The Call Of Nature
Saint (what else!)
hey, you made a mistake. 2 letters all at once!
(amazing intellectual achievment, though, compared to your other posts)
(amazing intellectual achievment, though, compared to your other posts)
Troll Kingdom
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The Call Of Nature
Saint (what else!)
soldier
Internet Troll
New member
shut up nigger jack
you need to take a spastic pill
you need to take a spastic pill
Kitty
Sinless and Purrfect
steel
'Gear
RIP 1970~2018
The ‘superman’ or ‘overman’ of Nietzsche's ethical vision. The Übermensch transcends the boundaries of classes, creeds, and nationalities; he overcomes human nature itself, and maintains a lordly superiority to the normal shackles and conventions of social life. Although Nietszche connects the character with Aristotelian virtue, the vision is essentially Romantic when Aristotle's is not. The idea of a transfiguring freedom finds more pessimistic echoes in the existentialist doctrine that existence precedes essence. See also will to power.
Donovan - Don't start with me.
SuN
.:~**~.~**~.~**~:.
You're too far, to bring you close
too high, to see below
just hanging on, your daily dose
and you never, needed anyone
but they're rolling, papers for your grass
how can you give, what you don't have?
You keep on aiming, for the top
and quit before, you sweat a drop
feed your empty brain, with your hydroponic pot
you start out, playing with yourself
you get more fun, within your shell
nice to meet you but, I gotta go my way
I'll leave again, cuz I've been waiting in vain
you're so in love, with yourself
if I say, my heart is sore
sounds like, a cheap metaphor
so I won't repeat it, no more
I'd rather eat, my soup with a fork
or drive a cab, in new york
cuz to talk to you, is harder work
so what's the point, of waisting all my words
if it's just the same, or even worse
than reading poems, to a horse
You keep on aiming, for the top
and quit before, you sweat a drop
feed your empty brain, with your hydroponic pot
I bet you'll find, someone like you
cuz there's a foot, for every shoe
I know what you like, but i've other things to do
I'll leave again, cuz I've been waiting in vain
you're so in love, with yourself
if I say, my heart is sore
sounds like, a cheap metaphor
so I won't repeat it, no more
[YOUTUBE]
dSQdjvnNYiU&feature=related[/YOUTUBE]
too high, to see below
just hanging on, your daily dose
and you never, needed anyone
but they're rolling, papers for your grass
how can you give, what you don't have?
You keep on aiming, for the top
and quit before, you sweat a drop
feed your empty brain, with your hydroponic pot
you start out, playing with yourself
you get more fun, within your shell
nice to meet you but, I gotta go my way
I'll leave again, cuz I've been waiting in vain
you're so in love, with yourself
if I say, my heart is sore
sounds like, a cheap metaphor
so I won't repeat it, no more
I'd rather eat, my soup with a fork
or drive a cab, in new york
cuz to talk to you, is harder work
so what's the point, of waisting all my words
if it's just the same, or even worse
than reading poems, to a horse
You keep on aiming, for the top
and quit before, you sweat a drop
feed your empty brain, with your hydroponic pot
I bet you'll find, someone like you
cuz there's a foot, for every shoe
I know what you like, but i've other things to do
I'll leave again, cuz I've been waiting in vain
you're so in love, with yourself
if I say, my heart is sore
sounds like, a cheap metaphor
so I won't repeat it, no more
[YOUTUBE]
dSQdjvnNYiU&feature=related[/YOUTUBE]
SuN
.:~**~.~**~.~**~:.
Protein phosphorylation and protein ubiquitination regulate most aspects of cell life, and defects in these control mechanisms cause cancer and many other diseases. In the past decade, protein kinases have become one of the most important classes of drug targets for the pharmaceutical industry. In contrast, drug discovery programs that target components of the ubiquitin system have lagged behind. In this Perspective, we discuss the reasons for the delay in this pipeline, the drugs targeting the ubiquitin system that have been developed, and new approaches that may popularize this area of drug discovery in the future.
SuN
.:~**~.~**~.~**~:.
Protein Phosphorylation Drug Discovery
It can take years, even decades, before a field of research reaches
the stage of maturity at which its discoveries can obviously
be exploited for the improvement of health. An excellent example
of this paradigm is the regulation of protein function by reversible
phosphorylation. Phosphorylation was identified in the mid
1950s as a mechanism for controlling glycogenolysis. Twentyfive
years later, it was still largely thought of simply as a control
switch for metabolism. Indeed, researchers finally realized that
protein phosphorylation regulates most aspects of cell life only
after many advances made throughout the 1980s and early
1990s (Cohen, 2002a).
Surprisingly, the idea that it would be possible to treat diseases
with drugs targeting protein kinases was even slower to take
root. Indeed, as late as 1998, the Head of Research and Development
at one major pharmaceutical company (which no longer
exists) told one of the authors that ‘‘there was absolutely no
future in kinase drug discovery.’’ Later that same year,
researchers revealed the remarkable clinical efficacy of a tyrosine
kinase inhibitor, called Gleevec, for treating chronic myelogenous
leukemia. Quite quickly, protein kinases then became one
of the most popular classes of drug targets for the pharmaceutical
industry, especially in the field of cancer treatment.
