Greg Cochran says:
I Want a New Drug
Big pharma has taken a new course over the past few years. In the past, most useful drugs originated in some kind of living organism – penicillin, quinine, insulin, etc etc. Nowadays, big pharmaceutical companies use combinatorial chemistry and computer modeling. Merck has sold off its biological-products research arm. This new approach, combined with doubled spending on drug R&D, has been a resounding failure. The rate of development of fundamentally new drugs – ‘new molecular entities’ - is running about 40% of that seen in the 1970s. Since big pharma makes its money from drugs that are still on patent, this slowed innovation is a real threat to their bottom line.
Yes, but pharmaceutical companies do still seem to manage to come up with the brilliant innovation of a new version of their pills with a "slow release" coating just before the old version goes off patent. Thank God they figure out the complexities of the SR version just in the nick of time.
You get more complicated molecules from biological products, molecules that have been optimized by billions of years of evolution. Sometimes they do what you want or need. ...
I think that this is an instance of a more general trend: often a modern, advanced approach shows up, and it persists long after it’s been shown to be a miserable failure. You can see some of the reasons why: the people trained in the new technique would lose out if it were abandoned. Hard to imagine combinatorial chemists rooting around in a garbage can looking for moldy fruit.
There's a related general trend that many things take longer to get working right. For example, the F-22 fighter plane goes back to a 1981 Air Force request for proposals, but the Air Force is still trying to figure out how to keep the F-22 from asphyxiating its pilots.
Posts
67 comments:
The Air Force just doesn't want to admit failure and go back to liquid oxygen systems, which worked, because they have largely gotten rid of or are phasing out the LOX facilities on bases. Zeolite systems are dependent on steady bleed air, which the latest generation of jet engines don't supply as reliably as assumed.
For example, the F-22 fighter plane goes back to a 1981 Air Force request for proposals, but the Air Force is still trying to figure out how to keep the F-22 from asphyxiating its pilots.
That's a cheap shot, suitable for a venue such as National Public Radio.
Please show some evidence that the 1981 request for proposals for an aircraft to replace the F-15 fighter had a flaw that caused flaws in the F-22's bug-y rebreather.
In most cases, its still the case that nature trumps man+machine for drug design. Man often has to settle for tweaking a design found in nature.
One advantage we do have is that we can run something through the gauntlet alot faster than mother nature. So give it another generation or two. Computer prediction accuracy, and processing speeds are still improving in leaps and bounds.
Assuming we don't collapse into a dystopia that is....
What about all those new drugs that would come from the Rain Forest if we would only stop destroyng it? It doesn't appear that anyone is even looking there anymore, that is, if they ever did. But, if someone wants to start searching down there, they might want to keep their ears open for a decent song. We can't seem to do that these days either.
scott locklin on takimag often talks about this - for example the sr71 took about two years from drafting table (not computer!) to being built and its speed was only recently surpassed. Also the manned craft speed record was set during the apollo missions and no one has since come close.
Aren't manned fighter aircraft pretty much obsolete?
"I think that this is an instance of a more general trend: often a modern, advanced approach shows up, and it persists long after it’s been shown to be a miserable failure."
All attempts to come up with logical, consciously thought-out systems of morality and societal setups are also failures - communism, libertarianism (well, it would be if libertarians ever came to power anywhere), PC liberalism, feminism, atheism. Naturally-evolved systems (monarchy, theism, traditional gender roles, traditional morality) are more enduring, i,e, more successful. They show greater signs of life: above replacement birth rates, a tendency to recur. Monarchy pops up after vigorous attempts to stamp it out - look at North Korea, Azerbaijan, Syria.
A PR problem of naturally-evolved systems of morality and naturally-evolved societal setups is that their practitioners can rarely explain or justify them intelligently. A kidney couldn't tell you how it works either, yet it works, better than any man-made substitutes. These systems were created by processes that resembled evolution more than conscious reason. Example: sodomy really is a bad idea, but not because it will send you to hell, at least not to the kind painted by Bosch. The complexity of available arguments for systems is a bad criterion for evaluating them. Endurance, persistence, longevity, real-world success are better criteria.
If humanity ever comes up with a workable consciously thought-out system of morality, it will probably be many centuries after it comes up with fake leather that looks like real leather (hasn't happened yet, I don't think) and with wigs that look like real hair. Why? Because hair seems vastly simpler.
