First came RNA, which combines the catalytic properties of proteins and the hereditary properties of DNA in a single molecule. So RNA can provide a template for new RNA (by base complimentarity) and also catalyse the polymerization of RNA onto itself. The odds of randomly assembling such an RNA are of course excruciatingly low - but we have a hundred million years and many, many RNA polymers floating around during that period. Furthermore, if we were on a planet where this had never occurred - would we be here to talk about it?
RNA molecules form spontaneously in conditions like those on the early earth, given the right organic ingredients (i.e. in the presence of the molecules we see in that gas cloud, if they were on a planetary surface).
Phospholipids (or other molecules, with similar charge properties) also form spontaneously, and arrange spontaneously into lipid bilayers.
Since these lipid bilayers would have a strong tendency to concentrate whatever was in them when they floated away, the insides of these lipid bilayers would be ideal locations for these self-replicating RNA to congregate. I will refer to these proto-cells as "collectives of RNA molecules".
Over time, these RNA molecules evolve new catalytic activities. It has been well established - in experimental studies - that randomly varied RNA can, indeed, evolve new catalytic activities. It takes a while, but we've got an aeon to burn.
Three new RNA activities are key: a) Creating a "template" version of themselves/eachother consisting of DNA, rather than RNA. This will eventually become the inherited genome - but originally, this would confer a selective advantage because DNA molecules are more stable than RNA. Even today, no organism can synthesize DNA without first synthesizing a little RNA as a "primer" to get synthesis started. b) Making proteins as an aid to catalysis. The first proteins were probably non-informative polymers (like starch). Most likely, they served as bound cofactors (like heme iron in hemoglobin) and the like for RNA enzymes. Since proteins are almost universally superior catalysts to RNA, the first collective of RNA that had the ability to synthesize protein would have a great advantage. Even today, the fundamental reaction of protein synthesis is catalyzed by the RNA component of the Ribozome, although modern Ribozomes have a great many proteins that "help" the process. c) Synthesising additional phospholipids to make more membrane. As time goes on and the amount of free phospholipid floating in the water declines, this becomes a great selective advantage to any proto-cell, since it can reproduce more proto-cells limited only by available energy and reduced carbon.
With these three - perfectly understandable - adaptations, you have evolved from a soap bubble full of RNA into a cell.
---
Obviously, this story need not be true, and there are many details missing (or incorrect.) At the moment, however, it is the best explanation we have, and it is certainly possible.
"Let's talk about the question of why people are wealthy. There is a myth that it's a function of enormous personal attributes... the individual wealth which is generated in this economy is, in my judgment, and I doubt that there is much that anyone could disagree with about this, is a function of the innovative businesses which are created as a result of federal research. But you understand that the people who benefit from that research get it free... It starts from this incredible research activity which is going on with federal money."
With 9 revenue categories, correctly predicting the category 37% of the time (RTFA), is, ehem, unimpressive - a dartboard would guess correctly 11% of the time.
So we have a predictor that makes 0.63/0.88 ~= 70% as many mistakes as a dartboard. If you give it one category of "wiggle", it makes 0.25/0.66 ~= 40% as many mistakes as a dartboard.
People are making a lot of hay out of this. It tells you that small movies (opening on fewer screens) are very seldom blockbusters, and that heavily promoted movies almost always make at least ten million or so. How is this unexpected? I bet I could get similar predictive power using a SINGLE variable - the promotion budget for each of the films. If it could tell us something actually interesting (or useful to hollywood types) - like "why are some big budget movies successful while others are not?" - that might be worth something.
Also, the journalist is a nitwit - "North American ticket sales currently total $7.6 million."
The Post Chronicle article is nonsense - refusing to talk to the press is evidence that he was not actually assaulted? That's completely ridiculous. The article also accuses the professor of not keeping his story straight - either that he is unable to say exactly where it happened, or that he has contradicted himself - but doesn't provide sources for that assertion, let alone quotes.
It is true that he may be lying (although I doubt it). Anyone could be lying - but no evidence that he is lying is actually presented in the article to which the parent links.
Other posters are making a lot of hay over the responsible programmers portion of the statute - obviously, if you need to list everyone who contributed code that would tend to be impossible (although a few projects could probably comply.)
However, I'm fairly sure that you could meet that requirement with a list of the *responsible* programmers - i.e., the people in charge making decisions. Thus, you don't need to list every programmer - the person in charge of your particular embedded system fork ought to be sufficient.
The article is a little light on the scientific details, but I assume (making an ass of u and me) that the evidence they're talking about are enzymatic activity assays from isolated tissues. A significant minority of all human genes have been implicated in the development of cancer - finding a compound that downregulates some of them in tissue culture isn't really surprising.
Similar evidence has been accumulated regarding a host of other compounds - as far as I'm aware, none of them have ever proven useful either as treatments or as prophylactics. That said, by all means, dose a population of mice with hops extract and see if it prevents them from getting cancer.
Evidently you skipped class when they covered photosynthesis.
All that reduced carbon in the plant-oils COMES FROM CARBON DIOXIDE IN THE ATMOSPHERE.
Thus, biodiesel is sustainable.
The *real question* is, how much energy from fertilizer does it take to make this biodiesel? I'd understood that to be the big expense (along with the water,) and not the processing, but I could be mistaken.
As an American I am in a better position to fix the problems than anyone. If I move to Canada (and even if I become a Canadian subject, or whatever) I have given up on influencing the course of events because I don't want to deal with some sort of guilt over my failure to do so recently?
We don't know how much worse things might have been, either. We say, and it's true, that the domestic opposition didn't prevent the administration from invading Iraq. Well, that was a failure. There is literally no way of knowing what else they might have done if given free reign - Miers on the SCOTUS is only the start of it.
In case you haven't been paying attention - the two last US elections have been very close, and their outcomes (especially in 2000) have had a tremendous impact on the rest of human history. In spite of those election results, public opinion here in the US still plays a big role in determining what the administration can and cannot get away with. If you're really concerned with human civilization, and not with melodrama, you move to a purple state, not to Canada.
But there is a reason for reverence for peer review - as a procedure, it weeds out a lot of bullshit. There are many scandals - but far more successes (the entirety of biology, from the sometime in the early 20th century to the present.) I'm a biologist, so I cannot speak with confidence on the impact in other disciplines, or where the corresponding institutions of peer review may lie on the continuum between old boys network and tireless defenders of the scientific method, for other journals in other disciplines. In Biology, in spite of some failings, the record is overall very good.