Over the past decade, 16 drugs targeting one or more protein
kinases have been approved for clinical use in cancer, 12 taken
orally as pills and 4 that are injected. As of 2009, 153 other
protein kinase inhibitors were undergoing clinical trials, and 23
of these drugs were in the most advanced stage of development,
termed Phase III (Table 1) (Lawler, 2009). The current global
market for kinase therapies is about US$15 billion per annum,
and this value is forecasted to double by 2020. Research on
protein kinases currently accounts for 30% of the drug
discovery programs in the pharmaceutical industry and over
50% of cancer research and development. The kinase inhibitors
undergoing Phase III clinical trials include Pfizer’s JAK3 inhibitor
for rheumatoid arthritis (CP-690550) and Incyte Pharmaceutical’s
JAK1/JAK2 inhibitor (INCB18424) for treating inflammatory
diseases. If these drugs are approved, it will likely spark a new
wave of interest in developing kinase inhibitors for the treatment
of diseases other than cancer.
It can take years, even decades, before a field of research reaches
the stage of maturity at which its discoveries can obviously
be exploited for the improvement of health. An excellent example
of this paradigm is the regulation of protein function by reversible
phosphorylation. Phosphorylation was identified in the mid
1950s as a mechanism for controlling glycogenolysis. Twentyfive
years later, it was still largely thought of simply as a control
switch for metabolism. Indeed, researchers finally realized that
protein phosphorylation regulates most aspects of cell life only
after many advances made throughout the 1980s and early
1990s (Cohen, 2002a).
Surprisingly, the idea that it would be possible to treat diseases
with drugs targeting protein kinases was even slower to take
root. Indeed, as late as 1998, the Head of Research and Development
at one major pharmaceutical company (which no longer
exists) told one of the authors that ‘‘there was absolutely no
future in kinase drug discovery.’’ Later that same year,
researchers revealed the remarkable clinical efficacy of a tyrosine
kinase inhibitor, called Gleevec, for treating chronic myelogenous
leukemia. Quite quickly, protein kinases then became one
of the most popular classes of drug targets for the pharmaceutical
industry, especially in the field of cancer treatment.
Over the past decade, 16 drugs targeting one or more protein
kinases have been approved for clinical use in cancer, 12 taken
orally as pills and 4 that are injected. As of 2009, 153 other
protein kinase inhibitors were undergoing clinical trials, and 23
of these drugs were in the most advanced stage of development,
termed Phase III (Table 1) (Lawler, 2009). The current global
market for kinase therapies is about US$15 billion per annum,
and this value is forecasted to double by 2020. Research on
protein kinases currently accounts for 30% of the drug
discovery programs in the pharmaceutical industry and over
50% of cancer research and development. The kinase inhibitors
undergoing Phase III clinical trials include Pfizer’s JAK3 inhibitor
for rheumatoid arthritis (CP-690550) and Incyte Pharmaceutical’s
JAK1/JAK2 inhibitor (INCB18424) for treating inflammatory
diseases. If these drugs are approved, it will likely spark a new
wave of interest in developing kinase inhibitors for the treatment
of diseases other than cancer.
SuN
.:~**~.~**~.~**~:.
Furthermore, far from being a disadvantage, lack of specificity
can actually be an advantage. For example, Gleevec was developed
as an Abelson kinase inhibitor for the treatment of a specific
type of leukemia. However, it is also an effective treatment for
gastrointestinal stromal cancers because it inhibits the c-Kit
receptor and the platelet-derived growth factor (PDGF) receptor
tyrosine kinases, which are overexpressed or mutated in gastrointestinal
cancers (Demetri et al., 2006). In addition, the efficacy
of several anticancer drugs depends on their combined inhibition
of several different kinases, and these drugs may be less prone
to the development of drug resistance than ones that act on only
one specific kinase. Thus, some of the original prejudices against
protein kinases as drug targets have subsequently turned out to
have little substance.
The beauty of targeting protein kinases for therapeutics and
the basis for their popularity is that the same technologies and
small-molecule libraries can be used to develop inhibitors of
many types of protein kinases in almost every therapeutic
area. However, the vast amount of medicinal chemistry that
has been carried out in recent years has meant that novel patent
space is becoming quite difficult to find. Plus, there is a growing,
but probably unfounded, concern that the most important drug
targets in this area have been fully exploited. Therefore, the pharmaceutical
industry has begun to wonder where they may find
the next large set of drug targets that can be tackled in a manner
analogous to protein kinases. In this Perspective, we discuss the
premise that components of the ubiquitin system are prime
candidates for these new targets.
Ubiquitination More Versatile than Phosphorylation?
Ubiquitination is the covalent attachment of a small protein,
ubiquitin (8.5 kDa), to other proteins. In the first step, a thioester
bond is formed between the C-terminal carboxylate group of
ubiquitin and the thiol or sulfhydryl group of a cysteine residue
on an E1-activating enzyme. Next, the ubiquitin is transferred
to a cysteine on an E2-conjugating enzyme. In the third step,
the E2 interacts with an E3 ligase, and the ubiquitin is then transferred
from the E2 enzyme to substrates, which also interact with
the E3 ligase. This last step can occur directly, as in the RING E3
ligases, or it can occur indirectly with the ubiquitin first transferred
to a cysteine residue on the E3 ligase before being linked
to the substrate, as in the HECT family of E3 ligases. Chains of
ubiquitin are created by the same enzymatic process.
