"Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration."
The keywords are "experiment was too novel, and thus, too risky for consideration". Unfortunately, this seems to have become the rule rather than the exception in scientific research. All the young folks (pre-tenure) are on a treadmill to get funding and publish something in the top journals/conferences. I wish there was some accountability in the system ... the geniuses who rejected funding this research will go about completely unaffected.
Several years ago I read an article in Fortune about cancer research. Government funding is extremely conservative. They're happy to pay you to nail down another tiny detail about some kind of cancer, but try an innovative cure and they balk. They also take three years to get the money to you, by which time your research might be obsolete.
When Michael Milken got out of prison, he was diagnosed with prostate cancer, and started a foundation to fight it. He asked researchers for the crazy ideas they really wanted to work on, and got the money to them in three months. In return, he insisted researchers immediately share what they learned. No patents, no waiting for prestigious publication.
According to Fortune, people in the field generally credit Milken's foundation with cutting prostate cancer death rates in half.
"Criminal" is a good qualifier for the way most medical research decision are done. I was once told, out of the blue, by a commercial in the field, that research for a HIV cure was a very low priority given how profitable the tritherapy was.
I've probably got him to thank for still having a stepfather - he was just treated for prostate cancer and it seems to be working. (In his case, they put tiny radioactive beads into the tumor to kill it over six months, which is really pretty damned awesome.)
The problem here is one of sampling bias. You're seeing an example of one "outside the box" idea that worked out of thousands that didn't. The NIH and pharmas are constantly getting pitched on (and funding) ideas for innovative new therapies. The problem is that cancer therapies under development fail at a rate >95% in the clinic. Therefore, most new approaches to cancer treatment turn out to be abject failures. The fact that funding agencies and pharmas passed on this specific one isn't surprising. They just can't fund everything.
The good news is, these guys should have no trouble getting funding now.
This is an important point. Medical innovation can be perilous. I'm reminded of the setbacks for gene therapy in the 1990s. The case of Jesse Gelsinger was emblematic:
Every time I recall this, I mean to lookup whatever became of this guy. Finally did. A bit of a follow-up here:
A test of his protocol, published in 2009, found that Gonzalez's patients died faster than those treated with conventional chemotherapy, and had significantly worse quality of life.
Just to update this since there was so much interest, I looked into the literature a bit more closely.
First off, at the end of the article it says "Supported in part by grants from the National Institutes of Health (K24 CA11787901, 1PN2-EY016586, and R01CA120409), the Alliance for Cancer Gene Therapy, and the Leukemia and Lymphoma Society (7000-02)." So the funding system was working as expected.
It also looks like people have been trying this for a long time and for various reasons it has actually not worked very well. This paper is noteworthy not because they used the HIV modified T-cells. It's noteworthy because people have been banging their heads against this specific brick wall for a long time and coming up empty-handed. The key innovation appears to be the addition of extra machinery that made the T-cells more potent and also the ability for the T-cells to hang around and expand in the patient.
Also, to give people a sense of how much time something like this takes. This specific viral mechanism was tested by the same group in mice first and published in August of 2009 (open access: http://www.nature.com/mt/journal/v17/n8/full/mt200983a.html)
My guess is they balked when the researchers decided to use a modified HIV virus to implant the new genes. If it went badly everyone would point to the HIV and the bad press could be devastating.
Thankfully these researchers were able to take some big risks and prove out the theory in a fairly successful trial.
HIV is used to insert the genes into the white cells in-vitro. They are not inserted in the patient. So I guess the risk of HIV infection is quite small (how small, I have no idea).
The entire pharmaceutical industry is basically going to collapse by the end of 2014 anyway, so it's largely irrelevant. There will be much less funding for everything no matter how promising it is, unless the government steps in and reinvents the entire process. Seems unlikely at this point though:
On the other hand, as research tools are becoming more affordable to smaller institutions and universities, we may witness a shift from big pharma to smaller and more focused independent research.
The article doesn't touch on one aspect of the research likely to have been particularly unpalatable to pharmaceutical companies: Potential cures are bad business.
Of course, there is no conspiracy here. It's just the human tendency to rationalize when money is involved. Imagine you run a pharmaceutical company: Your products save lives, right? You want to be able to continue saving lives, so you have to stay profitable. And to stay profitable, you have to make good investments. Products that are used in long-term treatments are good investments. One-time cures aren't.
