The Critical Importance of
Agnotology: The Study of Ignorance

By

Leonard Zwelling

         This is not a rant about the idiots in charge of some
organizations. I have surely written enough of those.

         Nope, this is about an op-ed in the NY Times on Monday, August 24, by Jamie Holmes who is an expert on
the subject of ignorance. That seems a bit oxymoronic in itself.

         Here’s the link:

http://www.nytimes.com/2015/08/24/opinion/the-case-for-teaching-ignorance.html?ref=opinion&_r=0

         The piece is called “The Case for Teaching Ignorance” and
what it is really about is acknowledging the limits of what we truly know as a
starting place for research into the unknown, which is the place where the best
research is done.

         There is a groundswell of resistance to the study of
ignorance, agnotology is the name given the discipline by Robert N. Proctor, a
Stanford science historian. But it is really important and I would argue is the
absolute basis for knowledge because to know what you don’t know you have to
acknowledge what you do know and be ready to sort through the difference
between the two as well as the level of certainty you have in what is known vs.
unknown. You better be sure which bucket any belief really falls in.

         (The latest issue of the
New England Journal of Medicine
has three articles that speak to the issue
of what we really know vs. what we think we know—373: p. 689 on the use of
testosterone replacement in aging men and pp. 691 and 726 on the use of
genomics in clinical oncology).

         Let’s stick with something I putatively KNOW something
about—cancer. I actually know very little, but that puts me in good company
albeit sometimes I feel a bit isolated when I am among all the rest of the
cancer experts who know little, but pretend to know a lot.

         Here are a bunch of questions the answers to which I know I
don’t know, but serve as the basis of the manner in which modern medicine
approaches patients with cancer:

1. A recent study suggests that very early stage breast
cancer can be treated in a very limited fashion despite it often being
approached with aggressive surgery. The consequences of minimal treatment vs.
more aggressive surgical treatment for DCIS may be of no clinical significance.

2. The same may well be true for localized prostate
cancer despite the industrial grade attempts to cut out or incinerate every
gland in a male with a PSA outside normal range, often without knowing if the
net effects of the therapy are beneficial if not harmful or who needs the
treatment and who can live without it–literally.

3. As far as I can tell, radiotherapy is a localized
treatment often used in what is known to be a systemic disease (cancer). How
does radiotherapy work anyway? Do we really know?

4. On that subject, how do any of the curative
chemotherapy regimens work? You pick your favorite alphabet soup, MOPP, POMP,
ABVD, etc. The miracle is not that they often aren’t curative. The miracle is
that in some cases they are. Does the cured patient care how the miracle
occurred? Does the doctor who gets credit for the cure care? If the magic
works, let’s use it whether or not we understand it.

5. Given the evidence that: (a) cancer is often
disseminated at clinical diagnosis (thus the utility of adjuvant chemotherapies
in some patients with breast, osteosarcoma and other cancers), (b) the critical importance to
the totality of the clinical presentation of the dysfunction of normal
physiology and biochemistry in cancer patients (immune deficiency and altered
microenvironment, e.g., vasculature), (c) the protean heterogeneity of any
given human cancer, and (d) the success of some immune therapies that do not
act on the cancer at all, why are we sequencing the genes of human cancers to
develop fingerprints for therapeutic concoctions of putatively targeted
precision medicines (see NEJM
articles and editorial, above)?

Any
way, you get my drift.

It
would probably be worthwhile for us all to admit what we don’t know by being
certain to the extent possible of what we do know and be very careful about
distinguishing the two.

I
am reminded of a patient from my days as an intern at Duke Hospital. He was a
very sick middle-aged man with a huge liver palpable in his upper right
quadrant. No one could figure out what was wrong with him, but most were
convinced he was an alcoholic with failing hepatic function. I was not so sure.

I
felt the liver, or at least what I thought was a liver, but I really didn’t
know and this was in the days before MRIs, CT scans or even ultrasounds. So
against the protests of my attending, the late great Dr. Grace Kirby, I ordered a
liver scan (ask your senior attending what this is).

Normal
uptake. Normal study. No liver pathology.

A
subsequent biopsy revealed the mass to be metastatic renal cancer from the upper pole
of the right kidney.

I
was willing to be the ignorant intern who rubbed against the grain of the
established thought about the patient. (Did you think I got this way
yesterday?)

Knowledge
starts with ignorance. Mixing in a healthy helping of humility is also a worthy
thought experiment.

In
the article in the Times Holmes talks
about a concept advanced by Michael Smithson. Knowledge is an island. “The
larger the island of knowledge grows, the longer the shoreline–where knowledge
meets ignorance–extends.”

We
in academic medicine must work at the shoreline. We cannot hide safely at the
interior of the explored and mapped part of the island. Those advocating that precision
medicine be applied to cancer make the assumption that they have mapped enough
of the island to clearly extend the shoreline into the clinic. Color me
skeptical.

When
I was younger and ran a lab, I hope I spent as much time on the shoreline as I
could. Today, I think the leaders of the cancer-industrial complex would have
us believe that the island is large and well mapped. Perhaps. But the shoreline
isn’t. But if you don’t know the limits of the island and how small it really
is, it is unlikely you will be among those to push the boundaries of the
shoreline out any further.

You
want to Make Cancer History? Vote yourself off the island. Head for the coast
and and swim in the sea of ignorance. The water is fine!

Leonard Zwelling