Two possible explanations for this phenomenon, which aren't mutually exclusive:
1. We are running up against real physical limits that are making innovation legitimately more difficult. For example, within physics, it is said that nothing fundamentally new has been discovered for many decades. Even the recent potential discovery of the Higgs boson doesn't really mean all that much in the big picture, and is quite useless technologically. We may have just tapped out what the laws of physics allow us to easily do.
2. People aren't smart as they used to be. While it's often discussed that genotypic average IQ has declined, I suspect that among the best and the brightest, the real geniuses—those with IQs of 160 or greater, there have been serious losses. Off the top of my head, I don't seem to gather that there are many eminent scientists with large broods of children. Many of the highest-IQ types seem to have no children at all. If so, then this is perhaps a more serious problem than the loss of people who are the more common gifted range, because to paraphrase Greg Cochran, the more facts in one brain, the greater the chance of it finding connections between these facts. It seems to me that true revolutionary innovation results only (or mostly) from the greatest minds; you'll have more progress from one individual with an IQ of 180 than you'll have from a team with IQs of 140. It might be that we, sadly, are losing those.
If we are to concentrate on eugenics in a positive sense, it would seem wise to me to find our true best and brightest and get them breed—prodigiously.
The F-35 has the same oxygen system of the F-22...
I haven't seen much, if any, evidence that CAD has led to greater progress, compared to the days when mechanical design was done by a draftsman with a tilt-table and a T-square.
I'm guessing nano technology seems very promising as a new source of drugs, especially as a delivery system. The most obvious risk is creating a prion-like substance that will never die and never degrade, possibly making asbestos seem like cotton candy.
Let's face it, we destroyed the homogeneous core that was capable of so much creativity. What most don't realize is that it can never be put back. It will be very slow progress from here on out. No cancer cures, no trips to Venus, no Amazing Future.
Welcome to Diversity.
big harma
There are several good candidate explanations for the tailing off in new drug approvals. Firstly, the low-hanging fruit has been plucked already; a perfectly reasonable argument. Secondly, a lot of medical needs are by now reasonably well met; there's just no incentive to develop yet another diuretic, eg. Thirdly, there is now an enormous congregation of people living off medical research, some of them extracting more value than they contribute; in many ways it's a shake-down.Fourthly, the educational system (especially in medicine) is very good at producing docile conformists and there are far fewer rebels and mavericks; as a result you tend to get a lot of low-risk copy-cat stuff masquerading as research. Fifth, the bureaucracy in clinical trials research is now simply mind-boggling and very intimidating. Finally, the cost of protecting intellectual property has gotten completely out-of-hand, so that lone operators can frankly forget it; and we all know how creative large organizations (eg drug companies) are likely to be.
Anon.
Is it only medicine, though? Is the DualCore Pentium under your desk principally different from microprocessors of the 80s? What part of an Iphone isn't essentially Cold War technology?
Why? Viagra and Cialis not doing the trick?
I'm always fascinated about the way scientists adapt deadly venoms from such creatures as snakes and carnivorous oceanic snails (yes, they exist), into pharmacologically useful compounds.
Apparently the active compound in snail venom is a narcotic of tremendous effect.
Welcome to the Disneyworld. Where intellectual property does not benefit the inventor.
Where is the Creative Destruction? All we see is mergers, mergers more mergers. What good can come out of BMW buying Porsche?
This is a global ownership society now.
isteve readers believe that intelligence and wealth goes hand in hand.
Be ready for the structural change to bring correlation coefficient down...
Why? Viagra and Cialis not doing the trick?
incidentally
wikipedia on viagra patents
the novelty drug was brought to market 14 years ago.
I know it feels like yesterday.
Maybe biochemists, as well as everyone else, were killing time on the intarwebz for the last decade and a half.
>Is it only medicine, though? (...) What part of an Iphone isn't
>essentially Cold War technology?
what I meant was that the phenomenal advance in science and technology may have been not due to capitalism and democracy and whatnot, but simply because in the time span between roughly 1870 and 1970 man really dicsovered all there was to be discovered, as Lord Kelvin said in 1900, except that now he would be right.
