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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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February 23, 2012

Remember When We Were Going to Eliminate Deaths from Cancer?

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Posted by Derek

When I mentioned former FDA commissioner Andy Eschenbach the other day, I alluded to some other things about his approach that have bothered me. I thought I should follow up on that, because he's definitely not the only one. You may or may not remember this business from 2003, where Eschenbach wanted to set a goal for the National Cancer Institute to "eliminate death and suffering" from cancer by 2015. Here's what Science had to say at the time:

The nation's cancer chief, National Cancer Institute (NCI) director Andrew von Eschenbach, has announced a startling new goal in the battle against cancer. His institute intends to “eliminate death and suffering” from the disease by 2015. The cancer research community is abuzz over the announcement. Some say that however well intended, the goal is clearly impossible to reach and will undermine the director's credibility.

Von Eschenbach, who has headed the $4.6 billion NCI for a year, announced the 2015 target on 11 February to his National Cancer Advisory Board. He told board members that he did “not say that we could eliminate cancer.” Rather, he continued, his goal is to “eliminate suffering and death due to this disease.” NCI is working on a strategy to do that by discovering “all the relevant mechanisms” of cancer, developing interventions, and getting treatments to patients.

We have three years to go on that deadline, and it's safe to say that we're not going to make it. And that's not because we failed to follow Eschenbach's plan, because saying that you're going to figure out everything is not a plan.

Now, I'm actually kind of an optimistic person, or so I'm told. But I'm not optimistic enough to think that we can eliminate deaths from cancer any time soon, because, well, because I've worked on drugs that have attempted to do so. As has been detailed several times here (and many times elsewhere), cancer isn't one disease. It's a constellation of thousands of diseases, all of which end up by showing uncontrolled cell growth. Calling cancer a disease is like calling headache a disease.

But I'm operating on a different time scale from Eschenbach. Here he is in 2006, in The Lancet:

“Think of it”, von Eschenbach says, “for thousands of years we have dealt with cancer working only with what we could see with our eyes and feel with our fingers, then for a 100 years we've dealt with cancer with what we could see under a microscope. Now, we have gone in 10 years to a completely different level.” This new science “is going to change how we think, it's going to change how we approach things; it's going to change everything.”

. . .He points to the example of testicular cancer. The development of treatments for this cancer was a great success, von Eschenbach says, but one that “took decades of trial and error, one trial after another, after another, after another”. That hit-and-miss approach is no longer necessary, von Eschenbach says. Now, if 10% of patients responded to a treatment, he says, “you take the tools of genomics and go back, reverse engineer it, and ask: what was different about that 10%? Well, they had an EGF [epidermal growth factor] receptor mutation, ah ha!”

Ah ha, indeed. Here's more in a similar vein. The thing is, I don't disagree with this in principle. I disagree on the scale. No one, I think, knows how to eliminate deaths from cancer other than the way we're doing it now: detailed investigation of all sorts of cancers, all sorts of cellular pathways, and all sorts of therapies directed at them. Which is all a lot of work, and takes a lot of time (and a lot of money, too, of course). It also leads to a huge array of dead ends, disappointments, and a seemingly endless supply of "Hmm, that was more complicated than we thought" moments. I don't see that changing any time soon. I'm optimistic enough to think that there is a bottom to this ocean, that it's of finite size and everything in it is, in principle, comprehensible. But it's big. It's really, really big.

There are people who defend goal statements like Eschenbach's. Such things force us to aim high, they say, they focus attention on the problem and give us a sense of urgency. Taken too far, though, this point of view leads to the fallacy that what's important is to care a lot - or perhaps to be seen to care a lot. But the physical world doesn't care if we care. It yields up its secrets to those who are smart and persistent, not to the people with the best slogans.

Comments (32) + TrackBacks (0) | Category: Cancer


COMMENTS

1. Anatoly on February 23, 2012 9:36 AM writes...

Why stop at death and suffering from cancer? Lets eliminate all death and suffering! 8-)

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2. Anonymous Academic on February 23, 2012 10:08 AM writes...

