Coherent Processes in Biological Systems - American Chemical Society

Coherent Processes in Biological Systems. H. FRÖHLICH. Department of Physics, Oliver Lodge Laboratory, The University of Liverpool,. Oxford Street, L...
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12 Coherent Processes in Biological Systems H. FRÖHLICH

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Department of Physics, Oliver Lodge Laboratory, The University of Liverpool, Oxford Street, Liverpool, L69 3BX, U.K.

The success of molecular b i o l o g y i s based on the d e r i v a t i o n of the d e t a i l e d molecular s t r u c t u r e of b i o l o g i c a l l y important molecules such as enzymes, DNA. Frequently the o p i n i o n has been expressed that the a c t i v i t y o f b i o l o g i c a l systems can be understood i n terms of standard chemical r e a c t i o n s , based on a knowledge of s t r u c t u r e , i n conjunction w i t h d i f f u s i o n of molecules. I t must be pointed out, t h e r e f o r e , that b i o l o g i c a l systems exh i b i t s e n s i t i v i t i e s , a t times, that equal those o f the best a v a i l a b l e modern i n s t r u m e n t a t i o n . As an example we mention the s e n s i t i v i t y a t low l i g h t i n t e n s i t i e s of the human v i s u a l system which according t o a c a r e f u l a n a l y s i s by Rose (jL) i s c l o s e t o the t h e o r e t i c a l l i m i t . The s y s tem thus can be considered as an image converter o f the highest p o s s i b l e s e n s i t i v i t y , though i t uses m a t e r i a l s of q u i t e a d i f f e r e n t nature from those used by t e c h n o l o g i s t s . In a more general sense, b i o l o g i c a l systems r e c e i v e energy through metabolism (or l i g h t ) , and use a p a r t of t h i s energy t o develop and maintain a complex o r g a n i z a t i o n . I n simple p h y s i c a l systems, i n g e n e r a l , supply o f random energy leads t o an increase i n temperature. Exceptions a r i s e i n the case of machines which r e q u i r e complex arrangements. More simple, i n p r i n c i p l e , i s the case of l a s e r where the supply of energy y i e l d s the well-known coherent l a s e r s t a t e s . Long range coherence, moreover, i s a very general concept which may a r i s e subject t o a few m a t e r i a l p r o p e r t i e s , and i t has been proposed, t h e r e f o r e , that b i o l o g i c a l systems make c o n s i d e r able use o f t h i s p o s s i b i l i t y Ç2,43,4). Do b i o l o g i c a l m a t e r i a l s , from the point of view of p h y s i c s , possess some common m a t e r i a l p r o p e r t i e s ? They do i n t h e i r e x t r a o r d i n a r y d i e l e c t r i c p r o p e r t i e s 05). Most remarkable, here, are the strong e l e c t r i c f i e l d s , of order 10? volt/m, that are maintained i n a l l b i o l o g i c a l membranes, although the only use that c l a s s i c a l b i o l o g y has made of t h i s i s r e s t r i c t e d t o nerve membranes. Such f i e l d s , c l e a r l y , lead t o a strong e l e c t r i c p o l a r i s a t i o n of a l l m a t e r i a l s i n a membrane; o s c i l l a t i o n of these m a t e r i a l s then lead t o e l e c t r i c p o l a r i s a t i o n waves. 0097-6156/81/015 7-0213$05.00/0 © 1981 American Chemical Society

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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Coherent E l e c t r i c P o l a r i s a t i o n Waves

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E l e c t r i c p o l a r i s a t i o n waves can be c l a s s i f i e d i n terms of t h e i r normal modes. I n g e n e r a l , these normal modes form bands, though i n some cases i s o l a t e d modes may a l s o e x i s t . The lowest frequency of a l l these modes i s d i f f e r e n t from zero. A band of normal modes covering a frequency range between and u^,

i s assumed to be i n very strong i n t e r a c t i o n w i t h the r e s t of the system which i s t r e a t e d as a heat bath w t i h temperature T. I t i s e s s e n t i a l that not only f i r s t but a l s o second order terms i n t h i s i n t e r a c t i o n a r e of importance, whereas terms l e a d i n g to an i n t e r ­ a c t i o n between the modes of p o l a r i s a t i o n wave are considered n e g l i ­ g i b l e . These are the main requirements which the m a t e r i a l must e x h i b i t i n order to be capable of showing e x c i t a t i o n of a s i n g l e mode under the i n f l u e n c e of random supply of energy a r i s i n g from metabolic processes. For l e t n^ be the number of quanta i n the mode w i t h frequency ω^, l e t s^ be the r a t e of supply of energy to t h i s mode, and l e t and χ^£ = χ», a p p r o p r i a t e t r a n s i t i o n pro­ b a b i l i t i e s , then the r a t e of change of n^ s a t i s f i e s the k i n e t i c equation ( 2 , 4 0 D e

where

A formal s t a t i o n a r y s o l u t i o n of (2) can be e a s i l y presented (6) though we s h a l l give here only the s o l u t i o n f o r the s i m p l i f i e d case i n which a l l are equal to φ, and a l l χ ^ equal t o χ,

where

and

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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FRÔHLICH

