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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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August 29, 2013

How Goes the War?

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Posted by Derek

There's an article at The Atlantic titled "More Money Won't Win the War on Cancer". I agree with the title, although it's worth remembering that lack of money will certainly lose it. Money, in basic research, is very much in the "necessary but not sufficient" category.

The article itself is making the case of a book by Clifton Leaf, The Truth in Small Doses, a project that started with this article in Fortune in 2004. Here's the pitch:

What if a lack of research funding isn’t really the problem? One reason we aren’t making faster progress against cancer, according to Leaf, is because the federal grant process often chases the brightest minds from academic labs, and for those who do stay, favors low-risk “little questions” over swinging for the fences.

“More money by itself is not going to solve anything,” Leaf said. “Let’s say we doubled the [National Institutes of Health] budget, that isn’t going to make the lives of researchers better.”

The problem, as Leaf sees it, is with the business of cancer research. Over the last decade or so, “doing science” has reached a crisis stage—a claim many in the cancer community agree with, even if they don’t quite see eye-to-eye with Leaf on all of his conclusions.

His take is that the grant-money situation is making academic researchers spend more and more time just trying to get (or stay) funded, and that they tend to avoid anything that might sound a bit unusual in their applications. He also fears that academic researchers are taking too long to get established, that what might be some of their more creative years are being wasted in lengthy post-docs and struggles for tenure. I think that these are real problems, although they've been coming on for a long time now.

The article seems a bit too focused on the academic side of things; I don't know yet if the book makes the same mistake. Looking at it from industry, I think that the odds are that the first fundamental insights are more likely to come from academia, but I also think that the heavy lifting of turning these into real treatments will be done by industry. The difference between these has come up many times on this site, but it's safe to say that the general public does not appreciate it. The only place a breakthrough in the lab means an instant breakthrough in the clinic is in the movies.

To the extent, though, that people are told that "More Money" is the answer in this field, I think it's good to make the point that it isn't necessarily the limiting factor. Problem is, there's no way to hold a charity insight-raiser, or to set up a box to Donate Good Ideas For the Cure. Medical research, whether industrial or academic, is a pretty esoteric field to most people. There's not much way for an interested lay person to help out directly; the technical background is too much of a barrier. So people raise money, (while some just raise "awareness", a particularly slippery term), because it's the only way that they feel that they can make any difference.

Also, as has been said many times before, the "war on cancer" term is an unfortunate one, because it makes it sound as if there's a single enemy to be defeated. What we have is a war on our own ignorance of biology and medicinal chemistry, and that's going to be a long one. But perhaps I'm making the mistake that oncology pioneer Sidney Farber warned about:

(The patients) with cancer who are going to die this year cannot wait; nor is it necessary, in order to make great progress in the cure for cancer, for us to have the full solution of all the problems of basic research…the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures"

Problem is, the only way I can think of to come up with cures without such understanding is to do a lot of out-there clinical trials, at high risk. Farber himself took that approach, famously, and managed to win out. But I'm not sure what appetite we'd have for it on a broad scale.

By the way, if you take a look at the comments section to the Atlantic piece, you'll find the usual stuff. You know - the drug companies don't want to cure cancer, no way. If people would just follow Doctor So-And-So's Miracle Diet, they'd be fine. According to these folks, all this talk of cancer research is a sham to start with. Of course, the number of such "cures" is beyond counting, and since so many of them claim to cure most everything, you'd think that they can't all be right. But somehow this doesn't seem to faze their adherents, who are often enthusiasts for several broad miracle cures simultaneously.

Comments (33) + TrackBacks (0) | Category: Cancer


COMMENTS

1. Keith Robison on August 29, 2013 8:36 AM writes...

"the history of Medicine is replete with examples of cures obtained years, decades, and even centuries before the mechanism of action was understood for these cures"

Yes, but those low-hanging fruit are pretty much cleaned out. And, as you point out, there would be a lot of risk involved -- and risk primarily to the patients in the trials.

It's also a curious viewpoint to take given how many significant successes there have been in recent years in specific cancers, successes driven by gaining an understanding of the underlying disease. Gleevec would be the poster child, but Rituxan would be another. Neither had any shot of coming out of a "throw compounds at the wall and see what sticks" approach; that certainly won't work for biologics.

Of course, there is the flip side where drugs such as Velcade came from great basic research, but the specific indications for those drugs came primarily through lots of Phase I trials, many unsuccessful.

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2. Calvin on August 29, 2013 8:40 AM writes...

Read some of the comments.....

"If you claimed to have a cure for cancer, you would be jailed. (It is illegal to claim a cure for cancer.)"

