On March 16, the NYTimes ran two stories on Cerezyme, an expensive protein-based drug used to treat a rare genetic disorder, Gaucher’s disease. Both articles covered issues that might be emblematic of those that will be encountered when gene transfer applications are commercialized.
One article described uncertainties clinicians face in establishing the appropriate dose for Cerezyme. At $350K/year to treat a typical adult, lowering doses can have important economic benefits for patients. But with the drug licensed at a particular dose level, reliable clinical evidence on response at lower dose is not available. And Genzyme isn’t about to run trials testing whether Gaucher’s patients can get away with less of their product. Similar issues are raised by the treatment of wet age-related macular degeneration (AMD), where some ophthalmologists use Avastin off-label at a fraction of the cost of Lucentis, which is licensed for AMD. So are Gaucher’s physicians practicing substandard medicine by considering their patients’ pocketbooks, or are they treating the whole patient instead of the disease? (photocredit: banner from Genzyme website (www.cerezyme.com/home)
@Manual{stream2008-171,
title = {Cutting Recombinant Protein Pills?},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = mar,
day = 17,
url = {https://www.translationalethics.com/2008/03/17/cutting-recombinant-protein-pills/}
}
MLA
Jonathan Kimmelman. "Cutting Recombinant Protein Pills?" Web blog post. STREAM research. 17 Mar 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/03/17/cutting-recombinant-protein-pills/>
APA
Jonathan Kimmelman. (2008, Mar 17). Cutting Recombinant Protein Pills? [Web log post]. Retrieved from https://www.translationalethics.com/2008/03/17/cutting-recombinant-protein-pills/
What are the benefits of participating in a clinical trial? Ethicists have tended to divide benefits into three categories: direct, collateral, and aspirational. The first involves medical benefits flowing from the study intervention; the second, from increased medical monitoring. The third refers to the benefits that flow to society from the knowledge gained.
But are aspirational benefits external to the individual? That is, do they flow to society exclusively, or do they accrue to individuals who participate in studies– a sort of satisfaction that comes from having “given back” to society?
This Sunday’s NYTimes featured an article by David Leonhardt, titled “What Makes People Give?” The article describes some emerging findings from a branch of economics concerned with philanthropic behavior. One area of bioethics that calls out for further empirical and analytic research is what might be called corporal philanthropy. What makes people give their bodies? And to what extent is it ethical to harness these motivations, or perhaps even to prime them, in order to induce them to give more?
@Manual{stream2008-172,
title = {Gimme (and ’em) More},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = mar,
day = 10,
url = {https://www.translationalethics.com/2008/03/10/gimme-and-em-more/}
}
MLA
Jonathan Kimmelman. "Gimme (and ’em) More" Web blog post. STREAM research. 10 Mar 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/03/10/gimme-and-em-more/>
APA
Jonathan Kimmelman. (2008, Mar 10). Gimme (and ’em) More [Web log post]. Retrieved from https://www.translationalethics.com/2008/03/10/gimme-and-em-more/
Inder Verma has won the Vilcek Foundation annual award for, among other things, his work in gene transfer (for those of you who, like me, enjoy contemporary music, this year’s other recipient was Oswaldo Golijov– an eclectic Argentine-born composer).
As a former editor of Molecular Therapy and in other writings, Verma has often offered thoughtful and circumspect commentary on gene transfer. I leave you with a few quotes. From a 2005 interview in the journal Gene Therapy: “the big problem in gene therapy will be immunology. We don’t know whether the vector is immunogenic, or more importantly, whether the transgene is immunogenic….” Same interview: “there has to be more… back and forth [between clinicians and basic science researchers]. That hasn’t happened as much as I would have liked to have seen.” From an editorial in Molecular Therapy, 2001: “new and highly experimental technologies have inherent risks and uncertainties. Scientists must find a balance between excitement and eagerness, problem and promises, and hopes and hypes. The reality is that the timeline of promises kept is unpredictable, but the reaction to unfulfilled expectations is predictable.” (photo credit: Salk Institute, Aaronbflickr 2007)
@Manual{stream2008-173,
title = {Verma Wins Vilcek Prize},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = mar,
day = 6,
url = {https://www.translationalethics.com/2008/03/06/verma-wins-vilcek-prize/}
}
MLA
Jonathan Kimmelman. "Verma Wins Vilcek Prize" Web blog post. STREAM research. 06 Mar 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/03/06/verma-wins-vilcek-prize/>
APA
Jonathan Kimmelman. (2008, Mar 06). Verma Wins Vilcek Prize [Web log post]. Retrieved from https://www.translationalethics.com/2008/03/06/verma-wins-vilcek-prize/
“It’s Health Care Costs, Stupid.” So says Ezekiel Emanuel, paraphasing James Carville, in a Feb 29, 2008 commentary in JAMA. Emanuel argues that expanding health care coverage to the uninsured will be impossible and unsustainable unless the health care system gets a handle on cost inflation.