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Thus μ = 0 i n thermal e q u i l i b r i u m (s=0), when (4) becomes a Planck d i s t r i b u t i o n , and

Now from (2) i t can be shown that f o r s u f f i c i e n t l y l a r g e s, the t o t a l number of quanta Ν=Ση^ i n c r e a s e s p r o p o r t i o n a l l y to the t o t a l r a t e of supply s. Equation (4) then shows that a c r i t i c a l r a t e of supply S Q , e x i s t s , such that f o r S > S Q something analogous to E i n s t e i n condensation of a Bose gas must occur. This i m p l i e s that μ, which a c t s as chemical p o t e n t i a l , must approach very c l o s e l y such that the occupation, n^, of becomes very l a r g e . Since ω-^ represents a normal mode, i t f o l l o w s that t h i s e x c i t a ­ t i o n i s coherent. The above o b s e r v a t i o n has been confirmed w i t h the use of a number of more s p e c i f i c models, some using f i e l d theory, others using a f i n i t e number of modes (7-14). Consequences The p o s s i b i l i t y of coherent e x c i t a t i o n , discussed i n the pre­ v i o u s s e c t i o n , r e s t s on the i n t r o d u c t i o n of the n o n - l i n e a r χterms. For i f χ=0, then (6) y i e l d s μ=0 and the p o s s i b i l i t y of coherent e x c i t a t i o n disappears. When the e x c i t a t i o n i s achieved, on the other hand, then the system i s capable of c o l l e c t i v e be­ haviour and can e x h i b i t p r o p e r t i e s that at f i r s t s i g h t do not appear to be inherent i n the unexcited system. Most important i s a f r e q u e n c y - s e l e c t i v e long-range i n t e r a c t i o n of such e x c i t e d systems (15,4) which may l e a d , i t has been suggested, to c o n t r o l of c e l l d i v i s i o n i n an organ, to long-range a t t r a c t i o n (e.g. of enzyme and s u b s t r a t e ) and to other consequences. Once such a t ­ t r a c t i o n has been achieved, of course, the u s u a l short-range chemical i n t e r a c t i o n s w i l l take over. These, together w i t h the s p a t i a l rearrangements due to long-range i n t e r a c t i o n , w i l l , i n g e n e r a l , l e a d to new frequencies which, i f e x c i t e d , w i l l lead to the a t t r a c t i o n of d i f f e r e n t groups, so that a u n i d i r e c t i o n a l development of the system may be a n t i c i p a t e d . Amongst p o s s i b l e f r e q u e n c i e s , lO^O-lOU Hz has been estimated f o r p o l a r membrane v i b r a t i o n s , higher f r e q u e n c i e s , up to 1 0 l 3 l O ^ Hz, f o r p r o t e i n s , lower frequencies (16), of order 10^ Hz, f o r RNA. These frequency regions i n c l u d e those corresponding to m i l l i m e t e r and centimeter electromagnetic waves, and i t may be expected then that b i o l o g i c a l processes that make use of e l e c t r i c v i b r a t i o n s i n these frequency regions may be i n f l u e n c e d by ex­ t e r n a l l y a p p l i e d electromagnetic waves. This should p a r t i c u l a r l y a r i s e when the r e l e v a n t s i z e of the m a t e r i a l i s s m a l l compared w i t h the vacuum wavelength. Otherwise, however, e x t e r n a l r a d i a ­ t i o n w i l l i n t e r a c t w i t h o p t i c a l l y - a c t i v e modes o n l y , and i t i s u n l i k e l y that those modes are r e l e v a n t f o r b i o l o g i c a l purposes. In such cases, i n t e r a c t i o n i s r e s t r i c t e d to s u r f a c e e f f e c t s and e f f e c t s of i r r e g u l a r i t i e s . 1

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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EFFECTS OF NONIONIZING RADIATION

Consider now a complex b i o l o g i c a l process that i s i n i t i a t e d by the consequences of strong e x c i t a t i o n of a c e r t a i n mode, l e a d ­ ing to s e l e c t i v e long-range i n t e r a c t i o n . L e t t-4 be the time r e ­ q u i r e d f o r t h i s process, and l e t t be the time of the subsequent chains of b i o l o g i c a l processes. The t o t a l r a t e R thus i s 2

