Friday, September 12, 2014

GDF11- the Elixir of Youth??


A feature article in SCIENCE this week (1) summarized some very impressive work from Amy Wagers (Harvard) and other researchers on blood factors that seem able to partially reverse age-related tissue degeneration. Several groups have used a technique termed parabiosis to establish a shared circulation between old and young mice.  This resulted in improved function in muscles, heart, and nerves of the older mice. One possibility is that blood factors from young mice restore the ability of stem cells in older animals to repopulate damaged tissues. In an exciting new development Wagers and colleagues have identified a protein termed GDF11 as the rejuvenating blood factor. GDF11 is a member of the TGB-beta family of growth factors that regulate many aspects of tissue differentiation and growth.

These results would seem to open up new opportunities for clinical approaches that address ageing per se rather than individual diseases associated with ageing. Some strong arguments have been made that this approach would make a much greater contribution to human health and longevity than disease specific therapies (2).




Friday, September 5, 2014

Re-branding the PhD


This week’s NATURE has a rather bizarre editorial regarding careers for PhDs (1). The editors acknowledge that currently many individuals with PhDs do not find academic positions, or even positions actually doing research, but rather wind up in a variety jobs that really do not require intensive research training, ranging from high school teaching to investment banking. However, rather than viewing this as a problem in PhD supply-demand economics, the editors chose to put a cheerful spin on the situation and brand all of the ‘alternative careers’ as a good thing.

To my mind the American Society for Cell Biology (2) has a more realistic perspective when it states that in the current context, where less than 10% of enrolled biomedical PhD students will become tenure track faculty, “A faculty job is an ‘alternative’ career”. To be sure NATURE has previously discussed the PhD glut from a more balanced perspective (3). However, the current attempt to view a bad situation through rose-colored glasses is not helpful.

As discussed several times on this blog (4,5) the PhD oversupply is the result of self-interested actions on the part of faculty and university administrators. Cheap labor is needed to keep the grants and publications coming.

(1)  http://www.nature.com/news/there-is-life-after-academia-1.15808

(2) go.nature.com/vh1ewm




Thursday, August 28, 2014

Pharmaceutical Failures and Near Misses: More Examples of Why Finding New Drugs is Too Important to be Driven Solely by the Profit Motive.


Recent stories arising from medical areas as diverse as breast cancer and Ebola illustrate the failures and near-failures of drug discovery by for-profit pharmaceutical companies.

An article in SCIENCE (1) recounts the twists and turns of the highly promising anti-cancer drug palbociclib. This agent selectively inhibits CDK4, a kinase that is involved in cell cycle control and that is crucial to the growth of certain cancers. The history of this drug goes back to the 1990s when it was developed by researchers at Parke-Davis Co. When the giant pharmaceutical company Pfizer acquired Parke-Davis in 2000 palbociclib was almost dropped and its development was delayed for years during the various twists and turns of Pfizer’s recent corporate history. Its re-emergence as a promising drug for breast cancer is primarily due to several independent clinical researchers who championed its use. This type of on-again off-again drug research is all too common in ‘Big Pharma’ where science is often subverted by marketing and corporate strategy issues.

The recent explosion of concern regarding anti-Ebola drugs reflects another aspect of the failure of for-profit major drug companies to deal with problems of great public health concern. As stated nicely in a recent blog post (2) from the CSPO at Arizona State “when we rely on a market-based system to drive medical research that may not be profitable in the short term or even medium term, that system is unlikely to respond to potential future threats — no matter how high the potential cost — if there is not a reasonable promise of economic return in the end“. This of course exactly describes the situation with Ebola as well as with many other diseases that primarily affect less-developed countries and that thus do not provide the prospect of lucrative profits.

The BBC website has summarized recent efforts on Ebola drug development (3). Although several companies are involved in this process, it is important to note that much of the early-phase research on drugs for exotic diseases has been sponsored by governments. For example, promising drugs for Marburg and Ebola viruses being developed by Sarepta Therapeutics and Tekmira Pharmaceuticals, two small biotech companies, have been sponsored by the US Dept. of Defense.

The role of governments in developing innovative technology is often under-appreciated (4); in contrast private companies (particularly pharmaceutical companies) use highly developed public relations tools to claim a leading role in innovation. The emergence of pandemics such as the current Ebola outbreak should be readily anticipated based on the phenomenal increases in both population and mobility occurring in Africa in recent years (5). However, it has been governments and non-profits rather than Big Pharma that have led the way in preparing for such public health emergencies. All of this inevitably leads to the conclusion that drug discovery and development is too important to be driven solely by the quest for corporate profits.








Friday, August 15, 2014

Incomprehensible Drug Prices? Yes They Are!


