Eubios Journal of Asian andInternational Bioethics
EJAIB Vol. 28 (4) July 2018www.eubios.info
ISSN 1173-2571 (Print) ISSN 2350-3106 (Online)
Official Journal of the Asian Bioethics Association (ABA)

Copyright ©2018 Eubios Ethics Institute(All rights reserved, for commercial reproductions).

Contents

page
Editorial: Bioethics, Stress and Moral Responsibility 103- Darryl Macer
Repeated administration of high dose caffeine induces
oxidative damage of liver in rat: Health and ethicalimplications
104- Nasrin Akhter, Ashraful Alam, Md. Anower Hussain
Mian, Hasan Mahmud Reza, Darryl Macer, Saiful Islam
Some beneficial effects on the physical heath andacademic achievement of middle years secondary school
students through studying environmental ethics 112- Alexander Waller
Stem Cell Tourism: Addressing the Challenge ofRegulatory Cosmopolitanism
118- Patrick Foong
The Struggle unto Death127- Jasper Doomen
The Question of Moral Responsibility and Physician’s
Practice in Nigeria
130- Joseph N. Ogar, Ushie Abel Idagu, Samuel Akpan
Bassey
ABA Renewal and AUSN Update
134

Editorial address, and all correspondence to:Prof. Darryl Macer, Ph.D., Hon.D., MPH
President,
American University of Sovereign Nations
https://ausovereignnations.org
Email: darryl@eubios.info
EJAIB adopts and complies with the Committee on
Publication Ethics (COPE) Publication ethics andmalpractice policy. All potential authors shouldhave read these guidelines and by submission of anarticle for publication you acknowledge that you
have complied with this policy. Violations will behandled in proportion to the intention andseriousness of the violation.
Registered address of EJAIB: P.O. Box 16 329,
Hornby, Christchurch 8441, New Zealand

Editorial: Bioethics, Stress andMoral Responsibility
One of the ultimate issues of bioethics is whotakes responsibility for our health and thequestions of life and death. If we can live a life
according to the principle of bioethics as the love oflife, perhaps we can reduce the stress that life
brings to us. This issues has two papers exploring
two different perspectuves of this question.

Nasrin Akhter et al. conducted experiments andreview some of the research studies that address one of
the most popular drugs that is used all around the world– caffeine. Maybe some of you are reading this paper
and issue are in arm’s length of caffeine, in a delivery
form such as coffee, or soda based drinks. Please put
your drink down while you read the study! As someone
who almost never drinks these substances, I feelsomewhat relieved to have not become addicted to them,nor list them as something which I need or desire.
Perhaps an alternative solution is bioethics education,
as presented in the findings of Alex Waller in use ofenvironmental ethics among teenagers in aninternational school in Khao Yai, Thailand. Even in thevicinity of the nature of famous National Park, there
were positive effects in the health and academic
performance of students taking those courses.

This issue of EJAIB also includes a review by

Patrick Foong of laws regulating stem cell therapies thatare so popular among many persons, that a growing
number of medical tourists travel in order to avail of thistechnology. How do we regulate this?
Jasper Doomen reviews the ethics and law ofeuthanasia in the Netherlands, which is a topic of muchinterest to persons around the world, who usually live incountries that do not allow active euthanasia.
Joseph N. Ogar, Ushie Abel Idagu and Samuel Akpan
Bassey discuss how some of the ethical principles of
medical ethics affect the responsibility of physicians, andhow this is applied in Nigeria today. Please enjoy thearticles, and be encouraged to submit your own!

- Darryl Macer(Please note the print edition is always in Black and white,
but the pdf version online is in colour)

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Eubios Journal of Asian and International Bioethics 28 (July 2018)

Repeated administration of highdose caffeine induces oxidative
damage of liver in rat: Health andethical implications- Dr. Nasrin Akhter, PhD,
Senior Lecturer, Dept. of Pharmaceutical Sciences,
Faculty of Life Sciences, North South University, Dhaka,Bangladesh
Email: luckyayon@hotmail.com
Corresponding Author: nasrin.akhter@northsouth.edu- Dr. Md. Ashraful Alam PhD
Assistant Professor, Dept. of Pharmaceutical Sciences,
Faculty of Life Sciences, North South University, Dhaka,Bangladesh, Email: sonaliagun@yahoo.com- Prof. Dr. Md. Anower Hussain Mian, PhD, MPH,
Head, Dept. of Community Dentistry, Faculty of Public Health,Bangladesh University of Health Sciences, Mirpur-1, Dhaka,Bangladesh
Email: ayonshafi@hotmail.com- Prof. Dr. Hasan Mahmud Reza PhD
Chairman, Dept. of Pharmaceutical Sciences,
Faculty of Life Sciences, North South University, Dhaka,Bangladesh
Email; hasan.reza@northsouth.edu- Darryl Macer, Ph.D., Hon.D., MPH
President, American University of Sovereign Nations,Arizona, USA
Email: provost@ausn.info- Prof. Dr. Md. Saiful Islam PhD
Dept. of Clinical Pharmacy and Pharmacology
University of Dhaka
Bangladesh, Email; saifulpharmacy@yahoo.com

Abstract
Caffeine, a known CNS stimulant is given as an adjunctcomponent in most abused drugs which could be fatalwith repeated administration in many circumstances.
This paper presents a study to investigate the effect of
repeated administration of caffeine at high dose on rat
liver, and discusses ethical and policy issues of caffeineuse.
Long Evans rats were treated with pure caffeine
solution in distilled water through intragastric route
once daily for consecutive 56 days. Three groups of rats
recognized as low dose, high dose and control group
received 6mg caffeine / kg BW, 12mg caffeine / kg BW
and distilled water, respectively. Rat plasma was
examined for liver transaminases (ALT, AST) andalkaline phosphatases (ALP) concentrations which weresignificantly increased in plasma as compared to thecontrol. Both rat plasma and liver homogenate were
subjected to estimate malondialdehyde (MDA), advanced
oxidation protein product (AOPP), nitric oxide (NO),antioxidant enzyme catalase (CAT), glutathione (GSH)and superoxide dismutase (SOD) activity. MDA, AOPP,
NO levels increased and SOD activity decreased
significantly in both plasma and liver as compared tothose of control where as CAT and GSH activity remainunchanged.
Rat
liver
tissueswerestudiedhistochemically with Hematoxylin and Eosin, and Picro
Sirius Red staining. Significantly increased infiltration of
inflammatory cells and progressive deposition ofcollagen fibre were visible in liver tissue of caffeine
treated both dose groups as compared to the control.

Long term administration of caffeine at higher dose,
significantly contributes to liver inflammation andconsequent fibrogenesis. This raises significant ethicaland policy issues .
Key Words: Caffeine, Liver, Inflammation, Fibrogenesis.
Introduction
There are many legal ways available for caffeine intake
including soft drinks, chocolates, drinking coffee,
beverages, energy drinks and so on. There is expanding
caffeine consumption around the world with the rise of
global brands such as Starbucks. There is an apparent
lifestyle choice in many societies to demand morechemical stimulants through soft drinks and coffee tokeep awake and active for longer hours. Recreational useof CNS stimulant are rising globally. Most recreational
drugs contain caffeine as an adjunct stimulant.
Development of addiction eventually increases
caffeine intake due to repeated use of those drugs.
Regular coffee intake has been reported as an attenuatorof liver fibrosis progression in several studies. Sung Gon
and Dae Won found caffeine inhibits hepatic stellate cells(HSCs) adhesion and activation and increased HSC
apoptosis (Shim et al., 2013). Another study suggested
that regular coffee intake lowers plasma livertransaminase level, inhibits the cAMP/PKA/CREB signal
pathway through adenosine A2A receptors in HSC(Wang et al., 2015). However, caffeine has shownvariable stimulating effect on acetaminophen induced
hepatotoxicity mediated by microsomal CYP3A
subfamily (Jaw et al., 1993). Caffeine increases
respiratory rate and exert broncho-dilatation effect. On
GIT, caffeine exerts stimulating effects on gastric acidand pepsin secretion and is sometimes reported toincrease acid reflux by weakening lower esophageal
sphincter (Robertson et al., 1978; Pincomb et al., 1985;
Williams et al., 1985; Davis et al., 1988; Prineas et al.,
1980; Sutherland et al., 1985; Benowitz et al., 1985;
Smits et al., 1985; Murat et al., 1981; Gong et al., 1986;
Benowitz, 1990).
Overall the literature identifies that caffeine
consumption is associated with lower risk for multiple
diseases including type II diabetes, heart disease andstroke, but the mechanism underlying these protective
effects is not known. Interestingly, epidemiologicalstudies have also established an association between thecommon consumption of coffee, or other caffeinatedbeverages, and a reduced risk of developing Parkinson’s
disease. Caffeine (1, 3, 7-trimethylxanthine) exerts dose
dependent effects on nervous system, heart andmetabolic process. On average 250 mg of caffeine may be
administered to get bodily positive effects like feelings ofalertness, decreased fatigue, and eased flow of thought
and so on.
Caffeine intake more than 250 mg and up to 500 mg
can result in adverse effects like restlessness,
nervousness, insomnia, and tremors (Yew et al., 2014).
The fatal dose of caffeine for adults is more than 10g.
Renata et al. suggested that chronic coffee and caffeine
ingestion protected the endogenous antioxidant system
in rat brain and reduced lipid peroxidation of brain
membrane; thus prevented age related cognitive
function turn down. Caffeine mainly acts by antagonizing
adenosine receptors (A1 &A2) non selectively andEubios Journal of Asian and International Bioethics 28 (July 2018)
reversing the action of adenosine. On central nervous
system, caffeine induces low blood flow byvasoconstriction and releases catecholamines frompresynaptic neurone by opposing action of adenosine(Abreu et al., 2011; Fredholm, 1985; Mathew et al.,1985).
On the cardiovascular system, caffeine, by a moderateintake, induces peripheral vasoconstriction, slightincreased blood pressure, reduced heat rate, systemic
release of catecholamine and renin, a balanced change in
cardiac output and contractility. Chronic coffee
consumption is found to be associated with increased
level of serum LDL cholesterol and cardiac arrhythmia.
In contrast, high dose of caffeine decreases bloodpressure by vasodilatation and increases systemic
catecholamine extremely. Glomerular filtration rate andtubular reabsorption, increased by caffeine createshyponatraemia. Contribution of caffeine to increased
body temperature is not supported by any strong
evidence.
Investigation on rats treated with caffeine revealed
that coffee or caffeine intake inhibits calcium
metabolism and results in higher levels of calcium in theurine and plasma as compared to bone, decreased bonemineral density and bone volume. Moreover, caffeine has
negative effects on osteoblast function and bone matrix
formation and thus bone repairing process is delayed.
Caffeine suppresses calcium absorption from intestine tosome extent. Thus people, with a habit of caffeine intake
and lack of calcium in diet, are highly at risk ofdeveloping osteoporosis. A separate study reported thathigh dose caffeine intake inhibits the secretion ofparathyroid hormone (PTH) through the mechanism ofdecreasing intracellular cAmp. PTH contributes directly
to the survival and differentiation of osteoblast cell andhence increased population of osteoblasts useful for thetreatment of osteoporosis and bone formation. A
correlation between high coffee consumption and low
PTH serum levels has been observed in men which was
opposite in a separate study with young women.
However, this relationship requires further detailed
investigation.
Caffeine undergoes N-demethylation and/or ringoxidation through its biotransformation process andmetabolites produced are theophylline, paraxanthine,
theobromine and 1, 3, 7-trimethyluric acid in man.
Further decomposition of these compounds takes place
to
give
rise
dimethylated
uricacids,
monomethylxanthines and monomethyluric acids. A
separate study suggested that CYP1A2 isozyme catalyzes
the demethylation process of caffeine which is further
reportedly acetylated to 5-acetylamino-6-formylamino3-methyluracil (AFMU) by the polymorphic acetyltransferase (Huang et al., 2002; Tassinari et al., 1991;
Wink et al., 1996; Lacerda et al., 2010; Heaney, 2002; Lu
et al., 2013; Jilka et al., 2007; Landin-Wilhelmsen et al.,
1995; Paik et al., 2010; Tang-Liu et al., 1983; Butler etal., 1992).
To investigate liver toxicity by caffeine we haveestimated liver marker enzymes (ALT, AST) and alkaline
phosphatases (ALP) level in rat plasma; antioxidant
enzyme activity such as catalase CAT), glutathione (GSH),
superoxide dismutase (SOD) and oxidation end products
like advanced oxidation protein product (AOPP), lipid

105

peroxidation product, malondialdehyde (MDA) and levelof nitric oxide (NO) in both plasma and liver tissue after
long term administration of caffeine on rats.
Histopathologic study of rat liver tissue was performed
for inflammation and fibrosis from all groups.
Methods
Chemicals and reagents
Pure caffeine of pharmaceutical grade used in ourstudy was kindly supplied by Pharmadesh Laboratories
Limited. Alanine aminotransferase (ALT), aspartate
amino transferase (AST) and alkaline phosphatases(ALP) assay kits were obtained from DCI diagnostics(Budapest, Hungary), Thiobarbituric acid (TBA) was
purchased from Sigma Chemical Company (USA), 50,50dithiobis-2-nitrobenzoate (Ellman’s reagent) from Sigma(USA), glutathione (GSH) in reduced form andtrichloroacetic acid were purchased from J.I. Baker (USA)and sodium hydroxide from Merck (Germany). All otherchemicals and reagents used were of analytical grade.
Animal experiments
18 male Long Evans rats (180-200g) were obtained
from animal production unit of Animal House in the
Department of Pharmaceutical Sciences, North South
University, Dhaka, Bangladesh (aged between 10-12
weeks old). The animals were kept in ordinary cages (18inch X 12 inch per individual) at room temperature of25±3˚C with 12 h dark / light cycles (65% relative
humidity). They had free access to standard laboratory
feed and water. The present study protocol wasapproved by the Ethical Committee of the Department ofPharmaceutical Sciences, North South University foranimal care and experimentation.
To study the effects of caffeine on liver, the animals
were equally divided into three groups (6 rats in each).
Animals of group 1, considered as low dose group, weretreated with 6mg caffeine / kg of body weight
intragastrically, once daily. Rats of group 2, consideredas high dose group, were treated with 12 mg caffeine /kg of body weight intragastrically, once daily. Group 3
considered as control group where rats received only
distilled water. Rats of all groups were treated for eightweeks. Body weight, water and food intake of animals
were monitored and recorded daily.
After 56 days, all the animals were weighed andsacrificed. Blood samples were collected and plasma
separated from it and stored at -20˚C until used. Some
major organs like liver, kidney, heart, spleen were alsocollected and weighed immediately. Half of the organs
were stored at -20˚C until used for biochemical tests andhalf were processed for histological study.
Assessment of liver enzymes
Rat plasma of three groups was assayed for livertransaminases, ALT and AST and another isozyme,
alkaline phosphatases (ALP). Chemical analysis was
conducted by following the standard protocols of
manufacturer provided with DCI diagnostics kits
(Hungary).
As biochemical markers of liver dysfunction, some ofthe enzymes and end products of the metabolic pathway,
such as serum bilirubin, alanine amino transferase,
aspartate amino transferase, ratio of aminotransferases,

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Eubios Journal of Asian and International Bioethics 28 (July 2018)alkaline phosphatase, gamma glutamyl transferase, 5′
nucleotidase, ceruloplasmin, α-fetoprotein, are said to bevery sensitive, reported by several studies. Among them
the three enzymes ALT and ALP, AST are considered as
the classical markers of any kind of liver cell injury
whose levels are elevated in plasma in liver disease.
(Gowda et al.;2009).
Assessment of oxidative stress markers and antioxidant
enzyme activity
Oxidative stress markers and antioxidant enzyme
activity were measured in both blood plasma and livertissue. Liver tissue was homogenized in 10 times volumeof ice cold phosphate buffer having pH 7.4 andcentrifuged at 12,000X g for 30 min at 4°C. The
supernatant was collected and used for thedetermination of protein and enzymatic studies.
Estimation of malondialdehyde (MDA)
Following a colorimetric method, we measured MDA,
one of the products of lipid peroxidation in plasma andliver tissue extract using thiobarbituric acid (TBA) as per
method described by Niehaus and Samuelsson (Niehaus
et al., 1968). The procedure briefly described astreatment of 0.1 ml of tissue extract or plasma in TrisHCl buffer (pH 7.5) with 2ml of TBA-TCA-HCl reagent
mixture taking equal amount of each (thiobarbituric acid
0.37%, 0.25 N HCl and 15% TCA). The final mixture washeated in hot water bath for 15 min and then cooled. The
clear supernatant was taken and absorbance measured
against reference blank at 535nm.
Assay of nitric oxide (NO)
Nitric oxide, in the form of nitrate, was measured
following the method described by Tracey et al.(1995).
In the present study, Griess-Illosvoy reagent was
modified by replacing 5% 1-napthylamine with naphthyl
ethylene diamine dihydrochloride (0.1% w/v). The
reaction mixture containing tissue extract or plasma(2ml) and phosphate buffer saline (0.5ml) was incubatedat 25°C for 150 min. The mixture color changed into pink
due to formation of a pink colored chromophore. Using
corresponding blank solutions, the absorbance of thesesolutions was measured at 540 nm. A standard curve,
expressed as nmol/ml, was prepared to measure plasma
and liver tissue content of nitric oxide.
Measurement of advanced oxidation protein products(AOPP)The methods described by Witko-Sarsat et al.(1996)
and Tiwari et al.(2014) were followed with slight
modification to detect AOPP level. In brief, 2 ml mixture
was made by diluting plasma or tissue extract with PBS
in 1:5 ratio; then 0.1 ml of 1.16 M potassium iodide wasadded to each tube; after 2 min, 0.2ml acetic acid wasadded to it. The absorption of the reaction mixture wasmeasured immediately at 340 nm using a blankcontaining 2ml of PBS, 0.1ml of potassium iodide and 0.2
ml of acetic acid. AOPP concentrations were expressed as
nmol/L as chloramine-T equivalents where theabsorbance of chloramine–T was linear within the rangeof 0 to 100 nmol/L at 340 nm.
Estimation of catalase (CAT) activity