The comments by the royal society are nakedly self serving. The fear at the royal society is that organizations like the Public Library of Science will sideline them. This will only happen if organizations like PLoS can maintain the same quality of peer review as the Royal Society (I will assert - so far they are doing better) without charging money. The implicit claim, that free journals deliver a lower quality of review, does not stand up to even cursory examination. I will say (and this is a subjective assertion on my part) that PLoS actually provides a better grade of peer review, and that a system where professional editors preside over large budgets and a permanent base of prestige breeds the sort of cronyism and corruption that the parent post is (legitimately) concerned about.
From a moral standpoint, of COURSE research done at public expense should be freely available to everyone, now that the technology exists to easily do so. In sum: if the royal society doesn't want to adapt to a modern era where real publication costs approach zero, let them be sidelined.
In general, the quality of the education suffers considerably.
Furthermore, as others have pointed out, lack of contact with professors essentially kills your chance of getting into graduate school.
If you're just interested in it as a certificate, I again second the advice of others, you should get it from a real university's online program.
My mother got a Master of Science Education from the Univ. of Montana, which had a big online component (about half of the courses). BUT, it was not *entirely* online, there were significant summer courses. Nonetheless, she liked the program greatly overall.
Read this before you enroll, though. David noble's anti-technology stance is a little extreme for my taste, but he makes excellent points regarding the weakness (and distasteful history) of correspondence-based education. It's out-dated
"This is the kind of arrant pedantry up with which I will not put." - Erroneously attributed to Sir Winston Churchill (probably another anonymous contributor to the same publication, AFAIK, identity unknown.)
"Where is the library at?" "At Dartmouth, we don't end a sentence with a preposition." "Oh, okay. Where is the library at, asshole?" - Anyone know the attribution to this joke?
Private systems are also wasteful. The drug industry spends twice as much money on advertizing as it does on R&D - and the companies that spend more money on advertizing are not the ones going out of business. You think the government would waste 66% of their research money?
In any case you are speaking of "government" in vague terms - I am speaking specifically of the NIH, which is, as I've discussed elsewhere, extremely efficient at identifying and funding promising research. We can argue about why this is, but no-one credible disagrees that the NIH does a good job - it is in fact far *less* wasteful than private sector research, which involves a great deal of secrecy and duplication. You can have all the vague platitudes on government waste you want but they simply are not relevant to the specific issue.
The largest hospital operator in the US is the holy and apostolic catholic church. I can assure you that hospitals are not placed based on economic viability. Nor should they be, any more than fire departments should be. Yes, many jurisdications have volunteer fire departments - but they still have budgets, and they still have government provided equipment. Do you think the government does a bad job of identifying those jurisdictions that require a full-time fire department, and those where a volunteer department is sufficient? I don't - I think the government is doing a very good job at that.
Yes, everyone benefits from the medical research. There is overwhelming public support to raise such budgets, and it is entirely rational - if you are a citizen of the US or Switzerland, the benefit to your quality of life per research $ is great enough that you'd have to be nuts to oppose spending on medical research - even if the nasty French also benefit. Of course not every disease is equally common in every nationality.
Of course this presupposes meaningful democracy, where the interests of the public are reflected in decision making - but then, so does ending the current patent regime in the first place.
Nor am I arguing that the government should be the sole source of innovation - merely that the public does not benefit from patent protection provided to private drug research. Private research would continue, in a much reduced form, without patent protection.
Gah, I can't sleep. I didn't even notice this response and it's the best among the lot.
When I said "public" I meant to include non-profits as well as "private" universities; non-indutry would be a better term - in my lab this equals about 20% of federal funding, which is probably about typical, although in cancer research is it much, much higher.
I would say that you should also include a variety of tax-breaks - often at the State level - which are given in some way theoretically conditioned on R&D, as non-industry funding. State governments, or funds that pass through state agencies in one way or another (from tuition, etc.) also pay, indirectly, a varying but sometimes significant portion of the cost for research at some state universities, the accounting is not transparent so this is much more difficult to tally. So the State share is non-zero, but hard to say how big it really is.
Industry also spends a significant amount on R&D actually located in Universities, but I'm pretty sure they include that in their filing. My lab gets hardly any industry money but my Dad gets a fair amount.
On the other hand, Columbia (my institution) in particular makes a fair amount of money from patent income, and it would be highly disingenuous of me to include that in the "non-industry" R&D total, given what I am proposing.
Finally, the federal number has not grown as much as I would have expected, I haven't actually seen these numbers for a few years, I'm pretty sure that the Federal pharma R&D was bigger when last I looked.
Anyway, thank you for the correction, but you can change "most" to "comparable amounts" in my original post it doesn't really change anything.
Your prediction is simply not holding up to recent history - my evidence here in anecdotal, but when a scientist develops a new drug, they start up a little company - so that they can sell the patent to Pfizer. For them to actually make the drug themselves depends on assumptions regarding low cost of entry which simply do not hold in this case. The result of this is that we have a sustained oligopoly which will not fix itself through competition, and is in fact becoming more entrenched.
No, corporate power centers have incentives to make *profitable* decisions.
We will simply have to disagree that such decisions are automatically "good" (in some cases they are), and that the drug companies have a track record of making good/effective decisions. This is a judgement call, but if you really believe that, obviously you would not reach the conclusions that I have. I think it is clear, given how much trouble elderly in the states are having affording drugs, that pricing at the most profitable pricepoint is not good for the health and welfare of the US population.
You are correct that this would have some effect in de-incentivizing biopharma research in small countries. I would maintain that the benefits far outweigh this cost, and that public support for medical research funding is so overwhelmingly high that it would not be a problem.
I also have some factual disagreements but they certainly won't change your mind in light of that gulf of difference in opinion.
Firstly, your assumption about differential pricing in different nations pre-supposes an extensive system of trade barriers as well as a system of patents, and while, as a result of public pressure (not to mention threats of outright revolt), some drugs do have the pricing scheme you suggest - it is a tiny minority.
Secondly, you are simply mistaken that the marginal cost of manufacturing most drugs is near-zero - presscription generics cost about 30% as much as patented medications, typically (see refs in the cousin article,) which is far from where they'd land by market forces if they could be manufactured for free. For a few famous AIDS drugs the marginal cost is near zero, and marginal cost always drops with increased scale, but you can't take those numbers and generalize them to all drugs.
