Paradigms regained

uo/iji'y

11x1(11

Vaccines and infectious disease — i^uUl. ho/ii ji >^])hages

duced, ;is well as the nature o\ the cellular res|>onses. Naturally oecurrint^ changes in the balance of these sometimes lead to 'self-cure\ A />iior/ this gives one hope that mani[)ulations of the immune system by the clinician could lead to similar salutorv results. Indeed, some of the significant regulatory factors in immune responses are becoming understood; for example the immune resjjonse genes and their products, the !a antigens (discussed by Ethan M. Shevach. NIH), which control T-c;e!i and macrophage activation. However, nothing presented at this symposium suggested that such therapeutic hne tuning of immune regulation will be possible in the near future. Similarly, while there is considerable progress in understanding the mechanisms of antil>odv-mcdiated effector functions, the activation and action of complement, macro-

m

and granulocytes {reviewed by Henr\ Metzger (Nil I), Irma (iigli (New \'ork L'niversitv. Celso Bianco Sl.'W Medical Clenter) and John Ciallin (Nlil)), the possibility of manipulating these effector functions, for example pharmacologically, still seems a bit futLiristic, The free discussion at the end of the meeting led by John David (Harvard), touched on the relative contributions towards the eradication of these infectious scourges by basic research into immune mechanism.s on one hand and on the other, research on vaccine development. There was general agreement that, leaving all other issues aside, those working in countries in which these diseases are prevalent need to follow both approaches. Strategy for future w-ork is common to most infective diseases: clarification of effective immunity, be it cell-mediated or antibodv-

meciiated; the isolation of antigens which can induce protective immunity and the search for successful vaccination procedures. However, a concensus on whether the pnricipa/ effort should be to develop vaccines as rapidly as possiljle using currently available technic^ues and knowledge, rather than to develop new knowledge, was more difhcult to achieve. Ihniry Mcizurr i\ Si'd'claryjl reasurcr of ihr Anirriiari Asux ial/(»i nj Iiiuniin()l<)i^is!.\. 2f>:')() RncknUf Pikr. Brihrsda. Ml) 2(X)l.f. (\S.A. Hn^iilli' Askuiias is m fhf Division of hni>iuunloi]^y
Mrnk

Cni>.T-;id,.d

,k

, Ko^s l . a l i o n i r o r i c s ; WJdiai.i'. .md Wilkins

Shiirpo .ind l l o l i m c Kcsciiri li I.;ilnir;iUii ies, Nt'w N.iuonal

Xuumum.,

<\v M C X K U

-

Kniona.

SfiifiHri:i .\(ad<'iiiii.i. Ksiiu-la \ , K mnal clr(.u-ni las Hioloi:i<',is - S i ' K i u n dc(,r;Kiii;Hli.s, S<>i . I'turi.t dc S;ilnt,nd;id \

\Oslciid;i,

N a u o n a l l n d i t , i t i v i d . - S < , l u d . I n M i l u t . K k Seiiund.id v S^'rMUus SOM;II('S d<- l o . h-Ml);iiii(lui,>. dri l,M;id<), Jiinssi^ii I'har-

rastrum Paradigms regained Edward S. Golub Department of Biolos^ical Sciences. Purdue University, West Lafayette, IN 47907, U..S.A.

The final arlicle in a shmi scries an the niiliim iiffHirnrhgins and their place in basic and applied immiinnloi;y In the first two articles in tliis series ' - I addressed the nature of paradigms and their role in basic and appUed science, pointing out that each branch of science uses paradigms differently. In this third and final article I want liriefly to address the manner in which basic and applied science (or perhaps more correctly, science and technology) depend upon each other, even though they function differently. Historians of technology have long been engaged in a detjate over the role played by the practical needs of society in the choice of (juestions that scientists choose to examine. In the earlier articles 1 developed the idea that the practical application of basic science lasts even after the paradigm in which it was spawned has changed. If this idea is correct, then it follows that basic scientists and applied scientists use different sets of values in rheir evaluations of validity and progress. Basic scientists must function with constantly changing notions of truth because their paradigms change, while applied scientists rccjuire the constancy of a repeatable phenomenon which gives predictable results no matter what the paradigm. The ultimate test of a bridge, aher all, is if it can bear a certain load