The method described by Khan et al. (2012) was used
to test catalase activity with some modifications. The 3
ml reaction mixture used for CAT activity contained: 0.1
ml of plasma or liver tissue enzyme extract, 2.5 ml of 50
mmol phosphate buffer (pH 5.0) and 0.4 ml of 5.9 mmol
hydrogen peroxide. 1 min later changes in absorbance ofthe reaction mixture were determined at 240 nm. An
absorbance change of 0.01 as units/min corresponds to
one unit of CAT activity.
Assay of glutathione (GSH) in reduced form
Reduced glutathione in liver was estimated by themethod of Mitchell JR et al. (1973). 1.0 ml of 4%
sulfosalicylic acid was added to 1 ml of 10% tissue
homogenate. Then the precipitated mixtures were kept
for one hour at 4ºC. After 1 hour, mixtures were
centrifuged at 1200 × g for 20 min at 4ºC. 0.1 ml filteredaliquot, 2.7 ml phosphate buffer (0.1 M, pH 7.4) and 0.2
ml of 100mM DTNB (5,5-dithiobis-2-nitrobenzoic acid)
were mixed to make 3 ml assay mixture. A yellow colorof the mixture developed which is immediately subjected
to take absorbance at 412 nm using Smart SpecTM plus
Spectrophotometer. The calculated result was expressedin ng/mg protein.
Estimation of superoxide dismutase (SOD) activity
SOD was assayed in plasma and tissue homogenates
by using previously described method (Tripathi et al.,2010). Sufficient amount of tissue extract mixed with
PBS to make the volume 2.94 ml. Then 0.06 ml of 15 mM
epinephrine is added to the mixture to start the reaction.
Taking an interval of 15 sec, change in absorbance ofreaction mixture was recorded for one min at 480 nm.
Blanks prepared with all the ingredients, except enzyme
preparation were used simultaneously for taking
absorption. Auto-oxidation of epinephrine present insample solution will be reduced to 50% with the actionof one unit enzyme.
Histopathological observation
Liver tissues of all groups were prepared forhistology study according to standard procedure. In
short, tissues were fixed neutral buffered formalin,treated with ethanol and xylene, then embedded inparaffin. Using microtom, tissue paraffin blocks weresectioned at 5µm. Tissue sections were then stained with
Hematoxylin and Eosin and Picro Sirius Red separately
for microscopic observation of the inflammatory cell
invasion and deposition of collagen fibre respectively inliver. Stained tissue sections were examined under lightmicroscope at 40X magnifications.
Statistical analysis
The experimental results were evaluated by using thestudent’s t test in Graph Pad Prism Software. The values
were expressed as mean±standard error of mean (SEM).
In all cases, statistical significance was considered p< 0.5.
Results
Physical and behavioral changes observed in rat during
caffeine treatment
During the period of experiment, rats of both dosetreated groups were found restless with palpitation. No

Eubios Journal of Asian and International Bioethics 28 (July 2018)107

lesions were observed on skin. Body temperature wasnormal after caffeine administration.

Figure 4: Comparison of weights of whole heart, left
ventricle and right ventricle of caffeine treated rat with
control group

Liver Wet weight

Effects of caffeine on body weight, food and water intake
in ratDuring the experimental period, daily body weight,
food and water intake of rats of all groups were recorded.
Body weight of rats increased equally (Figure 1) in drug
treated and control groups. Food and water intake was
the same for all groups (Figures 2 and 3).

Figure 1: Daily body weight record of rats during caffeine
treatment

Figure 2: Daily food intake record of rat during caffeine
treatment

Figure 3: Daily water intake record of rat during caffeine
treatment
Effects of caffeine on organ weight in rat
Liver weight of caffeine treated rats increased
significantly from that of control in high dose group (P <0.05, n = 6). Other vital organs such as heart, kidney andspleen showed no significant change in weight ascompared to control values.

Figure 5: Comparison of liver, kidney and spleen weights
of caffeine treated rat with control
group
Effects of caffeine on liver marker enzymes in rat
By caffeine treatment, transaminase ALT increased
significantly to 71.78 ± 8.22 in low dose group and to
73.21 ± 5.33 in high dose group from 43.07 ± 4.45 U/L(p< 0.01, n= 6 in both groups). Another liver marker
enzyme AST increased significantly to 41.63 ± 3.46 inlow dose group and to 47.37 ± 4.85 in high dose groupfrom 22.97 ± 2.87 U/L( p< 0.01, n=6 in both dosegroups). Alkaline phosphatase (ALP) increased
significantly to 51.10±3.85 in low dose group and to
48.75 ± 3.88 in high dose group from 30.88 ± 4.59
U/L( p< 0.01, n=6 in both groups). The livertransaminases, ALT increased 1.7-fold in both dosegroups; AST increased 1.8-2.0 fold in low dose and highdose group, respectively; ALP increased1.6-1.7 fold in
low dose and high dose group respectively as compared
to control value.

Figure 6: Effect of caffeine on liver transaminases andalkaline phosphatases in rat
Effects of caffeine on oxidative stress in rat
In our study, we have evaluated the MDA, nitric oxideand AOPP content in rat plasma and liver homogenates
as markers of oxidative stress. The level of lipid
peroxidation product, MDA in caffeine treated rats
significantly increased from 97.72 ± 7.30 to 169.79 ±11.09 by low dose and to 146.85±14.08 nmol/ml byhigh dose (p< 0.01, n=6) in plasma. In liver homogenate,

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Eubios Journal of Asian and International Bioethics 28 (July 2018)

this value increased from 130.82±10.89 to 179.08±6.76
by low dose and to 194.46 ± 5.85 nmol/ml by high dose(p< 0.01, n=6). Caffeine increased MDA 1.5-1.7 fold byhigh and low dose respectively in rat plasma and 1.4-1.5
fold by low and high dose respectively in liver.

Figure 7: Effect of caffeine on lipid peroxidation inplasma and liver in rat

high and low dose respectively in plasma where as 2.63.0 fold by high and low dose respectively in liver ascompared to control.
Effects of caffeine on antioxidant enzyme system in rat
Caffeine treatment significantly reduced superoxide
dismutase activity by low dose from 20.83 ± 3.52 to
10.00 ± 1.83 in plasma; from154.17 ± 17.77 to 83.33 ±8.82 by low dose and to
94.17 ± 6.38 by high dose inliver. SOD activity reduced 2fold by both dose groups inplasma and liver. Activities ofother antioxidant enzymes
such as GSH and CAT foundunchanged in plasma andliver tissue in both dosegroups when compared tocontrol values.

NO, measured as nitrate, increased significantly from
14.1 ± 0.91 to 17.24 ± 0.34 nmol/ml (p<0.05, n=6) by
low dose in plasma and in liver tissue, from12.63 ± 0.48
to 29.05 ± 2.01by low dose and to 35.57 ± 4.08 nmol/ml(p<0.05, n=6) by high dose when compared with control
values. Caffeine induced increase in NO level 1.2-fold by
low dose in plasma and in liver 2.0-2.3 fold by low andhigh dose respectively as compared to control values.

Figure 8: Effect of caffeine on nitric oxide level in plasma
and liver in rat

Figure 9: Effect of caffeine on advanced oxidation protein
product level in plasma and liver in rat
Caffeine treatment induced significant increase in
AOPP concentration to 292.62 ± 19.03 and to 285.08 ±15.40 from 207.70 ± 16.05 nmol/ml equivalent tochloramines-T (p<0.01, n=6) in plasma by low and highdose respectively. In liver it increased to 682.06 ± 72.34
and to 776.51 ± 139.36 from 256.11 ± 18.44 nmol/ml
equivalent to chloramines-T (p<0.01, n=6), by low andhigh dose respectively. AOPP increased 1.3-1.4 fold byFigure 10: Effect of caffeine on glutathione and catalase
activities in plasma and liver in rat

Figure 11: Effect of caffeine on superoxide dismutase
activity in plasma and liver in rat
Histological changes after caffeine treatment in rat liver
Inflammation in drug treated rat liver was seen in
stained tissue section. Massive invasion of inflammatory
cells was found in the centrilobular part of liver section
stained with H &E in low dose group, which
progressively increased in the high dose group (Figure
12).

Eubios Journal of Asian and International Bioethics 28 (July 2018)
Liver fibrosis was evaluated histologically byvisualizing the red color of collagen fibres deposition
using Sirius red stain in both dose groups. The collagenfibres were heavily deposited around portal tracts andcentral veins in caffeine treated group and extended
from central vein to portal tract resulting in theformation of pseudolobules which was not seen incontrol rats. Extent of collagen fibre deposition wasenormous in high dose group than that of low dosegroup (Figure 13).
Discussion
In the present study, we have performed
investigations to figure out the effect of caffeine on liver.

Control

109

This study illustrates how biochemistry can be applied toinvestigate potential health affects of a popular dietarycompound. The biochemical test results indicated thecontribution of caffeine on ROS induced liver cell damage
through lipid peroxidation or protein oxidation. Other
effects such as increased nitric oxide and decreased
activity of antioxidant enzymes suggest the stressed
condition with reactive oxygen or nitrogen species
produced by caffeine. High and low doses of caffeine
induced elevation of serum ALT, AST and ALP levels ascompared to control.

Low doseHigh dose

Figure 12: Invasion of inflammatory cells in the centilobular part of rat liver after caffeine treatment
treatment

Control
Low dose
Figure 13: Deposition of collagen fibre in rat liver after caffeine treatment
In our study, we have focused on the oxidative
damage of liver cells with chronic administration of highdose of pure caffeine targeting reactive oxygen species(ROS) and reactive nitrogen species (RNS) mediateddamage of cell components. To observe liver cell damage
the plasma levels of three liver marker enzymes(ALT,AST,ALP) have been estimated. As a proof ofincreased oxidative stress some antioxidant enzymes(CAT,GSH, SOD) level in plasma and liver tissue havebeen measured. Moreover, to check damage by oxidationsome reaction end products such as AOPP, MDA, NO
were determined in plasma and liver tissue.

High dose

The cytotoxic effects of caffeine have been
demonstrated as indirect action with several enzymes orxenobiotics in some studies includedi. Caffeine increased glioma cell death by decreasing
HDAC1 activity and/or by increasing p300 activity (JinCherng Chen et al., 2016).
ii. The synergistic cytotoxic activity of caffeine withdifferent anticancer agents to treat several cancers has
also been reported (Line. Saeb H et al., 2017).
iii. Caffeine has been shown to induce apoptosis andautophagy in different cancer cells. (Bøhn, et al., 2014).
iv. Importantly, caffeine has also been shown to inhibit
ATM and ATR -two important protein kinases involved

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Eubios Journal of Asian and International Bioethics 28 (July 2018)

in DNA damage– and to induce cell cycle
arrest/apoptosis signaling process (Wang, et al., 2015).
v. In a different study, combined effects of caffeine withalprazolam (Alp), a member of benzodiazepine group of
drugs, have been shown to elevate level of ROS anddepletion of GSH. Presence of caffeine augmented
necrosis in a well-regulated pathway whereas
alprazolam alone induced apoptosis in human cells.
(Saha et al., 2009).
The magnitude of aminotransferase alteration defines
the severity of liver disease as “mild” (elevation less than
5 times of normal) “moderate” (elevation 5–10 times ofnormal) or “marked” (elevation more than 10 times ofnormal). Besides liver, alkaline phosphatase levelindicates bone disease even though this enzyme may
also be released from other tissue damage included theplacenta, kidneys, intestines or leukocytes. In drug
induced liver damage, alcoholic liver disease and nonalcoholic fatty liver disease, viral hepatitis (hepatitis B
and C) and hemochromatosis, liver transaminases(ALT,AST) exhibit mild elevation (Green et al., 2002;
Pratt et al., 2000; Gopal et al., 2000; Robert et al., 2011;
Fishman, 1990). In present study, we found themagnitude of ALT and AST elevation in caffeine-treated
rat as representing mild liver disease when comparedwith control values.
Drug toxicity can play significant role by triggering
inflammatory response and activating innate immune
cells by release of damage –associated molecular pattern.
Resident kupffer cell, neutrophils, monocytes areactivated in the liver after toxic induction of drug. ROS
produced by the phagocytes mediates killing of target
cells (e.g. the invaded organisms). In absence of bacteria,
especially when injury is drug induced, hepatocytes andother liver cells becomes target of ROS; hence thedamaged host cells initiate chronic inflammation.
However, the nature of oxidative stress specifies thetarget and damages particular cellular component. The
mechanism of ROS induced cell killing involves
mitochondrial dysfunction leading to oncotic cell
necrosis rather apoptosis.
Very few studies presented the effect of caffeine on
metabolism as:i. Caffeine mobilizes fatty acids from adipose tissue andincreases its plasma level at rest in an exercising muscle(Graham et al.; 2008)
ii. Few studies supported the fact that the carbohydrate
and fat metabolism in active muscle was generally
unaltered after caffeine ingestion (Graham et al. ; 2000)
iii. Oral doses of caffeine increase the urinary excretionof calcium, magnesium, sodium and chloride for at least
3 h after consumption. Uncompensated losses of calcium
would be a risk factor for development of osteoporosis(Linda et al., 1993).
iv. A Retrospective cohort study presented that
consumption of green tea, coffee, and total caffeine wasassociated with a reduced risk for type 2 diabetes.
However, the mechanism of action of caffeine for
reducing risk for type 2 diabetes has not been studiedyet (Iso et al., 2006).
Chronic release of cell contents amplifies the
inflammatory injury. Jaeschke et al. described that
inflammatory ROS cause cell death in sufficientconcentration where as insufficient ROS triggers theresistance against future inflammatory oxidative stressby inducing transcription of antioxidant genes and thus
promoting tissue repairing process (Jaeschke, 2011).
Among ROS, superoxide anion (O2.-) and hydrogen
peroxide (H2O2) mostly capable of damaging biochemicalmolecules including nucleic acids and aminoacids.
However, the most damaging effect is the induction oflipid peroxidation. The cell membrane, composed ofpoly-unsaturated fatty acids, is a primary target forreactive oxygen attack leading to cell membrane damage(Ghiassi-Nejad et al., 2008). Our study revealed that
caffeine administration resulted in a significant
reduction of SOD in plasma and liver by both doses
variably which was accompanied with a significant
increase in lipid peroxidation product TBARS as
compared to the control group. This finding suggested
the elevated production of superoxide anion by caffeine
treatment in rats.
It is known that stress on rats dilates the endoplasmic
reticulum (ER), and that caffeine induces release of
calcium from the ER (Macer and Koch, 1988). Further
investigation of the effects of caffeine related to stressresponse will be useful. As indicated at the beginning of
the paper, the effects of caffeine on various body systems,
and overall health requires more clarification. Also
given the genetic diversity of all human populations,persons with particular genotypes (and epigenetic
patterns) may respond differently. This study may beparticularly important to those with a genetic
predisposition to liver damage, who will suffer morefrom the effects described in this paper. Will we apply
nutrigenomics to those who are contemplating different
forms of stimulants?
Also people in particular life stages, such as during
pregnancy may be particularly vulnerable. Prospective
observational studies have indicated that maternal
caffeine intake during pregnancy is associated with ahigher risk of excessive infant growth and overweight inchildhood. Studies such as these support the current
advice to reduce caffeine intake during pregnancy.
Increased level of oxidized protein is an indicator ofincreased oxidative stress. Oxidized protein productequivalent to chloramines-T increased significantly inplasma and liver after caffeine treatment indicatedincreased ROS production by both doses of the drug.
Catalase and glutathione, which protect body fromoxidative harm by reactive oxygen species, showedunchanged activity in caffeine treated groups whencompared with control value. Nitric oxide (NO), anothercomponent of reactive species, takes part in lipid
peroxidation. Role of NO in apoptic cell death ofneuronal cells was described by Taotao et al. The same
paper suggested that NO- induced apoptosis is partly
mediated by ROS. In our study, caffeine induced
significant increase in NO level in rat plasma and liver ascompared to control indicating hepatic cellular apoptosisor necrosis.
In response to liver inflammation, the pro-fibrotic
mediators are stimulated and initiate liver fibrogenesis(Cui et al., 2003; Galli et al., 2005). Sign of liver
inflammation,due
tosignificantly
increased
inflammatory mediators, detected by biochemical tests,
was supported by the histopathological assessment ofliver tissue. Typical hepatotoxic signs appeared inEubios Journal of Asian and International Bioethics 28 (July 2018)
histopathological study of caffeine treated rat liver tissue
as described in previous literature of Nabeshima et al.,2006 and Jin et al., 2013. Inflammatory cells wereaccumulated in the necrotized region and along the bileducts and blood vessels in liver of drug treated rats.
However, we could not identify the inflammatory cell
type in present study. Research suggested that immune
cell infiltration coupled with liver-resident kupffer cells,
contribute significantly to the development of liver
fibrosis. Investigation on mice with drug induced liver
injury revealed the involvement of monocytes in bothacute and chronic inflammation (Karlmark et al., 2009).
At the initial stage of fibrosis, macrophages derived frommonocytes release several cytokines which initiates
chronic inflammation through the activation of hepatic
stellate cells. The activated hepatic stellate cells,
proliferated and trans-differentiated into myofibroblasts
start to produce collagen (Imamura et al., 2005). In ourstudy, dose dependent collagen fibre deposition wasseen in Sirius red staining of rat liver. Progressive
deposition of collagen fibre supported the sustained
inflammatory cell damage of rat liver, treated withcaffeine.
Conclusions
As discussed in the introduction the effects ofcaffeine on human beings is complex. To our knowledge,
the cytotoxic effect of caffeine have been investigated as
combined therapy or using human cell line in vitro. In
our study, we have used pure caffeine alone in vivo tomonitor its cytotoxic effect on rat liver after long term
administration at high dose. In the present study,
inflammation and consequent fibrogenetic effect on liverby caffeine was uncovered. The possible mechanism
might be increased lipid peroxidation of hepatocytes andprotein oxidation by increased ROS (especially O2.) or
RNS (especially nitric oxide); consequent chronic
inflammation stimulated by damaged cells andprogressive collagen fibre deposition by myofibroblasts.
Additionally histochemical findings revealed theexistence of inflammation and fibrogenesis in liver.
However, in contrast with inflammatory response,
antioxidant enzyme catalase and glutathione activity
remain unchanged. Another enzyme superoxide
dismutase activity significantly decreased suggesting
abundance of superoxide ion as compared to otherreactive species. Further study on other molecularmechanisms might be conducted to clarify the process offibrogenesis mediated by caffeine.
There are significant ethical implications of this study
given the widespread use of caffeine in society. There isan urgent need to further studies to assess the effects oflifelong use, given that many persons start use of caffeine
at a young age. This is more than a significant publichealth issue, but also a question of social policy. How do
we assign risks to popular substances when the overall
health affects likely vary between individuals.
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Some beneficial effects on thephysical heath and academic
achievement of middle years
secondary school students
through studying environmental
ethics- Alexander Waller, Ph.D.
St Stephen’s International School, Khao Yai, Thailand Email:alexandera55@email.nu.ac.th

