Politics Discussion Thread (Heated Arguing Warning)

[Krill]

Positive to Cheney, not me.

[Krill]

Also aren't most of the posters on this site scientists by training? I think I am one of the few that works in a different field but I've still got that chemistry degree.

[Mardoc]

Stereoisomers. Some molecules can 'lock' into two different forms, which can be very biologically different - it's commonly said that thalidomide is only dangerous in one of its two stereoisomers. I... don't actually know how to test for these, to be honest. They're chemically identical, so you need to delve into biology for that.

Most of these are optically active.  If you can pass polarized light through the material and observe rotation in the plane of polarization, you can determine the isomer.  If I remember my Organic chemistry history correctly, this is actually how isomers were originally discovered.  I don't think I've actually heard of a drug that doesn't have isomers, so this would definitely need to be in the suite of tests.

Could also pass your sample through some of the chiral separation methods and see if you end up with two samples.  I know I've heard of chiral chromatography, so some form of HPLC ought to do the trick here.

Testing for every functional group that should be in the substance - and every one that shouldn't be, but might have gotten in there. Do we have a double bond? An alcohol? An ester? We need to check for all of these.

You don't mention IR spectroscopy, I think.  Or maybe that's what you're referring to here?  I thought this sounded more like NMR but maybe you meant to include both.

And after all that? I still wouldn't be comfortable saying it was definitely the same stuff. 90%, maybe higher if I could get that more precise x-ray result at the beginning. How do you feel about a nine-out-of-ten chance that your medicine will do what it says on the tin?

I feel like you could get a higher certainty with more work and more overlapping tests, especially since you should have reference samples of the compound of interest and likely side-products to compare to.  It's not like there's any shortage of money in the industry, and the development of a suite of chemical tests for drug-verification should only have to be done once per drug.  Running the tests and rejecting anything that diverges requires a lot less expertise than developing the tests in the first place, so should be cheaper.

Well, possibly with the addition of a chemist at the FDA whose job is to study the analytical literature and propose additions and changes to the standard suite for Drug X.

Could an electron microscope be used to do an atom by atom structural analysis?  I guess if there is variance from molecule to molecule you'd have to take a statistically significant sample size...there's also the problem of this being Physics coming to the rescue of Chemistry mischief...

No, not really.  Electron microscopy of molecules is still in the research phase, 'holy cow that's possible?' from experts in the field.  Not something that could be deployed for routine analysis.  Maybe in a decade this will be different.

Also, most of what we would care about is contamination.  It's a lot easier to prove that there is some of the active compound, than to prove that there definitely *isn't* a significant amount of anything else.  Electron microscopy would need a ridiculous amount of samples to prove that.

[Krill]

The majority of drugs that aren't chiral are stuff like lithium, which is licensed as lithium carbonate or lithium citrate for use in bipolar as a mood stabilizer. Technically the drug is the full salt therefore only lithium carbonate is not chiral, even if the pharmaceutical active component is just the lithium.

[Huinesoron]

That is truly a top-tier threadjack. This forum rules sometimes.

Thanks, I think!

Most of these [stereoisomers] are optically active.  If you can pass polarized light through the material and observe rotation in the plane of polarization, you can determine the isomer.  If I remember my Organic chemistry history correctly, this is actually how isomers were originally discovered.  I don't think I've actually heard of a drug that doesn't have isomers, so this would definitely need to be in the suite of tests.

Could also pass your sample through some of the chiral separation methods and see if you end up with two samples.  I know I've heard of chiral chromatography, so some form of HPLC ought to do the trick here.

See, and now I've learnt something.  This does ring some bells, so yes, I like it. Though if your drug is a poly-ene, this still isn't a perfect identifier.

You don't mention IR spectroscopy, I think.  Or maybe that's what you're referring to here?  I thought this sounded more like NMR but maybe you meant to include both.

Aha! Yeah, we sent our IR off to another site a year back, so I've managed to forget it exists. These are both very valuable techniques, though again they end up being deductive reasoning rather than 'this is what it is' indicators - you have to work out what the peaks on the chart are most likely to correspond to.

(That said, for verifying identity they work pretty well - if they show the same peaks as the original sample, it's likely the same stuff... but this goes back to your contaminants point, later.)

I feel like you could get a higher certainty with more work and more overlapping tests, especially since you should have reference samples of the compound of interest and likely side-products to compare to.  It's not like there's any shortage of money in the industry, and the development of a suite of chemical tests for drug-verification should only have to be done once per drug.  Running the tests and rejecting anything that diverges requires a lot less expertise than developing the tests in the first place, so should be cheaper.

