19 replies to this topic

[mentatpsi]

NewsWeek: Desperately Seeking Cures
How the road from promising scientific breakthrough to real-world remedy has become all but a dead end.

I thought this might be interesting to many. I decided to place it in the political section because of its high potential to inspire conversations of that nature. Enjoy.

[bgwowk]

Anyone who thinks that cures for aging, or even comprehensive cures for cancer, are coming anytime soon needs to read and understand this article. There is a tendency to assume that the Law of Accelerating Returns applies to medical progress, when nothing could be further from the truth. The political and regulatory environment surrounding medicine is so different from the information technology world that it might as well exist on a different planet.

[rwac]

1. When the going gets slow, it's a sign that the underlying research is on the Wrong Path.

2. Who would care to discover and publicize cures that made nobody any money ?

Edited by rwac, 21 May 2010 - 04:48 PM.

[mentatpsi]

Anyone who thinks that cures for aging, or even comprehensive cures for cancer, are coming anytime soon needs to read and understand this article. There is a tendency to assume that the Law of Accelerating Returns applies to medical progress, when nothing could be further from the truth. The political and regulatory environment surrounding medicine is so different from the information technology world that it might as well exist on a different planet.

Excellent statement...

The actual newsweek article features a comedic graphical representation of the flow of discovery to cure... was a nice addition.

Here's an interesting quote:

... A decade-long search led to the discovery of a molecule on the surface of blood stem cells that turns out to be the master molecule used by those cells to home in on any site in the body.

Sackstein named the molecule HCELL. If stem cells were tagged with HCELL, he thought, they would make a beeline for the correct tissue—say, to regenerate bones in patients with osteoporosis. In 2008 he and colleagues announced in a paper in Nature Medicine that they had managed to do just that: when he injected human bone-forming stem cells tagged with HCELL into mice, the cells headed for the mice's bones and began forming human bone there. HCELL-tagged stem cells, in other words, could be the long-sought cure for osteoporosis, as well as other diseases that might be treatable with stem cells.

But because Sackstein had described HCELL in a scientific paper, the U.S. patent office told him it was rejecting his application. Ten years of appeals have cost hundreds of thousands of dollars in attorney fees. Sackstein fervently believes his discovery deserves a patent, and it was granted one in Europe and Japan. "You have to persevere," he says. "I can't let it go, because I think the impact on patients could be so great. We've cured osteoporosis in mice." But without patent protection, no company will develop HCELL for people, even in Europe or Japan. For a multinational drug company to go forward, it needs patent protection in the U.S. as well.

[bgwowk]

1. When the going gets slow, it's a sign that the underlying research is on the Wrong Path.

It's not the research per se that is necessarily deficient. There's no shortage of promising leads in the lab. As the article explains, it's the Valley of Death between the lab and the clinic that's the problem. The problem is the system, not the science.

[mentatpsi]

Btw, I recently found out the url is no longer functional. For that cause, here is the current url:

NewsWeek: Desperately Seeking Cures

[mentatpsi]

There is one particular counter-point I'd like to put on the table.

Have you ever noticed that we are beginning to discover that our technology harbors inherent risks, such as high radiation emission from cell phones possibly resulting in cancer or wireless technology linked to autism? In our ever-increasing growth of technology, will the advent of the very technologies which give us great prowess over the elements begin to be our very downfall? I know it is cliche, but it has been argued that technology's growth is a good thing, and a result of the lack of regulation in comparision to medicine. But I want to point out some of the negativity of such a open progress. Not that I am against it, just being a devil's advocate.

[JonesGuy]

So, where in the breakdown can the common person help?
The best I can see is that we need to be putting up more venture capital on projects we hope have some benefits.

[bacopa]

I guess you could write to the FDA, or NIH, and voice your concern. Or become an expert in disease pathology, and work or start up your on biotech company.
Talk to Brokenportal a director here at imminst. He's all about how the common person can help.

Edited by dfowler, 03 June 2010 - 07:03 PM.

[bacopa]

here's and equally if not more upsetting article.

http://www.scienceda...00601101420.htm

[mentatpsi]

An idea, rather straightforward:

Have a ImmInst fund for promising research to finance the drudge work. It could either be a permanent aspect, or a competition in which they are voted upon and then ImmInst can raise funds for donations. Likely to get media attention, in addition certain big pharma companies could show support by putting money as well. Would be good for public relations all round. The pharma part isn't necessary, but seems to have potential.

[JonesGuy]

The drudge work is terribly expensive. And the drudge work really does seem to have a lack of motivation. As Dr. Wowk points out, though, it's something that needs to be fixed sooner rather than later.

[mentatpsi]

The drudge work is terribly expensive. And the drudge work really does seem to have a lack of motivation. As Dr. Wowk points out, though, it's something that needs to be fixed sooner rather than later.

It doesn't have to be entirely, but I do understand where you're coming from.

[JonesGuy]

What could also help are easy diagnostics that a lab could tack onto a research protocol, in order to boost the translation speed.

If I'm looking at how "compound X reduces heart ischemia damage", that's what my paper is going to be about. If there were a couple of easy diagnostics I could throw in (e.g., does this compound hurt the liver? the brain?), then I'd throw them in. Compounds that protect the heart could continue to be explored for mechanism: compounds that also don't hurt the liver and the brain have already had initial work done.

[niner]

What could also help are easy diagnostics that a lab could tack onto a research protocol, in order to boost the translation speed.

