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believe it embarrasses their religious convictions.
The theory of the cell and the conclusions to which it led were based
on inference, not experiment. The images that von Baer, Schleiden,
Schwann, Remak, Virchow, and Weissman saw through their micro-
scopes were static, frozen in time and space. Thus, the dynamic fea-
tures of the cell theory as conceived in the nineteenth century were tri-
umphs of the human imagination. A century more would pass before
experimental science could give the dynamic behavior of cells tangible
reality.
Cells and Cancer
Cells are the bricks with which all creatures are built there are 300
trillion of these bricks in each of our bodies. But these are not ordi-
nary bricks: they have an elaborate internal structure that allows them
to live and breathe; they move from one place to another with pur-
pose; they have distinctive personalities and assignments; they con-
verse by means of chemical and molecular languages; and they multi-
ply ten thousand trillion times during the course of each human
lifetime. The greatest wonder of cells, though, is that each knows what
it is to do, and when and where. Cancer is a failure of the order that
creates this wonder. The cancer cell violates its social contract with
other cells, proliferating and spreading in an unfettered way.
The manner in which the proliferation and spread of cancer cells
140 Opening the Black Box of Cancer
occurs was first appreciated in accurate detail by Wilhelm Waldeyer.6
In 1867, Waldeyer published a microscopic description of how human
breast cancer develops, beginning as a nidus of hyperproliferation in
the glands of the breast, then proceeding to invade adjacent tissue,
penetrate blood vessels, and spread to distant sites by transport of can-
cer cells through the lymphatic and blood vessels. Coming just a dec-
ade after the enunciation of the cell theory and produced with micro-
scopes of dubious optics, Waldeyer s description was an astonishing
achievement that has stood the test of time and could be little im-
proved on today. But again, the images were static and the conclusions
were inspired inference. To achieve a dynamic image of cancer cells
and ascertain their individual properties, scientists turned to studies
not in animals, but in petri dishes, applied in a way that Robert Koch
could not have anticipated.
We can trace the beginning of this strategy to Alex Carrel, who in
1912 received the first Nobel Prize in Physiology or Medicine ever
awarded to a scientist working in the United States. Although born
and trained in France, Carrel was ostracized by the academic commu-
nity there because of his pungent personality and his sympathies to-
ward faith healing. He eventually settled at the Rockefeller Institute in
New York City, faith healing no longer on his agenda. There he consol-
idated the pioneering work on vascular surgery and organ transplan-
tation that earned him the Nobel Prize.
Carrel had learned the intricate stitching required for his work from
the renowned lace makers of Lyon, one of whom was his mother. But
Carrel left another legacy, one more pertinent to the study of cancer.
He was among the first scientists to successfully propagate vertebrate
cells outside of the living body, a procedure we now call cell culture.
He claimed to have kept one batch of chicken cells alive and propagat-
ing for thirty-two years. We no longer consider that claim credible, but
there can be no denying the influence of his work. Carrel s personality
never moderated. He spent his last years in France, espousing a toxic
anti-Semitism.
Why has the cell culture pioneered by Carrel been so important
to cancer research? The answer lies in simplification. Whole tumors
are not easy objects for experimental study. So we resort to the as-
Opening the Black Box of Cancer 141
sumption that the properties of individual cancer cells account for the
behavior of tumors. We can define those properties by growing the
cancer cells in glass or plastic vessels, using an artificial mixture of nu-
trients to feed the cells. Under these circumstances, cancer cells misbe-
have exactly as we might expect from the behavior of tumors in living
organisms. The cells continue to grow even when crowded by their
neighbors. They develop a very different appearance from their nor-
mal counterparts. And they behave like misfits, crawling over one an-
other in a convincing caricature of the cells in an invasive cancer.
The early steps in the genesis of cancer probably occur in many of
our cells during a lifetime, only to be aborted before matters get out of
hand. But occasionally, the course of events continues to a lethal end, a
homogeneous colony of cancer cells with the potential to expand un-
endingly. Biologists suspect that billions of cells may take the first step
toward cancer in each of us during the course of our lives. Why then
do any of us survive to tell the tale? The answer to that question has at
least two parts.
First, one step is not enough. Several insults are required to produce
a fully malignant cell, and the likelihood that these will combine in a
single cell is very low. We will speak more of these combined insults
later. Second, the immune system of our body can mount potent de-
fenses against both foreign intruders (such as microbes and trans-
planted tissues) and errant natives (such as cancer cells). These factors
combine to limit the frequency of cancer among humankind and to
delay the emergence of most cancers until the later years of life.
What changes the cellular personality in a way that gives rise to can-
cer? Science has spent the last century trying to answer this question.
Now, in a breathtaking sequence of discovery achieved over a brief pe-
riod of time, an answer has emerged. All cancer can be attributed to a
single underlying malady of the genetic program that directs the lives
of our cells.
Genes and Cancer
The command center for our cells is located within a compartment
known as the nucleus. Within the nucleus, the commands are carried
142 Opening the Black Box of Cancer
on structures known as chromosomes. Individual human chromo-
somes can be released from the nucleus of the cell and stained so that
each displays a distinctive pattern of bands that can be identified
through a microscope a sort of microscopic fingerprint. We Homo
sapiens possess twenty-four different chromosomes, including the X
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