A chronomic tree of life: ontogenetic and phylogenetic ‘memories’ of primordial cycles — keys to ethics

I

& BIOMEDICINE PHARMACOTH ERAPY Biomedicine & Pharmacotherapy 58 (2004) S 1-S 11

ELSEVIER

www.elsevier.com/locate/biopha

Preface

A chronomic tree of life: ontogenetic and phylogenetic 'memories' of primordial cycles - keys to ethics Franz Halberg a,*, Kuniaki Otsuka b, George Katinas a, Robert Sonkowsky a, Philip Regal a, Othild Schwartzkopff a, Rita Jozsa b, Andras Olah b, Michal Zeman °, Earl E. Bakken d, Germaine Corndlissen a ~Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA bTokyo Women's Medical University, Daini Hospital, Tokyo, Japan cUniversity of Pets, Hungary °Comenius University, Bratislava, Slovakia dNorth Hawaii Community Hospital, Kamuela, HI, USA

Abstract A scientific optimization may become possible in ethics to the extent to which any reproducible since cyclic features of spirituality and of criminality become measurable. Should either or both the 'good' or the 'bad' be found to be at least passively influenced by cyclic physical environmental factors, as is putatively the case, these aspects of behavior may eventually become actively manipulable, perhaps utilizable for human survival. Toward this goal, chronomics has already mapped time structures in religious behavior that can lead to a study of underlying geographic/geomagnetic latitude-associated mechanisms. This paper, with further but clearly insufficient data, revealing the hurdle of relative brevity of the available time series constitutes a plea for much longer and denser worldwide time series, for further endeavors in various methods of analyses, some of which are promisingly available. © 2004 Elsevier SAS. All rights reserved. Keywords: Chronobiology; Chronomics; Primordial cycle; Chronobioethics; Ontogeny; Phylogeny

1. Prologue The senior author was pleased to consider how chronobiology and chronomics can serve in dealing with civilization and culture, b e c a u s e this invitation f o l l o w e d the recommendation by a philosopher who was president of his national academy of science [1], and was himself a scholar of chronomics (time structures) [2]. The task of dealing with diseases of society (read: ethics) is usually outside the scope of both experimental and clinical science. It was brought into the realm of numerical inferentially analyzed evidence by the similarity of a physical environmental [3] and a moti-

*Corresponding author. E-mail address: halbe001 @umn.edu (E Halberg). © 2004 Elsevier SAS. Tous droits r6serv6s.

vational [4] cycle length, a first hint. It was further encouraging when clergymen who happened to be physicists as well provided invaluable data, related not only to physics but also to ethics [4,5]. This article is written with the hope that sooner rather than later, time series on religiosity now available and successfully analyzed covering only the past 50 years but fortunately from over 103 geographic locations [4] will become available with a similar coverage of latitude and longitude in a length matching as much as possible the 2556 years of wars [6]. In turning to culture and civilization, the two words have overlapping spheres to the point that they are often used as synonyms. Each term has been applied to societies (read: cultures) compatible with cannibalism of one sort or another. Once this is acknowledged it is difficult to relate cul-

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

$2

INFRAANNUAL (CIRCADECENNIAN?) R E S O L V E D by C O S I N O R i n C R I M E

A 6"

SIMPLE ASSAULT

A

COMPONENTS C H R O N O M E '~

INFRAANNUAL RHYTHMS in CRIME* and TWO CIRCADECENNIAN ENVIRONMENTAL CYCLES

AGGRAVATED ASSAULT

3

A

B

4"

USA, 1973 - 1999

2

PROPERTY

2"

CRIME

1 ......................

0

J,

0

-2

"Vehicletheir s •.............................. Total PropertyCrime

-1

-4 e~iod = t2.83 (1157 to t428) y Alnpllt ude = 2•7 (t.6 t o 3.$) A e m p h a ~ ~ -113 ( ~ ? t o -130) d ~

-6 -8

v

pe~ad= 1 4 2 9 ( 1 1 3 0 to 17.74) y Amplitude ~ 0.92 (8.24 to t.62) A c m o h a ~ = -1981-154to -2421 ¢k~nrees ; i

-2

i -3'

i

•

VICTIMIZATION Rape

..................................................

Robbe~J

.....................................................

A

ROBBERY

A

RAPE

.

0.8 . . . . . . . . . . . . . . . . . . . . . . . . . ~~

c

~

.

, . ........... P,ggravated Assault

, .., ..................................... Simple Assault

~

....................................

........................................... rotal Victimization

m

I.O

Burglaqt

............................ Thefts

0•4'

0.5'

ENVIRONMENT

0.0'

0.0

m Q

-0.5'

..................................................................

ltp

......................................................................

WN

-0.4 ' -1.0 '

IP~lod = 11 B5 (932 to 12.99) Y

~lnp/itudc ~ 0.601(L35 t o t.04) Ac~pha~ = ~ (~225t o ~Sq) d ~ reds I |

-t.5 '

1970

1980

1990

2000

i

Arl~liUJde = 0,26 (8.09 t o 0.43) Acr~ha~ - I ~ ~-1G8to -188~ d c ~ r ( ~

-0,8 '

~

1970

,

1900

,

1990

9

10

14

12

13

14

15

Period

16 17 18 (years) =

19

20

21

22

23

2000

Time (calendar year) * Original data from

http:/ojp.usdoj.govtbjslglancelproptrd.txt

~" Resolved by linear-nonlinear r h y t h m o m e t r y , s h o w n as dot w i t h 9 5 % confidence interval (bracketing dark continuous l i n e ) . Kp: planetary geomagnetic disturbance i n d e x ; W N : W o l f ' s relative s u n s p o t n u m b e r .

Chr~aorne ffrtwaehronos -time; norris = rule)= time structure. A= Change along all four ordinates as follows: eventsp er 1,000 papulaUan age 12 and aver in residual number of victknizatlons, after fitting a first order polynceniaL Data frNla websiteht~://ujp.usda].govlbis/glance/proptrd.Lxt. *

Fig. la. T i m e p l o t s o f c r i m e a n d m o d e l s fitted n o n l i n e a r l y to list u n c e r t a i n t y

Fig. lc. C h a r t o f c i r c a d e c a d a l (also c a l l e d c i r c a d e c e n n i a n ) cycles i n socie-

o f p e r i o d s found. © H a l b e r g .

tal and e n v i r o n m e n t a l v a r i a b l e s b a s e d as yet o n l i m i t e d data a w a i t i n g anal y s i s o f m u c h l o n g e r t i m e series. © H a l b e r g .

INFRAANNUAL (CIRCADECENNIAN?) R E S O L V E D by" C O S I N O R i n C R I M E

A ALL VICTIMIZATIONS** ~- ...................................................

60 -

40

A

COMPONENTS CHRONOME*

TOTAL CRIME

10 ¸

1

20

i Amplitude- ¢412,61o 6.2)

0

A

WN

A

100

~ i

-10

10

C

Kp D

50 0 ~0

-100

period= 10,24 (9.B4 to 10.6B) y

Peal

~mphtud¢ = 71,~ ~57,4to BZ.~)

k mpIRude = 3.9 [ 14to ~.41

-150 1970

.