Abstract
Some of the results from a case study at a smallinternational school in Thailand indicate a possible
relationship between increased naturalistic intelligence,physical health and subsequent academic performance.
These rises follow the introduction of an Environmental
Ethics and Renewable Energy Education (EEREE)
programme into the curriculum for middle years
students. The health estimations are from Body Mass
Index (BMI) and records of students seeking medical
attention. The tools to assess naturalistic intelligence arestatistically validated and the results from subsequentInternational General Certificate of Secondary Education(IGSCE) are analysed. There is a suggestion for a possible
causal link, although this is not proven.
Key words: self-esteem, body mass index, bioethics,
environmental ethics, naturalistic intelligenceEubios Journal of Asian and International Bioethics 28 (July 2018)
Introduction
During the four academic years 2013/14 to 2016/17 a
one year Environmental Ethics and Renewable Energy
Education (EEREE) course was delivered to Year 10
students at St Stephen’s International School, Khao Yai(SISKY). It consisted of forty one hour lessons that were
included within the Personal Health and Social
Education Programme (PSHE) or within Science lessons,depending on the timetable allowances each year. The
course introduced the main ethical frameworks,
principles applied in ethical decision making as well as
introducing a range of socioeconomic topics related tosustainability, the science behind renewable energy
technologies and related environmental issues. A casestudy was conducted to determine the benefits ofstudying EEREE for the students and the wider schoolcommunity. The specific objectives were to determine if
there were changes in multiple intelligences and values
or attitudes towards sustainability. This paper refers
some data that emerged from searching for long term
benefits within the school that arose during the years ofthese trials.
In this case study two indicators of health were used.
Firstly, the Body Mass Index (BMI) of students wascalculated. Secondly, records of visits to the medical toseek medical attention were tallied for students fromeach academic year group. The BMI records wereavailable for six years prior to the introduction of the
EEREE course as well as the years 2013 to 2017 during
which the course was taught at SISKY. The log visitors to
the medical room was only available from 2013-14 until
2016-17, which were the years that the EEREE course
was delivered.
The hypothesis is that learning EEREE required thefrequent use and development of higher order thinking
skills such as analysis and evaluation. This induced anincrease in naturalistic intelligence. This increase of
intelligence lead to higher confidence and self-esteemthat in turn lead to measurable improvements inphysical health. Collectively these factors supported
students learning Sciences in general and Biology inparticular.
A brief review of some relevant literature
The third UN Sustainable Development Goal (SDG)1 is
specifically concerned with health and wellbeing; surely
there is little point in aiming for unsustainable
development without ensuring sustained or improved
good health. Therefore it is appropriate to consider
physical and mental health in the case study of the
impacts of studying EEREE on students’ attitudes
towards sustainability.
Following a survey of 757 adults in Australia, Kermodeand MacLean (2001) determined a positive correlation
between quality of life (QOL) and self-esteem, long term
stress lowered QOL as did illness. Although someresearchers such as Ross and Broh (2001) argue that selfesteem has little benefit on academic achievement, it isgenerally agreed that ideally students will grow in selfesteem. Booth and Gerard (2011) conducted a case study
in two Western schools that demonstrated a fall in selfesteem was directly related to subsequent poorer
academic performance. Trzesniewski et al (2006) foundthat low self-esteem in teenagers is a predictor of poor
1
listedontheUNwebsitehttp://www.un.org/sustainabledevelopment/sustainabledevelopment-goals/

113

health in later life. Von Hinke Kessler Scholder et al(2010) used genetic markers to check findings that
increased adipose tissue levels correlated with lower
academic achievement. They cite bullying, absenteeism,
sleep apnoea and ostracism by their peers as all being
contributing factors to these lower achievement levels.
Al Drees et al (2016) correlate higher levels of physicalactivity with higher academic performance in medical
students. Alswat et al (2107) found, in a survey of 424
students from 14 Saudi secondary schools, a correlation
between obesity and poor performance in Physics, but
not in their overall Grade Point Average (GPA) scores.
Oketayo et al (2010) that within a group of 110 Nigerian
Physics students there was a strong negative correlation
between BMI and academic performance. One of themost compelling studies is from Korea involving over 72
000 adolescents aged 12 - 18 years, which shows verystrong correlations between obesity and poor academic
performance (Kim and So, 2013).
Several studies also report no significant difference inachievement comparing individuals with different BMI
values (Wehigaldeniya et al, 2017; Fletcher and Lehrer,
2009; Kaestner and Grossman, 2009). In addition tothere being a possible link between BMI and academic
performance there are many other factors that do or
could influence achievement, such as socio-economic
background, parental education levels, regular quality
sleep, access to online learning support and resources,
travel times to and from school. This list is not
exhaustive, for example Wang et al (2017) found that theconsumption of nutrient fortified milk lead to increased
performance in mathematics, ethics and languages.
Methodology
The nursing staff at SISKY calculated the Body Mass
Index (BMI) of all students each year. The BMI iscalculated using:
BMI= mass (Kg) / height 2 (m)The BMI value is used an indicator of potential for ill
health related to body mass issues such being
chronically underweight, overweight or obesity. The
significance of the BMI value is dependent upon the age
and gender of the student as shown in Figures 1 and 2
below.2
Figures 1 and 2 show the World Health Organisation(WHO) BMI chart for boys (above) and girls (below) aged 5
to 19 years old. Interpretation: The numbers of thecoloured lines are standard deviations (SD) from themedian (50th percentile): >1SD is overweight (equivalent
to BMI 23.7 kg/m2 at 15 years for girls and 22.7 kg/m2 forboys of the same age), >2SD is Obesity <-2SD is thinness,and <-3SD is severe thinness. The number of students
with “healthy” BMI values within each academic year
group was calculated.
The number of visits to seek medical attention was
simply a tally of the recorded visits. These included thoseseeking genuine medical attention for physical problems
and visits from students seeking emotional support as
the nurses are often a first port-of-call for students
needing comfort.

2 These graphs of the percentiles related to BMI age and genderinterpretations are available from the WHO website at
http://www.who.int/growthref/who2007_bmi_for_age/en/

Eubios Journal of Asian and International Bioethics 28 (July 2018)

114

Figure 2: Graph for interpretation of girls BMI values
taken from WHO (2007)

Figure 1: Graph for interpretation of boys BMI values
taken from WHO (2007)

Table 1. Demography of SISKY students with BMI values within first quartile "healthy" showing the numbersof students below Year 10 as well as in Years 10 and 11.
Number of students who are neither overweight, obese, underweight or at risk
Y10

29

NO on roll
< Y10
56

Y11

9

NO on rollin Y10
12

11

NO on rollin Y11
16

Total SISKY
NO on roll
84

29

61

5

7

10

12

80

41

64

5

8

5

8

80

47

73

10

11

2

3

87

64

101

5

6

4

5

112

60

85

16

18

5

7

110

75

119

3

4

18

141

86

138

8

9

16
N/A

0

147

93

142

9

10

N/A

< Y10

Naturalistic intelligence was assessed using a pre-test
post-test assessment tool based on that developed by
Tirri and Nokelainen (2008). It was also assessed using a
64 item Multiple Intelligence Diagnostic Assessment
Scale (MIDAS) questionnaire. Both the naturalistic
intelligence tool and the MIDAS tool were trialed on acontrol group to determine the repeatability of these
instruments.
The academic progress of the students from the 20132014 cohort of the EEREE course was also tracked totheir performance in subsequent internationallystandardized examinations that are certified by the
Cambridge International Examination (CIE) board. The
performance of this cohort is compared to previous theperformances of previous examination cohorts at SISKY.
Results
1. Health related
The results of the BMI calculations for all students at
SISKY from 2008 until 2017 are summarized in Table 1.

There isaclear
trend in0152
the BMIdata that older students in Y10 and Y11 have historically(since 2008) tended to have healthier BMI values than
younger students at SISKY. There is no significant change
to this pattern in the years 2013-2014 onwards.
The demography of the school changes during thetimescale of this data, partly due to growth in numbers
on roll of younger students. However it was also due to anumber of older students leaving the school before
completing Y11, to complete secondary education atother institutions.
Prior to 2013-2014 in the years 2008 to 2013 thepercentage of Y10 who were within the first quartile of
the BMI was 77%. Following the introduction of the
EEREE course in 2013-2014 the percentage of Y10 in theyears 2014 – 2017 within the first quartile of BMI scoresis 88%. This indicates a small rise in health in Year 10
compared to former years, as measured by BMI.
The Y11 cohort in 2014 -2015 were the first students
to have completed the EEREE and maintained theirpercentage of 89% being within the first quartile of BMI
values. The percentage of Y11 prior to 2015-2016 in Year
11 in this healthy range of BMI is only 73%. Therefore,
these data indicate that not only did Year 10 EEREE
students have become more “healthy” they also
maintained these healthy BMI values for the year
following the EEREE course. A possible, and lasting,Eubios Journal of Asian and International Bioethics 28 (July 2018)
relationship between studying EEREE and physicalhealth, however does not prove a causal relationship, but
a pattern can be seen.
To summarise this data Table 2 contains acomparative tally of all senior students at SISKY before
and after the introduction of the EEREE course to Year
10 students in 2013-14. This data generates a PearsonChi Squared value of 4.064 with one degree of freedom
and p 0.044 which demonstrates a statisticallysignificant association at the 95% confidence limit, using
Minitab Pearson Chi Squared test.
Table 2: The tallies of senior SISKY students healthy andunhealthy BMI values with expected values for PearsonChi Squared test in parentheses.
Combined
Combined
number of
number of
Academic Years
students
students
with
since
with
Total
healthy BMI
2008/2009 tounhealthyin Y102016/17
BMI in Y10
and Y11and Y11
Prior to EEREE
course71 (75.88)

24(19.12)

95

Post first EEREE
course52 (47.12)

7 (11.88)

59

123

31

154

Total

students on roll has increased. It also shows thatstudents below Year 10 tend to require more attention
than more senior students. On closer study the data also
shows that for the academic years, 2013-14, 2015-16 and2016-17, Y10 (EEREE) students (n= 37) made relatively
less visits to the medical room than the students who
were younger than them. For these three years of thetrial collectively Year 10 made up 9.7% of the schoolcommunity and yet Y10 constituted only 6.6% of thevisits to the medical room. This trend was also true andshowed a further improvement for the 2014-15 Y11(former SISKY (2013) EEREE) students (n=18) who
represented 12.8% of the school population but wererecorded as being 5.3% of the population seeking medical
assistance. However, the Y11 students (n= 7) in013-14 had
not studied the EEREE course. They represented 6.4% of
the school population and also made 6.4% of the visits tothe medical room.
Multiple Intelligence assessments
The mean average values for the naturalistic
sensitivity and MIDAS test in Table 4 provide a baseline
value against which the test groups can be measured.
The results of the Wilcoxon Signed Rank (WSR) statisticalanalysis for non-parametric data are shown in Table 5
Table 4 Control group Pre-test Post-test data
mean
sd
EnvS
MIDAS

Table 3. Number of visits to medical room by students
below Year 10 as well as students in Years 10 and 11
2013 20142014 2015

2015 20162016 2017

total visits

1295

1293

1232

1042

No visits by <Y10

1090

1180

1171

988

No visits by Y10

122

44

61

54

No visits by Y11% visits by < Y10

83
84.2

69
91.3

0
95.0

0
94.8

% visits by Y10

9.4

3.4

5.0

5.2

% visits by Y11

6.4

5.3

0.0

0.0

Total no on roll

110

141

147

152

No on roll <Y10

85

119

138

142

No in Y10

18

4

9

10

No in Y11
% on roll < Y10

7
77.3

18
84.4

0
93.9

0
93.4

% on roll = Y10

16.4

2.8

6.1

6.6

% on roll = Y11

6.4

12.8

0.0

0.0

The records for visits to the medical room were tallied
and then calculated as ratios of visits per year group. The
data was only available from 2013-14 until 2016-17. It issummarized in Table 3. The data in Table 3 shows thatthe total number of visits to seek medical attention has
decreased in recent years even though the number of

115

Pre-test

3.1

0.54

Post-test

3.3

0.44

Pre-test

3.4

0.30

Post-test

3.4

0.35

The WSR analysis of the environmental sensitivity and
MIDAS assessment of the control group in Table 5 bothgive P values that are greater than 0.05 so it can beconcluded that there are no significant differences
between the pre-test and post-test scores in the control
group. This demonstrates the repeatability of theseassessment tools.
Having established the validity of the assessment tools
the results of the pre-test post-test data from the test
groups could now be collated from all students who havecompleted the EEREE course in the years since 2013.
In Table 6 it can be seen that there is a rise in the posttest results for both environmental sensitivity and
MIDAS scores compared to the pre-test mean averagevalues. To determine the statistical validity of theseresults WSR test was employed. The results of this are in
Table 7.
The results of the WSR analysis in Table 7 show thatthe environmental sensitivity test showed a significant
increase at the 95% confidence level as the P value
generated by the WSR analysis is less than 0.05. The WSR
analysis of the pooled MIDAS test results shows that therise indicated are not statistically significant at the 95%
confidence level. However, it must be remembered that
this MIDAS score is the mean average score of the ratings
for all eight intelligence dimensions. Therefore, a closer
analysis of the changes of the naturalistic intelligence inthe test groups at SISKY have been summarized in Table
8 and the results of the WSR analyses are presented inTable 9.

