Ion-free water ... Isotopes

[Alexander Berezin]

On Thu, 17 Oct 1996, Beverly Erlebacher wrote:

> In article <Pine.SGI.3.93.961014225602.16957B-100000 at freenet.npiec.on.ca> kveress at FREENET.NPIEC.ON.CA (Karoly Veress) writes:
> >Hi! again, I have one query more
> >	Someone had stated that there was about 1-10% D2O in water of the
> >human body. Where does this rather suprisingly high amount occur in the
> >human body?
> >
> >thanxs again for anyone that answering or atleast considering the above
> >query.
> 
> The best way to consider such a statement is to do a reality check.
> 
> Independent of the question of how the human body would manage to do
> a several-orders-of-magnitude concentration of deuterium from water,
> consider that if this statement were true, the cheapest method of 
> producing D2O would be by distilling human corpses, or perhaps by
> plasmapheresis from paid volunteers, and D2O by the bottle would be
> much much cheaper.
> 
> Beverly Erlebacher
> Toronto, Ontario Canada
> 


This thread has on-going discussion on the
role of D2O (deuterated) water and other
isotopic replacement. The following article
has some references to this effect.
Reprints of this, as well well as of some 
earlier (and later) papers available from me
on the request.
**********************************
Alexander A. Berezin, PhD
Department of Engineering Physics
McMaster University, Hamilton,
Ontario, Canada, L8S 4L7
tel. (905) 525-9140 ext. 24546
e-mail: BEREZIN at MCMASTER.CA
**********************************
------------------------------------------

ISOTOPIC RANDOMNESS AS A BIOLOGICAL FACTOR

Alexander A. BEREZIN

Department of Engineering Physics,
McMaster University, Hamilton,
Ontario, Canada, L8S 4L7

Abstract

We discuss an alternative source of randomness 
originating at the atomic level due to the 
diversity of stable isotopes. This randomness
could contribute to mutation mechanisms through 
atomic scale variations of bond lengths and 
strengths, differences in the reaction rates, etc.
In terms of purposeful experimentation, isotopic 
replacements in living organisms give an 
independent parametrization which allows to 
correlate the global biological variables with 
the level of individual atoms. We review the work 
done so far, and suggest some further experimental
possibilites by analogy with some isotopic 
effects and isotopic structuring in solid state 
physics. 
____________________________________________________________

Key words:  Stable isotopes, isotopic randomness, 
isotopic replacements, carbon-14, 
isotopic fluctuations

____________________________________________________________

Introduction
 
Earlier I discussed the model of alternative genetic 
code based on combinations of stable isotopes 
(Berezin, 1984 a). The concept was later developed 
further (Berezin, 1986). Here I would like to 
discuss a yet another line of research in fundamental 
and applied biology which somehow seems to be 
underestimated. The subject is the purposeful 
shift of isotopic abundancies of stable isotopes 
in living organisms in order to establish some 
physiological and behaviorial correlations with
isotopic content.

In the present paper we suggest some types of 
experiments on isotopic replacements in living 
organisms. To some extent, the possibilities to 
be discussed here arose by analogy with some less
known manifestations of isotopic randomness and 
isotopic structuring in solid state physics. We 
should stress that the subject of isotopic
replacements in biology should not be confused 
with studies on radioactive and stable trace 
isotopes which constitute one of the pillars of 
nuclear medicine and will not be discussed in 
the present paper.

Some isotope-related effects in biology
 
It is known, that physical characteristics of 
isotopically pure substancies are generally quite 
close, but not exactly the same. For example, 
there are some differences (about 1 part per 
several thousand) in equilibrium lattice constants 
of natural (i.e. isotopically blended) and 
isotopically purified crystals; the thermodynamical
characteristics of heavy water are not the same as 
light water (e.g. critical temperature is 643.9 
and 647.1 K respectively), etc. We live in the
environmenrt of fixed isotopic ratios. For example, 
carbon is 98.9 % carbon 12-C and 1.1 % 13-C, 
nitrogen is mostly 14-N, oxigen is 16-O, etc. 

At the same time, minority stable isotopes 
(13-C, 15-N, 17-O, 18-O, etc.) are also have 
their share, they are relatively easily obtainable
as pure isotopes, and nonradioactive. One may ask 
what will happen with a living organism if we 
intentionally shift naturally occuring isotopic
ratios ? Will such change affect the rate of 
metabolism, aging processes, adaptability, etc.?

Previously several authors discussed various 
unexpected roles which isotopes can play in life 
matters. Mann and Primakoff (1981) have indicated 
the possible origin of biological chirality 
(asymmetry between left and right) from beta-decay 
of isotopes 14-C and 40-K. The present author have 
mentioned 14-C decays as a possible contributing
factor of carcinogenesis and genetic mutations 
(Berezin, 1984 b) while Keswani (1986) pointed 
on random disintegrations of 14-C as a likely
source of spontaneous and unpredictable 
triggerings of brain processes (e.g. sudden 
memory flashes).