Similar to phosphorylation, ubiquitin can be linked covalently
to only one or several amino acid residues on the same protein
(Figure 1). However, in contrast to protein phosphorylation, ubiquitin
can also form polyubiquitin chains. Ubiquitin has seven
lysine residues and an a-amino group; thus eight different types
of polyubiquitin chains can form (and probably more because
chains with ‘‘mixed’’ linkages are also present in cells).
Even greater versatility is provided by ubiquitin-like proteins,
such as Nedd8, SUMO (1, 2, and 3), FAT10, and ISG15, which
are also attached covalently to proteins in processes called neddylation,
SUMOylation, tenylation, and ISGylation, respectively.
The formation of polyubiquitin chains and the existence of these
‘‘ubiquitin-like modifiers’’ make the ubiquitin system a more
complex and potentially more versatile control mechanism
than phosphorylation.
can actually be an advantage. For example, Gleevec was developed
as an Abelson kinase inhibitor for the treatment of a specific
type of leukemia. However, it is also an effective treatment for
gastrointestinal stromal cancers because it inhibits the c-Kit
receptor and the platelet-derived growth factor (PDGF) receptor
tyrosine kinases, which are overexpressed or mutated in gastrointestinal
cancers (Demetri et al., 2006). In addition, the efficacy
of several anticancer drugs depends on their combined inhibition
of several different kinases, and these drugs may be less prone
to the development of drug resistance than ones that act on only
one specific kinase. Thus, some of the original prejudices against
protein kinases as drug targets have subsequently turned out to
have little substance.
The beauty of targeting protein kinases for therapeutics and
the basis for their popularity is that the same technologies and
small-molecule libraries can be used to develop inhibitors of
many types of protein kinases in almost every therapeutic
area. However, the vast amount of medicinal chemistry that
has been carried out in recent years has meant that novel patent
space is becoming quite difficult to find. Plus, there is a growing,
but probably unfounded, concern that the most important drug
targets in this area have been fully exploited. Therefore, the pharmaceutical
industry has begun to wonder where they may find
the next large set of drug targets that can be tackled in a manner
analogous to protein kinases. In this Perspective, we discuss the
premise that components of the ubiquitin system are prime
candidates for these new targets.
Ubiquitination More Versatile than Phosphorylation?
Ubiquitination is the covalent attachment of a small protein,
ubiquitin (8.5 kDa), to other proteins. In the first step, a thioester
bond is formed between the C-terminal carboxylate group of
ubiquitin and the thiol or sulfhydryl group of a cysteine residue
on an E1-activating enzyme. Next, the ubiquitin is transferred
to a cysteine on an E2-conjugating enzyme. In the third step,
the E2 interacts with an E3 ligase, and the ubiquitin is then transferred
from the E2 enzyme to substrates, which also interact with
the E3 ligase. This last step can occur directly, as in the RING E3
ligases, or it can occur indirectly with the ubiquitin first transferred
to a cysteine residue on the E3 ligase before being linked
to the substrate, as in the HECT family of E3 ligases. Chains of
ubiquitin are created by the same enzymatic process.
Similar to phosphorylation, ubiquitin can be linked covalently
to only one or several amino acid residues on the same protein
(Figure 1). However, in contrast to protein phosphorylation, ubiquitin
can also form polyubiquitin chains. Ubiquitin has seven
lysine residues and an a-amino group; thus eight different types
of polyubiquitin chains can form (and probably more because
chains with ‘‘mixed’’ linkages are also present in cells).
Even greater versatility is provided by ubiquitin-like proteins,
such as Nedd8, SUMO (1, 2, and 3), FAT10, and ISG15, which
are also attached covalently to proteins in processes called neddylation,
SUMOylation, tenylation, and ISGylation, respectively.
The formation of polyubiquitin chains and the existence of these
‘‘ubiquitin-like modifiers’’ make the ubiquitin system a more
complex and potentially more versatile control mechanism
than phosphorylation.
SuN
.:~**~.~**~.~**~:.
The Future of Ubiquitin Drug Discovery
There are striking parallels between the histories of protein phosphorylation
and protein ubiquitination and their exploitation for
the development of drugs to treat diseases (Table 1). Both biological
control mechanisms were identified many years ago,
but interest in targeting them for drug discovery only started to
take off in the 1990s. Indeed, the first compounds inhibiting
components of these systems entered clinical trials at around
the same time (Bortezomib—1997, Gleevec—1998), and these
drugs were among the fastest ever approved for clinical use
(Gleevec—2001, Bortezomib—2003). Both Gleevec and Bortezomib
subsequently achieved ‘‘blockbuster’’ status with current
sales of about US$3 billion (Gleevec) and US$1.4 billion (Bortezomib)
per annum.
However, that is where their similarities end. Since the development
of Gleevec, 15 other drugs targeting a specific protein
kinase have been approved for clinical use, but no other drug targeting
a particular component of the ubiquitin system has yet
been approved. In addition, kinase inhibitors currently undergoing
clinical trials also outnumber the inhibitors of the ubiquitin
system by more than ten to one (Table 1).
Why has drug discovery in the ubiquitin system lagged so far
behind that of protein kinases, and what is needed to change
this state of affairs in the future? In retrospect, one factor driving
the kinase field forward at such a rapid pace is the ease with
which large and varied chemical libraries can be synthesized
and exploited to develop inhibitors of many protein kinases.