.

.

.

J

1980

1990

2000

t970

1980

1990

2000

T i m e (calendar year)

* Chrtmome ffrom chranos = tkne; norrms = rule) = tirae structure. A = Change al~g ordinates as ftlllaws:A - Original data, events per 1,(I)0 population age 12 and over, B-residualnumber of victimizations after fittingfirst order polynomial, C - Waif's active sunspat numb er, D - gem-no,eeOc disturbance index. ** 1 - total cr~ne, 2 s~aple assault, 3 - aggravated assault, 4 - robbery~ 5 - rap e. Data from website ht~://o]p.usdo~.govYb~s/~lonce/pruptr d.t.xt. Fig. lb. Time plots of crime, of W o l f ' s relative sunspot numbers (WN) a n d o f t h e p l a n e t a r y g e o m a g n e t i c i n d e x K~ a n d f i t t e d m o d e l s y i e l d i n g p e r i o d s w i t h their uncertainties. © H a l b e r g .

ture to spirituality and civilization to technology. According to Merriam-Webster Online, 'civilization' is defined as "a relatively high level of cultural and technological development; specifically the stage of cultural development at which writing and the keeping of written records is attained"; and according to the same source, ' c u l t u r e ' is "acquaintance with and taste in fine arts, humanities, and broad aspects of science and civilization". This overlap of the spheres of the two definitions is also found in an Encyclopaedia Britannica of the 1970s. Against this background, we here distinguish issues of the mind (=noes), i.e. the noosphere [7], from concerns of spirituality [8], morality or to use simpler words, custom and habit (=ethos), the ethosphere. Science can try to join the endeavor to eliminate barbarism and irrational behavior with an optimal use of physical, spiritual and other human resources. Whether or not this distant goal is ever achieved, we aim for countermeasures, preferably preventive ones against crime, war and atrocities. These could be sought by a scientific approach, by the study of cycles in data on 'good' and 'bad' customs and habits, in an ethosphere including spirituality and morality as a putative key to an understanding of underlying mechanisms and thus to rational remedies for diseases of 'cultures' and 'civilizations'.

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

PROSELYTISM in SOUTHERN BAPTIST CHURCH (MILLIONS of NEW MEMBERS/YEAR)

$3

GROWTH RATE of 7th-DAY ADVENTISTS in WORLD COMMUNITY (% / year) in 1975 - 1998" 9'

0.3"

8.

e

0.2"

o e

0.1'

7.

0.

6

-0.1 5

e e

-0.2 4.

-0,3 0'

-0,4

i

1975

.

.

.

.

i

1980

.

.

.

.

i

,

.

•

1985

.

i

1990

,

.

,

,

i

.

1995

Time (calendar year) -0.3

,

•

i

1975

.

.

.

.

i

.

1980

.

.

.

i

.

.

.

.

1985

,

.

1990

.

.

.

,

•

,

•

1995

Time (calendar year) Original data from "Yearbook of American and Canadian Churches". Best fitting period = 11.3 years (95% confidence interval: 9.7 to 12.9), Amplitude = 0.13 {0.05 to 0.2), Acrophase = -262 (-226 to -297), expressed in (negative) degrees, with 360 = 11.3 years and 0 = 1 Jan 1973.

Fig. 2a. A church membership hints at a circadecennian cycle based on limited data. © Halberg.

* Original data from http://www.adventist.org (Statistics - Statistical reports Rates of growth). Best fitting period = 19.0 years (95% confidence interval: 14.2 to 23.7), Amplitude = 1.t% (0.6 to 1.5), Acrophase [] -230 (-203 to -256), expressed in (negative) degrees, with 360 = 19.0 years and 0 = 1 Jan 1975.

Fig. 2b. A church membership record hints at a much longer cycle, as compared to that in Figure 2a. © Halberg.

2. Introduction PROSELYTISM in ROMAN CATHOLIC CHURCH (MILLIONS of NEW MEMBERS/YEAR)

e e

o

e

1975

1980

1985

1990

1995

Time (calendar year) * Original data from "Yearbook of American and Canadian Churches". Best fitting period = t9.3 years (95% confidence interval: 13.9 to 24.7), Amplitude = 0.96 (0.6 to 1.5), Acrophase = -9 (-331 to -49), expressed in (negative) degrees, with 360 = 19.3 years and 0 = 1 Jan 1973.

Fig. 2c. A church membership shows a pattern differing from that in Figs 2a and 2b. © Halberg.

Humanity needs transdisciplinary science for spirituality assessment as a critical step to optimizing ethics. Genetics has shed light on the biosphere, technology upon the noosphere, in which, the achievements of the information age notwithstanding, no obvious spinoff for morality is yet apparent [1]. For ethical purposes, we focused elsewhere on outcomes as different as religious motivation [4], if not spirituality [8], criminality [9] and atrocity, and on the underlying dynamics as states at least partly within the brain and in the brain's relations with the circulation of blood, the heart and the broad neuroendocrines. A critical role is usually also played by the socioecological environment acting as a synchronizer, influencer, resonator or reverberator [10]. The finding of reciprocal cycles in and around us [6] may prompt the alignment and scrutiny of physical environmental as well as socio-psycho-physiological cycles with those in measurable aspects of spirituality in individuals and populations. The coincidence of certain stages, such as peaks and/or troughs of rhythms and/or of cycles with many different frequencies may lead to deviant behaviors, i.e. to times of heightened susceptibility and resistance to a variety of stimuli and thus to diseases of individuals and societies. We anticipate finding an understanding of any physiologic bases of spirituality and thus, perhaps, the possibility to predict and prevent diseases of society, such as crimes and atrocities, by focus on cycles that

$4

F. Italberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

are desirable and undesirable and by defining their similarities and, importantly, if they can be found and manipulated, their differences. Quasi-reciprocal cycles are found in and around us [6]. Some are seen and/or felt and thus obvious, like the light and heat involving the photic environmental and biological day and calendar year. Other cycles are unseen but assessable; they are primordial insofar as they are prominent early in life and may be vestiges, i.e. ontogenetic and phylogenetic 'memories'. The non-photic cycles include about-halfweekly, about-weekly, about-half-monthly, about-monthly, about-half-yearly, cis-yearly (with 95% confidence intervals [CI] between 0.5 and 1 year length, overlapping neither of these lengths), yearly (with CIs overlapping the calendar year), trans- (beyond, i.e. longer than) yearly (with 95% CI between 1 and 2 years length, again overlapping neither of these lengths), about-decadal, about-multi-decadal and about-semi-millennial cycles to mention but a few. All may intermodulate with ultradians, notably with the rhythms of the heart, the circulation and the brain. The known spectral element of rhythms covers in frequency 10 orders of magnitude and is still broader in populations. Chronomes consist of trends and, among others, of probabilistic chaos [11], complementing cycles and rhythms. Chaos will also have to be explored in assessing brain function in disease as in health. Non-photic cycles - circadecadais and circadidecadals - characterize crime (Figs la-c) and religious motivation, the latter approximated by church membership (Fig. 2a--c). While church membership may be a multifactorial variable, activity on behalf of a church seems more reliable as a gauge of spirituality. Under 'activity', Fig. 3 summarizes the hours spent in work for one church in over 103 geographical locations, and takes a step far beyond the data herein, allowing for a check of geographic/geomagnetic latitude dependence [4]. The circadidecadals found in religious motivation correspond to the bipolarity cycle of sunspots [3]. Moreover, the characteristics of some of these cycles show a geomagnetic/geographic latitude dependence [4]. Can the spectra in and around us become a key to health vs disease of society? There is the precedent that an alteration of the circadian rhythmic behavior has already proved to be a key to an elevated cardiovascular or oncological disease risk of individuals [8,9]. An answer to ethics may be sought by continuing research on the extent to which spiritual, including religious, activity depends upon physical environmental factors; the encouraging geomagnetic/geographic latitude-associated circadidecadal evidence of activity on behalf of one' s faith in Fig. 3 bears upon this point. An approach to morality seems to be important, since technology has contributed to the development of several different customs and habits, if not cultures, not invariably with humaneness in mind [2]. A set of universally adhered to unified guidelines of behavior is missing, notwithstanding the development of religions precisely to fill this void. The motto 'Never Again', persuasive immediately after each of two world wars, was forgotten by each succeeding