That is definitely one of the best comments I've read recently, if not ever.

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3. alig on August 29, 2013 8:57 AM writes...

If you claim you have A cure for All cancers, you probably are a fraudster and should be jailed. However, there are already many cures for many cancers. Just like there are many cures for many bacterial infections. The problem lies in that we can't cure a high enough percentage of cancers yet.

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4. John Wayne on August 29, 2013 8:59 AM writes...

I thought that the original article suggested a fairly insightful view of both current academia and current industrial drug discovery. Science is becoming more focused on Powerpoint slides and less focused on testing hypotheses in the lab. This isn't good for patients, and it isn't good for most scientists (it is good for the charismatic).

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5. Anonymous on August 29, 2013 9:05 AM writes...

One day the only things the human race will actually produce are Powerpoint slides and carbon dioxide.

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6. Anon on August 29, 2013 9:08 AM writes...

Once again...this all can be traced back to an over supply of basic researchers.

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7. Anon on August 29, 2013 9:17 AM writes...

I just want to elaborate. If you increase basic science funding investigators will just hire more grad students and import more postdocs.
If you are looking for new and better ideas, I believe this goes back to what we all mention in every other posting [yet what still can't be heard by academics, or management of big-pharma] which is to allow for a career to exist for these people and let them do what they were trained to do.
Visionaries tend to be able to see whats coming, and a bright kid isn't going to spend 4 years undergrad, 6 years on a PhD just to land in a $39k postdoc. Those students will do the "smart" thing and trend towards fields with better pay and job security. Until the supply is controlled (both domestic production and importation) nothing will every change. Period.

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8. JAB on August 29, 2013 9:32 AM writes...

Well, right now the cancer money is shrinking, and rapidly, thanks to the sequester. It seems that NIH grants breed more graduate students and postdocs in a Malthusian expansion. If there are no academic positions for them to go to, wouldn't it be better to limit the number of students and spend more of the available money on technicians and other permanent lab researchers?

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9. Toad on August 29, 2013 9:34 AM writes...

Derek,

You need a link for The Atlantic article.

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10. bank on August 29, 2013 9:46 AM writes...

@Keith Robison,

You state that the "low hanging fruit are pretty much cleaned out"; what would these fruit be? Are they modern forms of older therapies? If so, it re-emphasizes the random nature of discovery in biomedicine, as the "low hanging fruit" were themselves discovered by accident.

As to careers, I think the only answer is going to be the one that has a well-established pedigree in famous research labs, i.e. a high barrier to entry followed by a secure career. Though it should not necessarily a high-paying one, maybe on par with similarly qualified people in public service. Grad students should no longer be hired with the sole purpose of exploiting their naivete as to their prospects, and being later fobbed-off by asserting the value of "transferable" skills they acquire. At least 50% of PhD candidates should fail to graduate in order to maintain the value of a PhD.

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11. Derek Lowe on August 29, 2013 9:52 AM writes...

#9 - that I do! Knew I'd forgotten something by the time I got to the end of the post. It's on there now.

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12. Suleman on August 29, 2013 9:53 AM writes...

I think one issue that is very relevant, but very difficult to get right, is choosing exactly which areas of research to fund. As far as I can tell from the way it happens in the UK more successful academics are better at getting further funding for their favourite areas of research based on who they are rather than the merits of working in that area. It means that other areas get neglected, until they are rediscovered 20 years later.

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13. sciencemonkey on August 29, 2013 10:07 AM writes...

I agree that limiting supply of graduating scientists would limit the hyper-competitiveness of the grant application, and allow academics freedom and security to pursue useful research. MDs are an oft-quoted example of the limited supply strategy.

It would also help to create academic positions equivalent to the fairly independent Research Scientist job title you might find in industry, where PhDs are paid a decent salary to be independent bench scientists.

-----

However, I think we need to look at the wider picture. Why does every profession (see also the veterinarian thread on chemjobber) need to limit supply to maintain decent wages? Why can't the economy expand to use talented, technically trained people?

Also on a similar but different note, what do people do when they are replaced by technology? In the industrial revolution I suppose the farmers worked in factories, but I worry this time there will be excess humanity relative to the economy. For example, when we have reliable computer-driven cars in a decade, what do all the people who drive for a living go on to do?

I think it might be a combination of a) high oil prices stifling economic growth, b) corporations who lobby for laws that lead to a large pool of workers with consequently depressed wages, and c) the different time scales of human breeding versus economic change. Assuming people make rational decisions about their ability to support children and their children's future prospects (BIG assumption), it's still quite difficult because the economy can change on a much faster time scale.

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14. Anon on August 29, 2013 10:09 AM writes...