Further, receptor tyrosine kinases have extracellular domains
that can also be targeted with therapeutic antibodies. In
contrast, although E3 ubiquitin ligases outnumber protein
kinases, researchers still have not developed a general approach
for identifying inhibitors of many E3 ubiquitin ligases. This is
because, thus far, researchers have focused primarily on disrupting
the interaction between E3 ligases and their substrates,
which is specific to particular E3 ligase-substrate pairs. Moreover,
finding compounds to disrupt the interface of two proteins
can be intrinsically more difficult to achieve than searching for
small molecules that block catalytic activity.
Surprisingly, little effort has been devoted to developing
compounds that disrupt the interactions between E2-conjugating
enzymes and E3 ligases. E2-E3 interactions are usually relatively
weak (Ye and Rape, 2009) and may therefore be relatively easy
to disrupt. Moreover, compounds that disturb the interaction
between anE2-conjugatingenzyme andanE3ligase could, in principle,
exert their effects by binding to the E2, the E3, or the E2-E3
interface, creating the potential to identify three types of inhibitors
from a single screen. There are 40 E2-conjugating enzymes encoded
by the human genome; therefore, on average, each E2
must interact productively with 15 E3 ligases. Compounds that
disrupt E2-E3 interactions by binding specifically to the E3 ligase
could be identified by counterscreening with another E3 ligase
that also forms a productive interaction with the same E2. Indeed,
focusing efforts on large families of E3 ligases, such as the Cullin
RING ligases, may lead to the development of chemical libraries
with the capability of disrupting many E2-E3 interactions.
By analogy with kinases, perhaps the key to developing inhibitors
of specific E2-E3 interactions is to find compounds that
bind to small hydrophobic pockets on E3 ligases located
proximal to the E2-E3 interface itself or to identify allosteric inhibitors
that disrupt the E2-E3 interaction by inducing long-range
conformational changes. The three-dimensional structure of an
E2-ubiquitin thiol ester-E3 ligase complex has yet to be reported,
but such a structure might be extremely helpful in understanding
how E2-E3 interactions could be disrupted. To crystallize such
a complex, it might be necessary to stabilize the E2-ubiquitin
thiol ester-E3 interactions by including a small molecule that
inactivates E3 ligase function without affecting its ability to
bind to the E2-conjugating enzyme.
There are striking parallels between the histories of protein phosphorylation
and protein ubiquitination and their exploitation for
the development of drugs to treat diseases (Table 1). Both biological
control mechanisms were identified many years ago,
but interest in targeting them for drug discovery only started to
take off in the 1990s. Indeed, the first compounds inhibiting
components of these systems entered clinical trials at around
the same time (Bortezomib—1997, Gleevec—1998), and these
drugs were among the fastest ever approved for clinical use
(Gleevec—2001, Bortezomib—2003). Both Gleevec and Bortezomib
subsequently achieved ‘‘blockbuster’’ status with current
sales of about US$3 billion (Gleevec) and US$1.4 billion (Bortezomib)
per annum.
However, that is where their similarities end. Since the development
of Gleevec, 15 other drugs targeting a specific protein
kinase have been approved for clinical use, but no other drug targeting
a particular component of the ubiquitin system has yet
been approved. In addition, kinase inhibitors currently undergoing
clinical trials also outnumber the inhibitors of the ubiquitin
system by more than ten to one (Table 1).
Why has drug discovery in the ubiquitin system lagged so far
behind that of protein kinases, and what is needed to change
this state of affairs in the future? In retrospect, one factor driving
the kinase field forward at such a rapid pace is the ease with
which large and varied chemical libraries can be synthesized
and exploited to develop inhibitors of many protein kinases.
Further, receptor tyrosine kinases have extracellular domains
that can also be targeted with therapeutic antibodies. In
contrast, although E3 ubiquitin ligases outnumber protein
kinases, researchers still have not developed a general approach
for identifying inhibitors of many E3 ubiquitin ligases. This is
because, thus far, researchers have focused primarily on disrupting
the interaction between E3 ligases and their substrates,
which is specific to particular E3 ligase-substrate pairs. Moreover,
finding compounds to disrupt the interface of two proteins
can be intrinsically more difficult to achieve than searching for
small molecules that block catalytic activity.
Surprisingly, little effort has been devoted to developing
compounds that disrupt the interactions between E2-conjugating
enzymes and E3 ligases. E2-E3 interactions are usually relatively
weak (Ye and Rape, 2009) and may therefore be relatively easy
to disrupt. Moreover, compounds that disturb the interaction
between anE2-conjugatingenzyme andanE3ligase could, in principle,
exert their effects by binding to the E2, the E3, or the E2-E3
interface, creating the potential to identify three types of inhibitors
from a single screen. There are 40 E2-conjugating enzymes encoded
by the human genome; therefore, on average, each E2
must interact productively with 15 E3 ligases. Compounds that
disrupt E2-E3 interactions by binding specifically to the E3 ligase
could be identified by counterscreening with another E3 ligase
that also forms a productive interaction with the same E2. Indeed,
focusing efforts on large families of E3 ligases, such as the Cullin
RING ligases, may lead to the development of chemical libraries
with the capability of disrupting many E2-E3 interactions.
