A new way to create new drugs

I noticed this piece on Ethical Insight. It points toward interesting new directions in the realm of high-stakes philanthropy:

The Bill and Melinda Gates Foundation was already a multi-billion dollar enterprise when Warren Buffet, then the world’s second richest man after Gates, turned over the bulk of his fortune to the Gates Foundation. The Buffet donation will eventually increase the foundation’s current endowment of US$33 billion to over US$60 billion. One of the Foundation’s major causes in developing countries focuses on improving health. According to a report by pharmaceutical information group IMS Health Inc, the money available from Gates Foundation for developing new medicines and cures is changing the way the pharmaceutical industry operates. Companies in the sector are likely to find it more practical and better for public relations to cooperate with a foundation that has the resources to compete with both government-funded institutions and commercial pharmaceutical firms. As an example, the report cited the program proposed by the Gates Foundation in July 2006 to create an international network of 16 laboratories to develop new approaches to finding a vaccine to combat AIDS. The Foundation offered US$287 million dollars to the laboratories that successfully developed an innovative idea. The idea of rewarding success also encourages companies to collaborate with rivals to develop a vaccine. Indeed, the IMS report suggests that pharmaceutical companies might even face pressure to collaborate with the foundation, even if it impacts their bottom line. "The alternative is for pharma to allow itself to be perceived as indifferent to global health concerns – or to be unseated in the pursuit of advances in world health," IMS said.

Essentially, the Gates Foundation is stepping in and directly stimulating pharmaceutical research that would not happen otherwise because of its conflict with the profit motive. (Drug companies cannot justify spending billions of dollars developing a drug that will not recoup its costs-- say, a drug that will mostly be used in poor countries). Throwing $60 billion around can alter this attitude, however.

I find this interesting for a number of reasons. It used to be the government that encouraged research in areas that might not turn out to be profitable. But with the rising cost of some types of research-- especially drug research-- the government's pockets are hardly deep enough to fulfill this role along with all its other duties. Now a private foundation has gotten large enough to play this role. It's definitely a shift in the R&D players and landscape.

We are discussing "social entrepreneurship" in my Business and Social Justice class right now. This is like regular entrepreneurship, but includes a dimension of social benefit. In fact, the social purpose of the venture outweighs the profit motive in cases where the two conflict. I find this is exciting new direction for entrepreneurship to be going in because it (1) challenges the notion that economic profit is the only worthy goal, and (2) also challenges the notion that money-making is inherently opposed to charitable work. Social entrepreneurs may be non-profit, but they may also be for-profit and simply willing to accept lower profits than the absolute maximum possible.

This is a surprisingly radical notion. Our current capitalist system actually legally requires a corporation (at least a public one) to seek the greatest profit above all other considerations. There is no model for wanting some profit, but not the maximum if that involves too much other harm (say, to the environment or to social well-being). The current system seems quite restrictive to me. After all, in my own life I can choose to work at a lower-paying job if I want to. I have no "duty" to make the maximum amount of income possible, much less profit! Instead, I make a balanced choice based on myriad considerations (and available opportunities). Why can't businesses do the same?

Back to the Gates Foundation. It is not quite social entrepreneurship-- it's basic philanthropy-- but I like the innovation Gates is introducing into the funding landscape. And the way it is actually reshaping some of the structure of the pharmaceutical industry. Maybe we can start some new habits.

Less Formaldehyde-- breathe easier!

Congratulations to Elizabeth Whalen, my esteemed classmate and friend at BGI, for playing a pivotal role in setting limits on the use of formaldehydes in wood resins in California. This legislation, just adopted by the California Air Resources Board (CARB), protects public health, given that formaldehyde is linked to cancer.

All wood has some naturally occurring formaldehyde. But more formaldehyde is added to composite wood in the form of certain resins, which are used to bind wood particles together. New methods are available and others are quickly being developed that reduce and even eliminate the need for formaldehyde. When ARB's standards are in full effect in 2012, annually there will be 500 fewer tons of formaldehyde in California's air.

This was a several-year battle. Thanks, Elizabeth!

Everything I Need to Know about Mindfulness...

... I learned in elementary school?

Yes. A school in Oakland is incorporating basic mindfulness training for children into its curriculum. There is story about it here. I know the teacher, Richard Shankman, and he is a very clear guide in this technique. As the kids and teachers say, mindfulness really works.

Actually, it's like poetry: It works on many levels. It's great for basic relaxation and calmness. It also goes a lot deeper.

Bravo, Richard. This benefits not just the kids, but everyone.

Microclimates

I often take a walk around the neighborhood near my house, and out of habit it ends up being the same route much of the time. Occasionally I think about how I ought to go a different way for variety, but suddenly, on a recent walk, I noticed something new about this supposedly old, tired route.

There are particular places along the route that are distinctly warmer or cooler in a consistent way. It's not just that the breeze kicks up or the sun comes out from behind a cloud. Now that I've walked this route many times, I see that certain little patches really are "warm spots" and "cold spots." I have discovered the microclimates along this route.

They vary in size, but are generally about 1/2 to 1 block's length. It would be fun to bring a thermometer and actually see how great the temperature variation is, but empirically, the cold spots make me want to zip up my jacket and the warm spots make me want to take it off. And although my internal thermostat is set a little cold (I tend to feel cold when others are comfortable, and comfortable when others are hot), I am not unduly sensitive to small changes in the temperature. So I think these microclimates must have significant temperature deltas.

How interesting! Imagine if you buy a house in a "warm spot" or a "cold spot" -- you might have a very different impression of weather in your town compared to a neighbor just up the street.

Dual-use neural pathways: Warm thyme

My father has always described the taste of certain soups as "warm" -- it is, to him, the absolute best adjective he can come up with. Now we know why.

Certain herbs, when applied to the tongue or the skin, elicit a neural response that is the same as if the temperature had been raised. The neural pathways evoked by thyme, oregano, and cloves are (at least for some people) the same as those used in a thermal response. The soup really is "warm"!

I have tried this experiment with thyme flavor myself, and can sort of perceive the temperature effect, but it is not distinct enough to be certain. Probably I feel it because I know I am looking for it. Perhaps only some people have these dual-use pathways, or perhaps some people are more able to perceive the two effects.

I looked for a reference, but the clearest version seems to have been publised in Nature, to which I don't have online access. Here is an abstract that may be relevant:

Nat Neurosci. 2006 Apr 16; : 16617338

Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels.

Haoxing Xu , Markus Delling , Janice C Jun , David E Clapham

Carvacrol, eugenol and thymol are major components of plants such as oregano, savory, clove and thyme. When applied to the tongue, these flavors elicit a warm sensation. They are also known to be skin sensitizers and allergens. The transient receptor potential channel (TRPV3) is a warm-sensitive Ca(2+)-permeable cation channel highly expressed in the skin, tongue and nose. Here we show that TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol. Tongue and skin epithelial cells respond to carvacrol and eugenol with an increase in intracellular Ca(2+) levels. We also show that this TRPV3 activity is strongly potentiated by phospholipase C-linked, G protein-coupled receptor stimulation. In addition, carvacrol activates and rapidly desensitizes TRPA1, which may explain the pungency of oregano. Our results support a role for temperature-sensitive TRP channels in chemesthesis in oral and nasal epithelium and suggest that TRPV3 may be a molecular target of plant-derived skin sensitizers.