What does this have to do with translational research? A lot. Most economists agree that new technologies are one of the largest drivers of health care cost inflation. Though unmentioned in Emanuel’s piece, any attempt to rein in cost inflation will need to address incentive structures in biomedical innovation. This would have major implications for translational research (for example, cost controls would adversely affect the ability of biotechnology firms to raise capital). (photocredit: Sister72, 2006)
@Manual{stream2008-174,
title = {Inflation, Health Care Reform, and Translational Research},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 29,
url = {https://www.translationalethics.com/2008/02/29/inflation-health-care-reform-and-translational-research/}
}
MLA
Jonathan Kimmelman. "Inflation, Health Care Reform, and Translational Research" Web blog post. STREAM research. 29 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/29/inflation-health-care-reform-and-translational-research/>
APA
Jonathan Kimmelman. (2008, Feb 29). Inflation, Health Care Reform, and Translational Research [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/29/inflation-health-care-reform-and-translational-research/
Epidemiologists and biostatisticians have evolved numerous ways of reducing bias in clinical trials. Randomization of patients, and masking them to their treatment allocation are two. Another is masking clinicians who assess their outcomes.
Why are these simple measures so rarely used in preclinical animal studies? And do animal studies show exaggerated effects as a consequence of poor methodology?
The March 2008 issue of Stroke reports a “meta-meta-analysis” of 13 studies comprising over fifteen thousand animals. Perhaps surprisingly, the study did not show a relationship between the use of randomization or masked outcome assessment and the size of treatment effect. It did, however, show a positive relationship between size of treatment effect and failure to mask investigators during treatment allocation.
This is probably the largest analysis of its kind. It isn’t perfect: publication bias is very likely to skew the analysis. For example, size of treatment effect is likely to strongly influence whether a study gets published. If so, effects of methodological bias could be obscured; preclinical researchers might simply be stuffing their methodologically rigorous studies in their filing cabinets because no effect was observed.
The conclusion I draw? Preclinical researchers should randomize and mask anyway. There is some evidence it matters. Moreover, the logical rationale is overwhelming, and the inconvenience for investigators seems more than manageable. (photocredit: Chiara Marra 2007)
@Manual{stream2008-175,
title = {Masks and Random Thoughts on Preclinical Research Validity},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 28,
url = {https://www.translationalethics.com/2008/02/28/masks-and-random-thoughts-on-preclinical-research-validity/}
}
MLA
Jonathan Kimmelman. "Masks and Random Thoughts on Preclinical Research Validity" Web blog post. STREAM research. 28 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/28/masks-and-random-thoughts-on-preclinical-research-validity/>
APA
Jonathan Kimmelman. (2008, Feb 28). Masks and Random Thoughts on Preclinical Research Validity [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/28/masks-and-random-thoughts-on-preclinical-research-validity/
Small interfering RNA molecules (siRNA) are generating a lot of excitement in biomedical research for their ability to “knock down” specific genes– say, those of an invading virus or a tumor cell.
But because viruses tend to produce small pieces of RNA, the body often “interprets” siRNA as a viral infection and launches an immune response. In the Februrary 2008 issue of Human Gene Therapy, Adam Judge and Ian Maclachlan of Protiva Biotherapeutics describe some of the consequences of this. A major one is that studies testing siRNA in animals or humans might be prone to false positives, especially for medical conditions where the immune system is implicated in disease control. The problem is (according to these authors, at least), there seems to be little consensus about how to design experimental controls to sift true from spurious claims of specific efficacy. Yet another complication in the interpretation of preclinical studies, as well as the decision to initiate human testing.
@Manual{stream2008-176,
title = {siRNA: Caveat Emptor for Preclinical Studies?},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 27,
url = {https://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/}
}
MLA
Jonathan Kimmelman. "siRNA: Caveat Emptor for Preclinical Studies?" Web blog post. STREAM research. 27 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/>
APA
Jonathan Kimmelman. (2008, Feb 27). siRNA: Caveat Emptor for Preclinical Studies? [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/27/sirna-caveat-emptor-for-preclinical-studies/
In the February 20th edition of the New York Times, Reed Abelson reports a “New Tack on a Muscle Disease.” The “new tack” is, in fact, a scaling back of ambition in muscular dystrophy (MD) research. Since identification of various genetic mutations that cause muscular dystrophies, gene transfer has been a logical goal. But because the gene is so large, and delivery to all of a patient’s muscles so difficult to achieve, gene transfer against MD has presented a formidable challenge to researchers.
What is so striking about Abelson’s article, in my view, is his suggestion that the ambition of a one-off cure has clouded the clinical and research community from recognizing and advancing interventions that extend life and improve its quality for MD patients. Abelson writes “the lack of interest in the mundane has… slowed progress in knowing what available therapies are the most useful.”