I spent 8 years in pharmaceutical industry R&D and this is so ill-informed I feel compelled to refute it every time someone says it. I know it sounds like it makes sense on the surface, but it's just outright false.
I worked in cancer research with some really, really smart people. Every single one of them was sincerely hopeful that the drug they were working on would be a total cure. I know it's hard to believe, but pharma companies are composed of real people who have seen patients, friends, and relatives die of cancer or similar diseases. Researchers want so badly to find a cure for the disease they are working on. The existence of vaccines are proof that when pharma companies can cure something, they do it. I have been in conversations where business factors for a drug were discussed and I can tell you the one thing that was never said was, "Hey guys, make sure it's not an actual cure, or we'll need to kill the project".
Nice to see that not everybody is a greedy asshole :)
A commenter on Slashdot gave another good point on why the industry HAS a reason to develop a cure for cancer:
If any "Big Pharma" company invented a cure for cancer tomorrow, you can bet your ass that they'd be all over it in a heartbeat.
Why? Because, then that company would forever be known as the company that cured cancer. Every new product they make would be a pot of gold. Every ad they put out would be "Muhdikard, a new treatment for erectile dysfunction, from Drugco. We cured cancer.". Every drug company on the face of the planet would kill for that kind of marketing, not to mention the money from selling the cancer cure.
Firstly: You're right; I am ill-informed on this. I haven't any doubt that you or your colleagues had and continue to have strong humanitarian convictions in your work, and I was out of line to speak so broadly.
I recognize that the argument I made earlier is something of an old saw. But you and I both know that businesses on the scale of most pharma companies are not run only by researchers and engineers, and that the explicit reasons for business decisions anywhere often stem from any number of unspoken ones. I don't imagine even the coldest of bean counters ever says "we need to make sure this research doesn't lead to a cure," and I doubt such a black-and-white assessment of a complex R&D process even occurs to them. But incentives are incentives, and humans are masters of rationalization.
I'm heartened to learn that your teams never felt pressure to put business interests ahead of patient interests. I sincerely hope your experience is common.
Thanks for your comments. The pharma industry has a lousy public perception, some of which is quite justified, so it can be hard to separate the reality from the perception.
There is also a practical reason why I can assure you that people are usually swinging for the fences, especially in cancer: most of the time you don't even know if a drug will work, let alone work well. There is no way to predict (with the obvious exception of vaccines which owing to biology are destined to be cures from the beginning) what your drug will really do until it hits the clinic. So there isn't even a mechanism to offer people an incentive to develop a drug someone has to take over and over vs. a cure, especially in cancer. Certainly, there are chronic conditions like diabetes where there is no real "cure" on the horizon because of the biology of the situation. But in the case of cancer, you almost have to try for a total success because you know you're likely to get far, far less than that when you hit the clinic. Because of this problem, one of the bigger issues in pharma is that flawed projects are allowed to linger long after they should have just been scrapped because powerful scientists believed they would work and convinced management to keep funding them despite some of their issues.
Boo! Disagree. JunkDNA gave you a perspective from the Pharmaceutical company side. Here's a perspective from the finance side:
I worked for 2.5 years in a finance firm which specialized primarily in biotech stocks. (We were on the "sell side", meaning our clients were hedge funds and mutual funds, and our product was research reports advising whether to buy or sell the stock of certain biotech companies.)
Without fail, the biggest catalysts for moving the stock price were study results, and the better the results, the bigger the jump. Every company absolutely wants that blockbuster drug that cures a disease.
With CLL, for instance, as in the article, there are a number of treatments, in 1st line and 2nd line after relapse, 3rd line, and so on. And doctors prescribe this one or that one, depending on context and what side effects you can tolerate, etc. If your drug is a complete cure and you can jump straight to first line and everyone prescribes your treatment, then that's a gold mine.
A recent example is Cougar Biotechnology, whose cancer drug abiraterone was so insanely successful the company's stock price rocketed and then was acquired shortly thereafter by Johnson & Johnson.