If I'm looking at how "compound X reduces heart ischemia damage", that's what my paper is going to be about. If there were a couple of easy diagnostics I could throw in (e.g., does this compound hurt the liver? the brain?), then I'd throw them in. Compounds that protect the heart could continue to be explored for mechanism: compounds that also don't hurt the liver and the brain have already had initial work done.

That's a good idea and it's being worked on. One example is the "lung on a chip", mentioned here recently. A big area of interest in the Induced Pluripotent Stem Cells field is the creation of disease models for screening purposes, which could include "organ on a chip" models as well.

[niner]

This Newsweek article was pretty good in terms of its description of the barriers to translation of research to therapies. It fell down in the beginning in its discussion of a peptide lead, as though it was a great tragedy that it wasn't in the clinic. This betrays a lack of understanding of drug discovery. Peptide leads are a dime a dozen, and they usually don't amount to much.

Newsweek is correct that we aren't delivering as many drugs as we used to. There are a number of reasons for this, but they don't have much to do with national politics, regulation, or the FDA. For starters, it has been looking for a while now like we have already plucked most of the low-hanging fruit in drug discovery. The targets that are being looked at today are just tougher to make drugs for. For example, there are lots of interesting kinase targets, but with hundreds of kinases in humans, specificity becomes a big problem. Engineering specificity into a kinase inhibitor is possible, but it isn't easy.

Another problem is that society is more risk-averse today than we used to be. We just don't seem to have the stomach for a few thousand people being injured by a drug that helps millions. The FDA is a reflection of society. They are more risk-averse today too, but it's a response to the pressure that we the people put on them to make us safer.

The main reason for the "Valley of Death" is the high cost and high failure rate when attempting to turn promising research into treatments. With apologies to Alex, perhaps the problem is Capitalism. The requirement of profitability and attendant IP coverage is a huge barrier in a lot of these cases. Foundations and non-profits are starting to fund research that is more directed, almost like contract research. This is already bearing fruit, particularly in diseases of the third world. This is part of the Open Science trend that I suspect will have a huge impact over time. As many of you know, ImmInst is at the forefront of this model. There is a move afoot to redirect some of the money that NIH devotes to basic research into a more applied realm. I hope we see more of that.

[bio123]

Another problem is that society is more risk-averse today than we used to be. We just don't seem to have the stomach for a few thousand people being injured by a drug that helps millions. The FDA is a reflection of society. They are more risk-averse today too, but it's a response to the pressure that we the people put on them to make us safer.

You seem to be omitting the obvious here: LAWYERS! (Nothing to do with people's stomachs; wallets maybe.)
Think of a host covered in millions of blood-sucking leeches and you have modern America. All doctors and
Big Pharma are terrified of them, and it gets worse every year as law schools churn out more and more of them,
all rushing out into society looking for someone to sue. It's no accident that America today is the most
litigious society that's ever existed on Earth. And you can't pass laws to prevent the spread of this contamination,
as guess who's making the laws?

[JonesGuy]

What could also help are easy diagnostics that a lab could tack onto a research protocol, in order to boost the translation speed.

If I'm looking at how "compound X reduces heart ischemia damage", that's what my paper is going to be about. If there were a couple of easy diagnostics I could throw in (e.g., does this compound hurt the liver? the brain?), then I'd throw them in. Compounds that protect the heart could continue to be explored for mechanism: compounds that also don't hurt the liver and the brain have already had initial work done.

That's a good idea and it's being worked on. One example is the "lung on a chip", mentioned here recently. A big area of interest in the Induced Pluripotent Stem Cells field is the creation of disease models for screening purposes, which could include "organ on a chip" models as well.

Thanks for the reply, because it shows I was unclear.

Thousands of animals are being subjected to treatements in laboratories, right now, ostensibly to show whether some treatment has a deleterious or beneficial effect. Or, to unlock some biological secret.

What I was suggesting are additional diagnostics that could be done on those same animals, easily, that could be included in a paper. Something worth data mining, even though it doesn't add much to the science being elucidated.

[mentatpsi]

In regards to the notion of capitalism being the fault, I wouldn't necessarily blame it entirely on this. Money is the most intrinsic incentive, the issue is the high costs. Could it not be said to be a consequence of the issue of gene patenting and the costs inherent in the legal process? Remedy the cost and maybe the rest will follow.

[thefreeaccount]

I felt that the Newsweek article was so simplistic and one-sided as to be completely non-informative. As little as twenty years ago, it would have been rare and very controversial for a researcher to apply for a patent on his works and attempt to directly profit from them. It was completely unheard of for a university to attempt to develop a product from lab discovery to manufacture to market.

These discoveries are, after all, paid in large part by public funds. Would it truly have been a disaster if the researcher in question had left HCELL unpatented and allowed the drug companies - which exist for the sole purpose of bringing products to market - to develop the drug?

I can't argue that the old model was perfect, or that the new model doesn't have many advantages. But what about the disadvantages? The vast shift of funding and tenured positions from the humanities to the applied sciences, the shift in research from basic science to what amounts to glorified product development, the conflicts of interest that occur when the outcome of a scientist's research can directly affect his own income and the income of his department - none of these problems are considered, or even mentioned, in the article.

The article's basic thesis - that drug development has slowed because the university-as-industry is stymied by regulation - simply can not be possible when the idea of the university as industry was born only in the last twenty to thirty years.

Edited by thefreeaccount, 23 July 2010 - 01:35 AM.