Which in turn means that any sufficiently modern and scientifically-minded (in short, white) society (Russia only started to fall behind the West in the mid 60s or so, which, imo, may have something to do with her not having had a "fresh cell therapy" that the year 1968 and beyond was in the West), would have sooner or later come up with the same things, and also that they may be our new clay pottery, writing and horse, meaning that they will be with us for a whole while (if we don't lose them in some kind of dystopic Roman scenario) and, thirdly, that capitalism will be in big trouble if it continues to presuppose the erstwhile pace of scientific advancement.
by "fresh cell therapy" I meant, of course, not mass immigration from the 3rd world, but simply that people aren't so uptight about stuff anymore as they were pre-1968.
Steyn has a similar routine where he complains that the household appliances aren't getting cooler or bigger. After the dishwashing machine and refrigerator and microwave, we haven't invented anything cool except the roomba, which doesn't work. Of course, it's always possible that penicillin and the polio vaccine were the easy pickins, and incremental new discoveries are running up against the limits of the logical space of new discoveries (just came up with that by myself).
"Is it only medicine, though? Is the DualCore Pentium under your desk principally different from microprocessors of the 80s? What part of an Iphone isn't essentially Cold War technology?"
Peter Thiel has been arguing for a widespread slowdown in innovation. He says tech is the last frontier and it must outpace a regulatory event horizon or innovation stops.
"Is the DualCore Pentium under your desk principally different from microprocessors of the 80s? "
I think we finally hit the limits of moore's law. Now processors are adding cores. This in turn is driving innovation in programming languages to make better use of multiple cores. Maybe the renewed interest in functional programming will trigger a renewed interest in AI. I think there's a lot of room for innovation there.
"Where is the Creative Destruction? All we see is mergers, mergers more mergers. What good can come out of BMW buying Porsche?"
The governor of Tokyo, Shintaro Ishihara, said the same thing 20 years ago.
I think the problem is a combination of physical limits combined with lack of innovation. Finding a problem and then saying "let's use this computer to design a molecule to fix this problem" is not really innovative. We need more biology hackers and less "drug development."
An example of the right direction is Kary Mullis' Altermune idea.
We also need to start asking the question what new drugs we really need. Should we pursuing the efficient elimination of disease or the increase in human happiness and flourishing? If the latter, it's possible that we have what we really need for medicine (a few exceptions of course) and that the frontier for improvement is in changing the normal state rater than getting people back there.
"Monarchy pops up after vigorous attempts to stamp it out - look at North Korea, Azerbaijan, Syria"
And...you actually want to live in any of these places?
Agree about traditional values and gender roles.
Just because the stuff evolving for billions of years is more complex, doesn't mean that it's necessarily evolved to do what we want. In fact, it would be miraculous if that were the case.
Might the slowdown in innovation just be in the nature of things? In any technology, you pick the low hanging fruit first and then anything new is harder to create.
Those older drugs weren't developed in a system that demands a $1.5 billion investment for clinical trials.
Regulatory demands kill innovation.
Right now, Big Pharma is betting the whole pot on anti-Alzheimer's drugs.
ll attempts to come up with logical, consciously thought-out systems of morality and societal setups are also failures - communism, libertarianism (well, it would be if libertarians ever came to power anywhere), PC liberalism, feminism, atheism. Naturally-evolved systems (monarchy, theism, traditional gender roles, traditional morality) are more enduring, i,e, more successful. They show greater signs of life: above replacement birth rates, a tendency to recur. Monarchy pops up after vigorous attempts to stamp it out - look at North Korea, Azerbaijan, Syria.
There are some interesting thoughts here, but some silliness too. Monarchies used to rule the entire planet. In a regime that's going to fall within the next few months and North Korea you see a general trend towards its return?
Democracy has triumphed. I wonder whether we should put that into the organic or man-made category.
This is troubling. I seem to be reading more accounts of flesh-eating bacteria and other superbugs. Cancer research seems to have tapped out. Treatment is still along the lines of cut it, zap it or poison it. Nobody seems to be able to crack the code of metastasis but maybe I'm wrong.
On the supply side, billions of dollars warp the research into things like global warming and "the virus that causes AIDS." The Affordable Cartelization Act (Obamacare) will further stunt innovation. Malthus may yet be laughing from the grave.
Ah. Yes. The case of the Better Mousetrap redux,
Wheels of God grind very slowly; but they grind exceedingly well.