By analogy with kinases, perhaps the key to developing inhibitors
of specific E2-E3 interactions is to find compounds that
bind to small hydrophobic pockets on E3 ligases located
proximal to the E2-E3 interface itself or to identify allosteric inhibitors
that disrupt the E2-E3 interaction by inducing long-range
conformational changes. The three-dimensional structure of an
E2-ubiquitin thiol ester-E3 ligase complex has yet to be reported,
but such a structure might be extremely helpful in understanding
how E2-E3 interactions could be disrupted. To crystallize such
a complex, it might be necessary to stabilize the E2-ubiquitin
thiol ester-E3 interactions by including a small molecule that
inactivates E3 ligase function without affecting its ability to
bind to the E2-conjugating enzyme.
SuN
.:~**~.~**~.~**~:.
The U.N. independent investigator promoting physical and mental health on Monday urged decriminalization of narcotics use, saying punishment and sanctions don't cure drug dependency.
Anand Grover, a well-known lawyer from India, also said the war on drugs has ignored drug users' human rights.
Grover is the U.N. Human Rights Council's special rapporteur on physical and mental health. He told the General Assembly committee dealing with rights issues that people who use drugs may not get the health care they need for fear of being arrested, or may be denied health care if they seek help.
Drug users also may be sent to compulsory treatment centres where they undergo forced labour, detention, military-type drills, physical exercises and other types of interventions whose effectiveness he said is not backed by scientific evidence, he said.
"People who use drugs and people who are dependent on drugs possess the same freedoms and entitlements guaranteed by international legal instruments," said Grover. "Both groups experience violations of their rights" under current international drug enforcement practices, he said.
He said decriminalization of drug use would not make it legal, but would eliminate prison terms and other sanctions that do not cure addiction.
"The current international system of drug control has focused on creating a drug-free world, almost exclusively through use of law enforcement policies and criminal sanctions," Grover wrote.
"Mounting evidence, however, suggests this approach has failed, primarily because it does not acknowledge the realities of drug use and dependence,' he said. "While drugs may have a pernicious effect on individual lives and society, this excessively punitive regime has not achieved its stated public health goals, and has resulted in countless human rights violations."
Grover said "nearly 90 to 100 per cent of people who use drugs returned to drug use after being subjected to forced treatment."
"The United Nations entities and member states should adopt a right-to-health approach to drug control," he argued.
As for legal drugs, he complained that people in many countries have limited access to essential medications, especially for emergency obstetric procedures and management of epilepsy.
"An alarming availability gap exists between the developed and developing world in relation to the supply of essential medicines," he said. "About 89 per cent of all legally controlled medicines, including morphine, is consumed by North America and Europe."
Anand Grover, a well-known lawyer from India, also said the war on drugs has ignored drug users' human rights.
Grover is the U.N. Human Rights Council's special rapporteur on physical and mental health. He told the General Assembly committee dealing with rights issues that people who use drugs may not get the health care they need for fear of being arrested, or may be denied health care if they seek help.
Drug users also may be sent to compulsory treatment centres where they undergo forced labour, detention, military-type drills, physical exercises and other types of interventions whose effectiveness he said is not backed by scientific evidence, he said.
"People who use drugs and people who are dependent on drugs possess the same freedoms and entitlements guaranteed by international legal instruments," said Grover. "Both groups experience violations of their rights" under current international drug enforcement practices, he said.
He said decriminalization of drug use would not make it legal, but would eliminate prison terms and other sanctions that do not cure addiction.
"The current international system of drug control has focused on creating a drug-free world, almost exclusively through use of law enforcement policies and criminal sanctions," Grover wrote.
"Mounting evidence, however, suggests this approach has failed, primarily because it does not acknowledge the realities of drug use and dependence,' he said. "While drugs may have a pernicious effect on individual lives and society, this excessively punitive regime has not achieved its stated public health goals, and has resulted in countless human rights violations."
Grover said "nearly 90 to 100 per cent of people who use drugs returned to drug use after being subjected to forced treatment."
"The United Nations entities and member states should adopt a right-to-health approach to drug control," he argued.
As for legal drugs, he complained that people in many countries have limited access to essential medications, especially for emergency obstetric procedures and management of epilepsy.
"An alarming availability gap exists between the developed and developing world in relation to the supply of essential medicines," he said. "About 89 per cent of all legally controlled medicines, including morphine, is consumed by North America and Europe."
SuN
.:~**~.~**~.~**~:.
Professor Roger Hood
Those of us who have attempted to provide an accurate and up-to-date account of the status of capital punishment in all countries of the world know how difficult this task proves to be. This is especially so in relation to crimes other than murder, such as drug offences.
The researcher is faced with discovering whether existing laws prescribing the death sentence for such offences are still extant or whether new ones have been enacted and whether they mandate death as the sole sentence that can be imposed or whether the courts have discretion over when to impose the ultimate penalty. It is also, of course, necessary to gauge the extent to which in practice death sentences are imposed and executions carried out. It is not merely that information on legislation may be out of date, the statistical data on the number of death sentences imposed and persons executed in each year may be hidden from view by state security services or simply not reported by Ministries of Justice in a systematic fashion. Furthermore, many of the countries that actively retain the death penalty do not respond to the UN Secretary General’s quinquennial surveys which seek such information, despite a resolution from the Economic and Social Council as long ago as 1989 (1989/64) calling upon all UN states to make such information available to the Secretary General on an annual basis.