Lastly, if you finished reading the article, you'd see this part:
"With results for the three patients published Wednesday simultaneously in the New England Journal of Medicine and Science Translational Medicine, money for further studies -- not just in this one type of leukemia, but in other cancers -- will likely pour in from both the government and drug companies."
That's why I think medical research should be funded by the insurance companies.
The main impediment: free-loading companies could take advantage of the companies funding the research. One solution would be to start a patent pool, making their inventions freely available to all the companies participating in funding the research.
A senator (Bernie Frank maybe, not sure) recently introduced a bill to tax insurance companies and apply the funds for medical research. That'd be another way to fix the freeloader problem, but then you're stuck with the government choosing the research, and it tends to be overly conservative.
Wrong mind set, they could easily charge 100k+ for the treatment and insurance companies would still jump for joy since it's cheaper over the long run.
Surely a cure to an otherwise generally terminal illness is worth 100k though. I know I would be grateful to pay such a price, the alternative seems to be no cure, and eventual death.
I'm sure there are tons of people who would be grateful to be in a position to be able to pay such a price.
I think a company would be hard-pressed to have a pill that cures cancer -- letting millions die each year, because the pill costs $100k. I think there's a non-trivial possibility that the gov't would take that drug for its own uses.
No they wouldn't there are a lot of procedures that cost more than a 100k (any transplant, open heart, high end implants are more). Really the government and insurance companies would save a fortune if the cure cost between 100k - 200k.
Apparently when the negotiations broke down (Brazil wanted the same rate as Thailand but Merck wanted to charge them more), Brazil declared sovereign property rights in the good of it's citizens.
This was for Cipro for Anthrax. Bayer, at the last minute, gave in to some pricing concessions. There's also been talks about it happening during some H1N1 and avian flu scares.
A $100k pill that cures cancer? I'm not saying it would be taken by the gov't, but I think you'd have to seriously consider it.
Quick research tells me that there ar about 45,000 cases of leukemia in the US per year. Equally quick research tells me traditional treatment easily comes to $400k, and comes with terrible side effects.
So, if you had a fairly reliable (at achieving remission) injection, and especially one without the terrible side effects, you should be able to charge at least $400k.
Please inform me which pharmaceutical company would not like an $18 billion/year revenue stream.
The problem is that this phenomenon (funding research where you know there is a good probability it will work before you even start) is not limited to medical research, it can be found even in fields where there are no commercial interests involved.
Opinions differ as to why that is - I personally suspect the grants system that is used for funding science.
One thing I was left wondering about and maybe someone here can shed some more light on this, what happens to the supposedly enormous amount of "serial killer" white blood cells after they're done with the cancer cells? Do they function normally, until a new "infection" comes, basically serving as a permanent leukemia antidote?
(I hope no one is offended by my quite flimsy grasp of medicine and the human body)
According to the New England Journal of Medicine article, those white blood cells are still targeting and killing the B-cells. From my (non-biologist) reading of the article, they crafted a virus which targeted all B-cell, of which, some were lukemia. Apparently there are treatments to restore B-cells in a person, so the article seemed to imply once the T-cell count (the "serial killer" white blood cells) went down, they would treat him to restore his normal B-cell count.
Like you, I'm unclear on what exactly the side-effects are here. If they boost the B-cell count in the patient, do they risk re-introducing lukemia? Are these "serial killer" white blood cells a general immunosupressant? There was a part of the article about a developed resistance in the B-cells that I didn't understand.
Either way pretty amazing, and it sounds like while the patient had the worst flu of his life for five days, it's way better than chemo
"More good news stems from the fact that the modified cells remain in the body and have been seen to reactivate and kill new cancer cells as long as 12 months after they were first injected."
Came up with an idea (edit: wrote in generalization, took to much credit, sorry, didn't want to bore everyone with details) 10 years ago, everybody thought I was crazy for wanting to inject HIV into people. The idea I had was to treat the human immune system like a computers anti-virus software and upload treatments using the HIV virus. Didn't think the FDA would even allow something like this for at least another decade. Really believe HIV is the key to ending disease in humans, even possibly aging.
Wonder how they handled its affinity for mutation? That was the big hurtle.
EDIT: xd corrected me. They did it in vitro. Which explains how they got around the FDA.
