A point ofview on

MAKING EVERYDOLLAR COUNTA top-of-the-line liquidscintillation systemis a majorinvestment.Reason enoughto demandthe mostvalue andquality you can getforyour research dollars.

If you pay for top counting performance,be sure it's the performance vou need.Mark 1® Systems let you specify highefficiency, high E2/B, or standard per-formance.

If you pay for top cooling performance,be sure its right for all of your samples.Mark I Systems let you program thecounting temperature to make it preciselycompatible with the composition of yoursamples.

If you pay for top external standardiza-tion performance, be sure the efficiencycurves cover the widest possible range ofquench. Mark I Systems perform channelsratio on a Ba133 external standard to

develop accurate calibration curves over

the full useful range of intermixed H3 andC14 counting efficiencies.

If you pay for top data readout per-formance, be sure the system tells youmore about your samples than any other.Mark I Systems have a "computer-with-a-memory" that does just that.Make all of your liquid scintillation

dollars count. Ask your Nuclear-Chicagosales engineer about Mark I Systems or

write to us. B-235

We try to work to a point of view: yours.

cixNUCLEAR-CHICAGOCORPORATIONA SUBSIDIARY OF G. 0. SEARLE & co.

349 E. Howard Ave., Des Plaines, III. 60018 U.S.A.Donker Curtiusstraat 7, Amsterdam W.

1288

)f Biological Sciences had in refusingto support the executive committee'sagreement for cosponsorship by AIBSand Fort Detrick of two symposia("Detrick birthday: Dispute flares overbiological warfare center," 19 Apr., p.285 ).These symposia, honoring the

25th anniversary of the establishmentof Fort Detrick, were concerned withbasic research in two fields: "entry andcontrol of foreign nucleic acids" and"leaf abscission." These fields impingeon areas of importance to biologicalwarfare research, which may be directedagainst civilian populations, and overwhich scientists have no control. Thereasons for our action were as follows:

1) It is not appropriate nor properfor an organization representing alarge segment of the biological com-munity to actively participate in a cele-bration honoring 25 years of biologicaland chemical warfare research.

2) It is not proper for the AIBS tolend its name and prestige to this cele-bration indirectly conveying the impres-sion that AIBS actively favors thisaspect of Defense Department activity.Although AIBS in this instance is act-ing simply as an agent of Fort Detrick,not having participated in planning theconference nor exerting any controlover the program, its sponsorship inthis way can be construed as tacitsupport.

3) It is not relevant whether thesymposium was involved with basicresearch problems in biology, whetherthe discussion was to be open or closed,or whether the published symposiumwill be available to the biological com-munity or will be classified.

4) The essential issue is a moralone: should an organization composedof life scientists participate in an an-niversary celebration of an installationconcerned primarily with research forthe purposes of biological and chem-ical warfare?

JOHN M. ALLENDepartnent of Zoology,Uniiversity of Michigan, A7nn Arbor

RALPH EMERSONDepartment of Botaniy,University, of California, Berkeley

PHILIP GRANTDepartmnent of Biology,University of Oregon, Eugene

HOWARD A. SCHNEIDERMANCase Western Reserve University,Cleveland, Ohio

PHILIP SIEKEVITZRockefeller University, New York

ThePerfect Pipet

The L/I Grunbaum pipet combinesall "specialty pipet" functions:

* self-adjusting

* self-filling

* self-cleaning-sampleout sample A

B washes

* reservoir for reagent, solvent orwaste

* non-dripping-100% of sampleheld until expelled

* low-ratio serial dilutions, 1:2:4:-8:, etc.

Guaranteed accuracy is as follows:5 lambda, ± 3 %; 10 and 20 lambda,+i2 %; 25 lambda and larger, -+-1%.

Use Grunbaum pipets for rapid andprecise pipeting, dispensing, trans-

ferring and diluting.

L/I stocks Grunbaum pipets in 5,10, 20, 25, 50 and 100 lambdas.Other sizes available on request.Price $5.00 each, quantity discounts.For more information, write to us

at 1802 H Second Street, Berkeley,California 94710.