The researcher is therefore reliant on reports from human rights NGOs, newspaper reports and other secondary sources, all of which can usually only estimate the extent to which nations have recourse to capital punishment for drug offences. Thus, in order to chart whether there has been any progress towards abolition of the death penalty for such offences, it is necessary to mount regular in-depth surveys of the situation.
This immensely valuable survey, carried out by Patrick Gallahue and Rick Lines at the International Harm Reduction Association, provides such an update. The message it conveys is admirably clear and gives cause for optimism. Article 6(2) of the International Covenant of Civil and Political Rights (ICCPR) grants an exception to the right to life guaranteed in Article 6(1) to countries that have not as yet abolished the death penalty, but only in relation to ‘the most serious crimes’. The jurisprudence, as this paper shows, has developed to the point where human rights bodies have declared that drug offences are not among the ‘most serious’ crimes: indeed that the death penalty, pending universal abolition, should be restricted to wilful murder, and even then be a discretionary penalty.
Going beyond this, the authors’ analysis shows that there are thirty-two countries that retain the death penalty in law for certain drug offences, but, in recent years, only six of them have enforced it through executions on a scale that could be described as indicating a ‘high commitment’ to the practice.
Singapore and Malaysia have recently greatly reduced the number of persons they execute each year and that Viet Nam may be giving serious consideration to its policy and practice. There are indications too that the number of executions in China may fall as the Supreme People’s Court further develops its guidelines to restrict the scope and application of the death penalty. It is now essential that all the countries in this small group of apparently committed states publish the data that would make their practices transparent to their own populations and the international community.
At the other end of the spectrum, five countries with the death penalty for drug offences on their statute books have executed no persons for any offence for over ten years and can therefore be truly regarded as abolitionist de facto. In another nine countries, executions for drug offences have dwindled so much and are so sporadically carried out (even though death sentences may continue to be imposed) that they can safely be classified as having only a ‘symbolic commitment’ to the policy of deterring the trade in illicit drugs through threatening certainty of execution for such crimes. Their practice of occasionally yet rarely carrying out executions is by definition arbitrary and therefore unjust. Given the political will, all fourteen of these countries could immediately abolish capital punishment for drug offences.
In the middle are eight countries that the authors describe as having a ‘low commitment’. It is especially regrettable that almost all these countries fail to provide statistical data that would have enabled this survey to provide an accurate count of death sentences and executions and thus an analysis of the progress towards cessation of executions. Nevertheless the material provided suggests that several of them, such as Pakistan and Bangladesh, may be already moving to a symbolic use of capital punishment for drug offences.
Regrettably, there were four countries where the data was so insufficient that it was impossible to put them reliably into any of the three categories.
Nine of the thirty-two countries which threaten drug offenders with death are not parties to the ICCPR: three of them are ‘high commitment’ states – namely Saudi Arabia, Singapore and Malaysia(and China has yet to ratify the Covenant, twelve years after becoming a signatory in 1998). The other six countries appear to have only a ‘symbolic’ commitment. Ratification of the treaty by all these countries would be likely to move them further towards agreement that to kill prisoners for drug offences is a breach of their right to life and their right to be free from the threat of a cruel, inhuman and degrading punishment.
Those of us who have attempted to provide an accurate and up-to-date account of the status of capital punishment in all countries of the world know how difficult this task proves to be. This is especially so in relation to crimes other than murder, such as drug offences.
The researcher is faced with discovering whether existing laws prescribing the death sentence for such offences are still extant or whether new ones have been enacted and whether they mandate death as the sole sentence that can be imposed or whether the courts have discretion over when to impose the ultimate penalty. It is also, of course, necessary to gauge the extent to which in practice death sentences are imposed and executions carried out. It is not merely that information on legislation may be out of date, the statistical data on the number of death sentences imposed and persons executed in each year may be hidden from view by state security services or simply not reported by Ministries of Justice in a systematic fashion. Furthermore, many of the countries that actively retain the death penalty do not respond to the UN Secretary General’s quinquennial surveys which seek such information, despite a resolution from the Economic and Social Council as long ago as 1989 (1989/64) calling upon all UN states to make such information available to the Secretary General on an annual basis.
The researcher is therefore reliant on reports from human rights NGOs, newspaper reports and other secondary sources, all of which can usually only estimate the extent to which nations have recourse to capital punishment for drug offences. Thus, in order to chart whether there has been any progress towards abolition of the death penalty for such offences, it is necessary to mount regular in-depth surveys of the situation.
This immensely valuable survey, carried out by Patrick Gallahue and Rick Lines at the International Harm Reduction Association, provides such an update. The message it conveys is admirably clear and gives cause for optimism. Article 6(2) of the International Covenant of Civil and Political Rights (ICCPR) grants an exception to the right to life guaranteed in Article 6(1) to countries that have not as yet abolished the death penalty, but only in relation to ‘the most serious crimes’. The jurisprudence, as this paper shows, has developed to the point where human rights bodies have declared that drug offences are not among the ‘most serious’ crimes: indeed that the death penalty, pending universal abolition, should be restricted to wilful murder, and even then be a discretionary penalty.
