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1156

the intensity of a voter's feelings," is akey to the error. Representative govern-ment, both in election of candidates andin legislative deliberations, works be-cause intensities of feeling can be ex-pressed (1). Failure to recognize thatbasic fact leads Savas to managementsolutions and evidently led Crowe (2) todespair.

Despite the 1 9th-century hamstring-ing of legislative power (at the statelevel) and the 20th-century strengthen-ing of executive power (at all levels),the system can make collective choicesonly through the legislatures. Pole (3)has elegantly detailed the origins andconsequences of this Whig heritage.

EDWIN T. HAEFELEResolurces for the Flututre, Inc.,1755 Massachusett.s Avenue, NW,Washington, D.C. 20036

References

I. E. T. Haefele, Puiblic Choice 8, 75 (1970).2. B. L. Crowe, Science 166, 1103 (1969).3. J. R. Pole, Political Representation in Enigland

and the Origins of the American Repuiblic (St.Martini's Press, New York, 1966).

Chichagof Island, Alaska

For 21/2 years we have been attempt-ing to establish a wilderness area onChichagof Island, a large island just tothe north of our island here in south-eastern Alaska. Chichagof has much torecommend it-mountains, shelteredcoves and bays, lakes, and forests. It isthe home of brown bear, bald eagles,swans, ducks, land otter, and sea otter,just to name a few species. Unfortu-nately it belongs, as does all of thesoutheast, to the Tongass NationalForest.We have repeatedly asked the U.S.

Forest Service for help in establishingthis area, and have been told it is impos-sible. Alternate sites in our area whichincorporate representative scenery areseverely limited. Howard Johnson, theregional forester, has informed us that98.4 percent of all marketable timber(in the Tongass Forest) has been soldand will be harvested.

In attempting to document our con-tention that surely some small part ofthis magnificent country should remaina wilderness, we have discovered we arelimited by our backgrounds. In oursmall community we have no scientiststo give us answers to such questionsas: What are the effects of clear-cutlogging on steep hillsides, especiallywith reference to salmon-spawningstreams? Do spruce seedlings really

rweighinnexpenditures

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PerformanceThe fastest, simplest, most accurateand durable balances at the lowestpossible cost come from Ohaus.Don't take our word for it. Get acopy of our comprehensive newcatalog. Compare what it offerswith what others offer in theircatalogs. Then choose theequipment that gives you the mostfor your hard-fought dollar. Wethink you will pick an Ohausinstrument-the one that best fitsyour needs. The choice is wide-geared to fill the many requirementsof today.But remember, too, that Ohaus isan innovator. Many of the balancescovered in our new catalog can bemodified to solve special problems.If you need something you don'tsee in our catalog let us knowabout it. If the potential is broadenough we'll produce it. Becauseour designers.know their business,you will get the mt fo0r_y_money. Firs e. caag.Then let's rer eyour copy today.

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Circle No. 77 on Readers' Service Card

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choke out older growth after clear-cutlogging? What of the pH factor? Inother words, we badly need some docu-mented answers and references.

Is there anyone who would be will-ing to help us? We will be glad to sendany further information, including acopy of the wilderness proposal.

DEE LONGENBAUGHSitka Conservation Society,Box 377, Sitka, Alaska 99835

Surmounting a Crisis

Harry A. Ackley's letter (26 June)regarding events at the department ofpediatrics of the University of Cali-fornia, San Francisco, needs clarifica-tion. On 7 May Governor Reagan re-quested that the university be closeduntil 11 May. The closing, plus eventsin Cambodia, Kent State, Augusta, andelsewhere stirred this campus as neverbefore in its history. "Informal" fac-ulty, staff, and student meetings wereheld continuously. All of the meetingswere emotionally charged, and count-less resolutions were passed. The entirecampus community was searching fora rational response to what many per-ceived as a campus and national"crisis." During the official closing, thepediatrics department met all of itspatient-care responsibilities, and whenthe campus reopened, it met its respon-sibilities to students, patients, and re-search.On 11 May when the Academic Sen-

