Tuesday, July 23, 2013

Glaxo in China: Another Step in Big Pharma’s Race to the Bottom

GlaxoSmithKline has been much in the news lately. Following a scandal where Glaxo executives apparently bribed Chinese physicians and hospital officials to promote use of GSK drugs, it now turns out that there are also major problems at GSK’s shiny new research center in Shanghai, as recently described in the NY Times.   Apparently key pre-clinical studies in animals were not reported (misplaced? suppressed?) before an important new drug went into clinical trials.  Ozanezumab, a monoclonal antibody for treatment of neurological diseases was being developed at the Shanghai facility when problems emerged during an internal audit in 2011 that has only recently become public.  Evaluating animal studies prior to initiation of clinical trials is crucial to protecting patients in the trials against potential harmful effects of the new drug.  An excerpt from the Times article highlights the issue ““If that’s true, it’s a mortal sin in research requirements,” said Arthur L. Caplan, the head of the division of medical ethics at NYU Langone Medical Center. “No one could approve human trials without having that information available, scientifically or ethically. That’s kind of a Rock-of-Gibraltar-sized ethics violation.”  As bad as it is, this is not the first scandal to hit GSK’s China operations. A few months ago the head of GSK R & D in China was fired for misrepresenting data in an article published in Nature Medicine.

So is this just an isolated case? I doubt it. Over the last decade or so big Pharma has sought to maximize profits by reducing expenditures for research, personnel, and materials.  To a considerable extent this has been done by seeking lower cost alternatives in China and other less developed countries. Thus research staff at sites in the US and Europe have been cut while new sites have been created in Asia. Production of the ingredients to make existing drugs has been outsourced to companies in India and elsewhere. The problem with this is that it is not only costs that are being cut, but quality as well.

As described elsewhere on this blog (1) there have been numerous problems with drugs produced by foreign manufacturers for the US market. Now it is emerging that research results from big Pharma’s outsourced labs can’t be trusted either. It is not that Asian researchers can’t do good science. More and more outstanding work is emanating from academic laboratories in China, India, Taiwan, Singapore and other Asian countries. However, when commerce enters the picture scientific probity seems to go out the window.

It makes one wonder whether we should entrust our future needs for important new drugs to the current profit driven system represented by the big pharmaceutical companies. There are other models for drug development (2) including the public-private partnerships that have been so successful in developing drugs for malaria and other neglected diseases. Some new approaches are clearly needed.

Tuesday, July 16, 2013

Mitochondrial replacement- disease therapy or a first step toward human enhancement through the germ line?

As reported in a recent commentary in Nature the UK has decided to allow human trials of mitochondrial replacement. This would involve a small group of women who have genetic defects in their mitochondria that could be transmitted to their offspring. The procedure would involve transfer of only the nucleus of the egg of the affected woman to a healthy enucleated egg from a donor with subsequent in vitro fertilization by the male partner. Simply put, it would result in a ‘three parent baby’ with male and female nuclei provided by the parents and mitochondrial DNA provided by the donor. The positive aspect is that it would allow women with mitochondrial defects to have normal children that share most of their genome. The mitochondrial genes account for only a tiny fraction of the total genome and thus the children born in this manner would be genetically very similar to those conceived normally. The aspect of concern is that this really is re-engineering the human germ line since the mitochondrial DNA could be passed on indefinitely through female offspring. On an ethical basis there has been great reluctance to engage in modification of the human germ line, but this would be a first step.

While the proposed trials are directed toward preventing offspring with genetic defects one could easily visualize a ‘slippery slope’ effect here. There is increasing momentum for using various pharmacological and genetic techniques to enhance human capabilities (I will be posting much more about this soon). Since mitochondria can contribute to endurance and athletic performance (1), it will be tempting to use this relatively simple technology to ‘improve’ one’s offspring with, for example, mitochondria from an outstanding female athlete.  Clearly stringent monitoring will be needed.

1. http://physiolgenomics.physiology.org/content/43/13/789.full