Going beyond this, the authors’ analysis shows that there are thirty-two countries that retain the death penalty in law for certain drug offences, but, in recent years, only six of them have enforced it through executions on a scale that could be described as indicating a ‘high commitment’ to the practice.
Singapore and Malaysia have recently greatly reduced the number of persons they execute each year and that Viet Nam may be giving serious consideration to its policy and practice. There are indications too that the number of executions in China may fall as the Supreme People’s Court further develops its guidelines to restrict the scope and application of the death penalty. It is now essential that all the countries in this small group of apparently committed states publish the data that would make their practices transparent to their own populations and the international community.
At the other end of the spectrum, five countries with the death penalty for drug offences on their statute books have executed no persons for any offence for over ten years and can therefore be truly regarded as abolitionist de facto. In another nine countries, executions for drug offences have dwindled so much and are so sporadically carried out (even though death sentences may continue to be imposed) that they can safely be classified as having only a ‘symbolic commitment’ to the policy of deterring the trade in illicit drugs through threatening certainty of execution for such crimes. Their practice of occasionally yet rarely carrying out executions is by definition arbitrary and therefore unjust. Given the political will, all fourteen of these countries could immediately abolish capital punishment for drug offences.
In the middle are eight countries that the authors describe as having a ‘low commitment’. It is especially regrettable that almost all these countries fail to provide statistical data that would have enabled this survey to provide an accurate count of death sentences and executions and thus an analysis of the progress towards cessation of executions. Nevertheless the material provided suggests that several of them, such as Pakistan and Bangladesh, may be already moving to a symbolic use of capital punishment for drug offences.
Regrettably, there were four countries where the data was so insufficient that it was impossible to put them reliably into any of the three categories.
Nine of the thirty-two countries which threaten drug offenders with death are not parties to the ICCPR: three of them are ‘high commitment’ states – namely Saudi Arabia, Singapore and Malaysia(and China has yet to ratify the Covenant, twelve years after becoming a signatory in 1998). The other six countries appear to have only a ‘symbolic’ commitment. Ratification of the treaty by all these countries would be likely to move them further towards agreement that to kill prisoners for drug offences is a breach of their right to life and their right to be free from the threat of a cruel, inhuman and degrading punishment.
SuN
.:~**~.~**~.~**~:.
Professor Roger Hood
Those of us who have attempted to provide an accurate and up-to-date account of the status of capital punishment in all countries of the world know how difficult this task proves to be. This is especially so in relation to crimes other than murder, such as drug offences.
The researcher is faced with discovering whether existing laws prescribing the death sentence for such offences are still extant or whether new ones have been enacted and whether they mandate death as the sole sentence that can be imposed or whether the courts have discretion over when to impose the ultimate penalty. It is also, of course, necessary to gauge the extent to which in practice death sentences are imposed and executions carried out. It is not merely that information on legislation may be out of date, the statistical data on the number of death sentences imposed and persons executed in each year may be hidden from view by state security services or simply not reported by Ministries of Justice in a systematic fashion. Furthermore, many of the countries that actively retain the death penalty do not respond to the UN Secretary General’s quinquennial surveys which seek such information, despite a resolution from the Economic and Social Council as long ago as 1989 (1989/64) calling upon all UN states to make such information available to the Secretary General on an annual basis.
The researcher is therefore reliant on reports from human rights NGOs, newspaper reports and other secondary sources, all of which can usually only estimate the extent to which nations have recourse to capital punishment for drug offences. Thus, in order to chart whether there has been any progress towards abolition of the death penalty for such offences, it is necessary to mount regular in-depth surveys of the situation.
This immensely valuable survey, carried out by Patrick Gallahue and Rick Lines at the International Harm Reduction Association, provides such an update. The message it conveys is admirably clear and gives cause for optimism. Article 6(2) of the International Covenant of Civil and Political Rights (ICCPR) grants an exception to the right to life guaranteed in Article 6(1) to countries that have not as yet abolished the death penalty, but only in relation to ‘the most serious crimes’. The jurisprudence, as this paper shows, has developed to the point where human rights bodies have declared that drug offences are not among the ‘most serious’ crimes: indeed that the death penalty, pending universal abolition, should be restricted to wilful murder, and even then be a discretionary penalty.
Going beyond this, the authors’ analysis shows that there are thirty-two countries that retain the death penalty in law for certain drug offences, but, in recent years, only six of them have enforced it through executions on a scale that could be described as indicating a ‘high commitment’ to the practice.
Singapore and Malaysia have recently greatly reduced the number of persons they execute each year and that Viet Nam may be giving serious consideration to its policy and practice. There are indications too that the number of executions in China may fall as the Supreme People’s Court further develops its guidelines to restrict the scope and application of the death penalty. It is now essential that all the countries in this small group of apparently committed states publish the data that would make their practices transparent to their own populations and the international community.
At the other end of the spectrum, five countries with the death penalty for drug offences on their statute books have executed no persons for any offence for over ten years and can therefore be truly regarded as abolitionist de facto. In another nine countries, executions for drug offences have dwindled so much and are so sporadically carried out (even though death sentences may continue to be imposed) that they can safely be classified as having only a ‘symbolic commitment’ to the policy of deterring the trade in illicit drugs through threatening certainty of execution for such crimes. Their practice of occasionally yet rarely carrying out executions is by definition arbitrary and therefore unjust. Given the political will, all fourteen of these countries could immediately abolish capital punishment for drug offences.
