Others and I have talked about the lack of publishing negative results. That’s a problem and I agree that bias is a problem. However, Sarewitz’s example of mouse models as an example of bias is horrible and to me disingenuous. There is no question that mouse models aren’t directly related to humans. There are a ton of reasons to use mouse models first. If you look at the FDA requirements for drugs you have to use at least one large species before moving on to human trials. No one expects to get direct data from mice that you can translate to the clinic. However, there are ethical, technical, and economic reasons to do the majority of the basic research using mouse models.
In the commentary by Sarewitz, he mentions the Begley “article” (see below) as evidence that “ironically” industry gets it right. Wrong, here’s my personal example where industry got it wrong and people died.
I’m sick of these commentaries that fan the fire of science is bad. I wish there was a “-1” button.
via Misha Belle
Originally shared by mary Zeman
this is a fantastic essay about bias, and the problems we are seeing now in cause-effect/ correlation-causation type assertions in the literature. worth a read.
“Alarming cracks are starting to penetrate deep into the scientific edifice. They threaten the status of science and its value to society. And they cannot be blamed on the usual suspects — inadequate funding, misconduct, political interference, an illiterate public. Their cause is bias, and the threat they pose goes to the heart of research.
Bias is an inescapable element of research, especially in fields such as biomedicine that strive to isolate cause–effect relations in complex systems in which relevant variables and phenomena can never be fully identified or characterized. Yet if biases were random, then multiple studies ought to converge on truth. Evidence is mounting that biases are not random. A Comment in Nature in March reported that researchers at Amgen were able to confirm the results of only six of 53 ‘landmark studies’ in preclinical cancer research (C. G. Begley & L. M. Ellis Nature 483, 531–533; 2012). For more than a decade, and with increasing frequency, scientists and journalists have pointed out similar problems.”
TL;DR there are no more Bell labs. Academic and government agency research is vital for the advancement of science and technology.
This is a partial dialog with Rajini Rao about my personal experience with industry lead or influenced research vs. academic or government research. (Too lazy to write a fresh post). I left the blood substitute field and learned medical imaging because of the state of research for blood substitutes. Blood substitute is a convenient name, just like artificial blood; it’s not really meant to replace whole blood. The research is really about Hemoglobin Based Oxygen Carriers or HBOC. People tried perfluorocarbons but it’s not allosteric like Hb. So you need a lot of oxygen which can be a fire hazard and it causes other issues. Some of the surfactants cause allergies in some people. So the field’s focus is on Hb. Free Hb falls apart and clogs up the kidneys. So Baxter Healthcare and others tried to cross link Hb to keep it as a tetramer. It turns out, that’s not enough. So people, like me, tried polymerizing Hb. I left the field before finding out if any of the large molecular weight formulations had other problems. I suspect there are still other issues since nothing is on the market yet. Oh, and NIH and DoD basically stopped funding research in this area.
Baxter Healthcare’s Hemassist failed clinical trial. There were several preclinical studies showing that it didn’t really work using the same compound made by the Army. Baxter claimed it was not the same formulation and proceeded with the clinical trial. Several patients died, prompting Baxter to halt the trial prematurely. I suspect that some of the people doing research with Baxter did not publish the negative results prominently enough.
From this review: “The study also criticizes the lack of timely data put forth by the companies and the lack of published studies. Both Hemopure and Polyheme published studies only several years after the completion of their trials. Additionally, unpublished studies render a thorough IRB review of trials difficult. Natanson et al. argue for the timely and complete disclosure of data to the scientific community to avoid exposing the public to unnecessary risks.”
From Rajini Rao: Oh I see, thanks. Interesting problem. It’s more about protein engineering of Hb to make it both efficient and stable as well as nontoxic. The little red cell does a good job of that.
The RBC could be fodder for the intelligent design folks. Well except for sickle cell. I’ve said in other threads when conservatives say that private industry can do better than government funded research such as NIH, NSF, or NASA, just look at Baxter, they are a huge company that dumped millions into to blood substitute research. What happened? People died in clinical trials and we still don’t have a product. The other startups have either failed or have stalled. The difference is private industry has to answer to shareholders and they don’t have to know why or how something works. They just have to find something that works. Academic research aims to find out why and how something works so that we can do it better in the future. So yea, without government funding, we haven’t been able to do better than RBCs.
A less personal example is in today’s Chicago Tribune.
TL;DR The flame retardant industry misused and misquoted research to say that flame retardants have a 15-fold increase in “escape time”. The author of one of the papers says “The fire just laughs at it”.
Great post by Koen De Paus please take the time to read it and re-share.
#scienceeveryday
Originally shared by DaFreak
This post was inspired by Mark Bruce who asked a rather interesting question, If you could share one message that would reach hundreds of millions of people… What would you share? #Words4Mankind
http://goo.gl/gj3U9 – From atoms to molecules to cells to fish, amphibians, reptiles, mammals to primates and here we are, trying to wrap our heads around deep time and the mindblowing change that it has produced.
We have come a very long way indeed… 13,7 billion years is a vast ocean of time, yet it just so happens that we are living in an age of vast importance that has the potential to change the future course of the universe itself. The change that lies behind us was not intelligently designed, the change that lies ahead of us will be. – Beginning of Infinity
We are not the endpoint of evolution and the change from fish to dinosaur to bird should give you an idea of the possibilities. A few million years from now we will be either dead or unrecognizable.
