This document summarizes silicon compounds' roles in biological systems and discusses three main topics: 1) Silicon's structural role in diatom cell walls and the processes of silica deposition. 2) Silicon uptake and roles in bacteria and plants, though it is not essential for growth. 3) Toxic effects of silicon compounds like silica in higher vertebrates, which is responsible for diseases like silicosis. The document proposes that silica's toxicity stems from its ability to damage lysosomal membranes through hydrogen bonding interactions.

1. Proc. Roy. Soc. B. 171, 19-30 (1968)
Printed in Great Britain
Silicon compounds in biological systems
B y A. C. A llison
Clinical Research Centre Laboratories, Mill Hill, London
(Plates 1 and 2)
The part played by silicon compounds in terrestrial life can be discussed under
three main headings. First is the important skeletal role which silica fulfils in
organisms such as diatoms. Secondly is the reduction of silicate which can be per­
formed by various micro-organisms and the question whether this can be regarded
as a specific participation in metabolism. Thirdly is the toxic effect of silicon com­
pounds in higher vertebrates, including man, which is responsible for the disease
silicosis in miners and for induction of certain types of malignant tumours. From
these observations it is clear that silicon compounds play an interesting, but
relatively minor and incidental role, in terrestrial life. The question then arises
whether this was a chance happening in the origin of life on our planet, or whether
there are any properties of silicon which disqualify it from more direct participa­
tion in metabolism, so that it could not substitute for some other central element
such as carbon in extraterrestrial life forms. Some general properties of silicon
compounds that bear on this problem will be discussed.
Silicon compounds in diatom cell walls
Diatoms are characterized by the presence of a silicon shell, often of great
beauty (figures 1 and 2, plate 1). The pattern and construction of the shells are
so regular within a species that for more than a century diatom taxonomy has
been based on these features. However, very little is known about the processes
which enable the cells to deposit silica in such a regular form. Only in the last few
years have detailed electron microscopic studies of the diatom shells revealed the
structural relationship ofsilica to the organic constituents ofthe cellwall. Reimann,
Lewin & Volcani (1966) have shown that the cell wall of the freshwater diatom,
Navicula pelliculosa, is composed of a silica shell and an organic skin which sur­
rounds it. The growth of the silica shell occurs intracellularly inside a vesicle de­
limited by a triple-layered membrane, the silicalemma. In most diatoms the silica
shell encloses the entire cell body. However, in the marine diatom, Cylindrotheca
fusiformis, wide unsilicified zones are present, and detailed structural studies were
presented by Reimann, Lewin & Volcani (1965). Every part of the silica shell is
tightly enclosed by organic material. In the valve region silica enclosed in this
way lies between layers of organic material. The whole cell wall is surrounded by
mucous material which stains with ruthenium red and may consist of pectin.
Studies have also been initiated on the mode of uptake and deposition of silica.
The most interesting result so far has been the observation that when Navicula is
grown in a medium without silicon, cell division is blocked after mitosis and
[ 19 ] 2-2

2. 20
cytokinesis have taken place; the addition of silicon induces synchronous silicon
uptake, wall formation and cell separation (Coombs, Halicki, Holm-Hansen &
Volcani 19676). The concentration ofnucleoside triphosphates decreased during the
period of silicon uptake, which confirmed previous evidence that energy is used in
the biochemical processes of silicon metabolism in wall formation. From studies on
incorporation of labelled precursors it appeared that the organic plasmalemma
formation took place before addition of silicon completed cell-wall formation.
Coombs and his collaborators (1967a) found that cell division of Cylindrotheca
could also be synchronized by growth in the dark and then at high light intensities.
Again it seemed that energy was required for silicon deposition, either through
active transport of silicon from the medium into the cell and/or its translocation
from the cytoplasm to the vesicles of the silicalemma in which deposition occurs.
The authors suggest that adenosine triphosphate may also be consumed in the
activation of silicon to a nucleoside diphosphate-silicon intermediate. This raises
the important question of whether silicon can be covalently bound to organic cell
constituents, which is discussed below.
A. C. Allison (Discussion Meeting)
Silicon compounds in bacteria and plants
In many organisms—bacteria, fungi and higher plants— silica can be taken up
from the growth medium or soil water and deposited in cell walls. Silicon is not
essential for growth although it can directly or indirectly affect growth. Thus, the
role of silica in plants has been reviewed by Comhaire (1966). In certain soils silica
increases the availability of phosphorus from soil by anion exchange. According to
Hunter (1965) there is no evidence that silica substitutes for phosphate within the
plant.
There are two interpretations of silica uptake by plant roots and its relocation
into growing shoots. One is that silica passively travels with water and is deposited
when transpiration takes place (Jones & Handreck 1965). The alternative view is
that there is active transport of silicon compounds. Inhibitors of aerobic respira­
tion were found to reduce uptake of 31Si by roots (Mitsui & Tokatoh 1963), but
water movements might also have been affected. According to Yoshida (1965),
there is in the rice plant a cuticular double layer and a silica-cellulose membrane
which limit water evaporation and serve as a barrier against pathogenic fungi and
insect pests. Silicon-deficient plants lost more water by transpiration than did
plants supplemented with silica.
Uptake of silica by bacteria has been extensively studied by Heinen (1965,1967).
Proteus mirabilis cells or particulate fractions were found to accumulate silicate
when incubated in the presence of an energy source. Heinen (1965) concluded that
Description oe plate 1
Figube 1. Phase-contrast photomicrograph of a colony of the diatom Licmophora flabellata
( x 650).
Figube 2. Electron micrograph of a carbon replica of the freshwater diatom
( x 4500).