My big problem with these statements is that they can lead to unrealistic expectations from the general public about what the NIH (and scientific research in general) can accomplish. If the president of a big pharmaceutical company bragged to stockholders that his company was going to have a universal psychiatric cure in 12 years, but couldn't deliver, the stockholders would not be happy. Why should we think that taxpayers are any different? As someone who effectively depends on the NIH, I'd prefer not to mislead people about what is and isn't possible, lest they start to wonder what their $30 billion per year is being spent on. (Telling them that it would take more like $300 billion/year to actually have any chance of stopping cancer deaths in a decade - if it's even possible, which I doubt - isn't a good answer.)

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3. libfree on February 23, 2012 10:11 AM writes...

What about the Leukemia treatment that we heard about last year that was so successful? As a layman, I understand it to be leveraging the immune system to cure the cancer? I'd appreciate hearing what you think about it.

http://www.msnbc.msn.com/id/44090512/ns/health-cancer/t/new-leukemia-treatment-exceeds-wildest-expectations/

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4. Anonymous on February 23, 2012 10:24 AM writes...

I was just reading Doonesbury.com and the video of the day is about a high school girl who developed a cure for cancer. The video doesn't tell what cancer and it looks more like a delivery mechanism than an actual cure, but hey, it works great in mice!

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5. luysii on February 23, 2012 10:52 AM writes...

Like #2 (Anonymous Academic) I used to worry about the public being turned off by the endlessly exaggerated claims with small (but definite) results. I was beginning practice when the "War on Cancer" was initiated (1971). It was part of the hubris of the time -- we put a man on the moon, why shouldn't we be able to cure cancer? The War is now in ripe middle age, with no sign of an end until well after it goes on Medicare.

But, not to worry, the electorate (and more important the legislators and the executive) know that, despite its lack of success, it's the only game in town.

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6. Hap on February 23, 2012 10:53 AM writes...

This sort of statement seems like the scenario in an Onion article making fun of W where he cuts the deficit out of the budget, and about as likely to work. Maybe I'm guiltier of this than others, but I don't thinking making expressions of fantasy and pretending they can be made real is good government policy.

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7. DCRogers on February 23, 2012 10:57 AM writes...

Not ambitious enough. 2015 will be a year *after* 100% of school kids will be proficient in reading and math, according to NCLB.

I'm sick of the low-expectations crowd holding us back!

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8. johnnyboy on February 23, 2012 11:19 AM writes...

von Eschenbach is evidently a 'Big Ideas' guy, and it's Big Ideas guys who get nominated to Big Positions, no matter how disconnected from reality their Big Ideas are. Because let's face it, this is what people want. People who on the contrary are exceedingly efficient managers, steeped in the day to day and entirely cognizant of the limits of what can be realistically achieved, these people don't get to top positions because they are generally seen as "lacking in Vision" by the powers that be, and by the general population too.
But to be fair to von Eschenbach's statement, it should be remembered that this kind of talk was rampant among the cancer community in the early oughts. Research had pointed out variabilities in oncogene mutations that seemed to point to specific vulnerabilities that could be targeted in individual tumors. Couple that with the buzz around genomics at the time, and it's natural that people with 'vision' could speak to a future where cancer would become a manageable chronic disease, like AIDS. It's only later that researchers realized that cancer cells were not necessarily driven just by one mutated oncogene, but by dozens (or hundreds), and that these keep mutating all the time. Reality has a tendency to catch up to wishful thinking...

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9. pete on February 23, 2012 11:20 AM writes...

Yeah and we should have had flying cars by now, too. What's up with that, Detroit!?

But seriously, I'm sometimes a little puzzled that health authorities don't do more to tout the fact that some of the major cancers (lung & colon, in particular) really are in decline, and that changes in behavior, exposure and screening have done a whole lot to reduce their incidence. That, on top of the fact that certain therapy combos have had remarkable effects toward a vast reduction of mortality in cancers: some childhood leukemias, for example.

