economics nuttiness

We are certainly seeing a serious schism in american political life. One might argue that it's time for the country to split into two. Not north versus south, but ultra conservative versus moderate (never mind about ultra liberal, they are a weak force in politics by now). Clearly there is a major fraction of the US population that does not really accept a real role for government - they don't accept the fundamental concept of civitas. They may think that police, fire, education and the arts should all be privately managed, i.e. only available to the well-to-do.

Let's review what actually happened during the past 10 years. After 9-11, the US became hugely militarized, and the the Patriot Act one could say pretty fascistic (when it needed to be, and not against most of the population, but against targeted groups certainly). As usual in time of (effectively) war, the country rallied around its government and its elected political majority party. Unfortunately, the actual military actions were rapidly hijacked by a totally irrelevant agenda, i.e. the conquest of Iraq rather than a focused campaign against Al-Qaeda and its associated groups. Clearly the entire Iraq campaign was unnecessary from a home security perspective (regardless of its possible value to Iraqis under their dictatorship, although it's arguable whether we've actually done the poor Iraqis any good at all). Moreover, it was hugely expensive. The failure to focus sufficiently on Al-Qaeda probably made the subsequent military expansion into Afghanistan necessary.

At the same time that these two wars were prosecuted, marginal tax rates were lowered and financial speculation was wildly over-encouraged, leading to the 2008 fiscal meltdown. The huge deficit incurred by now in the U.S. is a clear outcome of those mostly Republican policies (although plenty of Democrats played the banking deregulation game as well, to their shame). Now hard line Republicans want to finally pay for those wars and financial shenanigans by ultimately eliminating Social Security and Medicare (though most of them won't say as much in as many words). So the true vision of these hardliners is clear: a dog-eat-dog world where nice guys finish last, robber barons run the country, and the justification is that after all maybe I could be one of those robber barons if the rule of law is practically abolished. Sorry guys, but I don't agree with your basic premise. I think it is possible for the country to have sustainable "entitlements", in fact that is not even the right word for them. Social Security and Medicare are basically national savings plans, they are paid by everyone's taxes because everyone will need them some day. The way to prevent them from bankrupting the country is to manage them, which is hard, not to abolish them which seems easy but is in fact vicious and mean.

OK, my two cents today, inveighing against mean spirited fascists.

Rare genetic disorders

this is cribbed from my FB page, but liked it enough that I wanted somewhere more permanent for it. The topic is the genetic analysis of rare single-gene disorders, what are some of the rationales justifying that work.

Our genome has something like 20,000 genes and we need to know what the consequences are of mutations in all of them. In some cases they will be of very general significance, such as mutations causing breast cancer or diabetes or osteoporosis; in such cases even if the genetic disease is rare the genetic pathways identified may provide new drug targets for a much larger number of people who have the same disease due to non-genetic defects in that pathway.

Moreover, even though each of these single gene disorders is individually rare, in aggregate there are thousands of them and together they comprise a significant fraction of pediatric hospital patients. Since each disorder is different, the only way to diagnose and determine optimal patient management is to understand the molecular bases of all of them - so far the human genetics community has characterized about 2500 rare genetic disorders (I personally have been involved in discovering 15 of these). That is still fewer than 20% of all potential single-gene conditions. These include very well known things like Huntington disease, cystic fibrosis, and some forms of breast and colorectal cancers, but also tons of relatively unknown (to the public) things like Marfan syndrome (maybe Lincoln had it), neurofibromatosis (elephant man), achondroplasia (many forms of dwarfism), and metabolic disorders including one that all children born in the modern world are tested for (by enzyme activity, not by DNA test) phenylketonuria. In addition, by studying the genomes of patients with rare disorders, we are learning a lot simply about genetic variation, which is essential for when we move on to trying to understand the genetic component of more complex diseases which have multiple genetic and environmental factors. At the moment we are not really smart enough to tackle that problem (although many scientists are trying), we have to take baby steps. On a purely logistic note, these kinds of discoveries (for rare genetic disorders) cost on the order of thousands of dollars each, sounds like a lot but compared to hundreds of millions that are spent on diabetes, obesity, cancer it's a superb return on investment to the taxpayer