ate was able to resume official meetings,it stated: "The current nationwide andUniversity crisis makes normal conductof courses difficult if not impossibleand these circumstances place a specialobligation on faculty members to in-sure that the educational and personalneeds of students are protected." Ack-ley stated later: "I have no knowledgeas to whether research was interferedwith or stopped during this period oftime. Specifically my education was notinterfered with; the University was of-ficially closed 7 May through 10 May,and I was on vacation from 11 Maythrough 25 May."

These were trying days. The campuswas not "taken over" for use as a "po-litical machine." The fact that patient-care responsibilities were met is aneverlasting credit....

EDWIN F. RosINSKIOffice of the Chancellor,University of California Medical Center,San Francisco 94122

18 SEPTEMBER 1970

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there could be a shortage of low-estrogen pills on the market," Edwardstold the Fountain subcommittee.The decision to expedite the review

of Demulen was made despite the fol-lowing:

1) Several companies already hadlow-estrogen pills on the market.

2) When Representative BenjaminS. Rosenthal (D-N.Y.), a member ofthe Fountain subcommittee, asked Ed-wards "Is it your position that you are

to be guided in your priorities accord-ing to market conditions and the avail-ability of drugs?," Edwards answered,"Absolutely not."

3) The New Drug Application, ac-

cording to Fountain's subcommitteestaff members, did not adequately dem-onstrate the efficacy of the drug as re-

quired by law.After several hours of questioning

by the Fountain subcommittee, HenrySimmons, director of the FDA's Bu-reau of Drugs, explained the problemwith Demulen and other similar cases,which the agency faces. "We have a

difficulty here in being damned if we

do and damned if we don't. If we tryto be logical about the regulations anduse good sense we get tripped up be-cause we haven't followed the letter ofthe law," he said.

Goldberg had a different view of thecase: 'What we are dealing with here isnot hard science but the making of de-cisions on the basis of hypotheses, with-out the evidence required by law."

The Demulen approval was not theonly instance of the new FDA efficien-cy in speeding the process of getting a

new drug on the market. The approvalof L-dopa, which is used in treatingParkinson's disease, came after Edwardscharacterized as "an extraordinary ef-fort by the FDA to make the drugavailable as quickly as possible." Inannouncing its approval, Edwards notedthat clinical tests showed that one-thirdof the patients treated wih L-dopa didno respond favorably and that there was

a high incidence of side effects. Alsocited by the commissioner was the lackof information on the long-term effectsof L-dopa. Because of these considera-tions, the FDA required the drug'smanufacturer to continue clinical test-ing of the drug while it is on the mar-

ket, an unprecedented requirement bythe FDA. According to Simmons, theagency would not in the past have ap-proved the drug until the completionof long-term clinical studies.Yet while the FDA's new efficiency

has speeded up the process of approving18 SEPTEMBER 1970

new drugs for marketing, it has notappreciably expedited the removal ofineffective drugs from the market. Forexample, the agency has, to date, pub-lished only about one-third of the Na-tional Academy of Sciences-NationalResearch Council study of the safetyand efficacy of all drugs on the mar-

ket. This study, undertaken to imple-ment the Kefauver-Harris Drug Act,was completed in 1968. Edwards haspromised that all the findings will bemade public by the end of this fiscalyear and blames the delay on the needto formulate guidelines for relabelingand other changes which the FDA says

must accompany the release of thefindings, but which the overburdenedFDA staff has not yet found the time tocompile.

Lawsuit to Compel Release

The commissioner's promises andexplanations do not carry much weightwith FDA critics. Robert McCleery,for example, a former chief of theMedical Advertising section of theFDA's Bureau of Medicine and now a

consultant to Nader's Center for theStudy of Responsive Law, believes thateconomic considerations have playeda part in delaying the release of theNAS-NRC reports. He helped initiatea recent lawsuit to obtain immediate re-

lease of all the reports.FDA officials deny that economic

considerations play any part in theiroperations and insist that their onlycriterion in making decisions is thesafety and efficacy of drugs.