There are *six* articles. Get the full text of the first three from Dean and read them - or not, but they contain the information relevant to point a, and references relevant to point b, I'll let you judge his conclusions for yourself.
You said you wanted an example for blood pressure, and there it is. You never actually asked for an example for neurotensin (you asked the other guy), you just asserted that it was developed without any academic help, and since I don't know anything about chronic pain (I do know about blood pressure), it's a significant research project to recover the paper trail. *You* made the affirmative claim that it was uniquely developed by the relevant drug company. Post a link where you read that and I can use the names of the researchers to track to public research connections (if any exist) in the morning. Otherwise, it's too much work.
On valium, I can't answer the question definitively because I can't read German or Polish - and I would need to search physical archives anyway, any relevant research articles would be too old to appear on the web. In any case, you've ignored the primary thrust of my response and concentrated on something secondary. This example is too old to be relevant to the modern period.
I said: "As for blood pressure, yes, it was elucidated in public universities. You can easily get a list of thousands of references from medline - tell you what, if you actually care, tell me which journals you have access to (and regard as acceptable) and I can find the relevant publications for you."
You said, in direct response "Way to completely miss my point. I'm talking about more modern mechanisms of control directly related to the newer drugs and new research, not older knowledge that's been well established for decades or centuries. After all, then we have to give credit to 19th century doctors who dissected cadavers. Basic understanding of the mechanisms of blood pressure has happened eons ago, we're talking about a modern, more sophisticated understanding."
From which I conclude with certainty that you do not know that medline only returns modern research - and are not up to speed in the field generally, because angiotensin was discovered fairly recently.
"WHEN DID I EVER ASSERT THAT YOU COULD FIND THAT INFORMATION ON MEDLINE?! Seriously, I never came close to making that claim, now you're just grasping at straws. The point was that if you're going to give credit to people, you'd have to go back centuries to all past research."
The distinction between the NIH and other government agencies is NOT semantic. Decisions at the NIH are not, as a rule, made by political appointees at all, or by career beurecrats, they are made by volunteer scientists on panels. I think you will find virtually 100% agreement, it is a very effective system.
Anyway, the chief reason is that high tech industries should give people what they WANT - ipods and so forth. Panels are very bad at figuring this out - survival of the fittest in the market, despite many failings, works well.
Pharmaceutical research, like fire departments, should give people what they NEED. The market is dreadful at this. The actual manufacturing can be left to the market, it ought to be, keeps prices down on something vital to survival.
That said, yes, abolishing patents would bring us closer to pure capitalism, so if you think: closer to pure capitalism -> good idea you should favor abolishing patents. In the case of high-tech, this would actually have less of an impact than you might think, as many profitable electronics manufacturing concerns depend more on being first-to-market-with-latest-whizbang than on any ability to actually *patent* the latest whizbang. Anyway, I don't really care - even if abolishing all patents is a good idea, "all patents" don't kill people, so there are more important fish to fry.
Anyway, we are NOT proposing to nationalize an entire indusstry. The drug industry spends twice as much on advertizing as it does on R&D (cousing posts provide sources) - and we're here completely ignoring the money it costs to actually *make* the drugs.
If you're not used to being told you're from Mars, you'll never fit in on slashdot. I suggest going out on the street and yelling at cars for a while, so you have some common experience with other slashdotters. ONE OF US! ONE OF US!
Only a partial answer but I need to go to sleep. Enjoy slashdot.
There are two, independent questions here: a. The important question - can we save money by moving all drug R&D into the public sector,
and b. The ancillary question - how much of the money spent to do drug R&D is really private, under the current circumstances.
I'm not that interested in point b, which is the only one you seem to want to talk about.
1. They're not well-established and credible journals.
Challenge is a bit odd, but Health Letter and Journal of Health Policy are both reputable - more importantly, you already complained about the bibliography being too long, and the Challenge article contains a great many citations which you can follow, if you really care about the question and aren't just arguing for the sake of it.
2. They weren't studies, they were op-ed and promotional pieces in the journals.
How exactly are you concluding that if you cannot read them? The *second three* (helpfully labeled as position papers) are indeed opinion articles.
If you actually knew anything about medline you'd know that it only returned recently published articles - no 19th century cadavers. If you know anything at all about biology and chemistry, you'd know why I find your whole line completely baffling - drug companies do hardly *any* fundamental research at all, they just develop drugs. This is simply common knowledge among all researchers, the drug companies don't even deny it.
Here is one example: Telmisartan blocks the action of Angiotensin. As mentioned in this abstract.Angiotensin was discovered by this man, in the public sector. If you type angiotensin into medline (as I just did) you will find many examples of ongoing fundamental research on angiotensin, certainly useful to drug companies - of the ones I checked, all done by academic scientists. Comb the list for counter-examples, see if you can find any.
To be blunt, your assertion is from Mars. I'm not sure anyone even bothers to do a careful study of the question, it's regarded as so obvious. 40 years ago the situation was significantly different - private drug companies still depended heavily on public science, but it wasn't nearly so extreme as it is today.
Anyway, if you actually care about the question ask Dean for the articles, I have to go to bed.
Read my list of citations in the cousin post. This is not simply "the government" making decisions - it is specfically the NIH. Now, the NIH has made a great many mistakes, but if you think the NIH even *approaches* the corruption and incompetence of the drug industry, you're from Mars.
The industry - actually manufacturing drugs - stays in the private sector. No nationalization.
The only thing I'm proposing is that the government should stop distorting the market by allowing patents on drugs - at the same time, government financing of R&D should, as a policy question, be expanded to take up the slack. There's no nationalization here.
You say I'd be hard pressed to find an economist who'd regard this as a capitalist solution - maybe that's true but that doesn't answer the underlying question: *is it* a capitalist solution, or not?
I stand by my statement that public financing of R&D is less of a market distortion than are patents, and therefore is more capitalist. Why and in what way am I wrong?
Experimental build of firefox crashed, so I'm posting all responses here - includes responses to several "cousin" comments.
No, I am not proposing that we pay the estate of Sir Isaac Newton royalties every time we use newtonian mechanics - but it is equally absurd to pay royalties to any other scientist, given the collaborative and accumulative nature of science. This is an auxillary point, and to cover it in detail we'd have to go into the many ways in which a typical pharmaceutical patent is very different from, for example, patents on components in consumer electronics (which are, I would argue, deserving of patent protection.)
