Gurwitsch a.G., L.D. Twenty Years of Mi to Genetic Radiation

13
Introduction T wenty years’ existence of a new discipline gives a substantial basis for critical review of its successes and failures. This is particularly true for mitogenesis, because such a review may throw light on a very pecu- liar, and, in our opinion, unprecedented chapter in the history of science. The fate of mitogenesis is indeed very peculiar: A re- view by several authors, published in commemoration of the decennium of the discovery of mitogenetic radia- tion, appeared at the culmination point of the apparent success and acknowledgement of the new discipline. 1 Since then, the opposite trend has become more and 21st CENTURY Fall 1999 41 Alexander and Lydia Gurwitsch from a 1940s photo- graph. Twenty Years of Mitogenetic Radiation: Emergence, Development, and Perspectives A translation of the great Russian biologists’ 1943 review of the discovery and development of mitogenetic radiation. by Alexander G. Gurwitsch and Lydia D. Gurwitsch Courtesy of Biophotonics EDITOR’S NOTE This 1943 article was translated from Russian by Dr. Vladimir Voeikov and Dr. Lev Beloussov, a grandson of the Gurwitsches. It first appeared in English as an ap- pendix to the proceedings of the International A.G. Gurwitsch Conference, Sept. 28-Oct. 2, 1994, held in Moscow, titled Biophotonics: Non-Equilibrium and Coherent Systems in Biology, Biophysics, Biotechnol- ogy (Moscow: BioInform, 1995). It was originally pub- lished in the Russian journal Uspekhi Sovremennoi Bi- ologii (Advances in Contemporary Biology), 1943, Vol. 16, No. 3, pages 305-334. This translation has been ed- ited in collaboration with Dr. Voeikov. A report on the second International A.G. Gurwitsch Conference, held in Moscow in September 1999, will appear in the next issue of 21st Century.

Transcript of Gurwitsch a.G., L.D. Twenty Years of Mi to Genetic Radiation

Page 1: Gurwitsch a.G., L.D. Twenty Years of Mi to Genetic Radiation

Introduction

Twenty years’ existence of a new discipline gives asubstantial basis for critical review of its successes

and failures. This is particularly true for mitogenesis,because such a review may throw light on a very pecu-liar, and, in our opinion, unprecedented chapter in thehistory of science.

The fate of mitogenesis is indeed very peculiar: A re-view by several authors, published in commemorationof the decennium of the discovery of mitogenetic radia-tion, appeared at the culmination point of the apparentsuccess and acknowledgement of the new discipline.1

Since then, the opposite trend has become more and

21st CENTURY Fall 1999 41

Alexander and Lydia Gurwitsch from a 1940s photo-graph.

Twenty Years ofMitogenetic Radiation:

Emergence, Development, and Perspectives

A translation of the great Russian biologists’ 1943 review of the discovery and development of mitogenetic radiation.

by Alexander G. Gurwitsch and Lydia D. Gurwitsch

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EDITOR’S NOTEThis 1943 article was translated from Russian by Dr.

Vladimir Voeikov and Dr. Lev Beloussov, a grandson ofthe Gurwitsches. It first appeared in English as an ap-pendix to the proceedings of the International A.G. Gurwitsch Conference, Sept. 28-Oct. 2, 1994, held inMoscow, titled Biophotonics: Non-Equilibrium and Coherent Systems in Biology, Biophysics, Biotechnol-ogy (Moscow: BioInform, 1995). It was originally pub-lished in the Russian journal Uspekhi Sovremennoi Bi-ologii (Advances in Contemporary Biology), 1943, Vol.16, No. 3, pages 305-334. This translation has been ed-ited in collaboration with Dr. Voeikov.

A report on the second International A.G. GurwitschConference, held in Moscow in September 1999, willappear in the next issue of 21st Century.

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more evident: Interest and confidence in the new disciplinehave been gradually fading. Things have come to such apoint that now the publication of the next, even modest col-lection of papers seems to be impossible. And the gravity ofthe current moment [the authors are referring to the wartimeconditions of 1943] cannot be the only explanation for sucha situation.

Meanwhile, we, being devoted to mitogenesis, are con-vinced that the real development of this discipline during thesecond decade of its existence was very fruitful. Its achieve-ments have even exceeded the expectations of the broadestscientific circles. How could it happen that—under completeisolation and while seeming to fade on a worldwide scale—mitogenesis was undergoing a rapid and successful self-devel-opment? This question undoubtedly sounds like a challengefor anyone who seeks to reveal regularities in the generalroots of evolution of scientific thought.

We are attempting to review here the overall relations be-tween our laboratory and the scientific community. However,we would like to start from a general formulation of the rea-sons which led to the present situation.

The main reason for the hostility or, at least, the skepticismof scientific circles towards mitogenesis has been the absenceof any connection of the discovered phenomenon to the al-ready known facts, or rather, to their interpretation within thelimits of the conventional concepts. Such a discovery canfunction psychologically like a bomb blast. One can hardlyfind in the history of biology similar cases of the unwillingnessof scientific circles to accept the new fact. The second reasonfor skepticism, and the neglect that manifested itself later, butbecame dominating, was the non-classical character of thephenomenon discovered by mitogenetic methods. This con-clusion can be illustrated by the words of the well-knownphysiologist Hill: “The new era would come for neural physi-ology, if the claims of the Russian authors were correct. . . .”

From the psychological point of view, such an attitude iseasily understandable, although it is quite unworthy of sci-

ence. Unfortunately, most of the researchers educated withinthe frames of a given set of theoretical concepts are unwillingto re-evaluate these habitual concepts, because giving themup is always an unpleasant task. These two motifs are, so tospeak, natural. Conservatism is inherent in science and un-avoidable.

However, along with the above-mentioned reasons, the atti-tude to mitogenesis was fatally influenced by some other cir-cumstances, seemingly attendant and occasional. We meanthe attempts to test our main assertions in other laboratories,both in our country and abroad. With the remarkable excep-tion of the studies of a few authors who really contributed tothe new discipline (among them we may mention Magrou andMagrou, Ziebert, Blacher, Wolf, and Zirpolo), all the other nu-merous tests—with either positive or negative conclusions—led the authors to express doubt. Some of them expressed se-vere criticism.

The latter came primarily from those authors whose aim isto test the existence of the phenomenon, but who do not pre-cisely follow our recommendations with respect to methodsand, in some cases, even deliberately violate them.2

Another reason for distrust of mitogenesis seems to be ratherstrange and forces us to suspect a certain unfairness of somerepresentatives of the scientific community. Numerous re-viewers from various countries, who never sought to carry outtheir own experiments and were often absolutely ignorant ofthe literature on the problem, are claiming that from year to

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The editors of this volume found it appropriate to present,along with the conference papers, this review by

Alexander Gurwitsch and his spouse and devoted assistant,Lydia Gurwitsch. It was written in the full swing of WorldWar II, soon after the authors escaped from besiegedLeningrad, where all the laboratory documents had to beleft. Therefore, the bibliography is incomplete.