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R

1 t-L + t

=

(8)

2

Now the f i r s t process r e q u i r e s coherent e x c i t a t i o n , which i n t u r n r e q u i r e s the r a t e of energy supply s to be l a r g e r than the c r i t i c a l S Q . Thus t4 •> °°, i . e . , R -> 0, i f s < S Q . When s > S Q then we s h a l l assume 1

(s - s )

n

(9)

0

where η = 1, and _a i s a constant. that R

=

l

Together w i t h (8) i t f o l l o w s

(s - s ) n ( a / t ) + (s - s ) n , Q

t

2

2

0

s4s

(10)

0

i . e . , R i s a s t e p - l i k e f u n c t i o n whose value becomes l / t , indepen­ dent of s when s i s very l a r g e . Consider now that the system i s preparing f o r the p a r t i c u l a r process by supplying energy a t a r a t e s < S Q , say s = S Q - Δ. Then, i f the r e l e v a n t frequency r e g i o n i s i n the microwave o r millimeter-wave r e g i o n , and i f electromagnetic energy i s s u p p l i e d at a r a t e s > Δ, then the process w i l l take p l a c e , i . e . , i t w i l l be t r i g g e r e d by the e x t e r n a l l y s u p p l i e d energy. The dependence i n t h i s i n t e n s i t y w i l l again be s t e p - l i k e , w i t h the step s t a r t i n g at the r a t e s = Δ, which might be very low. A s l i g h t m o d i f i c a ­ t i o n of the s -independent r e g i o n w i l l a r i s e when the a b s o r p t i o n of the e x t e r n a l wave i n the system i s r e l e v a n t . This case has been t r e a t e d i n ( 6 ) . As a whole, however, these processes are c h a r a c t e r i z e d by t h e i r s t e p - l i k e dependence on i n t e n s i t y , and by t h e i r r e s t r i c t i o n to c e r t a i n frequency r e g i o n s . Furthermore, as f i r s t discussed i n (12), equation (2) i m p l i e s that a c e r t a i n nonn e g l i g i b l e time of i r r a d i a t i o n w i l l be r e q u i r e d to approach the stationary state. 2

fi

B

m

m

m

Experiments Electromagnetic waves may, under c e r t a i n circumstances, t r i g ­ ger b i o l o g i c a l events w i t h the use of r e l a t i v e l y low i n t e n s i t i e s , as discussed above. To t e s t t h i s p o s s i b i l i t y e x p e r i m e n t a l l y , i t i s r e q u i r e d to i n v e s t i g a t e the t r i g g e r e d b i o l o g i c a l event i n i t s dependence on the i n t e n s i t y , frequency, and d u r a t i o n of the ap­ p l i e d r a d i a t i o n . A great number of experiments a t a s i n g l e f r e -