Eubios Journal of Asian and International Bioethics 28 (July 2018)

116

Table 5. Results of WSR statistical analyses of environmental sensitivity (EnvS) and MIDAS control group pre-test and posttest data from non EEREE students at SISKY (2013)
number in group
number of differences W value
P value
median of differences
EnvS
14
9
36
0.062
0.1500
MIDAS
14
12
36
0.608
0.0000
Table 6. Collated Pre-test and Post test Environmental sensitivity and MIDAS data from SISKY (2013-2016) (n=41)
EnvS
Pre

Post

MIDAS
Pre

Post

mean

3.2

3.4

3.7

3.8

Sd

0.41

0.37

0.93

0.83

Table 7. Results of WSR statistical analyses of environmental sensitivity and MIDAS testing at SISKY (2013-2016) pre-test
and post-test EEREE students (n=41)
number in group
number of differences W value
P value
median of differences
EnvS
41
36
511.5
0.003
0.1500
MIDAS
41
39
442.5
0.234
0.1250
Table 8 SISKY (2013 - 2016) Changes in Interpersonal, Intrapersonal and Naturalistic Intelligences pre-test post-test means
and standard deviations
Multiple intelligence Dimension

Pre -test
mean average

Naturalistic MI 8

2.9

Post-test
standard deviation

mean average

1.55

standard deviation

3.8

1.41

Table 9 Results of WSR statistical analyses MI 6, MI7, and MI8 domains of MIDAS at SISKY (2013-2016) pre-test and posttest EEREE students (n=41)
MultipleIntelligence
MI 8number in group41

number of differences
31

MIDAS test consisted of eight items for each of theeight intelligences The EEREE course did not include any
opportunities for students to develop musicalintelligence, and few opportunities to exercise bodilykinesthetic intelligence. So the inclusion of these in theanalysis in Table 7 partly explains why the increase in
MIDAS scores between 2013-16 is not significant.
The naturalistic dimension of MI in Table 8 shows arise in the mean averages between the pre-test and posttest scores. Therefore the data in Table 8 has been
analysed using WSR test to determine if the changes in
Naturalistic Intelligence were statistically significant. The
results of that analysis are in Table 9.
The data in Table 9 shows that P values of less than
0.05 that were generated for naturalistic (MI 8)
intelligence does show a significant difference, at the 95%
confidence level, between the pre-test and post-testscores for the aggregated students following the EEREE
course at SISKY between 2013 and 2016.
The statistically tested assessments showed no
improvement in the control group pre-test post-testscores. But there were improvements in both the MI 8score of the MIDAS tests and using the environmental
sensitivity questionnaire. The use of these two separate
instruments provides sound evidence that students who
followed the EEREE course increased their naturalistic

W value

P value

median of differences

411

0.001

1.0000intelligence whereas students in the control group did
not.
Trends in IGCSE examinations at SISKY
Table 10. SISKY yearly mean average standardized IGCSE
scores in all subjects from 2011 – 2015Year
numberYear

Totalnumber of
examination
entries

Mean
Percentage
score for all
subjects

Mean
Percentage
score forsciences

2011

1

73

67.0

56.4

2012

2

58

72.6

65.1

2013

3

27

63.1

41.5

2014

4

42

59.5

58.2

5
139
61.6
63.0
An additional source of evidence to demonstratemeasurable changes in intelligence, knowledge andproblem solving is the analysis of results fromexaminations. At SISKY the students complete IGCSE
tests from CIE.
The data in Table 10 shows that the sciences
consistently scored a lower percentage on average,
compared the average score of all subjects combined for2015

Eubios Journal of Asian and International Bioethics 28 (July 2018)
each of the four years prior to the former 2013-14
EEREE students taking their IGCSE exams in June 2015.
This trend is verified in two ways.
Firstly, the students in each Year 9 cohort hadcompleted Cognitive Ability Test (CAT) assessments thatwere used as a predictor for their future performance in
IGCSEs examinations that followed two years later. The
IGCSEs are reported by CIE both as standardized
percentage scores and grades G –A*. The lowest grade, G,
given a score of 1 point and an A* is worth 8 points. Table
11 shows that there has been a general upward trend in
the value added from the CAT prediction to the actual
IGCSE grades obtained in the period 2011 – 2015. The
numbers of students sitting examinations in Year 11 hasvaried substantially and this may have caused a bump in
the trend in 2013. The students who participated in the2013 EEREE course took their IGCSE examinations in2015 and out-performed any previous cohort bysignificantly exceeding their expected outcomes showing
noticeable value added. Secondly, the trend inunderperformance in the sciences goes back evenfurther historically. In the years prior to 2011 the CIE
results of IGSCE examinations were not accessible aspercentage marks but as grades within set boundaries.
Also CAT data from that period was not available fromSISKY, so it was not possible to assess value added
during the years before 2010. However, in a comparisonby the residual analysis of the SISKY IGCSE results in the
period 2004 to 2010 do show that the combined science
results were consistently below the averaged results ofother subjects3.

Figure 3. SISKY 2015 core subject IGCSE residual scores.
Residual Value (Y axis) versus Subject Residentials
The results for the science can consistently be seen to
be noticeably lower than most if not all other subjects.
These residuals for each subject are calculated bysubtracting the mean of all IGCSE results for a cohort ofstudents from the mean grade of the results for the samecohort of students in that given subject. It is a simple but
useful technique to compare a group of students’performances in different subject relative to othersubjects. The IGSCE residual results for the core subjects
taken in at SISKY in 2015 from the students who
followed the 2013 EEREE course are shown in Figure 3.
It is clear that although Physics results are still
marginally below average, the overall science residuals
are considerably improved on the former years. They
also show significantly higher positive values for Biology,
which again links to the rise in MI 8 shown in table 8. The
significantly higher value for Biology will have made a
3 These data presented in graphs similar to Figure 3 from 2004
onwards are available upon request.

117

significant contribution towards the average percentage
scores in table 5 and towards the value added scores
given in table 6.
Table 11. SISKY Value added for IGCSEs
Number of Y11 valueYearcandidates
factor
2011
8
0.90
2012

6

0.95

2013

3

1.19

2014

4

1.06

2015

18

1.24

added

Discussion
Collectively the two sources of medical data, BMI
records and a log of students seeking medical attention,
show that there is a slight and lasting improvement ingeneral health and wellbeing of more senior students at
SISKY. Based on these criteria there has been a greater
improvement in recent years that happened since theinclusion of EEREE into the curriculum for those senior
students.
There is a strong link to show that improvements wereobserved in naturalistic intelligence. These increases
were shown to be statistically significant when assessedusing two different assessment tools. The inclusion ofmany evaluation exercises throughout the EEREE course
ensured students exercised and developed higher order
thinking skills. The benefit to their academic
achievements was determined through the comparisonof IGCSE results from former years with those of EEREE
students, the value added to IGCSE data relative to CAT
score predictors and the residual values when Science
subjects were compared to other subjects.
Collectively this is an indicator that students at SISKY,
since the introduction of the EEREE course, were indeed
living healthier and becoming more successful
academically. As education and health are both integral
for sustainability it may be argued therefore thatstudents ate SISKY who studied EEREE were able tofollow more sustainable lifestyles compared to students
in the same classes in former years.
Recommendations for further research
The benefits to health from studying EEREE require
greater verification. Both in terms of a longitudinal study
and through the use of a wider number of indicatorssuch as blood pressure, blood cholesterol levels andheart rate recovery times. There also is a need todetermine whether the students were consciously awareof having an increase in self-confidence or self-esteem.
Other activities such as participation in public speaking
events, analysis of diaries or records of participation in
extracurricular activities from school social media
records may prove useful sources of data for
determining this.
As for the mechanism that caused the greater increasein naturalistic intelligence and subsequent examination
grades it could be possible to analyse past examination
papers and determine which skills the students had
performed better than in former years or against theinternational examination cohort for that year as awhole.

118

Eubios Journal of Asian and International Bioethics 28 (July 2018)

Finally a longer term study into the potential healthbenefits of learning bioethics would also be of greatvalue. This longer term study could be achieved throughfollow-up of students form previous years and fromother comparable studies around the world in otherinstitutions.
Implications
From this small case study it does suggest that there
are measurable benefits to physical health and academic
achievement. The EEREE course sits well within
secondary PSHE curriculum and this could be an option
for other schools to include into their programmes ofstudy. If further research does verify that there arelasting impacts on health and wellbeing then an
economic argument for the inclusion of EEREE would
also be possible.
Acknowledgements
Thank you to Mr David Aitchison for permission to
conduct this research, to Mr Alwyn Chacko for assistancewith statistical analyses, to Ms Sutharat Suksangthongfor checking and counting through thousands of medicalroom log entries and to the nursing staff at St Stephen’sInternational School, Khao Yai.
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Stem Cell Tourism: Addressing the
Challenge of Regulatory
Cosmopolitanism- Patrick Foong, J.D.
Faculty of Law, Western Sydney University, Australia
Email: pckfoong@gmail.com
Abstract
Stem cell tourism is a serious worldwide problem.
This is where acute patients, especially the very ill, wholive in countries where stem-cell-based medical
treatments are not available, travel to other countries toseek such therapies. There have been reports of baselessclaims of cures, charlatans and adverse medical events
including deaths. These treatments are at theexperimental stage, and most are unregulated. Some of
the clinics offering these therapies are even supported bytheir local government, regulatory agencies and medical
associations. Stem cell tourism is vital to the economies ofsome developing countries, which may thus be resistantto prohibitions by law.
This article evaluates measures, legal as well as nonlegal, to control and mitigate it. Different countries havedifferent notions of right and wrong, and statesovereignty dictates that no state can enforce its laws on
another. In the international community, a nation cannot
enforce its laws on other nations. It is a challenge if aregulatory approach of a country attempts to dictate local
standards to another state, that is, where it seeks tosteamroller over local culture and difference. Stem cell
tourism is a prudential calculation for the individual and,
importantly, the state has a moral obligation to inform its
citizens of the potential risks of receiving experimental
and unregulated stem cell-based treatment in overseas.
Also, the ISSCR guidelines could raise awarenesseffectively of these critical issues in the international
community. While stem cell tourism is a challenging area
and appears to be irresolvable, local regulators still needto set up an effective national regulatory framework forregulating untested stem cell therapies within the
country.
Keywords: Ethics, law, stem cell tourism, guidelines
Introduction
Stem cell therapy is a treatment that uses stem cells
to replace or repair a patient’s cells or tissues that aredamaged. There are patients, primarily the very ill andEubios Journal of Asian and International Bioethics 28 (July 2018)
desperate, who will seek out unproven stem cell-based
medical procedures and are also prepared to travel
overseas to obtain these so-called treatments (known asstem cell tourism). There have been reports of claims of
miracle cures, charlatans and adverse medical events
including deaths (Kiatpongsan and Sipp 2009). The
challenge of regulatory cosmopolitanism is the problem
of regulating untested stem cell-based medical
treatments available in some countries, in bothdeveloped and developing countries.
Stem cell tourism is vital to the economies of somecountries, especially the developing ones, which may beresistant to prohibitions by law. Also, different countries
have differing notions of right and wrong, and statesovereignty dictates that no state can enforce its laws on
another. It is a challenge if a regulatory approach of anation attempts to dictate local standards to anothercountry, that is, where ‘it seeks to steamroller over local
culture and difference’ (Brownsword 2008).
In this article, I will explore the various ways, legal aswell as non-legal, to address the problem. The first partof the paper draws on the work of Professor Roger
Brownsword (from Kings College London), a bioethicist
and a leading scholar on issues of technology, ethics andlaw. He recognises the need for the exploration of thesocial, legal, ethical and regulatory matters arising fromthe emergence of modern technologies and he has
written extensively on these challenges.4 This is followedby an evaluation of the updated Guidelines for theClinical Translation of Stem Cells (ISSCR Guidelines). The
last part of the article explores the non-legal ways toaddress this severe problem of stem cell tourism.
Experimental and not established stem cell
treatments
Many medical discoveries are based on years, even
decades (Main 2014), of research conducted by research
institutes, universities and private companies (ISSCR
patient handbook 2008). It requires a tedious, expensive
and lengthy process that progresses from basic research
to clinical research and then phase 1,2 and 3 trials. Like
the development of a new drug, stem cell therapies mustbe evaluated and fulfil stringent criteria before receiving
the approval from the regulatory bodies to be used totreat humans. An accepted medical treatment is peerreviewed, its safety proven through large-scale clinical
trials and is regulated by government regulatory bodies.
The clinical translation of cell therapy, especially
stem-cell based interventions, is still in the embryonicstage (Kimmelman 2016). Presently, almost all stem celltherapies are experimental/ investigational andinnovative. The current spectrum of diseases and

4 Professor Roger Brownsword is a founding member of theCentre for Technology, Ethics, Law and Society (TELOS) at the
Dickson Poon School which aims to engage in policy-relevant
research examining the ethical, social and legal implications ofinnovative technologies. The interview was held on 18
November 2009 in his office in the law faculty, Kings College
London. Brownsword has been associated with the UK’s Houseof Commons Science and Technology Committee. This
committee’s role is to ensure that the UK Government policy
and decision-making are based on good scientific andengineering advice and evidence.

119

conditions from which there are established treatments
based on stem cells is minimal (Australian stem cell
handbook 2015). Disorders of the blood and immune
system and loss of bone marrow function could betreated with blood stem cell transplantation. While stem
cell research holds the promise for the treatment of abroad range of illnesses, there is still much work
necessary to translate this research into safe andeffective therapies. In the early stages, these treatments
may not be effective and worse; they may even cause
adverse effects. Accordingly, it is critical for patients, andtheir caregivers to know what to look out for andconsider before making a firm decision whether to opt
for a stem cell therapy.
Not only many stem cell-based treatments areexperimental, but they are also not stringently regulated.
With regulatory loophole and weak law enforcement, thepressing concern is that stem cell treatments are
currently being advertised and sold around the world
before they have been proven safe and effective. Stemcell clinics are a global phenomenon and patients went
to hospitals in China, with Mexico, Germany, theDominican Republic, and India the next most common
destinations (Stem Cell Therapies 2014). Some patientsare prepared to travel overseas and pay a high price toseek these medical treatments. Private clinics/
companies offering these services advertise theprocedures on websites, YouTube and blogs. Some ofthese clinics are even supported by their government,
regulatory bodies and medical associations and thus
remain in business (Kiatpongsan and Sipp 2009).
There was a research conducted by Timothy Caulfield(University of Alberta, Canada) where he and his teamanalysed websites advertising so-called stem celltherapies (Lau 2008). The study noted that these directadvertisements made to patients on a plethora of sites
were easily and readily accessible. It found that stemcell-based treatments were offered by privately operated
clinics around the world including China, Turkey andUkraine. The average expenses amounted to US$21,500
excluding travel and accommodation for patients andtheir carers. The authors assessed whether the claims
made on the websites were substantiated by reports
published in the medical literature and found that mostoftheseclinics
overpromised
results
andunderestimated the potential risks of the medical
treatments they offered. A follow-up study found that themarketing practices remain unchanged (Ogbogu 2013).
The common conditions being treated include
paralysis, multiple sclerosis, cerebral palsy, visual
disorders/ blindness, and brain injuries (Stem Cell
Therapies 2014). As there are no registries in which data
are compiled, it is not possible to ascertain the numberof patients who are receiving stem cell therapies, and it
is also a challenge to determine the home countries ofthese patients. Moreover, there are clinics that offer
treatments for an extensive array of illnesses andconditions (Lee 2012).
These stem cell clinics are providing these medical
treatments in nations by exploiting their regulatory
loopholes. The various types of harm that resulted topatients subsequent to receiving the treatments included
brain tumour growth (Amariglio 2009), autoimmune
disease (Bohgaki 2008), meningitis (Mendpara 2002)

