It's worse than that: by the time things like Alzheimer's or cardiovascular disease are symptomatic a lot of damage has already been done. To prevent the damage you may have to start treating a decade or more in advance of any symptoms, since healing the damage will only be partial at best. To develop a therapy and determine its efficacy means running clinical trials over a decade or more, something no Pharma wants to face. You can improve the situation a lot via biomarker tests - or just complicate it further. If the tests accurately determine who is at risk and accurately chart their progression into the disease then the trials can be much smaller and potentially much shorter. But if the tests are so-so then approving a therapy based on its ability to change the levels on a biomarker test (as opposed to waiting 5-10 years more to see if it actually changes the levels of Alzheimer's) could be an incredibly expensive and horrific mistake. The antibody based therapies could easily cost $10k or more per year and would need to be taken til death.
To compare the situation to aspirin: giving daily aspirin to people at lower risks of CVD increases their chances of serious/fatal brain bleeds and GI tract bleeds about as much as it decreases their risks of a big CVD event. Now imagine that baby aspirin cost $30 each.
Alzheimer's has been a multi billion dollar graveyard for Pharma over the past ten years - and Solanezumab isn't looking too healthy. Best of luck to Merck and TauRx.
They used mass spectrometry to analyse the blood plasma of 53 participants with mild cognitive impairment or Alzheimer’s disease, including 18 who developed symptoms during the study, and 53 who remained cognitively healthy. They found ten phospholipids that were present at consistently lower levels in the blood of most people who had, or went on to develop, cognitive impairment. The team validated the results in a set of 41 further participants.
I think they will need to look at a much bigger sample before calculated odds will be meaningful. Also, the test may well lose its predictive power if applied to the general population as opposed to people over 70.
The CRO (contract research organization; research without an ownership stake) model is already a big part of pharma and biotech. The NIH has started translational medicine programs to get things through preclinical trials, but is still planning on handing off to pharmas for the heavy lifting.
I think a big problem a public system would have to solve is going from having the wrong cooks (Wall Street) to having too many cooks spoiling the broth. While occasionally something stellar comes along, a lot of the time there's no clear way to look at a development pipeline and decide which drug candidates should be advanced and which should be abandoned. For Pharma marketing analyses make the final decisions, for better or for worse. With a public model Congress, lobbyists, and patient pressure groups would all have their fingers in the pie. They would all advocate for their own interests, but with little or no understanding of which drug candidates are likely to succeed and which to fail. After all, they wouldn't get fired or laid off for pushing batshit crazy drug candidates, just rewarded for pushing the "right" ones.
You hit on some of the reasons it would be difficult to replace the current business model for pharma with an NIH/academia model. I think there are a lot more perverse incentives in the Pharma/Wall Street model than the public one, but the public model would present different difficulties. For starters, we'd replace a system that chases the most profitable drugs with one that absolutely positively refuses to fund contraceptive development (thanks Congress). The NIH has been emphasizing translational medicine for a few years now, but it would have to majorly increase funding for those attempts (while its budget overall stays static: thanks again, Congress) to replace even one major Pharma company.
Lots of people think treatments are given a priority over cures because they think treatments are more profitable, but frankly the reverse would be true for any serious disease. A company that invented a cure for any major disease would wipe the floor with its competitors still selling treatments, furthermore insurance companies would happily pay a lot more for the cure than it would for a decade of drug therapy. Why? the cure would still be cheaper. Drugs are only part of the cost of treating a disease, there's also hospitalizations, surgeries, tests, etc. If a cure is one dollar cheaper than all of the combined (net present value) costs of treating the disease and all of its complications, the cure is cheaper for the insurer. A cure would quickly dominate over treatments in the market. Plus the pharma would get all of its revenue up front right now (as opposed to in dribs and drabs over years of prescriptions),
The problem is that cures are much much more difficult to create than treatments. For most non-infectious diseases it amounts to replacing a defective capacity in your body with something new. Want to cure cancer? Just invent a 100% accurate way to differentiate between cancerous and non-cancerous cells and attach it to a way to specifically and neatly kill the former but not the latter. Want to prevent cancer? Just come up with an error detection/correction system for DNA that is 100% accurate for all carcinogenic mutations and then successfully install it in all of the cells of your body. Til then we're stuck with trying to improve the immune system we have and more brutal methods.
You might also want to look at the ways drug manufacturers can get market exclusivity for drugs without a patent, both natural and synthetic. The incentive programs get abused to be sure (dimethyl fumarate), but a company can still have several profitable years if it can cheaply prove a drug answers an unmet medical need.