4* LABINDUSTRIESBerkeley, California

SCIENCE, VOL. 160

k,/Al

. . .One thing is certain-it's too latefor a scientist to merely boycott a

meeting or two.... The only argumentof any importance made by either sideis, to quote Boffey's article: "Outsidescientists should maintain contact withDetrick in accord with the principle ofcivilian control over the military." Thiscompressed statement contains theessential principle. If you let studentstake over the campus, you'll get action,but who is held really responsible whenthe fires are finally put out?

J. S. ROBOTTOM12115 Drujon,Dallas, Texas 75230

TV for Disadvantaged Children

The Children's TV Experiment("News in Brief," 26 Apr., p. 401)described a program to begin in thefall of 1969 for teaching preschoolchildren and aimed at "stimulating theintellectual and cultural growth of chil-dren-'particularly those from dis-advantaged backgrounds. "What disadvantaged preschool child

has a 1-hour attention span-and one

which can last 5 days a week for 26weeks? Should preschool children,whose eyes are not fully developed, bestaring at focal objects for protractedperiods? How many disadvantagedhomes have TV facilities? How aboutdisadvantaged rural children who donot have access to National Educa-tional Television? Isn't this discrimina-tion? Shouldn't an investigation ofthese factors be made before goingahead with a $6- to $8-million work-shop plan?

PEARL E. HACKMANP.O. Box 115,Handsboro, Mississippi 39554

Eclipse of Jacob

To bolster the morale of the scientificestablishment shaken by the flight ofour young from physics ("Physics andthe polity," 26 Apr., p. 396), I offer thissingular thread of hope. In answer to a

religious school exam question: "Namethe three patriarchs," one of our bright-est fourth-graders listed: "Abraham,Isaac, and Newton."

ELY E. PILCHIK320 Tillou Road,South Orange, New Jersey 07079

21 JUNE 1968

Better Research-Better Teachers

Bresler in "Teaching effectivenessand government awards" (12 Apr., p.

164) concludes that "the faculty mem-

ber who is interested in publishing andin acquiring funds for research andother means of personal development. . .is likely to be a better teacher."While we agree with this position, hehas not provided an answer to the as-

sertion "that research efforts by pro-

fessors were destructive to the teachingfunctions of universities." He also hasnot replied to the fallacious expressionthat research energy directed towardimprovement of instruction and help-ing students would make the professora still better teacher.

Science is a process, a way of think-ing, which cannot be transmitted fromteacher to student by the enumerationof encyclopedic content but which mustbe learned by participation. Since everystudent cannot participate in a mean-

ingful way, the solution must lie in hishaving contact with practicing scien-tists. When we substitute professionalteachers, full-time introductory instruc-tors, and teaching fellows we extendprep school training to the university.I expect that science is not unique;music is best taught by musicians, artby artists, and literature by writers.Surely the student does not pay hismoney and, more important, spendhis time, to receive third- and fourth-hand knowledge. He comes to the uni-versity to participate in the activity ofscholarship, and scholarship is research,writing, thinking, discussing, and par-ticipating in the subject.We deny the student and the finan-

cial supporters (taxpayer or alumni)their just due when we fail to providean atmosphere where the student can

participate in academia. When the bur-dens of the professor preclude his par-

ticipation in scholarship, we are notusing our very limited resources toprovide appropriate university instruc-tion. These burdens include oversizedteaching assignments, too much com-

mittee work, pointless clerical and de-manding money-raising duties. Do theburdens also include spending exten-sive amounts of time applying to grant-ing agencies for money to support a

program of scholarship compatiblewith the modern state of knowledge?

DAVID L. JAMESONDepartment of Biology,University of Houston,Houston, Texas 77004

Now in bead form forchromatography ofbiologic substances...

SephadexIon ExchangersBecause of its advantages-sta-bility and inertness-Sephadexhas been used to produce a newclass of ion exchangers: QAE-,DEAE-. CM- and SE-Sephadex.Since theirintroduction they havebeen used extensively, particu-larly in the biochemical and clin-ical field.In the new bead form they will bemore useful both for laboratoryand manufacturing scale proo-esses. Their spherical shapegives increased mechanicalstrength and leads to easier

i column packing. More uniform.particles result in Improvedhydrodynamic properties.

