thelial tissue is noted not only in the 
lungs but also in other areas of the pul- 
monary epithelium, such as the trachea 
and esophagus. 
An epithelial tissue in adults that ap- 
pears to be very sensitive to EGF is the 
corneal epithelium in the eye. This tis- 
sue is important for sight and can be 
easily injured. Research has shown that 
in both experimental animals and in 
humans, EGF accelerates the prolifera- 
tion of cells in a wounded area of the 
corneal epithelium, thereby hastening 
the wound-healing process. Because 
EGF is present in milk, a natural fluid, 
clinical trials are being conducted to de- 
termine whether milk might be a feasi- 
ble treatment for corneal lesions. In 
fact, the use of EGF as a general 
wound-healing agent is being consid- 
ered. In this regard, it is interesting to 
note that folk medicine often prescribes 
the application of urine to wounds. 
And in war situations this practice has 
been employed when other treatments 
were not immediately available. Urine 
is usually a sterile solution and contains 
high amounts of EGF. 
Nature is often remarkably inge- 
nious in devising strategies to maximize 
the utility of its products. In the case of 
protein molecules, it is not unusual for 
one protein to be capable of carrying 
out more than one distinct function. At 
the level of molecular architecture this 
is not a trivial engineering task. In addi- 
tion to its capacity to stimulate cell 
growth and differentiation, the EGF 
molecule has a second biological activ- 
ity. When administered to experimen- 
tal animals and to humans, this 
hormone blocks the release of excess 
gastric acid induced by a variety of 
chemicals, such as histamine or penta- 
gastrin. 
The ability of EGF to control acid se- 
cretion in the stomach was discovered 
unexpectedly in 1975 when a British re- 
search group at Imperial Chemical In- 
dustries isolated and determined the 
structure of urogastrone — a protein 
hormone known since the 1920s to be 
present in high quantities in the urine of 
pregnant women and to be an inhibitor 
of acid secretion. Computer compari- 
sons of urogastrone with other known 
proteins revealed that the primary 
structures (that is, the sequences of 
amino acids) of urogastrone and EGF 
are so nearly identical (within the limits 
of experimental technology) that one 
can conclude they are the same mole- 
cule. Thus milk-fed infants receive a 
hormone that may help to prevent dis- 
comforts and injuries to the stomach 
lining (ulcers, for example) resulting 
from excess gastric acid. 
Scientists have been increasingly suc- 
cessful at removing selected cells from 
the intact animal and maintaining these 
cells in a growing state for long periods 
of time in the laboratory. This tech- 
nique, called cell culture, involves plac- 
ing the cells in a plastic dish with a 
defined medium of glucose, minerals, 
vitamins, and amino acids. Under these 
conditions the cells remain viable but 
do not grow. For growth and cell divi- 
sion to occur, serum — a blood frac- 
tion — is added to the medium. Serum 
apparently contains hormones, or 
growth factors, necessary to regulate 
cell growth and division and for many 
years has been considered to be indis- 
pensable for this purpose. Recent ex- 
periments, however, have shown that 
milk is also able to stimulate cell prolif- 
eration in cell culture and can make up 
for approximately 95 percent of the se- 
rum requirement. Biologically, this 
suggests that milk is a fluid rich in the 
factors that control cell growth, and 
EGF appears to be a key ingredient in 
milk for the stimulation of cell division. 
This has been demonstrated by treating 
milk with antibodies to EGF. 
Antibodies are highly specific re- 
agents that are able to recognize one 
particular protein molecule in a mix- 
ture of thousands of slightly different 
protein molecules. Antibodies bind to 
the protein they recognize and often in- 
activate it. When milk is treated with 
antibodies to EGF, the capacity of the 
milk to stimulate cell growth is reduced 
by 90 percent. This has been demon- 
strated in cell culture with human fi- 
broblasts (connective tissue cells) and 
human glia cells (brain-derived cells). 
Different types of cells are known to 
vary in their responsiveness to any par- 
ticular hormone; therefore, it is possi- 
ble that milk may contain additional 
growth factors other than EGF that 
stimulate different cell types. For ex- 
ample, erythropoietin, a protein 
growth factor that controls the devel- 
opment of red cells in the blood, is 
known to be present in milk. 
In summary, we know that EGF is 
able to exert a significant influence on 
the proliferation and differentiation of 
various types of epithelial cells in the 
intact animal. We also know that this 
hormone is present in physiologically 
significant quantities in milk. Is there a 
connection? Is milk a physiological vec- 
tor for the delivery of important hor- 
mones to the infant? These intriguing 
questions will have to wait for further 
research before answers can be provid- 
ed. To resolve some obvious questions, 
however, a few additional comments 
can be made at this time. If the hor- 
mone is ingested in milk and affects the 
growth and development of tissue in 
the gastrointestinal tract, it must be 
able to resist conditions in the gastroin- 
testinal tract that cause the digestion of 
most protein molecules. Studies of the 
chemistry of EGF have shown that the 
hormone’s activity is not destroyed by 
exposure to strong acid or proteases 
(enzymes that digest protein mole- 
cules). Therefore, it is not unreasonable 
to suggest that this growth factor may 
remain biologically active in the nor- 
mally adverse conditions, for a protein 
molecule, of the gastrointestinal tract. 
If EGF also affects other epithelial 
tissues, such as that of the lungs, then 
there is a second problem: the growth 
factor would have to be absorbed into 
the circulatory system by passing 
through the lining of the gastrointesti- 
nal tract. That this apparently can oc- 
cur has been demonstrated in the 
experiments conducted with newborn 
mice. The results showed that oral ad- 
ministration, as well as subcutaneous 
injection, of EGF resulted in preco- 
cious eyelid opening, indicating that 
the hormone was absorbed from the 
gastrointestinal tract into the systemic 
circulation. This has not, however, 
been demonstrated with humans, and 
animal species differ in terms of which 
proteins will be absorbed. 
As already mentioned, large num- 
bers of babies in the United States are 
not fed with mother’s milk but receive 
commercial formulas with either a soy- 
bean or bovine milk base. Does this 
make a difference as far as growth fac- 
tors are concerned? Cells grown in cul- 
ture can be stimulated to grow and 
divide by either human or bovine milk. 
When various commercial formulas 
were tested, however, none were able to 
stimulate cell proliferation. This is not 
to be taken as an indictment of the com- 
mercial formulas — certainly many 
children have been raised on formula 
without apparent adverse conse- 
quences. These results indicate that hu- 
man milk is not duplicated by the 
industrial products and that our scien- 
tific technology is not always able to 
better or even equal nature. 
Graham Carpenter is an assistant pro- 
fessor of biochemistry and medicine in 
the Department of Biochemistry of Van- 
derbilt University's School of Medicine 
in Nashville, Tennessee. 
14 
