Sequestering the Future of Young Scientists

A recent editorial in NATURE described the many negative effects of the sequester and other budget cuts on the state of US science.  Among the immediate public effects are reductions in NOAA weather monitoring just prior to hurricane season and in USGS monitoring of snowpack (and thus water supply) in the west.

However, in the long term, the most damaging aspect of the recent science budget cuts may be their effect on career choices by talented young people. Discouraging prospects for research funding and for career advancement will lead bright, internet savvy young folks away from science and technology and into other fields. Even among those who choose to go to graduate school in a science field, many young people are now projecting non-research careers in industry rather than considering academic research. This country has already suffered immensely by having some of its brightest minds seduced by the high payoffs of non-productive financial hocus-pocus on Wall Street rather than pursuing jobs in science, engineering or medicine. The current budget restraints will just compound this trend. 

http://www.nature.com/news/uncertain-times-1.13028 

Recipe for Junk Science: take 1 part crowdfunding + 2 parts congressional oversight and mix.

 

Given the dire state of the economy it is not surprising that there is a lot of concern about the financing of research. This comes in two forms. Scientists anxiously seek new sources to augment limited federal funding, while government officials fret about the public getting value for its investment in science.

On the first issue, some investigators have been turning to ‘crowdfunding’, using sources such as Kickstarter, FundaGeek,  SciFund Challenge and others to raise money for their labs. The pluses and minuses of this trend are nicely discussed in a recent blog post on In the Pipeline (http://pipeline.corante.com/). While there may be some positive features of crowdfunding such as getting the public more involved in science, to this curmudgeon the pluses are far outweighed by the negatives. Ultimately success in public fundraising is contingent on ‘selling’ your science, leading inevitably to a race to the bottom where scientists/salesmen promise ever more to their supporters.

On the other issue, this week’s SCIENCE reports on a proposal from congressional Republicans to alter the way the National Science Foundation awards grants, ostensibly to improve the quality of the research being supported. The “High Quality Research Act” authored by Representative Lamar Smith of Texas would require the NSF to certify that its grant awards address ‘national interests’ and “problems of utmost importance to society”.  Aside from the obvious fact that most basic research does not immediately address ‘national interests’, this ploy is obviously a step toward squelching science that contradicts the ideology of the extreme right wing of the Republican Party. Will unbiased climate science be considered in the national interest by a Texas Republican? How about research on alternative energy sources? How about therapeutic cloning? However, maybe “research” supporting creationism could pass congressional scrutiny!

Political intrusion of this type is just about the worst thing that could happen to American science and technology. If we want to guarantee that we lose our technological leadership to competitors like China and India, then the “High Quality Research Act” is the way to go.

http://www.sciencemag.org/content/340/6133/670.full

Horns of the dilemma: value to cancer patients versus profits to drug companies.

The pharmaceutical industry has recently developed several drugs that produce remarkable benefits in certain cancers. These include both small molecules and monoclonal antibodies or other macromolecules.  However, in some cases these life saving drugs come with astronomical price tags of $100,000 per year or more. Patients and insurers have long been concerned about these costs, but now oncologists have also started to rebel (1). This began with a group of physicians at Sloan Kettering cancer center in NY who objected to the high price of Zaltrap®, a new drug from Sanofi. It has since spread, and many oncologists support a commentary in the April 25 issue of the journal Blood (2) advocating for lower drug prices. In addition to Sanofi, criticism has been leveled at Novartis the maker of Gleevec®, as well as at other producers.

One of the problems in this area is the increasingly fragmented nature of the cancer drug market. As studies in cancer genomics have progressed the existence of multiple cancer subtypes has emerged, with each potentially requiring a different therapeutic approach.  One of many examples of this is the recently published study of endometrial carcinoma (3) that has divided this disease into four distinct categories and also revealed previously unsuspected relationships to some forms of breast and ovarian cancers. Unlike ‘classic’ cytotoxic anticancer drugs like doxorubicin that are used in a variety of cancers, many of the newer agents are highly selective for particular cancer subtypes. Since each subtype involves far fewer patients than previous broader cancer classifications, the industry response has been to raise prices. The argument, of course, is that this is necessary to cover R& D costs.

The issue of drug pricing came to the fore at the recent Biotechnology Industry Association meeting in Chicago, as reported in C&EN (4). Business oriented consults advocated that drug and biotech companies carefully consider future value and reimbursement issues before proceeding too far down the development pathway. However, this approach would put profit considerations squarely in opposition to the advance of science. As understanding of cancer (and other diseases) advances rapidly it should become possible to design drugs that have dramatic impacts on individual disease subtypes. Gleevec® is the current hallmark of this, since it has revolutionized therapy of chronic myelogenous leukemia but is useful only in this disease plus a few rarer cancers.