As far as research-to approval timing goes, I'm going from the date the drug is invented. Picking a particular link in the chain of research that comes before then gets iffy. The day the target was sequenced? The day it was recognized as a target? the day it was confirmed as acting similarly in humans? The day they got a tool compound to produce the result they were looking for in an vitro assay system? The day of the first press release saying "this research could eventually lead to a drug"?
Got me.
Exact and complete molecular understanding of biomolecules and their interactions has been the goal for generations now. Turns out it's a bitch.
Ab initio simulations that can fully predict how proteins interact with each other and other biomolecules are still outside of our grasp, so we use fudged (empirical) models instead. Drug design based on these calculations has been... entertaining over the past 20 years, but not very successful. Alchemy indeed. If you happen to have a quick way to solve the full non-linear Poisson Boltzmann equation for ~50,000+ kD molecular weight proteins in cellular environments (as opposed to just a vague representation of water) the industry is all ears. Recently there's been a swing back to phenotypic screening from in-silico/rational drug design methods in drug discovery, because empirical methods just seem to be more productive.
Also: insurers have been emphasizing prevention. Insurers make the most money by taking your premium and NOT treating you at all. This is much more difficult to do if you are sick.
Pharmaceutical companies justify their prices and patents by saying that they're performing a public service. No pharmaceutical company needed an fscking patent to develop, test, and sell Viagra, even though they did get those patents. They say they need patents and tax loop holes to develop expensive drugs with small markets and low profit margins.
But companies aren't pursuing small markets and low profit margins. Big pharmaceutical companies pursue huge markets with huge profit margins.
Most genomic science-based drug development is spearheaded by the NIH, universities, and other non-profit centers. Although university labs suck at this because the moment a researcher makes a discovery, he immediately leaves the school to form his own for-profit lab and chase big money. Then some large company buys his company (smelling a publicly financed science windfall). Then, invariably, the research is left to wither on the vine because the company spends 99% of its time chasing weight loss, diabetes, depression, etc. And the CEOs don't care about this ridiculous cycle because as long as they keep buying up small labs at a reasonable pace, they reap asset gains in the stock market because investors equate these deals with progress.
No biotech or pharma would receive funding from investors to develop drugs without patents to protect themselves. Hate it or hate it, Wall street calls the tune. Companies spent up to $12B per successful drug approval in 2012.
Last year, about a third of the drugs approved were for orphan diseases (small markets). Most drugs last year were for cancer, but there was also two new treatments for Hep C, one of which will be a cure for many patients. Here's the list:
Which ones do you think should not have been developed?
Pharmas only pursue high profit margin projects. The risk of failure is way too high to pursue low profit projects.
Year in year out, about a quarter of new drugs are invented in academia; the rest are invented privately.
If universities are going to develop drugs they will essentially have to be reconfigured as for profit pharmas to get the job done. Is that really what you want?
Tell that to Winston Churchill. I think genetics probably explains at least as much of the variance as lifestyle. That said, folks should have a look at the promises made by the first generation of companies that cashed in on the Human Genome Project and compare them to Venter's promises now.
Wow, your chem labs had off hours? How quaint. A professor I knew was known for taking new hires aside and saying "The state says I have to give you 14 days vacation every year. Which weekends do you want?". He was half joking.
The big crunch isn't just academia, at least in organic/medicinal chemistry. Universities quit hiring more full time professors at the same time Pharma started unloading PhDs.
A model is as useful as its ability to precisely and accurately predict observations. A new model may be more comprehensive, precise, or accurate than an old one, but the old model is still useful within its own range, especially if it is easier to apply.
Except that neither apply to "greenhouse gas warming". There is lots of contrary science (although you don't generally hear about it on the news),
You do hear about in on the news (and on forums) completely out of proportion to its ability to explain natural phenomena when compared to the science that does support "greenhouse gas warming" though.
Evolution is a fact. The method of evolving is what is in dispute. What kills me is when people assume that there can be only one primary method, ie Natural Selection. I don't see much difference between most 'Darwinists', ie Natural Selection explains everything, to 'Creationists'.
How narrowly are you defining Natural Selection?
What other candidates do you have for a primary method?
Probably just as well. Back in the day academic chemists liked to think of themselves as cowboys to some extent, which resulted in lots of small fires, explosions, etc. Can't say as I remember hearing about many EE or ME students messing themselves up while I was in school, but I ended up taking two chemists to the ER for stitches. Also was evacuated from buildings several times due to explosions/fire and watched people wheeled out on gurneys due to burns/flying broken glass.