This idea has been around a hell of a lot longer than 10 years. Looks like you were late to the party. There also isn't a particular need to use HIV to do this in the general case either, the purpose of virii in general is to inject DNA into existing organisms.
Completely right. Didn't want to go into detail meant the anti-virus theory and why. I'll try to explain. You want to use HIV because of a few unique properties specifically the fact that you can split the gene material used in replication from the infection machinery. In addition it actual has most of the genes in place to do all the work you need since it's so well mapped and studied modifying the structure becomes much easier. My idea was to limit the insertion to only the original material (like a seedless watermelon) to remove the danger. And have virus upload the sequence needed to produce the antibodies or receptors required to target the foreign object. Then have the body kill it itself.
You had an idea, not a full theory. The gap between "Hey, maybe we can piggy-back on a virus to specialized white blood cells to target particular kinds of cells" and an actual treatment is enormous.
They're not injecting HIV into people. As far as I can make out, they are using a modified version of HIV to modify white blood cells which they then inject into the patient.
Granted, the odds of this translating to a plague of aggressive carnivores rather than dead quadraplegics are low, but if I were a novelist, I'd sequester myself in the attic and bang out a best-seller.
You appear to be confused. They're not talking about the cancer-destroying t-cells, they're talking about the DRACOs drug suite to kill viruses. Two totally different stories.
What is masked by some of the hoopla around cancer is exactly this, gene therapy is advancing, and it can rewrite your DNA in-situ. This meets pretty much every definition of the term 'game changing' from atheletes who want the Sherpa gene for making more red blood cells to a host of genetic disorders that lead to a myriad of complications in the patients life. Some resarch has been marred by some very serious negative outcomes [1] but if it can be mastered, the world will not be the same, for any of us.
It's important to note that they didn't release HIV into the patient in vivo. They infected T-Cells in vitro that then multiplied in the patient's body. By doing it in a test tube they can also throw out the bad results. Gene therapy isn't going to work quite yet inside of a body, but if you can grow replacement organs from scratch, you can definitely get somewhere.
Here's what I don't get about your hypothesis... very rarely is there a single gene for specific trait in humans, right? Usually it's a combination of genes, and often the trait produced is the effect of their impact on embryology.
So wouldn't it be impossible (and possibly extremely dangerous) to attempt to change many traits by performing in-situ DNA rewrites?
As I understand the current research, its focussed on 'fixing' problems where one link of the chain is broken. So when a specific set of enzymes are missing (think lactose intolerance) or immunodeficiencies.
Wholesale rewriting chunks of DNA would, as far as I can tell, likely kill the patient. That being said, the potential gain for some to have larger changes to their DNA will no doubt compel someone to try it. A biologist that gave a tech talk at Google on the technology said he had received calls from althetic trainers asking about how his work might be applied to other areas. He was convinced that there was already some efforts at using gene therapy to 'improve' some athletes capabilities.
has this method of cancer fighting been only applied to leukemia patients or could it work for other types of cancer as well? since T-cells reach almost every part of the body, couldn't they be reprogrammed to kill some other cells apart from carcinogenic white blood cells?
I love how they didn't get any funding. If the government stopped wasting it's money by funding a needless war, and actually put that money to good use in research and education... maybe America could be a leader in innovation once more.
Great outcomes for those patients, but it has to go >3 patients, and survival >5 years before people get worked up. This is a difficult disease and people will get hyped up quickly.
You can expect to live for a decade or two at more or less your current lifestyle until near the very end, while with aggressive forms of cancer we're talking more about months of extreme pain and suffering.
If you (a) use protection and (b) are taking medicine as prescribed, however, even the risk of infecting someone else isn't that high. Your viral load remains very low; I remember a study in Switzerland that suggested that two HIV-discordant monogamous partners engaging in anal sex aren't at significant risk of seroconversion even without a condom, if the HIV-positive partner uses his drugs at prescribed and there aren't compounding factors like STDs. Which isn't to say it's a good idea.
It's definitely a trade I'd make in a second, though. Then again, I've seen people waste away from leukemia and not from AIDS, so my perspective is admittedly skewed.
Edited to add: that study is most definitely not a license to have unprotected sex with someone who has HIV. Just to be clear.
the Nature has perfected the viruses as effective delivery system of genetic material ("DNA patches") into cells. We just need to produce correctly working "patches". Another example:
I haven't studied the details of the vector they used, but as a general comment HIV is a very well-understood virus, so removing its potential to infect a human should be easy to do in theory. Practice is another matter, since molecular biology is quite messy.