and paradigms be damned as long as it works. In a similar manner, no matter what the theory says, infusion of substance X into a patient must not have harmful effects. The applied is derived from the theoretical but, like an adolescent child, at some point it assumes an identity of its own because the needs it must meet are different from those the parent paradigm must satisfy, I want to argue here that technology causes the world to change in such a manner that the world view of the basic scientist is changed and this has a profound effect on the problems which he/she (the basic scientist) sets out to solve. In this essay I want to put forth the notion (which may or may not be original) that the interaction of society's needs with basic and applied research induces a form of regulatory circuit which drives forward both forms of science. O n e cannot, therefore, look at either the applied or the basic in isolation, Lewis Thomas has written' thai, 'I am willing to predict, uncertainly, provisionally, that there is one c e n t r a l , universal a s p e c t of h u m a n b e h a v i o r , genetically set by our very nature, biologically gover«. Llsevier BiDmedicnl Kress 19H2 01 (V ^ g 19/82/IHHKM)00()/S2.7n

60

ned, driving each of us along. Depending on how one looks at it, it can be defined as the urge to be useful. This urge drives society along, sets our behavior as individuals and in groups, invents all our myths, writes our poetry, composes our music.'* The genetics of this drive are certainly an open question but the [ihenotypic expression of a desire to be useful is, to my mind, passionately correct. The drive can sometimes seem to take strange turns, but I agree with Thomas that it is there. Now, one can be useful in many ways, not the least of which is by doing science, either basic or applied. This question of the need to be useful is at the very center of the historians' debate of how basic scientists choose their questions. The most extreme view of the effect of the needs of society on the choice of the problems which basic scientists study is that of the Marxists. This position has been argued most effectively in philosophical circles by Boris Hessen, a Soviet physicist who vanished in the Stalin trials of the 1930s. In an extensive analysis^ of Newton's Pnncifna Hessen outlines the major social and economic problems from the Middle Ages to the time of Newton and argues that commerce (and its handmaiden, war) were the primary determinants in the fundamental questions Newton examined. For example, land trans[)ort was so difficult that commerce depended on water transport and to enhance maritime practice one had to improve tonnage capacity and speed of vessels (problems of hydrostatics); improve floating qualities ( h y d r o d y n a m i c s ) ; solve problems of navigation (problems of time and tide which lead to the study of gravity; etc.). Hessen then goes on to argue that there is a causal relationship between these topics in the Pnmipia and economic imperatives. In sharp contrast to this is the view derived from Aristotle which says that at some point man asks questions for the sake of the question itself. 'For it is owing to their wonder that man first began and now begin to philosophise . . . for it is when almost all of the necessities of life and the things that make for comfort and recreation had been secured, that such knowledge began to be sought.'^ Since all of the things which make for comfort would be secured in the Golden Age, then people who seek after knowledge do it for its own sake. Well being, however, is a relative thing and with the passing of the Golden Age, Western man settled into a long period of acceptance of his lot. T h e idea of progress as a sequential change leading to a better life is a fairly recent innovation"" and it is not until the Industrial Revolution (ca. 1800) that the belief that one's lot can be improved begins to permeate society. Technology then became the tool by which life would be made better. The change in English life was so

*One could argue that we scientists really write society's myths as well as some of its greatest poetry and music, but that can keep for a later time.

Immunnliigy Today, ml. 3. ,VVy. 3, 19H2

rapid that writing in 1860 George Eliot looks back ruefully to 1800. Tngenious philosophers tell you, perhaps, that the great work of the steam engine is to create leisure for mankind. Do not believe them: it creates a vacuum for eager thoughts to rush in. Even idleness is eager now - . . . prone even to scientific theorising, and cursory peeps through microscopes.'" Certainly in matters of health our expectations have risen. Living our biblical allotted time is not sufficient. We want not only more years but also the improved quality of life which modern medicine promises. An article of faith in all of this is the idea that progress comes about through the interplay of basic and applied biomedicine. My thesis here is that the interplay of basic and applied science has helped initiate changing levels of expectations. However, the applied fruits of basic science introduce whole new areas of questions which the basic scientist begins to examine and these result in changing paradigms. It is the changing paradigms that give basic science the sensation of progress. This sensation of progress has the natural consequence of generating truths which can be applied directly to society's needs, thereby changing society and in the process raising higher still the levels of expectation of the society before the cycle begins again. Robert Good in his presidential address to the American Association of Immunologists in 1976'' made a wonderful analysis of the interplay of basic and applied science in immunology. (Jood's thesis is that the solution of medical problems initiated lines of thought which led to solution of those problems but opened new areas of basic investigation which then allowed other medical problems to be approached and solved. For example, the long known but dangerous practice of inoculation of smallpox pustules as a means of preventing smallpox led Jenner to use cowpox which led to the principle of a t t e n u a t i o n (Pasteur). The germ theory of disease (Koch) coupled with knowledge of immunity and attenuation led to active and passive immunization (von Behring). Good traces this interplay of applied and basic problems through the history of immunology and argues that the clinic has provided much of the impetus to the laboratory. All too often this interplay and interdependence of the basic and applied get lost. We all want to think that we are doing the most useful thing and we are by the nature of science bound up in our paradigms. The basic scientist will focus on the solution of the problem at hand but will move on to a new problem, perhaps with a new paradigm, which may be driven by a new sense of societal needs. The clinician will focus on the solution and the refinement of the benefits which the solution to that same problem has given and improve upon the usefulness of the solution. But whether we are extracting the useable bits, changing the paradigm or pushing it to its limit we are all part of a circuit which results in demonstrable beneficial results to society.