The only guy I know who electrocuted himself (a little) was a molecular biologist. There's a technique called electroporation where you zap DNA into bacterial cells by discharging a ~25 microfarad capacitor across the sample at 2500 V. Commercial rigs have lots of safety features; his (DIY) did not. Went home for the day after the oopsey, but was fine.
The "11x safer" part of the article seems to be referring to research labs at Dow vs university labs, not manufacturing facilities. Some of those industry labs will be doing work on scaling up synthesis, but overall since its research it's not that repetitive.
The big difference between industrial and academic labs is in the consequences for accidents and safety infractions. Accidents or not wearing safety gear or ignoring other safety rules can have a big effect on the bottom line of a company: OSHA, fire marshal, and other regulator problems, insurance rates, lawsuits, etc., so employees who don't follow rules get fired instead of just a wag of the finger. This difference may shrink now that Big Consequences are showing up in academia: a UCLA chem professor is standing trial on 3 felony charges for not properly supervising a student who burned to death.
Fair enough but you forgot to mention that one party has been strongly against spending money on public infrastructure and doubly so while Obama is in office. While building new roads and improving public transportation is only a delaying action for congestion it does at least delay it.
In my (quite limited) experience, if potential jurors make it clear they will be a pain in the ass and will be hating every second of it they get dismissed. This might go out the window in high profile cases, but judges and attorneys are looking for people who can work together to reach a decision without undue drama or delay.
Politician runs for office in district A. To meet the residency requirements he claims he lives in his Mom's spare room in District A. License plate scans reveal his car lives in District B - in the parking lot for his mistress's condo.
Cholesterol does get absorbed through the intestines. There's even an approved drug (ezetimibe) to inhibit the process. Plus diet does affect atherosclerosis.
That would get expensive, since grad students and postdocs tend to need access to equipment 24/7/365. Go check out a Chem department NMR room on Christmas Eve.
I think you've won the thread: two big ass surveillance cameras in the room would improve compliance in filling out the log and required user maintenance/cleaning quite nicely. Would only have to review footage when there were problems.
Cabinets might be tricky - the equipment he mentioned tends to be permanently mounted to the wall (water purifiers) or too big to move (centrifuges). Might be able to lock up the rotors for the centrifuge (different rotors for different jobs; they get swapped in and out of centrifuges pretty often)... but if it's a bio department rotors are typically stored in a refrigerator, which complicates things.
Slashdot Mirror
It's worse than that: by the time things like Alzheimer's or cardiovascular disease are symptomatic a lot of damage has already been done. To prevent the damage you may have to start treating a decade or more in advance of any symptoms, since healing the damage will only be partial at best. To develop a therapy and determine its efficacy means running clinical trials over a decade or more, something no Pharma wants to face. You can improve the situation a lot via biomarker tests - or just complicate it further. If the tests accurately determine who is at risk and accurately chart their progression into the disease then the trials can be much smaller and potentially much shorter. But if the tests are so-so then approving a therapy based on its ability to change the levels on a biomarker test (as opposed to waiting 5-10 years more to see if it actually changes the levels of Alzheimer's) could be an incredibly expensive and horrific mistake. The antibody based therapies could easily cost $10k or more per year and would need to be taken til death.
To compare the situation to aspirin: giving daily aspirin to people at lower risks of CVD increases their chances of serious/fatal brain bleeds and GI tract bleeds about as much as it decreases their risks of a big CVD event. Now imagine that baby aspirin cost $30 each.
Alzheimer's has been a multi billion dollar graveyard for Pharma over the past ten years - and Solanezumab isn't looking too healthy. Best of luck to Merck and TauRx.
In the sample 10% (53 out of 525) had or developed Alzheimers or other cognitive impairments within 5 years.
They used mass spectrometry to analyse the blood plasma of 53 participants with mild cognitive impairment or Alzheimer’s disease, including 18 who developed symptoms during the study, and 53 who remained cognitively healthy. They found ten phospholipids that were present at consistently lower levels in the blood of most people who had, or went on to develop, cognitive impairment. The team validated the results in a set of 41 further participants.
I think they will need to look at a much bigger sample before calculated odds will be meaningful. Also, the test may well lose its predictive power if applied to the general population as opposed to people over 70.
The CRO (contract research organization; research without an ownership stake) model is already a big part of pharma and biotech. The NIH has started translational medicine programs to get things through preclinical trials, but is still planning on handing off to pharmas for the heavy lifting. I think a big problem a public system would have to solve is going from having the wrong cooks (Wall Street) to having too many cooks spoiling the broth. While occasionally something stellar comes along, a lot of the time there's no clear way to look at a development pipeline and decide which drug candidates should be advanced and which should be abandoned. For Pharma marketing analyses make the final decisions, for better or for worse. With a public model Congress, lobbyists, and patient pressure groups would all have their fingers in the pie. They would all advocate for their own interests, but with little or no understanding of which drug candidates are likely to succeed and which to fail. After all, they wouldn't get fired or laid off for pushing batshit crazy drug candidates, just rewarded for pushing the "right" ones.