@8 JAB
You are stumbling onto the other side of the problem. If a lab has no money, it is cheaper to hire a grad student than to hire a technician(there is a 10-30k difference). So you bring in more students. If funding is good, the fastest and cheapest way to expand is by hiring grad students and import postdocs.

@10 bank
"i.e. a high barrier to entry followed by a secure career. Though it should not necessarily a high-paying one, maybe on par with similarly qualified people in public service."

Look at this like evolution/selection. The divergent path appears during undergrad. The students with the best grades and who are able to look far enough ahead at career stability/pay are going to trend towards medical/dental/pharmacy as those share the same prerequisites as graduate school. It makes the most sense to have comparable pay to so that salary isn't the influencer, but passion for a given field is.

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15. sciencemonkey on August 29, 2013 10:13 AM writes...

@10 bank:

I agree, based on merit alone 50% of graduate students should not earn a PhD, nor a conciliatory MS, because that degrades the name of excellent people with MS degrees. There really have been some terrible students and postdocs in my academic lab...

Permalink to Comment

16. ScientistSailor on August 29, 2013 10:59 AM writes...

@13 sciencemonkey
For an interesting essay on why the economy can't expand to use the increasing supply of talent, read "The Great Stagnation" by Tyler Cowen ($3.79 Kindle price on Amazon).

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17. Anon on August 29, 2013 11:08 AM writes...

@8 and @14: Plus there are direct incentives for PIs to take on more grad students in the form of reductions in teaching loads. At least, this was the case at my former institution.

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18. simpl on August 29, 2013 11:29 AM writes...

Yes, current economics and business is biased towards protecting your patch, selling small differences as real value, and fleecing the gullible. This is only worth bemoaning because you still have ideals like progress, along with very few others, as in the IT area.
But are we really going backwards on cancer? Pharma is under way to creating a tool-kit for influencing cancer growth - chemicals, antibodies and cell therapies. There is hope, for medics and sufferers, that they will work in better dosing regimes, on other unexpected cancers, they can be usefully combined with each other, they can be used to stop metastasis after surgery, or they can give tissue destruction more purpose.
The small molecules, at least, could even be sold with profit for less.

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19. DrugA on August 29, 2013 11:53 AM writes...

I find it deeply dispiriting to see my friends in academic biomedical science spending 80% or more of their time writing grant applications with little or no chance of being funded. Some selection process is surely needed, but when only the top 3% of applications gets funded (sometimes a bit more sometimes - bizarrely - none at all, because the money goes away after the RFP is posted), the system isn't working. Surely, we'd be better off with fewer scientists doing more net science.

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20. Nixon on August 29, 2013 12:06 PM writes...

What exactly constitutes "victory" in the "war on cancer"?

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21. Anonymous on August 29, 2013 12:28 PM writes...

Cure cancer and then everyone can live longer to take even more state pension and then die of much more expensive diseases like AD which require years of full time care and lost productivity instead. As a result, total health costs would quickly exceed GDP. Yet it's interesting that funding for cancer research dwarfs that of AD research. Cancer is good, at least you die quick and cheap.

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22. Doug Steinman on August 29, 2013 12:50 PM writes...

Funding issues are a universal problem in all areas of academic research, not just in cancer. Let's not forget that one of the problems is the amount that the institutions take off the top of research grants as "overhead". Maybe we should consider how to address that problem as that would mean more money would go to the research being funded. We should also consider that we are not able to effectively treat many cancers for the same reason that we can't effectively treat Alzheimer's; we just don't know enough about the cellular biology of the diseased cells. Maybe that will change with additional research but the solutions will not come quickly and will, most likely, require a great deal of time and money spent on learning enough about these disease states and others to know how to effectively treat them. It is true that asking the right questions is critical to discovering the answers that will solve some of these problems and that changing the way academic funding is done may address that but that will be a very tough fight.

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23. Doctor Memory on August 29, 2013 1:33 PM writes...

@21 you apparently have extremely idiosyncratic definitions of "quick" and "cheap".

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24. Anonymous on August 29, 2013 1:39 PM writes...

@23: Try comparing costs and time with AD!

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25. MTK on August 29, 2013 3:56 PM writes...

@16,

"@13 sciencemonkey
For a gigantic tome on why the economy can't expand to use the increasing supply of talent, read "Das Kapital" by Karl Marx (free at your local library)."

FIFY

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26. Anonymous on August 29, 2013 4:10 PM writes...

If talent can't create more value for the economy/society than it destroys, then is it really talent?

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27. Guest12 on August 29, 2013 5:58 PM writes...

