Where Drugs Come From: The Numbers

Wednesday, November 10th, 2010

Derek Lowe looks at a new Nature Reviews Drug Discovery paper that explains where drugs come from:

First, the raw numbers. In the 1997-2005 period, the 252 drugs break down as follows. Note that some drugs have been split up, with partial credit being assigned to more than one category. Overall, we have:

58% from pharmaceutical companies.
18% from biotech companies..
16% from universities, transferred to biotech.
8% from universities, transferred to pharma.

First, the raw numbers. In the 1997-2005 period, the 252 drugs break down as follows. Note that some drugs have been split up, with partial credit being assigned to more than one category.

46% from pharmaceutical companies.
30% from biotech companies.
23% from universities (transferred to either biotech or pharma).

And now to innovation — 118 of the drugs during this period were considered to have scientific novelty (46%), and of those:

44% were from pharmaceutical companies.
25% were from biotech companies, and
31% were from universities (transferred to either biotech or pharma).

So why does this happen?

This paper doesn’t put it one word, but I will: money. It turns out that the novel therapies are disproportionately orphan drugs (which makes sense), and although there are a few orphan-drug blockbusters, most of them have lower sales. And indeed, the university-to-pharma drugs tend to have much higher sales than the university-to-biotech ones.

The bigger drug companies are (as you’d expect) evaluating compounds on the basis of their commercial potential, which means what they can add to their existing portfolio. On the other hand, if you have no portfolio (or have only a small one) than any commercial prospect is worth a look. One hundred million dollars a year in revenue would be welcome news for a small company’s first drug to market, whereas Pfizer wouldn’t even notice it.

The Man Who Called the Financial Crisis

Tuesday, November 9th, 2010

Melchior Palyi, born in Hungary in 1892, is arguably the man who called the financial crisis — 70 years early:

In 1936, as part of reforms under the new Banking Act, the U.S. government mandated that federally regulated banks could no longer hold securities that weren’t rated investment-grade by at least two ratings firms.

To determine how to implement the new policy, the government launched a massive project — with experts from the Federal Deposit Insurance Corp., the National Bureau of Economic Research and the Works Progress Administration — to study how credit ratings should be used.

Mr. Palyi, then teaching at the University of Chicago, was a vocal skeptic from the outset. Looking back into the 1920s, he found that investment-grade bonds went bust with alarming frequency, often in the same year they were rated. On average, he showed, a bank that followed the new rules would end up with a third of its bond portfolio going into default.

The record was so unreliable that it would be “still more responsible,” Mr. Palyi growled, to “stop the publication of ratings altogether.” He was especially troubled that the new banking rules switched the responsibility for credit safety from bankers — and even bank regulators — to ratings firms.

“From there,” he warned, it “will have to be shifted again — to someone else,” presumably taxpayers. Liquidity, Mr. Palyi argued, was being replaced by what he scornfully called “shiftability,” a new kind of risk that could someday “be magnified into catastrophic dimensions.”

(Hat tip to Aretae.)

The Dark Side of the Left

Tuesday, November 9th, 2010

Foseti reviews another Moldbug-recommended work, The Dark Side of the Left, by Richard J. Ellis:

The radical leftists are uncompromising in a way that no other groups are. Thus, they inevitably win — everyone else compromises with them and the political equilibrium is thus constantly shifting leftward. Radically leftward.

Finally, the non-leftist reader will be struck by the similarities that run through all of the movements covered in the book. The abolitionists are the first group covered. The feminists are the second to last group covered. Yet, we don’t even have to leave the chapter on the abolitionists before we get calls for the end to “the patriarchy of marriage.” Let’s look closer at abolitionism.

Ellis quotes Stephen Foster as saying that “every family” is “a little embryo plantation.” Traditional marriage to many abolitionists was a form of slavery that needed to be eradicated like all other forms. Many of the abolitionists also rejected capitalism, as again, it creates “slaves.” Of course, the abolitionists also became militants. Many eventually gloried in the deaths of the Civil War which killed more Americans than any war. For example, Wendell Phillips said that “the bloodiest war ever waged is infinitely better than the happiest slavery which ever fattened men into obedience.” It would be hard to better distill the totalitarian mindset in one sentence.

