Since the discovery of D2O (heavy water) and its use as a moderator in nucl
ear reactors, its biological effects have been extensively, although seldom
deeply, studied. This article reviews these effects on whole animals, anim
al cells, and microorganisms. Both "solvent isotope effects," those due to
the special properties of D2O as a solvent, and "deuterium isotope effects"
(DIE), which result when D replaces H in many biological molecules, are co
nsidered. The low toxicity of D2O toward mammals is reflected in its widesp
read use for measuring water spaces in humans and other animals. Higher con
centrations (usually >20% of body weight) can be toxic to animals and anima
l cells. Effects on the nervous system and the liver and on formation of di
fferent blood cells have been noted. At the cellular level, D2O may affect
mitosis and membrane function. Protozoa are able to withstand up to 70% D2O
. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources
of a large number of deuterated molecules. D2O increases heat stability of
macromolecules but may decrease cellular heat stability, possibly as a res
ult of inhibition of chaperonin formation. High D2O concentrations can redu
ce salt- and ethanol-induced hypertension in rats and protect mice from gam
ma irradation. Such concentrations are also used in boron neutron capture t
herapy to increase neutron penetration to boron compounds bound to malignan
t cells. D2O is more toxic to malignant than normal animal cells, but at co
ncentrations too high for regular therapeutic use. D2O and deuterated drugs
are widely used in studies of metabolism of drugs and toxic substances in
humans and other animals. The deuterated forms of drugs often have differen
t actions than the protonated forms. Some deuterated drugs show different t
ransport processes. Most are more resistant to metabolic changes, especiall
y those changes mediated by cytochrome P450 systems. Deuteration may also c
hange the pathway of drug metabolism (metabolic switching). Changed metabol
ism may lead to increased duration of action and lower toxicity. It may als
o lead to lower activity, if the drug is normally changed to the active for
m in vivo. Deuteration can also lower the genotoxicity of the anticancer dr
ug tamoxifen and other compounds. Deuteration increases effectiveness of lo
ng-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdo
wn by target microorganisms. A few deuterated antibiotics have been prepare
d, and their antimicrobial activity was found to be little changed. Their a
ction on resistant bacteria has not been studied, but there is no reason to
believe that they would be more effective against such bacteria. Insect re
sistance to insecticides is very often due to insecticide destruction throu
gh the cytochrome P450 system. Deuterated insecticides might well be more e
ffective against resistant insects, but this potentially valuable possibili
ty has not yet been studied.