True. But this is where the Chemical Engineers come in. It's all well and good proving that you can make exactly the same material in the lab, but an industrial-scale plant is something else. And - from my own experience, which isn't pharmaceutical but is chemical - there's not really enough money to build a plant and then potentially have to scrap it because of slight differences in side products. That's tens of thousands of quidbucks - potentially hundreds of thousands if it's a particularly esoteric process - that you've just thrown down the drain.

Well, possibly with the addition of a chemist at the FDA whose job is to study the analytical literature and propose additions and changes to the standard suite for Drug X.

'A chemist'.   I'm pretty sure there are research chemists whose entire job is to do this for a single substance. Giving the FDA a research division large enough to do this would cost a lot of money, assuming there are even enough qualified applicants. You'd also be running headlong into the fact that the industry has a vested interest in keeping their new methods confidential, and would utterly hate the idea of it being widely published.

[To Darrell] No, not really.  Electron microscopy of molecules is still in the research phase, 'holy cow that's possible?' from experts in the field.  Not something that could be deployed for routine analysis.  Maybe in a decade this will be different.

Agreed. I remember seeing that first image of a polyaromatic molecule under EM, and 'holy cow' is exactly right. (That said, this is essentially what Single Crystal X-Ray Diffraction does, only it does it for crystals, rather than molecules per se. #DidMyMastersProjectOnIt)

Also, most of what we would care about is contamination.  It's a lot easier to prove that there is some of the active compound, than to prove that there definitely *isn't* a significant amount of anything else.

... and that's why it's a lot safer to control the manufacturing method, where the sources and routes of contamination are known. ^_^

Bottom line... I've forgotten what the actual topic under discussion was. Loosening regulations on how to manufacture drugs, right? Bottom line, a chemical company's driving goal is to make money. If it's allowed to not think about (say) vanadium levels in its product, it won't bother testing for them. And when the product in question is being injected directly into sick people's bloodstreams, that can be a very big problem.

[TheHumanHydra]

Also aren't most of the posters on this site scientists by training? I think I am one of the few that works in a different field but I've still got that chemistry degree.

Maybe we should make a thread about this; might be interesting. In fact, I think I will.

[RefSteel]

Dragging this bit over to the rabbit trails thread because it's getting political again:

Why? If the world's governments weren't so fixated on an economic system that gives the vast majority of the fruits of labour to the owners of capital, despite the minimal labour they put towards making those profits, we'd have well more than enough to be able to afford a decent standard of living for everyone. When 50% of the world's wealth is owned by a number of people so small they wouldn't populate a small village, a proper UBI is more than possible, given the proper will.

I think you and I disagree on too many matters of fact to have a productive conversation.

What? Disagreement about matters of fact is great for productive conversation (among reasonable people) online: Point out a fact you think is wrong, find a source for the correct version, and everyone will learn something instead of just fuming about each other's opinions. If people find conflicting sources, that's a chance to learn even more about the variety and reliability of different sources of information.

For example: Half the world's wealth is not controlled by 62 people, as it turns out. Half the world's wealth is controlled by a few tens of millions of people (the famous 1%) - but what the article Brian linked actually says is that the world's 62 richest people control as much wealth as the poorest half of the world's population. This is still pretty mind-boggling: The idea that the conglomerate wealth available to a few dozen individuals is equal to the amount available to over 3.6 billion people combined is pretty staggering ... but it must be understood that most of the world is incredibly poor by American and European standards. Of the 3.6 billion people who combine to equal the top 62, I suspect that all 3.6 billion live in third-world countries or e.g. rural China and India. Even a homeless beggar you pass on the street (in a first-world country) has access to more wealth and other resources from various government and non-profit agencies than most people in the third world get from all sources combined.

The problem of income disparity within the first world is a different story: In theory, as long as everyone's resources and prospects could improve continuously, then I (like Mardoc) wouldn't care who was benefiting most and least (as long as the continuing improvement was sustainable, which is another topic entirely). In reality though, this ... isn't happening. Median household income in the United States has increased slightly relative to inflation in the past several decades, but the increase has been very small, and the "inflation" figures used for this purpose only relate to the cost of consumer goods. The price of housing, medical care (though the Affordable Care Act helped with this) and higher education (the path people in theory are supposed to use to escape poverty) have increased at a much, much higher rate. Arguably, the average person in the United States is worse off economically today than a couple decades ago as a result - and this is a problem if the trends continue.

