Author: jlolds

Native Angeleno, professor of Neuroscience and Public Policy at George Mason University

Basic human neuroscience studies should not be treated as clinical trials…

In the last year of my service at NSF, the NIH issued a new policy with regards to a particular kind of neuroscience that has become the bread and butter of psychology departments, especially those that focus on cognitive science. These experiments are the modern versions of 20thcentury social psychology experiments where the experimental subjects would be healthy college students (and definitely not patients). In the modern versions, students receive brain scans using functional magnetic resonance imaging machines (fMRI; completely non-invasive) so that the investigator can actually visualize the functioning of the subject’s brains as they perform some task (or even play a game).

The new NIH policy will consider these studies to be “clinical trials”.

Clinical trials are a special animal from the standpoint of NIH’s regulations. In particular, the entire constellation of medical ethics: from informed consent all the way to how results are analyzed and revealed fall under the jurisdiction of a complex set of compliance requirements. That makes sense for patients because they are sick and on the vulnerable side of a power relationship with their caregivers (clinicians). The question is should this thicket of compliance rules apply to the above type of psychology experiments? I don’t think so. Yes, there should be rules but to my mind they should not rise to the levels seen in the medical trials context. These types of studies are qualitatively different. Let’s not force apples to be oranges. This piece in Science has the latest development in this story: NIH has agreed to postpone for one year putting this new policy in place.

Nitrogen: the chemical fertilizer connection

I’ve been thinking a lot about nitrogen lately. It plays a crucial role in the biosphere because all of the peptide bonds that make up proteins contain that element. And proteins are truly ubiquitous in living things from the very smallest bacteria up to giant redwoods. Because plants require nitrogen to grow, farmers must buy nitrogen containing chemical fertilizers to feed their crops. The run off from their fields pollutes by overloading our waters with nitrogen in the chemical form (called ‘fixed’) found in their fertilizers. The result of that artificial fertilization of lakes and streams (and even coastal estuaries) are algal blooms that crowd out the rest of the biosphere for resources. It’s not good.

Not all crops require fertilizer though. Some crops—legumes—have made a peace pact with the soil microbiome surrounding their roots. In the deal, the local microbes do the work of the farmer by fixing atmospheric nitrogen into the form that plants can use. In return the plants provide other nutrients to the bugs. One of the great challenges for the future of food is to figure out a way to make that peace pact work for our major commercial feed crops like wheat or corn. And that’s not only because it would be a good thing for our waterways. It turns out that chemical fertilizer is also very expensive and requires natural gas to synthesize urea. So if we figured out a way to replicate the microbial pact that legumes have, we could not only reduce pollution, we could save a whole lot of money.

Steven Brill’s book: Tailspin

I am reading it now. I did not realize that he would write about two of my favorite higher education institutions: Amherst College and UC Irvine, both in the context of bridging the moats that currently exclude many (if not most) from the benefits of 21st century American meritocracy. Amherst, because its former President, Anthony Marx, put in place a program to actively reach out beyond the usual legacies and elite high schools in its recruitment of freshman. UC Irvine, because like my own institution (George Mason), it has focused on educating bright students who are from under-represented backgrounds. And by that I mean backgrounds that historically have not had access to the top-flight resources that a UC education is all about. Reason to be a bit optimistic.

On the other hand, Brill really focuses on the legal and financial ecosystems, what he calls the Casino Economy. I wish he also wrote more about scientists and engineers in the same context of the American meritocracy.

How Valium works: in detail

This week, in Nature, the structure of a very important neurotransmitter receptor was revealed. The receptor, the GABA-A, allows the functioning nervous system to avoid the “brain super storms” that constitute epileptic seizures. When the neurotransmitter, GABA, binds to GABA-A, in synapses, in acts to inhibit neural activity. The inhibition of neural activity is critical to brain function because the brain can then compute in a very meta-stable state, quite like a marble on the edge of a saddle. That is one of the key design features of our brains that perhaps can be reverse-engineered someday for more power high performance computing a great energy efficiency.

It’s not surprising then, that the GABA-A receptor is also the target for some key drugs, like Valium and alcohol. Both of these drugs act to inhibit brain activity. When taken together with opioids, the effect is one of synergy and the effects can be deadly.

