TGN 1412 was a drug produced by genetic engineering.
I have not seen reports of this in the US media.
Tom
Subj: GMW: Calamitous GM drug trial raises questions about modern science
Date: 4/5/2006 5:21:48 PM Central Daylight Time
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http://www.gmwatch.org
---
1.Ziauddin Sardar takes a drugs trial
2.'No faults in calamitous drug trial'
The genetically engineered drug TGN1412 given to six men in a clinical trial
who subsequently suffered multiple organ failure has been found not to have
been contaminated during the manufacturing process. It also appears to have been
administered to the men according to the proper protocols.
This suggests the adverse reactions suffered by the trial volunteers were
caused by the nature of the drug itself. (item 2)
The first article below considers how "this tragedy provides us with an
opportunity to think about the nature of science itself." (item 1)
EXCERPTS: "The researchers were ignorant of their own ignorance. But, as a
New Scientist investigation revealed, they also failed to consider the
possibility of things going wrong. In other words, ignorance was written out of the
equation. This double ignorance, or ignorance-of-ignorance, is rapidly becoming a
dominant theme in science."
"this tragedy provides us with an opportunity to think about the nature of
science itself. How radically science has changed. How intrinsic uncertainty has
become to scientific practice."
"The only sensible way to handle risk is by learning to respect uncertainty.
The alternative is to stumble along blindly from tragedy to disaster. This
time it was a clinical trial that went wrong, with tragic consequences for six
volunteers. In the case of nanotechnology, for instance, there could be serious
repercussions for us all."
---
1.Ziauddin Sardar takes a drugs trial
Ziauddin Sardar
New Statesman, 3rd April 2006
http://www.newstatesman.com/200604030017
Science has ceased to be normal "puzzle solving". Welcome to the era of
post-normal science, writes Ziauddin Sardar
Science is not what it used to be. We tend to become aware of this every time
a disaster occurs in which science is implicated. The tragedy of the recent
drug trial at Northwick Park Hospital in London is a good example. The six
human guinea pigs suffered multiple organ failure within hours of taking an
experimental drug. Two of them are still in a critical condition.
So what went wrong? The volunteers were given the smallest possible dose of
TGN1412, an anti-inflammatory medicine made by the German pharmaceutical
company TeGenero. Intended to fight leukaemia, rheumatoid arthritis and multiple
sclerosis, it had already been tested on animals. TeGenero insists that it
followed "best practice". The Medicines and Healthcare Products Regulatory Agency
(MHRA), which halted the trial, is investigating whether the reaction suffered
by the men was caused by a manufacturing problem, contamination, a dosing
error, or whether it was some "completely unanticipated side effect of the drug in
humans".
The scope of the MHRA inquiry suggests we are dealing with a system involving
a range of actors and many different stages. Anything could have gone wrong
at any, or all, of these stages; and any one or all of the actors involved
could have botched things unwittingly. This is not "textbook" science, where
everything is arranged so that nothing goes wrong and there is only one answer to
every problem. Science in the real world is a dirty, highly complex business.
But the MHRA's brief tells us something more. "Completely unanticipated side
effect" is a euphemism for ignorance. In the real world, science and ignorance
go hand in hand. There are two aspects to this ignorance. The testers assumed
that we know enough about the immune system to proceed confidently. But the
immune system is mind-bogglingly complex and our understanding of it is rather
limited. The researchers were ignorant of their own ignorance. But, as a New
Scientist investigation revealed, they also failed to consider the possibility
of things going wrong. In other words, ignorance was written out of the
equation. This double ignorance, or ignorance-of-ignorance, is rapidly becoming a
dominant theme in science.
Normally, such testing is done with full awareness of its risks. That is why
we have the whole machinery of prior checks and approvals to ensure safety,
or, in other words, quality. Frequently, when something goes drastically wrong,
it turns out that the quality-control machinery was not operating well: that
is, the quality-of-quality was defective. This may turn out to have been the
case with the Northwick Park trials. What this implies is that regulatory checks
were either bypassed or rubber-stamped. Most of the time, it doesn't matter -
but sometimes it does.