3. Allison Proc. Roy. Soc. B, volume 171, plate 1
For legend see facing page.
(Facing p. 20)

4. Allison Proc. Roy. Soc. B, volume 171, plate 2
Figure 3. Electron micrograph of a thin section of a macrophage shortly after ingestion of
silica particles. The silica is seen in phagosomes (P). Lysosomes are marked L, and one
(L*) is attached to a phagosome. Cytoplasmic detail, including structure of mitochondria
(M) is well preserved ( x 24000).
Figure 4. Electron micrograph of thin section of a macrophage 18 h after uptake of silica
particles. These (S) have escaped into the cytoplasm, which is disorganized. Mitochondria
(M) above the nucleus are swollen and rounded ( x 24000).

5. 21
the silica is covalently linked to carbohydrate. This conclusion is based on the
observation that an alcohol-ether insoluble cell-wall fraction contained water-
soluble silicon compounds which upon hydrolysis released ‘molybdate-active’
silicic acid and hexoses. However, it seems equally possible that the silicic acid was
not covalently bound to the carbohydrate but complexed in some other way, e.g.
by multiple hydrogen bonding. The application of nuclear magnetic resonance
spectrometry or some other more sophisticated technique would be required to
show unambiguously that silicon is covalently linked to carbon.
Some of the particulate fractions described by Heinen (1967) were also able to
catalyse the reduction of silicate, a property shown by a number of micro­
organisms. However, it seems that this is a non-specific process analogous to the
reduction of selenate or tellurite. These organisms have a particulate hydrogenase
together with an unspecific reductase for inorganic electron acceptors. Silicate can
serve as electron acceptor and react with the ejected protons to form volatile
(oxy-)-hydrides. Thus the important question of whether silicon compounds can
actually participate in enzyme-catalysed reactions, with the formation of silicon-
organic compounds, is still open. Such reactions may occur, but available evidence
is insufficient to decide the point.
Toxicity of silicon compounds in vertebrates
Foreign particles, taken into the human body by inhalation, are usually in­
nocuous, like the carbon particles that remain in phagocytic cells of the lungs more
or less indefinitely. However, certain particles such as silica (silicon dioxide) or
asbestos (the generic name given to a group of fibrous silicates of complex composi­
tion) stimulate a severe fibrogenic reaction. This does not only occur in the lungs.
If silica is injected intravenously into experimental animals, for example, collagen
is deposited in nodules in the liver. Several different crystalline forms of silica are
fibrogenic (quartz, tridymite, coesite, crystatobalite), but one, stishovite, is not
fibrogenic (Stober 1966). Stishovite is an unusual crystalline form of silica de­
veloping under conditions of high temperature and pressure. It has been isolated
as natural mineral from Coconino sandstone of Meteor Crater, Arizona (Bohn &
Stober 1966), and some of its properties, which may be relevant to its lack offibro-
genicity, are discussed below.
It is generally accepted that the initial event in silicosis is the phagocytosis of
silica particles by alveolar macrophages and consequent death of the cells. The
particles so released are taken up by other macrophages which are in turn killed.
In this way death of macrophages continues and stimulates collagen synthesis by
fibroblasts in the neighbourhood. Analysis of pathogenesis must therefore proceed
in two stages: first determining how silicaparticles kill macrophages, and, secondly,
determining how this is related to fibrogenesis. As Marks (1957) showed, the cyto­
toxic effects of silica can be conveniently reproduced in cultures of peritoneal or
alveolar macrophages, and the relative toxicity of different forms of silica, and of
different forms of silica, and of different dusts, on cell cultures agrees with the
pathogenicity and fibrogenic activities of the dusts vivo (Marks &Nagelschmidt
Silicon compounds in biological systems