Wasn't UPenn banned from receiving federal funding for gene therapy research after the whole Jesse Gelsinger controversy in the late 90s? How did they receive funding for this?
Also, 3 patients isn't statistically significant. Having this in the national media is going to cause mass confusion in the general public. There needs to be many more studies on this therapy before it's actually used as a treatment.
For this particular study the numbers are fantastic, but there is no indication that this therapy will actually cure any other CLL patients. Just last year the NCI estimated there would be 15,000 CLL new patients. A favorable result with just 3 patients isn't a big enough percentage to call this new treatment anything but experimental.
However, that wasn't my original point. This therapy is obviously at a very early stage. Headlines like this in the lay media are extremely misleading to the general public, because a majority of people will not take the time to read or understand the entirety of the article.
(The distracting leading quote and music has been added by the uploader... but I can't find an alternate clip of this set-up scene that also includes the important cut to 'three years later' at the end.)
My father died of type 2 non hodkins lymphoma in 1997 when I was 17; he was sick for 4 years from two rounds of lymphoma, plus a marrow transplant. Every time I read about advances like this I feel bad about wasting my life building better advertising instead of doing biomed. I just wish biomed paid better wages -- I much more than doubled my income by leaving a wetlab and doing advertising instead. It's a lesson in what our society really values. And now I feel like Steve Yegge.
> It's a lesson in what our society really values.
Not to be a jerk, but it's about what _you_ value. If you value money (or lifestyle, or whatever drew you to advertising) over whatever you were doing previously, you've had your way. If you don't, you have the choice to go back.
Don't feel bad about not working in the right industry; just remember that there are thousands of ways to help progress the state of the art, raise money or awareness for those progressing the state of the art, or even just helping people and their families dealing with cancers.
I don't work in a philanthropic job. I would like to, but value the financial stability of something further removed from pure altruism.
Characterizing not wanting a lower middle class lifestyle as wanting "money or lifestyle [sic]" is ridiculous. Working in a wetlab is essentially me making a $80K annual donation to charity, and amongst other things, would turn my student loans from a minor nuisance into a major expenditure. If society actually valued medical and cancer treatments instead of mouthing the words (which is free), there wouldn't be disparities like that, and working in a wetlab wouldn't be a major life sacrifice.
In practice, we spend $31B or so on the NIH [1], but we have $170B in fiscal year 2010 [2] for Iraq and Afghanistan, plus all the tail costs involved.
You've implicitly dismissed the most likely case: there is an abundance of biology / chemistry graduates willing to work in a wetlab to help cure cancer. Supply & demand of skilled labor is a much more likely cause (ie: highly correlated) than what "society actually valued".
And, by the way, you have not refuted grandparent at all. Much on the contrary, you have only ratified that you have chosen money and lifestyle over working on something you believe in. I don't think gp was judging you for that, only saying that was indeed your choice.
> And, by the way, you have not refuted grandparent at all. Much on the contrary, you have only ratified that you have chosen money and lifestyle over working on something you believe in.
The two aren't incompatible. He chose the money. If society truly valued medical research, he wouldn't have had to make that choice -- the money would be in medical research.
I worked in the biomed industry as a research chemist and I can tell that there are plenty of pharma companies that would love to bring any profitable drug to market. Nobody is going to sit on a working cure. Drug research just happens to be really, really hard, with plenty of opportunities to fail right up to the last step with billions up in smoke.
I am normally not one to bemoan downvoting (I have enough karma that the occasional misstep doesn't really hurt me, and meta discussion is something I also don't want cluttering up HNN) but this one has me stymied at -3.
It seems patently obvious to me that the structure of our pharmaceutical system encourages maintenance doses over cures, and I'm not sure what about that would provoke at least four people to take action not to see it.
The problem with trying to cure most diseases is it's hard, not unprofitable. Most drugs are closer to replacing the oil early which can prolong the life of an engine, it's not as good as a refit but it's a lot simpler. Take diabetes, a cure requires you to fix any of a huge number of possible breakdowns in a wide range of systems; treatment requires administering a single chemical based on glucose levels. Which do you think is harder? Shure, in 100 years we might be able to repair someone’s DNA with minimal side effects based on what’s broken but that’s a long way off.