Yet the drug industry, which is one

that has consistently enjoyed high prof-its, is certainly given ample opportunityto collaborate with and influence FDAdecisions. When an NDA is submittedto the FDA, the manufacturer is ad-vised which FDA official will review thecase and is permitted to meet continu-ally with that official to answer any

questions and allay any doubts he may

have. When this reporter tried to findout the names of the officers who re-

viewed the Demulen evidence, how-ever, he was informed by Simmonsthat such information is not normallymade public.

In opposing FDA decisions the drugindustry is also a powerful force, oftenemploying legal delaying tactics to forcelong intervals between an FDA rulingagainst an ineffective drug and the ac-

tual removal of the drug from themarket (Science, 29 August 1969).FDA critics accuse the agency of in-

viting such proceedings and delays by

failing to declare ineffective drugs "im-minent hazards to public health." Sucha labeling would eliminate the courtproceedings and force the drug off themarket immediately. The FDA claimsthat it cannot evoke the ruling againstdrugs which are merely ineffective, butFDA critics contend that ineffectivedrugs can be hazardous because a pa-

tient can be jeopardized by an ineffec-tive drug. "Apparently people have tobe dropping like flies all over the coun-try before the FDA will employ theimminent hazard procedure," McCleerysaid.Under the new management, then,

criticism of the FDA has not appreci-

ably decreased. In addition the agen-

cy's financial outlook remains bleak.Edwards has asked Congress for a sub-stantial increase in the FDA budget forfiscal year 1972. The increase wouldmore than double the FDA budget,bringing it to $150 million from itscurrent $72-million level. A belt-tight-ening administration, however, has beenreluctant to back Edwards fully in hisrequest, and it appears unlikely thatCongress will grant more than a smallincrease.

Thus while the new-look FDA hasspeeded the approval of new drugs formarket'ing and reduced criticism fromindustry, many of its basic problemsremain to be solved, and criticism fromCongress and consumer groups has, ifanything, increased. Edwards still hasa long way to go before he convincesthese critics that the FDA's new-foundefficiency is not more in the interest ofthe drug industry than in the interestof the public-THOMAS P. SOUTHWICK

APPOINTMENTSW. J. Tietz, chairman, physiology andbiophysics department, Colorado StateUniversity, to vice president of studentand university relations at the univer-sity. . . . Roger F. Palmer, director,clinical pharmacology division, depart-ment of medicine, University of MiamiSchool of Medicine, to chairman, phar-macology department in the school.....Lionel E. Mawdesley-Thomas, directorof pathology, Huntingdon ResearchCentre, England, to director of researchat the centre.... Victor H. Hutchison,professor of zoology and director, Insti-tute of Environmental Biology, Univer-sity of Rhode Island, Kingston, tochairman, zoology department, Uni-versity of Oklahoma.

1189

It is this gap in the literature thatJohn Brandt's book fills with notablesuccess. Intended as an intermediate-level reference text, the book providesa comprehensive but highly readableaccount of the evolution of present-dayideas about the interplanetary mediumand its relation to solar activity. Thetreatment is self-contained, requiringlittle or no prior knowledge of inter-planetary physics. Pertinent supplemen-tary references are listed after eachchapter.

I found one of the most rewardingparts of the book to be the openingchapter, in which Brandt traces thehistory of early thoughts and theoriesof the interplanetary medium. In myopinion, even most experts in the fieldof space physics would benefit fromreading this brief account of little-knbwn facts.The obvious place to begin a discus-

sion of the solar wind is at the sun, andthe author sets the stage by summariz-ing current knowledge of classical solarphysics. Probably all of the material inchapter 2 is relevant to an understand-ing of the origin of the solar wind.Upon completing the book, however, Iam left with the impression that littlereference is actually made to it in sub-sequent chapters. This is not so much afault of the book as it is a reflection ofour present lack of understanding of therelation of observed solar wind proper-ties to visible features on the sun (apoint which, however, Brandt mightwell have stressed).