This review is of great scientific value, and still relevant. Itis an exciting human document of a “little scientific tragedy,”as Alexander Gurwitsch modestly noted in one of his pa-pers. It is written with his whole heart. Gurwitsch demon-strates here self-criticism, pointing to his previous mistakesand delusions—a feature not frequently met among scien-tists. However, as regards the essence of his main discover-ies, Gurwitsch strictly insisted on their objectiveness. Hewas disappointed by an inadequate and preconceived

attitude of the majority of the scientific community.Obviously, a scientist is free to accept or reject a certain

concept based on the direct experimental facts, but the his-tory of the problem, including the history of the emergenceand development of theoretical ideas also means a lot. Itseems that any reader, either completely unfamiliar withthe problem, or even prejudiced against it, will be im-pressed by the sincerity of the authors’ tone and by such animmense amount of a highly qualified and promising workmade in this field within the first 20 years. Probably, hewill become more open to the perspectives in this scien-tific field that are arising today.

The editors omitted about 10 percent of the original text;they hope to have succeeded in retaining and adequatelyreproducing the content and the style of the authors. Edi-tors’ notes appear in square brackets.

Editor’s Notes from the 1995 Publication in Biophotonics

1. A.G. and L.D. Gurwitsch, 1934. Mitogenetic Radiation. Leningrad: The All-Union Institute of Experimental Medicine Publishing House. In Russian.

2. What we mean here is that our recommendation and restrictions are basedon a firm empirical foundation. For example, our recommendation that theincubation period of a yeast culture should not exceed 2 hours, because themitogenetic effects can not be detected after a longer period, was not takeninto consideration by Schreiber and Nakaidzumi (1932). They tried to ob-serve the effects after a 4-hour incubation period and certainly failed. Inspite of the substantiated recommendation by Baron to use diluted cultures(no more than 200,000 cells/cm2), Bateman and Kruechen (1934) used cul-tures 10 to 15 times more dense.

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year the number of thenegative results is in-creasing, while thenumber of corrobora-tions of mitogenesis isdecreasing. The dis-crepancy between suchstatements and the real-ity is so shocking thatsimilar claims, if madeon the matters of every-day life, rather than onscientific questions,would not go withoutpunishment. Suffice itto say that, according tothe last and obviouslymost complete reviewby Maxia (1940), sev-eral hundreds of con-firming results comingfrom different countriescould be opposed bybarely a couple ofdozen reports of nega-tive results.

We abstain from elu-cidating logical andpsychological groundsfor such an unhealthyatmosphere around mi-togenesis. In any case,the reference to the in-herent conservatism ofscientific thought would be wrong here. But it is important tosay that we have never met in the scientific literature any mo-tivated arguments revealing errors in our central statements orpointing to their physical unattainability. However, as shownbelow in more detail, our long labor has forced us to con-clude that many of our initial suggestions and interpretationsappear to be completely wrong. Therefore, it is not surprisingthat our theoretical interpretations of the experimental resultshave been changing during these 20 years. But we may de-clare with full confidence, that in all cases of recent tests ofour initial experiments (even by the newcomers in this field),the results have always been confirmed.

Emergence of Mitogenesis And the General Trend of Reasoning

Many cases are known in the history of science in which er-roneous assumptions have led to valuable results and even todiscoveries. However, it is difficult to find any analogy to theemergence and development of mitogenesis. A long chain oftheoretical considerations and conclusions, which finally ledto the discovery of mitogenetic radiation, turned out to be aparticular combination of successful and correct ideas, on theone hand, and quite erroneous speculations, on the other.

It would be aimless and tiresome to follow step by step ourentire course of reasoning. We shall limit ourselves to the main

stage of the path taken.However, we shallstrictly preserve the real-ity, without reformulatingthe initial, immature orpoorly substantiated rea-soning according to ourcurrent logical consider-ation of the problem.

An inexhaustible inter-est in the miraculousphenomenon of karyoki-nesis was the startingpoint of the whole story.Having in mind purelycytological aims (shiftingyolk platelets out of theanimal parts of tritoneggs), we employed anintense centrifugation ofeggs. We were amazedby the resulting, chaoticpicture of cleavage thatdisobeyed all rules andregularities and lookedlike an “occasional”event. Was it really so?By a strange coinci-dence, just at that time,we became acquaintedwith a book on biomet-rics, containing an ele-mentary account ofprobability theory. Using

the elementary notions of normal, supernormal, and subnor-mal distribution, we could easily demonstrate on a number ofsubjects (and on onion roots in particular) that spatial distribu-tion of mitoses obeyed purely random distribution. This resultbrought about the following chain of reasoning that turned outto be crucial for the further discovery of mitogenetic radiation.

Cell division is an “occasional” episode in a cell’s life. Fol-lowing the division of a parent cell, two sister cells may havequite different fates, even under completely identical life con-ditions. One of them may remain intact, while the other onemay divide. From this, the following conclusion could be de-rived: An occasional event is the result of at least two mutu-ally independent factors. To create a theory of the emergenceof mitoses, we had to start with this dualistic concept. Weknow that such a formally correct conclusion from a largelyunconvincing and biologically improbable statement led tothe discovery of radiation. Only much later did it becomeclear that there are alternative explanations of the statisticaldistribution of mitoses, that are almost identical to the “occa-sional” one. It might be the result of a long succession of celldivisions, each having certain fluctuations of interkinesis du-ration. So it was biologically wrong to suggest the existenceside-by-side of sterile and repeatedly dividing cells. However,if the initial idea was correct, that at least two independentfactors were necessary for a cell division to occur, it would be

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From archives of L. Beloussov

Alexander Gavrilovich Gurwitsch (1874-1954)

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logical to assume that one of the factors is endogenous, thatis, it coincides with the whole complex of the internal “ripen-ing” processes (a factor of possibility), while another is exoge-nous, even if it originates in the same organism to which a di-viding cell belongs (a factor of realization). Such a distinctionof the two factors seems to be merely a theoretical construc-tion; nevertheless, it found substantial support and had beenintroduced into science.

We point therefore to an example of a correct conclusionfrom the incorrect premise used in our argumentation. Weshall see below that such a peculiar mixture of successful anderroneous conclusions occurs rather often.

After we had found experimentally that the impulses for celldivisions come from onion basement membranes, and after along series of measurements and calculations, a very simplelinear dependence between the surface area of meristem cellsand the probability of cell division was revealed. The new,quite arbitrary and thoroughly inconceivable conclusionswere derived from these facts. In spite of the physical naivetéof this reasoning, it provided the impulse for decisive experi-ments, instead of leading us down a blind alley.

Because, in those days, we were utterly seized by an unfor-tunate, preconceived notion of the complete “fortuity” of mi-toses, and rejected any possibility of regular cycles of cell di-vision, we suggested the following, quite artificialconstruction.3

Earlier we had demonstrated that the meristem cells growexponentially. From this fact we drew the correct conclusionthat cell surface growth has a strictly assimilative character.This conclusion is identical to an assumption that there existtwo kinds of substances at the cell surface. The quantity of thefirst one (K) does not change with growth, and K occupies thesame surface area during the whole growth period. The areaoccupied by the second component of the surface (A) is con-stantly increasing, because A is growing in an assimilativeway. This suggestion would imply that during cell growth, thecell surface retains all of its properties. Thus, surfaces of smallor large cells should differ only in continuous changing of theratio of the variable parameter A to the constant parameter K.Now, what is the explanation of the simple dependence be-tween the A/K ratio and the probability of mitosis?