All Sephadex Ion Exchangers have a highcapacity and low nonspecific adsorption.They are available in two types that differIn porosity, thus offering flexibilityforyourspecific requirements. Sephadex Ion Ex-changers are of analytic grade purity andare produced under rigorous quality con-trol, thus ensuring uniform products togive accurate and reproducible results.pA g/Ml Hexose moopopae.Fru-~ 6-P2%T2537Am0ono phsphates m

AMP ADP ATP

glycogen 5

40 glucose

Model experiment with glycogen, glucose.sugar phosphates and adenosine phosphateson a column of DEAE-Sephadex A-25.(From Biochim. Biophys. Acta 74 (1963) 588, by permissionof the author)

Anion ExchangersGaeIonic Cpcity Bed Volume'Type Grade Form (eq/g) (mug)

QAE- _ _ _ _ _ _ _

Sephadex A-25 40-120g Cl1 3.0 ± 0.4 5.8QAE- _ _ _ _ _ _ _ _

Sephadex A-50 40-120A Cl1 3.0 0.41 30.40DEAE-tSephadex A-25 40-120j& Cl 3.5

+

0.5 5-9DEAE-tSephadex A-SO 40120I Cl 3.5 ± 0.5 25-33

Cation ExchangersType Grade ionic Capacity Bed Volume'

Form (meq/g) (m/g)Cm.Sephadex C-25 40-120& Na' 4.5 ± 0.5 6-10Cm-Sephadex C-50 40-120p Na' 4.5 + 0.5 32-40SE-Sephadex C-25 40-120u Na' 2.3+ 0.3 5-9SE-Sephadex C-5 40-120g Na- 2.3 ± 0.3 30-38

1. In Tris-HCI buffer. pH=8.3. Ionic strength=005.2. In sodium phosphate buffer pH=6. ionic strength-0.0OFor additional technical Information. Includingbooklet on Sephadex Ion Exchangers, write to:- PHARMACIA FINE CHEMICALS INC.

800 Centennial Avenue. Piscataway, N. J. 06854Pharmacia (Canada) Ltd.. 110 Place Cr6mazie.Suite 412, Montreal 11. P.Q.

(inquiries outside U.S.A. and Canada should be directedto PfHtARMACIA FINE CHEMICALS AB. Uppsala. SwedenJ

1291

DON'T CALIBRATE!

: rotateX

and complete

an experimentin the timeit fornierly took

~to set up.ll1

£

£= E

- . 0 -

* - 0

* *

* 0 - 0 -

* .0 . - 0 -

0 -0. 0 0 0

s ~~~~0

*0-*- - -

* *

S~~~~00-006

M -d (.w R .;

. ....... . . X ..~ ~ ~ ~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..

EuiROPEAN Maluflcicturing Branich Gisori Mecl'iccl Electrorics FRANCE

69, Rue Garmbettc * 95 -ViliIers- Le Bel.S( IN I(T \()1 16()

--

1-V.

'],- J:I'll, Irl:.

:k

s

IlI7

I

k.

but it was important to have the proc-ess documented in detail.The present volume is directed to

another aspect of this second question.In following up the patients who werestudied ten years ago, Myers and Beanask whether the consequences of thetreatment received, in the form of re-covery and adjustment, are also class-related. The answer is a clear affirma-tive. And again, while this is hardlysurprising, the consistency and per-vasiveness of the findings could lead toa reconsideration of and possibly tochanges in present views of the problemof mental illness and in current waysof organizing psychiatric care and treat-ment. As will be noted below, however,the authors are themselves the captivesof a traditional medical-psychiatricpoint of view, and their proposals tendto trivialize the importance of their ownfindings.

After a thorough search of psychiat-ric agency records, combined with fieldsurveys, the investigators were able tolocate 99 percent of the original groupof patients who were to be includedin the follow-up study (patients origi-nally in treatment with private psy-chiatrists were not included for reasonshaving largely to do with original com-mitments regarding confidentiality andthe required approval of the phy-sicians). Interviews, focused primarilyon questions of personal and socialadjustment, were completed with 88percent of the former patients whowere no longer hospitalized, and witha member of their families; a matchedcontrol group of persons who had neverbeen treated for a mental illness wasalso interviewed, on similar topics.A central finding is that, of those

patients who were hospitalized at thetime of the original study, the per-centage still hospitalized ten years laterincreases steadily from 39 percent inthe highest social classes (designatedI-II) to 57 percent in -the lowest(class V). About four-fifths of thesepatients in each social class had beencontinuously hospitalized. There are noclass differences in the percentages whohave died in the interim-about 30percent of the original cohort. Thepercentage now living in the communitydeclines from 31 in classes I-II to10 in class V. This finding is not alteredwhen statistical controls are introducedfor sex, age, race, religion, maritalstatus, previous hospitalization or itslength, type of hospital, or type ofpsychiatric treatment. Clearly, socialclass is the most significant of thevariables studied in determining an

1332

individual's chances of being releasedfrom a psychiatric hospital to returnto life in his community.