6. 22
1959; Vigliani, Pernis &Monaco 1961). When my colleagues and I began working
on this problem in 1964, there was no satisfactory explanation of silica toxicity.
E. J. King, in his well-known ‘solubility’ theory suggested that silicic acid, liber­
ated into the tissues from silica particles, brings about deposition of collagen. Later
observations did not support this interpretation, as King (1947) himself pointed
out. Curran & Rowsell (1958) showed that silica particles implanted into the peri­
toneum in diffusion chambers do not induce any fibrogenic reaction, even though
silicic acid is liberated from the chambers. Vigliani & Pernis (1963) formulated an
auto-immune theory of silicosis, but several workers were unable to obtain experi­
mental evidence in support of this interpretation.
We therefore made a detailed study ofthe effects of toxic and non-toxic particles
on cultures of macrophages, using time-lapse phase-contrast cine-micrography,
histochemistry and electron microscopy (Allison, Harington & Birbeck 1966).
Particles of silica, diamond dust and other materials were rapidly included in
phagosomes surrounded by single membranes. Lysosomes become attached to the
phagosomes and discharged their lytic enzymes into the phagosomes (figure 3,
plate 2). So far there was no difference between toxic and non-toxic particles.
After about 18 h incubation, however, clear differences were apparent. The non­
toxic particles and associated enzymes were still enclosed in secondary lysosomes,
whereas many ofthe toxic particles and associated lysosomal enzymes had escaped
into the cytoplasm (figure 4, plate 2). The macrophages that had ingested non­
toxic particles were fully extended and moving about freely, whereas many ofthose
exposed to toxic particles were round and immobile. Thus it was evident that silica
particles, unlike non-toxic particles, can react with lysosomal membranes and
make them permeable.
This appears to be a relatively non-specific reaction of silica with a variety of
biological membrane systems. The simplest demonstration is provided by miying
washing erythrocytes with suspensions of silica particles or with silicic acid pre­
parations (Stalder & Stober 1965; Nash, Allison & Harington 1966). The erythro­
cytes are quite rapidly lysed by all forms of crystalline silica except stishovite, and
several other types of non-fibrogenic dust of comparable size and surface area pro­
duce very little haemolysis. We have presented reasons (Nash et al. 1966) for
believing that the toxicity of silica is due to the fact that the particles are easily
ingested and by interaction with water form on their surfaces silicic acid which
can act as a powerful hydrogen-bonding agent.
There are two classes ofhydrogen-bonding compounds. The larger class comprises
hydrogen acceptors such as ethers and ketones with active lone-pair electrons on
oxygen or nitrogen. The smaller class comprises hydrogen donors of which amine
cations and phenols (including tannic acid) are important among organic com­
pounds and silicic, boric, and some other weak acids among inorganic compounds.
Compounds of the one class interact with those of the other, so it is not surprising
that one group (hydrogen acceptors) are compatible with living cells whereas those
of the other class are damaging (Allison 1968).
Model experiments showed that hydrogen-bonding of phenolic hydroxyl groups,
of the type present in silicic acid, occurs with secondary amide groups of proteins,
A. C. Allison (Discussion Meeting)