Innnun'ii'iti]' Tii/h:]. ml.

Acknowledgements Several pe()[)lf' u c r e extrfniclv helpful in the writing i^t these three artieles. I would like espeeiallv to thank Ken Shaffner tof discussions of Kuhn and l-'oppcr; \ ern Ft)le\' for help with the history of technology; and Janet d e z a r i for discussion ol p(jetry. the \ iitorian niind and prose style. It has been called to tiiv attention that the title l'ni(iil)«iiis Ijisl has been recently used l)\ John Simon. I thought that I was borrowing this pun hoin my h'iend Leo Hoffmann and apologi7e to Mr. Simon.

2 Colub. K. S. (1981) limnuunl. T,„l,i} 2. v-vi 3 Thomas. I.. Sept./Oct. 1980. Ilaminl Maoirjuc 4 I lessen. B. (juoted in Iruilt. \\ . II. and Solomons. I. W. (!., (1974) .V,;™,.'. r,',hnnlu«\ anil Fnrilom. p.89, Houghton MiHin, Boston 5 .Xristotlc. Mi'lr:/ihvM,i (1960) (Hope. R. transl). p..5. I'nivcrsitv of Michigan. .\nn .Artjor 6 Bcng, J. B. (19,12) The UcnnI P,,i«rn^. .Macinillan. New York 7 Stent.'(;. S. (1978) Parmb.xr-. nf Pr,i«rc^.. \V. H, Freeman. San in anciseo 8 I'diot. (.forge A/lani llr/Ir. Penguin English Library edn. j). ,i57 9 Cood. R. .A. (1976)7. liinmuml. 117, 141.1

References 1 Colul). K. S. (1981)) Immmifil. 1',il„} I. v-vi

The first real human type-C retrovirus Kemarkablc advances over the last two decades have shown a clear actiolos
Sezary type. In addition tv\() further isolates of HTLV are said to have been made in the L'nited States from adult T-cell leukaemia patients and there is some suggestion that all four individuals in whom the virus has been found may have Carifjbean connections. In this regard, it is of considerable interest that in a group of some 30 sera from L'.K. patients with adult T-cell leukaemia, the only individuals with antibodies to H LLV have definitely been of Caribljean origin (XL F. (Jreaves - [)ersonal communication). f'Lxciting new information relevant to the possif:ilc s|)eciric regional significance of H T L V in adult T-cell leukaemia has now emerged unexpectedly from Japan, .'\dult I-cell leukaemia is rare in Japan in general, as elsewdiere in the world, but an unusual clustering of cases has been noted in the .Sotithern island of Kyushu, particularly around Kagoshima Prefecture"''. .\ T-cell line established from one of these Japanese cases" has been shown very recently to produce H'I'LV in vilrri (Y. Hinuma - submitted for publication) and there are further unpublished reports that co-cultivation of these HTLV-produeing cells with fetal cord blood lymphocytes has induced translormation, giving rise to fetal-derived T-ccIl lines (I. Miyoshi - unpublished results). T o complete the picture, the latest studies seem to indicate that Japanese [latients with adult T-cell leukaemia and an ap[)reciable number of normal indivicfuals from Kyushti possess antibodies to HTLV. For the first lime with claims for a human retrovirus, the ptiblished work on H'lTA' is solid and wellfounded and there is no reason to believe that the latest deveIo[)ments are not ec^ually so. From what is known so far it does not seem unreasonable to anticipate that H LLV will be shown eventually to have a strong actiological link with adult T cell leukaemia, in itself an unusual and pectdiar form of malignant disease. If this proves to be the case, H LLV will join I'.jjstcin-Barr (EB) virus with its compelling association to endemic Btirkitl's lymphoma and nasopharyngeal carcinoma, and hepatitis B virus, with its