Assuming that we are dealing only with an action of exter-nal factors upon the cell surface, we suggested first that thosefactors are similar to Haberlandt’s hormones. In this case, theonly plausible notion would be the following: The cell surfacecan be considered as a kind of mosaic in which K is a dis-persed, and A is a continuous, component. It is clear that as Aincreases, the dispersion of K will increase as well. Hence, ifK is permeable to a hormone but A is impermeable, the per-meability of the cell surface to the hormone will gradually de-crease. Under these circumstances, however, the relation be-tween A and the division probability will be expressed by afraction in which the A-variable is the denominator—that is,by a hyperbolic function. However, this dependence is in factlinear.

This discrepancy impelled us to reject the idea that divisionwas induced by a hormone, and we moved further in the di-rection of risky and far-reaching speculation. The linear de-pendence can be expressed by a formula:

P = aK � A,

where P is the probability of a mitosis, and a is a coefficient.It may follow from such a dependence that K is favorable

but A is unfavorable for the action of an external factor. As Aincreases, more regions occupied by K are inactivated. but acertain residue of K retains its properties. One may suggestthat K creates a regular mosaic which is gradually destroyedby continuously growing A. The fragments of the mosaicwould lose their function under these conditions.

These considerations were followed by a very risky leap ofthought. If the configuration of the K mosaic plays a decisiverole, one may suggest that the perception of an impulse by thecell surface is based upon something which can be defined asa resonance. This suggestion leads to the following: The “fac-tor of realization” which determines cell division is of an os-cillatory nature, that is, it may have something to do with a ra-diation process.

It is difficult to understand now, how such a chain of arbi-trary and physically rather naive reasoning could have led usto the valid result—the discovery of radiation. However, thefirst suggestion, that the cell surface is a decisive factor forperceiving mitogenetic radiation, seems to be true. This wasquite clear at the very beginning, when the nature of the divi-sion factor was completely unknown. Such a conclusioncould be directly deduced from the synchronism of cell divi-sions in various syncytia and polynuclear cells, as opposed tothe high degree of randomness in the distribution of mitoses inmost cell populations. On the other hand, the very idea of aresonance-like principle also contained a grain of truth, whichcould not be completely realized at that time.

Therefore, as now appears quite obvious, a reaction of thecell to one or several photons is possible only if the photonabsorption triggers a chain reaction largely dependent uponthe spatial arrangement of the molecules involved, that is, ingeneral terms, upon the supramolecular order.

We shall now resume the review of our ideas, delusions,and researches that led us to the discovery of mitogenetic ra-diation. It is trivial to claim that knowledge is gained only af-ter many errors and delusions. What may be instructive in ourcase is that blunders frequently intervened in the chain of ourdeductions, sometimes in its most crucial links. This hap-pened repeatedly after the discovery of the phenomenon andin the course of its further investigation.

The First Experimental ResultsAfter we had offered a risky suggestion that some form of

radiant energy constitutes an exogenous factor, we ran into anumber of problems and found ourselves in a rather miserablesituation. Because the visible and infrared parts of the spec-trum could be rejected, only two possibilities remained: eitherultraviolet or some new, unknown kind of radiation. It wasnatural that we tried to investigate the first case.

As followed from our previous experiments, only an onion

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3. It is clear now that the most simple and biologically plausible explanation ofthe linear dependence of division probability on cell surface area is that theduration of interkinesis increases in parallel with cell growth.

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basement membrane could be asource of radiation. It seemed rea-sonable to suggest, in addition,that rays could travel along thewhole axis of the root (not lessthan 10 to 12 cm long) towardsthe meristem. The latter could bereached only by a beam of paral-lel rays.

Strange as it may seem, thechain of our initial reasoningended here, and we did not im-mediately reach the natural con-clusion that at least part of thisbeam could be emitted from theroot. Such a simple idea came, asa kind of a revelation, only a fewweeks later, while I was walking;this may be qualified as one of aninconceivable number of cases ofinconsistency and a lack of logi-cal of thinking.

What came directly from theinitial hypothesis was a ratherdoubtful idea to trace the spread-ing of rays in a bent system, inthe hope that in this case someregions of the meristem zonewould be “illuminated,” whileothers would be “shadowed.” Alarge series of experiments gavethe expected results, that is, thosecalculated as a function of a rootdistortion. But we regret that wepublished them. Both the con-structions and the assumptionsare too complicated, and the re-sults could be explained on thebasis of quite different hypothe-ses. Experiments with frog corneawounding performed at the sametime had similar drawbacks. Inthe latter case, one extensiverounded wound was made by aheated needle and anotherwound, having a linear shape,was made at some distance fromthe first one. We suggested that the impulse to mitoses comingfrom the first wound is able to spread throughout the wholecornea, and that it will be at least partly screened by the linearwound. These experiments also gave some results whichcould be interpreted as positive. It is interesting to note thatthese doubtful considerations and results were accepted withwider sympathy (for example, by Wasserman) than the laterdata which were reliable and unambiguous.

The Main ExperimentEven before we reached, at last, the conclusion that if the

main hypothesis were correct, emission should come from the

root’s tip, we started to look for an appropriate detector. Andthe first successful idea, after so many unsuccessful ones, finallycame. Only a set of cells which is capable of dividing normallybut, at the same time, is sensitive to the action of an exogenous“realization factor” increasing the division probability, could beused as a detector. The result of such an action—that is, accord-ing to our hypothesis, irradiation—could be detected only in acomparison with a control set of identical cells not affected bythe same factor. The well-known onion root could serve againas the most suitable subject for such a study.

Straight roots are completely symmetrical. Thus, they canbe divided into two equal parts by any medial plane. The

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Courtesy of Vladimir Voeikov

Some of the participants at the First International Alexander Gurwitsch Conference onNon-equilibrium and Coherent Systems in Biology, Biophysics, and Biotechnology. held atM.V. Lomonosov Moscow State University in Moscow, September 1994. In the first row areProf. F.-A. Popp (third from left) and Prof. Lev Beloussov (fourth from left), co-chairmen ofthe conference. In the background is a statue of M. Lomonosov and the main building ofthe university, which he founded.

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number of mitoses in both parts is almost equal. Although indifferent roots the total number of mitoses is in the range of1,000 to 2,000, the difference between the two halves of thedicotyledonous plant is no more than 3+ to 5 percent. Even intwo halves of the same section, the difference is only a bitgreater. Therefore, the difference between an irradiated and a“shadowed” half caused by a unilateral, strictly localized irra-diation should be quite distinct.

The first experiments immediately gave brilliant, decisiveresults. Further experiments confirmed the initial data. Thisrequires discussion in more detail because the persuasivenessof even a single experiment appears to be much greater thanone might initially suggest.

