The Ticklish Gene
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ruary 1967 I presented our recent work. I played down the full role of
electricity in fracture healing, with its overtones of vitalism, and concen-
trated on our method for inducing dedifferentiation in vitro. That was
enough to call forth many attacks from the audience, most of which
were variations on "I just don't believe it." Some said we were just
electrocuting the cells, despite the fact that they survived for ten days in
culture.
One audience member responded with some thoughtful and con-
structive criticism, however. He accepted the fact that we'd seen what
we'd seen. Nevertheless, there were, he said, other barely possible expla-
nations. In particular, he stated, we hadn't gone far enough in proving
that the cells weren't slowly degenerating from some small but harmful
change caused by the current. While the cells in our chambers looked
like those we'd photographed in the fracture clot, our idea that these
cells were electrically dedifferentiated healing cells was so at variance
with current views that we must have more direct proof. For such a
radical departure, seeing wasn't quite believing.
Stimulated by this one honest reaction, Dave and I returned to Syr-
acuse and planned how we could use the latest knowledge about DNA to
test our evidence further. A few years before, James Watson and Francis
Crick had proposed what became known as the central dogma of genet-
ics. In simplified form, it stated that the active DNA in each specialized
cell imprinted its own specific patterns onto transfer RNA, which re-
layed them to messenger RNA. This second RNA molecule moved out-
side the nucleus to the ribosomes, where it translated the genetic
instructions into the particular proteins that made the cell what it was.
We reasoned that, since a dedifferentiating cell was not going to di-
vide immediately, it wouldn't duplicate its genes. Therefore there
should be no increase in the amount of DNA it contained. However,
since the cell changed its type by manufacturing a whole new set of
proteins, the amount of RNA—the protein blueprints—should increase
dramatically.
Using radioactive labeling and fluorescent staining techniques, we
found there was indeed no new DNA but dramatic increases in RNA.
Another test showed that our despecialized cells contained not only dif-
ferent proteins but also twice as many as their precursor red blood cells.
The most conclusive experiment was one suggested by Dan Har-
rington, a student who'd taken Fred Brown's place and who later went
on to a Ph.D. in anatomy. Dan proposed that we use certain well-known
metabolic inhibitors that disrupt the DNA-RNA-protein system, to see
if we could prevent dedifferentiation. One such inhibitor, an antibiotic