Bench to Bedside
A little background on translational research or medicine, often also called “bench to bedside”. In a post by Max Huijgen (http://goo.gl/VNT3Z) there was a lively discussion about an article in the Telegraph about a seemingly miracle cancer drug sitting in a freezer in Sweden. The article stated that because the scientist had published the work, no pharmaceutical company would touch it, to bring it to market. The idea was, no patent means no profit. A large part of the discussion was about crowdfunding for this frozen drug.
There were three things that Rajini Rao some others, and I tried to explain, about the article and the conversation. First, the cost of getting a drug “from bench to bedside” was grossly underestimated by people suggesting crowdfunding. Here’s the reference Rajini provided regarding the cost of clinical trials (http://goo.gl/YXD55). It can be $28k per patient, just to get started, i.e., Phase I. Which leads to the second issue; lack of understanding what is drug development or discovery. How do you get a compound from idea, to bench work, and finally to market. The last issue is the treatment in the story itself.
The figures below are from an excellent overview of the process of drug development. The example is for cancer research but it is applicable to essentially all drug discovery. So when you hear scientist like me, talk about Phase III clinical trials or INDs, you’ll know what they mean. http://goo.gl/ZF88v
There is also a good, albeit a bit old, review on translation research.
Review: Translational science: past, present, and future by S. H. Curry
BioTechniques 44, 2008 http://goo.gl/B5DV6
In that review, they mention acetaminophen being published and therefore the university couldn’t capitalize on the discovery. If the premise of the Telegraph article were true then acetaminophen should not be in every medicine cabinet today. Clearly the inability to directly patent a compound does not preclude getting it to market. I say directly because acetaminophen was patented at some point.
History of acetaminophen or paracetamol
http://en.wikipedia.org/wiki/Paracetamol#History
Getting back to the Telegraph article and the miracle drug. The Swedish group’s current paper, that has in vivo data (the rest are in vitro) has a 40% survival rate at 100 days, using six mice per group. I also find it curious that the virus is supposed to be targeted but they did not inject it systemically. It was injected directly into the tumor.
J Virol. 2011 Dec;85(24):13114-23.
http://www.ncbi.nlm.nih.gov/pubmed/21957304
Although it is interesting and promising work, I wouldn’t put any money towards it with such a small study. Typically, much more pre-clinical work is done before even thinking of putting a therapeutic agent into humans. As others stated in the thread, there are tons of therapies that cure mice but do not work in humans.
The adenovirus that I have worked on is not targeted per se. It has to be injected directly into the tumor. However, the gene is activated only where you irradiate. The tumor gets a double whamy: radiation and damage from the gene therapy. It was in a phase 1 trial, published here: Clin Cancer Res. 2004 Sep 1;10(17):5747-53. http://www.ncbi.nlm.nih.gov/pubmed/15355902?
I want to emphasize that I have nothing against the research done by the Swedish group. I do have an issue with the Telegraph article. The author talks about his keen investigative skills to find the Swedish group but yet doesn’t do due diligence in finding out the true potential of this therapy. Again, it’s interesting work but a 40% survival rate in mice, in a small single study, is not a miracle drug. The author even mentions the Amgen “investigation” (but gives no reference) as a reason to be cautious. It’s actually a commentary, not a peer-reviewed publication. My commentary about it was posted a while ago, here: http://goo.gl/98HmX? One should be cautious because a lot promising pre-clinical studies don’t pan out, not because of a commentary in reproducibility. Reproducibility is certainly important and is a problem in some areas of research. It’s frustrating that the post follows the same tone as the Telegraph article. However, as a proponent of science, I’m happy that there was a lively discussion and there was an opportunity to educate.
#ScienceEveryday when it isn’t #ScienceSunday
September 8, 2012
Thanks for the excellent commentary and links, Chad Haney .
