterial.

1 8 5 8Chemists Friedrich Kekuléand Archibald Coupershow that organic molecules are made up of carbon atoms combinedchemically into differentshapes.

1 9 2 0Hermann Staudinger proposes thatpolymers are long chains of smallerunits that repeat themselves hun -dreds or thousands of times. Helater receives a Nobel Prize for his research on the synthesis andproperties of polymers.

1 8 7 0John Wesley Hyatt mar-kets celluloid, a plasticmade of chemicallymodified cellulose, alsocalled cellulose nitrate.

1 8 8 7Count Hilaire deChardonnet introduces away to spin solutions ofcellulose nitrate intoChardonnet silk, the firstsynthetic fiber.

1 9 0 9Leo Baekeland creates Bakelite, the first completelysynthetic plastic.

TimelineThis timeline shows the chain of research that led to an understanding

of polymers and the development of some of their medical uses.

Late 1920s Wallace Hume Carothersand his research group at DuPont synthesize anddevelop applications forsynthetic polyesters, neoprenes, and nylons.

1920s Kurt Meyer and Herman Markuse x-rays to examine theinternal structure of celluloseand other polymers, providingconvincing evidence of themultiunit structure of somemolecules.

1 9 3 0Germans develop two types of synthetic rubber (Buna-S and Buna-N) frombutadiene, a petroleum byproduct.

high temperatures and pre s s u res, yielding polymerswhose pro p e rties left much to be desired. The poly-merization of propylene remained to be achieved.

In 1953, while engaged in basic re s e a rch on thereactions of compounds containing aluminum-carbonbonds, the German chemist Karl Ziegler, working at the Max Planck Institute for Coal Research inMulheim, discovered that adding salts of cert a i nother metals such as titanium or zirconium to thesec o mpounds resulted in highly active “catalysts” (substances that speed up chemical reactions) for the polymerization of ethylene under relatively mild conditions. F u rt h e rm o re, the polymers formed in this

w a y, because the chains were longer and more linear,had greatly superior pro p e rties such as stre n g t h ,h a rdness, and chemical inertness, making them veryuseful for many applications.

Building on Ziegler’s discovery, Italian chemistGiulio Natta, working at the Milan PolytechnicInstitute, demonstrated that similar catalysts were eff e c-tive for the polymerization of propylene. Furt h e rm o re ,with such “Ziegler-Natta catalysts” it was possible toachieve exquisite control of the chain length and stru c-t u res of the resulting polypropylene polymers and,t h e re b y, of their pro p e rties. Among other re m a r k a b l eachievements of this class of catalysts was the synthesisof a polymer that is identical to natural ru b b e r.

Industrial applications of “Ziegler-Natta catalysts”w e re realized almost immediately and with varioussubsequent refinements continue to expand. To d a y,polyethylene produced with such catalysts is thel a rgest volume plastic material and, together withp o l y p ropylene, accounts for about half of the U.S.’sc u rrent annual 80 billion pound production of plasticsand resins. The uses of polyethylene and polypro p y-lene extend to virtually every facet of industry anddaily life, including building and construction materials,containers, toys, sporting goods, electronic appliances,textiles, carpets and medical products. In many ofthese applications polymers replace other substances,such as glass and metals, but their distinctive pro p e rt i e s

1 9 4 0 sPeter Debye develops a light-scattering tech-nique for measuring themolecular weight oflarge polymers.

1 9 3 0 sPaul Flory develops a mathe-matical theory to explain thecreation of polymer networks“in which polymer fluids formcross-links and become, likerubber, elastic.” Flory wouldreceive a Nobel Prize for hislifetime contributions to polymer chemistry in 1974.

1 9 5 3Karl Ziegler discoverscatalysts for polymer-ization of ethylene.Giulio Natta synthe-sizes polypropylene.Their discoverieswere recognized by a Nobel Prize.