You say the burden of proof is on me and then you dismiss the three peer reviewed journal articles I provided because you don't like the journals they are published in? I have provided proof - the burden is now on you to debunk it, and if you're only argument is that you don't know anything about economics: that doesn't debunk squat. If you really want copies, Dean Baker can be contacted at his email address, baker at cepr dot net. I'm sure he'll send them to you, and probably fairly promptly.
Did you even read the piece that you do have access to? It has the most salient point. Cost to public, drug patents, per year - approx $150 mil R&D expenditures of pharmaceutical industry, per year - approx $41 mil
The methodology here is pretty transparent.
As for blood pressure, yes, it was elucidated in public universities. You can easily get a list of thousands of references from medline - tell you what, if you actually care, tell me which journals you have access to (and regard as acceptable) and I can find the relevant publications for you.
The question *you* didn't answer is - do you know anything about chemistry or biology?
There's no point in my arguing specifics (e.g. how much of a role did public sector neuroscience research play in the successful development of neurotonin) if you don't know anything about the topic, is there? An argument from authority is hardly satisfying, especially if you don't have access to any journals.
In other news, GlaxoSmithKline has developed a new drug that will send you hurtling 40 years into the past, where this will have some relationship with reality.
Even in the case you raise, the techniques of organic synthetic chemistry he used were developed, largely, in what I would call the public sector (technically at royal expense, but hey) - and the development costs for those were, in constant dollars, stratospherically higher than the money that was spent funding Leo Sternbach and his group.
In many specific cases, corporate decision makers may make better choices than the public sector regarding allocation of resources, I don't want to get into a discussion of this as a general principle - however, you seem to have taken this as a religious creed.
I'll raise exactly one counter-example: Should fire departments be run as for-profit enterprises, and only purchase fire trucks in jurisdictions where they can make money charging for fire protection services? Drug research is high tech, but it is a question of public health and safety, and the fundamental decisions should be made with that in mind - so it is more like the fire department, and less like high end consumer electronics.
Beyond that, corporate decision makers are also very corrupt. For example, in the vioxx case, concealing the evidence of deaths, and so forth. In the case of ipods this really isn't a big deal - so the screen scratches now, so what? But when people like that make public health decisions, other people die.
Shifting all drug control resource allocation to the NIH (or a parallel body structured along the same lines) - would not only make better decisions than corporate power centers, it would also make them a transparent way, subject to the full force of peer review. This isn't a 100% guarantee against fraudulent research, but it's a good start!
So, we get better decisions and we get them at a huge costs savings - no need even to rock the boat, we can simply hire the entire existing research apparatus of the american drug industry, let them keep their current generous salaries, and we can spend a tiny fraction of the savings giving them government-employee retirement benefits.
To continue this discussion I'd have to get into the nitty gritty of decisions that pharmaceutical companies have made in the past, and why they have been so disastrous.
If it makes you feel any better, this is really capitalist solution.
Which is a greater distortion of the market: granting patents, or increasing (by about two fold) the money the government spends on life sciences research? Certainly, if the government is making free R&D available to anyone who wants it, that is a market distortion of a kind. In the past, similar market distortions have lead to epic disasters like the Internet, also the modern aerospace indudstry, sattelite communications, am I leaving out any other great mistakes of 20th century America? My god, what fools we where, to meddle with the market!
Anyway, the drugs would still be manufactured by for-profit companies, they'd just be manufactured in a true market, without the market distortions introduced by patents, which is actually a purer form of capitalism, isn't it?
njyoder - do you have any background in biology or chemistry?
How were the mechanisms of blood pressure regulation discovered (picking a drug from that list at random)?
The techniques commonly used to perform high throughput screening of new drugs - who discovered those?
The synthetic organic chemistry required to actually *make* all these novel compounds? Where do you think that was developed?
The research in fundamental biology has been absolutely *essential* to the development of modern pharmaceuticals - every bit as vital as DARPAnet was to the creation of the internet.
Yes, it's true, the public sector does not develop drugs - because when public sector entities get close to developing a drug, they sell their data to a drug company to let the drug company finish the process. However, this is not a law of nature - or even of convenience. It's a massively inefficient mess, with huge amounts of wasted effort and redundant work, driven entirely by the patent system (and the desire by University administrations to secure the profit from those patents.)
Here are the refs: (journal articles) "Patent fiction," Health Letter (Washington, DC): vol. 20, iss. 6, Jun 2004; p. 1. "A Free market solution to prescription drug crises," Challenge (Armonk, NY): vol. 46, iss. 5, Sep/Oct 2003; pg. 76 "Medicines and the New Economics Environment," Journal of Public Health Policy (South Burlington, VT): vol. 23, iss. 2, 2002; p. 245.
(also a policy paper you should read) "Bird Flu Fears: Is There a Better Way to Develop Drugs?" Washington, DC: Center for Economic and Policy Research, October 2005 "Bigger Than the Social Security Crisis: Wasteful Spending on Prescription Drugs", Washington, D.C.: Center for Economic and Policy Research, April 2005 "The Benefits to State Governments from the Free Market Drug Act," Washington, D.C.: Center for Economic and Policy Research, November 2004
The majority of the expenses associated with new drug discovery are actually made in the public sector - by Universities and so forth. In broad outline the story is very similar to the Internet, also developed at public expense.
Now, the private sector does contribute significant additional resources to drug development. HOWEVER, these additional resources are a *fraction* of the total increase in drug prices that result from the patents they are awarded (vs. what the same drugs would cost if prices were governed by a free market.)
The upshot is that if you look at it over the long run, we would be much better off if we violated all the patents, let the patent-dependent drug companies go out of business, and funded an equivalent amount of research in the public sector, making the results available to anyone who wished to sell the resulting drugs on the market.
The research I'm citing here was done by a fellow named Dean Baker. I'll dig up an exact ref if you like.
That's inaccurate - there is a *monopoly* value for the drug, which Taiwan refused to pay.
Patents are market distortions - every bit as much as tariffs and trade barriers.
More traditional exercise of emminent domain recognizes similar principles, by the way - the government gets to set the price, the owners of the property can't hold out for more than market value in the event that there is an emergency and sudden demand.
Slashdot Mirror
Here's the best story available at the moment:
First came RNA, which combines the catalytic properties of proteins and the hereditary properties of DNA in a single molecule. So RNA can provide a template for new RNA (by base complimentarity) and also catalyse the polymerization of RNA onto itself. The odds of randomly assembling such an RNA are of course excruciatingly low - but we have a hundred million years and many, many RNA polymers floating around during that period. Furthermore, if we were on a planet where this had never occurred - would we be here to talk about it?