In the middle are eight countries that the authors describe as having a ‘low commitment’. It is especially regrettable that almost all these countries fail to provide statistical data that would have enabled this survey to provide an accurate count of death sentences and executions and thus an analysis of the progress towards cessation of executions. Nevertheless the material provided suggests that several of them, such as Pakistan and Bangladesh, may be already moving to a symbolic use of capital punishment for drug offences.
Regrettably, there were four countries where the data was so insufficient that it was impossible to put them reliably into any of the three categories.
Nine of the thirty-two countries which threaten drug offenders with death are not parties to the ICCPR: three of them are ‘high commitment’ states – namely Saudi Arabia, Singapore and Malaysia(and China has yet to ratify the Covenant, twelve years after becoming a signatory in 1998). The other six countries appear to have only a ‘symbolic’ commitment. Ratification of the treaty by all these countries would be likely to move them further towards agreement that to kill prisoners for drug offences is a breach of their right to life and their right to be free from the threat of a cruel, inhuman and degrading punishment.
Those of us who have attempted to provide an accurate and up-to-date account of the status of capital punishment in all countries of the world know how difficult this task proves to be. This is especially so in relation to crimes other than murder, such as drug offences.
The researcher is faced with discovering whether existing laws prescribing the death sentence for such offences are still extant or whether new ones have been enacted and whether they mandate death as the sole sentence that can be imposed or whether the courts have discretion over when to impose the ultimate penalty. It is also, of course, necessary to gauge the extent to which in practice death sentences are imposed and executions carried out. It is not merely that information on legislation may be out of date, the statistical data on the number of death sentences imposed and persons executed in each year may be hidden from view by state security services or simply not reported by Ministries of Justice in a systematic fashion. Furthermore, many of the countries that actively retain the death penalty do not respond to the UN Secretary General’s quinquennial surveys which seek such information, despite a resolution from the Economic and Social Council as long ago as 1989 (1989/64) calling upon all UN states to make such information available to the Secretary General on an annual basis.
The researcher is therefore reliant on reports from human rights NGOs, newspaper reports and other secondary sources, all of which can usually only estimate the extent to which nations have recourse to capital punishment for drug offences. Thus, in order to chart whether there has been any progress towards abolition of the death penalty for such offences, it is necessary to mount regular in-depth surveys of the situation.
This immensely valuable survey, carried out by Patrick Gallahue and Rick Lines at the International Harm Reduction Association, provides such an update. The message it conveys is admirably clear and gives cause for optimism. Article 6(2) of the International Covenant of Civil and Political Rights (ICCPR) grants an exception to the right to life guaranteed in Article 6(1) to countries that have not as yet abolished the death penalty, but only in relation to ‘the most serious crimes’. The jurisprudence, as this paper shows, has developed to the point where human rights bodies have declared that drug offences are not among the ‘most serious’ crimes: indeed that the death penalty, pending universal abolition, should be restricted to wilful murder, and even then be a discretionary penalty.
Going beyond this, the authors’ analysis shows that there are thirty-two countries that retain the death penalty in law for certain drug offences, but, in recent years, only six of them have enforced it through executions on a scale that could be described as indicating a ‘high commitment’ to the practice.
Singapore and Malaysia have recently greatly reduced the number of persons they execute each year and that Viet Nam may be giving serious consideration to its policy and practice. There are indications too that the number of executions in China may fall as the Supreme People’s Court further develops its guidelines to restrict the scope and application of the death penalty. It is now essential that all the countries in this small group of apparently committed states publish the data that would make their practices transparent to their own populations and the international community.
At the other end of the spectrum, five countries with the death penalty for drug offences on their statute books have executed no persons for any offence for over ten years and can therefore be truly regarded as abolitionist de facto. In another nine countries, executions for drug offences have dwindled so much and are so sporadically carried out (even though death sentences may continue to be imposed) that they can safely be classified as having only a ‘symbolic commitment’ to the policy of deterring the trade in illicit drugs through threatening certainty of execution for such crimes. Their practice of occasionally yet rarely carrying out executions is by definition arbitrary and therefore unjust. Given the political will, all fourteen of these countries could immediately abolish capital punishment for drug offences.
In the middle are eight countries that the authors describe as having a ‘low commitment’. It is especially regrettable that almost all these countries fail to provide statistical data that would have enabled this survey to provide an accurate count of death sentences and executions and thus an analysis of the progress towards cessation of executions. Nevertheless the material provided suggests that several of them, such as Pakistan and Bangladesh, may be already moving to a symbolic use of capital punishment for drug offences.
Regrettably, there were four countries where the data was so insufficient that it was impossible to put them reliably into any of the three categories.
Nine of the thirty-two countries which threaten drug offenders with death are not parties to the ICCPR: three of them are ‘high commitment’ states – namely Saudi Arabia, Singapore and Malaysia(and China has yet to ratify the Covenant, twelve years after becoming a signatory in 1998). The other six countries appear to have only a ‘symbolic’ commitment. Ratification of the treaty by all these countries would be likely to move them further towards agreement that to kill prisoners for drug offences is a breach of their right to life and their right to be free from the threat of a cruel, inhuman and degrading punishment.