1 9 7 5Robert Langer and M. JudahFolkman use polymers to isolatechemicals that stop the formation ofblood vessels, suggesting a new wayto attack cancer. These studies alsoestablish the feasibility of controlledrelease of macromolecules.

1 9 6 3Edward Schmitt andRocco Polistina file a patent for the firstabsorbable syntheticsutures, made ofpolyglycolic acid, a key plastic in tissueengineering.

1 9 9 6The U.S. Food and DrugAdministration approvespolymer wafer implants for treating brain cancer.

1 9 8 6Langer and Joseph Vacantidemonstrate that liver cellsgrown on a plastic frameworkcan function after being trans-planted into animals, openingthe door to the new field of tissue engineering.

1 9 9 7Clinical trials show thatartificial skin can healdiabetic skin ulcers,establishing the poten-tial clinical feasibility of tissue engineering.

Polymerization of ethylene and propylene to polyethylene andpolypropylene.

also have given rise to entirely new applications,including medical uses.

In 1963, the Nobel Prize in chemistry was award e dto Ziegler and Natta “for their discoveries in the fieldof the chemistry and technology of high polymers.” Inhis acceptance speech, recalling the circumstances of hispioneering discovery and the scientific obstacles thathad to be overcome, Ziegler went on to say:

“But a much more formidable impediment mighthave presented itself. In order to illustrate this, I mustelaborate on the paradox that the critical concludingstages of the investigations I have reported took placein an institute for ‘coal research.’ When I was calledto the Institute for Coal Research in 1943, I was dis-turbed by the objectives implied in its name. I wasafraid I would have to switch over to the considera-tion of assigned problems in applied chemistry. Sinceethylene was available in the Ruhr for coke manufac-ture, the search for a new polyethylene process, forexample, could certainly have represented such aproblem. Today I know for certain, however, and Isuspected at the time, that any attempt to strive for aset goal at the very beginning would have completelydried up the springs of my creative activity.”

Working with Nature

As new applications for polymers were beingfound, some re s e a rchers wondered whether theycould also play a role in the human body, perhaps in repairing or replacing body tissues and cart i l a g e .The idea was not entirely new. The natural polymercollagen, found in animal connective tissue, hadbeen used as surgeon’s thread for more than 2,500years. And as early as the 1860s, an artificial poly-mer called collodion, invented a decade earlier bythe French chemist Louis Ménard, was used as a liquid dressing for minor wounds. Collodion, madef rom a solution of cellulose nitrate in alcohol ande t h e r, formed a solid film that could be peeled offafter the wound healed. The excellent barrier pro p-e rties of polymers were also central to an experimentin 1933 by Italian biologist Vincenzo Bisceglie, whoimplanted tumor cells encased in a nitro c e l l u l o s emembrane in a guinea pig. The cells survived, pro-tected by the membrane against attack by the hostanimal’s immune cells.

Meanwhile, the question of contending with thebody’s immune system was becoming a critical one inmedicine. Scientists were beginning to recognize that

many diseases of the heart, liver, and kidney actuallyinvolved failures of these organs, and they were initiat-ing eff o rts to replace damaged organs with healthyones. However, the body’s immune cells—which aredesigned to seek out and destroy any foreign tissue—a re unable, for example, to distinguish between anunwanted bacterial infection and a much-desired trans-planted kidney. Although some early drugs, such asc o rt i c o s t e roids, azothropine, and 6-merc a p t o p u r i n e ,helped in combating rejection, the problem began tofade only after 1969, when Swiss microbiologist JeanB o rel discovered that a soil fungus, cyclosporin A,would selectively interf e re with the specific immunecells that drive the rejection reaction. The 1983a p p roval of cyclosporin A by the U.S. Food and Dru gAdministration (FDA) gave transplant surgeons a toolthat has since saved the lives of thousands of patientswith heart, liver, or kidney failure .

