drug trial raises questions about modern science

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GMW: Calamitous GM drug trial raises questions about modern

science

" GM WATCH " <info

Wed, 5 Apr 2006 23:20:32 +0100

 

 

 

GM WATCH daily

http://www.gmwatch.org

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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. "

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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)

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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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