A Critique of the Hypothesis, and a Defense of the
Question, as a Framework for Experimentation
David J. Glass
Scientists are often steered by common convention,
funding agencies, and journal guidelines into a
hypothesis-driven experimental framework, despite
Isaac Newton’s dictum that hypotheses have no place
in experimental science. Some may think that New-
ton’s cautionary note, which was in keeping with an
experimental approach espoused by Francis Bacon, is
inapplicable to current experimental method since, in
accord with the philosopher Karl Popper, modern-day
hypotheses are framed to serve as instruments of falsi-
ical rationalist” framework too is problematic. It has
been accused of being: inconsistent on philosophical
experimental science, which is verification and not
falsification; and harmful to the process of discovery
as a practical matter. A criticism of the hypothesis as a
framework for experimentation is offered. Pre-
sented is an alternative framework—the query/
model approach—which many scientists may dis-
cover is the framework they are actually using, despite
being required to give lip service to the hypothesis.
© 2010 American Association for Clinical Chemistry
In the early 1600s, Francis Bacon, the Lord Chancellor
to King James I of England, was arrested for accepting
bribes, briefly imprisoned, and forbidden thenceforth
to hold office. He thus found himself with ample time
ganon, which he criticized for its nonempirical ap-
proach to scientific exploration (1).
method can be boiled down to 2 main facets: (a) a call
for an inductive, rather than a deductive, approach to
science and (b) an advocacy for a reliance on experi-
ments rather than dogma for induction.
tion means that what happened can be said to be pre-
dictive of what will happen, so that one can induce
from the experience that a released apple falls toward
the ground that the next time one releases the apple it
will fall again. Second, induction refers to the ability to
ered by experiments on a specific case, so the fact that
an apple fell might allow the scientist to induce that an
one did the original experiments on an apple, not an
As for then-current practice, Bacon further
pointed out the problem with starting with an un-
proven premise and deducing rules from that premise.
If the premise is unfounded, then the resulting deduc-
tions from that premise will be equally unfounded. Al-
it was the thing he was criticizing, hypothesis being
defined as “whatever is not derived from phenomena,
an unproven premise, advanced without evidence, as a
tentative explanation” (3). The hypothesis as a frame-
work was in turn explicitly rejected by Isaac Newton, a
ton’s Principia had been organized around hypotheses
(4). It has been argued that Newton’s evolution from
an alchemist to a scientist forced him to move away
from the hypothesis construct in later editions of his
great work and then in his Opticks to eschew the hy-
pothesis in favor of rules he could prove, rules derived
inductively from experiments. Newton wrote in the
Principia (4) (translated from Latin):
I have not as yet been able to discover the reason for these
properties of gravity from phenomena, and I do not frame
hypotheses. For whatever is not deduced from the phenom-
ena must be called a hypothesis; and hypotheses, whether
chanical, have no place in experimental philosophy. In this
philosophy particular propositions are inferred from the
phenomena, and afterwards rendered general by induction.
Furthermore, when Newton was writing the
Opticks, he started out Part I as follows: “My design in
this book is not to explain the properties of light by
Novartis Institutes for Biomedical Research, Cambridge, MA.
* Address correspondence to the author at: Novartis Institutes for Biomedical
Research, 100 Technology Square, Cambridge, MA 02139. E-mail david.
Received April 5, 2010; accepted April 7, 2010.
Previously published online at DOI: 10.1373/clinchem.2010.144477
Clinical Chemistry 56:7
answers to these questions first would help in tailoring
medical care and, second, would point scientists to the
potential mediators of treatment resistance that still
require their attention. Once these mediators are dis-
covered, new mechanistic questions can be asked—all
in a particular focused program directed toward dis-
covery and innovation. This approach seems to be the
is called “scientific inquiry” and that at no stage re-
quires a hypothesis.
the intellectual content of this paper and have met the following 3 re-
quirements: (a) significant contributions to the conception and design,
acquisition of data, or analysis and interpretation of data; (b) drafting
or revising the article for intellectual content; and (c) final approval of
the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors
declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the
of data, or preparation or approval of manuscript.
Acknowledgments: I thank my colleagues at Novartis for their sup-
port, especially M. Fishman and B. Richardson, and the entire Mus-
for their critical reading and suggestions. Thanks to A. Abrams for
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