Lots of people think treatments are given a priority over cures because they think treatments are more profitable, but frankly the reverse would be true for any serious disease. A company that invented a cure for any major disease would wipe the floor with its competitors still selling treatments, furthermore insurance companies would happily pay a lot more for the cure than it would for a decade of drug therapy. Why? the cure would still be cheaper. Drugs are only part of the cost of treating a disease, there's also hospitalizations, surgeries, tests, etc. If a cure is one dollar cheaper than all of the combined (net present value) costs of treating the disease and all of its complications, the cure is cheaper for the insurer. A cure would quickly dominate over treatments in the market. Plus the pharma would get all of its revenue up front right now (as opposed to in dribs and drabs over years of prescriptions),
The problem is that cures are much much more difficult to create than treatments. For most non-infectious diseases it amounts to replacing a defective capacity in your body with something new. Want to cure cancer? Just invent a 100% accurate way to differentiate between cancerous and non-cancerous cells and attach it to a way to specifically and neatly kill the former but not the latter. Want to prevent cancer? Just come up with an error detection/correction system for DNA that is 100% accurate for all carcinogenic mutations and then successfully install it in all of the cells of your body. Til then we're stuck with trying to improve the immune system we have and more brutal methods.
You might also want to look at the ways drug manufacturers can get market exclusivity for drugs without a patent, both natural and synthetic. The incentive programs get abused to be sure (dimethyl fumarate), but a company can still have several profitable years if it can cheaply prove a drug answers an unmet medical need.
As far as research-to approval timing goes, I'm going from the date the drug is invented. Picking a particular link in the chain of research that comes before then gets iffy. The day the target was sequenced? The day it was recognized as a target? the day it was confirmed as acting similarly in humans? The day they got a tool compound to produce the result they were looking for in an vitro assay system? The day of the first press release saying "this research could eventually lead to a drug"?
Got me.
Exact and complete molecular understanding of biomolecules and their interactions has been the goal for generations now. Turns out it's a bitch.
Ab initio simulations that can fully predict how proteins interact with each other and other biomolecules are still outside of our grasp, so we use fudged (empirical) models instead. Drug design based on these calculations has been ... entertaining over the past 20 years, but not very successful. Alchemy indeed. If you happen to have a quick way to solve the full non-linear Poisson Boltzmann equation for ~50,000+ kD molecular weight proteins in cellular environments (as opposed to just a vague representation of water) the industry is all ears. Recently there's been a swing back to phenotypic screening from in-silico/rational drug design methods in drug discovery, because empirical methods just seem to be more productive.
Also: insurers have been emphasizing prevention. Insurers make the most money by taking your premium and NOT treating you at all. This is much more difficult to do if you are sick.
"Pharmas aren't, but that isn't their job."
Pharmaceutical companies justify their prices and patents by saying that they're performing a public service. No pharmaceutical company needed an fscking patent to develop, test, and sell Viagra, even though they did get those patents. They say they need patents and tax loop holes to develop expensive drugs with small markets and low profit margins.
But companies aren't pursuing small markets and low profit margins. Big pharmaceutical companies pursue huge markets with huge profit margins.
Most genomic science-based drug development is spearheaded by the NIH, universities, and other non-profit centers. Although university labs suck at this because the moment a researcher makes a discovery, he immediately leaves the school to form his own for-profit lab and chase big money. Then some large company buys his company (smelling a publicly financed science windfall). Then, invariably, the research is left to wither on the vine because the company spends 99% of its time chasing weight loss, diabetes, depression, etc. And the CEOs don't care about this ridiculous cycle because as long as they keep buying up small labs at a reasonable pace, they reap asset gains in the stock market because investors equate these deals with progress.
No biotech or pharma would receive funding from investors to develop drugs without patents to protect themselves. Hate it or hate it, Wall street calls the tune. Companies spent up to $12B per successful drug approval in 2012.
Last year, about a third of the drugs approved were for orphan diseases (small markets). Most drugs last year were for cancer, but there was also two new treatments for Hep C, one of which will be a cure for many patients. Here's the list:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm381263.htm
Which ones do you think should not have been developed?
Pharmas only pursue high profit margin projects. The risk of failure is way too high to pursue low profit projects. Year in year out, about a quarter of new drugs are invented in academia; the rest are invented privately.