Steve,
Regarding the slow down in technology, read "The End of the Future by Peter Thiel:
http://www.nationalreview.com/articles/278758/end-future-peter-thiel
He has also given many speeches regarding the topic, which have been posted to YouTubne: http://www.youtube.com/watch?v=tw-rxtwhzcY
For another very interesting look at the slowdown in technology, read Chapter 1 of Mark Steyn's most recent book, "After America". He takes a person on an H.G. Wells time machine from 1890 to 1950 and then 2010. Very cleverly written....
"Let's face it, we destroyed the homogeneous core that was capable of so much creativity. What most don't realize is that it can never be put back. It will be very slow progress from here on out. No cancer cures, no trips to Venus, no Amazing Future."
Ah, crap.
I agree with Jay Mann's first point (I'm skeptical about his second) and Anonymous 11:14/ 1:51. This appears to be mostly a matter declining marginal returns; eg the low hanging fruit has already been plucked.
The reason you don't have more biological based drugs is probably because there are only so many useful bugs in nature -though yes more could be found in the rain forest- and they have all been identified. Because modern capitalism depends on continued growth of profits, companies have attempted to continue to grow with chemical based drugs, and found it doesn't work as well.
Incidentally, that is also the likely reason why we don't get good songs anymore. We already have heard all of them. There are only so many pleasing combinations of notes.
I don't think its really a matter of existing employees at these companies keeping failed processes alive to keep their jobs. Why weren't the biologists able to keep the older processes in favor to keep THEIR employment prospect?. Executives are pretty ruthless about these things.
We live in the shadow of an unprecedented two centuries of innovation and discovery (mid eighteenth to mid twentieth century) and some veins of discovery have been literally exhausted. Its time for the big brains to switch to an almost Medieval mindset of conservation. Either that or collapse, and then maybe later some renaissance will go through the exciting process of re-discovery.
"Many of the highest-IQ types seem to have no children at all. If so, then this is perhaps a more serious problem than the loss of people who are the more common gifted range, because to paraphrase Greg Cochran, the more facts in one brain, the greater the chance of it finding connections between these facts. It seems to me that true revolutionary innovation results only (or mostly) from the greatest minds; you'll have more progress from one individual with an IQ of 180 than you'll have from a team with IQs of 140. It might be that we, sadly, are losing those"
This is not new.
Isaac Newton died a virgin.
Nikola Tesla "The Man who Invented the 20th Century" had no children.
Though he was good-looking and the ladies all came a-runnin', he felt his life's purpose was to invent, and he mustn't be distracted by triflings like love.
So,
No Isaac, Jr., no Little Nicky.
Ah, crap.
The Air Force just doesn't want to admit failure and go back to liquid oxygen systems, which worked, because they have largely gotten rid of or are phasing out the LOX facilities on bases.
The USAF would like to fly without bottled O2 in its aircraft for two reasons:
(1) The oxygen bottles in aircraft have to be replenished, which requires more maintenance;
(2) Bottled oxygen is a fire hazard. Note the warnings on bottled oxygen used in hospitals.
...Zeolite systems are dependent on steady bleed air, which the latest generation of jet engines don't supply
I think you're confusing the F-22 with the Boeing 787 airliner.
I haven't seen much, if any, evidence that CAD has led to greater progress, compared to the days when mechanical design was done by a draftsman with a tilt-table and a T-square.
Then you haven't seen much engineering work. I agree, CAD may not be causing any breakthroughs in basic research. That is not the point of CAD. Computer aided design is an efficiency improvement, not a basic thinking or conceptual improvement.
Oh where are the blacksmiths, draftsmen, and other craftsmen of yore? Mechanization has done 'em in.
It's just as well:
"It is simply no longer possible to believe
much of the clinical research that is published,
or to rely on the judgment
of trusted physicians or authoritative medical guidelines.
I take no pleasure in this conclusion,
which I reached slowly and reluctantly
over my two decades as an editor
of The New England Journal of Medicine."
—— Marcia Angell
“Drug companies and doctors: a story of corruption”
New York Review of Books, 56 #1, 15 January 2009
Jared Taylor has pointed out that multiculti societies conversely become more and more complex to manage, but decline in output and don't have the homgenity and high iq to maintain complex systems like, for example, the logistics of silicon chip production or even an electrical grid.