For those now in the community, thefindings with regard to current psy-chological and social adjustment aremore complicated. Members of thehigher social classes, for example, aremore likely to be receiving outpatienttreatment either privately or in clinics.There is the interesting and at first ap-parently anomalous finding that amongthose who had originally been hos-pitalized the higher social class groupsare more impaired psychologically,whereas among those formerly in clinictreatment it is class V that shows mostcurrent impairment. In their discussionof these findings the authors attributethe differentials both to the social con-trol functions of hospital psychiatrists,who, they argue, may use more strin-gent criteria for the release of lower-class persons, and to unequal accessto resources, psychiatric and otherwise,of the different class groups.

There is much more in the volume-other measures of adjustment, re-sponses of family members, economicand social role performance patterns-which serves to underscore andstrengthen the general trends outlinedabove.

Follow-up studies are still relativelyrare in this field, and each new onemust be welcomed. Further, this studyis unique both for the time spancovered and for the attention given tosocial class. Its findings bear directlyon the planning of psychiatric facilitiesand on the training of psychiatrists. Itis my view, however, that the force andimpact of the work are limited by theauthors' implicit and unquestioning ac-ceptance of the contemporary medical-psychiatric model of mental illness andtreatment. Since they accept the psy-chiatrist's definition of the problem,their solutions are restricted to tinker-ing with the system or patching it up;essentially, they exhort the psychiatriststo behave better as psychiatrists. Onewould never guess from reading theanalyses and the proposals that moreradical approaches to definitions of ill-ness and to forms of treatment havebeen proposed in recent years. Moresearching questions might have beenraised about, for example, the relationof mental illness as deviant behavior toother forms of social deviance, aboutthe role of psychiatrists as social con-trol agents in the very definition ofsome problems as "psychiatric," andperhaps about possibilities of non-psychiatric forms of intervention.

The book merits and will undoubted-ly receive serious attention from ad-ministrative psychiatrists. It does not,however, challenge their basic assump-tions. More radical critics of the pre-sent system of psychiatry will findmuch support here for their views, andthe book could serve as a resource forthe development of more far-reachingand more profound proposals than areoffered here or were intended.

ELLIOT G. MISHLERDepartment of Psychiatry, HarvardMedical School and MassachustttsMental Health Center, Boston

Books Received

Advances In Biomedical Engineeringand Medical Physics. Vol. 1. Sumner N.Levine, Ed. Interscience (Wiley), NewYork, 1968. viii + 407 pp., illus. $16.

Advances in Freeze-Drying. Louis Rey,Ed. Hermann, Paris, 1966. 214 pp., illus.120 F.

Biochemistry: A Brief Course. AbrahamMazur and Benjamin Harrow. Saunders,Philadelphia, 1968. vi + 450 pp., illus.$8.75.

Biographical Memoirs. Vol. 39. NationalAcademy of Sciences of the United Statesof America. Published for the Academyby Columbia University Press, New York,1967. x + 572 pp., illus. $5.

Calculation of the Properties of Vacan-cies and Interstitials. Proceedings of aconference, Shenandoah National Park,Va., May 1966. U.S. Department of Com-merce, Washington, D.C., 1966 (availablefrom Superintendent of Documents, Wash-ington, D.C.). viii + 202 pp., illus. $2.50.National Bureau of Standards Miscella-neous Publication 287.The Chemical Physiology of Mucopoly-

saccharides. Proceedings of a symposium,Milan, Italy, September 1965. GiulianoQuintarelli, Ed. Little, Brown, Boston,1968. xvi + 240 pp., illus. $13.50.

Class Field Theory. E. Artin and J.Tate. Benjamin, New York, 1967. xxvi+ 259 pp., illus. Cloth, $9.50; paper,$3.95.