7. 23
and this can lead to protein denaturation. However, the interaction with phospho­
lipid groups is stronger, and we have presented evidence that this is more important
in interactions with biological membrane systems. Evidence in support of the
interpretation that hydrogen bonding is important in silica toxicity comes from
experiments with poly-2-vinylpyridine-iVr-oxide ( ). Schlipkoter, Dolgner &
Brockhaus (1963) found that this substance markedly diminishes the amount of
fibrous tissue formed after intravenous injection of silica. The toxic effects of silica
on cultures of macrophages and other phagocytic cells are also diminished in the
presence of, or after exposure to, PPNO. We have shown (Allison et al. 1966) that
PPNO is taken up into lysosomes in much the same way as dextran, polyvinyl­
pyrrolidone and other polymers (see de Duve & Wattiaux 1966). However, PPNO
has oxygen atoms which (like other dative oxides) very readily form hydrogen
bonds with phenolic hydroxyl groups. Thus PPNO can preferentially interact with
silicic acid on the surface of the silica particles before the latter can attack lyso­
somal membranes.
These two facts are sufficient to explain why silica is so toxic to macrophages:
the particles are taken up into lysosomes and readily damage lysosomal membranes
through hydrogen-bonding interactions. Various secondary reactions may occur.
Thus, Munder, Modolell, Ferber &Fischer (1966) have found a considerable increase
in the concentration of lysolecithin, as compared with lecithin, in macrophages
damaged with quartz. This could follow activation of the enzyme phospholipase A,
which catalyses the reaction lecithin -» lysolecithin, and which is known to be
lysosomal (Blaschko, Smith, Winkler, van den Bosch &van Deenen 1967). How­
ever, the fact that silica lyses erythrocytes (membranes of which do not contain
demonstrable amounts of phospholipase A) shows that this process is unneces­
sary for interaction of silica with membrane systems, although the formation of
surface-active lysolecithin could well accelerate damage induced by silica in macro­
phages. Suspensions of silica particles release enzymes from isolated liver lyso­
somes in v
i
t
r
o
, as Stalder’s experiments and our own have shown. The relatively
low-temperature coefficient for this release suggests that physico-chemical rather
than enzymic reactions are involved.
The non-toxicity of stishovite can now briefly be discussed. Crystallographic
studies by Stishov & Belov (1962) and Preisinger (1962) have shown that the
structure of stishovite is isotypic with that of rutile. Silicon ions are regularly
octahedral with six oxygen ions, with a Si—0 bond length of 1*77 A. This is quite
different from all other crystalline forms of silica. Stishovite is also unique in that
it is insoluble in hydrofluoric acid, although it is readily soluble in water (Bohn &
Stober 1966). The simplest explanation of the non-toxicity of stishovite is that the
different crystal structure and bonding prevent the formation of surface—OH
groups.
The second question remains: how macrophage death is related to fibrogenesis.
An interesting lead has recently been obtained by Heppleston & Styles (1967).
They found that macrophages incubated in culture with silica particles released
into the supernatant fraction a factor which, when added to fibroblast cultures,
stimulated collagen formation as judged by synthesis of hydroxyproline. This
Silicon compounds in biological systems

8. 24
stimulation appeared to be due to a specific product of the macrophage-silica inter­
action. It was not seen in normal macrophages, or in macrophages exposed to non­
toxic particles or to silica in the presence of sufficient PPNO. The nature of the
stimulating factor is still unknown, but it seems clear that no direct interaction of
particulate silicate with fibroblasts is involved.
The biological effects of silicon compounds have acquired additional interest as
a result of observations that they can induce malignant tumours in man and
experimental animals. It has long been known that miners and other workers
exposed to asbestos develop asbestosis, a fibrogenic reaction around asbestos
particles in the lungs. Wagner, Sleggs & Marchand (i960) drew attention to an
association between exposure of asbestos (crocidolite) dust and the development of
diffuse mesothelial tumours of the pleura. Since 1962 many cases of mesotheliomas
of the pleura or peritoneum have been discovered in people exposed to asbestos
dust, which has thus become recognized as a major industrial hazard (Wagner
1966). Some of these patients had been exposed only to chrysotile, and Wagner has
found that in experimental animals intrapleural injections of any one of three
types of asbestos (crocidolite, chrysotile or amosite) induce development of meso­
theliomas or other tumours. Crocidolite extracted with organic solvents was as
effective a carcinogenic agent as unextracted crocidolite, from which it seems
unlikely that the low concentration of polybenzenoid hydrocarbons in the latter
plays an important part in their carcinogenicity.
Wagner (1966) has also found that rats which had received intrathoracic injec­
tions of silica developed malignant tumours of the thymus. Why asbestos and
silica are carcinogenic is not certainly known, but the observations support other
evidence that lysosomes may be involved in malignant transformation (Allison
1968). The simplest explanation is that enzymes released from lysosomes can
damage chromosomes, and that a chromosome mutation leads to malignancy.
A. C. Allison (Discussion Meeting)
Possible existence oe life on other planets
Before the role that silicon compounds might play in extraterrestrial life forms
is considered, it is perhaps worth reviewing very briefly why such considerations
need not be relegated to writers of science fiction. Sagan (1966) has estimated that
there must be at least 1021to 102
3other planets in the Universe. Thus, if the Earth
is the only abode of life, the probability of the origin of life on a planet must be as
small as 10-21 to 10~23. Especially in view of contemporary experiments on the
formation of complex polynucleotides and polypeptides vitro, it seems that the
independent origin and evolution of life elsewhere than on the Earth cannot be
regarded as an almost infinitely improbable event. Within a decade exploration for
living organisms on other planets in the solar system can be foreseen. Apart from
the philosophical excitement that the discovery of even one example of extra­
terrestrial life would provide, the characterization of any extraterrestrial biological
system would provide something now lacking in biology: perspective. Since all
organisms that the biologist can study are almost certainly common descendents
of a single instance of the origin of life, it is difficult to determine which biological