As for jet planes -how much die-virsity hiring do they have to do?
Look at NASA #1 mission: make muslims feel good about themselves. AA guy in charge of it. .. and people wonder why they can't get a rocket off the launch pad??
Northwestern economist Robert Gordon asks “Is U.S. Economic Growth Over,” in a presentation that can be found at http://faculty-web.at.northwestern.edu/economics/gordon/researchhome.html, under Presentations. (Yes, it’s economics, but it’s PowerPoint).
Gordon argues that economic growth is not necessarily continuous but depends on exploitation of great inventions, like steam power, electric power and the internal-combustion engine, all of whose potential we have pretty much exhausted. Information Technology is nice, but it's not power.
Simple Steve, Pharma is so highly regulated that the incentive to develop profitable new drugs is very low. Pharma is going where the money is. A highly regulated monopoly behaves like one, Pharma is now like SCE or Con Ed.
But two pluses to the commenters who noted the decline in reproduction of the smartest (intelligence among men is a turnoff as much as it is desirable among women); and diversity destroying the unity and amiability of the technology creating classes.
Slashdot had an article yesterday linking to Vanity Fair's article on the decline of Microsoft. Various comments on the VF article note how female managers boasted of firing "older White guys" in favor of "diverse" hires -- Indian, Chinese, along with "stacking" (lowest ranked team members fired each year) which produces competition for rank not cooperation for great product. Those two measures alone insure MS no matter how much money they invest cannot succeed, and are doomed to wither away slowly like GM.
As this thread appears to be trendy general technology, I thought this was a interesting take on the futurology dreamers: Three arguments against the singularity. Note that the dude is a sci-fi author w/ what looks like a legitimate tech background. He is admirably skeptical of the nerd rapture.
Note that I got to that from this reddit iama thread: IAmA: Charles Stross, science fiction writer. In there he does point out some legitimate (in his mind) possibilities with things like Google glasses. Real-time display on virus/bacteria/toxins in your immediate vicinity. Information on various objects (competitors pricing, tech reviews). Police records of people via face recognition. Etc. Or some of that I may have made up. The general point would be that the idea of sensory input being increasingly technologically generated is not that far fetched.
I think you have been seduced by the romance of Penicillin.
The discovery of Penicillin is one of the great romances of medicine. The reason it is such a compelling story is that it is carefully crafted fiction.
The story goes that Alexander Fleming working alone and without any formal financial backing just came across a petri dish in which a bread mold had inhibited a bacterium. He yelled 'Eureka' and saved millions - while whistling "Rule Britannia".
Not quite.
Howard Florey an Australian scientist set out to find some means of controlling infection. He was an establishment scientist and he headed a large research team. One of his researchers in his exhaustive document review came across Fleming's forgotten paper.
Fleming to his credit had made an observation and had written it up. He did no more until Florey's team, looking for odd observations thought that observation might be worth pursuing. There were many others that went nowhere.
All the refining and development of penicillin was done by Florey and his team. Fleming wasn't involved. Fleming was like a lottery winner who was just going about his business when fame and fortune came to call.
Wikipedia lists at least a dozen medical researchers who had stumbled onto penicillin previous to Fleming. The anti-bacterial properties of mold had been known since the ancients.
Florey and his big state of the art medical research establishment created penicillin as a practical drug. Fleming should have been no more than a footnote.
The Australians claim Churchill needed an authentic British hero and so they invented a bigger role for Fleming - the lonely isolated British genius.
In any case it was big medicine and big science that actually succeeded. That was true then and it's still true today.
It may very well be true that the tempo of creating new drugs from components has slowed but it is also true that discovering miracle cures in nature has likewise slowed - if it ever really existed. The idea that we should preserve the rain forests because they contain a cure for cancer is an environmentalist fantasy. A appealing fantasy first seen in the Myth of Alexander Fleming.
Albertosaurus
Speaking or regulation stifling innovation... I read not too long ago that the cost of dealing w/ diversity requirements in a company was something like 10% of all costs. Or it might have been something like the cost of making sure you didn't get sued for discrimination. Google is not being my friend right now; all i'm finding is "how great diversity is!!!" Anyone have any references to this?
Though he was good-looking and the ladies all came a-runnin', he felt his life's purpose was to invent, and he mustn't be distracted by triflings like love.