RNA molecules form spontaneously in conditions like those on the early earth, given the right organic ingredients (i.e. in the presence of the molecules we see in that gas cloud, if they were on a planetary surface).
Phospholipids (or other molecules, with similar charge properties) also form spontaneously, and arrange spontaneously into lipid bilayers.
Since these lipid bilayers would have a strong tendency to concentrate whatever was in them when they floated away, the insides of these lipid bilayers would be ideal locations for these self-replicating RNA to congregate. I will refer to these proto-cells as "collectives of RNA molecules".
Over time, these RNA molecules evolve new catalytic activities. It has been well established - in experimental studies - that randomly varied RNA can, indeed, evolve new catalytic activities. It takes a while, but we've got an aeon to burn.
Three new RNA activities are key:
a) Creating a "template" version of themselves/eachother consisting of DNA, rather than RNA. This will eventually become the inherited genome - but originally, this would confer a selective advantage because DNA molecules are more stable than RNA. Even today, no organism can synthesize DNA without first synthesizing a little RNA as a "primer" to get synthesis started.
b) Making proteins as an aid to catalysis. The first proteins were probably non-informative polymers (like starch). Most likely, they served as bound cofactors (like heme iron in hemoglobin) and the like for RNA enzymes. Since proteins are almost universally superior catalysts to RNA, the first collective of RNA that had the ability to synthesize protein would have a great advantage. Even today, the fundamental reaction of protein synthesis is catalyzed by the RNA component of the Ribozome, although modern Ribozomes have a great many proteins that "help" the process.
c) Synthesising additional phospholipids to make more membrane. As time goes on and the amount of free phospholipid floating in the water declines, this becomes a great selective advantage to any proto-cell, since it can reproduce more proto-cells limited only by available energy and reduced carbon.
With these three - perfectly understandable - adaptations, you have evolved from a soap bubble full of RNA into a cell.
---
Obviously, this story need not be true, and there are many details missing (or incorrect.) At the moment, however, it is the best explanation we have, and it is certainly possible.
"Let's talk about the question of why people are wealthy. There is a myth that it's a function of enormous personal attributes... the individual wealth which is generated in this economy is, in my judgment, and I doubt that there is much that anyone could disagree with about this, is a function of the innovative businesses which are created as a result of federal research. But you understand that the people who benefit from that research get it free... It starts from this incredible research activity which is going on with federal money."
-- Bill Gates Sr., 2003
With 9 revenue categories, correctly predicting the category 37% of the time (RTFA), is, ehem, unimpressive - a dartboard would guess correctly 11% of the time.
So we have a predictor that makes 0.63/0.88 ~= 70% as many mistakes as a dartboard. If you give it one category of "wiggle", it makes 0.25/0.66 ~= 40% as many mistakes as a dartboard.
People are making a lot of hay out of this. It tells you that small movies (opening on fewer screens) are very seldom blockbusters, and that heavily promoted movies almost always make at least ten million or so. How is this unexpected? I bet I could get similar predictive power using a SINGLE variable - the promotion budget for each of the films. If it could tell us something actually interesting (or useful to hollywood types) - like "why are some big budget movies successful while others are not?" - that might be worth something.
Also, the journalist is a nitwit - "North American ticket sales currently total $7.6 million."
The Post Chronicle article is nonsense - refusing to talk to the press is evidence that he was not actually assaulted? That's completely ridiculous. The article also accuses the professor of not keeping his story straight - either that he is unable to say exactly where it happened, or that he has contradicted himself - but doesn't provide sources for that assertion, let alone quotes.
It is true that he may be lying (although I doubt it). Anyone could be lying - but no evidence that he is lying is actually presented in the article to which the parent links.
Other posters are making a lot of hay over the responsible programmers portion of the statute - obviously, if you need to list everyone who contributed code that would tend to be impossible (although a few projects could probably comply.)
However, I'm fairly sure that you could meet that requirement with a list of the *responsible* programmers - i.e., the people in charge making decisions. Thus, you don't need to list every programmer - the person in charge of your particular embedded system fork ought to be sufficient.
The article is a little light on the scientific details, but I assume (making an ass of u and me) that the evidence they're talking about are enzymatic activity assays from isolated tissues. A significant minority of all human genes have been implicated in the development of cancer - finding a compound that downregulates some of them in tissue culture isn't really surprising.
Similar evidence has been accumulated regarding a host of other compounds - as far as I'm aware, none of them have ever proven useful either as treatments or as prophylactics. That said, by all means, dose a population of mice with hops extract and see if it prevents them from getting cancer.
Evidently you skipped class when they covered photosynthesis.
All that reduced carbon in the plant-oils COMES FROM CARBON DIOXIDE IN THE ATMOSPHERE.
Thus, biodiesel is sustainable.
The *real question* is, how much energy from fertilizer does it take to make this biodiesel? I'd understood that to be the big expense (along with the water,) and not the processing, but I could be mistaken.
As an American I am in a better position to fix the problems than anyone. If I move to Canada (and even if I become a Canadian subject, or whatever) I have given up on influencing the course of events because I don't want to deal with some sort of guilt over my failure to do so recently?
We don't know how much worse things might have been, either. We say, and it's true, that the domestic opposition didn't prevent the administration from invading Iraq. Well, that was a failure. There is literally no way of knowing what else they might have done if given free reign - Miers on the SCOTUS is only the start of it.
In case you haven't been paying attention - the two last US elections have been very close, and their outcomes (especially in 2000) have had a tremendous impact on the rest of human history. In spite of those election results, public opinion here in the US still plays a big role in determining what the administration can and cannot get away with. If you're really concerned with human civilization, and not with melodrama, you move to a purple state, not to Canada.
But there is a reason for reverence for peer review - as a procedure, it weeds out a lot of bullshit. There are many scandals - but far more successes (the entirety of biology, from the sometime in the early 20th century to the present.) I'm a biologist, so I cannot speak with confidence on the impact in other disciplines, or where the corresponding institutions of peer review may lie on the continuum between old boys network and tireless defenders of the scientific method, for other journals in other disciplines. In Biology, in spite of some failings, the record is overall very good.
