New leukemia treatment "exceeded our wildest expectations"

http://www.msnbc.msn.com/id/44090512/

by xd • 15 years ago

289 106 15 years ago

msnbc.msn.com

spottiness• 15 years ago

I voted up your posting, but please use the original title "New leukemia treatment exceeds 'wildest expectations'". The HIV part is pretty irrelevant.

xd3• 15 years ago

Makes sense. Changed.

ryanisinallofus• 15 years ago

To me the use of a harmless, modified HIV was the most interesting part.

MatthewPhillips• 15 years ago

Me too, I'd like to know whether a consensus exists that this HIV is harmless or whether it's just these researchers' opinions.

scarmig2• 15 years ago

Thing is, even if the HIV were as deadly as regular HIV, it'd likely give them a longer lifespan than they'd have without it.

VladRussian• 15 years ago

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:

http://researchnews.osu.edu/archive/smnrescue.htm

iqster• 15 years ago

From the article:

"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.

msie• 15 years ago

NYTimes article on the sad state of National Cancer Institute funding:

http://www.nytimes.com/2009/06/28/health/research/28cancer.h...

Alex3917• 15 years ago

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:

http://www.nytimes.com/2011/03/07/business/07drug.html?_r=1

jobu• 15 years ago

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.

jdkoeck• 15 years ago

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).

AlfaWolph• 15 years ago

Sounds like there is room for some creative approaches funded by entrepreneurs in this area just as has been happening in space exploration.

mortenjorck2• 15 years ago

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.

curt6• 15 years ago

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.

DennisP3• 15 years ago

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.

frossie• 15 years ago

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.

JunkDNA4• 15 years ago

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".

losvedir• 15 years ago

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."

derobert• 15 years ago

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.

curt6• 15 years ago

This is what I wanted to do and the exact reason why I left the biotech industry. They don't like crazy ideas.

DennisP3• 15 years ago

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.

http://money.cnn.com/magazines/fortune/fortune_archive/2004/...

bh42222• 15 years ago

According to Fortune, people in the field generally credit Milken's foundation with cutting prostate cancer death rates in half.

If this is true, it's crime we have not reproduced Milken's strategy for all deadly diseases.

Vivtek5• 15 years ago

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.)

ristretto• 15 years ago

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.

JunkDNA4• 15 years ago

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.

klenwell• 15 years ago

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:

http://en.wikipedia.org/wiki/Jesse_Gelsinger

Speaking of radical therapies, this also reminded me of this New Yorker article I read years ago:

http://www.michaelspecter.com/2001/02/the-outlaw-doctor/

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.

http://en.wikipedia.org/wiki/Nicholas_Gonzalez_%28physician%...

JunkDNA4• 15 years ago

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)

WalterBright• 15 years ago

Breakthroughs usually come from unexpected sources that are not in the mainstream thought. Mainstream funding will only fund mainstream thought.

justinph• 15 years ago

As someone with a genetic disorder, this type of gene therapy is really amazing to read about.

ChuckMcM2• 15 years ago

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.

[1] http://www.medpagetoday.com/Genetics/GeneralGenetics/6275

cal5k• 15 years ago

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?

SapphireSun• 15 years ago

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.

yread• 15 years ago

In the case you linked to the death apparently wasn't caused by the gene therapy http://www.fiercebiotech.com/story/gene-therapy-misses-arthr...

testcock1• 15 years ago

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)

camtarn• 15 years ago

According to this article: http://www.geek.com/articles/geek-pick/hiv-virus-used-to-tur...

"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."

Incredible stuff :)

orblivion• 15 years ago

It almost sounds like a cancer vaccine.

edave• 15 years ago

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

yxhuvud• 15 years ago

Ok, so what has happened after the article was printed the first time?

EDIT: ok, looks like it was just an error by msnbc. It does seem fresh: http://hosted.ap.org/dynamic/stories/U/US_MED_GENE_THERAPY_L...

ComputerGuru• 15 years ago

Original New England Journal of Medicine paper on this subject: http://www.nejm.org/doi/full/10.1056/NEJMoa1103849

curt6• 15 years ago

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.

pavel_lishin2• 15 years ago

This is how zombie movies start.

burgerbrain4• 15 years ago

Zombie movies have also started with re-entering spacecraft and teenage experimentation with the occult. Don't think much of it.

xd3• 15 years ago

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.

curt6• 15 years ago

You're right, missed that part. Was wondering how they got around the FDA. Now it makes complete sense.

burgerbrain4• 15 years ago

https://secure.wikimedia.org/wikipedia/en/wiki/Viral_vector

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.

curt6• 15 years ago

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.

scott_s• 15 years ago

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.

ck22• 15 years ago

So this means it will be $10k a shot in the USA and $500 everywhere else until India clones it?

oxtopus• 15 years ago

$10K? A bargain if you ask me. Especially considering the current cost of Leukemia treatment.

ck22• 15 years ago

So if you cannot afford the $10k you should just die quietly?

tomjen3• 15 years ago

So? It is better, cheaper and safer than the alternative. 10k is an absolute bargin.

But yeah, lots of politicians will complain.

badhairday2• 15 years ago

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.

ellyagg• 15 years ago

Actually, statistical significance has a definition. Not to be snide, but you should look it up before commenting.

badhairday2• 15 years ago

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.

yaix• 15 years ago

>> ...several pharmaceutical companies declined to pay for the research.

Great! No greedy corporation to patent it and sell off the method at overpriced rates.

jcfrei• 15 years ago

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?

earl2• 15 years ago

Wow, that's amazing. I hope the results hold up.

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.

Iv2• 15 years ago

You can help by working in biomed or by giving them money. In your situation the obvious choice is not to change career.

tapp• 15 years ago

> 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.

reasonattlm• 15 years ago

The short term solution is venture philanthropy, something that Peter Thiel has spoken on recently:

http://www.fightaging.org/archives/2010/12/peter-thiel-encou...

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:

http://www.fightaging.org/archives/2004/06/the-curious-case-...

nimrody• 15 years ago

Don't hold your breath...

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.

bdr• 15 years ago

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.

tocomment• 15 years ago

Ewww wierd

zasz• 15 years ago

Uh, typically when society "values" an industry more, they show their appreciation of this value through a higher salary.

huxley• 15 years ago

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.

jonhohle• 15 years ago

> 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.

earl2• 15 years ago

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.

[1] http://www.nih.gov/about/director/budgetrequest/NIH_BIB_0209...

[2] http://www.infoplease.com/ipa/A0933935.html

checoivan• 15 years ago

Similar story here. Mom died of the same disease.

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.

rokhayakebe• 15 years ago

In each of the patients as much as five pounds of cancerous tissue completely melted away

I always thought the entire cancerous tissue would be no more than 1/8 pound.

gojomo• 15 years ago

I am hopeful but also reminded of the opening of 'I am Legend':

http://www.youtube.com/watch?v=8aouT6EMJh8#t=00m21s

(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.)

sweetchar• 15 years ago

This is definitely promising!

whiskyant• 15 years ago

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.

kingkawn• 15 years ago

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.

New leukemia treatment "exceeded our wildest expectations"

Related Stories