As radiation is detected from a root tip at a distance of sev-eral millimeters from the surface of a detector root, the rays,for purely physical reasons, should be directed at the normal.Thus, they should act only on that part of the detector surfacethat intersects the extension of the axis of the radiating root.Therefore, if the detector root is dissected into a series of lon-gitudinal sections coinciding with this direction, the effect—that is, the excess of mitoses on one side compared to theother—should be expected to take place only within the me-dial and paramedial sections, and in any case should de-crease on both sides of the medial plane.

At that time, we already knew that there are fluctuationsin the number of mitoses, equally probable for both halvesof the section. If the probability of an excess within one sec-tion is 0.5 , the probability for x successive sections shouldbe 0.5 ex. That means that if x = 5, this probability should

be as small as 1/64. The following also confirms this reason-ing: The probability of successive unilateral excesses of thenumber of mitoses in the absence of irradiation would bethe same for both exactly medial and much more laterallyprolonged sections. When, under medial irradiation, the ex-cess is detectable just within the medial, rather than the lat-eral regions, the probability that the observed phenomenonwill be of a purely occasional nature becomes very low.

Finally, the last and most convincing argument is that theexcess can be observed within several medial sections of theinduced side; this amount was several times greater than thelevel of statistical fluctuations in other sections. We seetherefore that the result of even one experiment can be con-vincing.

After it was observed that the effect is not inhibited by in-serting between the roots a thin glass plate (several dozen mi-crometers thick), but the effect disappears when a cover-glasswas used, all doubts about the radiant character of the im-pulse were gone. It became clear that we were probablydealing with ultraviolet irradiation. Strict evidence of this wasobtained much later.

Critical analysis of our interpretation of this undoubtedlyreal phenomenon should reveal the following point, whichescaped us at that time, and escaped our critics, whodoubted the experimental fact itself. If the assumptions thatthe irradiation is coming from an onion basement mem-brane and that we are dealing with ultraviolet are correct, itseems impossible that radiation emerging from the onionbasement membrane could pass a distance of 10 to 15 cm,

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The cells at the root tip ofa growing onion divide

quickly. During growth, thecircular cross-section, char-acteristic of the whole root,is maintained. Although in-dividual cell divisions ap-

pear to occur in an unordered, even random distribution,the number of divisions in all directions from the axis mustnevertheless be approximately equal. The root would other-wise not have a cylindrical form.

Gurwitsch supposed that at least some of the cells mustbe emitting light that regulated the rate of division of theother cells; he proved it by means of the experimental set-up shown here. The roots (W) of two onions (Z) were po-sitioned perpendicularly, so that the tip of one rootpointed to one side of the other root. He then examinedunder the microscope the second root, at the site facingthe tip of the first root. He was able to establish a statisti-cally significant increase in cell divisions there, comparedto the opposite, “unirradiated” side. This effect disap-peared when he placed a thin piece of window glass be-tween the two roots, and reappeared when he replaced itwith quartz glass! That meant that ordinary glass is opaquefor mitogenetic radiation, while quartz glass is translu-cent. Hence electromagnetic radiation must be operative,and ultraviolet light in particular, since it passes throughquartz, but is stopped by window glass.

Source: A.G. Gurwitsch, Das Problem der Zellteilung (The Problem of Cell Divi-sion), 1926

Gurwitsch’s Famous ‘Onion Experiment’

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through a meristem layer, down to a root tip in a mediumrich in proteins.

We realized this problem much later, when we had al-ready observed the phenomenon of “secondary” radiationunder the influence of irradiation. The idea of secondary ra-diation came to us when we recognized that the effect of ir-radiation, that is, the excess in the number of the mitoses onthe irradiated side, is spread along the meristem up to 1.5 to2 mm from the area that was briefly irradiated with a pointsource. The diameter of this area did not exceed fractions ofa millimeter. If an irradiated cell transmits the same impulsefurther, by way of secondary radiation, it is obvious that thephotons reaching the meristem are generated not in theonion basement membrane but in the vicinity of this verycell which started to divide after absorbing the photon.

In a short time after our first studies had been published,various laboratories reported their own results, both positiveand negative. Very soon the regrettable situation alreadymentioned in the introduction became obvious. With theexception of a quite reliable investigation of Magrou andMagrou (1927), which was a corroboration of the discov-ered phenomenon, both the positive results by Wagner(1927) and the refutations by Rossman (1928) and Moi-seewa (1931), as well as many later studies, were of no sig-nificance.

We shall discuss these papers from the general point ofview. Our opponents, of which Rossman is an example, usu-ally claim that in several experiments that they performed,the radiation effect could not be reproduced. They opposedtheir results to at least several dozens and, later, more than130 sets of experimental data which we have published.However, we pointed out that we published all of our re-sults, which means that there was no lack of the effects ob-served. In spite of that, our opponents insisted that the de-scribed phenomenon does not exist at all. We consider itreasonable to ask the following direct question: How can theauthors explain our numerous positive results—by a system-atic error made by all of the authors, or by their dishonesty?This question has hardly any answer worthy of the attentionof the scientific community. We consider that negative re-sults may be used as a refutation of the positive ones only insome exceptional cases.

On the other hand, it is not difficult to explain the sourcesof the negative results. Usually, they came from methodolog-ical errors. For example, Rossman used roots of Legumi-nosae as a detector. This dicotyledonous plant obviously hasa certain bilateral symmetry, even in a hidden form (insteadof the required radial symmetry). He centered the roots withthe naked eye, instead of using the horizontal microscope,and so on.

We pay such attention to these incidents because of theirgeneral importance, because they are equally applicable tofurther “refutations” of our data obtained with the use of bio-logical detectors and also to some investigations in whichphysical methods have been used. At this point we finishwhat can hardly be qualified as “scientific polemics.” Wehad to mention these sorrowful facts in our retrospective re-view only because we were often saddled with the reproachthat we ignore weighty objections.

Corroboration of the Ultraviolet Nature Of Mitogenetic Radiation

The hypothesis that mitogenetic radiation belongs to theultraviolet range was experimentally corroborated rathersoon. First, it was found that a crystalline quartz plate iscompletely transparent to radiation, while even the thinnestgelatin plate is nontransparent. Second, Gleb Frank madethe first spectral analysis of radiation from a biologicalsource, which was muscle tissue. Finally, it was established,in collaboration with Frank, that the positive effect uponroots can be obtained from the spectrally dispersed UV fromphysical sources, if the intensity of emission is considerablyreduced and the time of exposure is very short. Incidentally,the latter finding disproved an established view that the bio-logical action of UV can only be inhibitory. It became evi-dent to us (but, unfortunately, not to biologists at large) thatthe mitogenetic phenomena imply very special microevents,which can be neither corroborated nor disproved by em-ploying UV of commonly used intensities and doses.

The second way to prove the identity of mitogenetic radia-tion with UV is to use purely physical methods which over-step the limits of our competence. Therefore, they will bementioned only briefly here. Rajevsky’s data, published pre-viously, were not quite convincing from the standpoint ofquantitative criteria. Later, he obtained additional quantita-tive data and thus removed any doubts.