Disk-Elektrophorese. Theorie und Praxisder diskontinuierlichen Polyacrylnamidgel-Elektrophorese. H. Rainer Maurer. Gruy-ter, Berlin, 1968. xvi + 221 pp., illus.The Drug Scene in Great Britain. Jour-

ney into Loneliness. Max M. Glatt, DavidJ. Pittman, Duff G. Gillespie, and DonaldR. Hills. Arnold, London, 1967 (distrib-uted in the U.S. by Williams and Wilkins,Baltimore). viii + 117 pp. Paper, $2.95.Endotoxin Susceptibiity and Endotoxin

Hypersensitivity. Tibor G. Kovats. Szeged,Hungary, 1967. xii + 101 pp.

Energy Bands in Semiconductors. Don-ald Long. Interscience (Wiley), New York,1968. xiv +212 pp., illus. $9.95.The Epidemiology of Multiple Sclerosis.

Milton Alter and John F. Kurtzke, Eds.Thomas, Springfield, Ill., 1968. xiv + 204pp., illus. $10.50.

(Continiaed on page 1382)

SCIENCE, VOL. 160

uo,I.sod UO!.!ROd

AWt.A!!SU

f4fAj!*U*

gQI 9Z

qsn,j;A9 311A313

9 & do4s UO IU9AOX_i_~~~~~~~~~~ Af.z &%&4 Iliau.

Write-side up?Why not? New Mark 220 by Brush featurespressurized-ink writing. Puts trace intothe paper. . . not just on it. And you cansee you don't have to pamper it! Now, anyonecan take this remarkable new 25 lb. portable anyplace,plug it in ... and put it in writing. And what writing!Fine, sharp traces you can read at a distance-991 2%accurate! Rectilinear writing, of course, on two easy-to-read 40mm analog channels plus left and right -handevent markers. And there's enough ink in the throw-

away ink cartridge to last for about a thousand miles.There's more. Rugged, reliable solid state electronicsto give you position feedback pen control ... no springs,no strings. Pushbutton choice of chart speeds. Fre-quency response that's flat (± 2%) from d-c to 40cps at 50 div, or from d-c to 100 cps at 10 divisions.The price? Less than $1700. For a portable chartrecorder the likes of which you've never seen!Bulletin 942-1 has all the details. Call or write:Clevite Corporation, Brush Instruments Divi-sion, 37th & Perkins, Cleveland, Ohio 44114. -

CLEVITE-b----rush IN ST RU MENTS DIV ISION

IA

,K4!A!11OU

IU@A

N--

4:

1;000-7

uotwlloouol4looi

&x

be

=----

Aiii. AA

NEW REPRO-JECTORmakes quality chromatogramswith 0.6% reproducibilityThe Repro-Jector enabled a typist to make the

three chromatograms illustrated. That's howsimple this automatic sample injector is to use.The Repro-Jector entirely eliminates human j-inconsistency by mechanically metering thesample size and then reducing the discharge -r-time to a split second by a constant force spring.

Damage to syringes is practically impossible Sample specifications andthrough protection devices, and only standard details for these chromato-syringes are used. Other features of this remark- grams outlined on daia sheet

able instrument are that either horizontal or verticat injections can bemade with equal ease, and that it may be easily adapted for either right-or left-hand operators. The cost is just a little more than one standardsyringe. Write now for data sheet to Shandon Scientific Company, Inc.,515 Broad Street, Sewickley, Pa. 15143 (Pittsburgh District).

"uick,Henry, tescrevwdriver.!

All you need is a screwdriver to adaptConflex lab furniture to changing R & D requirements.

S. Blickman Inc.*BLIC~~6906 Gregory Ave

Weehawken, N.J.'

Send free CONFLEX LAB FURNITURE catalog

Name/Title

Institution

Address __ _|

City/State/ZipL.__ _ _ _ _ _

Whenever a new project comes along -or there's a new wrinkle in an old project

you can set up quickly. Over 800possible arrangements. Change doors todrawers ... Turn 31/2 " depth drawersinto 7¼/4 " depth drawers. . Adjust fulldepth shelves to 1 " increments. .. Mixand match door and drawer sizes to yourneedsJust a twist of the wrist andeverything fits.Write for your free catalog today.