9. characteristics are evolutionary accidents and which are necessary for living
systems in general.
Perhaps it would he useful to define what one means by a living system. Two
features are essential: the system must be able to replicate, and it must be able to
mutate, conserving the mutations in subsequent replications. This would allow
generations of diversity and evolution. Hence three components are necessary:
first, structural polymers of which organisms consist, together with reasonable
steps for their biosynthesis; secondly, provision for energy storage and transfer
through molecular rearrangements; and thirdly, there must be aperiodic, but
informationally significant, polymers that have a genetic role comparable with
that fulfilled by nucleic acid in terrestrial organisms.
The range of environments on different planets is likely to be very wide. Some
will have much higher temperatures than those on the surface of the earth, others
lower temperatures. Some will have atmospheres similar to those covering the
primitive Earth, others very different atmospheres. Reactions which on the Earth
take place too rapidly or too slowly to be of importance in metabolism may occur
at suitable rates in other environments. One thing we can be confident about: the
structure of elements and the chemistry of combination are likely to be universal.
Silicon compounds in biological systems 25
Suitability of H, O, N and C for living systems
About 99 % of the living parts of organisms are composed of four elements—
hydrogen, oxygen, nitrogen and carbon. Most of this is water, but even with that
removed 95% of what remains is made up of these four elements. Wald (1962,
1964, 1968) has emphasized that what singles them out among the 92 natural
elements is not primarily their availability—oxygen and nitrogen are plentiful,
hydrogen and carbon relatively rare—but their fitness. Among all the elements,
these alone offer the combination of properties on which life depends. For this
reason, Wald concludes that these elements are irreplaceable. Life, wherever it
occurs in the Universe, must probably depend for its substance primarily upon
these four elements.
Wald (1968) has recently drawn attention to another remarkable fact: that the
same four elements, H, 0, N and C, together with He, are principally responsible
for the thermonuclear reactions generating energy in the Sun and other stars.
There are three main sets of reactions. The first is the so-called proton-proton
chain: fusion of hydrogen atoms, heated by gravitational condensation to about
5 million degrees, to form helium. The second is the ‘burning’ of helium in older
stars at about 100 million degrees: successive stages of condensation of helium
nuclei to form an unstable beryllium intermediate (two helium nuclei) and then
carbon (three nuclei) and oxygen (four nuclei). This is how carbon and oxygen
enter the universe, expelled from red giants to circulate and condense elsewhere.
In those later-generation stars, such as our Sun, at temperatures of some 10 to
15 million degrees, another way of ‘burning’hydrogen to helium occurs, catalysed
by carbon and oxygen, in which nitrogen occurs as an intermediate. It is estimated
that the Sun generates about half its radiation by the proton-proton chain, the

