Unsexy Science?

Newsweek's cover story is "Desperately Seeking Cures: How the road from promising scientific breakthrough to real-world remedy has become all but a dead end." In it, Sharon Begley tries to break down the reasons we're all not living to 150 yet. Her main argument is that finding cures for disease is "unsexy." Unfortunately for an article about science, the article is thick on anecdotes but thin on statistics, and deteriorates into yet another Begley diatribe about how basic research fails to fill the public good.

First off, I take issue with the notion that curing disease is the only goal of the NIH or of academic science. Science actually shows that ~2/3 of human disease is self-inflicted, as the WHO points out: "Seven leading risk factors... account for almost 60% of all ill health in the Region." The NIH, correctly, takes a broad view of applied science: "NIH’s mission is to seek fundamental knowledge... to enhance health, lengthen life, and reduce the burdens of illness and disability." If you ask me, weapons and global warming are greater health threats than diseases caused by overeating.

While Begley claims disease is "unsexy," the reality is that the NIH pours money into medical school research campuses and every scientist has wet dreams about curing cancer. In fact, the last guy to run the NIH (Elias Zerhouni) was an MD who focused almost solely on translational stuff. Begley's argument boils down to a "lack of cures," but that's a loaded metric. As I've pointed out here before, testing a single cure can cost the same as 1,000 research labs per year. The $50b NIH budget just couldn't accomodate that, although we could fund it if we cut back our military. You want better cures? Pay scientists what they deserve.

From the article, it's clear that Begley (who holds only a B.A. and has never done research) thinks science is simple: find a drug, cure a disease. So she can't understand what's holding up the works. But what we've learned over time is that conventional small molecule therapeutics may not work for chronic disease. On the other hand, stem cell technologies and genomics are showing a lot of promise for curing disease. The system is by no means perfect, but I think in 50 years we will look back and realize that it was working, at least as much as we let it work.

Even a Caveman Should Know It

The evolution wars are over. This may seem hard to believe, considering that 55% of Americans don't believe humans evolved. But behind the scenes there is growing a quiet revolution - of data. It used to be that the strongest evidence for evolution came from the fossil record, how whale nostrils turn into blowholes over millions of years. But now we've got a second, even better source: our genes.

Our genetic code is a biological history book, so long and convoluted that it takes millions of years to erase a single typo. And as we learn to read that book, we discover time and again that Darwin was right. A good example is the recent discovery that most humans share genetic markers with Neandertals (in other words, we dated them). When you compare our genomes to those of other animals, you can see the random changes that happened over time to differentiate our species. There are also special places in the genome that are protected from mutation called CpG islands, and we can tell how the rest of the genome has changed by comparing it to these special sections.

None of this is understood by the Young Earthers. One reason is that sciences continue to be woefully underrepresented in liberal arts curricula. The average American college graduate therefore has very little basic understanding of biology or any other science. Thanks to this institutionalized ignorance, the debates going on in newspapers today are based on data 20 years old - and are about as relevant. We are flapping our gums, spending energy and time, over questions that are already settled. If America is going to lead the world in the 21st century, we are going to have to do better than that.

The Anxiety Gene

Fear is a very useful evolutionary trait. Species have survived for millions of years simply by running away at the slightest hint of a threat. Considering how useful fear can be, it comes as no surprise that mother nature occasionally deals out an overdose, which we humans recognize as anxiety, nervousness, or neurosis.

Animals can be neurotic, too. Just as humans bite their nails, some Dobermans have a nervous habit of chewing on their paws. A recent genomics study examined these paw-chewing Dobermans, and found that they tended to have a special version of one gene called CDH2. This appears to be a bona-fide behavior gene, a kind of holy grail in the field of behavioral genetics.

In humans as in dogs, inbreeding may permit neurosis genes to rise to the top and manifest themselves. For instance, I have been told that the Baba Nyonya, a group of Chinese-Malays who traditionally marry within the family, suffer from a high degree of mental illness among their females. Similarly, some researchers are studying whether certain neuroses are overrepresented among Ashkenazi Jews, thus explaining the ouvres of Woody Allen and Larry David.

Although fear might be useful from an evolutionary standpoint, too much of it can be crippling, and can even result in unnecessary violence. As Yoda put it, fear is the path to the dark side. Ultimately, neurosis/fear/anxiety are products of not only nature, but also nurture. We can't easily control our genes, but by diversifying our social interactions we can distinguish true enemies from those who exist only in our heads - a step towards a less anxious and less stressful life.

I was blind but now I see

It's easy to get caught up in the political tailwinds, but the truth is that politics rarely makes progress. Science, however, is constantly surprising me with its ability to power science fiction into science fact.

Take gene therapy. Fifteen years ago, the field seemed dead (some of its early adopters actually died, which did not help matters). Today? It's the future of medicine. Gene therapists have literally given sight to the blind, cured bubble boys (left), and most recently reversed beta thalassemia - and sickle cell anemia is not far behind.

The secret? Two words, my friend: Evo and Lution. Gene therapy works because the body selects for successful cells. The healthy cells - the ones with the good copy of the gene - outcompete the shitty ones mother nature dealt you. And your body is so highly optimized, even a small population of good cells is enough to keep the bad apples at bay.

So what's next for gene therapy? Well I'll put it to you this way: of the ~4,000 human diseases, only a few are currently treatable. As genomic data explodes, so will our understanding of the genetic basis of these diseases - and so will the cures. So in our lifetimes we can expect to see cures for Fanconi's anemia, Huntington's disease, polycystic kidney disease, and stubborn old cystic fibrosis, just to name a few. That is what scientists are bringing to society - but what is society bringing back? Only 39% of Americans believe in evolution. I wonder sometimes who we are busy saving.

Is cancer incurable?

All of the livers above are from the same strain of mouse, which develops liver cancer. The livers on the right are from mice injected with virus that expresses a special microRNA that is usually lost in liver cancers. The livers on the left are from mice that were injected with a control virus. The animals were injected with the virus at the time when their livers had already developed small tumors, and then sacrificed for autopsy 8 weeks later. The same issue of Cell features another article about a microRNA that prevents breast cancer metastasis.

Despite their power, microRNAs are pretty new, and were discovered only through basic research:

The first microRNA was discovered in 1993, in worms. It took seven years for the second one to be found, also in worms, but then the floodgates burst.

Lebron's mom, the natural juice

When Lebron first came into the league a few years ago, I was shocked at how BIG he was for an 18 year old. I have to admit, the first thing that came to my mind is that this kid must be juicing. But over the years, I've come to realize that King James doesn't need performance-enhancing drugs. He was born with a far more formidable competitive advantage: his mother Gloria.

Gloria is fearless, and Lebron's biggest fan. Last year in the playoffs, she almost decked Paul Pierce after he flagrantly fouled her son to stop an easy basket (luckily, Kevin Garnett was there to calm her down):

Lebron's response: Momma, sit down!

Now, she may not look like much standing next to these NBA all-stars, but Gloria's tall, buff, and aggressive - traits Lebron seems to have inherited. Looking at the kid, I suspect she fed him some pretty big breakfasts, too. It wasn't easy for Gloria to raise Lebron - his dad was a deadbeat, and at times she had to send her son to live with another family. But despite all the instability, Lebron always knew there was one person out there who always had his back. With a mother like that, who needs steroids?

Here are some of King James' most amazing plays this year - he was named league MVP a few days ago. Happy Mothers Day!