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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quency ( u s u a l l y 2450 MHz) do e x i s t ; they are not s u i t a b l e to t e s t the theory, though some of them do e x h i b i t e f f e c t s at very low i n t e n s i t i e s so that thermal a c t i o n i s u n l i k e l y . In a r e p o r t of the USSR Academy of Science (January 1973) (17) the r e q u i r e d set of experiments have been c a r r i e d out on a number of b i o l o g i c a l m a t e r i a l s w i t h the use of coherent m i l l i m e t e r waves, vacuum wave length 6-7 mm, a l a r g e range of i n t e n s i t i e s and of d u r a t i o n of i r r a d i a t i o n , as r e q u i r e d to t e s t the theory. They confirm, q u i t e i n g e n e r a l , the t h e o r e t i c a l r e s u l t s and can thus be considered as c o n f i r m a t i o n of the theory (18). Subse­ quently experiments on the i n f l u e n c e of the growth of yeast c u l ­ tures have e x h i b i t e d the e x i s t e n c e of narrow frequency resonances (19), and r e c e n t l y , Grundler (20) , working w i t h very high r e s o l u ­ t i o n , has .been able to demonstrate c o n c l u s i v e l y the e x i s t e n c e of very narrow resonances. R e p r o d u c i b i l i t y of r e s u l t s i s sometimes d i f f i c u l t to achieve, and t h i s may be due to a number of reasons. Thus Grundler f i n d s a narrow p o s i t i v e maximum adjunct to two negative minima. As a consequence, working w i t h lower r e s o l u t i o n w i l l average over these and y i e l d no n o t i c e a b l e e f f e c t . Other parameters, however, o f both p h y s i c a l and b i o l o g i c a l nature are l i k e l y to be r e l e v a n t ; i n v e s t i g a t i o n s to determine these are i n progress. At higher f r e q u e n c i e s , the laser-Raman e f f e c t a f f o r d s , i n p r i n c i p l e , the p o s s i b i l i t y of d e t e c t i n g non-thermal e x c i t a t i o n of v i b r a t i o n s . These would be found from a higher than thermal r a t i o of a n t i - S t o k e s to Stokes l i n e s . The Raman e f f e c t i n b i o ­ l o g i c a l systems has r e c e n t l y been reviewed by Webb (21). Un­ f o r t u n a t e l y only two r e l e v a n t measurements have been c a r r i e d out, so f a r , but both demonstrate non-thermal e x c i t a t i o n . A d i f f i c u l t y a f f e c t i n g r e p r o d u c i b i l i t y a r i s e s here from the e f f e c t of a l a s e r beam on a b i o l o g i c a l system as discussed i n (21), i n the case of i n d i v i d u a l c e l l s . The best way to avoid t h i s appears to be the use of a flow i n s t r u m e n t a t i o n so that each c e l l i s subjected to the l a s e r beam f o r a very short p e r i o d only (22). F i n a l l y , one may q u e s t i o n whether the a c t i v a t e d p o l a r v i b r a ­ t i o n s i n i n d i v i d u a l c e l l s can be expected to have e x a c t l y the same frequency f o r a l l c e l l s . For assume t h a t , through a f l u c t u a t i o n , a water molecule or a hydrogen i o n i s attached to the v i b r a t i n g r e g i o n i n one c e l l but not another. The non-homogenuous p a r t of the a r i s i n g f i e l d w i l l then a l t e r the r e l e v a n t frequency by an amount which i s s m a l l compated w i t h t h i s frequency but may w e l l be of order of the frequency d i s t a n c e between resonances r e ­ ported i n (19) and (20). NOTE ADDED IN PROOF Meanwhile l i t e r a t u r e has been found (e.g., B.L. Epel i n Photophysiology 84, 209, 1973) according to which v i s i b l e l i g h t i n h i b i t s v a r i o u s b i o l o g i c a l processes i n Ε c o l i . A l s o experimen­ t a t i o n w i t h flow i n s t r u m e n t a t i o n has begun and appears to y i e l d i n t e r e s t i n g r e s u l t s which w i l l be p u b l i s h e d i n due course by F. D r i s s l e r .

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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ABSTRACT The model leading to the excitation of coherent electric vibrations in biological systems is reviewed and the experimental evidence for it is briefly discussed. LITERATURE CITED 1. Rose, A. Image Technol. 1970, 12, 13. 2. Fröhlich, H. Int. J. Quantum Chem. 1968, 2, 641. 3. Fröhlich, H. Riv. Nuovo Cimato 1973, 3, 490. 4. Fröhlich, H. IEEE Trans. Microwave Theory Tech. 1978, 26, 613. 5. Fröhlich, H. Proc. Natl. Acad. Sci. U.S.A. 1975, 72, 4211. 6. Fröhlich, H. "Advances in Electronics and Electron Physics" Vol. 53, Academic Press, New York, 1980, 85. 7. Bhaumik, D.; Bhaumik, K.; Dutta-Roy, B. Phys. Lett. 1976, 59A, 77. 8. Bhaumik, D.; Dutta-Roy, B.; Lahiri, A. Phys. Lett. 1978, 68A, 131. 9. Wu, T.M.; Austin, S. Phys. Lett. 1977, 64A, 151. 10. Wu, T.M.; Austin, S. J.Theor. Biol. 1978, 71, 209. 11. Wu, T.M.; Austin, S. Phys. Lett. 1978, 65A, 74. 12. Wu, T.M.; Austin, S. Phys. Lett. 1979, 73A, 266. 13. Mills, R.E. Phys. Lett. 1972, 39A, 153. 14. Moskalenko, S.A.; Miglei, M.F.; Khadshi, P.I.; Pokatilov, E.P.; Kiselyova, E.S. Phys. Lett. 1980, 76A, 197. 15. Fröhlich, H. Phys. Lett. 1972, 39A, 153. 16. Prohofsky, E.W.; Eyster, J.M. Phys. Lett. 1974, 50A, 329. 17. Devyatkov, N.D. Soviet Physics US PEKHI(Translation) 1974, 16, 568. 18. Fröhlich, H. Phys. Lett. 1975, 51A, 21. 19. Grundler, W.; Keilmann, F . ; Fröhlich, H. Phys. Lett. 1977, 62A, 463. 20. Grundler, W. Personal communication 21. Webb, S.J. Physics Reports 1980, 60, 202. 22. Drissler, F.; MacFarlane, R.M. Phys. Lett. 1978, 69A, 65. RECEIVED October 31, 1980.

In Biological Effects of Nonionizing Radiation; Illinger, Karl H.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.