From: Josh Bembenek (jbembe@hotmail.com)
Date: Thu Mar 27 2003 - 13:30:18 EST
ASA Folks:
I have heard several times from various responses that the fact that humans
and apes are related through common descent is most supported by the fact
that both genomes have incorporated the same retrovirus at the same locus on
some chromosome. I have thought about this a lot, and I came across the
following discussion of the gene therapy trials that have recently been
halted due to issues discussed in the article below. Question: How do we
know that the related virus insertions into the chromosome between man and
apes are indeed derived through common descent and not similar viruses
attacking both organisms and inserting themselves at similar loci? In the
case below, we have random insertion in two patients to the same loci giving
the same cancer phenotype. In your answer, please refer to the original
findings so I can learn more about the virus insertions that support common
descent of monkey to man.
Josh
Second cancer case halts gene-therapy trials
ERIKA CHECK
[WASHINGTON]
A. & H.-F. MICHLER/SPL
Blood cancer: leukaemia has been detected in two patients who have received
gene therapy.
The world of gene therapy was shaken last year when a child treated in a
French trial developed leukaemia. Researchers had pinned their hopes on this
being an unfortunate one-off. Now those hopes have been dashed with the
emergence of a second, almost identical case that could jeopardize the
future of gene therapy.
The latest case centres on a three-year-old boy treated in a gene-therapy
trial led by Alain Fischer at the Necker Hospital for Sick Children in
Paris. Just under three years ago, the child was cured of severe combined
immunodeficiency disease (SCID), a condition that disrupts the development
of the immune system. But researchers revealed last week that the boy was
diagnosed with leukaemia just days before Christmas.
The news last August that a child in Fischer's trial had developed cancer
left nations divided over their regulatory response (see Nature 419,
545–546; 2002). This time there was greater accord. Britain has stopped the
world's only active SCID trial, and the US Food and Drug Administration
(FDA) has suspended more than two dozen similar gene-therapy trials in a
variety of diseases — trials it had allowed to continue after August's
incident.
The setback is all the more serious because it arises in a trial that was
widely viewed as gene therapy's only true success. Fisher has so far cured
nine boys — including the two who now have leukaemia — out of 11 patients.
And when the first child was diagnosed with cancer, some argued that it was
an isolated event (see Nature 420, 595; 2002).
But Christof von Kalle of the Cincinnati Children's Hospital says analysis
of the two boys' cells shows that the same molecular events probably caused
the cancers. In both boys, the retroviral vector used to deliver the
corrective gene has integrated itself into a stretch of DNA in or near a
gene called LMO2, which can cause childhood leukaemias. Scientists are now
satisfied that the disease behaves enough like leukaemia to describe it as
such.
Kalle estimates that the vector is likely to insert itself near to LMO2 in
between 1-in-50,000 and 1-in-100,000 cells. And because each child in the
trial receives a dose of about a million corrected cells, each patient could
carry at least one cell with the vector near LMO2. Kalle is analysing
samples from all of the children — about 15 in all — who have been treated
in SCID gene-therapy trials to find out whether they are carrying such
cells.
In the meantime, an FDA advisory committee on gene therapy will meet on 28
February to decide what the adverse event means for other studies. The
American Society of Gene Therapy will also convene a committee to examine
data from human and animal trials of retroviral vectors. And the National
Institutes of Health's Recombinant DNA Advisory Committee (RAC) postponed
its planned meeting on 17 January, but will convene shortly to discuss these
issues.
At their last meetings, both the FDA committee and the RAC recommended that
gene therapy in SCID could proceed with appropriate monitoring and
informed-consent programmes. RAC chair Ted Friedmann of the University of
California, San Diego, says that this approach is "still valid", although it
could be revised in light of the new case.
The case is an enormous setback for the field — and for patients with SCID.
"The treatment works very well," Fischer says, "but the risk is not
acceptable."
P.S. This is my response to Stephen's comment earlier:
Just wanted to stimulate interesting discussion, but also know that I don't
have excessive time to nurture the thread (I have started threads before and
not kept up with them.)
>From: "Stephen J. Krogh" <panterragroup@mindspring.com>
>To: "asa" <asa@calvin.edu>
>Subject: RE: leaving
>Date: Wed, 26 Mar 2003 18:33:55 -0600
>
>Jon,
>
>So sorry you feel like leaving. If you don't find the conversations
>stimulating, feel free to start your own thread that you would find
>interesting. My archives show that you have posted 16 times since December.
>That last being this notice that you are leaving, like we are supposed to
>notify the media regarding your departure.
>
>
>Stephen J. Krogh, P.G.
>The PanTerra Group
>http://panterragroup.home.mindspring.com
>
>==========================================
>
> > -----Original Message-----
> > From: asa-owner@lists.calvin.edu [mailto:asa-owner@lists.calvin.edu]On
> > Behalf Of jdac
> > Sent: Wednesday, March 26, 2003 4:08 PM
> > Cc: asa
> > Subject: leaving
> >
> >
> > Regretfully I am finding the volume of emails on subjects I find
> > uninteresring and unhelpful overwhelming. Farewell.
> >
> > Jon
> >
> >
>
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