generation. We seem to be in cycles bringing humanity to the brink of wars and other recurrent carnage of millions of humans. In this context, Western language and extensive refined communications, notably the media, have not fostered a humane approach that may compete with effectiveness in some of our current customs [1]. The noosphere - the realm of the mind - has developed, without much progress within an ethosphere, especially without applying science to spirituality, as the church missed an opportunity offered by Galileo [12].

3. Spirituality Albert Einstein, among many others, has explicitly regarded religion as a topic inappropriate for science, if not inapproachable or unassailable [13], while other physicists and academic engineers have addressed spirituality as intentionality ([14]; cf. [15]). It is the more noteworthy that, in addressing scientists in 1983 [12], Pope John Paul II "spoke therapeutically toward the historical rift between the (Catholic) Church and science", providing more than an "apology to the memory of Galileo". Albert Di Canzio interprets this address as a bright ray of hope (which could become) a hint of better things to come". First, the bright ray: "Let us think of how the results of scientific research help us to know the universe better, to understand better the mystery of man; think of the advantages which the new means of communications and contact among people offer to society and to the church; let us think of the ability to produce incalculable economic and cultural wealth, and especially to promote the education of the masses, and to cure diseases previously thought incurable. What admirable achievements. And the hint: yes, the church appeals to your capacities for research in order that no limit may be placed upon our common quest for knowledge" [12]. Many pertinent data could be studied in this context, starting in earliest church records providing time series, which are still accumulating today.

4. Cycles in spirituality and related variables A physiologist, just as any person on the street, in turn can try to look at the predictable cyclic mechanisms involved in all aspects of the uoo- and ethospheres of our mind and 'emotions' with 'feelings' or our 'psyche', the latter including whatever of morality and spirituality can be rendered measurable. If the ethosphere is time-varying, we need to map its chronomes (time structures) consisting of cycles, trends and chaos, as one deals with the circulation [ 16]. Underlying some of the interactions in a transdisciplinary context is a neuroendocrine network of hormones from the hypothalamus, pituitary, adrenal, gut and pineal [17]. Descartes had located the seat of the soul in the pineal, apparently only on the ingenious basis of symmetry. Unfortunately, as yet, discoveries that this gland produces widely

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

C Y C L E S in R E L I G I O S I T y , C R I M E and THE E N V I R O N S

RELIGIOUS MOTIVATION MEMBERSHIP (1973 1998)* -

~.__~_

. . . . . Roman Catholics ~ ................................................... 7th-day Adventist_=

Southern Baptists Ass. Jehovah's Witnesse~

.....................................

ACTIVITY (t950 - 1999)** ........................................ Jehovah'S Witnesse~

CRIME***

PROPERTY (1973 - 1999) ~ -

.....

-,4

~i. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vehicle theR!

Thefts

"..................................................................... Surgiar~

VICTIMIZAWON (1973 - 1999) ~

Aggravated Assaull Simple Assault

...........................................................

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .]t. . .................................................................................

-:~"~

Robbery Rape

"-

Total

.................

ENVIRONMENT

~4===.................................. BHC .~..I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WN

;

t'1

1;

1;

1'7 17

z'l

13

2;

Period (years) ~ * * FrOm YearbOOk of American and Canadian Churches 1973 -2O0O (N -sg,OOO,OO0). From Yearbook of dehOvah~ Witnesses 1949.2OOO (N - 2,0OO,OO0). N = average membership per year.

original data from: http:/ojp.usdoj.gov/bjSgglance/proptrd.tXt; not shown are results on human productivity, reflected in the number of scientific publications. Resolved by linear-nonlinear rhyChmometry, Shown as dot with 95~ confidence interval (el 1 (bracketing dark continuous line), Non-overlapping CIS hint at d~eMng mechanisms. Kp: planeta W geomagne~¢ disturbance index; WN: Wolf's relative sunspot number; BI4C: Bipolarity "Hale Cycle", computed by changing the sisn of WH at each WN minimum.

Fig. 3. C h a r t o f c i r c a d e c a d a l a n d c i r c a d i d e c a d a l c y c l e s b a s e d on l i m i t e d data a w a i t i n g a n a l y s e s o f l o n g e r series. © H a l b e r g .

active secretions have not been applied to optimizing the psyche. Investigations of cycles, in various aspects of an ethosphere have not kept pace with information technology [1]. It seems pertinent to involve chronobiology, with focus on neuroendocrinological variations, in order to explore mechanisms contributing to how elements in time interact around and/or in us, and to undertake chronomics, the cartography of these internal-external, partly cyclic and to that extent also partly predictable interactions now being mapped in vivo with leads in phase of the circadian melatonin rhythm in gut in rats and chickens (confirmed) but not of quail (yet to be confirmed). Chronobiology started with circadian rhythms [17] and led to the mapping of chronomes with a spectral element consisting of photic and non-photic (visible and invisible) cycles. Photic cycles involve electromagnetic radiation in the visible domain; non-photic cycles involve corpuscular emissions from the sun and beyond, including helio-, seleno- and geomagnetics, ultraviolet flux and gravitation, and other stimuli such as anthropogenic ones. Cycles include, at one extreme, those in the action potentials of the major generators of electric and magnetic fields, the heart and the brain, recorded in ECGs and EEGs and in encephalo- and cardiomagnetograms. When such records become long, they reveal decadal cycles found not only in demographic and other data bases, but also in much needed longitudinal data, e.g. in heart rate, one record now covering the 38th year with about 5 measurements/d [18], another