To me, some more emphasis on the shining victories, along with hard-headed discussion of the complexity of different cancers, is the way to go in rationally engaging the public imagination.

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10. Curious Wavefunction on February 23, 2012 11:29 AM writes...

These kinds of statements astound me, especially in light of our present knowledge regarding cancer. It's not just that cancer is a constellation of diseases, it's also that cancer is an inevitability. If you give your body enough time, the probability of a cell going rogue and causing cancer essentially approaches one. In fact they are now finding out that cancers may even begin in early teens and stay benign and small enough not to be detected for a long time. Any idea of curing cancer in its entirety is a pipe dream. At best we will be able to turn cancer into a chronic disease like heart disease or diabetes which will have to be managed till we die from something else. The bottom line is that we may be successful in evading death, but not in evading cancer and it's time we realize this.

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11. Vader on February 23, 2012 12:11 PM writes...

luysii (@5):

Yes, I remember Nixon's War on Cancer.

Cancer won.

Which hasn't prevented any number of similar foolish attempts to micromanage government-funded research.

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12. Anonymous on February 23, 2012 12:19 PM writes...

The big problem with this statement was that it reinforced the already prevalent idea among academics that von Eschenbach was not too bright. Of course no one really cares what academics think...

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13. dece on February 23, 2012 12:20 PM writes...

This ignorant fool needs to be asked directly how come his assessment was so spectacularly wrong. And no matter the answer he needs to be dismissed from his position as he clearly lost all contact with reality.

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14. Student on February 23, 2012 12:23 PM writes...

"Such things force us to aim high, they say, they focus attention on the problem and give us a sense of urgency."
I strongly disagree. We previously had a model where mechanisms and the like were predominantly discovered in academia, and the private sector took on the drug. It worked in the early years because there were talented people on both sides. Grant money was decent, there wasn't an oversupply of PhDs (so the career wasn't avoided like it is now), and pharma was tackling big markets (that gave them big profits and us a treatment for a significant patient population).
Now both sides have collapses and we are in survival mode. Academics just want to make it to the next grant and pharma managers just want to push into the next clinical phase, both happening regardless of what is best for those suffering.
Personally, I blame 1.Too many PhDs 2.Too much "management" with too much authority

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15. JB on February 23, 2012 12:30 PM writes...

It's the old sprint vs. marathon dichotomy.

Eschenbach thinks the race is a sprint. You carry on like crazy, and get everyone to expend everything they have in an epic, mad dash towards the goal. When the goal is reached, they can collapse in a heap and feel fantastic.

Cancer (and most drug research) isn't a sprint. It's a marathon. You plod forward, sometimes faster, sometimes slower. Occasionally you have to stop running and walk. If you go all out, and expend every bit of energy you have, you will never reach the end of the race. You have to learn to keep going. And ignore the crazies that are championing unrealistic strategies and goals.

I worked for a guy once who would declare "research emergencies." He'd get the lab together and tell us all we had to work 24 hours a day to solve problem X, Y or Z. The first two or three times we would do it. Come in all hours of the day or night, give up vacations and holidays and time with the family - because it was an emergency.

Well, I soon came to realize that there was an unending supply of "emergencies." Every month or two, we would have another meeting. It was just him attempting to inspire us. It did the opposite. We were exhausted, and basic lab maintanence was undone. Our work areas were a mess. Projects that we should have been keeping up with had been abandoned. Emergencies began to look a lot like another name for poor management.

The only people that had any real success in that lab were the ones who ignored the "emergency" and kept plodding along doing the real day-in, day-out lab work.

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16. partial agonist on February 23, 2012 12:33 PM writes...

It's like saying we will eliminate death and suffering from all infections. Lofty goal, but every realist knows that there are an almost limitless number of infectious agents and each treatment treats at most a small subset of infectious diseases.