It is known that microorganisms could shift 
isotopic abundancies of heavier elements, e.g. 
32-S and 34-S (Thode, 1980). These shifts,
however, are due to some tiny differences in 
reaction rates leading to some preference in 
isotope incorporation, gravitational (weight)
fractionation, etc. The observed shifts usually 
do not exceed 1 % in relative change of isotopic 
proportions in comparison with standard
abundancies. At the same time, some reactions 
sensitive to nuclear magnetic moment (NMM) could 
lead to a much greater segregation efficiency.
While the mass difference between stable isotopes 
is at best a few per cent (except, of course, 
hydrogen & deuterium pair) the difference of NMM 
could be much more drastic. For instance, 12-C has 
zero NMM while 13-C has a non-zero NMM and, 
consequently, responds very differently to a 
magnetic interaction. Using reactions involving
magnetic (hyperfine) interactions the single-stage 
segregation efficiency of about 50 % for 13-C 
and 12-C has been obtained (Epling and Florio, 
1981).    

Numerous studies on heavy water enrichment in 
living organisms have been undertaken since 
1930-s starting almost immediately after the 
discovery of deuterium in 1932. In his review 
Katz (1960) gives interesting examples of 
deuteration effects on mice and rats showing
that both animals cannot survive replacement of 
more than about one-third of the body water by 
D2O. Most of the changes induced by deuteration 
(e.g. loss of reproductive capacity) are 
reversible upon the replacement of deuterium 
back by ordinary hydrogen. Katz (1960) have 
also mentioned the possibility of isotopic 
replacements for stable isotopes of C, O, N 
and S. The actual experiments on isotopic
replacements in animals for elements heavier 
than hydrogen have been reported for 13-C 
(Gregg et al., 1973) and 18-O (Wolf et al. 1979).

Both experiments succeeded in replacing of 
about 60 % of all body carbon or oxygen in mice 
by 13-C or 18-O (their normal isotopic abundance 
is 1.1 % and 0.2 %, respectively). No 
pathalogical changes have been found in any 
organs. However, I did not find any specific 
studies of how such metamorphosis affects 
various physiological responses. Several 
experimental suggestions are mentioned in 
the next Section. 

Some possibe experiments on isotope effects 
in biology

The presence of the majority of elements in 
two or more stable isotopes is one of the prime 
facts of Nature. Therefore, even from the general 
point of view it seems unlikely that the diversity 
of stable isotopes could remain totally irrelevant 
to Earth's biology. Here I will list several 
lines of possible studies, complimentary to
those which have been mentioned in the preceeding 
paragraph. It should, of course, be kept in mind 
that the following list inevitably has some degree 
of subjectiveness and speculativeness.     

1) Combinations of isotopes. 

An obvious extension of studies on 13-C and 18-O 
mice (or for that matter on simplier organisms, 
e.g. drosophila) would be a combination of two 
or more stable isotopes in variable ratios. For 
instance, the cummulative effect of triple 
replacement 12C -> 13C, 16O -> 18O and 14N -> 15N 
could lead to much stronger effects than either 
of them separately.

2) Thermal regulation. 

Isotopic replacement of C, O and N changes 
densities of all structures by several per cents. 
Diffusivities and other kinetic characteristics, 
especially those related with tunneling, could 
change even more strongly. Thus, isotopic
replacements may lead to a "fine tuning" of 
thermal regulation mechanisms in mammalia. 
Similarly, isotopic shift can change a speed
of propagation of nerve impulses and other 
related characteristics.

3) Magnetic effects. 

Magnetic effects in biology are generally 
considered to be subtle, but could be of 
importance for some specific cases (e.g. 
orientation of birds, responce of some 
microorganisms, etc). In view of the differences 
in NMM between 12-C and 13-C (see above),
magnetic experiments on 13C-organisms may 
lead to non-trivial insights.  
 
4) Isotopic fluctuations. 

Any carbon chain contains 1 % of 13-C atoms.
This, in fact, is a very large concentration. 
If similar concentration relates to an impurity 
in crystal this will change its properties in a
noticable way (i.e. Rayleigh scattering of light 
on isotopic fluctuations, modification of thermal 
conductivity, etc.). Same applies to minority 
isotopes of oxygen and nitrogen. Performance 
of DNA, for example, can be affected by positional 
fluctuations of minority isotopes. This, in turn, 
could contribute to mutability and, consequently, 
one may suggest that isotopic randomness may act 
as an additional genetic factor. Fluctuations 
are proportional to the square root of number 
of particles. Therefore, the effective (average)
size of isotopic fluctuations will be appreciably 
different if, say, the concentration of 13-C is 
changed from 1 % to 0.1 % (in this example the 
size of fluctuation will increase by 10^(1/3) = 
2.15, if the distribution is uniform in 3 dimensions; 
for low dimensional systems, e.g. carbon chains, 
the size scales differently). One may think, 
therefore, of some kind of "inverse" experiments 
to those done with 13-C and 18-O mice (Gregg et al., 
1973; Wolf et al., 1979). Namely, the use of 
major isotopes (12-C, 16-O, 14-N) but purified
from the admixture of minor isotopes could 
suppress fluctuations and this may result in 
"improving" of genetic stability
("isotopic eugenics"?). 