$5

covering nearly 17 years by half-hourly values with but few gaps [19]. Considering populations, there are even more and longer cycles (Table 1). The individual's cycles have led from the detection to the treatment of elevated vascular disease risks in the physical health of individuals [16,17]. In this case, chronobiology has led the proverbial horse (culture or civilization) to water but as yet cannot make more than a few colleagues drink [20]. The systematic inferential statistical rather than descriptive cartography of our status quo, whatever we call it, as a domain not only of our mind but also of our ethosphere as yet is sadly lacking, as is hence a scientific approach to the health of societies. Ethospheric guidelines are needed, as a universally acceptable and implementable set of do's and don'ts and of countermeasures to hurdles on the way toward achieving a harmonious coexistence of behaviors, if not cultures [1]. Thus started, what seems indispensable, an inferential aligned transdisciplinary mapping of the cycles in the cosmos and in the biosphere, as they are now and as they may have been in an evolutionary past, as they are coded in all living matter, assuming that early in ontogeny we deal with vestiges of ancestors, of progenitors (Fig. 4). In two of the stages of biological evolution - first, the origin of life, and second, hominization, i.e. the origin of humans [7] - lie a phylogenetic and an ontogenetic memory in the form of a past and current display of cycles, that may help us trace our past back to the origins of life by the relative prominence of the amplitudes of biological near-matches of photic and non-photic environmental cycles (Table 1 and Fig. 4). Non-photic as weU as photic cycles are found in bacteria [21-23]. In air bacteria, a transyear can have an amplitude only slightly greater than that of the yearly spectral peak, but in most cases the transyearly amplitudes are smaller than those of the calendar year, distinctly different from the nonphotic/photic amplitude relations of a unicell studied in alternating light and darkness (every 12 hours). Indeed, a transyear [23-27] is also found in the giant eukaryotic unicell Acetabularia, presumably on earth for 500 million years. The transyear and some other non-photic cycles (e.g. about-weekly ones) also characterize Acetabularia released into continuous light and the human newborn's circulation more prominently at birth than the calendar year. Babies, the living fossils, seem to 'remember' at birth (by contrast to maturity) what we find in air bacteria and prominently in Acetabularia. The week as a schedule in contemporary society and, unseen and unknown, the transyear may be genetic codes, rather than mere imprints of natural cyclic processes. Also, half-yearly and other (apparently 'reactive') non-photic environmental cycles characterize humans and their societal 'health', including economics and wars [26]. Whether or not the environmental cyclic counterparts may have been more prominent long ago and/or may be the result of the internal integrative [28] rather than of an externally adaptive evolution, they can now free-run. The relatively large amplitude

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) SI-Sl l

$6

Phylo~enetic and h u m a n onto.qenetic t r e e of life, based on a m p l i t u d e ratios of biological n e a r - m a t c h e s of n o n - p h o t i c (NP) and p h o ti c (P) e n v i r o n m e n t a l cycles

OE: oxygen evotution

UNIVERSAL ANCESTOR

TY: transannual. (about 1.3 year) I Y: annual {about 1 year)

*Direction of tines based on analysis of 16S rRNA and rooted with paralosous protein sequences after Dr. Bharat Pate[,

http:t ltHshut.sd.gu.edu.aul-bharatlcourses/ss13brnm/archaea.htmL

Fig. 4. Phylogenetic and ontogenetic memories sketched based on limited data to invite the collection of longer series. The seed of a chronomic tree of life, eventually to complement the genomic tree of life. © Halberg.

Table t: Phylogenetic and ontogenetie memories based on the amplitude ratios (AR) of biological near-matches to non-photic/photic physical environmental cycles .........

When (in the

Who

Variable

distant past) Very long ago Universal ancestor*

, When (in an individual lifespan)

.... - ................. AR . . . . . . . . . . . . . . . . . . . . . . Ciroaseptan (CS)l Transannual (TY)/ =10-Y/Y ~-21-Y/Y circadian(CD) annual (Y) ............

?

Bacteria =1 bitli(~n"years

E. coli

ago

Cyanobacteria Air bacteria

Colony advance or growth

<1

Luminescence

<1 =1

Sectoring; genetic change

<1

Staphylococci =500 million years ago

Eukaryotic unicell (Acetabularia) Crayfish

Electrical p'otential; oxygen evolution; chloroplast rnigrat!en Motor activity

Rat Pig

Digestive variables

LD

<1 <1 <1

LL

Early

>1

Early

>1

Early

>1

>1 >1 >1

>1

>1

Human ..... ............

Systolic and diastolic blood pressure & heart rate

17-ket0steroidexcretion; urine volume Body weight Body lenclth *If originating from the earth's surface

Baby...........

>>1

>>1

Adult

<<1

<<1

Eldedy

>1

>1

Adult

<<1
>1 <1

tewhom /ewbom

>>1 <1 >1 >1

H..

t~\ Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

of the transyear and near-week in the circulation of human newborns and o f A c e t a b u l a r i a may tell us a story about our cosmos half a billion years ago [26]. We have looked for and found evidence that a near-week characterizes current and past geomagnetics and, intermittently, heliomagnetics. Since there is some evidence suggesting that the biological decade, the biological transyear and the biological near-week may be genetically coded [23-27], this will have to be explored for other non-photic cycles originally viewed as 'reactive' phenomena, such as a biological half-year. Didecadal and quindecadal cycles also characterize humans and their societal 'health' and disease, including wars and economics ([9,29,30]; cf. [25]). That religiosity undergoes cycles corresponding in length to Hale's bipolarity cycle of sunspots is noteworthy. The similarity of cycle length could be chance, Important is the added finding that various characteristics of this cycle show a geographic/geomagnetic latitude dependence [4]. Further inferential statistical mapping of couplings among environmental and biological cycles is the main challenge: these cycles represent the reproducible aspects of behaviors and their understanding may someday perhaps lead to a world-wide acceptable ethosphere as well. Having met challenges like those by ferocious animals with more muscle power than that of homo sapiens, having found or built some means of protection against excessive cold and heat, and having optimized (at least in some areas) the availability and quality of food and clothing, having found herbs or other means to protect against illness, and seeking a comfortable environment, the inventive and constructive human (homo faber) must also guard against what threatens him/her in the ethosphere. We have to advance toward more than the recognition of the risks of diseases of the heart and circulation, among others, a field where the study of time structures could transform a spotcheck medicine into one of continuous monitoring to detect elevated risks rather than wait for disease to occur. But now, beyond heat and cold and beyond food and drugs, we also inquire into electricity, magnetics and electromagnetics, generated, among others, by hearts and brains as fields in us as well as around us, for quantifying cycles for the study of mechanisms underlying spirituality. The reward may be survival with an optimization of the setting for the electromagnetics not only of the mind and its consciousness, but also in particular of those neuroendocrines involved in the heretofore neglected ethosphere. A first task for health care, environmental care and beyond is to ascertain that in knowledge about a sea of cycles with immense numbers of waves, one makes a transition equivalent to that from alchemy to chemistry. We need to uncover, among others, the inferential statistical limits of the dynamics of interacting and continuously timevarying periodic systems in and around us. There is no alternative to m a p p i n g , i.e. to c h r o n o m i c s , in ethics, as elsewhere, realizing that circa-periodicities are reproducible only within limits. Accordingly, information on such limits is indispensable; sooner or later they will have to be provi-