Numerous attempts were made to use physical methods todetect mitogenetic radiation that were capable of reproduc-ing the data obtained with biological detectors. Some of thefavorable studies, however, could not be considered techni-cally perfect. As well, several reliable, positive studies (forexample, Frank and Rodionow 1932; Barth 1937) were criti-cized by authors who could not detect radiation. And againit was convincingly demonstrated (Barth 1937) that the nega-tive results may appear because of the deficiency of the de-vices, but mostly because the authors neglected our recom-mendations and used unsuitable sources of radiation.

However, a substantial study by Krost and Peuchert, andthe extensive, and largely acknowledged studies by Audu-bert, completely clarified the situation. Mean-spirited at-tempts of the latter author to conceal the truth and neglectthe relationship of his data to our own are a manifestation ofthe grievous symptoms of modern scientific ethics, but theycannot change the essence of the matter.4

Further Development of MitogenesisThe above-mentioned experimental findings were ob-

tained while still in Simferopol [up to 1924] and during thefirst period of our work in Moscow [1924-1929]. Later, par-ticularly because of the introduction of a new detector—

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4. It is interesting that in some reviews of the discovery of mitogenetic radia-tion, even in favorable ones such as Huxley’s, it is stated that I (A.G.) ini-tially claimed to have discovered some specific “rays of life,” and this notionis still widely used in low-pitched popular literature. It is scarcely necessaryto say that this is pure fantasy on the part of the authors. A reasonable initialcautiousness in our first report, with some doubts as to whether the newphenomenon could be related to a poorly studied range of Lyman wave-lengths (shortwave UV), was probably not adequately estimated. But oneshould be astonished that it is possible to ascribe such a childish idea as“rays of life” to me.

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yeast cultures (M.A. Baron)—the scope of our work increasedtremendously. At the same time, the main lines of investiga-tion began to branch off rather chaotically. Such a situationseriously complicates the main task of this review, namely,to attempt to present a systematic account of the develop-ment of the general idea. The rest of this account, therefore,will have a rather fragmentary character. Moreover, we havelost the opportunity to use our notebooks [those left behindin besieged Leningrad] and thus to recover the exact se-quence of our thoughts and the motivations of the new trendsin our work. However, we can say that we were guided by

the following major considerations.First of all, it was but natural to see

whether mitogenetic radiation is a generalbiological phenomenon, and we still re-member our excitement when we suc-ceeded, while still in Simferopol, in de-tecting emission from certain animaltissues (amphibian tadpoles). But later,when it turned out that all the tissues wereemission sources, the problem certainlybecame much more complicated and re-quired new, extensive studies.

We would like to mention one incidentwhich put forward the problem of emissionfrom blood. When studying photon emis-sion from early chicken embryos cultivatedin physiological solutions outside the egg,we ascribed the initial negative results tothe lack of blood circulation. We came tothe idea of studying blood as a possiblegeneral source of radiation. However, itwas established later that the negative re-sults appeared to be caused by the pres-ence of Bunsen burners for heating em-bryos in the near vicinity of the sample.The burners were found to emit much moreintense UV than mitogenetic radiation.

The addition of blood to the range ofexperimental materials initiated a newtrend in our studies that persisted for along time. What was done later in thisfield was mainly the accumulation of oc-casional facts and the results of scientificcuriosity, rather than of a well-definedand substantiated plan.

This applies mostly to the studies ofblood radiation under the influence ofvarious diseases. Many experiments ofthis kind had already been performed byL.D. Gurwitsch at the very beginning ofthe blood studies. In any case, one of themost important chapters in mitogenesis—the study of the “cancer extinguisher”—did not at all emerge as a link in a logi-cally developing chain of events.

An extensive study of various plant andanimal subjects yielded results that couldnot be adequately interpreted in the early

period of our studies, and still cannot: Radiation could not beobserved in all tissues. For example, it was not detected inparenchymous tissues characterized by intense metabolism(liver and kidney). So long as this fact remains enigmatic, onecannot interpret the mechanisms of radiation arising in livingtissues. Up to now, therefore, there are no satisfactory solu-tions to the questions related to the universality of radiationand the conditions of its emergence in living systems.

Moreover, the main problem of mitogenesis, namely, theanalysis of the basic mitogenetic phenomenon—of stimula-tion of cell division by UV photons—was for a long time con-

From archives of L. Beloussov

The Gurwitsch laboratory at Simferopol (1923-1924). Gurwitsch is first row, sec-ond from left; his wife is third from left.

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sidered ambiguous. It is obvious now that consideration ofmitogenesis using the concepts of the usual classical opticswas wrong, because the latter can be applied only to highlight intensities and completely ignores quanta of light. Wetried to analyze the results of our experiments with intermit-tent irradiation, as well as creeping effects and the mecha-nism of a continuous increase of intensity, and so on, assum-ing the concept of continuity of light. For example, inexperiments in which the detector was irradiated with inter-mittent light, this treatment was considered a strictly rhythmicprocess. However, it now became clear that, with the rota-tion frequencies and angular values of sectoral slits used inthe experiments, some of the slits did not let even a singlephoton through. [The routine method involved the insertionof a rotating disk with one or several windows between theradiation source and the detector.] It is obvious that any at-tempts to analyze the process of mitosis induction with inad-equate equipment were doomed to failure.

It was very important to realize that the process of stimulat-ing mitosis with mitogenetic radiation is based on the chainreactions that could be triggered by a single photon. A studyof the chain reactions became possible only because of thediscovery of the secondary radiation, and because of the re-sults of studying processes developing in nonorganized sys-tems (homogeneous solutions) after their irradiation. A studyof these phenomena appeared to be so complicated that wewere diverted for a long time from the main task—the eluci-dation of mechanisms of the mitogenetic effect.

But there was another reason for our excessively slowmovement toward the solution of the main problem. Formany years we could not establish whether mitogenetic radi-ation was really a specific factor that triggers cell division. Toprove its specificity, one should arrest cell proliferation com-pletely by the action of a certain factor X and then restore itcompletely by irradiating the detector from the outside.

Such a crucial experiment was first performed by Zalkind.It yielded the results that permitted us to move forward. Thestudy was made on yeast cultures in a liquid medium. Byadding a negligible amount of the so-called “cancer extin-guisher” from the blood of a cancer patient, a complete,temporary arrest of cell proliferation can be achieved. Afterirradiation of the culture from the outside, proliferation wasrenewed and brought to its initial level. It was also demon-strated that the addition of the extinguisher, besides sup-pressing proliferation, inhibits mitogenetic emission fromthe culture itself. The extinguisher did not disturb any otherconditions necessary for cell division, except for self-irradia-tion of the culture. Thus, it was found that external irradia-tion completely substitutes for self-irradiation of the culturein the process of initiating mitogenesis. These experimentshave proven the specificity of mitogenetic radiation as a fac-tor inducing mitosis in cultured cells which are ready forthis event.

Only later did we establish that not only the impulse for apremature division, but also the development of the mitoticprocess, is controlled by mitogenetic radiation. A series of in-vestigations of photochemical processes opened the possibil-ity for rational analysis of the crucial role of UV photons.