If you read biographies of him it's clear that he was likely somewhere pretty far along the autism spectrum, and that this was likely his impediment as far as reproduction goes, rather than idealism.
Warfarin is another example of a, created by nature, discovered by man, medicine and it wasn't in a rainforest, just a farm.
Smart guys who see patterns, like Steve, are needed in medical research. I can't believe that all of nature's processes have been discovered.
Let's preserve the rainforest, at least until man has shown that he can produce a spinerette to make a spider web.
There is no such thing as low hanging fruit - the term is an ungrateful denigration of the work of previous inventors and observers.
I have a lot of thoughts on this matter, but I'll just mention this one: for years I've wondered why countless complex non-alkaloidal products from plants weren't converted over to amines and amides and tested for biological activity. This really is a target-rich environment, an area where you could create vast numbers of alkaloid-like products of unknown activity for pharmacological screening. You'd get a whole new universe of potential drugs from such efforts and it wouldn't require any additional efforts at isolating and characterizing novel plant compounds whatsoever.
A new energy source would be nice, but how about some less than genius applications of energy conservation. What ever happened to economies of scale? Hot water heating and air conditioning are almost ubiquitous. Why aren't chill water for cooling, hot water for heating and domestic hot water distributed via mains like other utilities. Instead every house is a miniature boiler and refrigeration plant with all the maintenance and dangers involved. Imagine the additional benefits of extra space and reduced air and noise pollution. Even if alternative energy is discovered, the loops will not be obsolete.
@Anonymous @ 2:13
We can already do that. Inject bacteria into goats genetically engineered with the genomes meant for making some kind of silk (i forgot what it's called), they will secrete the silk when they lactate.
It's been a while since AP bio, but it's something along those lines...
For all we know, our time is full of important inventions that we either don't know about or don't recognize as such. These things are usually apparent only in retrospect, sometimes decades later.
Well, one other thing I'll mention:
One big problem you've already alluded to is the combinatorial approach. Pharmaceutical companies rely heavily upon in vitro ligand studies rather than animal studies to find potential agents these days. You can screen a vast number of compounds this way, but the problem is that ligand studies don't help you very much when it comes to finding new sites of action, only in optimizing agents at the sites you're screening.
Now take the hallucinogenic compound Salvinorin A. If it had been screened only for the most obvious routes of action: serotonergic activity (LSD, mescaline, psilocybin) or NMDA activity (PCP) you would have come up empty. And it's only the ethnobotanical knowledge of the Indians in Mexico that the plant was psychoactive that would have even got you to look for a mechanism. Eventually, you would discover that the agent exerts its effects through the kappa opioid receptor and the D2 receptor. If the local Indians hadn't preserved the knowledge of this plant, it would have been forgotten forever. And if the agent didn't work through any previously identified site, then it would not have been picked up at all in any ligand study.
Ligand studies are lousy at identifying entirely new target sites, new allosteric sites on old targets, and entirely new mechanisms of action. That's where good old-fashioned animal studies and the herbal knowledge of the locals can be helpful, but it's also more time-consuming, uncertain, and expensive to proceed that way. It doesn't look as flashy as cranking out some new agent that is super-selective for an identified receptor or enzyme site.
http://www.jameslefanu.com/books/the-rise-and-fall-of-modern-medicine-introduction
Read, Mark, Learn, and Inwardly Digest.
Fourthly, the educational system (especially in medicine) is very good at producing docile conformists and there are far fewer rebels and mavericks; as a result you tend to get a lot of low-risk copy-cat stuff masquerading as research.
I have to agree on that one, had a relative who often proctored exams in premed classes, and she told me most of the people were sons and daughters of doctors, and that among them a lot of cheating would go on. They would rotate one person in their social circle taking an exam early and then that person would inform all of his or her clique what was on the test. That person would sacrifice their grades on that one exam, and then it would be someone Else's turn. By that way they would all pass despite one bad test grade. Don't know if that goes on in med school as well, but wouldn't be surprising. Having parents who were doctors, they knew how to game the system.
"Simple Steve, Pharma is so highly regulated that the incentive to develop profitable new drugs is very low. Pharma is going where the money is. A highly regulated monopoly behaves like one, Pharma is now like SCE or Con Ed."