The comments by the royal society are nakedly self serving. The fear at the royal society is that organizations like the Public Library of Science will sideline them. This will only happen if organizations like PLoS can maintain the same quality of peer review as the Royal Society (I will assert - so far they are doing better) without charging money. The implicit claim, that free journals deliver a lower quality of review, does not stand up to even cursory examination. I will say (and this is a subjective assertion on my part) that PLoS actually provides a better grade of peer review, and that a system where professional editors preside over large budgets and a permanent base of prestige breeds the sort of cronyism and corruption that the parent post is (legitimately) concerned about.
From a moral standpoint, of COURSE research done at public expense should be freely available to everyone, now that the technology exists to easily do so. In sum: if the royal society doesn't want to adapt to a modern era where real publication costs approach zero, let them be sidelined.
As I was saying, it's out-dated, but in most cases the situation has not changed that much from when he was writing (8 years or so ago.)
And now slashdot is making me wait before I finish the thing. Razifrazin'.
In general, the quality of the education suffers considerably.
Furthermore, as others have pointed out, lack of contact with professors essentially kills your chance of getting into graduate school.
If you're just interested in it as a certificate, I again second the advice of others, you should get it from a real university's online program.
My mother got a Master of Science Education from the Univ. of Montana, which had a big online component (about half of the courses). BUT, it was not *entirely* online, there were significant summer courses. Nonetheless, she liked the program greatly overall.
Read this before you enroll, though. David noble's anti-technology stance is a little extreme for my taste, but he makes excellent points regarding the weakness (and distasteful history) of correspondence-based education. It's out-dated
"This is the kind of arrant pedantry up with which I will not put." - Erroneously attributed to Sir Winston Churchill (probably another anonymous contributor to the same publication, AFAIK, identity unknown.)
"Where is the library at?"
"At Dartmouth, we don't end a sentence with a preposition."
"Oh, okay. Where is the library at, asshole?" - Anyone know the attribution to this joke?
Their for they're is wrong.
Private systems are also wasteful. The drug industry spends twice as much money on advertizing as it does on R&D - and the companies that spend more money on advertizing are not the ones going out of business. You think the government would waste 66% of their research money?
In any case you are speaking of "government" in vague terms - I am speaking specifically of the NIH, which is, as I've discussed elsewhere, extremely efficient at identifying and funding promising research. We can argue about why this is, but no-one credible disagrees that the NIH does a good job - it is in fact far *less* wasteful than private sector research, which involves a great deal of secrecy and duplication. You can have all the vague platitudes on government waste you want but they simply are not relevant to the specific issue.
The largest hospital operator in the US is the holy and apostolic catholic church. I can assure you that hospitals are not placed based on economic viability. Nor should they be, any more than fire departments should be. Yes, many jurisdications have volunteer fire departments - but they still have budgets, and they still have government provided equipment. Do you think the government does a bad job of identifying those jurisdictions that require a full-time fire department, and those where a volunteer department is sufficient? I don't - I think the government is doing a very good job at that.
Yes, everyone benefits from the medical research. There is overwhelming public support to raise such budgets, and it is entirely rational - if you are a citizen of the US or Switzerland, the benefit to your quality of life per research $ is great enough that you'd have to be nuts to oppose spending on medical research - even if the nasty French also benefit. Of course not every disease is equally common in every nationality.
Of course this presupposes meaningful democracy, where the interests of the public are reflected in decision making - but then, so does ending the current patent regime in the first place.
Nor am I arguing that the government should be the sole source of innovation - merely that the public does not benefit from patent protection provided to private drug research. Private research would continue, in a much reduced form, without patent protection.
Gah, I can't sleep. I didn't even notice this response and it's the best among the lot.
When I said "public" I meant to include non-profits as well as "private" universities; non-indutry would be a better term - in my lab this equals about 20% of federal funding, which is probably about typical, although in cancer research is it much, much higher.
I would say that you should also include a variety of tax-breaks - often at the State level - which are given in some way theoretically conditioned on R&D, as non-industry funding. State governments, or funds that pass through state agencies in one way or another (from tuition, etc.) also pay, indirectly, a varying but sometimes significant portion of the cost for research at some state universities, the accounting is not transparent so this is much more difficult to tally. So the State share is non-zero, but hard to say how big it really is.
Industry also spends a significant amount on R&D actually located in Universities, but I'm pretty sure they include that in their filing. My lab gets hardly any industry money but my Dad gets a fair amount.
On the other hand, Columbia (my institution) in particular makes a fair amount of money from patent income, and it would be highly disingenuous of me to include that in the "non-industry" R&D total, given what I am proposing.
Finally, the federal number has not grown as much as I would have expected, I haven't actually seen these numbers for a few years, I'm pretty sure that the Federal pharma R&D was bigger when last I looked.
Anyway, thank you for the correction, but you can change "most" to "comparable amounts" in my original post it doesn't really change anything.
Your prediction is simply not holding up to recent history - my evidence here in anecdotal, but when a scientist develops a new drug, they start up a little company - so that they can sell the patent to Pfizer. For them to actually make the drug themselves depends on assumptions regarding low cost of entry which simply do not hold in this case. The result of this is that we have a sustained oligopoly which will not fix itself through competition, and is in fact becoming more entrenched.
No, corporate power centers have incentives to make *profitable* decisions.
We will simply have to disagree that such decisions are automatically "good" (in some cases they are), and that the drug companies have a track record of making good/effective decisions. This is a judgement call, but if you really believe that, obviously you would not reach the conclusions that I have. I think it is clear, given how much trouble elderly in the states are having affording drugs, that pricing at the most profitable pricepoint is not good for the health and welfare of the US population.
You are correct that this would have some effect in de-incentivizing biopharma research in small countries. I would maintain that the benefits far outweigh this cost, and that public support for medical research funding is so overwhelmingly high that it would not be a problem.
I also have some factual disagreements but they certainly won't change your mind in light of that gulf of difference in opinion.
Firstly, your assumption about differential pricing in different nations pre-supposes an extensive system of trade barriers as well as a system of patents, and while, as a result of public pressure (not to mention threats of outright revolt), some drugs do have the pricing scheme you suggest - it is a tiny minority.
Secondly, you are simply mistaken that the marginal cost of manufacturing most drugs is near-zero - presscription generics cost about 30% as much as patented medications, typically (see refs in the cousin article,) which is far from where they'd land by market forces if they could be manufactured for free. For a few famous AIDS drugs the marginal cost is near zero, and marginal cost always drops with increased scale, but you can't take those numbers and generalize them to all drugs.