$7

ded as ever more conservative confidence intervals for each cycle's characteristics, including their often very wobbly periods; eventually, there will also be a need for accounts of the many intermodulations among cycles with different frequencies. When these intermodulations are incompletely sampled, they may look like trends, that are but ascending or descending parts of waves. When a lifetime is covered by a trend, these trends, in their own right for the individual, may become cycles for populations [31]. Chronomics, the systematic mapping not only of the chronomes, but also of their interactions, has now begun for the biosphere in the context of an aligned physical environmental monitoring. New results reveal time-varying multifrequency synchronizations for instance among indices of terrestrial and solar activity and myocardial infarctions in populations [32,33]. We need to analyze with similar methodology religious and other spiritual as well as socioeconomic motivation by focus on underlying, or at least contributing, processes, related directly or indirectly, photically or nonphotically, to the sun and to drummers from the galaxies and beyond. Alexandrov and Gamburtsev in Russia deserve great credit for starting the mapping and analysis of cycles in natural processes [34-36]. If hominization, as visualized by Edouard le Roy [7] and Vladimir Ivanovich Vernadsky [36] time-macroscopically, is to proceed time-microscopically and internationally, it has to extend far beyond biomedical endeavors [20,38]. A most meritorious mapping of temporal variations in natural, anthropogenic and sociologic processes in Russia, will have to be continued with inferential statistical criteria, to eventually provide a better map of the international ethosphere. Alexander Leonidovich Chizhevsky started it when he turned to 100 years of data on the incidence of cholera: by superposed epochs and timemacroscopically, he clearly demonstrated circadecadal cycles on stacked data [39,40] 1. As a follow-up, important contributions were made by Miroslav Mikulecky, emeritus head of the department of internal medicine and professor of statistics at Comenius University of Bratislava, in cooperation with Jaroslav Strestik ([41-43]; cf. [44]), and Suitbert Ertel, emeritus head of the psychology department at GeorgAugust-University of G6ttingen [45,46]. Unless we clarify the mechanisms of the cycles involved, we can only continue to speculate. Progress will depend, to a critical extent, on recognizing scientifically what and how neuroendocrines [47,48] may contribute to internal-external cyclic interactions as they became genetically coded; the observation that the same variables, such as heart rate, currently resonate with environmental cycles and can be amplified or dampened in the presence and absence of external periodicities, respectively is most pertinent [49]. 1. Chizhevsky'smajor contributions earned him an offer of a Nobel Prize in 1939, which StaIin's governmentforbadehim to accept. In 1942, he was arrestedand imprisoneduntil 1958 [52].

$8

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) SI-Sl l

If life consists of indispensable rhythms, a scientific approach to an ethosphere may rest on the recognition that in each sphere of our biological concern, we may find a cyclic counterpart for our environment's dynamics, i.e. in the litho-, hydro-, atmo-, bio-, noo- and perhaps ethospheres. Spiritual, including religious motivation is influenced by physical environmental factors [4,50-54], which in turn may also contribute to economic cycles [31,55-58]; spirituality may also become amenable to optimization by the cycles' underlying mechanisms. 2 By physical measures, one could then try to optimize the ethosphere. What we do, on the small magnet that is earth, may be in part driven from the larger magnet the sun and from beyond; some effects may be contributed via the climate and weather as in agriculture and economics 3. Understanding these couplings of personal and national wealth and individual and societal health may serve to develop generally acceptable norms of behavior in different settings. Ethics and biology need not be separate. There were indeed substantial attempts to develop bioethics albeit without focus on cycles [59] 4. A hurdle in bioethics and ethics more broadly may lie in the failure to pursue our cyclic ontogenetic and phylogenetic memories, perhaps underlying mechanisms contributing to hate or envy vs love among individuals and populations. A scientific approach to mechanisms of and countermeasures to hate and envy by individuals and by communities is overdue, and it cannot involve hungry people. Francesco Redi's short-term view was O m n e v i v u m e vivo; a longer-term view resting on the quasireciprocity of already mapped cycles in and around us is: O m n i s rhythmus, omnis cyclus e cosmo. This hypothesis can be put to the test in the scientific pursuit of what for too many people was beyond the scope of science. Herbert H6rz [1,2] rightly questions whether the developing world's behavior can bring about a set of general human values in differentiated forms. He answers that at this time there is little evidence for any world 'culture', stating that humanity can destroy itself or as a responsible community work on the development of a modus operandi which can accommodate different values, different religions, different arts and different languages, which could each try to serve the development of universally acceptable behaviors. Both the question and the statement by H6rz are sober and realistic; the 2. Indeed, the finding of cycles in the activities of a highly religiously motivated communityof faithful - who recorded the hours spent per month in proselytizing for 50 years in over 103 geographic/geomagnetic locations [4], to reveal a latitnde dependence of the cycle's characteristics is worth further study, along with a search for any similar associations in crime and in a 2556-yearrecord of wars. 3. We refer to rhythms as phenomena validated by the rejection of the assumption of 'no cycle with an anticipated period', documented earlier by many replicated cycles and usually synchronized by one or more interacting environmental synchronizersor influencers, sometimes at more than one frequency. 4. We refer to cycles as phenomena validated by the same inferential statistical rejection of the zero-amplitude assumption, as in the case of a rhythm, but not (yet) meeting other conditions for a rhythm.

answer may come, in keeping with earlier concerns about time by H(~rz himself, from a scientific approach based on the time structure of such a dynamic entity as consciousness or rather spirituality, as a scientifically resolvable entity. Chronomics may be tried as a scientific way to identify the underlying mechanisms of the risks involved, not only for the individual as in the case of stroke prevention [60,61], but also for diseases such as cancer [61], and most important for other diseases of society [9,62]. The development of countermeasures to self-destruction by war or other terror is the most urgent task of national and international institutes of health, with a truly broadened scope. This task should be shared by science (read chronobiology and chronomics leading to preventive measures) at the level of society as well as of the individual. In this multifactorial situation, the mapping task of the physiologist is just one endeavor among very many. But a start should be made somewhere, and mapping chronomes, notably of our presumably genetically coded ontogenetic and phylogenetic memories, may lead us to information not available from the study solely of photic cycles which can depend on non-photic modulations. Thus, a circadian rhythm in a most p o w e r f u l vasoconstrictor, endothelin-15, m a y be demonstrated at one time [63,64], but not at another [65-68], in the very circulation in which cortisol remains circadian periodic [65]. The role of the cosmos remains to be elucidated in this and other 'secular' variation ([69]; cf. [39-48]). When we are focused on crime or morality, ignoring scientific facts and approaches based upon time [70-73], we may actually be unfocused. By chronomes, as a minimum, we broaden our perspective; as an optimum, we may strive to implement the often-forgotten axiom, 'Never Again', in our behavior, whether we call it civilization, culture or better transdisciplinary science. Eventually, science must focus upon ethics and examine its couplings with available methods [73,74], so that it is not too late to treat diseases of civilization and we might preferably endeavor to prevent them. Whether the time-microscopic mapping of melatonin in gut as well as in pineal, among other tissues, is a step in the right direction, only the future can tell [75-82]. Physical agents may act upon the n e u r o e n d o c r i n e s o f individuals. These individual networks may resonate notably in public gathering places in response to what is seen or heard, i.e., in response to actors in a theater, to athletes in a sports arena, or charismatic speakers at a political rally. The role of hunger in the same context is important and accompanies the association of 'bread and circuses' (Juvenal, Satires, 10.79-81) in ancient Rome. Hunger drives much behavior, including aggression; hence gut-brain relations are critical and have yet to be elucidated. It is stimulating to find, as noted, that physiologically, the peak of the circadian melatonin rhythm leads that in the pineal [78-80] in the rat and chicken, but not in the quail. 5. To the point that circadian rhythms in a major vasoconstrictor,endothelin-1 (ET-1) [63,64], can become about 8-hourly and/or about half-weekly, not only in blood [65-68] but even in ear dermis, in the population density of the cells producingET-1 [68].