that obtalined by the direct proteolvsisof m1licrosomes. SaIto conliuILdLed thliltInlatix e c tochronlie containTs aIhdIropphohic cetiter. essential fto its

hindilln to the microsonall menmiranendi sLsCeCptihle to loss ihen cxtochrome

is lpiLrifiei hb proteolx tic dilCest1ion.J. (Gillette dlirectedi attention to the

po)OSt1ula;ted role ol' cxtochrome P-4 5in iZO edL et'taSe an11d nit ro red itctaseactsixitV of lixer tilicrosomiles. -I-he efTectsof' trea-ltnient of animals w ith induLICin-1ctiints, or carhoin tetralchloridle. ria

tion x ithl sex or species. as x\ Cli as inh1li-bitioll if iliti-O rCdiLetaLse bh sLhsti1ltes Of'iCrosoni.I IIIixedI fuinction oxidation

re,ctions, suI)pported the h! pot hesis of

a r(ole for cxtochlrotie 1'-4'5( in thecti liol isll of t - iitro bet iozate aIidneoprontosil. Gillette also described

xper itIIeiit s -elat inII teie ratec ot cN to-

chronic P -450) redioCtiOl ixy I)DPith tfie ox er.ll rtte ot demICthl aLttion

ot ethliltiiorphiite He concluded tilhLt

the step i mitiJinc the rate ini the 0\i-tld tioll Ot d i-els -the reC(itCti lti

of aI subst rate-e \toc hi roiiie 1P-4 0( om-

plex.

I. 1. (: 0o0 descihbed tile isol:itioufrom lix%er iiicrosoiiles of thiree compo-ICItI Cd LIctaSC lr- ctiori d epiC idetitonl NADP[HI: traectiotl contaniling cxto-

chronie P-450:;andtid heatt-stahile. oir-

caltitC solxnci extractalble fraction. Allcotillionreits are required for- the recotn-stitutIoiI of oItIC_ecal oxidati on1 of anticiacid. These studies eptresent tile fit strerort of the resolutiton ol at iiierosoiliX'dI'\ledInet Iori oxIdattion reaction in

xhich cxtochlrome P-4-5t is Iulnlctioiall.Purificatioti xx a1s achie \ed treati iI

tilicrosotlics it h deoxx cholate inI tlie

presence of VCxcrol sIucrose, citrIte.pOtIssiLii chiloriie, ardi ditiliothrelitol.and tractionatioll on [)' AFF-cellulose.The relation o(f the iiiicrosomiia1l etix iie

sx stemii to t hat iso ited romi bacteriaxx(asiioiitedt oLt hb J. Peterson I)

Ziecler thenic dCscribed tthe isoltitioll and

40 -fold puirificaltioni of a flax otoprteinitroioi pork lixer imicrOsolmls functionainI teFrt alrx aliMimit oxidationi fotr t lie

tormatioti of N oxice prodiuct. Thehroadt slcciticitx tFi sULhstrates, t'ot ex-

amiple. t ratiquil izers, t ropitie alkaloids.

narcotics, and hallulC'ino}cens, a1, doCu-miietited bx /Zieloer for this microsomaloxidationi reaction sx stetil in xx liiclicx tochrotme 1-450) does iiot participate.

Hj. Staldinicer dlescribed resLIlts xxithai ;arietx ol mcodecl xNstetms, in order to

difteretiti.te thrce cetierall mtiechatliismof considerinc "activated oxxcXen.' 1-lierole of OH-rladicals, an oxene miech.a-

'1f-(ttNCE, VOL. 160

t i~~~~~-~

I* , aD--P I T T S B U R G 11 . L O N D O N . F R A N K F U R T

1 3 701

nism, or hydroxylation by peracids (byOH- ), was evaluated in terms of cur-rent information on microsomal mono-oxygenase reactions. Staudinger con-cluded that "active oxygen" must be anelectrophilic oxygen species with sixelectrons. S. Udenfriend discussed thesignificance of the "NIH shift" withrespect to liver microsome hydroxyla-tions. The intramolecular migration ofa methyl group, halogen, deuterium, ortritium during hydroxylation of aro-matic compounds permits the design ofa variety of experiments to determinethe multiplicity of microsomal hydrox-ylases.