120

Eubios Journal of Asian and International Bioethics 28 (July 2018)

and deaths (Coghan 2010, Tenenbaum 2014). A patient
had bone fragments growing in her right eye after acosmetic stem cell treatment in Beverly Hills threemonths earlier (Jabr 2012). Moreover, there is economic
harm with a therapy costing between US$20,000 and
US$50,000, which excludes travel (National Academies2014). As regards the lack of efficacy, a patient sufferingfrom urinary incontinence sued the hospitaladministrator as the treatment did not improve his
symptoms (Abbott 2008).
Patients are motivated to seek treatments at theseclinics since they believe they have no choice (Stem Cell
Therapies 2014). For acute patients, they cannot afford
to wait for stem cell treatments to be formallyauthorised through the slow conventional processes.
They feel desperate, frustrated and victimised by thesystem. Whereas clinics abroad connect with thepatients by providing some hope and offer the patientssome control over their lives so they can choose themedical treatments they desperately need. Patients
leapfrog their doctors and go directly to the therapy.
As Alta Charo said, ‘Patients are potentially being
exposed to treatments that are not proven, notapproved, not regulated and possibly dangerous’ (StemCell Therapies 2014). This issue is becoming even more
problematic as untested stem cell therapies are
becoming more commonplace in this globalised andconnected flat world with speedy internet access andeasy travel. The provision of such so-called ‘therapy’ isscientifically and clinically unacceptable as well as
unethical. The harms caused to patients have eroded
public confidence and undermined the legitimacy of thestem cell field. In the next sections, I will consider thevarious possible ways to address the problem of stem
cell tourism. I will begin by exploring Professor Roger
Brownsword’s insights on the challenge of regulatory
cosmopolitanism.
Addressing stem cell tourism: Brownsword’s
regulatory cosmopolitanism
The problem of regulatory cosmopolitanism is that
regulation confined within national boundaries cannot
be entirely effective in controlling stem cell tourism.
Stem cell tourism is a complicated issue, but there areways, legal and non-legal, to manage and mitigate it.
Professor Roger Brownsword introduces the conceptof regulatory prudence. He stresses that one of theconcerns with new technologies is whether they are safe.
While he concedes there are risks associated with newtechnologies, the risks are borne only by the person(s)who elects to use the technology. He, therefore, argues
that regulators prudently ought to leave that decision to
the individual concerned. He gives the example of thevarious screenings currently available, “If you submit toscreening, it can be risky particularly if there are matters
you’d rather not know. So long as the risk is only to you
and the benefit is only to you, it seems to be only amatter of personal prudential judgment; so regulatorsneed to hand it back to the individual. But where there
are risks to the third party, the regulators need to set a
regulatory framework”. He argues that with stem cell
tourism, regulators need to leave the decision to theindividual patient. He explains, “what can we do otherthan alert people to the risk of taking this stand? Unless

we can actually stop people at the airport- somethingthat we would not do. We rely on there being local
control in places where these experimental treatments
are being offered ... that local control is only going to be
put in place where there is some external pressure, someoverarching control. The stem cell community can exert
some external pressure. They could try to isolate thosecountries which are not properly regulated. In the end,
people need to be informed with the question: “should I
take the risk with this?”
Brownsword stresses the importance of the moral
obligation of the state to inform its patients of the risks
associated with the stem–cell-based treatments. He
explains, “it’s a judgment of what I prefer to do to myself:
the calculation of risk and benefit. Regulators should
hand the decision back to the individual provided these
individuals are properly informed ... in the end, people
need to be properly informed. In the individualised
prudential calculation, for desperate people, it’s a matterof life and death. They are going to use up part of theirsavings; they are going to die, so there’s no good to themoney. This is provided they are informed of the risks”.
Whether ill patients at the airport can be prevented
from departing the country, Brownsword opines that it
is not practical in stopping people from leaving thecountry. Similarly, with suing/ prosecuting the overseas
doctor who administers the medical treatment, he says
there are also practical difficulties in pursuing thatcourse of action. Besides these challenges, resorting to
the traditional law such as tort law and consumer law isreactive, and there are also evidentiary issues.
About the possibility of prosecution of a person who
returns home after receiving medical treatment that is
not legal in his/her country, Brownsword explains thatthe current UK prosecution guidelines do not favour theprosecution of terminally ill patients. He adds that even
if there is a prosecution, there will be sympathy from thejurors. He continues, “Where regulators are making a
prudential calculation, there is prudential pluralism ...
different people have very different ideas about thebalance of benefits and risks. Regulators sometimes haveto make a collective decision”.
Brownsword is of the view that it is a challenge toregulate stem cell tourism and it is ultimately aprudential calculation for the individual patient. The
next section will critically analyse the comprehensive
and aspirational ISSCR guidelines to determine whether
it could resolve some if not all of the issues surrounding
stem cell tourism.
Addressing stem cell tourism: the Guidelines for theClinical Translation of Stem Cells 2016 (ISSCR
Guidelines)
Recognising the risks to health and welfare posed bystem cell tourism, the scientific community and advocacy
groups have begun to respond to the problem byformulating guidelines for doctors and scientists
engaged in the clinical translation of stem cell research.
The International Society for Stem Cells Research(ISSCR) developed the Guidelines for the ClinicalTranslation of Stem Cells (ISSCR Guidelines) in 2008,
updated in 2016. The ISSCR is an independent, nonprofit organisation established in 2002 to foster theexchange of information on stem cell research. It is theEubios Journal of Asian and International Bioethics 28 (July 2018)
world’s largest international professional organisation
engaged with stem cell science.
The 2016 ISSCR guidelines were prepared by the
ISSCR Guidelines Updates Task Force, a multidisciplinarygroup of 25 scientists, ethicists and regulatory officials
from nine countries. It is noted that most of thesenations are developed countries. Before the guidelines
were finalised and published, there was feedback
received on the drafts from more than 100 individuals
and organisations including regulators, funding bodies,journal editors, patient advocates, researchers andmember of the public.
The ISSCR’s objective is to provide guidance on theproper and responsible translation of stem cell research
into safe and appropriate applications. The guidelines
build on a set of widely shared ethical principles inscience, research with human subjects, and medicine
such as the Nuremberg Code, 1949, Department of
Health, and Education and Welfare, 1979, European
Science Foundation, 2000, Medical Professionalism
Project, 2002, Institute of Medicine, 2009 and the World
Medical Association, 2013.
By way of recommendations to institutions, review
committees and investigators, best practice standards tobe observed in preclinical translational applications ofstem cell technology are established. These ISSCR
Guidelines provide comprehensive guidance for the
future development of responsible stem cell therapies
from research to clinic. In the following sections, thevarious recommendations in the guidelines that deal
with the problem of stem cell tourism are explored.
Addressing stem cell tourism: Fundamental ethicalprinciples of ISSCR guidelines
Core ethical tenets of the ISSCR guidelines, found insection 1, include primacy of patient welfare, respect for
research subjects and transparency. The guidelines
promote an efficient and sustainable research enterprisefor stem cell research and medical interventions that will
enhance human health. The main objective of biomedical
research and its clinical translation is to prevent, reduceor even eliminate the human suffering caused by injury
and sickness. Accordingly, it is essential that patients
participate in clinical research trusting that the studies
are justified and risks are reasonable in relation to thebenefits. Also, doctors can be sure that the evidence they
rely on to make vital decisions is concrete and rigorous.
Doctors, and doctor-researchers, owe a duty of careto the patient/ research subject, and they must not place
their patients at risk. Application of stem cell-based
interventions should be evidence-based and subject toindependent expert review. Promising novel methods
should be assessed early and before use to larger
populations. To advertise and offer stem cell-based
interventions to a large patient population prior toreceiving rigorous and independent expert review ofsafety and efficacy tantamounts to breach of professional
ethics. Also, patients/ research participants should
provide informed consent to researchers, clinicians, andclinics. Accurate and comprehensive information about
the risks and the state of evidence for stem cell-based
interventions should be submitted to the subjects before
treatment is offered to them. Moreover, researchers
should promote open and timely sharing of ideas,

121

methods, data, and materials on the latest scientific stateof the art including uncertainties about the safety,
reliability or efficacy of the potential applications. There
should be prompt communication with the groups
including the patient communities.
Addressing stem cell tourism in ISSCR guidelines:
Well designed clinical trials
Like testing new drugs and innovative clinicaldevices, clinical trials/ interventional studies/ clinicalresearch interventions are crucial in translating cellbased treatments. A clinical trial is a type of researchstudy using human subjects to assess biomedical or
health-related outcomes. The clinical trials process isparticularly relevant for the development of stem-celltherapies. This rigorous process will determine its
efficacy and safety/ lack of serious side-effects.
The private clinics providing unproven stem cell
treatments leapfrog this vital stage of conducting clinical
trials. The ISSCR condemns the administration of
unproven stem cell based-interventions outside of thecontext of clinical research or medical innovation (forthe discussion of medical innovation, see next section).
Given the importance of clinical trials, the ISSCR
guidelines recommend standards as discussed below.
Well designed clinical trials of stem cell-based
intervention will safeguard the welfare of the patients/
research subjects, show respect to them and ensuretransparency. Properly and adequately developed trials
will incorporate essential matters like the provision ofconsent including informed consent, adverse event
reporting and monitoring of the patient. Members of theresearch community have the moral responsibility forpromoting the ethical conduct of clinical trials including
sponsors, investigators, host institutions, oversightbodies, and regulators.
Essential requirements in these clinical trials include
having adequate pre-clinical data, informed consent,
independent oversight, peer review, research subject
monitoring, auditing of study, and trial registration andreporting. Clinical trials of stem cell-based interventions
should follow universally recognised principles on
ethical conduct of clinical research and the safeguard ofresearch subjects (World Medical Association, 1964,
Department of Health, and Education and Welfare, 1979;
European Parliament and Council of the European
Union, 2001). These steps are examined below, startingwith measures that will safeguard the patient’s welfare
and also show respect to the patient in a clinical trial
setting.
First, there must be an identification of risks andbenefits. With reference to recommendation 3.3.2.2,‘risks should be identified and minimised, unknown risks
acknowledged, and potential benefits to subjects/ andsociety estimated. Studies must anticipate a favourable
balance of risks and benefits.’ The potential benefits to
the research subjects must be realistically delineatedand not overemphasised. Studies should be done toensure there is maximum data on the safety of theapproach being tested. A well-designed clinical trial
includes measures that reduce risks and recruit thesmallest number of research subjects. The eligibility
criteria should consider comorbidities that may
increase the risk or change the risk/benefit ratio.

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Next, rigorous informed consent must be provided by
the patient/ research subject participating in the clinical
trial. This is an essential and established aspect of the
ethical conduct of clinical research. Its goal is to protect
the patients as this process ensures they make an
informed decision to participate, entirely out of their free
will and they are not pressured to participate in theclinical trial. Recommendation 3.3.2.6 provides that
informed consent should be given by the researchsubjects or by their legally authorised representatives.
During the informed consent process, the subjects
should be informed that their participation in the trial isentirely voluntary. They should be provided with awritten document (reviewed and approved by thereview board) containing all vital information, e.g. therisks and potential benefits of the study, in clear andeasy to understand language about the study. Moreover,it should be emphasised to the subjects that their
participation is not needed for their continued clinicalcare, and also their non-participation will not affect their
ongoing clinical care. These steps will ensure that the
subjects are not under duress and their consent to be
involved in the clinical trial, based on full information
communicated to them, is genuine.
The ability to provide consent by the patient/research subject should be assessed carefully. Very sick/acute patients’ judgments could be impaired and thus
there is diminished capacity. Also, there are young
patients (below 18). Just because these people who lacksuch ability to provide consent are vulnerable does notmean they should not be excluded from potential
biomedical advances involving stem cells. According torecommendation 3.3.2.7, before obtaining permission
from subjects who have diseases or conditions that could
affect their cognition, their capacity to give permission
should be evaluated. Appropriate steps should be taken
to get the consent from their guardians or surrogates tomake judgments on the patient’s behalf.
Recommendation 3.3.2.6 provides that re-consent of
the research subjects is necessary if there are significant
changes in risks or benefits of a study intervention and if
alternative therapies arise over the course of theresearch. Furthermore, the subjects should be allowed tochange their minds and withdraw their consent toparticipate in clinical trials without penalty.
It is essential to conduct follow-up and trial
monitoring of the patient/ research subject of the clinical
trial. Recommendation 3.3.5.1 of the guidelines provides
that ‘an independent data-monitoring plan is requiredfor clinical studies. When deemed appropriate, aggregate
updates should be provided at predetermined times oron demand. Such updates should include adverse event
reporting and ongoing statistical analyses if appropriate.
Data monitoring personnel and committees should be
independent of the research team.’ Recommendation
3.3.5.2 of the guidelines provides for long-term follow-up
of the patient/ research subject.
Stem cell-based intervention clinical trials arecharacterised by dynamic developing science anduncertainties. Thus, it is essential that the patients/
research subjects are observed throughout the stem cellbased clinical trials. Over the course of clinical research,
the risk/ benefit balance may change. Long-term followup of the subject serves an essential purpose. It enables

the researcher to observe the emergence of late adverse
events. If the patient/ research subject wishes towithdraw from the research, this should be conducted in
an appropriate manner to promote his/ her physical andpsychological welfare. As performing long-termmonitoring may be challenging, it is vital for researchers
to maintain contact with the research subjects. They
could adopt mechanisms that facilitate long-term followup.
Adverse event reporting of the patient/ researchsubject is essential. As discussed earlier, there arepatients who have reported suffering from adverse
medical effects after receiving the untested stem cellbased-treatments, some severe (e.g. deaths or lifethreatening conditions), others less (e.g. side effects).
According to recommendation 3.3.7.2 of the guidelines,
adverse events should be reported. The report should
include the severity of the event and the causal
connection with the experimental stem cell intervention.
Adverse events associated with cells, procedures, and allother aspects of the intervention should be reported.
Moreover, the absence of severe or fatal adverse eventsshould be stated in the report. Understanding the safety
profile of these interventions is critical for effective
translation. Timely evaluation of safety information canminimise the uncertainties surrounding stem cell-based
interventions.
A well-designed clinical trial promotes transparency.
As provided in recommendation 3.3.7.3, researchers
should promptly publish results of their research. This isirrespective of whether the results are positive, negative
or inconclusive. Studies should be released in full, timely,
accurate and should follow the international reporting
guidelines. To ensure the development of clinicallyeffective stem cell-based treatments, publication offindings is encouraged. Not only this will promotetransparency in the clinical translation of stem cellbased therapies, but it will also prevent patients in later
clinical trials from being subjected to unnecessary risk.
And this will acknowledge the research subjects’
contribution to the research. However, it is rare to see
publications of negative or inconclusive findings of thestudy.
Provided there are sufficient privacy protections forthe research subjects; researchers should explore
different ways to disseminate their research data. The
research project can be written according tointernationally recognised reporting guidelines. Editors
of journals also should include
publications ofinconclusive and disconfirmatory findings.
Registration of the clinical trials in databases
provides openness and transparency regarding stem
cell-based interventions. Recommendation 3.3.7.1
provides that clinical trials should be registered in public
databases. In this way, patients, regulators and thescientific community can monitor their efforts, reducerisks and maximise benefits of clinical trials. Also,
registration in databases enables access to clinical trials
for patients who might not otherwise know of them.
As mentioned, some patients spent vast amounts ofmoney on receiving the so-called untested stem celltherapies. In clinical trials, often the question raised iswhether the patients/ research subjects should pay forthe trials at all. This may pose ethical challenges forEubios Journal of Asian and International Bioethics 28 (July 2018)ensuring scientific merit, integrity, and fairness. The
patient sponsors may not have the skills to differentiate
between meritorious protocols and dubious ones. They
may insist on trial designs that eliminate essential
features like eligibility criteria and randomisation to acomparator arm which are necessary for promoting
scientific validity and patient welfare. Recommendation
3.3.2.9 provides for patient funding for clinical trials anddirect payments by patients to participate in clinical
trials. Those issues could be managed by requiring thatthe protocols are subject to independent expert review
for scientific rationale and design. Such oversight will
ensure the responsible conduct of analysis andreporting.
The last feature of a well designed clinical trial
involving stem cells is the use of placebo or shamcomparator in the later stage of the trial. According torecommendation 3.3.4.2, ‘where there are no proveneffective treatments for a medical condition, and stem
cell-based interventions involve invasive delivery, it may
be appropriate to test them against placebo or shamcomparators,
assuming
earlyexperiencehas
demonstrated feasibility and safety of the intervention’.
If initial phase trial demonstrates safety and efficacy,
there may be justifications to adopt a placebo or shamarm in later stage trials. Thorough assessments of stem
cell-based interventions may involve randomised trials(by chance) where sham procedures are used ascomparators.
These procedures may be cumbersome for patients/
research subjects who will not derive a direct benefit.
The adoption of sham comparators should be necessary
for the study. It is vital that researchers explain the useof placebos/ sham procedures to the patients withclarity so that they are aware and agree that there may
be no anticipated clinical benefits. To reduce thesubject’s burdens, researchers should choose the least
invasive option and the choice of arms type should bejustified.
The discussion above indicates the various
recommendations in the ISSCR guidelines that propose
well-designed, elaborate and stringent clinical trials
involving stem cells could address the ethical issues thatarise from unproven stem cell treatments. Thus, theconduct of a well designed clinical trial is a crucial step intranslating cell-based therapies but this vital stage is
bypassed by doctors offering untested stem celltherapies to the public. Members of the medical andresearch community have an ethical responsibility forpromoting the ethical conduct of clinical trials. Properly
conducted clinical trials of stem cell-based intervention
will ensure the welfare of the patients, provide respect tothem and encourage transparency as well as
accountability. The next section explores stem cell
medical innovations.
Addressing stem cell tourism in ISSCR guidelines:
Medical innovations
In the absence of clinical trials, medical innovations
have been introduced into clinical practice such as
surgical techniques. Thus there should be attempts to
add legitimate stem cell-based medical innovations. As
provided in recommendation 3.4.1, ‘clinician-scientists
may provide unproven stem cell-based interventions to123