"Cancer" is as broad a term as "infection" and more daunting in that it is so much harder to target your own cells than a foreign invader.

If the battle is to be won, it is by conquering one genetic form of cancer at a time with one drug (or much more likely one cocktail of drugs) at a time, at affordable costs, with acceptable toxicity.

Overly grandiose unreachable goals only frustrate people that are expecting miracles when miracles were promised. Let's substitute wishing for miracles with a dose of reality, with more reasoned expectations: That for each generation we will add more and more genetic forms of cancer to a list of maladies that are considered survivable, managed conditions. Not a sexy, political, and headline grabbing objective, but rather reasoned, achievable, yet still quite ambitious.

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17. processchemist on February 23, 2012 12:33 PM writes...

"pharma managers just want to push into the next clinical phase"

Maybe a bit naive... the crowd here would say that they just want to push into their next bonus....

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18. Luigi on February 23, 2012 1:58 PM writes...

Derek
You can reuse all these comments in 2025 - substituting Alzheimer's for cancer - when you review the "success" of the Obama (aka King Canute) AD initiative. Now he's fixed the economy and brought peace to the world - AD is a piece of cake.

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19. darwin on February 23, 2012 4:16 PM writes...

johnyboy nailed it. microarray, combinatorial chemistry,microdosing, outsourced R&D etc etc etc...were all going to solve the Rx development ailments. They come and go in 5 year increments, just like the executive mgmt that embraces it-wonder if that is serendipidty?

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20. dearieme on February 23, 2012 6:44 PM writes...

von Eschenbach: fool or knave?

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21. dearieme on February 23, 2012 6:58 PM writes...

"It yields up its secrets to those who are smart and persistent...": smart, persistent and lucky. The latter is out of our hands.

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22. LJStewartTweet on February 23, 2012 9:40 PM writes...

Derek. How do you find so much time to do such a cool blog and keep a job at Vertex?

Ever since the NIH announced they would "Sequence the Human Genome" and actually did it, you see NIH officials all over the place grabbing for some sort of milestone statement that is meant to be achievable. But that's the problem... its REALLY HARD to know what is achievable. Bill Gates is famous for saying that people tend to overestimate what is possible in 3 years and to underestimate what is possible in 5 years.

I don't think any of us would have predicted the multitude of technologies from nanopores to microspheres, for sequencing the genome at

Who knows.... maybe the underpinnings of cancer will be figured out in the next 3 years by sequencing the genomes of single cells in tumors? If that happens then what...?

Sincerely,

Lance.

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23. Anonymous on February 23, 2012 10:05 PM writes...

Agree with #22. Nanopore sequencing is a reminder of how fast science fiction becomes reality when a specific technology turns the corner. The question is what will be the technology that transforms drug discovery, and how far away are we. I don't think it's DNA sequencing, but probably something we can't imagine yet.

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24. Anonymous on February 23, 2012 10:17 PM writes...

May be we should go back to where it all begins. Many articles suggest existence of cancerous cells in every human - which takes over and become significant at certain times and we diagnose cancer. May be we should look at how stem cells differentiate and how abnormal cells can form. Rather than turning off some of the overexpressed kinases/enzymes, we should understand the root cause of this over expression.

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25. jellyroll on February 24, 2012 8:06 AM writes...

In a sense, HIV is also thousands of diseases, and with the exception of bone marrow transplantation, nobody's yet been "cured" of HIV through human intervention. Do you consider that effort a failure? Maybe Magic Johnson could offer is opinion?

To me, combination therapies coupled with genomic profiling (and soon, phenotypic profiling) hold the true promise for cancer therapy. If, instead of shooting for 100% killing of each clone that arises, we aim to make cancer a managable, chronic disease, there is hope that Eschenbach's words will be closer to the truth than those of the naysayers and NIH budget cutters.

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26. Agman on February 24, 2012 8:11 AM writes...