We seem to be coming to a sort of end game with current models of cancer drug development.  Patients need advanced drugs but our health system cannot sustain outrageous costs. Some new ideas about drug development strategies have been published recently (5) and more thought needs to be given to this critical area.

1.    http://www.nytimes.com/2013/04/26/business/cancer-physicians-attack-high-drug-costs.html?pagewanted=all&_r=0

2.    http://bloodjournal.hematologylibrary.org/content/early/2013/04/23/blood-2013-03-490003.long

3.    http://www.nature.com/nature/journal/v497/n7447/full/nature12113.html

4.    http://cen.acs.org/articles/91/i17/Drug-Firms-Face-Value-Questions.html

5.    http://spp.oxfordjournals.org/content/early/2013/02/07/scipol.scs125.full?sid=a930235d-43a2-4619-b2eb-4b0134742d85; Mol Interv. 2010 Apr;10(2):65-8.

Science Policy and the H-1 Visa Dilemma

Like many senior academics, I have often helped young colleagues from other countries who intend to pursue their careers in the USA to obtain H-1B visas.  In most cases the goal was to allow these young scientists to be able to apply for federal grants and start building an academic career. In general I think this process has been quite positive for American science. An interesting recent sidelight is, that with the growth of research support in countries such as China and India, an increasing proportion of foreign scholars wants to return home rather than develop a career here.

However, the relatively benign process of seeking permanent residency for foreign scientists trained at US universities stands in stark contrast to the current attempts of big technology companies to import inexpensive foreign engineers and technologists on a massive scale. The immigration legislation currently pending in Congress (1) will make it much easier for that to happen.  The companies claim that they cannot fill available high tech jobs with people in the US. This is really risible! With today’s historically high unemployment including many tens of thousands of technically trained people desperately seeking work, it strains credulity to think that we need to import foreign technologists. Obviously these companies simply want to fill their positions with people who will work for lower salaries than Americans, and who will accept a form of indentured servitude that ties the worker to the company via the visa. In particular this thrust is explicitly designed to get rid of older US workers and replace them with young, poorly paid foreign workers (2).  This is a perfect example of corporate shortsightedness. Each company expects to reduce its costs, yet counts on a thriving market in the US to sustain its products. As Henry Ford found long ago, you need to pay workers enough to buy your products. Apparently corporate America has forgotten this fundamental lesson.

Many responsible organizations such as the Institute of Electrical and Electronics Engineers have opposed the new legislation (3). Additionally there are all sorts of loopholes in the current program that allow more visas than the stated limits (4). But perhaps the most telling argument against increasing the visa pool is a simple economic one. If there really were such a need for tech workers then compensation for those workers should have increased, but this has not happened (5). Indeed, as we have stated many times in this blog, the US is probably already producing more scientists and engineers than the economy can absorb.  The notion promoted by the tech companies that only by foreign recruitment will we have access to the 'best and brightest' technologists has been thoroughly de-bunked in a recent report from the Economic Policy Institute (6).

This would be a good time for those of us in the R & D game to make our voices heard about the negative consequences of the proposed immigration changes.

1. http://www.nytimes.com/2013/01/29/us/politics/science-workers-focus-of-second-bipartisan-immigration-plan.html

2. http://abcnews.go.com/blogs/politics/2012/02/are-americans-losing-high-skilled-jobs-to-foreigners/

3. http://articles.economictimes.indiatimes.com/2013-03-30/news/38145676_1_h-1b-visas-h-1b-programme-american-jobs; http://www.ieeeusa.org/communications/releases/2013/041613.asp

(4) http://www.cbsnews.com/8301-505124_162-57577726/h-1b-visas-more-than-the-quotas-indicate/

(5) http://www.nytimes.com/2013/02/08/opinion/americas-genius-glut.html?_r=2&

(6) http://www.epi.org/publication/bp356-foreign-students-best-brightest-immigration-policy/
 

Treating disease with electrons: the emergence of electroceuticals.

As described in a recent article in NATURE, the emergent field of ‘electroceuticals’ is an exciting new thrust for therapeutic research. GSK should be congratulated for boldly seeking to catalyze rapid development of this area. The connections are readily apparent between the electroceutical approach, the Brain Activity Map efforts announced recently, and continuing developments in nanotechnology.

However, this novel approach comes with many questions and problems. Assuming that progress is made in treating a disease state using neuronal stimulation, how does one go about assessing benefit versus risk? In conventional drug discovery there are well-established approaches for evaluating potential toxicities at the pre-clinical and clinical levels. But it is not clear yet how risk assessment will be conducted in the new realm of electroceuticals where therapies may need to be based on the unique neuronal wiring patterns of individuals. An interesting issue for the future.

http://www.nature.com/nature/journal/v496/n7444/full/496159a.html

The Brain Activity Map (BAM): The Pluses and Minuses of Science Policy in the Making.

