the sphinx - a more appropriate rorschach symbol is it time for a change?

1
TIPS - August 1985 7 Graziani, G., Tirone, F., Barbadoro, E. and Testa, R. (1983) Arzneim.-Forsch. 33, 1155-1160 8 Spencer, R., (1984) BYTE 9, pp.129, 135 9 SAS User's Guide; Statistics (1982), pp. 415-473. SAS Circle Cary NC 27511, USA 10 Closse, A., Frick, W., Drawid, A., Billiger, G., Hanser, D., Sauter, A. and Tobler, H.J. (1984) Naunyn-Schmied. Arch. Pharmacol. 327, 95-101 315 11 Everitt, B. S. (1980) Cluster Analysis, 2nd edn, Heineman, London 12 Afili, A. and Azen, S. (1979) Statistical Analysis, 2nd edn, Academic Press, London The sphinx- a more appropriate Rorschach symbol Is it time for a change? Science used to be so much fun. You could put on your lab coat, rattle a few test tubes, record some muscular contractions, and at the end of the day hang up your lab coat with a feeling of genuine satisfaction. With a little careful planning, one could even hope for a reasonable career contributing to our understanding of Nature. The laboratory attire and all of the attendant equipment provided visible and readily identifiable symbols to colleagues and friends that the power of the 'scientific approach' was at hand. The importance of these sym- bols should not be under- estimated. Symbols and logos have fueled many ventures: sports teams, national armies, govern- ments and advertisement com- panies. They allowed the public an easy means for identification. Frequently the symbols even re- flected some characteristic that the originator found desirable. A casual glance at the current pam- phlets employed by granting agencies illustrates the pervasive !o - employment of logos and sym- bols. The current Rorschach em- blem found on the principal vehicle for supporting research investigators in the US (Grant Application Form PHS--398) is one such example (Fig. 1). It appears as a human face being reshaped into an eagle. Perhaps the originators felt that completion of the 32 page booklet, with budget, biographi- cal sketch, sources of support, check-list, etc. would hone the investigator to the sharpened state of the eagle eagerly clawing for cherished research monies. Perhaps this emblem, which was adopted in the early 1980s, should be revised. Clearly the recent movement by the Reagan Administration to reduce by 1526 the number of funded grants per year signals a change in attitude toward the importance of basic research. At a time when less than 25% of approved grants will be funded, many investigators feel that the painstaking completion of PHS-398 provides little hope for the production of research funds. Even the claws of an eagle are insufficient. One small mistake or omission and the grantee finds his or her grant with a priority score below the almost unreachable cur- rent limit. Is not the Sphinx a perfect candidate? For she, who had the face and voice of a virgin, the wings of a bird, and the claws of a griffin inhabited the foot hills outside Thebes awaiting wayward travellers. Propounding dark and mysterious questions reportedly given to her by a Muse, the Sphinx would quickly slay the traveller, who was unable to answer the question correctly. No time for thinking was allowed; no mistakes permitted. Is it time for a change? JOHN S. LAZO Department of Pharmacology, Yale Univer- sity School of Medicine, New Haven, CT 06510, USA. Buffers may have pharmacological actions We wish to bring to the attention of the pharmacological commun- ity an effect of a biological buffer, that is unrelated to its control of pH. Good and coworkers who syn- thesized these biological buffers have been properly circumspect in pointing out 1,2 that the so-called Good buffers may not be devoid of pharmacological effects. The particular Good buffer we have been using in our studies with the isolated semicircular canal of the frog is HEPES (N-2- hydroxyethylpiperazine N'-2- eth- ane sulfonic acid). In our studies on the cholinergic physiology and pharmacology of this prepar- ation we have been applying various cholinergic agonists and antagonists and monitoring the effects these have on the firing rates of afferent neural units in the ampullar nerve of the semicircular canal. Application of acetylcholine produces a biphasic effect on the firing rate of these afferent units causing both a facilitation and an inhibition of firing when a bicar- bonate buffer is used. When HEPES buffer is used, acetyl- choline produces only an inhibi- tory effect. This is exactly the effect that the muscarinic antag- onist atropine has on acetylcho- line's action in this preparation. We therefore conclude that, in our preparation, HEPES appears to act as an antagonist of acetyl- choline at what is probably a muscarinic site. We also note that a chemically-related substance, piperazine citrate, which is used to treat ascaris infestation is thought to exert its therapeutic effect by an anticholinergic action on the worm. CHARLES H. NORRIS AND PAUL S. GUTH Departments of Otolaryngology and Pharma- cology, Tulane University School of Medicine, New Orleans, LA 70112, USA. References I Good, N. E., Wingert, G. D., Winter, W., Connolly, T. N., Izawa, S. and Singh, R. M. M. (1966) Biochemistry 5, 467-477 2 Ferguson, W. S., Braunschweiger, K. I., Braunschweiger, W. R., Smith, J. R., McCormick, J. J., Wasmann, C. C., Jarvis, N. P., Bell, D. H. and Good, N. E. (1980) Anal. Biochem. 104,300-310 1985,Elsevier SciencePublishers B.V., Amsterdam 0165 6147/85/$02.00

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TIPS - A u g u s t 1985

7 Graziani, G., Tirone, F., Barbadoro, E. and Testa, R. (1983) Arzneim.-Forsch. 33, 1155-1160

8 Spencer, R., (1984) BYTE 9, pp.129, 135 9 SAS User's Guide; Statistics (1982), pp.

415-473. SAS Circle Cary NC 27511, USA 10 Closse, A., Frick, W., Drawid, A.,

Billiger, G., Hanser, D., Sauter, A. and Tobler, H.J. (1984) Naunyn-Schmied. Arch. Pharmacol. 327, 95-101

315

11 Everitt, B. S. (1980) Cluster Analysis, 2nd edn, Heineman, London

12 Afili, A. and Azen, S. (1979) Statistical Analysis, 2nd edn, Academic Press, London

The sph inx - a more appropriate Rorschach symbol

Is it time for a change?