We turn now to the recent investigations that clarify the mi-

togenetic action of UV photons. Irradiation of peptone solu-tions or of a mixture of amino acids (which should include atleast one dicarbonic amino acid, that is, glutamate or aspar-tate) induces their polycondensation into peptide molecules.This conclusion is based on the susceptibility of these pep-tides to cleavage by pepsin that was revealed by the detec-tion of a typical mitogenetic “peptide” spectrum after the ac-tion of a pepsin. To initiate the process in an amino acidsolution, the photon energy should exceed 105 kcal/mol.This energy may be supplied either by a single photon with awavelength not exceeding 270 nm, or by two photons. Theenergy of the first should be not less than 87.4 kcal/mol (326nm), while the second can belong to the visible or infraredrange with an energy limit of 18 kcal/mol, that is, around1,500 nm. Such sharply limited energy requirements may beexplained as follows.

Amino acid polycondensation requires cleavage of one hy-drogen atom from the amino group of one amino acid and ofthe hydroxyl residue from another. The first event requires 87kcal/mol, while the second requires 66 kcal/mol. Total energyexpenditure for both processes is completely compensated bytwo exothermic processes: the formation of a water moleculeand a peptide bond, CO-NH. The additional 18 kcal/mol,which is necessary for the process, represents probably theenergy of activation. We established that from 326 nm, up tothe short wavelength limit of a quartz spectrograph, effective-ness of the UV radiation depends exclusively upon the de-gree of UV absorption by the peptone or amino acids, ratherthan upon the photon wavelength.

Polycondensation may also take place under other experi-mental conditions. After addition of a very dilute liver extractto a mixture of amino acids or to a peptone, polycondensa-tion occurs without UV irradiation by bright visible light, butnot in the dark. It was found that diluted liver extracts irradi-ated with visible monochromatic light, emit UV with a wave-length roughly corresponding to the energy of two photons ofthe monochromatic light. In this case, the process of poly-condensation is triggered only when the energy of the result-ing UV photon exceeds the value mentioned above.

A detailed investigation of the energetic parameters of themitogenetic action of UV has shown that they coincide pre-cisely with those required for polycondensation. All of theabove-mentioned facts remove every doubt that the mecha-nism of mitogenetic action of UV photons consists in, and islimited by, the stimulation of the processes of peptide syn-thesis.

In relation to the main mitogenetic effect, the cancer prob-lem first attracted our attention long ago. An extremely lowlevel of mitogenetic radiation in cancer patients’ blood, be-cause of the presence of the extinguisher, led us to look forthe place of its formation. The mitogenetic analysis provideda definite answer: The extinguisher is a product of cancercells and is obviously located in the superficial monofilmcovering the cell, together with the specific enzymes: gly-colytic, proteolytic, phosphatases, and probably some oth-ers. Their specific feature is that they bear negative charge,while the corresponding blood enzymes are charged posi-tively. Both the extinguisher and the enzymes can be obtained by washing intact cancer tumors. Using spectral

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analysis we obtained evidence that enzymatic activities ofproteases and peptidases in cancer cells are located mostlyepicellularly. That means that their substrates are derivedfrom nutrient medium as well as from tissue elements locatedin close vicinity to the cancer cell. On the other hand, the in-tercellular splitting of proteins in the cancer cell is obviouslyminimal.

Such a peculiar localization of peptidase activity can deter-mine an extremely parasitic character in cancer cells. Alongwith some other discoveries, the following fundamental factthat reveals the origin of cancer was discovered: It appearedthat a number of tested carcinogenic substances emit mitoge-netic radiation, while some similar chemical substances, in-cluding noncarcinogenic resins, lack such a capability (Kan-negiser).

Taking into consideration the peculiarity of the mitogeneticstate of cells exposed to a source of radiation for a long time,as well as the versatility of the action of UV photons uponcells, we may suggest that UV photon emission by carcino-genic substances plays an important role in their action.

The problem of the basic mitogenetic effect was studied formany years with ups and downs. It was typical of all of theimportant problems that we had been studying during thepreceding two decades. We would not be surprised, if some-one said that our school gives the impression of having noprincipal idea, or that it uses the trial-and-error method in re-search work. One should never forget, however, that mitoge-nesis did not have any relationships with the allied sciences,and that all of our results had a “non-classical” character.That is, they did not fit within the usual cytological, chemi-cal, or physical concepts. We therefore had to propose newconcepts for approaching problems, which seemed, at firstglance, to have no connections among them. Later it turnedout that these problems are interrelated. Sometimes it be-comes possible to make a step forward in solving a certainproblem only with the help of new data obtained in theneighboring field of science, which depends, in its turn, uponsome other, often remote, field. After successful achieve-ments in one direction, further progress may be delayed oreven blocked for a long time, until new steps in some otherdirection open the way.

The present status of mitogenesis is, to a considerable ex-tent, determined by the method itself, which appeared to bereally miraculous because of its sensitivity. Mitogenesis im-plies microprocesses in both the organized and non-organ-ized systems. These microprocesses are “non-classical” in thesense that, on one hand, they do not allow easy extrapolationinto the realm of macroscopic events and, on the other hand,they seem to proceed independently of the latter. However,they are usually shadowed by macroscopic processes thatcan be easily studied by the classical methods.

Each section of mitogenesis is supposed to be a narrowgateway into an immense new field. Let us analyze some ofthem.

One of the main achievements was the discovery of so-called “degradational irradiation,” described in the followingbrief history. Studying the mitogenetic process of corneal ep-ithelium, Yu. N. Ponomareva came across the fact that irradi-ation of the enucleated frog eye results in an increase of the

number of mitoses only 20 to 25 minutes after enucleation. Itwas found, at the same time, that the enucleated frog eye didnot itself emit during the whole refractory period, and thatrestoration of its own radiation occurred just at the timewhen its epithelial cells recovered their ability to react to ex-ternal irradiation. At first, she [Ponomareva] could not findthe explanation for this finding.

Investigations of the effect of cooling the cornea revealed aphenomenon that seemed to be quite paradoxical: a verystrong mitogenetic effect was observed when a freshly enu-cleated cornea, being cooled down to 2° to 5°C, was sub-jected to external irradiation. Trying to explain such a strangefinding—that cooling is a factor that favors the effect of theexternal irradiating source—we came to the conclusion thatunder the condition of rapid and intense cooling, the cornealtissues start to irradiate themselves, though this suggestionseemed to be rather unlikely.

This somewhat improbable suggestion was confirmed inthe very first experiment: A burst of radiation under such atreatment lasted for about 5 minutes. This fact had innumer-able consequences in our further investigations. Here againthe work was of the same irregular and scattered character asin the other fields of mitogenesis. The research bifurcated im-mediately into two lines: First, much attention was directedto purely phenomenological aspects of the newly discoveredphenomenon; its universality and the specificity of the emis-sion spectra had nothing in common with the spectra of thesame organs and tissues under physiological conditions. Sec-ond, attempts to provide a theoretical interpretation for theseunexpected events were undertaken, and led us to some new,and again non-classical concepts, such as “non-equilibriummolecular constellations” (NMCs). The latter was, in fact. alogical jump, because it was based on intuition, which gaveus a feeling that NMCs constitute the main apparatus for per-forming quite varied processes that can be considered the ba-sic manifestations of life.