S. Orrenius described recent experi-ments on the influence of PB treatmenton the metabolism of steroids by livermicrosomes. Using radioactive labelingof phospholipids as an indicator of E.R.synthesis, Orrenius proposed a time-table for the changes observed duringinduction of liver microsomes by bar-biturates. The initial reaction between0 to 3 hours after treatment of animalsis a binding of the drug to the E.R.followed at 3 to 6 hours by an increasein phospholipid turnover. Concomitantwith this change is an increase in thecontent of rough E.R. enzymes (4 to6 hours) after which there is a detecta-ble increase in the nuclear RNA poly-merase (8 to 12 hours). Longer termeffects are related to the increase in theenzyme content of the smooth E.R. (10to 24 hours) and a decrease in the rateof breakdown of the E.R. (12 to 24hours). Orrenius suggested that druginduction is a consequence of an altera-tion in the steroid balance of the ani-mal, since drugs and steroids are com-petitive inhibitors. This concept wassupported by studies with adrenalec-tomized and castrated animals.

A. Conney then discussed the ques-tion of the presence of a single enzymesystem or multiple enzymes in livermicrosomes for steroid hydroxylation.Alterations in the pattern of 6/3-, 7a-,and 1 6a-hydroxylation of testosteroneduring the development of rats, as wellas differential effects on enzyme activityby chlorothion, led Conney to concludethat separate rate-limiting componentsparticipate in the hydroxylation oftestosterone, and that one or more CO-sensitive cytochromes (P-450) functionin these hydroxylation reactions. Fol-lowing the theme of the presence ofmultiple enzymes for hydroxylation inliver microsomes, G. Mannering pre-sented data on two-substrate kineticsand the ability to detect, from the pH-dependence of the ethyl isocyanide-21 JUNE 1968

induced spectral changes of cytochromeP-450, the presence of a different reac-tive form of cytochrome P-450 in livermicrosomes from animals treated with3-MC. Studies of stability of micro-somal pigments, changes in the patternof substrate interaction as determinedspectrophotometrically, and the influ-ence of thioacetamide in causing amarked decrease in some enzyme activi-ties, led to the conclusion that differentforms of cytochrome P-450 might bepresent in microsomes. Another dem-onstration of this difference in variousforms of P-450 modified by inducingagents was presented by R. Kuntzman,who described subtle spectral shifts inthe location of the maximum of the COderivative of reduced P-450 in livermicrosomes from animals treated withbenzpyrene, that is, a displacementfrom 450 nm to about 448 nm. H.Remmer and A. Hildebrandt then pre-sented studies directly demonstratingspectral properties of the two forms ofcytochrome P-450 preferentially alteredby treatment of animals with barbitu-rates or polycyclic hydrocarbons. Theability to identify and characterize twoforms of cytochrome P-450 and assessthe content of each form (termedP-450 and P-446) in microsomes fromvarious sources now opens the possi-bility of resolving the complexity ofdifferences in enzyme activities whichhave been observed with various species,sex, age, or pretreatment of animals.

D. Nebert described studies showingthe increased incorporation of aminoacids in rat liver microsomes after treat-ment of animals with PB and the rela-tionship of this change to the increasedlevels of messenger RNA. In contrast,treatment with 3-MC causes an increasein the rate of nuclear RNA synthesisand the content of RNA in the nu-cleus. Studies of polycyclic hydrocarbonstimnulation of benzpyrene hydroxylaseactivity in tissue culture of embryoniccells indicate that the inducer hydro-carbon may be acting on mRNA trans-lation, resuLlting in a feedback controlaffecting an increased synthesis of nu-clear RNA. Thus it is concluded thatinducing agents may exert their influ-ence not only by causing an activationof specific genes but also by affectingthe translation of mRNA. E. Bresnickthen discussed the activation of chro-matin by 3-MC by ascertaining thetemplate efficacy of chromatin fromlivers of animals treated with 3-MC.Differences in nearest neighbor fre-quency in the product of RNA poly-merase suggest that 3-MC causes an

WORTHINGTON

III

New 1968Catalog

of Enzymesfor Research

fromWorthington

Worthington's new catalog is thelatest, most complete listing ofenzymes and related biochemi-cals for research. It lists morethan 220 products. It includessource, activity, purity and assaydata on each.At Worthington, we make vir-

tually all our own products, car-rying them from raw materialthrough packaging. With com-plete control over every step, wecan give important guarantees ofenzyme quality that other sup-pliers can't.Use the coupon to request your

catalog or other Worthingtonliterature.Canadian distributor: Winley-MorrisCo., Ltd., Montreal.