Nearly 20% are thinking of leaving:
http://www.salon.com/2013/08/29/nearly_a_fifth_of_scientists_are_considering_abandoning_the_u_s/

Permalink to Comment

28. Cellbio on August 29, 2013 6:41 PM writes...

@Doug#22

Overhead is a problem, imo, not because it dilutes the impact on research, but because overhead is the economic driver that makes this whole bubble economy spin out of control. No longer is education at large public research universities the focus of top administrators, nor is the ideal of creating benefit for the public at large. It is, in large part, creating the infrastructure to attract more funding, more overhead. To fuel that, in addition to buildings paid for with bonds and donor money, one also needs a work force within that economy. At the scale PhD's are produced, PhD's are not trained for known job markets or social need (despite some who promote scientists shortages), they are the workforce for the economy that keeps a PI employed and his/her University's overhead funds flowing.

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29. srp on August 29, 2013 7:15 PM writes...

Derek points out that laypeople give money to cancer research because they can't think of any other way to promote the cause. How about volunteering for Phase I trials?

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30. Kendrik on August 30, 2013 9:46 AM writes...

The problem why the war on cancer is a near total calamity is much more basic than stated here. The dominance of a healthcare model, i.e., allopathy, that has become more and more commercialized (particularly since around 1980), focusing only on treating -not curing- diseases with those types of products and services of the funding sources (i.e., allopathic entities such as the pharmaceutical companies).

The commercialized medical industry's theories of cancer and cancer progression are deeply unscientific, rooted in flawed research and staunchly perpetuated by dogma and defended by politics (read "The Mammogram Myth: The Independent Investigation Of Mammography The Medical Profession Doesn't Want You To Know About" by Rolf Hefti. Also see http://www.TheMammogramMyth.com). It's an accurate reflection of what is happening in the political arena.

Giving more money to "science", or breast cancer awareness organizations, or democrats/republicans, is just feeding the monster.

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31. Nuclear Option on August 31, 2013 7:33 AM writes...

There is much truth to this article from the perspective of my work as an academic cancer researcher. Like many academic labs we provide mechanistic granularity to pathways of interest in cancer biology, and like many pharma companies we discover and characterize new chemical antagonists to these pathway components. In truth both activities are  steadily besieged by the distractions of conference travel, book chapters, committee meetings, institutional meetings, meetings to plan meetings, and grant writing which when successful brings  progress report writing, study section responsibilities and fundraising activities for foundations. Admixed also are the vital activities of patient care, thesis meetings, group meetings and time with family. Grant horizons are perhaps two years longer than discovery horizons in pharma, but of course limited by 1/10th the level of funding. Still, we rally together with like-minded colleagues and march these new technologies into the literature and clinic. I remain optimistic, and necessity breeds invention, but the climate of bureaucracy is threatening to innovation, that which is most immediately needed - at the risk of being jailed - to cure this disease..

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32. gippgig on September 1, 2013 2:34 AM writes...

Instead of trying to get more money for research why not try to make research cheaper? For example, some researchers recently figured out how to make equipment for an optics lab using a 3D printer for a tiny fraction of the cost of commercial equipment (www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059840).
#7: "Those students will do the "smart" thing and trend towards fields with better pay and job security." It's not the smart thing if you're more interested in making discoveries than making money. If your main concern is money you have no business being in scientific research in the first place (try scientific development instead).
#13: Look at what happened when agriculture was developed. Up until then most people produced their own food. Once agriculture was established a fraction of the population could produce all the food that was needed. It no longer made sense for most people to produce their own food - so they stopped doing it. We have reached a similar point - only a fraction of the population needs to produce wealth to produce all the wealth we need. Just as the idea that everyone should produce their own food was abandoned we need to abandon the idea that everyone should support themselves. There are plenty of other worthwhile things to do such as creating, helping others, & discovering (research). One long-term solution is for people to own shares of businesses that would generate wealth for them (which would still work fine even if robots & artificial intelligence eliminated the need for 99% of the population to work). The problem is that people haven't realized - or simply won't accept - this and haven't planned accordingly, spending their money on extravagances rather than investing it for the future.
#29: Other ways they could contribute: join distributed computing projects, play Foldit, help out in a lab (surely labs could use a few unskilled or minimally trained helpers), donate supplies (anybody in the Bethesda, Md. area want some free paper?).

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33. Anonymous on September 6, 2013 12:05 PM writes...

I do agree with Derek's point of view. Money cannot solely be the reason behind pending invention of drug for cancer treatment. Instead of trying to always complaining on it, why not we find a better way to lower down the costs on the research and development. Anyway this article diverted many people mind from looking at this issue from one side only.

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