This reminds me of a story on dichloroacetate as a “cure for cancer” that supposedly could not be patented because it was a common chemical. Oddly, it went viral on the internet, 4 years after the study was published, including here in G+: http://goo.gl/cJxdB
Many of us tried hard to inject some caution and balance to this story on G+, with limited success. Even the New Scientist that originally published the news article had to put out a disclaimer against “false optimism”: http://goo.gl/wg6kF
It’s a tough problem: science needs public exposure and enthusiasm but without the hype. More blogs and interaction by independent and practicing scientists who are not looking to sell a story, are needed, IMO.
September 8, 2012
P.S. I really don’t keep up on patent law, but in our case, we were told we had a year after publication to file a provisional patent, and we did.
September 8, 2012
Fascinating +Chad haney thanks for the detailed post. I saw the original article but just rolled my eyes and moved on. thanks for taking the time to educate.
September 8, 2012
ping Sophie Wrobel
September 8, 2012
I’ll let mary Zeman comment in more detail about patent law. I’m actually working on a Nature.com Soapbox post with Laura Wheeler about how intellectual property can be handled poorly (which was the case with my thesis) and how it can be done correctly and generate valuable revenue for universities. From my experience, you have 1 yr after publishing for a US patent. Most other countries would void any patent once the work is public.
Thank you Rajini Rao and mary Zeman for your comments and support.
September 8, 2012
I will say, while an old chemical may not be available for a patent, a NEW method of using that chemical could be patented (all other issues aside). so, for example, while you can’t get a patent anymore on aspirin, if you discovered aspirin is useful in cleaning car windows, that might be patentable.
September 8, 2012
In the case of the Swedish virus, they could easily (in my opinion) change something slightly, e.g. delivery, encapsulation, etc. and bingo you can patent it.
September 8, 2012
Good point, mary Zeman , thanks.
Hmm..finally, some use for all that expired aspirin sitting in my medicine cabinet 🙂
September 8, 2012
Chad Haney very possible. or change the chirality, or make an interesting substitution or mutation…. the patent process is not the dead end here.
September 8, 2012
When the blockbuster drug omeprazole (“purple pill” used to treat ulcers) finally went over the counter, the company made some minor change and brought out a new patent 🙂
Ref: http://www.cbsnews.com/2100-204_162-559770.html
September 8, 2012
Rajini Rao yep! same with Ambien going to AmbienCR (Controlled release). frustrates some, but that is possible.
September 8, 2012
Lexapro vs. Celexa, just change the chirality.
September 9, 2012
Great, informative post Chad Haney ~ thanks.
My favorite drug development story is Gleevec for CML, and Dr. Brian Drucker. I had the honor of meeting him a long time ago. Excellent physician and great person. From the NYT article:
“Q. Do you see any of that? [the money]
“A. I don’t see a penny, though that never was an issue for me. When I obtained the compound, it was already patented. I wasn’t going to get to test it if I tried to put my mark on it. I wanted to work on it because I thought it was going to be the way to treat C.M.L.”
https://www.nytimes.com/2009/11/03/science/03conv.html?_r=1&pagewanted=all
September 9, 2012
Thanks for the link Mara Rose I’ll check it out tomorrow. It’s getting late here.
September 9, 2012
Good post Chad Haney 🙂
September 9, 2012
Thanks The Final Colony – Author Lacerant Plainer I’m glad some people are finding this useful. The #ScienceSunday team is really all about promoting science and educating people about what we do.
September 9, 2012
I have some Chem and Pharma background, so molecules to market is something I can empathize with:)
There are three other lines of investigation on cancer therapies which sound promising, not least of which is the ENCODE project, the Australian investigation on bee venom and the Oncosec trials (which may end up in the bin even though its been patented).
September 9, 2012
Mind you, I’m not a practicing chemist, but it’s great to see the work you do here 🙂
September 9, 2012
Ironically I have a BS in Chem Eng but the Telegraph article and the example I gave are both viruses.
September 9, 2012
lol yes, I read that 🙂 M.Sc.Tech here.
September 9, 2012
I enjoyed reading this post. It’s really cool that you’re doing this kind of research.
September 9, 2012
Thanks Michael Davis