I’ve chosen to focus on the most controversial topic (i.e. slavery). Don’t let this shade your view of the book. Ellis is best discussing the violence of the New Left, but I found the initial chapter on abolitionism more interesting.

I should conclude by saying that the reactionary will agree with many positions held by the radical leftists. Specifically, the radical leftists have a disdain of the masses that the reactionary will find appealing. However, the radical leftists believe that this makes the masses expendable. Further, the radical leftists believe that the deficiencies of the masses can be fixed with the right program. The reactionary believes neither. The radical leftist despises the masses but continually embraces democracy — his movements, therefore, fizzle in this inherent contradiction. Unfortunately, the don’t fizzle before the damage has been done.

Ellis believes that the core of radical leftism is radical egalitarianism, but Foseti shares Molbug’s belief that it’s really radical protestantism, which has evolved into a secular religion.

Public Choice Ignorance Everywhere

Tuesday, November 9th, 2010

Patri Friedman sees public choice ignorance everywhere:

Since learning about public choice economics, I have been constantly shocked by how little it has been internalized by economists. For example, the phenomenon of Donald Boudreaux, Director of the Center for Public Choice, spending his time on the activism strategy of writing letters to the editor when I would describe Public Choice as “the study of how writing letters to the editor doesn’t accomplish anything.”

Imagine the Director of the Center for Einsteinian Physics calculating spaceship trajectories using Newtonian mechanics in all of his consulting work, and getting the answers wrong every time because he fails to take relativity into account, and you’ll understand my bewilderment. Public Choice provides awfully compelling reasons to Change Incentives, Not Minds, yet in the end it appears that the teacher’s urge to teach and to have teaching be the answer is so strong as to overwhelm mere economics.

More recently, Megan McArdle gave a shining example of public choice ignorance with a very sensible, reasonable piece about why we should abolish the corporate income tax. The piece concludes:

Want to get corporate money out of politics? Want to erode the power of the Chamber of Commerce? Take away one of their primary motives to get involved.

I don’t say this will persuade everyone. But I hope that liberals will at least consider that there might be a better way than the corporate income tax to achieve their goals.

Pointing out a more efficient policy is classic Folk Activism – it assumes that we don’t have efficient policies because no clever economist has yet designed them or eloquently described their advantages. That might have been a reasonable argument 100 years ago, but we’re in the post-Mancur Olson world: we have a whole school of economics explaining how democracy is systematically biased towards policies that transfer from dispersed interests to concentrated ones.

And what is McArdle doing? She’s complaining about a policy that does exactly what we expect democratic policies to do, and advocating for a different policy that would be against the goals of special interests (“Want to get corporate money out of politics?”) and better for society as a whole. As I said in a Students For Liberty talk this past weekend, for all the good this approach does, McArdle might as well have called a press conference and farted into the microphone.

My metaphor is deliberately provocative because I find this pattern so appalling, and it seems absurd that economists so often ignore these basic results in their own field. It moves me to shout: We do not live in a world that mainly suffers bad policies due to lack of ideas about better ones, or lack of elegant explanations supporting good policies, but one that suffers bad policies due to system and meta-system level incentives.

The Dogs of War Go Airborne in Afghanistan

Tuesday, November 9th, 2010

The dogs of war go airborne in Afghanistan — literally:

Members of Britain’s Special Air Service (SAS) special forces have begun parachuting into enemy strongholds in Afghanistan with Taliban-seeking German shepherds strapped to their chests. Once on the ground, the dogs hunt for Taliban insurgents in buildings and — with cameras strapped to their heads sending back video — act as forward scouts for the British special forces unit. The work is every bit as dangerous for the dogs as it is for their human counterparts, The Guardian reports. Eight SAS paratrooper pups killed in combat thus far.

Though the missions are officially secret, earlier reports of the pups’ training shed some light on how the British special forces are likely using them. SAS pooches are trained for High Altitude High Opening (HAHO) jumps, in which parachutes are deployed at a high altitude and long horizontal distance away from a target location in order to allow jumpers to glide in without detection. The SAS dogs are trained to jump tethered to their handlers from heights as high as 25,000 feet and up to 20 miles away — or a 30 minute glide — from a target location. At that height, the lack of oxygen puts them at risk for hypoxia, or oxygen deprivation, so the dogs are fitted with special masks to give them breathable air. The Brits reportedly borrowed the tactic from America’s super-secret Delta Force, which first trained dogs to make HAHO jumps.