10. 26
other half by the C—N—0 cycle (Reeves 1966). Thus H, He, C, N and 0 are in
that order the most plentiful elements in the Sun, and probably in the universe.
However, the abundance is different in evolving planetary systems such as those
of the solar system.
Wald also stresses that, apart from the question of cosmic abundance, two main
sets of properties of H, 0, N and C are especially favourable for their inclusion in
living systems. First is the fact that they are the four smallest elements in the
Periodic System that achieve stable electronic configurations by gaining, respec­
tively, 1, 2, 3 and 4 electrons. Gaining electrons, in the form of sharing them with
other atoms, is the means of making chemical bonds and so forming molecules.
The special point of smallness is that these smallest elements form the strongest
bonds and so the most stable molecules. The second point is that—as recognized
by Lewis (1923), Coulson (1953) and others—O, N and Care the only elements that
regularly form multiple bonds, thereby satisfying all their tendency to chemical
combination. Thus, in C02the carbon is joined to each of two oxygen atoms by
double bonds, each involving the sharing oftwo pairs of electrons. Each ofthe atoms
in C02 achieves a complete octet of outer shell electrons as found in the neigh­
bouring inert gas, neon. All the combining tendencies are satisfied and the molecule,
free and independent, escapes into the atmosphere as a gas. It readily dissolves in
and combines with water, the forms in which living organisms use it. An additional
point is that conjugated systems of double bonds absorb radiation in the long
ultraviolet range, and energy so obtained can promote the formation of polymers.
Thus important steps in the origin of life could take place under conditions when
water vapour, ozone or other atmospheric constituents absorb short wavelength
ultraviolet radiation before it reaches the planetary surface.
A. C. Allison (Discussion Meeting)
Why not silicon?
Silicon falls just below carbon in the Periodic System. Like carbon it can com­
bine with itself to form long chains, although the familiar silicon-containing
polymers, the silicones, are actually made up of silicon-oxygen chains. In the upper
layers of the earth silicon is about 135 times as common as carbon. Why, then, is
life based upon the relatively rare element carbon rather than on the more pre­
valent silicon?
Table 1. Bond lengths and energies
bond
interatomic
distance
(A)
bond energy
(kcal/mole)
C—C 1-54 83
Si—Si 2-34 43
Si—0 1*50 108
Wald (1964) points out that the first difference is in the strength of bonding. As
shown in table 1,the interatomic distance is much smaller in a C—Cthan in an Si—Si
bond, and the bond energy of the former is almost twice that of the latter. More­
over, the Si—Si bonds are unstable in the presence of small molecules possessing

11. 27
lone pairs of electrons, such as oxygen, water or ammonia. The reason for this
is that silicon possesses not only one 3s and three 3 electron orbitals (comparable
to the one 2s and three 2 po
rbitals in carbon) but also, five 3 orbitals
electron shell. Hence, even when the 3s and 3 orbitals of silicon are filled as the
result of chemical combination the third shell is still left unsaturated.
Carbon dioxide C02
xx xx
X O xx C xx O X 0 = C = 0
x x
Silicon dioxide (Si02)n
f . . . X
X
X I I I
O x Si x O O—Si—O —Si—O
X x ' | | | |
O—Si—O
O—Si—
Figure 5. Comparison of carbon dioxide and silicon dioxide (after Wald, 1964).
Silicon compounds in biological systems
The failure of silicon to form double bonds can be illustrated by comparison of
Si02and C02(figure 5). In Si02 silicon is joined to the oxygen by single bonds,
leaving two unpaired electrons on the silicon and one on each of the oxygen atoms.
Unable to pair by forming multiple bonds, these pair instead with the electrons
on neighbouring molecules of silicon dioxide. This process, repeated many times
over, leads to the formation of a large polymer of silicon dioxide, as in quartz,
which is hard because it can be broken only by disrupting covalent bonds. Wald
(1964) concludes that this is why silicon is fit for making quartz but living systems
must be of carbon.
These are very interesting arguments, but I do not believe that the issue is
finally settled. Under conditions of relatively low temperature, in the absence of
oxygen and nitrogen, silicon—silicon chains of the type shown in figure 6A would
be stable. Fully alkylated chains (Siw
R2n+2) are stable to air and water (Sidgwick
1950). Under conditions more like those on the Earth, and even at higher tempera­
tures, silicon-oxygen chains of the type shown in figure 6 would be stable. The
high stability of Si—0 bonds sometimes has been adduced as evidence that they
(A)
(B)
r 2 h r 4 h
Ri
1
OH
1 r 3 OH
Si—
1
0 — Si —
I
0 — Si —
|
0 — Si
OH r 2 OH R
>
2
Figure 6. Silicon—silicon and silicon—oxygen chains with aperiodic but
non-random functional appendages