at most a very small number of patients outside thecontext of a formal clinical trial and according to thehighly restrictive provisions outlined in this section.’
Compared to clinical research, medical innovations
have disparate objectives. The goal of clinical research is
to create generalised knowledge about new drugs orinnovative approaches to surgery or cellular treatments,
not the individual patient’s benefit (Lindvall 2014). In
contrast, a medical innovation is aimed at providing
benefits/ improvements to the particular patient’s
medical condition, and it is not research per se. As aprofessional imperative, medical innovation will later
progress to a more formal clinical trial so that these
innovations can benefit society.
Unfortunately not every medical innovation leads tomajor advancements in clinical care; some have beenless effective or even risky to the patient (ISSCR
guidelines 2016). Stem cell-based products involve
complicatedmanufacturing
procedures
requireconsiderable expertise to exploit for clinical benefit. Only
in limited circumstances, it could be justified to embark
on medically innovative stem cell-based interventions,i.e. in cases where there is a small number of patients,
and these patients are seriously ill. Also, there is adistinction between commercial purveyance of unprovenstem cell treatments and legitimate attempts at medical
innovation.
Stem cell-based medical innovations have to besensitive to the uniqueness and complexities of stem cellscience. Compared to new drugs or innovative surgery
techniques, stem cells may behave in much moreunpredictable ways due to its novelty. Thus, a medical
innovation should be subject to stringent oversight toprotect the patients. The provider of the medical
innovation should be subject to rigorous independent
expert review. Moreover, he/ she should not advertise,promote, recruit or commercialise this practice. The
highly restrictive conditions in recommendation 3.4.1
include requirements of peer review approval, informed
consent by the patient, an action plan for adverse events,
insurance coverage or other forms of financial support tocover complications arising from the procedure and thatthe personnel have the appropriate skills/ qualifications.
The provisions also include writing a detailed plan
which is must be approved by experts through a peer
review process. The plan should provide a scientificrationale that justifies why this particular method has afair chance of success, full characterisation of the kindsof cells being transplanted, description of how the cells
will be administered and follow up. Adopting thesehighly restrictive provisions is critical to building publictrust in the conduct of stem cell-based medical
innovation.
It is important to reserve space for stem cell-based
medical innovation. If conducted with strict oversight,
stem cell medical innovation in synergy with the stem
cell clinical trials process could be a formidable route fordeveloping future therapeutic treatments.
Addressing stem cell tourism in ISSCR guidelines:
Accurate and effective communication
It is easy for the general public to be confused overmixed messages. On the one hand, stem cells are often
touted as the next medical breakthrough therapy, on the124

Eubios Journal of Asian and International Bioethics 28 (July 2018)

other hand, patients are informed that these treatments
may not work. Section 4 of the ISSCR Guidelines is aboutcommunications and description of the stem cell science.
According to recommendation 4.1 of the ISSCR
guidelines, ‘the stem cell community should promoteaccurate, balanced, and responsive representations ofstem cell research’ (ISSCR guidelines 2016). In thisincreasingly connected world, the public portrayal of thestem cell field puts it in the spotlight in the media andsocial networks. The high profile of stem cell science isunderstandable given its clinical potential. The risks tothe clinical application are sometimes downplayed
whereas the potential benefits are exaggerated (Caulfield2016). Public forums on stem cell-based medical
treatments have been markedly positive, ‘lending an airof legitimacy to stem cell therapy that hasn’t beenvalidated by research’ (Lee 2012). Such hype,misrepresentations and overselling are exploited by forprofit clinics which aggressively promote stem cells foruntested clinical uses. Inaccurate, incomplete and halftrue claims could profoundly impact society.
Regular engagements with the general public are
essential. The research community should be proactive
through outreach work. As there is keen interest in thestem cell field, scientists could communicate their workthrough a number of ways including public talks andsocial media. Not only these public engagements provide
understanding for their exemplary work among lay
people/ non-specialists, but the scientists also receive
public recognition and respect for their significant
contributions to society and subsequent impact.
However, it is possible that there could be confusions
and distorted perceptions formed about the present
state of the science of stem cells such as its potential for
application, risks and various uncertainties (Kamenova
and Caulfield, 2015).
Aspirational claims on uncertain imminent
developments should be restrained. Even goodintentioned researchers may prematurely publish theirwork, for instance, in the 1980s, women with breast
cancer were receiving transplants before data
demonstrated the lack of efficacy (Stem cell therapies
2014). These claims include forecasts on the clinicalapplication, the likelihood of product approval, or
speculation on the future economic impact of currently
unrealised technologies. Researchers should be cautious
about disclosing research findings that have not passed
peer review as premature reporting can undermine
public confidence if conclusions are later disproven. And
they have a duty to make prompt corrections of errors,
inaccuracies or misleading statements in their research.
Media departments exist at large establishments suchas universities and scientists could consider working
with communications experts at their institutions. They
could produce materials that are readable andintelligible without oversimplifying, and do notunderstate risks and uncertainties. Similarly, researchsponsoring institutions and communications specialists,
including editors and journalists, have a responsibility toensure that the informational materials follow theseprinciples. The scientists in charge of the findings must
review the content before release. It may be necessary toseek feedback from independent experts.

Accordingly,
scientists,
clinicians,
sciencecommunications professionals at academic and research
institutions, and industry spokespersons have a duty toensure that benefits, risks, and uncertainties of stem cellscience are not misrepresented to the public. Adequate
care should be practised for the entire communication
process. These include the use of social networks, print
media, broadcast media and the presentation of results.
Addressing stem cell tourism in ISSCR guidelines:
Articulating standards development
Finally, a way to address stem cell tourism is throughstandards development in stem cell science. According torecommendation 5.1, ‘researchers, industry andregulators should work towards developing andimplementing
standards
ondesign,conduct,
interpretation, and reporting of research in stem cellscience and medicine’. For instance, to encourage
uniform standards for consent and procurement ofbiomaterials, the ISSCR has created a template donor
consent form found in appendix 2 of the guidelines.
Not only standards development will promote theclinical application of stem cells, but it will also promotecollaborations among many actors including scientists,
clinics, industry, regulators, and patients. There shouldbe the development of standards for matters such asconsent and procurement, manufacturing regulations,reference materials for calibrating instruments,
minimally acceptable changes during cell culture, amethod of delivery and selection of recipients for novel
stem cell-based interventions, reporting of animal
experiments, the design of trials and reporting of trials.
Such efforts limit uncertainties and promote trust among
patients.
Moreover, stem cell science is dynamic and rapidly
evolving and the ISSCR guidelines 2016 is not intended
to be the last word. Recommendation 5.2 provides that
the ISSCR guidelines should be periodically reviewed
and if necessary, amended, to accommodate scientificinnovations, fresh ethical challenges, and evolving social
priorities. Thus revisiting the guidelines is required
where there are reflection, review, reinterpretation andpossibly revision (Daley 2016).
This recommendation does not state how regular thereview should be conducted. In some nations, forinstance, in Australia, their laws on this area provide thatthe law review should be performed every 3-5 years. It is
debatable whether this time frame is too long as thescience is developing rapidly; ideally, there should be
reviews earlier. It is noted, however, that conducting arevision of laws/ guidelines is an onerous and timeconsuming task which involve many stakeholders.
Ethical problems in the conduct of stem cell researchshould be addressed promptly. With regular reviews andrevisions, stem cell science can progress in a responsible
and ethically acceptable manner. This could also
increase the probability that the international scientificresearch community will be governed by a standard setof principles.
The discussions in these sections indicate that thevarious recommendations in the ISSCR guidelines that
propose well-designed clinical trials, accurate
communications and standards development could
address the serious ethical issues that arise from

Eubios Journal of Asian and International Bioethics 28 (July 2018)
unproven stem cell treatments. Nations that areconsidering adopting a strict regulation to control the
problemcould
follow
thesecommendable
recommendations in the guidelines based on bedrock
principles.
Legal effect of ISSCR guidelines
While the ISSCR guidelines are exemplary, they are
not legally binding. States have no obligation to follow
them. These guidelines are merely a set of guidance andprinciples that direct the conduct of responsible andethical stem cell research and clinical applications. No
guidelines can be the last word (Daley 2016). As stem
cell tourism is critical to the economies of somedeveloping nations, their governments may evensupport or condone it. Likewise, countries which alreadyhave well-developed laws and policies may supercede
the ISSCR guidelines. Also, societies have different
concepts of right and wrong, and no state can enforce its
laws on another.
There is scepticism expressed about the effectivenessof the ISSCR Guidelines. Wise Young is of the view thatthe guidelines would not stop clinics that are already inbreach of ethics from giving misleading information(Baker 2008). He adds that the ISSCR guidelines are not
likely to influence a patient’s decision whether to travel
overseas to receive the medical treatment at his/ herrisk. I submit that I agree with his opinion and theguidelines are not going to filter all quacks easily andquickly and it is entirely up to the individual patientwhether to pursue an untested stem cell therapy. As Jill
Lepore said, ‘there is a “kind of faith in science thatdraws” some people to any promise of a cure for disease,no matter how specious’ (Stem cell tourism 2013).
Despite doubts expressed as regards the value of the
ISSCR Guidelines, I argue that they are neverthelesssignificant. The guidelines set high global yardsticks andprovide robust mechanisms for the conduct of stem cellresearch and its clinical application. (Daley 2016).
Backed by evidence and sound reasoning, they are an
essential preliminary step in raising the awarenessabout the various critical issues in the international
community. Nations, institutions, and funders could
promote a culture of compliance by incorporating the
ISSCR guidelines into their policies (Kimmelman 2016).
While the ISSCR guidelines do not override domestic
laws and regulations, they can inform the development
and interpretation of local laws and they can guideresearch practices not covered by legislation(Kimmelman 2016). They set the norms concerning preclinical evidence and clinical trial design. Not only theguidelines facilitate a structured basis to resolve
disputes, but they can also provide proof of professional
standards to the courts of law (Campbell and Glass
2001). While the ISSCR guidelines are highly
aspirational, they are intended to provide a benchmark
for researchers in clinical trials in less regulated nations,and it is hoped that the guidelines will encourage
governments to adopt appropriate regulations (Nelson2008).
Arguably, guidelines to govern professional conduct
may be more effective than the traditional law. The latteris reactive, post hoc and there are challenging
evidentiary issues, and the burden of proof is on the125

plaintiff. Also, the law is ‘confined to single jurisdictions,can be blunt regulatory instruments and change too
slowly to keep pace with cutting-edge research’(Kimmelman 2016). Also, as in other highly politicised
matters, there is a complexity of constant amendmentsin the laws on stem cells with each change in leadership,
creating uncertainties. For instance, in the USA,
President Bush was conservative and against embryonicstem cell research whereas President Obama was
supportive of the research and had reversed Bush policy.
And there are uncertainties with the current Trumpadministration as to their stance on this controversial
area (Khazan 2017).
Recognising the seriousness of the challenge of stem
cell tourism and with the professional support offered by
ISSCR, it is strongly recommended that regulators innations with less developed regimes for the regulation ofresearch and clinical trials should, as a matter ofurgency, establish effective national regulatory
frameworks to oversee all stem cell research and stem
cell-based clinical trials conducted within their borders.
The ISSCR guidelines provide stem cell scientists withprofessional standards for the responsible conduct of
research.
Addressing stem cell tourism through non-legal
means
There are non-legal ways to address stem cell
tourism. Brownsword suggests that external pressure,
such as peer pressure, might be exerted on the nations
that resist prohibitions, by ‘isolating those countries’. He
further argues that law may not be the answer in every
situation. He explains, “On a day to day basis, the things
we do are governed by signals for prudential reasons.
For the most part, the law is in the background. It must
be governed by local etiquette. In the same way, withconsensus statements or guidelines, it could be part of
the foreground understanding. I think the law isrelatively unimportant. What makes the world go round
isn’t law, it’s governed in a much looser sense. Moneyand peer pressure are two key drivers of how webehave. If we can’t afford it, we don’t do it. If I’m going to
run into criticism by my immediate peers, then again I’munlikely to do it. So if the consensus statement isincorporated into the workplace environment, thenthat’ll have a real regulatory effect.” As such, there are
non-legal as well as legal measures that could be taken
against these companies that offer such dubious medical
treatments such as media reports of such proceduresthat could create awareness and flag down thoseunscrupulous companies.
Conclusion
Stem cell tourism is highly complex, challenging and
not easily resolvable. With these unproven stem celltherapies, there are serious safety concerns andeconomic harm. Even if there is no adverse medical
event, the treatment may not work. Some patients would
rather continue trying until they are proven wrong
rather than waiting till it is proven right. As Brownsword
said, whether to pursue these therapies is ultimately aprudential calculation for the individual patients.
However, it is critical for nations to acknowledge andaddress this serious problem. Patients need accurate and126

Eubios Journal of Asian and International Bioethics 28 (July 2018)reliable information and they lack the context tounderstand. Given the present state of scientificknowledge about stem cells, patients should be advised
against travel for untested stem cell-based treatments.
They need guidance and with sufficient efforts, thecomprehensive and highly aspirational ISSCR guidelines
will first raise awareness of the critical issues
surrounding unproven stem cell therapies in theinternational community. These guidelines should be
widely disseminated to doctors, patient communities,
institutions, review committees, regulators, andinvestigators all around the world. These groups arethen urged to collectively inform, caution and better
educate the broader community. They could also
exercise their influence to discourage the patients fromseeking the unproven stem cell therapies. Explicit andstrong messages in lay language are necessary.
It is also vital for local regulators set up an
appropriate and effective national regulatory framework
within their country to regulate unproven stem cell
treatments. And scientists should work together with theregulatory bodies to tighten regulation. A mechanism isneeded to ensure that unproven stem cell therapies are
not marketed to patients. The regulation, coupled withstrict enforcement mechanisms, could be in the form ofguidelines and or legislation and the exemplary ISSCR
guidelines can be referred to as a model. An individual
country attempting to address the regulatory challenges
is less likely to be effective. The ISSCR and other stem
cell professional organisations could proffer their expert
assistance to government agencies. Such constructive
engagements and collaborations could lead to useful
harmonised global strategies and standards to tackle theproblem.
This is a continuing dialogue. As Alta Charo said,‘people … need to be informed that stem cell therapies
have great potential, that clinical trials are under way
and that regenerative medicine bears tremendous
promise for the future.’ While these steps will not
eliminate untested stem cell treatments, they will likely
mitigate and control the problem. And there is muchwork ahead for professional organisations, patientadvocates, doctors, researchers, clinicians, institutions
and regulators.
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The Struggle unto Death- Jasper Doomen
Assistant Professor of Constitutional law, Open
University, Valkenburgerweg 177, 6419 AT Heerlen, The
Netherlands
Email: jdoomen@gmail.com
Abstract
This article focuses on the legality of euthanasia andassisted suicide in the Netherlands. Euthanasia andassisted suicide are allowed in certain cases, but there isno consensus with respect to the extent of the situations
in which physicians should not be prosecuted. I argue
that the individual, and, more specifically, his/her
suffering, should be the focal point, and that the present
legislation falls short in this respect; no solution can as
yet be offered to individuals whose suffering cannot be
resolved through medical means and which cannot be
subsumed under the terms the law specifies.
Keywords: euthanasia; assisted suicide; depression;
existential suffering
Introduction
That the interests of the individual should in principle
be guiding in medical practice is not seriously
questioned by anyone.5 The way in which psychiatrists
and other physicians are to treat the individual andwhich options should be open to the individual, bycontrast, continues to be an important topic of debate.
Termination of life on request and assisted suicide areillegal on the basis of articles 293 and 294 of the Dutch
Criminal Code, but physicians are not punished as longas they adhere to the following criteria, specified in the
Termination of Life on Request and Assisted Suicide Act.
a. The physician must hold the conviction that therequest by the patient was voluntary and wellconsidered;b. The physician must hold the conviction that thepatient's suffering was lasting and unbearable;c. has informed the patient about the situation he was inand about his prospects;

5 I say ‘in principle’, for in some cases difficult choices must be
made. For example, it has recently been debated whether the
medication to treat Pompe disease, Fabry disease and Cystic
fibrosis, which is relatively costly and used by very few
patients, should continue to be paid collectively. Such issues
will presumably increasingly be raised as medical progress is
made.