My problem with von Eschenbach's statement is that it somehow undermines the effort that the scientific community is doing now - or at least, it can be misinterpreted that way by the public. It's like saying "we're going to wake up and do something about it now cause it can be done, but we just haven't been doing enough." Add to that, some people already believe that the government and the pharma are in cahoots but already has the magic cure. Big pictures can relate you to the public, but too much of it simply undermines the experts' efforts and more importantly, does not tell the whole story about this disease.

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27. anonie on February 24, 2012 8:12 AM writes...

Hype, hype, hype. It's the way of the world. It's the way of human beings. It's one way "big picture" science tends to be done. Big Pharma need such concepts to convince themselves that they have a sustainable future. Biotechs need such verbage to raise funding, to go from nothing to something and (typically) back to nothing while some founders, managers, investors make "Wall Street" quality money pushing paper, but making little scientific or medical progress.

Cancer is not one disease; there is no one origin for the many types. The idea for a single "magic bullet" to cure all is naive. Yet, there has been great progress in some areas for, essentially cures; in others, current treatments have not changed for over 20 years, and are not particularly hopeful.

The ideas for "grand schemes" that will "transform" science are common: combinatorial chemistry, sequencing the human genome, identification of human mutations for targeting therapy, etc, etc. Most of the time, these come down to "grand failures" of the promise, where real progress is made in little identified areas with hard-working, insightful folks woking diligently, quietly, minus too much HYPE. The successes are rare, becoming rarer, but still attract the key goal of money, money, money.

Science & medical research needs to get back to basics, get "back to the future". It's not the way of Westphall, aka Sirtris, even though this grand type of grand scheme made some people a ton of money, but there's still no drugs, nothing truly promising, nothing transformational.

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28. Paul on February 24, 2012 3:15 PM writes...

Why stop at death and suffering from cancer? Lets eliminate all death and suffering! 8-)

Eliminate all death and suffering, and everyone gets a pony!

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29. anon on February 24, 2012 6:07 PM writes...

The good news: By 2015 we will eliminate deaths from cancer. The bad news: In 2014 we will unleash the Zombie virus...

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30. metaphysician on February 25, 2012 10:03 AM writes...

My own unsupported supposition is that the only way we will "cure cancer" is through some form of nanotechnology that can actually identify and destroy cancer cells individually. Of course, we are nowhere near being able to provide a cybernetic immune system, so. . .

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31. Anonymous BMS Researcher on February 26, 2012 10:07 AM writes...

Once upon a time lots of experts thought infectious diseases would be gone by the end of the twentieth century.

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32. Dave on February 27, 2012 5:59 PM writes...

I remember within a couple of years of Nixon's War on Cancer we *knew* it wasn't one disease with one "cure" likely/possible. Saying that in 2003 this had either been forgotten or re-thought is just silly. We knew better in 1980, in 1990 and in 2000, and we know better today.
One good reason that both Politicians and CEOs are old guys is that their 'tenure' is limited (usually). This allows them to make promises that can't be kept to get backing that would otherwise be spent on pet rocks and larger sports stadiums. The cost benefit analysis will virtually always lead to a negative outcome if the actual time and costs are guestimated.
So, unlike Science, should policy be based on an analysis of the facts and hard-headed bean counting or should it be based on values and the willingness of certain sacrificial goats to prevaricate, and ultimately save lives. R&D Directors, if they're doing their jobs, should be
retired or moving on to greener pastures in well under 10 years. A R&D Director (as well as a CEO) hasn't assumed enough risk if they're around 10 years hence. Is it moral to create an 'extremely unlikely' narrative if the result of not doing so will maintain the status quo (in terms of human suffering) while adopting a semi-delusional stance will advance our knowledge and (as perhaps we all here believe) ultimately lead to a better life for the inhabitants of this place. A corallary of this is that the work of private business must be *published* to be justifiable (especially when it is NOT sucessful).
Cancer - Spontaneous remission = immune response is another likely treatment option.

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