In Utero: Gene Transfer Nirvana?

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The February 2008 issue of Molecular Therapy has an editorial by Charles Coutelle defending in utero gene transfer (that is, the application of gene transfer to fetuses).  Coutelle makes several attractive arguments in its favor.  Among them: that many parents opt against abortion after receiving  a prenatal diagnosis, and that in utero gene transfer would provide these parents with a therapeutic option.


What troubles me about this position is this:  1- what makes in utero gene transfer attractive–favorable “vector-to-cell” ratio, and the “presence of expanding and developing stem cell populations,” is precisely what makes this procedure risky as well; 2- how often do parents opt against pre-implantation diagnosis, but then go on to seek prenatal pregnancy screening?  Specifically, does the frequency of the latter justify the risks of the former?

BibTeX

@Manual{stream2008-182,
    title = {In Utero: Gene Transfer Nirvana?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 18,
    url = {http://www.translationalethics.com/2008/02/18/in-utero-gene-transfer-nirvana/}
}

MLA

Jonathan Kimmelman. "In Utero: Gene Transfer Nirvana?" Web blog post. STREAM research. 18 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/18/in-utero-gene-transfer-nirvana/>

APA

Jonathan Kimmelman. (2008, Feb 18). In Utero: Gene Transfer Nirvana? [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/18/in-utero-gene-transfer-nirvana/


Why the Title “Lost in Translation?”

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The title of this blog derives from that of my book on the ethics of human gene transfer research, which is contracted with Cambridge University Press.

As the title suggests, the translation of gene transfer into clinical application has not gone as smoothly as predicted.  The word “lost” is not intended to suggest incompetence, or blanket moral culpability on the part of gene transfer researchers, nor to disparage the field in particular.  My thesis is that nearly all parties to gene transfer research– ethicists, patient advocates, members of the public, news organizations, policy-makers, and researchers– have in a sense been lost in appreciating the distinctive ethical, policy, social, and scientific challenges in making gene transfer a reality.

There’s another way in which the title is intended.  Many of the ethical frameworks and principles for evaluating human experiments were derived with randomized controlled trials in mind.  These concepts often apply awkwardly to the setting of the highly technical first-in-human experiment. In a sense then, the research ethics has been lost in translating approaches from the controlled clinical trial to the exploratory, early phase human study.

BibTeX

@Manual{stream2008-183,
    title = {Why the Title “Lost in Translation?”},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 15,
    url = {http://www.translationalethics.com/2008/02/15/why-the-title-lost-in-translation/}
}

MLA

Jonathan Kimmelman. "Why the Title “Lost in Translation?”" Web blog post. STREAM research. 15 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/15/why-the-title-lost-in-translation/>

APA

Jonathan Kimmelman. (2008, Feb 15). Why the Title “Lost in Translation?” [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/15/why-the-title-lost-in-translation/


The Scope of this Blog

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Though my primary focus is on gene transfer, I will occasionally wander into other areas of translational pharmaceutical research, including cell transfer (also sometimes called “cell therapy”), monoclonal antibodies, small-molecule drugs that target novel biological mechanisms, or large-molecule drugs.


These types of translational clinical research raise a similar cluster of issues– namely, high degrees of uncertainty, risk, scientific complexity, desperately ill volunteers, ambitious investigators, financial interests, and complicated intellectual property issues.

BibTeX

@Manual{stream2008-184,
    title = {The Scope of this Blog},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 14,
    url = {http://www.translationalethics.com/2008/02/14/the-scope-of-this-blog/}
}

MLA

Jonathan Kimmelman. "The Scope of this Blog" Web blog post. STREAM research. 14 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/14/the-scope-of-this-blog/>

APA

Jonathan Kimmelman. (2008, Feb 14). The Scope of this Blog [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/14/the-scope-of-this-blog/


Why not call it Gene Therapy?

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What I term “gene transfer” is often also called “gene therapy.”  I prefer the former, which is based less on aspiration than fact.  That is, therapy implies validation for efficacy.  There are, at best, only two examples of gene transfer interventions where efficacy seems well established.  Use of the term “gene therapy” potentially misleads members of the public— and even experts not steeped in the gene transfer literature—into thinking that interventions are in advanced stages of development.


I realize “gene transfer” presents some grammatical problems (as in: “the patient received gene transfer for her disease” sounds awkward).  I’m afraid this is a compromise we’ll have to live with.  In general, I tend to prefer using “gene transfer” as an adjective—say, the way people use “thrombolytic” to modify “drug.”  I note that it is not uncommon within medicine for adjectival terms to graduate to noun status (e.g. anxiolytic).

BibTeX

@Manual{stream2008-185,
    title = {Why not call it Gene Therapy?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 8,
    url = {http://www.translationalethics.com/2008/02/08/why-not-call-it-gene-therapy/}
}

MLA

Jonathan Kimmelman. "Why not call it Gene Therapy?" Web blog post. STREAM research. 08 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/08/why-not-call-it-gene-therapy/>

APA

Jonathan Kimmelman. (2008, Feb 08). Why not call it Gene Therapy? [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/08/why-not-call-it-gene-therapy/


What is Gene Transfer?

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In this blog, I define gene transfer as the use of genetic materials or genetically modified organisms for therapeutic or research purposes.  This is a much broader definition than typical.  For instance, the American Society of Gene Therapy defines gene therapy as “…an approach to treating disease by either modifying the expressions of an individual’s genes or correction of abnormal genes.”  My definition would include gene-marking protocols (whereby a patient’s cells are genetically modified not for therapeutic purposes, but instead so that researchers can track their growth or location in the body).  My definition also includes the administration of genetically modified organisms– like genetically modified gut flora—for therapeutic purposes.  My definition also includes vaccines made by genetically modifying viruses; several of these are presently being tested against cancer and HIV.

BibTeX

@Manual{stream2008-186,
    title = {What is Gene Transfer?},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 7,
    url = {http://www.translationalethics.com/2008/02/07/what-is-gene-transfer/}
}

MLA

Jonathan Kimmelman. "What is Gene Transfer?" Web blog post. STREAM research. 07 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/07/what-is-gene-transfer/>

APA

Jonathan Kimmelman. (2008, Feb 07). What is Gene Transfer? [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/07/what-is-gene-transfer/


Introduction to Lost in Translation

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Within the past six months, a fifth patient developed a lympho-proliferative disorder in an X-SCID gene transfer trial.  The RAC has all but cleared AAV vector as a causal agent in the death of Jolee Mohr in a rheumatoid arthritis study.  A Merck HIV-vaccine trial involving adenoviral vectors was terminated after a data safety monitoring board found that volunteers receiving placebo had lower rates of sero-conversion.


I created this blog to establish a forum to report and comment on developments in gene transfer—and other areas of translational clinical research— that raise interesting or important ethical questions.  The first several posts will contain some introductory material that provides definitions and describes the scope of this blog.

BibTeX

@Manual{stream2008-187,
    title = {Introduction to Lost in Translation},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = feb,
    day = 6,
    url = {http://www.translationalethics.com/2008/02/06/introduction-to-lost-in-translation/}
}

MLA

Jonathan Kimmelman. "Introduction to Lost in Translation" Web blog post. STREAM research. 06 Feb 2008. Web. 25 May 2019. <http://www.translationalethics.com/2008/02/06/introduction-to-lost-in-translation/>

APA

Jonathan Kimmelman. (2008, Feb 06). Introduction to Lost in Translation [Web log post]. Retrieved from http://www.translationalethics.com/2008/02/06/introduction-to-lost-in-translation/


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