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1- Sl l

Acknowledgments T h i s s t u d y w a s s u p p o r t e d b y the U S P u b l i c H e a l t h Serv i c e ( G M - 1 3 9 8 1 ) (to F H ) , t h e U n i v e r s i t y o f M i n n e s o t a S u p e r c o m p u t i n g I n s t i t u t e (to G C , F H ) , E T T 8 2 / 2 0 0 3 (to

[18]

RJ), a n d V E G A 1 / 1 2 9 4 / 0 4 (to M Z ) .

References [1] [2] [3] [4]

[5]

[6]

[7] [8]

[9]

[10]

[11]

[12] [13] [14]

[15] [16]

[17]

H6rz H. Technologien zwischen Effektivit/it und Humanit~it. Sitzungsberichte der Leibniz-Sozietaet 2001;50:56-8. HOrzH, Philosophie der Zeit. Berlin: Deutscher Verlag der Wissenschaften; 1990. 190 pp. Hale GE. Sun-spots as magnets and the periodic reversal of their polarity. Nature t924; 113:105-12. Starbuck S, Corn~lissen G, Halberg F. Is motivation influenced by geomagnetic activity? Biomed Pharmacother 2002;56(Suppl. 2): $289-97. Corn61issen G, Engebretson M, Johnson D, Otsuka K, Burioka N, Posch J, et al. The week, inherited in neonatal human twins, found also in geomagnetic pulsations in isolated Antarctica. Biomed Pharmacother 2001;55(Suppl. 1):32-50. Halberg F, Corn~lissen G, Wen& H, P611mannL, POllmann B, Katinas G, et al. Chronomik yon KomplementSxsystemen der Namrwissenschaften und Medizin: Reziproke Zyklizit~iten der Biosphiire und des Kosmos. In: Schr6der W (editor). Arbeitskreis Geschichte der Geophysik und Kosmische Physik. Meteorological and geophysical field dynamics (a book to commemorate the centenary of the birth of Hans Ertel). Bremen: Wilfried Schr6der/Science Edition/Arbk Geschichte Geophysik: 2004. p. 284-302. Le Roy E. Les origines hnmaines et l'~volution de I'intelligence, vii. Paris: Boivin; 1928. 375 p. Halberg F, Corn61issen G, Conti A, Maestroni G, Maggioni C, Perfetto F, et al. The pineal gland and chronobiologic history: mind and spirit as feedsidewards in time structures for prehabilitation. In: Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke W, Eds. The pineal gland and cancer: neuroimmunoendocrine mechanisms in malignancy. Heidelberg: Springer; 2001. p. 66.116. Halberg F, Corn61issen G, Otsuka K, Katinas G, Schwartzkopff O. Essays on chronomics spawned by transdisciplinary chronobiology: witness in time: Earl Elmer Bakken. Neuroendocrinol Len 2001 ;22:359-384. Halberg F, Halberg E, Barnum CP, Bittner JJ. Physiologic 24-hour periodicity in human beings and mice, the lighting regimen and daily routine. In: Withrow RB, Ed. Photoperiodism and related phenomena in plants and animals, No. 55. Washington DC: AAAS; 1959. p. 803-78. Burioka N, Corn61issen G, Halberg F, Kaplan DT. Relationship between correlation dimension and indices of linear analysis in both respiratory movement and electroencephalogram. Clin Neurophysiol 2001;112:1147-53. Di Canzio A. Galileo: his science and his significance for the future of man. Portsmouth, NH: Adasi; 1996. 389 pp. Einstein A. Science and religion. Nature 1940;3706: 605-7. Tiller WA. Science and human transformation: subtle energies, intentionality and consciousness. Wahmt Creek, CA: Pavior; 1997. 316 pp. Jahn RG. Information, consciousness, and health. Alternat Ther Health Med 1996;2:32-8. Otsuka K, Corn61issen G, Halberg F. Circadian rhythmic fractal scaling of heart rate variability in health and coronary artery disease. Clin Cardiol 1997;20:631-8. Halberg F, Corn61issen G, Katinas G, Syutkina EV, Sothern RB, Zaslavskaya R, et al. Transdisciplinary unifying implications of circa-

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

$9

dian findings in the 1950s. J Circ Rhythms 2003;1(2): 61 pp. www.JCircadianRhythms.com/content/pdf/1740-3391/1/2.pdf Sothern RB, Katinas GS, CornOlissen G, Halberg F. A 38-year record, albeit informative, is not yet enough: Womb-to-tomb monitoring is overdue. Appendix 2 in Halberg F, Corn61issen G, Otsuka K, Wang ZR, Katinas GS, Siegelova J, et al, Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, nearweeks, near-decades, phylogenetic and ontogenetic memories. Bioreed Pharmacother (this issue). Watanabe Y, Nintcheu-Fata S, Katinas G, Corn~lissen G, Otsuka K, Hellbragge T, et al. Methodology: partial moving spectra of postnatal heart rate chronome. Neuroendocrinol Lett 2003;24(Suppl. 1): 13944. Halberg F, Corn~lissen G, for the International Womb-to-Tomb Chronome Initiative Group: Resolution from a meeting of the International Society for Research on Civilization, Diseases and the Environment (new SIRMCE Confederation), Brussels, Belgium, March 17-i8, 1995: fairy tale or reality? Medtronic Chronobiology Seminar No. 8, April 1995. URL http://www.msi.umn.edu/-halberg/. Faraone P, Corn61issen G, Katinas GS, Halberg F, Siegelova J. Astrophysical influences on sectoring in colonies of microorganisms. Scripta Med (Brno) 2001;74:107-14. Faraone P, Cornfilissen G, Konradov A, Vladimirskii B, Chibisov S, Katinas G, et al. A transyear in air bacteria and staphylococci. In: Conf., Biological Effects of Solar Activity, Pushchino, Russia, April 6-9, 2004. Halberg F, Corn61issen G, Faraone P, Schack B, Syutkina EV, Chibisov S, et al. Chronomics: a cartographic memory in chronomes (time structures) of exophased human to prokaryotic endocycling. Abstr, Conf., Biological Effects of Solar Activity, Pushchino, Russia, April 6-9, 2004. Halberg F, Corndlissen G, Schack B. Self-experimentation on chrohomes, time structures; chronomics for health surveillance and science: also transdisciplinary civic duty? Behav Brain Sci, http:// www.bbsonline.org/Preprints/Roberts/Commentators/Halberg.html. Corn~lissen G, Masalov A, Halberg F, Richardson JD, Katinas GS, Sothern RB, et al. Multiple resonances among time structures, chronomes, around and in us. Is an about 1.3-year periodicity in solar wind built into the human cardiovascular chronome? Fiz Cheloveka (Hum Physiol) 2004;30(2):86-92. Halberg F, Corn~lissen G, Schack B, Wendt HW, Minne H, Sothern RB, et al. Blood pressure self-surveillance for health also reflects 1.3year Richardson solar wind variation: spin-off from chronomics. Biomed Pbarmacother 2003;57(Suppl. 1):$58-76. Halberg F, Corn~lissen G, Stoynev A, Ikonomov O, Katinas G, Sampson M, et al. Season's appreciations 2002 and 2003. Imaging in time: The transyear (longer-than-the-calendar year) and the halfyear. Neuroendocrinol Lett 2003;24:421-40. Halberg F, Marques N, Coru61issen G, Bingham C, Sanchez de la Pefia S, Halberg J, et al. Circaseptan biologic time structure reviewed in the light of contributions by Laurence K. Cutkomp and Ladislav Derer. Acta Entomol Bohem 1990;87:1-29. Halberg F, Corn61issen G, Katinas G, Appenzeller O, Otsuka K, Sothern RB, et al. System times and time horizons for biospheric near-matches of primarily non-photic environmental cycles. Biomed Pharmacother 2002;56(Suppl. 2):$266-72. Halberg F, Corn6lissen G, Watanabe Y, Otsuka K, Fiser B, Siegelova J, et al. Near 10-year and longer periods modulate circadians: intersecting anti-aging and chronoastrobiological research. J Gerontol A Biol Sci Med Sci 2001 ;56:M304-24. Komlos J, Corn61issen G, Woitek U, Otsuka K, Halberg F. Time structures, chronomes, of soldiers' stature mimicking about 21-year Hale cycle in neonatal body length. Biomed Pharmacother 2004; (this issue). Corn~lissen G, Halberg F, Breus T, Syutkina EV, Baevsky R, Weydahl A, et al. Non-photic solar associations of heart rate variability and myocardial infarction. J Atmos Solar Terr Phys 2002;64:707-20.

