Monday, June 8, 2015

Yes Paul Ehrlich Was Right! Its Just a Matter of Timing.

The NY Times had an Opinion Page today on whether overpopulation is a threat, with mixed opinions being expressed

I don’t understand how there can even be a debate on this?
Population growth is not slowing as rapidly as the experts expected. The UN keeps revising its population projections upward.
The billions in Asia, Latin America and Africa will not be denied their chance to experience the consumerist life style long enjoyed by developed countries.
The net result will be the complete destruction of the natural world. Will humans survive? Probably- but living on yeast protein and cowering from the mega-storms unleashed by global warming.

Friday, June 5, 2015


As described in a recent article in Nature, the advent of a powerful gene editing technique based on the CRISPR-Cas9 system is leading to a revolution in molecular biology and possibly in medicine. For a couple of decades scientists have known how to introduce or modify genes in cells by a process called homologous recombination.  When done in stem cells, the gene modified cells can be re-implanted and can give rise to tissues, including reproductive tissues, and thus eventually to genetically modified organisms. A major problem is that the entire process is very inefficient. Several previous attempts to increase the efficiency of gene editing have involved ‘designed’ proteins such as the Talens nucleases or zinc finger nucleases that can cut DNA at specific sites thus creating opportunities for recombination. However, preparing these designed proteins is difficult and time consuming.

The great advantage of the CRISPR-Cas system is that it uses a short RNA molecule to target the site in DNA that needs to be cut, with the cutting provided by the Cas enzyme.  It’s easy to design RNAs that can hybridize with specific DNA sites, and the entire CRISPR-Cas system can be engineered into a viral vector that is also quite easy to use.  Thus this approach has revolutionized laboratory practices for gene modification in cells for basic research purposes.

CRISPR can also impact in vivo studies. For example, an animal with a gene defect can provide stem cells. The stem cell gene can be ‘corrected’ in the lab using CRISPR and the corrected stem cells re-infused into animals. Potentially the stem cells can then engraft in tissues and thus fully or partially correct the defect in the animal. This has already been done in a number of studies in mice.  Obviously the same is potentially possible in humans but has not yet been done.  Some investigators have tried to correct genetic defects in mice by directly injecting the entire CRISPR-Cas9 system, but this is very inefficient in its current state of development.

The very power of this technique is beginning to cause ethical concerns. For example a group in China reported editing the genes of human embryos. The potential for this type of activity has caused leading scientists in CRISPR research to advocate restraint and careful design of projects to avoid risks to humans.

The CRISPR-Cas technology clearly has enormous potential. However, it needs to be viewed in the same perspective as all new biomedical technologies. Monoclonal antibodies, siRNA, nanomedicine- each of these potentially transformative technologies has followed the same path, with an initial period of almost irrational exuberance, followed by disillusionment as problems inevitably emerged, followed by a more considered assessment of ultimate therapeutic potential. So will it be with CRISPR.  

Friday, May 29, 2015

Smart Machines Getting Too Smart For Humans?

This week’s Nature has a section on ethical aspects of robotics and artificial intelligence. Reading this article, the associated comments, and the accompanying special section on Machine Intelligence in this week’s issue, has left me deeply concerned. The accelerating capabilities of both individual intelligent machines and the Internet itself raise all sorts of questions about whether human beings will be better off or not if artificial intelligence continues to evolve in its current uncontrolled fashion.  It seems we need a measured assessment of both the potentials and hazards of this thrust before we proceed much further. Clearly it is always difficult to accurately anticipate the path of an emerging technology and to create guidelines concerning its development and implementation. Nonetheless society has done this previously in the context of other transformative technologies such as nuclear weapons and genetic engineering. Although there is plenty of hype in the media, it surprises me how little the issue of Artificial Intelligence has been addressed by ethicists or by governmental bodies. 

Friday, May 22, 2015

Antibiotic Resistance: Big Pharma Fails to Address the Challenge

A recent report in SCIENCE is another example of ‘Big Pharma’ failing to address important public health issues.  The problem of resistance to conventional antibiotics is reaching crisis proportions, accelerated by the widespread use of antibiotics in mass agriculture. The technology to develop powerful new drugs is there, but the profit motivation is not.  In many respects this situation is similar to the problem of developing medications for diseases such as malaria that primarily affect poorer countries and thus provide little opportunity for large profits. It is encouraging to learn that some governments are seeking ways to break the roadblock on antibiotic development. However, is this enough?  One might argue that this key area of drug research be pursued through innovative public funding rather than be left to the dictates of Wall Street. 

