Final Exam of the Course - The application of the Theory of Science of falsification by Karl Popper and at least one example of the concept of paradigm. Philosophy of Science and the Concept of Health - 3073 HT23 Karolinska Institutet - oct - nov 2023 - Presented by Gert Helgesson, Tomas Mansson and Annelie Jonsson.

1. Daniele Amato MD – Karolinska Institutet 3073 HT23
1
Philosophy of Science and the Concept of Health – Section 3 Karolinska Institutet 3073 HT23
Exercise 4: Exam
My research project comes from the CCBIO – Center for Cancer Biomarkers, at the University of
Bergen in collaboration with Harvard University. It is about the Histopahological Features of
Cancer-Associated Venous Thromboembolism (VTE). The research Group from the University of
Miyazaki, Japan examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and
immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer
cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree
of organization in a time lapse of about 30 years. Vascular wall invasion or small cell clusters of
cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary
embolism cases. Most of the cancer cells in deep vein thrombi appeared to be invading the vessel
wall, whereas most pulmonary thrombi had cancer cell clusters, consistent with embolization via
blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or
podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in
thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone
H3 (specific for Neutrophils) was predominantly observed in the early stages of organizing thrombi.
There was no significant difference in thrombus components between VTE with cancer and
without cancer groups. Vascular wall invasion or cancer cell clusters in thrombi might influence
thrombogenesis of cancer associated VTE. The interplay between TF and podoplanin in cancer cells
and in monocyte/macrophages may induce coagulation reactions and platelet aggregation.
Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
(1)

2. Daniele Amato MD – Karolinska Institutet 3073 HT23
2
1)In the study, logical deductions started from singular observation statements as premises, then
showed as true: the specific positivity of the antibodies was tested to demonstrate the presence of
a singular cell line in the thrombus.
For example, a thrombus positive to Glycoprotein IIb/IIIa is highly suggestive of the presence of
platelets inside the thrombus.
My research starts from the lab observations of specific molecules expressed by specific cell-lines
used as a mean to test the presence of that single cell-line on the sample. In our case the presence
of TF as a sign of presence of tumoral cells in a thrombus.
Karl Popper’s FALSIFICATIONISM was applied to the study for example when it was demonstrated
the expression of TF (Tissue Factor) on cancer cells. TF is a molecule normally expressed by the
Alveolar Macrophages (false positive); in the case of lung cancer the evidence was debated using a
threshold of expression (88% of VTE cases): if TF was “overexpressed” that implies the presence of
tumoral cells in the thrombus, and the tumoral thromboembolism as the cause of death in the
case studied.
Falsificationism starts from Popper’s assumption according to which we should decrease or
eliminate our confidence in hypotheses; the good scientist, according to His theory is who is able
to falsify hypothesis; otherwise, the hypothesis is “corroborated” meaning not yet falsified.
The Falsificationist Scientific Methodology is based on:
1-the observation of the world to creatively decide which problem to solve.
2-the invention of a hypothesis with a creative act of imagination.
3-the decision of which testable things are implied by the hypothesis
4-the collection of the most relevant data to contradict the implications of Your test.
5-If the data are in line with the testable part of the hypothesis, the hypothesis has been
corroborated; then keep going on trying again to refute the hypothesis.
If it is not in line with the evidence (the empirical part of the hypothesis), the hypothesis has been
disconfirmed and scientific progress made. (2, 3)
The logical point in favor of the theory is because theories can be shown to be false:
it is possible to perform logical deductions starting from singular observation statements as
premises, to arrive at the falsity of universal laws and theories by logical deduction.
According to Falsificationism if it is to form part of science, a hypothesis must be falsifiable.
A hypothesis is falsifiable if there exists a logically possible observation statement or set of
observation statements that are inconsistent with it, that is, if established as true, would falsify the