On medical care in particular, since Mardoc commented on it above:

(Speaking only about the United States) 20-year old medical options are not an acceptable low-cost alternative to current treatments even if we accept the premise that it's okay to let poor people get by with now-substandard health care, because those 20-year-old options are not available today! Medical equipment only lasts so long, and the cost of maintenance keeps growing as it ages, particularly as service and parts cease to be available. Doctors and nurses who retired within the past 20 years aren't available at cut rates to compensate for their lack of recent training in new medical advances; they aren't available at any price at all. Infections that could be treated 20 years ago by then-current antibiotics have developed resistance to those drugs. (The latter is especially important even to the health of the wealthy elite, because if bacteria have a large breeding ground in a local population that lacks access to effective antibiotics, especially if many of those people are using older antibiotics instead, it's going to keep getting harder and harder for new antibiotic development to stay ahead of bacterial evolution.) Those are just the examples I could think of off the top of my head.

It's a problem without an easy answer though, and I suspect it comes down to what I perceive as the central problems of our economy: We aren't training nearly enough competent engineers or doctors (or nurses or medical technicians or medical researchers or...) to keep our society running, partly because of the growing complexity of our infrastructures, partly because of the growing financial (and related) hurdles that have to be cleared to complete the necessary education, partly because the training people do receive often has huge gaps, and partly because we as a society generally discourage people from entering most of these fields, socially and culturally. (The hours people have to work in these fields, both in school and on the job, are another important barrier that seems to me to be part of a vicious cycle with these types of positions.) We're temporarily compensating for this by importing engineers from other countries, but then compounding the problem by making it very difficult for them to actually become citizens and stay.

Er. So I didn't go into this thinking I was going to write a treatise, but ... eh ... sorry....

[SevenSpirits]

For example:  Half the world's wealth is not controlled by 62 people, as it turns out.  Half the world's wealth is controlled by a few tens of millions of people (the famous 1%) - but what the article Brian linked actually says is that the world's 62 richest people control as much wealth as the poorest half of the world's population.  This is still pretty mind-boggling:  The idea that the conglomerate wealth available to a few dozen individuals is equal to the amount available to over 3.6 billion people combined is pretty staggering ... but it must be understood that most of the world is incredibly poor by American and European standards.  Of the 3.6 billion people who combine to equal the top 62, I suspect that all 3.6 billion live in third-world countries or e.g. rural China and India.

Actually this isn't true - the statistic under discussion is even more misleading than you think.

Here's a longer explanation I just googled for: http://blogs.reuters.com/felix-salmon/20...-the-poor/

Many people (2 billion according to the above article) have a NEGATIVE net worth. People in truly poor countries have a net worth close to zero, while many Americans in enviable positions, with student loans or mortgages for example, are technically in debt. So there are two huge problems with this statistic:

1) It's making it out that present net worth is a useful measure of how well off someone is. (It isn't. Income and expected future income are so much more impactful.)

2) It's treating it as impressive that the X richest people have as much wealth as the Y poorest people, when many of the Y people are contributing a negative amount of money to the contest! I.e. if it were comparing the world's richest X people to the world's genuinely worst off poor people (in poor countries, without the ability to be in debt at all) the comparison would look a lot more reasonable.

So, although disparity of wealth, income, and opportunity is incredibly important to me, I have nothing but disdain for this particular statistic!

[Bacchus]

Economic statistics generally have this quality -- only a fairly knowledgeable specialist can make sense of them, and the abuse statistics are subjected to by journalists is just criminal. One of my favourites, regularly repeated, is comparing a stock of something (say, company value, or bank assets) to GDP, which is a flow value. GDP itself is of course is a pretty technical measure that you have to be very careful with.

[Mardoc]

What?  Disagreement about matters of fact is great for productive conversation (among reasonable people) online:  Point out a fact you think is wrong, find a source for the correct version, and everyone will learn something instead of just fuming about each other's opinions.  If people find conflicting sources, that's a chance to learn even more about the variety and reliability of different sources of information.

Brian is not even willing to admit that the US Democratic party is not participating in a conspiracy to disenfranchise their own base of voters.


But I'll talk with you, sure.

In addition to the points SevenSpirits and Bacchus have made, these statistics never include any claim on future income that is not purely financial.  None of the following are counted as wealth:
- Pensions
- Social Security
- Tenure
- Education
- Tenant/squatter rights (even when they make the occupant the de facto owner of the property)
- Alimony/child support
- Rich relatives who care about you
- Any illegal income
- Any wealth hiding from taxes
- Government-provided services such as:

Even a homeless beggar you pass on the street (in a first-world country) has access to more wealth and other resources from various government and non-profit agencies than most people in the third world get from all sources combined.

- Probably a bunch more that I'm overlooking

Admittedly, most of the above aren't counted because they're hard to quantify, but that doesn't make them less real.