These findings were followed by a series of experimentswhich, at first glance, had nothing to do with the precedingones, but whose results exceeded all of our initial expecta-tions, nevertheless. It turned out that negligible deviations inmetabolic processes and a wide variety of excitations of bio-logical subjects induced degradational radiation differing inits spectral pattern and in the character of evolution of thespectra. The results convinced us that, first, an important andeven a major reevaluation of what we mean by the term“protoplasm” should be made, and, second, new methods forclassical physiology should be proposed for the purpose ofrevealing mostly intimate functional relations among varioussystems and organs, avoiding the usual techniques.

The spectral analysis opened really unlimited perspectivesin quite different areas. Initially it was used by Frank only fordemonstrating that mitogenetic rays really do belong to theUV range. But after we obtained—mainly to satisfy our cu-riosity—the first rather sharply outlined spectral band, thespectral analysis became an autonomous field of investiga-tion. There was a great temptation to apply it in some otherfields that otherwise would not attract our attention, for ex-ample, in nervous system research.

We did not expect that, by performing a spectral analysis of

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nerve fiber emission, we would be able to demonstrate aqualitative variability of excitation processes. Nevertheless,the very first, timid experiment appeared to be the startingpoint for the development of one of the most fruitful and im-portant areas of mitogenesis. As a result, we came to the fol-lowing major conclusions: (1) the emitting substance of thenerve elements is at the same time the target of nerve excita-tion; (2) the analysis of mitogenetic phenomena makes it pos-sible to penetrate into the essence of the molecular substra-tum of excitation processes.

In light of new data concerning degradational radiation,the following concept of neural excitation was formulated(A.A. Gurwitsch): An excited substratum consists of NMCswhich form a three-dimensional “continuum” within thebrain cortex. Even under physiological conditions, the emis-sion of the elements of the neural system has the character ofdegradational radiation, that is, it arises as a result of continu-ous disintegration of NMCs just after their formation. Accord-ing to these views, the substratum for neural excitation is acontinuously oscillating system. Such a concept made it pos-sible to create a rather coherent system interpreting the vari-ous properties of neural excitation.

We shall finish our review with a brief account of a largenumber of investigations with great prospects, and a very pe-culiar path of development.

Starting from our earlier data about the disappearance ofblood radiation that correlated with various deviations from anormal physiological state, our collaborator S.N. Brainesssuggested that grave physical exhaustion should also be ac-companied by a temporary suppression of radiation. His in-vestigations completely supported this idea. As a develop-ment of this idea, it was suggested that blood radiation shouldalso be suppressed in the depressive psychical state which,according to Brainess, has some similarity to tiredness. Onthe other hand, he supposed that in maniacal states, the in-tensity of blood radiation should be higher than in the normalstate. These speculations were completely supported experi-mentally.

Then, Brainess took a rather risky step. He attempted tocure patients in depressive physical states by injecting a smallamount of blood from a maniacal individual. The result waspositive.

The spectral analysis of “maniacal” blood radiation (thelatter was not only intensive, but emitted mitogenetic rays fora long period after the blood was taken) revealed a singlenarrow spectral band in the 229 to 230 nm range. Accordingto our previous data, this band corresponded to the fluores-cence spectrum of amino groups liberated because of oxida-tive deamination of amino acids present in blood serum.Hence, “maniacal” blood is characterized by its increasedcapacity for deamination, while “depressive” blood, on thecontrary, by a sharp decrease of this capacity.

It was of considerable theoretical interest that the therapeu-tic effect of a single injection of a small amount of “mania-cal” blood into a depressive patient appeared to be ratherprolonged. Suggesting that the therapeutic effect of the “ma-niacal” blood injections is directly linked with its increasedirradiation rate, the author took the following step, althoughthere was only a weak theoretical basis for it: A sample of cit-

ric blood from a depressive patient was irradiated with a mi-togenetic source and injected back into the patient. This pro-cedure had a good therapeutic effect. The next step was sub-stitution of irradiation of blood for that of serum and then ofirradiation of amino acid solution, which also demonstratedthe healing effect after injection into patients. The latter pro-cedure was based on the previously discovered remarkablefact: An irradiated amino acid solution itself became a sourceof mitogenetic rays acting for many hours—almost a wholeday. It retained a therapeutic effect when injected at any timewithin this period. This led to a suggestion, that the injectedactive substance, which was analogous to the oxidativedeaminase enzyme, was capable of self-reproduction withthe organism. Such an idea—more intuitive than logicallygrounded—became an initial point for a new, extensivebranch of research into mitogenesis.

[Here the authors discuss further the results obtained in thestudies of self-reproduction of oxidative deaminase activityand of activities of various other enzymes in aqueous aminoacid solutions irradiated by mitogenetic rays. The more de-tailed, up-to-date consideration of this highly exciting andpuzzling problem is presented in the paper by A.G. and A.A.Gurwitsch, “The Problem of Autocatalysis (Autoreproduction)of Some Cyclic Compounds from Lower Amino Acids,” Enzy-mologia, Vol. XX, pp. 1-16, 1958.]

Let us now summarize the complicated development of in-vestigations and the present-day status of mitogenesis. Onemight forgive and forget its intricate, error-laden history oftwo decades if, at present, our major results and conclusionswere really regarded as trustworthy. However, according to aviewpoint that dominates in scientific circles generally, thesituation is unsatisfactory. Our own viewpoint is quite differ-ent, although we would certainly like the situation in thisfield to be much better than it really is. However, our motiva-tions differ from the reasons of our opponents. As we have of-ten mentioned, we cannot point to any case of a refutation ofany of our positive experiments, that is, those demonstratingthe existence of mitogenetic radiation. Thus, we have theright to object to a skeptical and distrustful attitude towardour data.

What seems to be absolutely unsatisfactory, and evenhopeless, is the completely isolated position of the science ofmitogenesis among other, neighboring sciences and the re-sulting fruitlessness of both our data and our theoretical con-structions.

We might consider it rather natural and, at the beginning,even tolerable, if our colleagues, while remaining skepticalwith respect to the theories derived from mitogenetic facts,accepted our experimental results as real. These facts couldthen be introduced into the everyday usage of the firmly es-tablished disciplines and, even if the conclusions drawn fromthem by specialists might differ considerably from our own,that would probably affect only our personal ambitions,rather than the interests of science. In any case, we would besatisfied that some fundamental problems within various dis-ciplines should be seen in the light of new discoveries.

However, just because the acknowledgement of our resultswould lead to an inevitable break with habitual concepts,scientific circles prefer to abstain from accepting them. Actu-

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ally, the hasty phrase of Hill, who we mentioned above, is agood illustration. As mentioned, mitogenetic spectral analysisof active nervous tissue brings new concepts to the fore,which are incompatible with the poor idea of the electriccharacter of nerve excitation. The unwillingness to breakwith these deep-rooted concepts is understandable and par-donable. What is completely inadmissible is to justify one’sown quietism by claiming, as Hill does, that “all of this seemsto exist only in the fantasy of the Russian authors.”