Topically, the chapter devoted tobasic theory is complete and up to date.Brandt has succeeded in extracting theimportant physics from many theoreti-cal analyses and presenting it in a con-cise manner. Occasionally, completenessof argument has been sacrificed for thesake of brevity, which is an unfortunatesituation. I was particularly dissatisfiedwith the section on subsonic versussupersonic solar wind solutions, a topicof such colorful controversy in the tech-nical journals. Brandt's discussion ofthe subject leaves me unconvinced(apart from observational evidence)that the supersonic solution is the onlyphysically acceptable one.

In the chapters dealing with observa-tions, the author presents representativefacts and figures about the averageproperties of the solar wind and de-scribes in some detail the experimentaltechniques by which they are obtained.At the same time, he impresses uponthe reader the importance of fluctua-tions of these properties. An important

1196

research problem in the future of solarwind physics will be to relate thesefluctuations to the evolution of specificcoronal features.As with any technical book written

by an active worker in the field, thebook under review shows some tend-ency to overemphasize the author'sown contributions to the subject. Ifound this to be true especially in thelengthy discussion of ionic comet tailsin chapter 4.

Introduction to the Solar Wind isbasically an excellent, well-organizedtext. It correctly delineates the mostimportant aspects of modern solar windresearch. In the style with which it waswritten, the book should appeal to read-ers with a wide variety of technicalbackgrounds. Each reader, however, ex-pects something different of a book.For instance, I would have liked to seegreatly expanded the final chapter, deal-ing with the impact of the existence ofthe solar wind on classical astrophysics.Without enlarging the book significant-ly, this might have been done by con-densing the review of solar physics inchapter 2. Certainly new ideas anddirections for future research are stimu-lated by discussions of the type en-countered all too briefly in the last 15pages of the book.

ROGER A. KoPPHigh Altitude Observatory,National Center for AtmosphericResearch, Boulder, Colorado

Books Received

Airway Dynamics. Physiology andPharmacology. A meeting, Haverford, Pa.,August 1968. Arend Bouhuys, Ed. Thomas,Springfield, Ill., 1970. xiv, 346 pp., illus.$29.50.

Analytical Chemistry. Vol. 10. D. C.Stewart and H. A. Elion, Eds. Pergamon,New York, 1970. viii, 480 pp., illus. $27.Progress in Nuclear Energy, Series 9.The Analytical Chemistry of Sulfur

and Its Compounds. Part 1. J. H. Karch-mer, Ed. Wiley-Interscience, New York,1970. xviii, 542 pp., illus. $35. ChemicalAnalysis, vol. 29.The Basic Ideas of Occult Wisdom.

Anna Kennedy Winner. TheosophicalPublishing House, Wheaton, Ill., 1970. ii,114 pp. Paper, $1.95. Quest Book Origi-nal.

Beaker Pottery of Great Britain andIreland. D. L. Clarke. Vol. 1 (xx, 280pp., illus.); vol. 2 (viii, pp. 282-576,illus.). $45 the set. Cambridge UniversityPress, New York, 1970.Beyond the Couch. Dialogues in Teach-

ing and Learning Psychoanalysis inGroups. Alexander Wolf, Emanuel K.Schwartz, Gerald J. McCarty, and Irving

A. Goldberg. Science House, New York,1970. xvi, 368 pp. $12.50.The Biochemistry of Inorganic Com-

pounds of Sulphur. A. B. Roy and P. A.Trudinger. Cambridge University Press,New York, 1970. xvi, 400 pp., illus.$18.50.The Biology of the Porifera. Proceed-

ings of a symposium and presentations atcolloquia, London, September 1968. W.G. Fry, Ed. Published for the ZoologicalSociety of London by Academic Press,New York, 1970. xxviii, 512 pp., illus.$22.50. Symposia of the Zoological So-ciety of London, No. 25.

