BY 2020, predicts Robert Horvitz of the Massachusetts Institute of
Technology, biologists may be engineering cells that can hunt down cancer cells
deep within human tissues.
鈥淵ou can begin to think about cells as potential micro-robots sent out to
search and destroy,鈥� Horvitz says. To design these killer cells, he says
biologists must first discover how cells communicate with one another and how
they kill themselves in a process called apoptosis. Unlike cell death as a
result of an injury, apoptosis does not trigger inflammation. It is a natural
process that, for example, enables a tadpole to lose its tail as it becomes a
frog and a human embryo to lose the webbing between its fingers and toes.
But how is apoptosis controlled? Horvitz has been trying to find out for over
two decades. In the mid-1970s, he and John Sulston, now director of the Sanger
Centre in Cambridge, ran a famous project tracking the development of every cell
in the tiny roundworm Caenorhabditis elegans. They found that as each
animal grew from egg to adult, 1090 cells were formed and 131 died. 鈥淐ertain
cells would become gut cells,鈥� says Horvitz, 鈥渃ertain cells would become muscle
cells, certain cells would become nerve cells and certain cells would die.鈥�
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Horvitz realised there must be genes that made them die. So far his team has
found 14, each controlling different steps in the process. One protein, called
CED-4, tells the cell that produces it to self-destruct. When the suicide signal
arrives, it activates enzymes called caspases that break down vital parts of the
cell. Other proteins tell a healthy cell to envelop a dead neighbour. 鈥淭he
engulfing cell surrounds and literally swallows the cell corpse,鈥� says Horvitz.
That prevents it from falling apart and releasing its contents, which in mammals
could cause inflammation and tissue damage.
With the outline of the process emerging, drugs companies are getting
excited. Conventional cancer treatments hit sick and healthy cells alike. So one
goal is to find drugs that trigger apoptosis only in cancer cells. Some proteins
seem to act as a brake鈥攚hen they鈥檙e not produced, apoptosis begins.
Pharmaceuticals companies are searching for ways to inhibit these proteins in
the hope of finding drugs that disable them only in cancer cells.
Although apoptosis research may lead to new cancer drugs, Horvitz emphasises
that the work began with researchers like him who were intrigued by the workings
of a tiny soil worm. That kind of basic research needs funding, and the bright
future promised by biotechnology will only come about if such work is allowed to
flourish.