124 • Alternatives to Animal Use in Research, Testing, and Education 
USE OF NONLIVING SYSTEMS IN BIOMEDICAL RESEARCH 
Chemical and Physical Systems 
Long before the advent of modern technology, 
researchers were constructing chemical models 
of certain phenomena that occur in living systems. 
There is a long and rich history in biochemistry, 
for example, of the application of nonliving sys- 
tems to experimentation (128,147). 
Enzyme biochemistry continues to be a principal 
area of application of nonliving methodology in 
biomedical research. Enzyme mechanisms may be 
studied in a totally chemical system. Magnetic res- 
onance imaging is used to obtain from enzymes 
in solution detailed structural data and informa- 
tion about the mechanism of enzyme action. By 
combining MRI with cryoenzymology— the use 
of enzyme solutions held at subzero temperatures— 
enzymatic reactions can be slowed enough to study 
intermediate products that would ordinarily ex- 
ist for too short a time to be detected. Investiga- 
tions that had been restricted to in vivo manipula- 
tions can now be expanded into a far wider range 
in vitro (131). 
In dental research, a chemical system mimics 
the mechanics of the formation of dental caries. 
A two-chambered diffusion cell pairs an excess 
amount of specific protein crystals with a chemi- 
cal solution of artificial "plaque -saliva.” Dissolution 
of the crystals can be studied under varying chem- 
ical conditions relevant to a better understanding 
of the caries process (40). 
In the field of membrane biophysics, the advent 
of synthetic membranes has proved a boon to re- 
search and stands as one of the premier examples 
of nonliving alternatives to animal use. Liposomes 
are synthetic vesicles made of protein and fatty 
molecules. Their structure can be dictated by the 
investigator, who can combine proteins and lipids 
of different types and in different ratios to yield 
COMPUTER SIMULATION 
Modern approaches to biomedical research de- 
scribe the functions of living systems at all organiza- 
tional levels by the language of science— mathe- 
matics. Knowledge is acquired by investigating 
an artificial membrane. As with true biological 
membranes, the barriers formed by liposomes are 
selectively permeable. These artificial membranes 
are particularly useful in basic studies of the trans- 
port of molecules across membranes and of mem- 
brane damage (12). 
Except for the use of mannequins to simulate 
accident victims in the transportation industry and 
in trauma centers, the principal use of physical 
and mechanical systems today is in education (see 
ch. 9) rather than in biomedical research. How- 
ever, it is not inconceivable that future combina- 
tions of mechanical and electronic technology 
could provide biomedical researchers with artifi- 
cial research subjects capable of independent, un- 
anticipated responses. 
Epidcmi ology: 
Using Existing Databases 
The use of existing databases to gain new infor- 
mation and insights in biomedical research may 
be a major underused resource, if the paucity of 
published results is any criteria. One study that 
relied on such information concentrated on the 
relationship between 17 nutrients and the poten- 
tial for development of hypertension cardiovas- 
cular disease in more than 10,000 people from the 
database of the National Center for Health Statis- 
tics’ Health and Nutrition Examination Survey 
(HANES I) (137). The results proved to be highly 
controversial, with some of the criticism aimed 
at the use of the database (119). 
Too little information is currently available to 
evaluate fully the potential dimensions of the salu- 
tary use of epidemiologic databases in basic bio- 
medical research. The possibility exists that their 
enhanced use may constitute an important non- 
animal method. 
IN BIOMEDICAL RESEARCH 
relationships among cells, tissues, fluids, organs, 
and organ systems. By the processes of trial and 
error and of hypothesis and testing, relationships 
begin to be understood and can be described by 