This week in his blog about the Pharma industry ‘In the Pipeline’ Derek Lowe discusses the trend toward increasingly high drug prices especially with regard to new drugs for cancer.  Refuting a post in Forbes by Peter Bach, “Cancer: Unpronounceable Drugs, Incomprehensible Prices” Lowe trots out the old arguments about research costs and patent lifetimes being the root of extreme drug prices. Bach says that drug companies charge what they think they can get away with. Lowe says, so what, so do all other corporations.

Usually I think that Lowe’s blog is excellent and often right on target about important issues in Pharma. However, here I think that he really misses the point. Drugs are not like potato chips. There really isn’t a free market of informed sellers and buyers. Drug prices need to conform to societal goals (better heath) rather than exclusively profit considerations.

The bottom line really is that drug development is too important to be left solely to an industry that is exclusively driven by greed.  We need to start looking at new modes of drug discovery and development that are driven by health needs and not by the need to boost stock prices and CEO bonuses.


Also see:
Pharmaceutical Innovation and Public Policy (ASIN: B00B79ULRK) Kindle ebooks
  

Thursday, August 7, 2014

The Robo-Chemist: Another Step Backward for Human Creativity


An unsettling report in NATURE this week describes efforts to develop a robotic chemist. While simple robots are widely used in chemistry labs these days, the ‘robo-chemist’ goes far beyond that. The idea is to develop a machine that will be able to analyze the vast array of information on molecular structures and chemical reactions that is available in public data-bases and use that information to design synthetic routes to new chemicals. The robo-chemist would then follow its own plan and actually synthesize the new entity. Thus massive data crunching would replace the creative intuition that experienced chemists currently use to design and synthesize new chemicals.

The chemical and pharmaceutical industries would love this of course. It would allow them to lay off thousands of experienced chemists and increase their profit margins. Not so great for the chemists though!

The robo-chemist is really a wake up call for educated people who may think that their occupation is safe from the inroads of artificial intelligence and robotics. If Ph.D. chemists can be replaced who is next?

The explosive penetration of computer technology into all areas of the economy comes at a time when rapid increases in total population and in longevity are occurring in the USA. How will our society provide continuous employment for all these long-lived healthy people while machines do more and more of the work?

Thursday, July 24, 2014

Treat Ageing not Disease


An interesting commentary in NATURE provides an overview of the concept that modern medicine should be seeking to increase the ‘healthspan’ rather than addressing individual diseases one by one. Since many diseases are linked to the gradual debilitation associated with old age, the thought is that by blocking those degenerative changes overall health, and perhaps even lifespan, will be enhanced.

Certainly studies in animals have begun to reveal the molecular underpinnings of degeneration during ageing. Thus the mTOR signaling system, telomerase, and damage mediated by free radical triggered inflammation are all clearly important. Drugs such as rapamycin that affect the mTOR system have been shown to extend lifetimes and ‘healthspans’ in animals. Despite this progress at the laboratory level there are many obstacles to implementing these concepts and approaches in clinical practice.

One is funding. Research on ageing per se receives a tiny fraction of that received by cancer or cardiovascular disease research. Another is the lack of good tools and models that would allow study of ageing processes in animals in a manner parallel to the approaches used to evaluate ageing in humans. Since ageing studies can obviously be of very long duration, good surrogate markers would also be important. Finally our entire health care system is set up to be disease and procedure oriented rather than focusing on promoting the overall health of the individual.

It seems to this observer that pursuing the ‘healthspan’ concept will be vital in addressing the health needs of our rapidly ageing population. Some of the exciting findings on life- and health-extension in animals need to be carefully validated and then gradually extended into clinical trials in humans. I am sure that many otherwise healthy older people would be interested in participating in tests of drugs or other approaches that might provide a measure of rejuvenation. I know I would.    

http://www.nature.com/news/medical-research-treat-ageing-1.15585    

Thursday, June 12, 2014

Antisense and siRNA: Parochialism in Research


I enjoyed reading an excellent review in Science Translational Medicine on problems and possibilities concerning therapeutic utilization of siRNA. The authors, from MD Anderson Cancer Center, covered all the key issues including target selection, delivery, toxicity and pharmaceutical feasibility. An interesting sidelight for me, however, was that the article focused solely on siRNA and completely ignored single stranded oligonucleotides such as ‘classic’ antisense or splice switching oligonucleotides although these molecules share exactly the same prospects and problems as siRNA. This reflects a schism of interests in the oligonucleotide therapeutics field with one group of investigators (and companies) promoting the virtues of siRNA while another cohort focuses on single stranded oligos. Fortunately there are venues where the two groups can communicate- one being the annual meeting of the Oligonucleotide Therapeutics Society where all forms of nucleic acid therapy are considered. It’s an interesting commentary on science, however, that even in a relatively small field a considerable amount of parochialism can come into play. 


http://www.oligotherapeutics.org/