If universities are going to develop drugs they will essentially have to be reconfigured as for profit pharmas to get the job done. Is that really what you want?
How many diseases have cheap preventable causes? Many How many cheap preventable causes are the medical "science" industry interested in finding? Zero
Well, bullshit. NIH is quite interested in finding them, as are many healthcare providers. Pharmas aren't, but that isn't their job.
What is the likelihood that insurance companies will want to use genetics to exclude benefits? Very high
And very illegal. Has been for years.
How long time will it take for new research to enter into medical practice? As long time as it will take for the practitioner to retire.
Depends. If it is leading to a new drug, could be 5-12 years. Diagnostics can be much faster.
http://www.technologyreview.com/review/524451/genome-surgery/
It is my understanding, that FDA's current stance is that all such person-specific treatments/medicines must be individually approved
There is already some flexibility on that front. Cancer immunotherapies like sipuleucel-T (Provenge, approved in 2010) are unique to each patient.
Tell that to Winston Churchill. I think genetics probably explains at least as much of the variance as lifestyle. That said, folks should have a look at the promises made by the first generation of companies that cashed in on the Human Genome Project and compare them to Venter's promises now.
Wow, your chem labs had off hours? How quaint. A professor I knew was known for taking new hires aside and saying "The state says I have to give you 14 days vacation every year. Which weekends do you want?". He was half joking.
The big crunch isn't just academia, at least in organic/medicinal chemistry. Universities quit hiring more full time professors at the same time Pharma started unloading PhDs.
A model is as useful as its ability to precisely and accurately predict observations. A new model may be more comprehensive, precise, or accurate than an old one, but the old model is still useful within its own range, especially if it is easier to apply.
Except that neither apply to "greenhouse gas warming". There is lots of contrary science (although you don't generally hear about it on the news),
You do hear about in on the news (and on forums) completely out of proportion to its ability to explain natural phenomena when compared to the science that does support "greenhouse gas warming" though.
Evolution is a fact. The method of evolving is what is in dispute. What kills me is when people assume that there can be only one primary method, ie Natural Selection. I don't see much difference between most 'Darwinists', ie Natural Selection explains everything, to 'Creationists'.
How narrowly are you defining Natural Selection?
What other candidates do you have for a primary method?
The only guy I know who electrocuted himself (a little) was a molecular biologist. There's a technique called electroporation where you zap DNA into bacterial cells by discharging a ~25 microfarad capacitor across the sample at 2500 V. Commercial rigs have lots of safety features; his (DIY) did not. Went home for the day after the oopsey, but was fine.
The big difference between industrial and academic labs is in the consequences for accidents and safety infractions. Accidents or not wearing safety gear or ignoring other safety rules can have a big effect on the bottom line of a company: OSHA, fire marshal, and other regulator problems, insurance rates, lawsuits, etc., so employees who don't follow rules get fired instead of just a wag of the finger. This difference may shrink now that Big Consequences are showing up in academia: a UCLA chem professor is standing trial on 3 felony charges for not properly supervising a student who burned to death.
http://www.latimes.com/local/lanow/la-me-ucla-prof-20130426,0,1938374.story
Fair enough but you forgot to mention that one party has been strongly against spending money on public infrastructure and doubly so while Obama is in office. While building new roads and improving public transportation is only a delaying action for congestion it does at least delay it.
In my (quite limited) experience, if potential jurors make it clear they will be a pain in the ass and will be hating every second of it they get dismissed. This might go out the window in high profile cases, but judges and attorneys are looking for people who can work together to reach a decision without undue drama or delay.
Politician runs for office in district A. To meet the residency requirements he claims he lives in his Mom's spare room in District A. License plate scans reveal his car lives in District B - in the parking lot for his mistress's condo.
Cholesterol does get absorbed through the intestines. There's even an approved drug (ezetimibe) to inhibit the process. Plus diet does affect atherosclerosis.
That would get expensive, since grad students and postdocs tend to need access to equipment 24/7/365. Go check out a Chem department NMR room on Christmas Eve.
I think you've won the thread: two big ass surveillance cameras in the room would improve compliance in filling out the log and required user maintenance/cleaning quite nicely. Would only have to review footage when there were problems.
Cabinets might be tricky - the equipment he mentioned tends to be permanently mounted to the wall (water purifiers) or too big to move (centrifuges). Might be able to lock up the rotors for the centrifuge (different rotors for different jobs; they get swapped in and out of centrifuges pretty often) ... but if it's a bio department rotors are typically stored in a refrigerator, which complicates things.