And, fundamentally, this discussion contains the assumption that wealth is just a thing that sort of happens, that's mostly luck or theft.  I believe the majority of wealth is created, not inherited or stolen.  There are obviously exceptions, but most of the disparities you see are the result of people being actually more or less productive, and being allowed to keep what they make.

Median household income in the United States has increased slightly relative to inflation in the past several decades, but the increase has been very small, and the "inflation" figures used for this purpose only relate to the cost of consumer goods.  The price of housing, medical care (though the Affordable Care Act helped with this) and higher education (the path people in theory are supposed to use to escape poverty) have increased at a much, much higher rate.  Arguably, the average person in the United States is worse off economically today than a couple decades ago as a result - and this is a problem if the trends continue.

Median household wages may arguably be stagnant-ish.  However, median per capita total compensation certainly is not. If you take into account the increasing value of non-wage compensation and the decreasing household size, the statistics are a lot less dire.

In addition, the statistics on income implicitly assume that we're comparing current Americans to their parents, but in reality a large fraction of the bottom percentiles are foreign-born, who should be compared to their prospects if they didn't immigrate if you're going to honestly assign credit and blame.  Taking someone from a dollar a day to $15K/year + access to governmental and non-profit assistance is still a huge improvement for them, but it will hurt US average and median statistics.  Even if it doesn't hurt any actual person.  In 1970, 4.7% of the US population was foreign born; in 2010 we were up to 12.9%, per the US Census Bureau, and the trend was still upward.  The increase is primarily from Latin America and Asia, too, so I think it's safe to assume the increase in population from immigrants is primarily in the bottom of the income distribution.  Thus, you should either compare today's 60th percentile to the 1970 median for an approximate comparison, or you should do the probably-impossible and adjust the 1970 numbers to include all the ancestors of current US citizens, no matter where they happened to be at the time.

Note that these are just the assumptions of which I've become aware.  None of them are lies, but they still create a false understanding.

---

It's a problem without an easy answer though, and I suspect it comes down to what I perceive as the central problems of our economy:  We aren't training nearly enough competent engineers or doctors (or nurses or medical technicians or medical researchers or...) to keep our society running, partly because of the growing complexity of our infrastructures, partly because of the growing financial (and related) hurdles that have to be cleared to complete the necessary education, partly because the training people do receive often has huge gaps, and partly because we as a society generally discourage people from entering most of these fields, socially and culturally.  (The hours people have to work in these fields, both in school and on the job, are another important barrier that seems to me to be part of a vicious cycle with these types of positions.)  We're temporarily compensating for this by importing engineers from other countries, but then compounding the problem by making it very difficult for them to actually become citizens and stay.

I don't think that any of our problems can be reduced to a single cause.  If any of them were that simple, we'd have been able to fix them.  Instead, they're multifactorial and interrelated, and often a local optimum.  Whenever someone attacks one source of inefficiency, those who benefit from it can truthfully respond: "That would only save a few percent of medical costs even if you went all the way to zero, while destroying good jobs, risking safety, causing long term problems, and letting $SOMEONE_ELSE continue to make out like a bandit".  

The main limit on engineers seems to be the number of people who are willing and able to learn math and science.  However, engineers are allowed to specialize and thus our education time doesn't increase with technology, while doctors and nurses are still expected to literally know all of medicine, so I wouldn't be surprised to find it difficult to increase their ranks as well.  To seriously increase the number of medical professionals would probably require a paradigm shift, such that a specialist would need *less* education than a generalist.

Medical licensure is one of those areas of somewhat increased cost.  Every requirement on licensure has the dual purpose of restricting the supply of new medical professionals, and having some effect on safety.  No one considers the trade-off of the actual effect on safety or cost is, though; we just assume more restrictions are better.

How about hospital 'certificates of need'?  That's where you're not allowed to open a new hospital unless all the existing hospitals in the area agree to allow you to open. If you want to to try to be more efficient and undercut them on price and put them out of business for being too expensive, they'll forbid you from opening.

Then there's the FDA, as I discussed with Huineorson.  Again responsible for a few percent, which could be cut but not to zero, nor quickly.

There's the enormous administrative burden imposed by third-party payment, where no one is quite sure what the cost of anything actually is, nor whether it will be paid, until a bunch of negotiation is done.

There's the professionalization of some costs, too.  Instead of expecting daughters to be housewives and take care of the elderly, we have nursing homes.  Which is a cost and benefit packaged together; we free women but add cost to the 'medical' bucket that was previously unpaid.  It increases cost reported by the statistics without necessarily burdening society any more.

To make a serious dent in the cost of medicine, we'd need constant pressure on cost, and right now every incentive is instead to remove any pressure on cost.