One researcher stated “for too long, I was stuck on [Duchenne] as the home run or nothing.” Though speculative, “home run” research deserves sanctuary in biomedical research, I regard a critical role for disease advocates, caregivers, and bioethicists to advocate on behalf of the quotidian needs of present day patients (and, I should add, gene transfer will likely play an contributions serving these quotidian needs). (photo credit: Evamol, “Still Life,” 2007)
@Manual{stream2008-178,
title = {Still Life with Duchenne Muscular Dystrophy},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 26,
url = {https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy-2/}
}
MLA
Jonathan Kimmelman. "Still Life with Duchenne Muscular Dystrophy" Web blog post. STREAM research. 26 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy-2/>
APA
Jonathan Kimmelman. (2008, Feb 26). Still Life with Duchenne Muscular Dystrophy [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy-2/
In the February 20th edition of the New York Times, Reed Abelson reports a “New Tack on a Muscle Disease.” The “new tack” is, in fact, a scaling back of ambition in muscular dystrophy (MD) research. Since identification of various genetic mutations that cause muscular dystrophies, gene transfer has been a logical goal. But because the gene is so large, and delivery to all of a patient’s muscles so difficult to achieve, gene transfer against MD has presented a formidable challenge to researchers.
What is so striking about Abelson’s article, in my view, is his suggestion that the ambition of a one-off cure has clouded recognition of interventions that extend life and improve its quality for MD patients. Abelson writes “the lack of interest in the mundane has… slowed progress in knowing what available therapies are the most useful.”
One researcher stated “for too long, I was stuck on [Duchenne] as the home run or nothing.” Though speculative, “home run” research deserves sanctuary in biomedical research, I regard a critical role for disease advocates, caregivers, and bioethicists to advocate on behalf of the quotidian needs of present day patients (and, I should add, gene transfer will likely play an important role in serving these quotidian needs). (photo credit: Evamol, “Still Life,” 2007)
@Manual{stream2008-177,
title = {Still Life with Duchenne Muscular Dystrophy},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 26,
url = {https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy/}
}
MLA
Jonathan Kimmelman. "Still Life with Duchenne Muscular Dystrophy" Web blog post. STREAM research. 26 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy/>
APA
Jonathan Kimmelman. (2008, Feb 26). Still Life with Duchenne Muscular Dystrophy [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/26/still-life-with-duchenne-muscular-dystrophy/
People often enter drug studies in order to access a promising new drug. But clinical trials take place over a set time period. So is it ethical to withhold from prospective trial subjects preliminary data on safety or efficacy that have been gathered from initial volunteers? In the Feb 1, 2008 issue of Journal of Clinical Oncology, Robert Wells argues it isn’t. Biostatistician Steven Piantadosi, in a rebuttal, argues that it is.
Wells argues (I paraphrase) that anything short of total transparency frustrates patient autonomy and breaches scientific and clinical duties. Piantadosi offers two counter-arguments: first, there are no obligations to disclose uninterpretable data, and second, in research, clinical obligations for full disclosure do not “supercede” societal interests in safeguarding the integrity of data.
The debate revolves around the tension between clinical research (which is primarily aimed at serving society) and clinical care (aimed at serving individual patients). Though I agree that the withholding of preliminary data should make us uncomfortable, total transparency in clinical research would necessitate abandoning well established practices– like blinding and placebo use– that maximize the reliability of knowledge gleaned from clinical trials. The key to navigating the ethical tension lies in making sure volunteers recognize that trials are aimed primarily at serving society. (photo credit: Kah Zanon, 2007)
@Manual{stream2008-179,
title = {Can You Keep A Secret?},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 22,
url = {https://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/}
}
MLA
Jonathan Kimmelman. "Can You Keep A Secret?" Web blog post. STREAM research. 22 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/>
APA
Jonathan Kimmelman. (2008, Feb 22). Can You Keep A Secret? [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/22/can-you-keep-a-secret/
As per usual when an article has moved into the post-galley stage, on Monday I woke to a string of friendly reprint requests mainly from Eastern European researches lacking good library facilities. I guess that means my review on the ethics of gene transfer has been published in Nature Reviews—Genetics. In it (the editors rejected my preferred title, “Vector Calculus”), I argue that despite numerous advances, researchers and policy makers continue to confront unresolved ethical and policy issues around gene transfer— among them a series of questions about research ethics, licensure of novel interventions, enhancement of human traits, and genetic modification of tissues that will be passed to progeny. I hope the review does justice to the complexity of the field, as well as the ethical issues associated with it. (photo credit: Nature Publishing Co.)
@Manual{stream2008-180,
title = {Vector Calculus is Out: Nature Reviews—Genetics Article},
journal = {STREAM research},
author = {Jonathan Kimmelman},
address = {Montreal, Canada},
date = 2008,
month = feb,
day = 20,
url = {https://www.translationalethics.com/2008/02/20/vector-calculus-is-out-nature-reviews-genetics-article/}
}
MLA
Jonathan Kimmelman. "Vector Calculus is Out: Nature Reviews—Genetics Article" Web blog post. STREAM research. 20 Feb 2008. Web. 14 Oct 2025. <https://www.translationalethics.com/2008/02/20/vector-calculus-is-out-nature-reviews-genetics-article/>
APA
Jonathan Kimmelman. (2008, Feb 20). Vector Calculus is Out: Nature Reviews—Genetics Article [Web log post]. Retrieved from https://www.translationalethics.com/2008/02/20/vector-calculus-is-out-nature-reviews-genetics-article/