Designer Polymers

Cyclosporin A encouraged a wave of transplantsand also helped set the stage for the current rise in“tissue engineering,” as scientists call the constructionof whole artificial organs. Transplant surgeons, who no longer lost patients because of the rejection of their transplants, now were faced with a new frustration—losing patients for lack of donor organs.One of those frustrated doctors was Joseph Vacanti at Boston’s Children’s Hospital, home of the first

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Physician Joseph Vacanti (left) and chemical engineerRobert Langer joined forces in the early 1980s in an effortto create artificial tissues. Within a few years they hadgrown liver cells on a polymer framework, giving rise tothe field of tissue engineering. (Photo of Vacanti courtesyof Charles Vacanti, of Langer courtesy of Robert Langer).

successful human organ transplant. In 1983, Vacantibegan talking with his friend Robert Langer, a chemical engineer at the Massachusetts Institute ofTechnology, about the feasibility of making an artifi-cial liver and possible other artificial tissues to save thelives of his young patients.

It was a tall order. Nobody had built any kind ofworking organ, let alone one as complex as the liver.In addressing this task, Langer called considerableexperience to bear on attacking the problem in arational way. In the mid-1970s, he had developedsome polymer systems for M. Judah Folkman ofHarvard University, who was then investigating therole of new blood vessels in promoting the growth ofcancerous tumors, and was looking for a slow-releasemechanism to release compounds that block thechemical messengers that control angiogenesis, theformation of new blood vessels. Langer discoveredthat polymers such as ethylene-vinyl acetate, whichabsorb very little water, could slowly deliver thesechemical messages.

One polymer that Langer eventually focused onwas polyglycolic acid, or PGA, which was also used in synthetic degradable sutures and had reached themarket in 1970. PGA itself had been known since atleast 1950, when Norton Higgins of DuPont patenteda three-step process for making it from glycolic acidby carefully manipulating temperature and pre s s u re .The patent Higgins filed did not mention medicalapplications, but in 1963 Edward Schmitt and RoccoPolistina of American Cyanamid Company filed apatent for the formation of sutures from PGA.When the sutures reached the market seven yearsl a t e r, they were rapidly adopted as a strong, re l i a b l e ,and workable replacement for the traditional colla-gen-based absorbable sutures that surgeons had used until then.

Using PGA and similar polymers, Langer crafteddegradable and nondegradable polymer pellets into an intricate porous structure that allowed the slowdiffusion of large molecules. (This finding is thefoundation of much of today’s controlled drug deliv-ery technology.) Loaded with chemical messengers,the pellets played a key role in Langer and Folkman’s1975 discovery in cartilage of the first compound thatblocks the formation of new blood vessels, therebyhalting tumor growth.

In 1984, at about the same time he wasa p p roached by Joseph Vacanti, Langer teamed upwith Henry Brem, a brain cancer surgeon at JohnsHopkins Medical Institutions, to test his new techniques using polymers against brain cancer.Although there were new tools for finding tumors,including computed tomography and magnetic re s-onance imaging scanners, the most malignant braincancers remained largely untreatable. Cancer cellsremaining after the tumor’s removal were pro t e c t e df rom chemotherapy drugs by the so called blood-brain barr i e r, which prevents a variety of blood-b o rne chemicals from penetrating the brain. Bre mw o n d e red if polymers could slowly release cancer-killing drugs right where they were needed—in thebrain itself.

Langer responded by designing surface-degradingpolymers that released medicines at a controlled rate.In 1992, Brem and Michael Colvin, now director of the Duke Cancer Center, implanted drug-bearingpolymer wafers after brain surgery. The wafers prolonged the lives of both experimental animals andhuman patients. Since the chemicals were releasedlocally, they did not result in the systemic toxicity typ-ical of anticancer drugs. With FDA approval in 1996,the wafers represent the first new treatment for braincancer in 25 years. Similar slow-delivery systems are

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Roughly the size of a dime,biodegradable polymerwafers (left) can beimplanted in specific placesin the brain after cancersurgery to deliver cancer-killing drugs at a controlledrate. The implanted wafersdeliver drugs only to thebrain (far right) ratherthan to the whole body.(Photos courtesy of GuilfordPharmaceuticals)

now being used to treat prostate cancer, endometrio-sis, and severe bone infections.