- The incentive to develop profitable new drugs is huge. Its what drives big pharma to spend hundreds of millions on R&D. Regulation is a b**ch, and most startups go bust instead of boom, but its not enough of a hurdle to make big pharma as a whole unprofitable...yet. Though wait and see if Obamacare changes things....
"I can't believe that all of nature's processes have been discovered."
Me neither. Salamanders can regenerate limbs after amputation. The Wikipedia says that Bowhead Whales, our fellow mammals, have been confirmed to live for as long as 211 years. From what I understand, birds of prey get more visual information into their brains than we do.
Posted below at Westhunter where the debate seems to have died.
Anyway, the story with antibiotics is as follows.
We have been isolating microorganisms from the environment (usually actinomycetes, also fungi and myxobacteria), growing them on plates and seeing if they will kill or inhibit other bacteria since the end of the second war. We can still do this, but we never find anything new. We still keep finding the same old antibiotics (see http://www.springerlink.com/content/huxgxj675ke4b7gh/). So there are several approaches:
-give up on antibiotics and try something completely new like viruses or combinatorial chemistry. No idea about this myself.
-try working with the uncultivated fraction of bacteria in the environment and see if we can get
their DNA out of the environment, put it into bacteria that we can grow in the lab and get the bacteria to express it (AKA metagenomics). A lot of technical challenges and not much progress so far. Google Sean Brady to see some limited results.
-scale up our efforts. Richard Baltz thinks that metagenomics is a waste of time. We should just go back isolation of bacteria from the environment but on a much larger scale using robots.
see http://www.springerlink.com/content/76700101q87513u6/
How much of the reason for people getting out of the natural products is due to bad PR ? If you want a real PR horror story google bioprospecting and chiapas.
The F-22 does use "bleed" air, in addition to an On-Board Oxygen Generating System (OBOGS). Seems that last year, some people said F-22 bleed air was the villain:
Bleed-Air Problem Caused F-22 Crash: Sources
Sep. 8, 2011 - 06:00AM | By DAVE MAJUMDAR | Comments
The November 2010 crash of a U.S. Air Force F-22 Raptor was caused by a malfunction with the aircraft engine's bleed air system, an industry source said. The pilot, Capt. Jeff "Bong" Haney of the 525th Fighter Squadron, was killed in the accident.
Another source, a pilot, confirmed that information. The fighter squadron is based in Alaska.
An Air Force accident report said the F-22, tail number 06-4125, had a bleed air problem that caused both the stealth fighter jet's Environmental Control System (ECS) and On-Board Oxygen Generating System (OBOGS) to automatically shut down, the sources said.
...
The bleed air system siphons off air from a jet engine's compressor section to generate power, supply oxygen and inert gases, and handle heating and cooling.
...
source:
Defense News
Every airliner you have ever travelled on uses bleed air to maintain cabin air pressure and breathability. The air goes into the engine intakes, through at least one compressor fan, and then into pipes that go to the wing roots. The new Boeing 787 airliner is different. It does not use bleed air. The 787 uses a separate, electrically powered air compressor -- maybe two of 'em -- for cabin air.
I haven't seen much, if any, evidence that CAD has led to greater progress, compared to the days when mechanical design was done by a draftsman with a tilt-table and a T-square.
7/6/12 9:49 PM
I agree with another poster. I have a friend in Puebla who runs an automated machine shop. He produces molds for machines which make things out of plastic. Once he gets the specs drawn up, a converter automatically converts the drawing to the numbers to run a numerically controlled tooling machine which makes the part. They save the data and next time the customer needs another, it is a few hours to delivery. To make one part manually would take days.
>>Cancer research seems to have tapped out.
Actually, practical cancer research has barely started. Warburg got the Nobel over 90 years ago for discovering that cancer gets its nutrition from glucose. But, only in the last two or three years, in Germany, has anyone actually tried a low glucose diet for cancer patients. That diet is called a ketogenic diet, and roughly equates to the Induction Phase of the Atkins Diet, which is really hated by doctors, most of whom are fat.
As far as i.q., not to worry. The problem is not lack of i.q., but certain political experiments which prevent high i.q. people from getting important jobs which can utilize the high i.q.