Biology of Termites. Kumar Krishnaand Frances M. Weesner. Vol. 2. Aca-demic Press, New York, 1970. xvi, 648pp., illus. $32.The Blacker the Berry.... A Novel

of Negro Life. Wallace Thurman. Collier,New York, 1970. xxii, 234 pp. Paper,$1.50. Reprint of the 1929 edition. Afri-can/American Library.

Briefwechsel, 1916-1955. Albert Ein-stein and Hedwig and Max Born. MaxBorn, Ed. Nymphenburger, Munich,1969. 332 pp. DM 24.80.The Challenge of World Poverty. A

World Anti-Poverty Program in Outline.Gunnar Myrdal. Pantheon, New York,1970. xx, 522 pp. $8.95. Christian A.Herter Lecture Series, Johns Hopkins Uni-versity School of Advanced InternationalStudies.COBOL Programming. Nancy B. Stern

and Robert A. Stem. Wiley, New York,1970. xiv, 354 pp., illus. $7.95.Community Psychology and Mental

Health. Perspectives and Challenges. Dan-iel Adelson and Betty L. Kalis, Eds.Chandler, Scranton, Pa., 1970. x, 342 pp.Cloth, $8; paper, $4.75.

Comprehensive Biochemistry. MarcelFlorkin and Elmer H. Stotz, Eds. Vol.18, Lipid Metabolism. Elsevier, NewYork, 1970. xvi, 400 pp., illus. $24.25.Data Display Systems. Their Use as Vis-

ual Planning Aids for Management in theAge of Computerization. W. Gray Hor-ton. Brandon/Systems Press, Princeton,N.J., 1970. xvi, 136 pp., illus. $8.25.The Determination of Carboxylic Func-

donal Groups. R. D. Tiwari and J. P.Sharma. Pergamon, New York, 1970. viii,132 pp., illus. $8. Monographs in Or-ganic Functional Group Analysis, vol. 3.

Dictionary of Electronics and Nucleon-ics. L. E. C. Hughes, R. W. B. Stephens,and L. D. Brown. Barnes and Noble,New York, 1970. viii, 444 pp. Boxed,$14.50.The Dictocrats. Our Unelected Rulers.

Omar V. Garrison. Books for Today,Chicago, 1970. 334 pp. Paper, $1.25.

D'seases of Attention and Perception.Monte Jay Meldman. Pergamon, NewYork, 1970. xii, 244 pp., illus. $13.50. In-ternational Series of Monographs in Ex-perimental Psychology, vol. 10.

Divisional Performance. Measurementand Control. David Solomons. Irwin,Homewood, Ill.; Irwin-Dorsey, Nobleton,Ontario, Canada, 1969. xii, 308 pp., illus.Paper, $5.25. Reprint of the 1965 edition.

Editing for Engineers. John B. Bennett.Wiley-Interscience, New York, 1970. x,134 pp., illus. $7.95. Wiley Series onHuman Communication.

(Continued on page 1246)SCIENCE, VOL. 169

The SolutionTo OxygenUptake &Evolution

Uptake rates of 3 to 300ul 02/hr can be monitoredwith 1% accuracy on YSI

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plication of human skin fragments dis-persed by bacterial collagenase as amultiple graft system to speed up thehealing of extensive burns. Dispersedskin cells in a freely flowing suspensionwere spread out evenly over the com-plete surface of the wound in smallcircular drops. After a few hours, skinregeneration had started from a numberof foci which gradually became conflu-ent. It was pointed out that this pro-cedure might be worthy of furthertrials. In another experimental use celldispersion with collagenase enabledCarlton Blackwood (Columbia Univer-sity) to successively transplant an ovar-ian papillary serous cystadenocarcinomaof human origin beyond 40 transfer gen-erations in rats and hamsters. Withoutcollagenase, increasing amounts of con-nective tissue accumulated betweentumor nodules; and serial transplantscould not be carried out beyond threeor four transfer generations. Removalof the collagen rendered the tumortransplantable indefinitely.