12. 28
could not be important in living systems. However, the even greater stability of
elemental nitrogen, N2(bond energy 225 kcal) does not prevent this element from
being assimilated by living organisms and occupying a central place in their
metabolism. This example shows that terrestrial living creatures have found many
ways of circumventing obstacles posed by thermodynamic stability or instability.
The volatility of C02is certainly an advantage, but phosphorus, metals and other
important constituents of living systems are obtained from soil or water, as is
silicon when required (e.g. in diatoms). Hence the failure of silicon to form stable
volatile compounds is not an insuperable difficulty.
Nor does the fact that silicon comes from a row of the Periodic System in which
double bonds are not important necessarily preclude it from participation in meta­
bolism. The Third Period elements P (adjacent to Si) and S play a central role in
metabolism ofterrestrial organisms, and the thermodynamics ofsilicon interactions
are not so dissimilar than those of P as to eliminate the possibility that group
transfer reactions involving Si might serve for energy storage and provision under
somewhat different conditions. Thus the reaction of Si—Si—Si— with oxygen or
an oxygen compound could be a reversible energy-yielding process.
The absence of double bonds in silicon compounds might actually be an advan­
tage under some circumstances, e.g. when there was no atmospheric shielding of
long wavelength ultraviolet light. Absorption of such light can damage biologically
significant polymers as well as facilitating their synthesis: the lethal effects of
ultraviolet radiation on all terrestrial living organisms shows that this is so.
We know that inorganic silica can have a skeletal function, as in diatoms, and
could perform this function at relatively high temperatures. Silicon polymers of
the type shown in figure 6 could serve as structural substitutes for amide or hydro­
carbon chains. The introduction of aperiodic but non-random functional append­
ages (R in the figure) could make such macromolecules informationally significant.
Hence, although it seems likely that if life exists elsewhere it will be composed
primarily of the familiar H, 0, N and C, the possible existence of what Pimentel
and his colleagues (1966) call ‘exotic biochemistry’ is by no means excluded. As
they point out: ‘Possibly the most interesting and important exobiological dis­
covery that could be made would be a life-form based upon chemistry radically
different from that on Earth. It would be as great an error to omit consideration of
non-Earth-like biochemical possibilities as it would be to fail to look for DNA.’
Because of its position in the Periodic System silicon is well placed to play a role in
exotic biochemistry. The very reasons that have contributed to the exclusion of
silicon from metabolism in most terrestrial organisms might favour its inclusion
elsewhere. Unlike Horatio, we should extend our philosophy to include Heaven
and Earth in all its possible manifestations.
Possible role of silica surfaces in the origin of life on the Earth
Returning to more mundane considerations, Bernal and others have raised the
possibility that the various polymer precursors of living organisms may have come
together at surfaces. The efficiency ofsuch systems can be illustrated by the method
A. C. Allison (Discussion Meeting)

13. of solid-phase peptide synthesis developed by Merrifield (1963). This involves the
stepwise assembly of the peptide chain anchored to an insoluble particle. Variants
of the system, and its practical usefulness, have been reviewed by Smyth (1965).
Silica or silicates might well have served as supports during the synthesis of poly­
peptides and polynucleotides, since both the latter could be extensively hydrogen
bonded to the surfaces. A possible origin of optical asymmetry—which is so charac­
teristic of living forms—might be the dissymetric action of an optically active
catalyst, such as an L-erystal of quartz. For example, a racemic mixture of2-butanol
was selectively dehydrated at high temperature on a catalyst consisting of a metal
deposited on a quartz crystal (Schwab, Rust & Rudolph 1934). Silicates contain
magnesium and a variety of other metals that might have facilitated polymeriza­
tion reactions. The key event in the origin of life was the interaction ofprotein and
nucleic acid, which eventually led to the former acting as an enzyme catalysing
the synthesis of the latter, while DNA became a genetic informational macro­
molecule. Perhaps protein and nucleic acid first came together on a surface. We
may never certainly know how life arose on our planet, but model systems provide
useful analogies, and further studies of polymerization reactions occurring on
asymmetric silica surfaces would be well worth undertaking.
Figures 1 and 2, plate 1, were taken by Mr M. R. Young and Miss P. A. Sims.
The latter is reproduced by permission of the Trustees of the British Museum,
Natural History. Figures 3 and 4, plate 2, are from Allison et al. (1966) repro­
duced with the permission of the editors of the Journal of Experimental Medicine.
Silicon compounds in biological systems 29
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A. C. Allison (Discussion Meeting)