3. Daniele Amato MD – Karolinska Institutet 3073 HT23
3
hypothesis. The falsificationist must try to make the hypothesis more precise so that it becomes
more readily falsifiable. “Falsificationists” also demand that scientific hypotheses be falsifiable, that
is discussed. They insist on this because it is only by ruling out a set of logically possible
observation statements that a law or theory is informative: Science progresses by trial and error.
“We believe that this is the way in which we can learn from our mistakes” (Carl Popper, 1969). (4)
In my research the general theory says that TF is an aspecific marker of the presence of
Macrophages/Fibroblasts in thrombus.
The overexpression of TF may be suggestive of the presence of tumoral cells in a thrombus, which
underlines the tumor as the cause of thromboembolism. Karl Popper’s FALSIFICATIONISM was
applied to the study as a methodology that can still survive the Quine-Duhem Thesis in the
search by the good scientists for the “main” evidence against their hypothesis and their
“auxiliary” assumptions, with a fully skeptical methodology and an attempt to falsify them. (5)
Just like in the following statement:
“The presence of an overexpressed TF on cancer cells is a sign of presence of tumor”; the normal
presence of TF on Alveolar Macrophages can deny this definition; the study defined a threshold
of 88% of expression plus a typical morphological overexpression immunohistological pattern (a
“Dante’s Inferno”-like pattern) as a limit between normal and pathological condition.
The study is based on the following specific statements of the study:
-Autopsy case of tumor-associated venous thromboembolism showed the presence of cancer cells
in thrombi with a direct invasive or small cluster patter (evidence not falsified considered as
one of starting points of reference from literature).
-Cancer cells in thrombi frequently showed the immunohistochemical expression of Tissue Factor
or Podoplanin, necrosis with platelet aggregation (GPIIb/IIIa) and fibrin formation (falsified: the
presence of TF or Podoplanin can be related to nontumoral-thrombosis).
-The frequency of TF-positive Monocyte/Macrophages in thrombi was higher in cancer-associated
venous Thromboembolism (TE) than in venous TE without cancer (falsified: TF is a molecule
normally expressed on Monocyte/Macrophages and Fibroblast; the definition of a threshold
and a morphological immunohistochemical pattern clarify the initial statement).
-The presence of another cell-line (Neutrophils) entrapped in the thrombus (Neutrophils
Extracellular Traps – NET) was related with the early phase thrombus-organizing process,
regardless of whether patients were in cancer-bearing state. (falsified: Neutrophilia is an
aspecific lab sign that can easily relate to an Acute Inflammatory disease). (6-7)

4. Daniele Amato MD – Karolinska Institutet 3073 HT23
4
2) For Thomas Kuhn (1922-1996) the definition of PARADIGM includes all the theories, goals
concepts, research methods, and standards of truth, rationally and observation, theories of
explanation and interpretation, all that is a part of a scientific discipline and that direct research in
that discipline.
The NORMAL SCIENCE includes where the scientists have confidence of their own paradigms that
allow them to solve all the “puzzles” they want to solve.
All normal science is paradigm-bound (8-9).
The CRISIS, ANOMALY or PARADIGM SHIFT is a phase where when scientists start doubting their
own paradigms, a scientific revolution, revolutionary science, or extraordinary science caused by
non-rational historical, sociological, or psychological conditions or forces that make those
paradigms incommensurable. Paradigm shifts change but do not progress science. In normal
science scientists have confidence of their own paradigms that allow them to solve all the puzzles
they want to solve.
In a time of crisis scientists are losing their confidence. This means that scientists become critical
of the paradigm, they start wondering what there should be changed, they become interested in
radical new ideas new theories, new methods new concepts; they start to think “out of the box”,
outside the paradigms that they have been using for all these years. The longer the crisis lasts the
more critical scientists become and the more radical and new ideas they take seriously.
There are two ways to end a crisis:
1-one possibility is that the anomalies are solved within the current paradigm, then the confidence
of the scientists in paradigm will be restored and we go back to normal science, the crisis is over.
2-the second possibility is more dramatic: there is the new paradigm emerges, a set of theories,
concepts and methods that promises to solve some of the most important anomalies; if most of
the scientific community embraces the new paradigm and abandons the old paradigm then we
have reached the fourth phase of science, a SCIENTIFIC REVOLUTION. (9-11)
Modern medicine, based on the positivistic criteria of what causes diseases (pathoetiology), and
how diseases develop (pathogenesis), is part of the Scientific Revolution and its stress on
experiments, observations, and human rationality.
According to the EPIPHENOMENALIST MATERIALISM an epiphenomenon is an existing
phenomenon existing as a mere side effect of something else; mental phenomena are real and
distinct from material entities, but they are assumed not to be able to react back on any somatic
processes.