All these efforts laid the groundwork forresearchers’ continuing search for a framework forgrowing replacement body parts and organs, such aslivers. By now scientists had learned that human cellsgrown on flat plates did not produce the normal arrayof proteins, while cells grown on three-dimensionalscaffolds had relatively normal biochemistry. At firstthe best results were obtained from PGA, but sincethe best source of fibrous PGA in 1984 was degrad-able sutures, hours were spent unwinding sutures totransform the fibers into meshlike plastic scaffolds tosupport liver cells. Still, by 1986, liver cells on plasticframeworks were surviving and functioning aftertransplantation into animals, laying the groundworkfor using polymer scaffolds to create a variety of tis-sues, from bone to cartilage to skin.

The polymer scaffolds, made with nonwoven fabric techniques borrowed from the textile industry,have now been used to grow at least 25 types of cellsin animals or people and have thus become a kind ofgeneric framework for artificial organs. Biotechnologyfirms are using the scaffolds to make artificial skin fortreating diabetic ulcers and severe burns. They multi-ply living cells in culture (from tissue that is normallydiscarded during surgery), and then “seed” the cellson the polymer scaffold. Applied to the patient’swound, the material protects against deadly infectionand fluid loss. More important, the cells it carriesrelease chemical growth factors, signals that stimulatenormal cellular growth at the wound site. Thesechemicals account for the roughly 60 percentimprovement in healing that diabetics like FrankBaker experience with artificial skin. As tissue engi-neers look to the future, they are talking about usingpolymer scaffolds to grow nerve cells for use in spinal

cord repairs, bone or cartilage cells for joint repairs,pancreatic cells to make insulin for diabetics, and livercells to make livers for transplantation.

Through all of these efforts by many kinds of scientists, several facts stand out. The path from needto benefit travels through many areas of science andtechnology and depends crucially on the insights pro-vided by basic research. The first polymer inventorsmade progress by transforming natural materials inhit-or-miss fashion, but their work greatly acceleratedafter basic researchers clarified the fundamental char-acteristics, such as the relation between size or molec-ular weight and physical properties, that govern thebehavior of polymers. Similarly, the progress in medicine and biology that gave birth to organ trans-plantation still relies on basic research into the role of chemical messengers, genetic codes, and cellularfunction. As polymer science and materials engineer-ing join forces with biology and medicine to producethese modern miracles, we again see how interdiscipli-nary collaboration and essential basic and appliedre s e a rch remain the true source of benefits as simple—and profound—as a living tissue that can be created inthe laboratory.

The article from which this account was adapted waswritten by science writer David J. Tenenbaum, with theassistance of Drs. Frank DiSesa, Robert L. Kruse, RobertS. Langer, Robert W. Lenz, William J. MacKnight,Jeffery L. Platt, Bruce Rosen, Richard Stein, Walter H. Stockmayer, Edwin L. Thomas, Valerie A. Wilcox,Charles A. Vacanti, and William Vining, for BeyondDiscovery™: The Path from Research to HumanBenefit, a project of the National Academy of Sciences.

The Academy, located in Washington, D.C., is asociety of distinguished scholars engaged in scientificand engineering research, dedicated to the use of scienceand technology for the public welfare. For more than acentury it has provided independent, objective scientificadvice to the nation. The project’s web site is accessibleat www.beyonddiscovery.org, from which the full text ofall articles in this series can be obtained.

Funding for this article was provided by the Camilleand Henry Dreyfus Foundation, Inc. and the NationalAcademy of Sciences.

O ffice on Public Understanding of Science2101 Constitution Avenue, NW, Washington, DC 20418202-334-1575 e-mail address: bsi@nas.edu

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© 1999 by the National Academy of Sciences November 1999

A scanning electron micrograph reveals cells growing on longpolymer fibers, the first step in creating artificial tissues.(Photo courtesy of Robert Langer)