PS: People talk about drug companies funding research, but mostly they just do refinements and late stage clinical trials. They have minimal impact on the type of research that actually discovers how things work or the basic ideas for how to fix things and if a cure for a major ailment was possible they would jump on even a modest cash cow.
Granted, insulin is a great solution that works well enough to save a lot of pain, and diabetes is a complex condition. I'm not saying maintenance doses are always wrong - nothing is ever always wrong. I'm saying maintenance doses are profitable, and there's little incentive to look farther, unless you're just one of those nuts who can't help it. The nuts end up dragging the rest of us along, usually - so in the end, we end up muddling through. And you clearly can't make it a policy to fund all the nuts, because most of them are, well, they're nuts.
I remain convinced that funds could be allocated somewhat better. In this as in so very many other things.
Reminds me of the Chris Rock skit. The money is in the medicine, not the cure.
I'm generalizing, but It seems as if institutions who have made a living researching treatments to major diseases don't seem that interested in cures. That could threaten their existence. So they put their money in providing hospital services instead of research. They can't get government money for research grants if their idea for research seems too unorthodox.
In the end, it's about protecting jobs and finding a way for you to live longer with the disease.
Well, you don't even have to be cynical (although, having worked years on contract at Eli Lilly, I'm pretty cynical). All you have to do is look at the way the FDA is structured to see that you have to generate a lot of money for any new drug or technique just to be able to pay for its approval. The only way you can do that reliably is by always shooting for the maintenance dose of $300 a month from every patient. A one-time shot just isn't going to pass the math test.
As is always the refrain, the system is broken - if what you want is cures instead of a large and lucrative pharmaceutical industry.
> I just wish biomed paid better wages -- I much more than doubled my income by leaving a wetlab and doing advertising instead. It's a lesson in what our society really values.
This bothers me greatly.
I don't want to threadjack, but are any HN'ers aware of discussion elsewhere about what concerned members of society who do value biomed progress more strongly than most, but who don't have Milken-level money might be able to do to promote faster progress?
I'd be very interested in exploring how YC-like entrepreneurial energy could be unleashed on improving human health, and would be willing to chip in.
In short big philanthropy needs a component that looks a lot like the venture capital industry, and doesn't currently have it. Lots of smaller, big risk, potentially game changing bets rather than stultifying into safe big-budget, incremental institutional irrelevance.
In this case, for example, this research was rescued from years further of oblivion by a funding source that was willing to take a risk.
Much thinking has taken place on this. You might look at some of Aubrey de Grey's early publications on the triangular log jam for example:
Product cycle is much slower in the biomed industry and much more expensive. Potential financial gains are high, but risk is also very high. Even getting started in this industry means a hefty investment is necessary.
In short, not really suitable for a YC-like incubator.
At least not at this point.
I did join a stem cell related company from their beginnings. It was cool to see it grow thinking I was doing good, until I realized at least in my case it was more about making the owners money rather than finding cures for these kind of diseases.
Quitting the day job and switching to biomed maybe could help, but I believe instead there's a need to start something more radical rather than being +1 cog.
I don't think your conclusion about society's values necessarily follows. In a society that valued biomed more, you'd have to pay the same candidate a higher salary to get them to work in advertising.
Exactly, a perfect example of this is how society values cleaning ladies much more highly than brain surgeons or CEOs.
Usually you have to pay brain surgeons and CEOs orders of magnitude more money to take those jobs, when normally they might prefer to live off the glory of cleaning up after slobs.
"Both the National Cancer Institute and several pharmaceutical companies declined to pay for the research. Neither applicants nor funders discuss the reasons an application is turned down. But good guesses are the general shortage of funds and the concept tried in this experiment was too novel and, thus, too risky for consideration."
The keywords are "experiment was too novel, and thus, too risky for consideration". Unfortunately, this seems to have become the rule rather than the exception in scientific research. All the young folks (pre-tenure) are on a treadmill to get funding and publish something in the top journals/conferences. I wish there was some accountability in the system ... the geniuses who rejected funding this research will go about completely unaffected.