5. Daniele Amato MD – Karolinska Institutet 3073 HT23
5
In the biomedical paradigm the direct causes of the health impairments can easily be divided into:
1.WEAR, normal aging as an unavoidable and normal process.
2.ACCIDENTS (e.g., fractures), also avoidable with statistical preventive measures
3.IMABALANCES (in hormones, vitamins, minerals, transmitter-substances etc.) due to either
external causes and/or internal causes such as genetic conditions
4.EXTERNAL ENTITIES (microorganisms, substances, sound waves, electromagnetic waves, and
even normal food in excessive doses) caused by intruding entities
5.BAD CONSTRUCTION/ CONSTITUTION by genetic and chromosomal factors.
6.IDIOPATHIC, from the Greek “of its own kind”, of unknown origin. (12)
In CONTEMPORARY WESTERN MEDICINE, medical researchers and practitioners instead seek to
explain medical outcomes using MECHANISTIC hypotheses about their causes—symptoms by
hypotheses about diseases, diseases by hypotheses about antecedents, epidemics by hypotheses
about changes in environmental or behavioral conditions; there is no presupposition concerning
number, form, or mode of action of the causes that explain the outcome other than there being
some cause or set of causes responsible.
The GOODNESS of a medical explanation depends in part on the context in which it is given.
The adequacy of a medical explanation is related to our ability as scientists to intervene on the
factor in question. (13)
In my field of study, Diagnostic Radiology, TNM criteria and the Seinsheimer Radiological
classification of femoral condylar fractures can be seen as examples of scientific paradigms.
In TNM (Tumor, Nodes, Metastases) of the Lung Tumor, for example:
“T” depends on the dimensions, size, airway locations (invasion of the carina or trachea, local
infiltration of the pleura, eventual presence of Pneumonitis).
“N” refers to the presence and location of regional lymphnodes involved: ipsilateral, peribronchial
/hilar or mediastinal/subcarinal lymphnodes.
-involvement of contralateral mediastinal, hilar, scalene, or supraclavicular lymphnodes.
“M” is related to the presence of distant metastasis (contralateral lobe / pleural or pericardial +-
effusion / single-multiple extrathoracic). (14)
According to the Seinsheimer Radiological classification of the femoral condylar fractures we move
from the Nondisplaced to the comminute fractures with/ without the involvement of
patellofemoral articular surface (in osteoporotic patients), the involvement of the medial and/or
the lateral condyle, the involvement of the femorotibial surface. (15)

6. Daniele Amato MD – Karolinska Institutet 3073 HT23
6
In my research the efforts of the scientific research are towards the cases of TE
(thromboembolism) with Neutrophilia without the radiological evidence of a thrombus: that “grey
area” between apparently healthy (asymptomatic) patients and tumoral patients with or without a
thrombus “at risk” of TE, with classes of risk based on anatomopathological – physiopathological-
lab criteria with possible relevant clinical-therapeutic implications for the survival of the patient.
One of the next scientific paradigms is based on an “aspecific” Neutrophilia associated to a high
risk of thromboembolism apart from the positive radiological findings for TVE as already
demonstrated by the strong scientific evidence of the last 10 years. (16-18)

7. Daniele Amato MD – Karolinska Institutet 3073 HT23
7
REFERENCES
1. “Histopathological features of Cancer-Associated Venous Thromboembolism: Presence of
intrathrombus Cancer Cells and Prothrombotic Factor”, Toshihiro Gi, Arterioscler Thromb Vasc Biol,
2023 Jan;43(1):146-159, Epub 2022 Nov 17.
2. Andrew Chapman “Scientific Methodology: Probability and the problem of induction”.
3. Victor Gijsbers 1.4 “Karl Popper and the logic of falsification”.
4. Alan Chalmers “What is this thing called science?” chapter 5.
5. Andrew Chapman “The demarcation problem: Falsificationism”.
6. Moik F, Prager G, Thaler J, Posch F, Wiedemann S, Schramm T, Englisch C, Mackman N, Pabinger
I, Ay C. Hemostatic biomarkers, and venous thromboembolism are associated with mortality and
response to chemotherapy in patients with pancreatic cancer. Arterioscler Thromb Vasc Biol. 2021;
41:2837–2847.
7. Hisada Y, Mackman N. Cancer-associated pathways, and biomarkers of venous thrombosis.
Blood. 2017; 130:1499–1506.
8. Victor Gijsbers 2.1 “Thomas Kuhn, normal science”.
9. Andrew D Chapman, “Scientific methodology: Paradigms and puzzle solving”.
10. Victor Gijsbers 2.2 “Thomas Kuhn, scientific revolutions”.
11. Alan Chalmers “What is this thing called science?” chapter 8.
12. Johansson & Lynoe “Medicine and philosophy” section 6.1.
13. Reiss & Ankeny “Philosophy of medicine” section 3-4, The Stanford Encyclopedia of Philosophy
(2016), Edward N. Zalta (ed.).
14. Lababede O , “The Eighth Edition of TNM Staging of Lung Cancer: Reference Chart and
Diagrams” Oncologist. 2018 Jul; 23(7): 844–848.
15. Seinsheimer, F., 3rd (1980). “Fractures of the distal femur.” Clin Orthop Relat Res (153): 169-
179.
16. “White blood cell count measured prior to cancer development is associated with future risk of
venous thromboembolism--the Tromso study”. Blix K, PLoS One. 2013 Sep 4;8(9): e73447.
17. “Clinical significance of the neutrophil-lymphocyte ratio in venous thromboembolism patients
with lung cancer”. Go SI, Lung Cancer. 2014 Apr; 84(1):79-85.
18. “Persistent neutrophilia is a marker for an increased risk of venous thrombosis”, M Kushnir J
Thromb Thrombolysis 2016 Nov; 42(4): 545-51.