127

d. The physician and the patient hold the conviction that
there was no other reasonable solution for the situation
he was in;e. The physician has consulted at least one other,
independent physician who has seen the patient and has
given his written opinion on the requirements of due
care, referred to in parts a – d; andf. The physician has terminated a life or assisted in a
suicide with due care.
Similar laws as those which apply in the Netherlands
have been adopted in Belgium and Luxembourg. In bothcountries, just as in the Netherlands, doctors are
exclusively allowed to euthanize; in addition, they haveto adhere to strict criteria, which do not differ
significantly from those that apply in the Netherlands. An
important respect in which these three countries differ
from others that allow euthanasia is that euthanasia on
non-terminally ill patients is legal. With respect toassisted suicide, by contrast, there are importantdifferences between Belgium and the Netherlands. The
Belgian law does not provide criteria under which
circumstances it would be allowed, from which it may beinferred that it is not allowed, but the issue has raised
doubts and debate.6
A known proponent of a perspective in which theright of self-determination is not decisive is the Belgian
philosopher Herman de Dijn, who states: “Theeuthanasia act displays a profound opposition in oursociety, a struggle between conceptions of man and ideas
about ethics that cannot be resolved by having everyone
act in accordance with his or her own ideas. According to
its opponents, the euthanasia act conveys a dangerous
message: that certain lives are no longer worthwhile.”7This is not the proper place to extensively evaluate thearguments for the various positions. I will instead focus
on the individual’s confrontation with his suffering, inorder to ascertain to what extent the current Dutch
legislation meets the demand that this suffering shouldbe terminated. What is said here may also be of interestfor readers who do not live in the Netherlands, for thetheme that is discussed here is not particular to a specificcountry.
An evaluation of the legislation
The Termination of Life on Request and Assisted
Suicide Act, which is based on articles 293 and 294 of the
Dutch Criminal Code and specifies under which
6 H. Nys, “A Discussion of the Legal Rules on Euthanasia in

Belgium Briefly Compared with the Rules in Luxembourg and
the Netherlands.” In: D. Jones, C. Gastmans, C. Mackellar (eds.),
Euthanasia and Assisted Suicide. Cambridge: Cambridge
University Press: pp. 7-25, 10.
7 This is a translation of the original Dutch text. The originaltext reads: “De euthanasiewet verraadt een diepe tegenstellingin onze maatschappij, een strijd tussen mensbeelden enopvattingen over ethiek die niet op te lossen is door ieder
volgens zijn/haar idee te laten handelen. De euthanasiewet
zendt volgens haar tegenstanders een gevaarlijke boodschap
uit: dat bepaalde soorten levens niet langer de moeite waard
zijn.” H. de Dijn, “Euthanasie: een cultuurfilosofische analyse.”
In: A. Burms and H. de Dijn (eds.), De sacraliteit van leven en
dood
voor
een
brede
bio-ethiek.
Kalmthout:Pelckmans/Zoetermeer: Klement, 2011: pp. 71-87, 86.

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Eubios Journal of Asian and International Bioethics 28 (July 2018)

conditions terminating the life of another person at that
other person’s express and earnest request or
intentionally assisting in the suicide of another person orproviding that person with the means thereto is notpunishable, has recently been re-evaluated; theproblems that individuals whose suffering cannot be
medically treated or even diagnosed face was discussed
at length. It is this suffering I wish to address here. The
crucial criterion in the law is that there must be ‘lasting
and unbearable’ suffering, to be determined by aphysician; 8 the exemption itself only applies tophysicians.9 It should be noted that unbearableness is“[…] a highly subjective and difficultly objectifiablefactor.”10 This given does not derogate from the fact thatthe assessment is still medical, which serves as ajustification for the monopoly of doctors to act when thetermination of life is concerned. This monopoly is,however, as I will argue, problematic in a number ofcases.
‘Unbearable suffering’ may be interpreted broadly,
covering both pain and (inter alia) “increasing
dependence, an ever greater loss of dignity or theprospect of a gruesome death.”11 Yet the government
does not go so far as to deem the prospect of suffering
lasting and unbearable, inter alia as ‘lasting’ and‘unbearable’ are indivisibly linked:12 “The mere prospectof suffering, irrespective of whether this will result from
pain, loss of dignity or fear of an undignified death,cannot, in light of the above, be characterized as lasting
and unbearable suffering.”13 It becomes apparent fromthe evaluation that the fact that precisely that prospect isoftentimes the motive behind requests for euthanasia
constitutes an important problem: “If one examines thereasons why people make a request to be euthanized,
pain appears to be a factor in only a small number ofrequests. In actuality, what drives the request is almost
always the loss of dignity that is to be expected.”14
If this is correct, it is justified to say that the present
legislation is not adequate to realize the desired goal.
8 Termination of Life on Request and Assisted Suicide Act, art.

2; Parliamentary Documents: House of Representatives,
1993/1994: 23877, no. 1: pp. 4, 5. ‘Lasting’ is to be understoodhere in the sense that no prospect of improvement exists.
9 Articles 293 and 294 of the Dutch Criminal Code.
10 The original text reads: “[…] een in hoge mate subjectieve, en
moeilijk te objectiveren factor.” Parliamentary Documents:
House of Representatives, 1993/1994: 23877, no. 1, p. 5.
11 The original text reads: “‘[…] toenemende afhankelijkheid,
steeds verdere ontluistering of het vooruitzicht van een
afschrikwekkende dood […].” Parliamentary Documents: Houseof Representatives, 1999/2000: 26691, no. 6, p. 70.
12 Parliamentary Documents: House of Representatives,
1999/2000: 26691, no. 6, p. 60.
13 The original text reads: “Het enkele vooruitzicht op lijden,
ongeacht of dit zal voortvloeien uit pijn, ontluistering of angst
voor een onwaardige dood, kan in het licht van het
bovenstaande niet als uitzichtloos en ondraaglijk lijden worden
aangemerkt […].” Parliamentary Documents: House ofRepresentatives, 1999/2000: 26691, no. 6, p. 60.
14 The original text reads: “Als je kijkt naar de redenen waarom
mensen een euthanasieverzoek doen, is pijn maar een heel
klein onderdeel van alle verzoeken. Eigenlijk gaat het bij het
verzoek bijna altijd om de te verwachten ontluistering, hetverlies van waardigheid.” Parliamentary Documents: House ofRepresentatives, 2013/2014: 31036, no. 8, p. 13.

The problems will possibly increase with the impending
population ageing. Research shows that a growing
number of elderly people imagine themselves requesting
euthanasia or having a suicide pill available. 15 The
introduction of such a pill is, however, at least for theforeseeable future, a politically sensitive issue. In any
event, world-weariness is not a recognized criterion toallow euthanasia or medical assistance in ending one’s
own life,16 and neither is a ‘finished life’.17
A reform in this respect is pleaded by, amongst others,
those who support the Citizens’ Initiative Finished Life(‘Burgerinitiatief Voltooid Leven’).18 In the wake of thisinitiative, political party Democrats 66 has submitted thebill Dignified End of Life (‘Waardig Levenseinde’), but
this only pertains to people of 75 years or older. If thepill is only made available to the elderly – leaving theissue of what the precise age limit should be19 –, nosolution has been offered to young people who face thesame problem. Their position remains outside thepurview of the law. This subject matter particularly
lends itself to a medical ethical reflection, since thequestions to which the subject matter gives rise cannot
be answered by the medical profession itself.
This became clear in a case in which a generalpractitioner was found guilty of having assisted thesuicide of a patient because the main criteria for
medically assisted suicide had not been met, namely,that there has to be (in accordance with was indicatedabove) ‘lasting and unbearable’ suffering; he wasdischarged, however, the act, while principally
punishable, not meriting a punishment in this case. As
the Dutch Supreme Court expresses it: “The integral carewhich is to be provided by a general practitioner topatients […] may result in him being assigned with thetask to alleviate the suffering of a patient which is not or
not predominantly caused by a somatic or mental
condition, but which is the consequence of the lack of alife perspective. Given, however, that that physician thenenters into a domain that lies beyond his professional
competence, he may not, in his capacity of medical
professional, form a judgment regarding theunbearableness, lastingness and untreatableness of that
suffering.”20
15 H.

Buiting, D. Deeg, D. Knol, J. Ziegelmann, R. Pasman, G.
Widdershoven and B. Onwuteaka-Philipsen, “Opvattingen vanouderen over levensbeëindiging.” Huisarts & wetenschap 56 (3)(2013): pp. 102-105, 104.
16 Parliamentary Documents: House of Representatives,
2007/2008: 31036, no. 3: pp. 4, 6.
17 Parliamentary Documents: House of Representatives,
1999/2000: 26691, no. 6: pp. 30, 60.
18 Parliamentary Documents: House of Representatives,
2013/2014: 31036, no. 8: p. 3.
19 It is difficult to generalize, and for some people the prospectof having to live until the age of 75 may be dreadful whileothers may welcome the possibility to live (well) beyond thatage.
20 The original text reads: “De door een huisarts te verlenen
integrale zorg aan patiënten […] kan meebrengen dat hij zichvoor de taak gesteld ziet om het lijden van een patiënt teverlichten dat niet of niet in overwegende mate zijn oorzaak
vindt in een somatische of psychische aandoening, maar het
gevolg is van het ontbreken van levensperspectief. Omdat die
arts zich dan evenwel begeeft op een terrein dat buiten zijn
professionele competentie ligt, zal hij zich niet als medicus een

Eubios Journal of Asian and International Bioethics 28 (July 2018)129

The question is, then, what, if any, recourse may beavailable to an individual who is confronted withsuffering that cannot be qualified in medical terms, i.e., acase where neither depression nor a physical illness isdiagnosed. In cases of ‘existential suffering’ the Supreme
Court commands that a physician “consult others who
may be helpful in finding a meaningful fulfillment of
one’s daily existence.”21 Who these ‘others’ might be is
not elucidated and this may differ from one case to thenext, so that a problem of referral will ensue (should apriest, rabbi or humanistic counselor – to mention just a
few possibilities – be approached?). More importantly,
no solution is provided for someone for whom, in spiteof the availability of such possible alternative support,
no meaningful fulfillment can be found.22 This is not tobe taken as criticism of the Supreme Court; thepossibility to provide adequate support in such cases
simply does not exist at the moment. Steven Pleiter,
director of the End-of-life Clinic (‘Levenseindekliniek’),expresses the problem as follows: “We, too, face patientswho ‘suffer from life’ – that is what we call it – and who
have become detached […]. We cannot aid these patients
under the present standard, since it is based on thepresence of medical suffering. At times, dire situations
occur, in which elderly people gravely suffer from life. In
my view a proper solution should be available in suchcases. The present Euthanasia legislation does not offer
such a solution.”23

as was pointed out above, assisted suicide; only
physicians who observe the demands specified in the
Termination of Life on Request and Assisted Suicide Act
are exempted. In order to confront the problems while
acknowledging that some cases do not concern medical
issues, non-physicians should also be exempted frompunishment.24 Certain precautions should obviously bein place – crucially, it must be clear that there is agenuine death wish. With this in mind, one may argue
that a physician still has a role to play: “If physicians’
professional expertise enables them to deal with theexistential questions arising in connection with VE[voluntary euthanasia] and PAS [physician-assisted
suicide] based on suffering caused by illness or injury –as the conventional view presupposes that it does – itwould be inconsistent to deny VE and PAS for persons inpurely existential distress by claiming that physicians’
professional expertise does not extend to existential
questions.”25
Young’s solution, to have both a physician and a nonmedical, professional counsellor assess individual cases,
may, since he argues that if consulting the latter does notchange the outlook of the person requesting assisted
suicide this should be allowed,26 be advisable. In any
event, it must be borne in mind that assisted suicide isstill suicide (killing oneself). It would be both peculiar
and undesirable to penalize assisted suicide if suicide (orattempted suicide) is not.27

Towards a solution
What is the best way to approach this problem? It
must, first of all, be acknowledged that removing lasting
suffering in some cases is tantamount to ending the lifeof the individual, namely, in those cases where sufferingfrom life itself is concerned: the suffering permeates life
to such a degree that it is no longer acceptable. The only
one who is able to determine this highly subjective given
is the individual: it is no longer acceptable to him or her.
In order to accommodate people whose suffering is
not covered by the Termination of Life on Request andAssisted Suicide Act it is necessary to change article 294,
section 2, of the Dutch Penal Code. This article penalizes,

Conclusion
The evaluation of the Termination of Life on Request
and Assisted Suicide Act makes it clear that no adequate
solution may be offered to elderly people who are‘through with life’. If they suffer unbearably and lastingly,
euthanasia or assisted suicide may be granted to themon the basis of a medical assessment, but it may bequestioned whether these possibilities are sufficient.
Perhaps even more pressing are the problems that are
not limited to the elderly, where individuals who ‘sufferfrom life’ are concerned: their suffering cannot begauged from a medical point of view, let alone be treated.
The physician’s role is limited in this respect, whichmeans that individuals have, on the basis of the present
legislation, few to no options to have their suffering –and thereby their lives – terminated. By regulating
assisted suicide it may become possible to find a solution

oordeel mogen vormen over de ondraaglijkheid, deuitzichtloosheid en onbehandelbaarheid van dat lijden.” Dutch
Supreme Court, December 24, 2002, NJ 2003, 167, par. 8.2.
21 The original text reads: “[…] het inschakelen van anderen die
behulpzaam kunnen zijn bij het zoeken naar een zingevende
invulling van het dagelijks bestaan.” Dutch Supreme Court,
December 24, 2002, NJ 2003, 167, par. 5.
22 Cf. M. Parker, “Words and reasons: psychiatry and assisted
suicide.” Australian & New Zealand Journal of Psychiatry 46 (2)(2012): pp. 80-83, 80: “[…] the person who competently asks
for [assisted suicide], in circumstances that we can sympathise
with, is not always motivated by psychological pain for which
there is an acceptable alternative.”
23 The original text reads: “Ook in onze praktijk hebben we temaken met patiënten die “lijden aan het leven” – zo noemen wij
dat – en die onthecht zijn […]. Wij kunnen deze patiënten
binnen de norm zoals die op dit moment geldt, niet helpen,
omdat de norm uitgaat van medisch lijden. Er komen soms heelschrijnende situaties voor waarin ouderen zeer lijden aan het
leven. In mijn ogen zou daar een goede oplossing voor moetenzijn. De huidige Euthanasiewet biedt die oplossing niet.”
Parliamentary Documents: House of Representatives,
2013/2014: 31036, no. 8, p. 9.

The cooperative Coöperatie Laatste Wil (‘Last Will
Cooperation’) has announced that it will communicate thedetails of an easily obtainable means to end one’s life without
pain to its members; there is no consensus among lawyers as towhether this is legal.
25 J. Varelius, “Medical expertise, existential suffering andending life.” Journal of Medical Ethics 40 (2) (2012): pp. 104107, 106.
26 R. Young, “‘Existential suffering’ and voluntary medicallyassisted dying.” Journal of Medical Ethics 40 (2) (2012): pp.
108-109, 108.
27 The idea that suicide itself is not illegal may seem, given thatthe person involved has deceased, evident, but this appears not
to have proven to be an impediment to penalize people in thepast (see, e.g., M. MacDonald, “The secularization of suicide in
England 1660-1800.” The Past and Present Society 111 (1986):
pp. 50-100, 52, 53).
24

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Eubios Journal of Asian and International Bioethics 28 (July 2018)

for the dire cases whose suffering must at present last
unabated.