Science used to be so much fun. You could put on your lab coat, rattle a few test tubes, record some muscular contractions, and at the end of the day hang up your lab coat wi th a feeling of genuine satisfaction. With a little careful p lanning, one could even hope for a reasonable career contr ibut ing to our unde r s t and ing of Nature. The laboratory attire and all of the a t tendant equ ipmen t p rov ided vis ible and readi ly ident i f iable symbols to colleagues and fr iends that the power of the 'scientific approach ' was at hand.

The impor tance of these sym- bols should not be under- est imated. Symbols and logos have fueled many ventures: sports teams, nat ional armies, govern- ments and adver t i sement com- panies . They al lowed the publ ic an easy means for identif ication. Frequent ly the symbols even re- flected some characterist ic that the or iginator found desirable. A casual glance at the current pam- phlets employed by grant ing agencies il lustrates the pervasive

!o -

employmen t of logos and sym- bols. The current Rorschach em- blem found on the pr incipal vehicle for suppor t ing research invest igators in the US (Grant Appl ica t ion Form PHS--398) is one such example (Fig. 1). It appears as a human face be ing reshaped into an eagle. Perhaps the or iginators felt that complet ion of the 32 page booklet , wi th budget , b iographi - cal sketch, sources of support , check-list, etc. would hone the invest igator to the sharpened state of the eagle eagerly clawing for cher ished research monies.

Perhaps this emblem, which was adopted in the early 1980s, should be revised. Clearly the recent movement by the Reagan Adminis t ra t ion to reduce by 1526 the number of funded grants per year signals a change in at t i tude toward the importance of basic research. At a t ime when less than 25% of approved grants will be funded, many invest igators feel that the pains taking complet ion of PHS-398 provides little hope for the product ion of research funds. Even the claws of an eagle are

insufficient. One small mistake or omiss ion and the grantee finds his or her grant wi th a pr ior i ty score below the almost unreachable cur- rent limit.

Is not the Sphinx a perfect candidate? For she, who had the face and voice of a virgin, the wings of a bird, and the claws of a griffin inhabi ted the foot hills outs ide Thebes awai t ing wayward travellers. Propounding dark and myster ious quest ions reportedly given to her by a Muse, the Sphinx would quickly slay the traveller, who was unable to answer the quest ion correctly. No t ime for th inking was allowed; no mistakes permit ted.

Is it t ime for a change?

JOHN S. LAZO

Department of Pharmacology, Yale Univer- sity School of Medicine, New Haven, CT 06510, USA.

Buffers may have pharmacological actions We wish to br ing to the at tention of the pharmacological commun- i ty an effect of a biological buffer, that is unrela ted to its control of pH.

Good and coworkers who syn- thes ized these biological buffers have been proper ly circumspect in po in t ing out 1,2 that the so-called Good buffers may not be devoid of pharmacological effects.

The part icular Good buffer we have been us ing in our studies wi th the isolated semicircular canal of the frog is HEPES (N-2- hydroxyethylp iperaz ine N'-2- eth- ane sulfonic acid). In our studies on the cholinergic physiology and pharmacology of this prepar- at ion we have been apply ing various cholinergic agonists and antagonis ts and moni tor ing the effects these have on the firing rates of afferent neural units in the ampul lar nerve of the semicircular canal.

Appl icat ion of acetylcholine produces a b iphasic effect on the firing rate of these afferent units causing both a facilitation and an inh ib i t ion of firing when a bicar- bonate buffer is used. When HEPES buffer is used, acetyl-

choline produces only an inhibi - tory effect. This is exactly the effect that the muscarinic antag- onist a t ropine has on acetylcho- l ine 's action in this preparat ion.

We therefore conclude that, in our preparat ion, HEPES appears to act as an antagonist of acetyl- choline at what is probably a muscarinic site. We also note that a chemically-related substance, p iperazine citrate, which is used to treat ascaris infestation is thought to exert its therapeut ic effect by an anticholinergic action on the worm.

CHARLES H. NORRIS A N D

PAUL S. GUTH

Departments of Otolaryngology and Pharma- cology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

R e f e r e n c e s

I Good, N. E., Wingert, G. D., Winter, W., Connolly, T. N., Izawa, S. and Singh, R. M. M. (1966) Biochemistry 5, 467-477

2 Ferguson, W. S., Braunschweiger, K. I., Braunschweiger, W. R., Smith, J. R., McCormick, J. J., Wasmann, C. C., Jarvis, N. P., Bell, D. H. and Good, N. E. (1980) Anal. Biochem. 104,300-310

1985, Elsevier Science Publishers B.V., Amsterdam 0165 6147/85/$02.00