We cannot accept the facts of the rejection of our meth-ods—methods that might be an inexhaustible source of newdata. Nor can we accept an attitude of indifference to our re-sults, which forces us to extend our studies into some fields inwhich we feel ourselves mere amateurs. No doubt, the spe-cialists are able to treat the same problems on a higher scien-tific level. However, because they show no interest in our re-search, we have to do this job by ourselves, being satisfied ifthe data obtained are at least trustworthy and if the relatedtheoretical concepts do not contradict those established inother disciplines. Even when our statements seem to be in-compatible with generally accepted views, this cannot be areason for the automatic rejection of the facts.

Our last task will be to outline the near, and probably moredistant, future of mitogenesis. In this context the followingquestion arises: Does mitogenesis remain as an unresolvedproblem, as a kind of scientific enigma, or, on the contrary,are the foundations of mitogenesis sufficiently elucidated toenable its use as a new, highly valuable concept applicableto a variety of fields in the natural sciences? Certainly wecannot draw boundaries between these alternatives. We canonly speak of one of them predominating.

We suggest that the second part of the question—the use ofthe mitogenetic method—will prevail and will gradually pushinto the background the first, the question of mitogenesis itself.

Within the limits of the purely mitogenetic problem we canraise only two questions: What is the origin of weak UVemission from homogeneous and organized systems, andwhat are the mechanisms of the mitogenetic effect, that is, ofthe control of cell division? We find it warrantable to claimthat the main question of the origin of UV emission duringchemical reactions is elucidated to such an extent that furtherwork will flow in a common physico-chemical channel, andthus UV emission will no longer remain a specific enigma forthis field of science.

The situation with degradational radiation seems to bemuch more complicated. Of course, our explanation of thisphenomenon is simply a preliminary construction in need offurther development. We suggest that in the near future it willbe the central, and perhaps even the only, problem of mito-genesis. It has already become a foundation for new conceptsrelated to the main problems of biology—a field theory.

As for the the main mitogenetic effect—the induction ofcell divisions by one or several photons—the striking paral-lelism between the action of weak UV of mitogenetic intensi-ties upon amino acids, peptides, and whole cells, leaves nodoubt that the mitogenetic effect of UV is identical to that ofsplitting (oligo)peptide (amino acid) molecules with a highprobability of detaching hydrogen from the amino group.This process triggers the peptide synthesis. Why such ele-

mentary reactions lead to cell division is certainly one of themost important and difficult biological problems, and mito-genesis plays its role here.

However, the initial and intermediate links of the radiation-stimulated process, the intermittent irradiation, the transfor-mation of stimulation into inhibition, and the striking dispro-portionality between the number of absorbed photons andthe number of initiated mitoses, all remain obscure.

As we have mentioned, mitogenetic methods disclose mi-croevents that cannot be extrapolated, as a rule, to macrosys-tems. This can throw doubt upon the prospects of studies inthis direction. We believe that this area should be highlyfruitful and that the discovery of microevents may be of greatimportance. First, these events may serve as signals of theexistence of other microprocesses escaping direct observa-tion. Application of our methods to the study of neuralprocesses appeared to be fruitful for the most part. Here therole of mitogenetic radiation may be similar to that of “ac-tion currents,” the latter also being the signals of somethinghappening. Because mitogenetic effects show extreme sensi-tivity, and especially quantitative variability, they have anadvantage over electrophysiological methods. The mitoge-netic method permits analysis of the subject and the processof excitation. Just as the familiar form of spectral analysis be-came the foundation of modern concepts of atomic and mo-lecular structure, mitogenetic radiation—being a signal ofmolecular processes—provides the possibility of deeper pen-etration into the properties of the excited biological sub-strata.

Only the future development of science will show whetherthe wall separating classical and mitogenetic physiology willcrumble.

The same can be said of the mitogenetic analysis of thecancer problem. Here, also, we have no connections withclassical oncology, except for some interest in the extin-guisher phenomenon for cancer diagnosis. We consider theseresults less important than other mitogenetic data related tocarcinogenesis.

An even more extensive field for mitogenesis has beenopened by the discovery of degradational radiation. Theamazing sensitivity of the degradational spectra, reflectingeven minute influences upon living systems or particular or-gans, provides new means for elucidating the functional in-terrelations between different systems. If, indeed, an irrita-tion (excitation) of a certain system A results in changes ofthe spectral composition of system B, the latter being, at firstglance, quite independent of A, we should claim that thetwo are interconnected, even if this can not be registered byroutine methods. But even in those areas where such con-nections are detected by classical methods, the use of degra-dational methods may disclose some new regularities.

Development of this boundless field belongs to the future.Mitogenetic methods should be in common use in physico-chemical studies. Yet, the technique for detection of free rad-icals, which we have elaborated, has been almost completelyneglected up until now, although the appearance of free radi-cals is not just a mere signal; sometimes this event is impor-tant for understanding the mechanism of a process. This con-cerns, in particular, the analysis of those enzymatic processes

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in which only the final products, but not the intermediateones, are known. This is true even for such a simple systemas, for example, urease + urea. Resonance illumination ofthis system with mitogenetic rays made it possible to detectthe existence of free radicals such as the carbonyl group(=CO). This may certainly be a determining factor for under-standing the whole process.

One should keep in mind that we are probably dealing herewith the main course of the enzymatic reaction, rather thanwith some negligible microevent. Such a conclusion is cor-roborated by the following: Mitogenetic analysis does not re-veal radicals as such, but only those radicals that are excitedby photons. It is appropriate to mention here that in somecases, even very weak UV illumination is enough for the de-tection of free radicals by our method of resonance scattering.Because the probability of photon absorption by a short-livedfree radical is very low, the number of radicals excited by ex-ternal irradiation will comprise a negligible part of the whole.

To summarize, the sphere of application of mitogeneticmethods in biology appears to be almost inexhaustible. Obvi-ously it would be ridiculous to make any scientific prognosishere, in light of the complete disregard for our results. But wemade it a rule to evaluate the results of mitogenetic investiga-tions regardless of predominant opinions.

It would be useless to enumerate all of the spheres in whichmitogenetic methods can be applied. The general progressand expansion of the application of mitogenesis—which hasalready given us, and should give in the future, a new biolog-ical horizon—seems to be very important.

We would like to point out at least that mitogenetic meth-ods permitted us to reveal the existence and importance forliving systems of chain processes and of a regular nonequilib-rium arrangement of molecules. Until now, these two con-cepts, although they are completely alien to classical biologyand cytology, have been necessary for understanding themain biological processes. It is extremely important to takethese concepts into consideration. Moreover, after they ob-tain general recognition, many conventional concepts will belooked upon in the light of new discoveries and will be sub-jected to reconsideration.

At the same time, this review, although incomplete, bringsus to the following general conclusion: If further develop-ment of the idea of the mitogenetic phenomenon and the atti-tude of science toward it were to become normal, “mitogene-sis” should become completely dissolved into the realm ofrelated disciplines. The very term “mitogenesis,” as the nameof a specific discipline, should disappear, as its role wouldhave been played out.

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From archives of L. Beloussov

Gurwitsch’s laboratory in Moscow in June 1948. Gurwitsch is second from right first row. His daughter, Anna, is third from right.