Are the Genomicists the Tea Party of Biomedical
Sciences?   June 1, 2013

By Leonard Zwelling

(This blog is dedicated to the last, great cancer biologist—Isaiah
J. Fidler)

            The
Tea Party faithful adopted their name from the Bostonians who tossed British
tea overboard in 1773. This was prior to the Revolutionary War in protest of
excessive taxation.

            The
modern Tea Party is probably best characterized as a loosely knit group  of governmental minimalists who, like
libertarians, strongly oppose any tax increases. This initiating philosophy has
been conflated with the social extremism of people like Michelle Bachmann and
Ted Cruz, which is most unfortunate for there really is nothing intrinsically
wrong about holding government accountable for its taxing and spending
policies. What started as a sane quest for budget balance and entitlement
constraint has morphed into a rebellious aspect of the Republican Party that
has probably cost the GOP control of the US Senate and the votes of millions
who view these folks as too fringy for them. It has also given John Boehner
pause as the Speaker of the House. He thought he was leading one party not two.
What started as a movement for a good cause has been transformed into a group
of idealistic zealots who would rather blow themselves up politically than come
to any compromise with the Democrats let alone more moderate members of their
own party. In a way, the Tea Party is like a terrorist cell within the GOP in
plain view of the world.

            In
2000, when the human genome was finally cracked and as the price of sequencing
began to drop, a new set of thoughts arose. Cancer is a disease of
genes—drivers that kick up carcinogenesis and mutant suppressors that can no
longer put the brakes on the process. If we could identify the individual
aberrancies in each person’s cancer genome, we could target these mutations and
reverse the process and cure cancer. This is an interesting and potentially
testable hypothesis that has at least some validity as certain human malignant diseases
are linked to (perhaps caused by) specific genetic mutations. Therefore, the
logic went, let’s sequence a whole bunch of human tumors and see what makes
them tick.

            Unfortunately,
like the absolutists in the Tea Party, the reductionists who believe that
genomics of human explanted cancers will lead to cures have neglected some big
chunks of the story. Human cancers that are clinically detectable have been
around for many months. Most cancers are really systemic diseases that, when
the patient is fortunate, are detected when anatomically localized and amenable
to surgery or radiotherapy. But human cancers are genetically unstable and
likely to have many genetic signatures, not one. Primary cancers and their
metastatic off-spring are likely to differ genetically. Along with the cancer
itself, the microenvironment of the host organism (i.e., the patient) can
greatly affect the tumor’s biologic behavior (see Paget Seed/Soil hypothesis
and/or anything by Fidler). So can signals from the bone marrow and reactions
of the immune system. Just as Tea Party members don’t live in isolation from
those who do not agree with them, human cancers do not spring up as independent
entities divorced from the patient’s biochemistry and perhaps even the
patient’s microbiome that can favor or fight the development of cancer.

            Why
does this matter?

            While
there have been some Tea Party successes in Congress and the Senate, for the
most part, extremism doesn’t play well with the American people who both vote
for their own interests and those of others to promote fairness. We may be
right of center politically, but we are all libertarians at some level when we
want to be left alone. Most Americans, however, do not equate the current
members of Congress with the King of England in 1775 as a despot whose yoke must
be thrown off, but rather Americans see their government as an inept group of
self-serving bureaucrats who are actually pretty ineffective, until the
services the government provides are the ones they need (fill in Medicare,
Medicaid, FEMA, etc).

            Currently,
the genomicists own cancer research. All the major big projects include some
degree of tumor gene sequencing and as the cost of sequencing drops the
likelihood that we will do more of it increases. Making it cheaper does not
make it smarter. It is fine that the sequencing machines are cranking out the
DNA code of cancers and trying to match the letters with clinical behavior but
this does ignore the microenvironment, signaling to and from the bone marrow,
the patient’s normal genetic make-up which could influence carcinogenic
proclivities, the microbiome and post-translational modification of non-DNA nuclear
elements. There may be many factors that go into the creation of a cancer
patient and genomics may not even provide a window into the most important of
these. But in a burst of single-minded spending, that’s the route we are
taking.

            I
have no idea how this will work out for the Tea Party or the genomicists, but I
would bet a balanced approach in both cases to be the best choice. No one
philosophy has a corner on the market for good ideas in the political arena.
The same is likely to be true in cancer research. Genomics is still research
not standard of care.  Just because
it seems to make sense and sometimes works (helps a patient) may not indicate
it is the only, best or most logical course for cancer research to take.