S10

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-SI1

[33] Halberg F, Com61issen G, Bingham C, Witte H, Ribary U, Hesse W, et al. Chronomics: imaging in time by phase synchronization reveals wide spectral-biospheric resonances beyond short rhythms CWenn man ueber kurze Rhythmen hinausgeht"). In memoriam - lost future: Dr Barbara Schack: 1952-2003. Neuroendocrinol Lett 2003; 24: 355-80. [34] Alexandrov SI, Gamburtsev AG. Atlas prirodnyh processov, vol.1 [Atlas of natural processes]. Order and chaos in the lithosphere and other spheres. Moscow: United Institute of the Physics of the Earth. i994. 176 pp. [35] Alexandrov SI, Gamburtsev AG. Atlas vremennykh variacij prirodnykh antropogennykh i social'nykh processov, vol. 2 [Atlas of temporal variations in natural, anthropogenic and social processes]. Cyclic dynamics in nature and society. Moscow: Scientific World; 1999.72 pp. [36] Alexandrov SI, Gamburtsev AG. Atlas vremennykh variacij prirodnykh antropogennykh i social'nykh processov, vol. 3 [Atlas of temporal variations in natural, anthropogenic and social processes]. Nature and social spheres as parts of environment and as objects of influence. Moscow: Janus-K; 2002. 651 pp. [37] Levit GS. Biogeochemistry - biosphere - noosphere: The growth of the theoretical system of Vladimir Ivanovich Vernadsky. Berlin: VWB; 2001. 116 pp. [38] Corn61issen G, Halberg F. Introduction to chronobiology. Medtronic Chronobiology Semin. No. 7, April 1994. Library of Congress Catalog Card 94-060580; URL http://www.msi.umn.edu/-halberg/. [39] Chlzhevsky AL. Action de l'ionisation de l'atmosphere et de l'ionisation artificielle de Fair sur les organismes sains et les organismes malades. In: Pi6ry M, Ed. Trait6 de climatologie: biologiqne et m~dicale, vol. 1. Paris: Masson; 1934. p. 662-73. [40] Zigel F. In: Goering H, Ed. Schuld ist die Sonne. Thun/Frankfurt am Main: Harri Deutsch; 1979. 215 pp. [41] Mikulecky M, Ed. The Moon and living matter. Kosice, Slovakia, September 23-25, 1993. Bratislava: Slovak Medical Society; 1993. 97 pp. [42] Mikulecky M, Ed. Sun, moon and living matter. Bratislava, Slovakia, June 28-July 1, 1994. Bratislava: Slovak Medical Society; 1994.159 PP. [43] Mikulecky M, Ed. Chronobiology and its roots in the cosmos. High Tatras, Slovakia, September 2-6, 1997. Bratislava: Slovak Medical Society; 1997.287 pp. [44] Strestik J, Prigancova A. On the possible effect of environmental factors on the occurrence of traffic accidents. Acta Geod Geophys Montan Hung 1986;21:155-66. [45] Ertel S. Influenza pandemics and sunspots-easing the controversy. Naturwissenschaften 1994;82:308-10. [46] ErteI S. Bursts of creativity and aberrant sunspot cycles: hypothetical covariations. In: Nyborg H, Ed. The scientific study of human nature: Tribute to Hans J. Eysenck at 80. New York: Elsevier Science; 1997. p. 491-508. [47] Halberg F, Corn~lissen G, Sothem RB, Wallach LA, Halberg E, Ahlgren A, et al. International geographic studies of oncological interest on chronobiological variables. In: Kaiser H, Ed. Neoplasms - Comparative pathology of growth in animals, plants and man. Baltimore: Williams and Wilkins; 1981. p. 553-96. [48] Halberg F, Com61issen G, Katinas GS, Watanabe Y, Otsuka K, Maggioni C, et al. Feedsidewards: intermodulation (strictly) among time structures, chronomes, in and around us, and cosmo-vasculo-neuroimmunity. About ten-yearly changes: what Galileo missed and Schwabe found. In: Conti A, Maestroni GJM, McCann SM, Stemberg EM, Lipton JM, Smith CC, Eds. Neuroimmunomodulation. Proc. 4th Int. Cong. Int. Soc. Neuroimmunomodulation, Lugano, Switzerland, September 29-October 2, 1999. Ann NY Acad Sci 2000;917:348-76. [49] Corn61issen G, Halberg F, Wendt HW, Bingham C, Sothem RB, Hans E, et al. Resonance of about-weekly human heart rate rhythm with solar activity change. Biologia (Bratislava) 1996;51:749-56.