As recently outlined in SCIENCE and other journals, as well as in the general media, President Obama’s announcement of the BAM has caused quite a stir. While many scientists welcome this large new thrust in neuroscience, others question the technological feasibility of the project. It is interesting that much of the initial energy and organization for this concept came from non-neuroscientists and from private groups such as the Kavli Foundation rather than arising from the NIH’s neuroscience mainstream.

Whether or not the BAM project becomes a major scientific success, it is a notable example of how science policy decisions are made. A relatively small group of scientists and foundation people were able to create a compelling vision and then ‘sell’ it to senior policy makers. This will entrain a significant new investment in neuroscience and in the technology needed to pursue the project’s goals.

In the broadest sense it will be good to see any new investment in basic science. However, is the BAM the very best use of the ~ $100M/year research investment? In terms of overall global good would the money be better spent on malaria research? On better antibiotics for drug resistant bacteria? On early detection of tumors?

The BAM episode highlights the fact that we do not have a systemic approach to assessing the nation’s need for research and development. While such approaches have been suggested (1) they have never really been implemented. For the most part, science policy, especially in the biomedical arena, is driven by pressures from interest groups, primarily patient advocacy organizations. The enormous investment in HIV research is a paramount example of this. While the interests of patients clearly need to be represented, sometimes disease-focused research is not the most rapid path to progress.  That is why the BAM project is so interesting; like its Genome Project predecessor, it is primarily driven by basic research issues rather than having a disease focus.

Thus the BAM project may provide a model for scientists in other areas to energize their fields with new funding. Unfortunately it also exemplifies the lack of a logical, systemic approach to public funding of science.

(1) Guston, D. & Sarewitz, D. (2002). Real-Time Technology Assessment. Technology in Society, 24(1-2), 93-109.

http://www.sciencemag.org/content/340/6128/15.2.full 

Drug Discovery- a Fair Share for Academia and the Feds?

 

An interesting letter from Senator Ron Wyden to Francis Collins, the NIH director, brings up the issue of public contributions to private drug discovery research (1). Specifically at issue is Tofacitinib a new anti-arthritis drug that grew out of a collaboration between Pfizer and an NIH funded academic investigator. Senator Wyden asks why isn’t some of the expected $2.5B in revenue from Tofacitinib being funneled back to the NIH. However, this letter underscores a much larger set of issues regarding the evolution of the partnership between academia, the pharmaceutical industry and federal funding agencies.

Currently much of the basic research that leads to new drugs is conducted in academia and is funded by the NIH or charitable foundations (2). Because of the Bayh-Dole act universities can glean some financial benefit by licensing intellectual property rights to companies that want to further develop the research. However, the feds are pretty much frozen out. Further, since much of the academic work deals with early stage research, usually the return on academic IP is small. 

While it is clear that the pharmaceutical industry must make major investments to convert early stage academic research to a drug, one wonders if the initial academic/federal component is being properly valued and rewarded. Rather than the haphazard system of shopping university IP around to various companies, a better approach might be to develop collaborative agreements that share both the risk and the reward of drug development. This would allow both academia and federal funding agencies to glean part of the enormous profits associated with successful drug development. Putting these funds back into fundamental research would create a sort of virtuous circle leading to increased numbers of promising drug candidates. An analysis of this type of activity has recently been published (3).

Interestingly the Wyden letter was recently discussed on the popular blog ‘In the Pipeline’.  Most of the commentary there stated that Sen. Wyden was wrong and the NIH had no business being compensated for its contributions. I think this is a very shortsighted viewpoint. We clearly need major changes in the drug development process to make it more efficient and less costly. A smoother integration of federal, academic and commercial research, with appropriate rewards to the parties, would go a long way toward that end.

(1) http://www.wyden.senate.gov/news/press-releases/wyden-urges-nih-to-reexamine-policies-

(2) Stevens, A. J. et al. The role of public-sector research in the discovery of drugs and vaccines. N. Engl. J. Med. 364, 535–541 (2011).

(3) R.L. Juliano Pharmaceutical innovation and public policy: The case for a new strategy for drug discovery and development. Science and Public Policy (2013) pp. 1–13 (http://spp.oxfordjournals.org/cgi/content/full/scs125?
ijkey=8StCkSiKrZOaKjb&keytype=ref)

http://www.wyden.senate.gov/news/press-releases/wyden-urges-nih-to-reexamine-policies- 

http://pipeline.corante.com/