5) "Isotopic indeterminism".

We can also note that isotopic randomness by 
itself creates an additional dimension in the 
genetic domain because the nominally identical 
molecules (e.g. symmetrical spirals of DNA) are,
in fact, never the same. Natural isotopes 
of H, C, N, O, etc. are randomly distributed 
among the correspondingly equivalent positions. 
The number of differnt combinations of isotopes 
in the structurally same molecule is practically 
uncountable and leaves far behind the number of 
electrons in the whole Universe. It is possible 
to speculate that this "isotopic uniqueness" of 
each multi-atomic structure could serve as an 
immanent (and virtually unexhaustable) resource 
of unpredictability and individuality in actual 
living beings. In this respect isotopic 
randomness could act as a counterpart (or 
competitor) of the "standard" quantum mechanical
indeterminism.  
                                                       
6) Positional correlations. 

As a supplement to item #5, it is also conceivable 
to think of possible positional correlations of 12-C
and 13-C during DNA reduplication. Namely, does 
a secondary spiral has any trace of the individual 
12C-13C pattern of the prime spiral ? The 
establishing of even a weak positional correlation 
would certainly be of interest, and experiments 
with organisms enriched by 13C to a variable 
degree (i.e. 10 %, 20 %, etc) could provide a
key for such studies.  

Conclusion

To summarize, we discussed the question of the 
effects of isotopic replacements in biology. 
Isotopic diversity is known to affect various
physical and chemical properties of solids 
(e.g. Berezin, 1984c).  Similarly, it likely can 
lead to some non-trivial manifestations
in biological domain. It is quite possible that 
substantial differnces may occur for only some 
selected properties (e.g. radiation resistance) 
while other characteristics may not change
drastically. We have stressed here the potential 
of studies of changes of isotopic ratios in 
biological systems. This gives a new parameter (in
fact, a whole range of continuosly changing 
parameters) to be correlated with global biological 
variables.
                       
There is, of course, a massive amount of 
biological and medical studies on radioactive and 
trace isotopes or on tiny variations of isotopic 
ratios in living tissues. What we are discussing
here, however, is related to the _stable_ isotopes 
for which isotopic ratios are purposefully shifted 
in significant proportions and in the entire
organism. The possibility of using isotopic ratios 
to control various processes could even have long 
range practical implications in the developing 
of "isotopic drugs", etc. In view of the above, it
seems likely that the isotopic option is worth of 
emphasizing, further thinking and experimentation.

References 

BEREZIN, A.A., 1984 a. Isotopic Biology.  
Il Nuovo Cimento, 3D, 914-916.

BEREZIN, A.A., 1984 b. Inherent genetic 
instability due to the presence of 14C-atoms 
in information bearing structures. Bulletin 
of the American Physical Society,  29, 635.

BEREZIN, A.A., 1984 c. Isotopic disorder as 
a limiting factor for the mobility of charge 
carriers.  Chemical Physics Letters,
110, 385-387. 
 
BEREZIN, A.A., 1986. On the mechanisms of 
information transfer inisotopic biology. 
Kybernetes (U.K.), 15 , 15-18.

EPLING, G.A. & FLORIO, E., 1981. Isotopoe 
enrichment by photolysis on ordered surfaces.
Journal of the American Chemical Society, 
103, 1237-1238. 

GREGG, C.T., HUTSON, J.Y., PRINE, J.R., 
OTT, D.G. & FURCHNER, J.E., 1973.
Substantial replacements of mammalian body 
carbon with carbon-13. 
Life Sciences,  13,  775-782.

KATZ, J.J., 1960. Chemical and biological 
studies with deuterium.
American Scientist,  48,  544-580.

KESWANI, G.H., 1986. Carbon-14 in the brain 
and other organs: chance within. Speculations 
in Science and Technology, 9, 243-244.

MANN, A.K. & PRIMAKOFF, H., 1981. Chirality 
of electrons from beta-decay and the 
left-handed  asymmetry of proteins.
Origins of Life, 11, 255-265. 

THODE, H.G., 1980. Sulphur isotope ratios 
in late and early precambrian sediments and 
their implications regarding early environments
and early life. Origins of Life, 10, 127-136.

WOLF, D., COHEN, H., MESHORER, A., WASSERMAN, 
I. &  SAMUEL, D., 1979. The effect of 18-C on the 
growth and reproduction of mice. In "Stable 
Isotopes", E.R. Klein and P.D. Klein (eds), Acad. 
Press, NY, S.Francisco, London, pp. 353-360.