Leonard Shulman and his associates(Harvard) treated tooth allografts withbacterial collagenase prior to trans-plantation. This procedure dissolved thecollagen fibers in the periodontal liga-ment and thus prevented early rejectioncaused by the immunogenicity of theperiodontum without damaging thetooth cement. When a tooth is trans-planted within the same mouth it re-attaches to alveolar bone within 3 weeksand survives indefinitely; but toothtransplants between individuals do notreattach normally and are ultimatelylost because of root resorption. It wasdemonstrated that, in the absence ofprior treatment with enzyme, at 3 weeksthere is extensive lymphoid infiltrationleading to rejection of the foreign perio-dontal ligament. Comparison of controlallografts and enzyme-treated allograftsin rhesus monkeys after 31/2 monthsshowed that enzymolysis of the perio-dontal ligament before transplantationsignificantly reduced inflammation aftertransplantation and increased ankylosisleading to prolonged survival of thetooth allograft.Two other applications of collagenase

of great potential use to human patientswere reported, though as yet both are

restricted to experimental animals. Ber-nard Sussman (Howard University) usedbacterial collagenase to dissolve the pro-truding cartilage which, through com-

pression of the nerve root, causes

severe pain in herniation of the inter-vertebral disk, the condition commonlyreferred to as slipped disk. This non-

Circle No. 81 on Readers' Service Card

surgical decompression of the nerve rootis possible because of the selectiveenzymatic dissolution of the disk whichassures a margin of safety not sharedby common proteolytic enzymes. Sterilecollagenase was injected directly intothe nucleus pulposus of dogs. Thecartilage was dissolved without anydamage to the surrounding tissue. Alldogs walked immediately after recoveryfrom anesthesia and showed no evidenceof dysfunction of any sort. Preliminarytrials in vitro against tissues removedfrom human patients in the operatingroom or at autopsy showed similarfavorable action. Collagenase mediatedcomplete destruction of the nucleus pul-posus and major dissolution of thefibrocartilage, the tissues that constitutethe bulk of the offending mass inclinical disk herniation while hyalinecartilage is usually spared and osseouseffects are insignificant.Dogs were used by Frank Longo and

John Lattimer (Columbia) in theirevaluation of collagenase as an adjunctin cryoprostatectomy. With increasinglife expectancy, more poor-risk patientsunsuitable for conventional surgerypresent themselves with obstruction ofthe bladder caused by benign or malig-nant enlargement of the prostate gland.Cryoprostatectomy-which is fast, re-quires no or little anesthesia, andresults in negligible blood loss ortraumna--has many advantages for pa-tients of advanced age. In this otherwisehighly successful procedure, the singlemost frustrating complication has beenthe retention of slough which plugs upurinary passages and prevents elimina-tion. Direct injection of collagenase intothe prostate glands of 15 dogs beforethe cryoprobe was put in place gavethe desired result of removing theslough and retaining normal urinaryfunction without producing demonstra-ble histologic damage to vital tissues. Inaddition, several commercially availableenzymes were tested for the purpose ofdegrading or decomposing "cryo-slough" from patients after cryoprosta-tectomy. Collagenase was significantlysuperior to the other agents tested. In aconcentration of 0.1 percent total dis-solution was accomplishedl in 18 hours.

In the clinical sessions, good thera-peutic effects were reported in morethen 1500 patients who were giventopical applications of bacterial col-lagenase in an ointment base for de-bridement of second- and third-degreeburns prior to skin grafting and for thetreatment of dermal ulcers. Ingo Mazu-rek (Knoll A.G.) summarized results

SCIENCE, VOL. 169