Mexican sales of Ford Lobo dip

Sunday, November 7th, 2010

In Asia and Africa, guerrillas rely on the Toyota Hilux, known to Americans as the Tacoma, to get around. In Mexico, the drug cartels rely on the Ford Lobo, known to Americans as the F-150. Now Mexican sales of the Ford Lobo have dippedbecause it’s so popular with the cartels:

Mexican sales of Ford’s Lobo pick-up, popular with drug cartel hitmen, are falling along with those of similar vehicles because motorists fear being mistaken for gangsters by soldiers and police, the head of the U.S. automaker’s local subsidiary said on Thursday.

“It’s a vehicle that is in high demand for committing crimes,” said Gabriel Lopez, the new president of Ford in Mexico. “There’s plenty of space in the pick-up’s cabin for more weapons.”

A slump in sales of the Lobo, part of the F-Series pick-ups made by Ford Motor Co, has helped pushed the company’s total market share in Mexico down to 10.7 percent from 16 percent a few years ago, Lopez told a news conference.

Heavily armed members of drug cartels are known to steal pick-up trucks when they launch attacks on rivals or security forces as part of Mexico’s increasingly bloody war on drugs.

Who does what

Saturday, November 6th, 2010

A three-term Republican Precinct Chairman — who retired a dozen years ago — explains who did what during his three terms:

The Country Club Republicans put up most of the money and provided meeting places. Important.

The religeous right provided a lot of work. It was they that walked precincts and they that worked phone banks. Very important.

The libertarians talked. The libertarians also complained. They were always too busy talking and complaining to do any work.

Daft Punk Derezzed

Friday, November 5th, 2010

You can question the decision to make Tron Legacy, but you can’t question the decision to have Daft Punk provide the soundtrack:

Walking Dead

Friday, November 5th, 2010

The 90-minute Halloween-night premiere of AMC’s The Walking Dead delivered 5.3 million viewers, the highest numbers for any series in AMC’s history — and enough to beat most non-sports programs on Sunday night.

For those not familiar with the genre, it’s not really about zombies:

A survivalist story at its core, the series explores how the living are changed by the overwhelming realization that those who survive can be far more dangerous than the mindless walkers roaming the earth. They themselves have become the walking dead.

After discussing the indestructibility of Toyota trucks, I was amused to see Toyota advertising its Corolla as equipped for a zombie attack… or just life with its hard-core dependability.

ZooBorns

Friday, November 5th, 2010

ZooBorns may deserve the title of cutest book ever — or pair of books, actually, based on a website:








Understanding Libertarian Morality

Thursday, November 4th, 2010

Jonathan Haidt turns his attention from understanding liberal and conservative intuitions about morality toward understanding libertarian morality — and what he and his colleagues conclude is not exactly earth-shattering:

We found that, compared to liberals and conservatives, libertarians show 1) stronger endorsement of individual liberty as their foremost guiding principle and correspondingly weaker endorsement of other moral principles, 2) a relatively cerebral as opposed to emotional intellectual style, and 3) lower interdependence and social relatedness. Our findings add to a growing recognition of the role of psychological predispositions in the organization of political attitudes.

Ronald Bailey of Reason reviews the piece. (Hat tip to Aretae.)

A Stimulus Fable

Thursday, November 4th, 2010

ASM826 shares a stimulus fable, in the tradition of Aesop:

Billy-Bob’s wife had been nagging him about the water level in the swimming pool. It was almost a foot low and the walls below the tile were showing. Billy-Bob knew that if his wife wasn’t happy, he would have no peace, so bright and early on a Saturday morning, he decided to fix the problem.

He went out and looked at the pool and, sure enough, it was low. Since he had a gas powered irrigation pump, he hauled it over from the barn. Pretty good sized pump, Billy-Bob thought, I ought to be able to fill this pool by lunch time.

He stuck the outlet hose in the swimming pool, and since he didn’t have any other source of water, he stuck the inlet hose in the swimming pool, too. Then he started the pump. Now the hoses were worn, and they leaked, and the fittings on the pressure side did too, but the motor ran strong and the pump was definitely moving water.