G'night.
There are *six* articles. Get the full text of the first three from Dean and read them - or not, but they contain the information relevant to point a, and references relevant to point b, I'll let you judge his conclusions for yourself.
You said you wanted an example for blood pressure, and there it is. You never actually asked for an example for neurotensin (you asked the other guy), you just asserted that it was developed without any academic help, and since I don't know anything about chronic pain (I do know about blood pressure), it's a significant research project to recover the paper trail. *You* made the affirmative claim that it was uniquely developed by the relevant drug company. Post a link where you read that and I can use the names of the researchers to track to public research connections (if any exist) in the morning. Otherwise, it's too much work.
On valium, I can't answer the question definitively because I can't read German or Polish - and I would need to search physical archives anyway, any relevant research articles would be too old to appear on the web. In any case, you've ignored the primary thrust of my response and concentrated on something secondary. This example is too old to be relevant to the modern period.
I said: "As for blood pressure, yes, it was elucidated in public universities. You can easily get a list of thousands of references from medline - tell you what, if you actually care, tell me which journals you have access to (and regard as acceptable) and I can find the relevant publications for you."
You said, in direct response "Way to completely miss my point. I'm talking about more modern mechanisms of control directly related to the newer drugs and new research, not older knowledge that's been well established for decades or centuries. After all, then we have to give credit to 19th century doctors who dissected cadavers. Basic understanding of the mechanisms of blood pressure has happened eons ago, we're talking about a modern, more sophisticated understanding."
From which I conclude with certainty that you do not know that medline only returns modern research - and are not up to speed in the field generally, because angiotensin was discovered fairly recently.
"WHEN DID I EVER ASSERT THAT YOU COULD FIND THAT INFORMATION ON MEDLINE?! Seriously, I never came close to making that claim, now you're just grasping at straws. The point was that if you're going to give credit to people, you'd have to go back centuries to all past research."
Typing in all caps raises your blood pressure.
G'night.
The distinction between the NIH and other government agencies is NOT semantic. Decisions at the NIH are not, as a rule, made by political appointees at all, or by career beurecrats, they are made by volunteer scientists on panels. I think you will find virtually 100% agreement, it is a very effective system.
Anyway, the chief reason is that high tech industries should give people what they WANT - ipods and so forth. Panels are very bad at figuring this out - survival of the fittest in the market, despite many failings, works well.
Pharmaceutical research, like fire departments, should give people what they NEED. The market is dreadful at this. The actual manufacturing can be left to the market, it ought to be, keeps prices down on something vital to survival.
That said, yes, abolishing patents would bring us closer to pure capitalism, so if you think:
closer to pure capitalism -> good idea
you should favor abolishing patents. In the case of high-tech, this would actually have less of an impact than you might think, as many profitable electronics manufacturing concerns depend more on being first-to-market-with-latest-whizbang than on any ability to actually *patent* the latest whizbang. Anyway, I don't really care - even if abolishing all patents is a good idea, "all patents" don't kill people, so there are more important fish to fry.
Anyway, we are NOT proposing to nationalize an entire indusstry. The drug industry spends twice as much on advertizing as it does on R&D (cousing posts provide sources) - and we're here completely ignoring the money it costs to actually *make* the drugs.
If you're not used to being told you're from Mars, you'll never fit in on slashdot. I suggest going out on the street and yelling at cars for a while, so you have some common experience with other slashdotters. ONE OF US! ONE OF US!
Only a partial answer but I need to go to sleep. Enjoy slashdot.
There are two, independent questions here:
a. The important question - can we save money by moving all drug R&D into the public sector,
and
b. The ancillary question - how much of the money spent to do drug R&D is really private, under the current circumstances.
I'm not that interested in point b, which is the only one you seem to want to talk about.
1. They're not well-established and credible journals.
Challenge is a bit odd, but Health Letter and Journal of Health Policy are both reputable - more importantly, you already complained about the bibliography being too long, and the Challenge article contains a great many citations which you can follow, if you really care about the question and aren't just arguing for the sake of it.
2. They weren't studies, they were op-ed and promotional pieces in the journals.
How exactly are you concluding that if you cannot read them? The *second three* (helpfully labeled as position papers) are indeed opinion articles.
If you actually knew anything about medline you'd know that it only returned recently published articles - no 19th century cadavers. If you know anything at all about biology and chemistry, you'd know why I find your whole line completely baffling - drug companies do hardly *any* fundamental research at all, they just develop drugs. This is simply common knowledge among all researchers, the drug companies don't even deny it.
Here is one example:
Telmisartan blocks the action of Angiotensin. As mentioned in this abstract. Angiotensin was discovered by this man, in the public sector. If you type angiotensin into medline (as I just did) you will find many examples of ongoing fundamental research on angiotensin, certainly useful to drug companies - of the ones I checked, all done by academic scientists. Comb the list for counter-examples, see if you can find any.
To be blunt, your assertion is from Mars. I'm not sure anyone even bothers to do a careful study of the question, it's regarded as so obvious. 40 years ago the situation was significantly different - private drug companies still depended heavily on public science, but it wasn't nearly so extreme as it is today.
Anyway, if you actually care about the question ask Dean for the articles, I have to go to bed.
Read my list of citations in the cousin post. This is not simply "the government" making decisions - it is specfically the NIH. Now, the NIH has made a great many mistakes, but if you think the NIH even *approaches* the corruption and incompetence of the drug industry, you're from Mars.
The industry - actually manufacturing drugs - stays in the private sector. No nationalization.
The only thing I'm proposing is that the government should stop distorting the market by allowing patents on drugs - at the same time, government financing of R&D should, as a policy question, be expanded to take up the slack. There's no nationalization here.
You say I'd be hard pressed to find an economist who'd regard this as a capitalist solution - maybe that's true but that doesn't answer the underlying question: *is it* a capitalist solution, or not?
I stand by my statement that public financing of R&D is less of a market distortion than are patents, and therefore is more capitalist. Why and in what way am I wrong?
Experimental build of firefox crashed, so I'm posting all responses here - includes responses to several "cousin" comments.
No, I am not proposing that we pay the estate of Sir Isaac Newton royalties every time we use newtonian mechanics - but it is equally absurd to pay royalties to any other scientist, given the collaborative and accumulative nature of science. This is an auxillary point, and to cover it in detail we'd have to go into the many ways in which a typical pharmaceutical patent is very different from, for example, patents on components in consumer electronics (which are, I would argue, deserving of patent protection.)