The paper by Zhu et al. used a technique called cryo-electron microscopy to reveal the detailed structure of GABA-A “frozen in the moment” of binding to a Valium analog. This is very important because it may reveal design hints at how to build a future Valium-like drug that relieves anxiety without sedation.

Humans are naturally curious….

Of course, we know that. And as a scientist, it’s a wonderful thing to get paid to be professionally curious. But too often, scientists and journalists, responding to the siren song of reductionism, act in their own worst interests and over-simplify what is inherently complex. Here is a wonderful piece  by Amanda Ripley on her own experiences with this challenge in the context of the charged political times that we are currently experiencing. I was happily surprised, mid-way through the article, to find my colleague Sara Cobb quoted extensively.

Rules of Life: James Lovelock version

So there are many very naive ways of looking at the Gaia hypothesis–and those have engendered a lot of “antibody-response” over the years from the scientific community. Here, Bruno Latour, the French philosopher lays out Lovelock’s scientific perspective on the biosphere in lay language. I think it’s really quite a good essay–and it would be the proper way to talk about it with a lay stakeholder such as a member of Congress. It reminds me of Harold Morowitz’s views on the subject.

Trees under duress…

I really like trees. When I was coming to the end of my time at NSF, I got interested in the local urban forestry commission. When I see mature trees come down in my neighborhood due to in-fill, I see a distinct loss. Those trees provide shade in the summer and  a nice windbreak in the winter. Trees are also extremely important to the health of the planet because they fix carbon. According to this paper in Nature, they account for approximately 45% of the terrestrial carbon stocks. But the paper is worth reading because it reviews how trees respond to the stress of droughts…of which there are likely to be a lot more in the future. What’s interesting to me is how trees respond to stress through a variety of mechanisms that are truly multidimensional. But…eventually they reach a threshold point where the mechanisms of homeostasis break down and mortality ensues. When this happens, it can be a mass-event with thousands of hectares dying at nearly the same time.

France and a new super R1 university…

From Inside Higher Education, here. Money quote:

Five grandes écoles (leading French universities) should be formally merged to form a Parisian science and technology university emulating the likes of the Massachusetts Institute of Technology, the French government has been told.

I think this quite a cool idea. And fits with President Macron’s recent interest in investing a lot of new money in science. Post-Brexit, France has a real opportunity in building a science powerhouse.

Broader impacts (NSF specific)

I thought today I would write down my thoughts on how I define broader impacts (BI) from an NSF perspective. First some background and a caveat: BI is one of two criteria that an NSF grant proposal is evaluated by (the other is intellectual merit). BI arrived at NSF as a criterion in 1996, but the notion really goes back to Vannevar Bush’s arguments for US R&D investments after the Second World War. You can read this in his report,  Science The Endless Frontier, a response to a letter from President Roosevelt.  And the caveat: I’m no longer with the NSF. But I was asked about this a lot when I visited panels and generally my response was as follows….

First, probably the most important BI from my point of view is to communicate the intellectual merit of the proposed science in plain language that the lay public (and especially Congressional stakeholders) can understand.  Even the title of a proposal can be thought of as part of this kind of BI. Far too often, proposers fall back on the pithy titles that are both humorous (to colleagues) and grab the attention of journal editors at places like Science or Nature. Bad idea. From the taxpayer standpoint, the case for the science needs to be sober and cogent.

But this notion of communication extends to the entire BI component of the proposal: a central broader impact is that the general public understands why the proposed science is worthy of investment. So public science communication as part of the BI is an extremely worthwhile activity–as long as it scales. What I mean by this is that if you are communicating the intellectual merit of your science in lay language, make sure to use a medium that reaches a lot of people.

Another excellent BI is to broaden participation (BP) in scientific research. Under-represented minorities and women are often discouraged from careers in science during K-12, but also later during undergraduate training. BP activities that are integral to proposals are definitely responsive to the BI criterion. But here again, they have to scale. Often proposers make the mistake of prioritizing novelty of approach at the expense of scale. If your institution is already actively and successfully engaged in a BP activity, consider, aligning your proposed BI to what is already on-going at your campus. Not only is that efficient use of scarce funds, but it also has the advantage of scaling beyond your own lab or field site.

Finally, understand that the basic big idea behind BI is that scientific research can have dual use: it can increase our knowledge about the universe around us and it can benefit society. BI is about explicitly making that connection clear.