Thursday, March 5, 2015

Global Warming? Capitalism to the Rescue!

In a very interesting article in Nature (1) Nathan Fabian discusses the role of global investors in the transition from a high carbon to a low carbon economy.  He points out that capital investments are trending toward lower emission energy sources such as solar and away from high emission sources such as coal. This is happening not because of the investor’s altruism but because of cold calculation about risk/reward ratios. Basically green energy may be a safer bet than coal for the long run.

However, the capitalist calculations are inevitably based on government policies. As the article admits, the expectation of political actions such as instituting carbon taxes, removing subsidies to oil and coal industries, and providing subsidies to green energy development are part of the investor’s calculus. Thus, as usual, it is up to governments to channel the behavior of capitalists into socially productive pathways.


Thursday, February 12, 2015

We Need Population Control Not Climate Engineering

The National Research Council has just issued a report that advocates increased research into 'climate engineering', that is, trying to retard global warming through human manipulation of atmospheric processes (1).

The NRC report on climate engineering is both depressing and upsetting. It is depressing because it essentially admits that we are totally failing in our attempts to prevent climate change through reductions in emissions. It is upsetting because it reflects incredible hubris. Do the originators of the report really think that we can meddle with global atmospheric patterns without huge unintended consequences? Haven’t we learned anything about the unpredictability of technology?

To my mind research funds would be far better spent investigating novel ways to restrain the tidal wave of global population growth. That would certainly impact climate change. The much-vaunted ‘demographic transition’ seems to be sputtering as the UN revises its global population projections ever upward.


Friday, February 6, 2015

21st Century Cures Act: Driving Innovation in Drug Development?

The US House of Representative has a new initiative for biomedical R& D “the 21st Century Cures Act “ (1) .  While the overall goal of this initiative, to advance new therapies, is laudable, as usual the politicians have gotten the details screwed up. Essentially what this initiative does is to provide financial rewards such as increased patent lifetimes to companies that engage in research in targeted areas (eg Alzheimers). It also provides directives to the NIH to strategize research.

The first aspect is just off base. Why do we need to incentivize drug companies to conduct research in vital public health areas? Why not simply use the type of non-profit public-private partnerships that have been so successful in developing drugs for malaria, TB and other diseases of less-developed countries? (2). Do we really need to squander public resources to fatten the wallets of Big Pharma executives?

The second aspect amounts to an unfunded mandate for the NIH. What is really needed to stimulate R&D in this country is to get the NIH and other research agencies back on a growth path. 

2. see Science and Public Policy. 40: 393-405, 2013

Friday, January 16, 2015

More People, No Fish

This week’s SCIENCE has an interesting review on the loss of oceanic fauna (1). The review points out that the loss of terrestrial fauna over the last 50,000 years or so has been far greater than loss of marine fauna. However, it also notes that humans have only had the technology to seriously impact the oceans for a couple of hundred years. The review ends on a somewhat upbeat note saying that we can learn from past experience on land and devise ways to protect the oceans. However, I can’t help but being more pessimistic in light of the ever-growing human population that will result in greater demands on fisheries and increasing pollution of marine environments both locally and globally.

While marine sanctuaries and controls on fishing may be helpful as the article suggests, it is often not possible reverse the effects of extreme over-fishing; witness the failure of cod stocks to return to the Grand Banks after twenty years of protection. Perhaps more importantly increasing human populations and increased economic development are leading to widespread degradation of the marine environment just as they do on land. Agricultural run-off, destruction of coastal marshes for housing and fish-farms, release of plastics and other chemicals into the sea, as well as the global warming created by our carbon based economy will all accelerate as the human population increases. Poor fish!

Thursday, January 8, 2015

Slow Career Development for Young Biomedical Scientists

In a recent commentary in PNAS (1) Ronald Daniels, the President of Johns Hopkins University, discusses the increasingly slow career progression for young scientists. He points out that the average age for attaining an initial medical school faculty appointment has gone up by about 5 years between 1980 and today while the average age for the first NIH R01 grant for MDs has gone from 38 to 45 yrs.  While Daniels mentions several possible contributory factors, clearly the key is the ever-increasing length of the postdoctoral training period. This in turn is built on the continuing over-production of biomedical Ph.Ds which raises the level of completion for ‘real’ jobs in academia or industry to impossible levels. 

As stated previously on this blog the solutions to this problem are first to reduce the supply of Ph.D trainees and second to begin to develop stable career paths in science that are distinct from the traditional professor/PI pathway.