The Question of Moral
Responsibility and Physician’s
Practice in Nigeria- Joseph N. Ogar, Ph.D
Department of Philosophy, University of Calabar, Calabarnkangjoseph@yahoo.com.
- Ushie Abel Idagu, Ph.D
Department of Philosophy, University of Calabar, Calabar- Samuel Akpan Bassey
Post Graduate Student, University of Calabar, Calabar,
Cross River, 540242, Nigeria
samuelbassey15@yahoo.com and 7060721631.
Abstract
Humans are composed of many complex units ororgans with diverse functions. Health challenges arebound to arise as a result of our daily interaction with ourenvironment. These necessitate the study of different
discipline to help overcome most of these challenges.
This paper is concerned with those trained in the field of
medicine with the aim of providing solution or treatment
to health maladies or challenges. Physicians who swore
to an oath of maleficence beneficence, to respect theauthority of their clients and adhere to the principle ofconfidentiality, are equally expected to operate side byside the societal moral demands.
It is the position of this paper that despite man being
created as a rational and free moral agent, upon which
the physician should be free to make his choice as
regards the course of medical treatment to be meted to
who in view of the scarce medical resources, saddled
him with difficulties in reaching decision. Hence, we
appeal to Utilitarian principles, Kant’s ethical principles,
the Ross ethical principles, Rawls ethical principles andso on, to buttress the argument of the challenge of moral
responsibility standing against the physician in his
practice of medicine. It is the position of this paper that
before subjecting physicians actions to the scrutiny ofmoral praiseworthiness or blame worthiness, certain
questions such as: is the physician really free to act outof his volition, does he have alternative choice to make, ishe under any influence, what is his state of mind, is hementally alert and so on? Must be taken into cognizanceto guide our attempts at resolving it. The expository,
analytic and critical methods are used to draw the paper
to a close.
Keywords: Medical Practice, Moral Responsibility,
Utilitarian principles.
Introduction
Well understood, the food we eat, the work we do, andthe environment wherein we live do contribute todetermining how in good health or otherwise we are as
humans. It follows that diseases or sicknesses are likely
experiences we have as mankind. Hence, the practice of
medicine as attempts at curing man’s health maladies

becomes very pertinent. Those who study the art of
medicine and graduate are known as medical doctors
otherwise “physicians”. Giving the sacred and allimportance nature of man, those whose studies andpractices concern with man (the highest creature), it
requires that certain stringent measures be put in place
to ensure that much care is taken by healthcare givers.
Consequently, it becomes a prerequisite for would bephysicians to swear to an oath. Commonly sworn to is
the Hippocratic oath, the modern version of which is asfollows;“I solemnly pledge myself to consecrate my life to theservice of humanity”- I will give to my teachers the respect and gratitude
which is their due;
- I will practice my profession with conscience anddignity, the health of my patient will be my firstconsideration.
- I will respect the secrets which are confided in me,even after the patient has died;- I will maintain by all means in my power; the honour
and the noble traditions of the medical profession;- I will not permit considerations of age, disease or
disability, creed, ethnic origin, gender, nationality,
party politics, race,, sexual orientation, or social
standing to intervene between my duty and mypatient;- I will maintain the utmost respect for human life fromits beginning even under threat and I will not use mypractical knowledge contrary to the laws of humanity;- I make those promises solemnly, freely and upon myhonour. (Asira and Ogar 2011:3)
It is incontrovertible to say that the claim ofrationality-ascribed human necessarily implies morality.
It follows that only the rational can be expected to chosethe right course of action from alternative courses ofactions. Rational quality with morals should guide man
to choose good and avoid evil.
Moral Responsibility
Action is moral if said to be intrinsically good andpraise worthy (Omoregbe, 1996:14). A person is said tobe living a moral life if we are living a good life
(Uduigwomen 2003:23). Lacey defines the term moral asthat which revolves around habits, customs and indeed
an acceptable ways of living within a given society orstate. it has to do with assessing a particular action of
behaviour as good or bad, right or wrong (1976:138).
We assess individuals and gatherings as capable or not,contingent upon how legitimately they take up their
responsibilities. Regularly we do this casually, throughgood judgment. Some of the time we do this formally, forexample in legal judgment. The first philosophical use of"responsibility" was political. At the point when John
Stuart Mill composes about responsibility his worry isn'twith free will, however with the doctrine ofrepresentative government. Toward the finish of thenineteenth century, one most striking scholar to talkabout responsibility is Max Weber, who propounds anethics of responsibility (Verantwortungsethik) for thegovernment officials. For Weber, the job of politics
requests a strong attention for the realities of theEubios Journal of Asian and International Bioethics 28 (July 2018)
circumstance and consequences of actions– and not to
abstract or grandiose principles.
Also, according to Encyclopedia of Philosophy, “aperson is regarded as morally responsible for some acts
or occurrence P if and only if he is believed:(a)
To have done P or to have brought P about
and(b)Done P or to have brought it about freely(1992:184).
Questions of what, when and how as it pertains togood life; when to know a person is living a good life andas well the criterion for making judgment about somebasic facts of life as it relates to the performance of ourduties, are key to our sense of moral rectitude.
There is no philosophical method for dividing or
dissecting the different segments of responsibility, and a
few parts are frequently disregarded by thinkers. To
adopt a more complete strategy, this article separates
the responsibility of people into four zones of enquiry.
Modern analytic moral philosophy has had a tendency to
ask two questions about responsibility: "What is it to beaccountable?" and "What is an individual accountablefor?"
The primary inquiry is generally taken as an inquiry
regarding moral agency, the second as an inquiry
concerning holding individuals responsible for past
activities.
Idea of moral responsibility therefore
concerns things we do within our power and for which
we can be held accountable without being forced or
coerce to do them. put otherwise, actions based orreached at as a result of the choices an individual makes.
Some may have argued that there is no universal ethicalcode rather in favour of the fact that ethical or moral
codes vary from one society to another. This paper is not
to occupy itself on ethical discrepancy but upholds thatin every society virtuous living like respect for thefundamental human rights; thou shall not kill; steal
among others appear to be universally acceptable (Evan,
2004:22-28). Moral responsibility can only be said in asituation to which the agent is at liberty to act without
coercion. That is, the absence of all impediments toactions, having his or her intrinsic quality and freedom
to perform a particular action or alternatively chooses
not to perform a particular action. (Oswald Hamflingcited in Uduigwomen, 2003:24).
Factors that Determines the Limit of Moral
Responsibility
Cardinally considered on issues of moral responsibility,
is whether the action is voluntary or involuntary.
Voluntary Action: Under this, the agent is said to bevery free to act; there must be alternatives of choice;there must be absence of compulsion; there must be
knowledge of the subject matter, and there must be
mental alertness or sound condition of mind.
Involuntary Action: This is the opposite of voluntaryaction. In this case, the agent acts under compulsion or in
ignorance. That is when other people manipulate theagent to act in their power; where the agent recalls his
action regrettably, in pain and wished he/she neveracted so. (Macltrye, 1979:69). To lend credence to this,Pascal observes that “where the ‘will’ becomes a sort ofmechanical reflex, activated by whichever delectation that
happens to be the strongest… in such circumstances no131

moral responsibility can be imputed to it” (Udugiwomen,
2003:25). It presupposes that for an agent to be morally
responsible for his/her action, to include murders, theft
and the likes he must have acted without external force
or influence acting on him, and ofcourse in good state ofmind and that his actions was consciously prosecuted or
executed. Also, on this subject, moral responsibility andmedical practice may depend on the principles of
freedom of the will and causality or determinism(Pellegspring 1981:46-50).
Freedom of the Will/Determinism
Here, holds that human actions are products of theirown volition, and as such he/she should be held morally
responsible for his actions. While determinism argues
that all human actions are products of certain forcestranscendental or beyond the control of the human agent.
Viewing this work in the light of the above conflicting
principles, complicate the challenge of moral
responsibility. To explore further, if we subscribe to theprinciple of determinism then no human being shouldbe blamed or punished for his actions, neither should
any be praised since they do not have control of theiractions and therefore the entire human society will bechaotic, brutish, short, lawless as captured by Thomas
Hobbes’ state of nature. If the contrary is the case that
determinism is false, then some events or actions are self
willed otherwise the acting agent acted out of freewill.
On the other way round, we find out that certain eventsoccur by chance. If this is true, it becomes an imposition.
Where then lies the freedom of the human agent?
(Encyclopedia of Philosophy 1972:184).
Arguing on this, some philosophers support moral
responsibility, that a person is morally responsible forhis actions, and if determinism is to be brought in, it is
the self that may determine action and to which end, theperson is to be held morally responsible for his/heractions. According to David Hume, it is only when an
action that is determined is also in some sense
constrained or compelled, is the actor morally
responsible for the act. (Cited in Uduigwomen, 2003:26 –
27). It becomes clear that both freewill and determinism
have not been able to strike a compromise as to which
actions are products of one’s volition, and those that are
determined. Except owed to some other moral schools ofthought, we are yet to have a generally accepted
criterion for judging human actions as praiseworthy or
blameworthy. Consequently, many resort to conscience
this however is not without contention (Evan, 2004:2228).
Competing Schools of Thought on Issue of Moral
Responsibility
We may have to consider the utilitarian anddeontological schools.
Utilitarianism
Utilitarians argue that praise or blame should beapportion accordingly to an active agent in relation to his
action. According to Bentham, an agent’s action should
be directed to maximize good and diminish or minimize
evil. It should be the satisfaction of greater minority anddissatisfaction of majority, or negligible few.
Utilitarianism is a Teleological theory. That is an act isjudged right or wrong based on its result or consequence.

132

Eubios Journal of Asian and International Bioethics 28 (July 2018)

An act is right depending on the volume of happiness orpleasure it produces, and wrong based on the pain
produced rather than avoided. Very key to utilitarianismis the principle of utility. Given this, the moral end thatshould be sought in all our actions, should insist on the
pursuit of the greatest possible good over evil.
This principle cautions that medical practitioners
should keenly pursue the attainment of the highest goodwhich is the security of lives by their painstaking
attention to patients to save lives above every otherpromptings (Omoregbe, 1996:172).
Utilitarianism divides into Act and Rule
Utilitarianism: Whereas Act utilitarian principle
advances the good and result of actions as the criterion
for judging rightness, Rule Utilitarianism encourages the
adoption and observation of only those moral rules thatwould produce happiness for greater majority. He
cautions therefore that it is morally responsible forhealth workers and authorities to see to it as their
responsibility to provide medical facilities and services
in good number as to promote good health for many.
The enhancement of patient’s pleasure should beseen as the key duties of the physicians, who are also
supposed to be altruistic as against being egoistic goingby the medical code of ethics. However, the challenge ofmoral responsibility as regards utilitarianism can bediscerned when a physician is in a fix as to who of thetwo or more patients billed for organ transplant should
receive the only organ available taking also into
cognizance the social and economic status of the said
two patients, one the governor, and a peasant fisherman.
The physician must following the utilitarian principle,
choose the governor at the expense of the peasantfarmer.
Kant’s Ethical Theory: To Kant, goodwill is the only
good thing that cannot be abused. Being the will to act
for the sake of duty. Kant’s therefore enjoins moral agent
in this case, medical practitioners to act freely from hisor her volition independent of any eternal force,pressure or influence. He endears the principle ofuniversalization as a yardstick for determining whether
an action is good or bad. He adds any action that would
not be universally approved is therefore bad. That any
person in a similar situation will be willing to allow sameaction apply to he/she.
Kant holds the view that every human being is arational worth. Therefore, to treat the president speciallywhile relegating or denying the peasant farmer ismorally wrong especially when the peasant-farmer
happens to get to the notice of the doctor first before thepresident. Medical doctors should have goodwill and by
implications morally responsible. Hence, their actions
should be out of reverence for moral law in a universally
valid and acceptable way (Iwe, 1986:235 – 237). He
holds the view of equality hence, nobody should betreated partially or in preference of the other. The
implication following Kant’s ethical theory is that in asmuch as the peasant (poor) farmer came before theGovernor (rich) man the principles of first come firstserve should be followed. So medical doctor is morally
responsible to do the right thing to gain the praises ofthe society or do the wrong thing and be blamed (Kant,
1982:236).

William David Ross Ethics: According to William Ross,
virtue, knowledge, pleasure and the allocation ofpleasure and pain according to desert are the four goodthings.
Again, he classified duties into three kinds such as:
reparation, gratitude and keeping faith. And moral
responsibility obligated medical doctor or physician nomatter what to insist in doing or carrying right action
which is the tendency to promote the general good of
his/her client (patient). We should now and always doprima facie duties as against less important duties. He
concludes by saying medical doctors are morally boundto be faithful to their clients in accordance with the oaththey swore to. The obligation to their employer shouldbe less than their obligation to render service according
to desert in such a virtuous way as would project themas gratuitous (Kelly, 1990:236 – 238).
Rawls’
EthicalTheory:Alternatingclassical
utilitarianism. John Rawls' hypothesis of equity, which isconsidered as a contemporary refection of egalitarian
ethical theories, addresses the issue of reasonablecirculation of social products.
He enjoins that
individuals and associations should advance theirrational ends without infringing on the rights of others.
To this, it is the moral responsibility of government toarrange medical institutions to achieve the greatest net
balance of satisfaction for her citizenry. It is also
required that medical doctors adopt the principle ofrational choice, be empathetic and as well, impartial intheir dealings with the sick ones before them.
Moral Responsibility and Physician’s Practice In Nigeria
Today, medical professionals face an unpopulardecision between two conflicting moral orders, one
situated in the power of our ethical obligations to thesick, the other in the supremacy of self-interest and themarketplace. These two orders are not essentiallyreconcilable and, similar, and the professional will becompelled to pick between them.
In that decision, ethical theories learnt and ethicalcode and conducts can play a focal and essential part.
Giving health services is a critical moral measure since
its significant point is to ensure the welfare of thegeneral population who require treatment and care (1).
Ethics not just priorities and the dispersion of healthcare
services, but in addition are apprehensive with moral
decision making at an interpersonal level (2). Moralsensitivity is the capacity to distinguish the existing
moral issue and comprehend the moral results of the
choices made on the patient's part (3). Doctors areconstantly presented to moral distress because of a few
conditions, for example, making a move in spite of one's
conscience, not giving full treatment because of thefinancial limitation of a patient, insufficient treatment,
absence of time, and patients on a long waiting list etc.
Acting against professional values and interests
destructs one's moral integrity and achieves job
dissatisfaction, leaving their occupation, and inparticular, not giving high quality and safe health care topatients (8). On the off chance that moral decision
making is countered with situation that cause moral
distress, a therapist won't have the capacity to perceiveEubios Journal of Asian and International Bioethics 28 (July 2018)
situations and moral issues, and make sound judgment.
Perceiving distressing and morally problematic
circumstances is exceedingly imperative in decision
making processes. Satisfying this exceptionallyimperative undertaking requires moral knowledge,
understanding the ethical theories above, as well as
requires moral sensitivity (9, 10). People who havemoral sensitivity are fit for solving moral clashes.
Besides, they are fit for forming a sensory and scholarly
perception of individuals’ vulnerable circumstances, andare aware about moral outcomes that are critical insettling on critical decisions for others (11). It is trusted
that in clinical settings, reacting to morally distressing
circumstances is identified with criteria, for example,
moral sensitivity (12). In healthcare, morality is an interrelated and dynamic process that is recommended bymoral sensitivity (13).
Over the span of obligation and relationship withpatients the doctor must hold fast to specific standardsof medical ethics (equity, nonmaleficence, equity andbeneficence), rules (confidentiality, fidelity, veracity andprivacy) as well as virtues (empathy, respects, kindness,and so on). A doctor might be sanctioned when he breaks
the rules and principles of medical ethics; however hemay not necessarily be liable or compelled to maintainthe virtues involved in his line of duty and practice. It is,in any case, morally upright (yet not compulsory) for agood doctor to be caring, kind and to show regard for
his/her patients. Regard for patients and the desires ofpatients are two distinct issues that must not be
confused.
Conclusion
The idea of free moral agency and rationality ascribedto humanity suggests that man is morally responsible forhis actions. It follows as has been observed earlier on in
the work that, for man to be held morally responsible,
there must be alternative of choice, absence ofcompulsion, knowledge of the subject matter andhealthy state of mind or mental alertness. With specificreference to medical practice, the physician has his
professional (oath) moral responsibility; and the societal
moral responsibility constitute a serious moral challenge
to him. it has been rightly observed that sometimes thesocietal moral responsibility may conflict with his
professional moral responsibility. At this point is heexpected to act professionally or complies with societal
demands for example where the societal demands willcompel the physician to divulge information gotten fromhis client in confidence.
Should physician’s oblige them and violate theprinciple of confidentiality? Again, his professional
responsibility and societal moral responsibility which
one is superior, and which is less important? Will he beworth the profession by violating his professional
responsibility partially or otherwise? Agreed, there may
be some exceptions no matter how slightly that maybe to
the rules but the work maintains that more attention
should be given by the physician working more inconformity with professional moral responsibility of
being accountable to his patient, ensures the patient iswell treated, and his/her well being is promoted at all

133

times for which reasons the patient came to him; andshould there be conflict arising from societal demands,
the society should carve any other way to resolving theconflict arising from the patient’s action and not throughthe physician into violating his obligation.
References

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Evans, M. Loubiala. Philosophy for Medicine: Applications in
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Iwe, N. S. S. The History and Content of Human Rights. New
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Kant, Immanuel, Critique of Pure Reason. Trans. Norman Kemp
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Kely, David. The Act of Reasoning. New York: W.W. Norton,
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Lacer, F. R. A Dictionary of Philosophy. London: Routleddge andKegan Paul, 1976.
Mactrye, Seven Traits for the Future. New York: The Hasting
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Omoregbe, J. I. Ethics: A Systematic and Historical Studies. 3rdedition. Lagos: Joja Educational Research and Publishers,
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Pelegrinspring, E. Thomson. A philosophical Basis of Medical
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Uduigwomen, A. F. Contemporary Issues and Problems in
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November 2018, Kaohsung and Pingtung, Taiwan.
Twelfth Kumamoto University and AUSN International Bioethics
Roundtable (KBRT12): Bioethics in the 21st Century, 30 Nov; 1-2
December 2018, Kumamoto University, JapanEJAIB Editor: Darryl Macer
Associate Editor
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