Billy-Bob went up on the porch and sat in the shade for a half an hour and then went back down to the pool. Water level looked about the same, although there was a small trickle running down the back side of the hill where the pump was sitting. He went over and pulled the outlet hose out of the pool, and water was shooting out of it. Reassured that he was pumping water into the pool, he dropped the hose back in, topped off the gas tank and went to do some other chores.

A couple of hours later, his wife came and got him. When he got to the pool, the water level was lower than when he started. Puzzled, he checked the hoses again, and again was reassured to see water pumping into the pool. Then he had a idea what the problem really was. Turning to his wife he said, “You keep an eye on this, I going to the farm supply store, we need a bigger pump.”

(Hat tip to Borepatch.)

Theoden’s Answer

Thursday, November 4th, 2010

Conservatives often ascribe evil motives to progressive leaders, but it’s not the ultimate evil of Sauron that drives them; it’s the lesser evil of Saruman, and it deserves Theoden’s answer:

[W]ere you ten times as wise you would have no right to rule me and mine for your own profit as you desired.

(That from The Two Towers, by J.R.R. Tolkien, in case you’re a fool of a Took.)

Boa constrictor virgin birth

Thursday, November 4th, 2010

Virgin births do occur among animals:

Many invertebrates, such as insects, can produce offspring asexually, without ever having mated. They usually do this by cloning themselves, producing genetically identical offspring.

But among vertebrate animals, it remains a novelty, having been documented among less than 0.1% of vertebrate species.

In 2006, scientists discovered that two komodo dragons (Varanus komodoensis), the world’s largest lizard species, had produced eggs that developed without being fertilised by sperm — a process called parthenogenesis.

Then in 2007, other scientists found that captive female hammerhead sharks (Sphyrna tiburo) could also reproduce without having sex.

Now researchers have discovered a female Boa constrictor that has produced two “virgin” litters — with an unusual chromosomal twist:

First impressions suggested there was something special about these babies: all were female and all had a particular, rare caramel colouration.

This colour is a rare recessive genetic trait, which is carried by the mother but not by any of the potential fathers.

So Dr Booth and colleagues conducted a series of genetic tests on the snakes to solve the enigma.

What they found was astonishing.

DNA fingerprinting revealed that the offspring had a number of genetic differences from any of their potential fathers, which ruled out all the males as sires of the litter.

That confirmed the first instance of a known virgin birth among boa snakes.

All the offspring also had very unusual sex chromosomes.

Sex chromosomes are packages of DNA that drive the development of sexual characteristics; they essentially make animals genetically male or genetically female.

Humans for example have X or Y sex chromosomes; females have two X chromosomes and males have a combination of an X and a Y chromosome.

In place of X and Y, snakes and many other reptiles have Z and W chromosomes. In all snakes, ZZ produces males and ZW produces females. Bizarrely, all the snakes in these litters were WW.

This was further proof that the snakes inherited all their genetic material from their mother, as only females carry the W chromosome. ”Essentially they are half clones of their mother,” says Dr Booth.

That is because the baby snakes have inherited two copies of one half of their mother’s chromosomes, including one W chromosome.

Antivenom

Thursday, November 4th, 2010

I always found it odd that the cure for a venom was an antivenin — and that inflammation of a tendon was tendinitis — but it looks like the sensible term, antivenom, has won out:

The name “antivenin” comes from the French word “venin”, meaning venom, and historically “antivenin” was predominant around the world. In 1981, the World Health Organization decided that the preferred terminology in the English language would be “venom” and “antivenom” rather than “venin/antivenin” or “venen/antivenene”.

Antivenoms are similar to vaccines, but immunity isn’t induced directly in the patient; it is induced in a host animal — a horse or sheep — and the hyperimmunized serum is transfused into the patient:

It is quite possible to immunize a person directly with small and graded doses of venom rather than an animal. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning; therefore this procedure is often called mithridatization.

However, unlike a vaccination against disease which must only produce a latent immunity that can be roused in case of infection, to neutralize a sudden and large dose of venom requires maintaining a high level of circulating antibody (a hyperimmunized state), through repeated venom injections (typically every 21 days). The long-term health effects of this process have not been studied.