It mattered in the fatal case of Jesse Gelsinger. In 1999, 18-year-old
Gelsinger volunteered to take part in gene therapy trials at the University of
Pennsylvania. To get the corrective genes into his system, he was injected with the
common-cold virus, laced with copies of the genes. Doctors had calculated
that he required a huge dose, but no one had done the maths which would have
shown that the virus itself could kill him. Is this what happened in the TGN1412
trial - no one had worked out that super-stimulating the immune system could
lead just as easily to a catastrophe as to a cure?
We do need to develop drugs that use the immune system. But this tragedy
provides us with an opportunity to think about the nature of science itself. How
radically science has changed. How intrinsic uncertainty has become to
scientific practice. How ignorance-of-ignorance is inherent in all scientific
endeavour. How every advance in science brings its own risks. In other words, science
has ceased to be normal "puzzle solving". Welcome to the era of post-normal
science.
The man who has pioneered our understanding of post-normal science just
happens to be my best friend. Way back in 1971, Jerry Ravetz established himself as
one of our most prominent philosophers of science with his book Scientific
Knowledge and Its Social Problems. In the 1980s, he highlighted the benefits and
risks of genetically engineered organisms - that work remains unsurpassed. In
the 1990s, he developed a whole new mathematics for dealing with scientific
risk and uncertainty. Now, once again, he is venturing where most scientists
and philosophers fear to tread.
Scientists don't like their critics; they are even less keen on philosophers
of science. But we ignore Ravetz at our peril. Science has become a
multidimensional process, says Ravetz, now at the James Martin Institute for Science and
Civilisation in Oxford. We need new ideas to understand it and new tools to
manage the risks involved. The only sensible way to handle risk is by learning
to respect uncertainty. The alternative is to stumble along blindly from
tragedy to disaster. This time it was a clinical trial that went wrong, with tragic
consequences for six volunteers. In the case of nanotechnology, for instance,
there could be serious repercussions for us all.
I think it's time we paid attention. Ravetz's ideas about risk, ignorance and
quality may just hold the key to our survival.
The No-Nonsense Guide to Science by Jerry Ravetz is published by Verso/New
Internationalist (GBP7)
---
2.'No faults in calamitous drug trial'
Staff and agencies
Wednesday April 5, 2006
http://www.guardian.co.uk/medicine/story/0,,1747611,00.html?gusrc=rss
There is "no evidence" that an experimental drug given to six men in a
clinical trial who subsequently suffered multiple organ failure was contaminated
during the manufacturing process, the government's medicines watchdog said today.
The Medicines and Healthcare Products Regulatory Agency (MHRA) said it
appeared that the drug TGN1412 did not contain "anything other than the correct
ingredients".
The regulator, which is responsible for the safety of medicines, also found
no evidence that the trial was run in a way that may have contributed to the
serious reactions suffered by the volunteers.
An interim report by the MHRA cautioned that it could not be certain about
its findings yet, but it seemed TGN1412 produced adverse reactions in humans
that were not picked up by earlier animal testing of the drug.
The medicines watchdog said the trial, which was carried out by the US
company Parexel, was run according to approved protocol with the correct dose of
TGN1412 given to the volunteers.
"If these findings were to be confirmed, it would indicate that this product
showed a pharmacological effect in man which was not seen in pre-clinical
tests in animals at much higher doses," the regulator's chief executive, professor
Kent Woods, said.
TGN1412 is one of a class of drugs known as monoclonal antibodies. They are
genetically engineered versions of antibodies, the body's natural immune
defences against infections.
Unlike traditional chemically-engineered compounds, monoclonal antibodies are
designed to be accepted by the human body, which experts say makes it
difficult to determine through animal testing what dose would be toxic to humans.
The health secretary, Patricia Hewitt, today announced the establishment of a
group of international experts to investigate whether trials of monoclonal
antibodies may need to be revised.
Five of the six volunteers have already been discharged from Northwick Park
hospital in north-west London, with the latest allowed home today. The
remaining volunteer is still undergoing treatment but is no longer in intensive care.
Two of the men, aged between 18 and 40, became critically ill and another
four were left in a serious condition after receiving the drug during the trial
last month.
The drug, developed by German pharmaceutical company TeGenero, was being
trialled for the treatment of leukemia, multiple sclerosis and rheumatoid
arthritis. The trial, carried out at an independent centre at Northwick Park, was the
first time it had been tested on humans.
The MHRA's initial findings appear to confirm speculation by pharmaceutical
experts that the adverse reaction suffered by the trail volunteers were caused
by the nature of the drug itself.
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