Anonymous age 70
In any gas turbine engine, the point of highest air pressure is not, as is commonly thought, the burner cans but the diffuser area immediately after the compressor section. Previous jet engines were designed with compressors a little too big, as that was better than a little too small. Now, CFD analysis is so good that they get it exactly right, which makes engine bleed air a precious commodity. That is precisely why separate compressors, driven by electric, hydraulic or mechanical drive from the engine, as in the piston days are used on the 787 and other current aircraft.
Zeolite systems separate nitrogen and oxygen from compressed air. The craze for putting nitrogen in car tires uses these at the car dealership or tire store. They throw away the oxygen. The oxygen systems throw away the nitrogen.
Civil aviation uses gaseous O2 systems, and in airliners and corporate jets a thermal oxygen generator sstem for emergencies. Military aircraft since the 1960s (at least US fighter and bomber aircraft) use liquid oxygen. When Chuck Thornton built a Talon out of junk parts (N38TC, Best Warbird/Best Jet/Best of Show Oshkosh '86)one change he had to make was to go to a gaseous oxygen system as no FBO has LOX available. LOX is a fire danger, but so is everything else in a combat aircraft. You have pyrotechnics everywhere, often a hydrazine EPU, fuel in every imaginable place, the ejection seat rocket, and of course the munitions.
The F-22 and the F-35 are poster children for why you want to build new aircraft each a little better every few years instead of "quantum leaps" where radically better designs come out every generation. The F-15, F-16 and F-18 are thirty-five or forty year old basic designs. We should have had three fighter generations between them and the F-22/F-35, or two at least. A basic fighter should cost a little more than a Gulfstream, and no one should get into the cockpit of one with less than 500 TT and a hundred in aerobatic, supersonic jets past the point where they need constant supervision from instructor pilots. But the electronics should be totally replaced three times in the fighter's lifespan, because electronics progresses so fast as compared to airframe design. The F-16 is still flying with a fly by wire system implemented in TTL with discrete gates and flip-flops. You can't hardly BUY TTL parts today. But the basic box is a hundred thousand dollars, even though the parts are worth fifty bucks at the Surplus Hut.
Whiskey:
"intelligence among men is a turnoff as much as it is desirable among women"
I think it was HBD chick had a recent link to a study showing much the opposite, that increased IQ negatively correlates with fertility among women, but is neutral for men.
Actually another problem which delays the discovery of novel chemical scaffolds is that we slack off one month a year for moustache growing competitions and associated events.
JayMan, most women especially modern women want nothing to do with highly intelligent men.
Also while there are smart women who would make good mothers and pass on excellent genes, there are fewer of them than smart men (thus making IQ's slump to the mediocre) and most of them are interested in careers of their own and trend smaller families.
Programs to correct this ala Singapore simply do not work.
Now we could have universal intelligence screening and trade college for eggs than pay moderately smart women to surrogate them that would require a kind of society we can't have.
If we did, we'd control borders (raising the national IQ) pay off the poor and stupid to not breed (also raising the national IQ) and make better choices all around.
And note, yes women do want good offspring, high IQ/high sociality sperm is in high demand but most smart men do not have the killer app, money, sociability, looks, dominance and brains to keep a woman.
Hypergamy sucks for smarter men.
"JayMan, most women especially modern women want nothing to do with highly intelligent men."
-Ah I see you are unfamiliar with Asian women. Well, at least those that grow up in the east; those who grow up here are upper middle class white girls inside.
"Isaac Newton died a virgin"
Neither Humphrey Davy nor Robert Hooke left offspring. On the other hand, the Darwin/Galton/Wedgwood clan are still IIRC providing scientists today. Be interesting to see any research on family size for scientists.
Cancer research seems to have tapped out. Treatment is still along the lines of cut it, zap it or poison it. Nobody seems to be able to crack the code of metastasis but maybe I'm wrong.
Cancer, as a class of diseases, is much more complicated than we thought it was. Not only is it not one disease in the sense that cancers starting in different cells are have different characteristics, but also cancer cells mutate incredibly fast. So a single tumor may have thousands of different types of malignant cells.
We do have treatments that aren't "cut it, zap it or poison it", e.g. Tamoxifen. But if you don't get all the cancer before it metastasizes eventually the cancer cells will mutate around the treatment.
It's really the same dynamic we're having with antibiotic resistance, only it's happening in one person's body instead of an entire population.
All the best scientists have been assigned to develop better drugs for giving old men erections.
Not much left to research other issues.
Post a Comment