You say the burden of proof is on me and then you dismiss the three peer reviewed journal articles I provided because you don't like the journals they are published in? I have provided proof - the burden is now on you to debunk it, and if you're only argument is that you don't know anything about economics: that doesn't debunk squat. If you really want copies, Dean Baker can be contacted at his email address, baker at cepr dot net. I'm sure he'll send them to you, and probably fairly promptly.
Did you even read the piece that you do have access to? It has the most salient point.
Cost to public, drug patents, per year - approx $150 mil
R&D expenditures of pharmaceutical industry, per year - approx $41 mil
The methodology here is pretty transparent.
As for blood pressure, yes, it was elucidated in public universities. You can easily get a list of thousands of references from medline - tell you what, if you actually care, tell me which journals you have access to (and regard as acceptable) and I can find the relevant publications for you.
The question *you* didn't answer is - do you know anything about chemistry or biology?
There's no point in my arguing specifics (e.g. how much of a role did public sector neuroscience research play in the successful development of neurotonin) if you don't know anything about the topic, is there? An argument from authority is hardly satisfying, especially if you don't have access to any journals.
Nice examples, njyoder.
In other news, GlaxoSmithKline has developed a new drug that will send you hurtling 40 years into the past, where this will have some relationship with reality.
Even in the case you raise, the techniques of organic synthetic chemistry he used were developed, largely, in what I would call the public sector (technically at royal expense, but hey) - and the development costs for those were, in constant dollars, stratospherically higher than the money that was spent funding Leo Sternbach and his group.
Practicality over ideology, nuggz.
In many specific cases, corporate decision makers may make better choices than the public sector regarding allocation of resources, I don't want to get into a discussion of this as a general principle - however, you seem to have taken this as a religious creed.
I'll raise exactly one counter-example: Should fire departments be run as for-profit enterprises, and only purchase fire trucks in jurisdictions where they can make money charging for fire protection services? Drug research is high tech, but it is a question of public health and safety, and the fundamental decisions should be made with that in mind - so it is more like the fire department, and less like high end consumer electronics.
Beyond that, corporate decision makers are also very corrupt. For example, in the vioxx case, concealing the evidence of deaths, and so forth. In the case of ipods this really isn't a big deal - so the screen scratches now, so what? But when people like that make public health decisions, other people die.
Shifting all drug control resource allocation to the NIH (or a parallel body structured along the same lines) - would not only make better decisions than corporate power centers, it would also make them a transparent way, subject to the full force of peer review. This isn't a 100% guarantee against fraudulent research, but it's a good start!
So, we get better decisions and we get them at a huge costs savings - no need even to rock the boat, we can simply hire the entire existing research apparatus of the american drug industry, let them keep their current generous salaries, and we can spend a tiny fraction of the savings giving them government-employee retirement benefits.
To continue this discussion I'd have to get into the nitty gritty of decisions that pharmaceutical companies have made in the past, and why they have been so disastrous.
If it makes you feel any better, this is really capitalist solution.
Which is a greater distortion of the market: granting patents, or increasing (by about two fold) the money the government spends on life sciences research? Certainly, if the government is making free R&D available to anyone who wants it, that is a market distortion of a kind. In the past, similar market distortions have lead to epic disasters like the Internet, also the modern aerospace indudstry, sattelite communications, am I leaving out any other great mistakes of 20th century America? My god, what fools we where, to meddle with the market!
Anyway, the drugs would still be manufactured by for-profit companies, they'd just be manufactured in a true market, without the market distortions introduced by patents, which is actually a purer form of capitalism, isn't it?
njyoder - do you have any background in biology or chemistry?
How were the mechanisms of blood pressure regulation discovered (picking a drug from that list at random)?
The techniques commonly used to perform high throughput screening of new drugs - who discovered those?
The synthetic organic chemistry required to actually *make* all these novel compounds? Where do you think that was developed?
The research in fundamental biology has been absolutely *essential* to the development of modern pharmaceuticals - every bit as vital as DARPAnet was to the creation of the internet.
Yes, it's true, the public sector does not develop drugs - because when public sector entities get close to developing a drug, they sell their data to a drug company to let the drug company finish the process. However, this is not a law of nature - or even of convenience. It's a massively inefficient mess, with huge amounts of wasted effort and redundant work, driven entirely by the patent system (and the desire by University administrations to secure the profit from those patents.)
Here are the refs:
(journal articles)
"Patent fiction," Health Letter (Washington, DC): vol. 20, iss. 6, Jun 2004; p. 1.
"A Free market solution to prescription drug crises," Challenge (Armonk, NY): vol. 46, iss. 5, Sep/Oct 2003; pg. 76
"Medicines and the New Economics Environment," Journal of Public Health Policy (South Burlington, VT): vol. 23, iss. 2, 2002; p. 245.
(also a policy paper you should read)
"Bird Flu Fears: Is There a Better Way to Develop Drugs?" Washington, DC: Center for Economic and Policy Research, October 2005
"Bigger Than the Social Security Crisis: Wasteful Spending on Prescription Drugs", Washington, D.C.: Center for Economic and Policy Research, April 2005
"The Benefits to State Governments from the Free Market Drug Act," Washington, D.C.: Center for Economic and Policy Research, November 2004
This is drug industry propoganda.
The majority of the expenses associated with new drug discovery are actually made in the public sector - by Universities and so forth. In broad outline the story is very similar to the Internet, also developed at public expense.
Now, the private sector does contribute significant additional resources to drug development. HOWEVER, these additional resources are a *fraction* of the total increase in drug prices that result from the patents they are awarded (vs. what the same drugs would cost if prices were governed by a free market.)
The upshot is that if you look at it over the long run, we would be much better off if we violated all the patents, let the patent-dependent drug companies go out of business, and funded an equivalent amount of research in the public sector, making the results available to anyone who wished to sell the resulting drugs on the market.
The research I'm citing here was done by a fellow named Dean Baker. I'll dig up an exact ref if you like.
That's inaccurate - there is a *monopoly* value for the drug, which Taiwan refused to pay.
Patents are market distortions - every bit as much as tariffs and trade barriers.
More traditional exercise of emminent domain recognizes similar principles, by the way - the government gets to set the price, the owners of the property can't hold out for more than market value in the event that there is an emergency and sudden demand.