Cancer and Genetic Modification 
target in many different organs at different times. 
A further interesting aspect of this system is that 
the unity of biology permits elements of the sys- 
tem that have been derived from the regulatory 
machinery of a simple unicellular organism, 
yeast, to be used quite readily in mammals. 
Host Defenses Against Cancer 
While transgenic mice are very useful in analyz- 
ing the action of oncogenes, they are also useful 
in exploring the host defense mechanism mobi- 
lized to prevent the development and spread of 
cancer. The immune system is one of the organ- 
ism's chief instruments against the spread of in- 
fectious disease and for the rejection of foreign 
tissues. For instance, the body's immune system 
must be neutralized to accomplish effective heart 
or kidney transplants. The role that the immune 
system plays in tumor rejection is poorly under- 
stood, but important discoveries in immunology 
indicate that the immune response is regulated 
by an array of hormone-like agents called lym- 
phokines. These are released by cells of the im- 
mune system to influence the growth and devel- 
opment of other cells. 
We are particularly interested in how lympho- 
kines influence the host's response to cancer. In 
the course of this work, we have focused on the 
action of two particularly interesting lympho- 
kines, IL-4 and IL-7. (These biologic response- 
modifying agents are frequently called IL, de- 
rived from "interleukin," an agent that mediates 
signals between white blood cells, or leuko- 
cytes.) Several cell-signaling functions have been 
recognized in IL-4. Although its precise role in 
the body has not been proved, IL-4 is suspected of 
playing a role in modulating the immune re- 
sponse. IL-7 is thought to be important for the 
orderly development of antibody-producing 
cells, the so-called B cells. 
We have been able to show that both IL-4 and 
IL-7 are potent antitumor agents, acting to induce 
host defense mechanisms. Further studies of the 
action of IL-4 have allowed us to identify two par- 
ticular cell types that may mediate this antitumor 
effect. One of these is the eosinophil, a cell in- 
volved in many allergic responses. Another is the 
macrophage, a scavenger cell concerned with 
cell-killing functions. Our most recent work has 
focused on identifying the active regions of the 
IL-4 molecule, with a view to distinguishing 
those structures required for antitumor activity 
from those that give rise to unwanted side effects. 
New Directions: Distinct Genetic 
Contributions from Mothers and Fathers 
Mendel's vision of genetics held that a particu- 
lar gene carried by an organism behaves in ex- 
actly the same way whether it is inherited from 
the mother or the father. For the most part, this is 
true. Nevertheless, in mammals, the highest or- 
ganisms, it has proved impossible to induce de- 
velopment artificially from the egg alone (a pro- 
cess known as parthenogenesis) , although this is 
possible in many lower forms. Some experiments 
using transgenic mice have helped us to under- 
stand this phenomenon and why it is that, at least 
for mammals, mother and father (that is, both egg 
and sperm) are necessary for development of the 
offspring. 
It turns out that a small number of genes are 
expressed differently if they are inherited from 
one or the other parent. In a particular example 
that we created, a transgene is only expressed if it 
is inherited from the father. The very same gene 
inherited from the mother is silent. We have now 
correlated this so-called "parentally imprinted" 
expression with a chemical modification of the 
gene whereby it is heavily altered (but not ex- 
pressed) if inherited from the mother or not al- 
tered (but expressed) if inherited from the fa- 
ther. During the past year we have worked out the 
rules that govern the modification of this gene 
during embryogenesis. Our most recent work is 
directed toward identifying the encoded signal 
that evokes this parental effect. 
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