1375

New Coors super-ceramic lab-ware is the strongest, mostcorrosion-resistant labwareavailable. It's made of 99.98%aluminum oxide-essentiallypure synthetic sapphire. Usethis new super-ceramic labwarefor carbonate, borate, peroxidefusions - even hydrofluoricacid digestions-without detri-mental effect. Use it forhigh-temperature ashing andignitions. Use it as a safesubstitute for platinum at one-fifth the cost. Shapes includecrucibles, dishes, boats, andtrays. See your local laboratory-supply dealer or write forcatalog.

Coors Porcelain CompanyGolden, Colorado 80401

1376

activ ation of liver chromatin resuLltingin an increased number of sites avail-able for the transcription of RNA.

I. Arias presented the restults of aseries of double labeling experimentsdesigned to determine whether the in-creased level of hepatic smooth E.R..observed after PB treatment of animals,was a consequence of enhanced pro-tein synthesis or decreased degradation(stabilization) of membranes. The re-sults indicate that smooth E.R. proteinshave considerably different tuLrnoverrates and that PB enhances svrnthesisof some microsomal proteins b'Ut notall.

T. OmuLra then discussed his experi-ments designed to establish that theturnover of cvtochrome b-, was uin-affected. whereas that of the flavopro-tein NADPH-cvtochrome c redLuctaseof liver microsomiies was affected upontreating the animals with PB. Since P13showed little effect on the incorporationof radcioactive amino acid into totalmicrosomal protein. OmnurL concl ldcicdthat the stimulation by PB seems to befairlv specific. In addition PB "x asshown to inflLence degradation of thereductase and cvtochrome bh. indicIt-ing that the increase in smooth L.R.rmna he mostlyr attributed to a relativevlnonspecific prevention of hreakdow\vi otmicrosomna,l protein componienits. H.Ma-rver then discussed stuLdies descrihb-ing the role of heme in the svnthesisand repressioni of microsomiial proteCin.Injection of I to 4 urmole of hemiie pei100 gram body weight represses drulg-indLuced synthesis of aminolevUlenicsvnithestase as well as drug-indUcedsyrnthesis of cvtochromne P-4-50.

During the general discuLssion at theend of the mneeting. J. Casida describedthe role of cvtochrome P-450 in themetabolismii of insecticides by fliespointincg ouLt the similarities between theliver microsomal hydroxylation systemof marmmals and the parallel enzymes\xstem in insects. A. Conney concludedthe session bv discuLssincg soime pre-liminary studies relating the content ofhenzpxrene hvdroxylase in placentasfromr1 women who were cig arettesmokers. The ability to directlx demlon-strate this activity in smokers. bLt notin nonsmokers. represents the first di-rect evidence for a compensatory enzy-matic mechanism by huLmans to detoxifycarcinogenic poly cyclic hydrocarbonspresent in cigarette smiioke.The meeting was sponsored by the

Commiiittee on Applications of Bio-chemical Stutdies in EvaluLating DrutgToxicity. Drul(g Research Board. Na-

DIAL A

GRADIENT

FOR CHROMATOGRAPHICELUTION

OR FILLINGZONAL ROTORS.

The ISCO Model 190 DIALA-GRAD Programmed GradientPump will form almost any twocomponent concentration, pH, orother gradient by simply settinga series of dials. A completelymixed, essentially non-pulsatingflow at a uniform rate is producedwith no cams to cut or multiplesolutions to mix at estimated con-centrations. The shape of thecurve is determined by settingeleven 0 to 100% dials which rep-resent the initial, final, andnine evenly spaced intermediateratios. This gives 10 program in-tervals, each of which are auto-matically subdivided into fivelinear interpolations to producea smooth gradient.

Calibrated flow rates from 0.5to 500 milliliters per hour andprogram durations from 10minutes to 12 days are set withpositive stop switches. The DIAL-AGRAD will produce linear orcurved gradients with equal ac-curacy and the program will beperfectly reproducible run afterrun. The instrument takes but afew seconds to program and re-quires no attention during aprogram run.

For more information, ask forbrochure DP37F.

3JINSTRUMENTATION/ 1'SPECIALTIES CO., INC.

5624 SEWARD AVE. LINCOLN, NEBR. 68507

SCIFNC E V01-. 160