[50] Holmes B. In search of God. New Scientist, April 21, 2001. http://' www.newscientist.com [51] Persinger MA. Religious and mystical experiences as artifacts of temporal lobe function: a general hypothesis. Percept Motor Skills 1983;57:1255-62. [52] Persinger MA. Neuropsychological bases of God beliefs. New York: Praeger; 1987. 164 pp. [53] Persinger MA. Geophysical variables and behavior: LV. Predicting the details of visitor experiences and the personality of experience: the temporal lobe factor. Percept Motor Skills 1989;68:55-65. [54] Persinger MA. The sensed presence as right hemispheric intrusions into the left hemispheric awareness of self: an illustrative case study. Percept Motor Skills 1994;78:999-1009. [55] Clarke H. On the political economy and capital of joint stock banks. Rail Mag 1838;27:288-293 (cited in Editor's Comments on papers 29 through 36. In: Schove DJ, Ed. Sunspot cycles. Benchmark Papers in Geology/68. Stroudsburg, PA: Hutchinson Ross; 1983: 226-38). [56] Clarke H. Physical economy: a preliminary inquiry into the physical laws governing the periods of famines and panics. Railway Register, 1847 (cited in Editor's Comments on papers 29 through 36. In: Schove DJ, Ed. Sunspot cycles. Benchmark Papers in Geology/68. Stroudsburg, PA: Hutchinson Ross; 1983: 226-38). [57] Turtoi C, Corn~lissen G, Wilson D, Otsuka K, Halberg F. About 21year Hale cyclic signatures in a~icnlture complement those in biomedicine. Biomed Pharmacother 2004; (this issue). [58] Woitek U. Height cycles in the 18th and i9th centuries. Econ Hum Bio12003; 1:243-57. [59] Potter VR. Bioethics: bridge to the future. Engelwood Cliffs, NJ: Prentice-Hall; 1971. 205 pp. [60] Halberg F, Com61issenG, Schwartzkopff O, Hardeland R, Ulmer W. Messung und chronobiologische Auswertung der Variabilit~itenyon Blutdruck und Herzfrequenz zur Prophylaxe schwerwiegender Krankheiten. Proc Leibniz Soz 2003; 54: 127-56. [61] Com61issen G, Bingham C, Siegelova J, Fiser B, Dusek J, Prikryl P, et al. Cardiovascular disease risk monitoring in the light of chronobioethics. Chronobiologia 1994;21:321-25. [62] Halberg F, Bingham C, Siegelova J, Fiser B, Dusek J, Prikryl P, et al. 'Cancer marker chronomes' assessed in the light of chronobioethics. Chronobiologia 1994;21:327-30. [63] Artigou JY, Salloum J, Carayon A, Lechat P, Maistre G, Isnard R, et al. Variations de l'endoth61ine plasmatique au cours du spasme coronaire. Arch Mal Coeur 1993;86:1581-6. [64] Tarquini B, Pini ME, Lapucci C, Navari N, Tarquini R, Curradi C, et al. Endothelin-1 circadian acrophase: a potential co-determinant in cardiovascular chronorisk. Abstr., 21st Conf., Int. Soc. Chronobiology, Quebec, 11-15 July, 1993: XV-8. [65] Herold M, Com61issenG, Loeckinger A, Koeberle D, Koenig P, Halberg F. About 8-hourly variation of circulating human endothelin-1 (ET-1) in clinical health. Peptides 1998;19:821-5. [66] Tarquini B, Perfetto F, Tarquini R, Com61issen G, Halberg F. Endothelin-l's chronome indicates diabetic and vascular disease chronorisk. Peptides 1997;18:119-32. [67] Tarquini B, Com~lissen G, Perfetto F, Tarquin R, Halberg F. Abouthalf-weekly (circasemiseptan) component of the endothelin-1 (ET-1) chronome and vascular disease risk. Peptides 1997;18:1237-41. [68] Katinas GS, Halberg F, Corn61issen G, Hawkins D, Bueva MV, Korzhevsky DE, et al. About 8- and ~84-hour rhythms in endotheliocytes as in endothelin-1 and effect of trauma. Peptides 2001 ;22:64759. [69] Yagodinsky V. Nami pravit kosmos [The cosmos rules us]. Moscow: Ripol Klassik; 2003. 567 pp. [70] Halberg F. Chronobiology. Annu Rev Physiol 1969;31:675-725. [71] Halberg F, Com61issen G, Wrbsky P, Johnson D, Rigamso J, Tarquini B, et al. About 3.5-day (circasemiseptan) and about 7-day (circaseptan) blood pressure features in human prematurity. Chronobiologia 1994;21:146-51.

F. Halberg et al. / Biomedicine & Pharmacotherapy 58 (2004) S1-Sl l

[72] Halberg F, Breus TK, Corn61issen G, Bingham C, Hillman DC, Rigatuso J, et al, for the International Womb-to-Tomb Chronome Initiative Group. Chronobiology in space. Keynote, 37th Ann. Meeting, Japan Soc. Aerospace and Environmental Medicine, Nagoya, Japan, Nov. 8-9, 1991. University of Minnesota/Medtronic Chronobiology Seminar Series No. 1; 1991. [73] Halberg F, Corn61issen G, Otsuka K, Watanabe Y, Katinas GS, Burioka N, et al., for the International BIOCOS Study Group. Crossspectrally coherent -10.5- and 21-year biological and physical cycles, magnetic storms and myocardial infarctions. Neuroendocrinol Lett 2000;21:233-58. [74] Witte H, Schack B. Quantification of phase coupling and information transfer between electroencephalographic (EEG) signals: Analysis, strategies, models and simulation. Theory Biosci 2003; 122( 1):361-81. [75] Halberg F. Quo vadis basic and clinical chronobiology: promise for health maintenance. Am J Anat 1983;168:543-94. [76] Falc6n J, Ravault J-P, Corn61issen G, Halberg F. Circaseptan-modulated circadian rhythmic melatonin release from isolated pike pineal in alternating light and darkness. Abstract, 4 °Convegno Nazionale, Societh Italiana di Cronobiologia, Gubbio (Perugia), Italy, June i-2, 1996:39-40. [77] Tarquini B, Corn61issen G, Perfetto F, Tarquini R, Halberg F. Chrohome assessment of circulating melatonin in humans. In vivo 1997;11:473-84.

S11

[78] Zeman M, Corn61issen G, Balazova K, Jozsa R, Olah A, Nagy G, et al. Circadian rhythm of melatonin in rat duodenum. Abstract, MEFA, Brno, Czech Republic, Nov 2004, in press. [79] Zeman M, Corn61issen G, Balazova K, Herichova I, Jozsa R, Olah A, et al. Circadian acrophase differences in plasma, pineal, hypothalamic and duodenal melatonin in rats -qualified in quail. Abstract, Proc 5th International Symposium, Workshop on Chronoastrobiology and Chronotherapy, Tokyo, 2004, in press. [80] Hardeland R, P6ggeler B, Huether G, Corn61issen G, Jozsa R, Zeman M, et al. Chronomics supports lead in phase of duodenal vs. pineal circadian rhythm of melatonin. Abstract, Proc 5th International Symposium, Workshop on Chronoastrobiology and Chronotherapy, Tokyo, 2004, in press. [81] Hardeland R, Ptiggeler B, Corn61issen G, Halberg F. Chronomics: modelling the circadian rhythm of melatonin in unicells, notably Lingulodinium polyedrum (syn. Gonyaulax polyedra). Abstract, Proc 5th International Symposium, Workshop on Chronoastrobiology and Chronotherapy, Tokyo, 2004, in press. [82] Edmunds L, Balzer I, Corndlissen G, Halberg F. Toward a chronome of Euglena gracilis (Klebs). Neuroendocrinol Lett 2003;24 (Suppl 1): 192-9.