The brain is finite and physical, it’s just a matter of time before we unravel all its mysteries. Biological immortality, reshaping your body, increasing mental capabilities as well as expanding your senses, … Sure this sounds crazy because its hard to imagine but can you honestly say that it sounds crazier than aquatic creatures turning into land walking killers who eventually take to the skies? Our imagination is limited because of our perspective and short lifespans. If we ever want to make it off this rock and survive the harsh conditions of space and other planets, we will have to adapt to survive.
>Nanotechnology, the art of manipulating matter on the atomic scale is already creating one wonder material after another. http://goo.gl/CM72i >Biotechnology is exploding in all directions; modifying old life, creating new life, printing organs, biofuels, … are all here today. http://goo.gl/YOFvw >Information technologies, from the AI we use today, to the software that controls the robotics of tomorrow, the Internet of things, programmable matter, augmented reality, … http://goo.gl/wa4Ae
If you have seen BCI’s (Brain Computer Interfaces) in action then you know that even the near future has tremendous potential for changing our relationship with technology. http://goo.gl/YCrPL
All the sciences will keep advancing, this technological storm will only grow more fierce in the coming centuries. It’s hard to predict what fruits these endeavors will produce in a decade, let alone how advanced these industries will be a 100 years from now, but it’s safe to say that as time goes by, we are only going to learn more and thus produce ever more sophisticated technological wizardry. From fusion to holograms, we are bound to see quite a few groundbreaking developments in our lifetime.
Mankind is stuck in “We ll see whatever comes next” while it’s time to actively start thinking about which future we want to make real. Scientists around the world are breaking new ground every day, expanding knowledge, adding pathways towards different futures. The time has come to actively start looking ahead and state mission goals. Every year technology grows more powerful, if we wait too long it will end up making the choices for us. – http://thehumanproject.us/
Transhumanism is an intellectual and cultural movement that embodies all I ask for. If you have a serious interest in mankind’s future, consider joining this community of thinkers and activists. Defend reason, defend science budgets, stress the importance of education and life long learning, go into debate with people who try to demonize new technologies such as GMOs, donate to science research & education as well as humanitarian projects, … Basically your job is to make the world a better place through the application of science and technology and one of the best ways to do that is to get smart yourself and to increase the amount of educated people on the planet. Invest in 3rd world education! These are some of our best bets to overcome the problems that lie ahead. – http://en.wikipedia.org/wiki/List_of_basic_transhumanism_topics
Make conscious decisions about what to do with your money, do you really need that gossip magazine, plastic toy or other luxury item? You could invest that money in the future, donate or invest in organizations active in education, health, energy or fundamental science research. You can check out sites like http://www.petridish.org/ or http://www.kickstarter.com/ for more information. We waste so much of our attention/brainpower/resources/money on trivial stuff, it’s time to unite the human race under the banner of adventure. If we set ourselves goals we can work together to achieve them.
A Fullo worked in a Fullonica, i.e., a place to launder Roman clothes. From my calendar: In ancient Rome, clothes were laundered in human urine, collected from public latrines. Urine contains ammonia, a natrual whitener. The clothes were then rinsed in water to remove the urine smell. The process was quite effective for cleaning clothes but no much fun for the workers at the laundry, or fullonica, who had to spend the day standing in vats of urine stomping on pee-soaked garments.
Edited to answer Rajini Rao’s question about the bile staining the Roman linens.
The clothes were then hung on a vessel of basket-work (viminea cavea), under which sulphur was placed in order to whiten the cloth; for the ancient fullers appear to have known that many colours were destroyed by the volatile steam of sulphur (Apul. Met. IX. p208, Bipont; Plin. H. N. XXXV.50, 57; Pollux, VII.41). A fine white earth, called Cimolian by Pliny, was often rubbed into the cloth to increase its whiteness (Theophr. Char. 10; Plaut. Aulul. IV.9.6; Plin. H. N. XXXV.57).
I have to dig out my photos of Ostia.
Hopefully appropriate for ScienceSunday if not maybe #scienceeveryday
Here’s a news article, In cancer science, many ‘discoveries’ don’t hold up, about an oncology researcher trying to replicate some preclinical studies before moving forward with potential drug development. (thanks to a post via Branimir Vasilić http://goo.gl/wJyMx)
The news article summarizes a commentary in the journal Nature, titled, Drug development: Raise standards for preclinical cancer research.
Notice the difference in the titles? Here’s a similar discussion where Rajini Rao points out that the news article is titled, Eggs unlimited: an extraordinary tale of scientific discovery vs. Potential Egg Stem Cells Reignite Debate in the journal Science. Similar discussion here: http://goo.gl/Yq1ls
I want to focus on the oncology debate since I do cancer research. However, the comments from the article and me are relevant to many areas of research.
Drug development: Raise standards for preclinical cancer research
C. Glenn Begley & Lee M. Ellis
Nature 483, 531–533 (29 March 2012) doi:10.1038/483531a
Published online 28 March 2012
Here are 5 reasons why oncology research might not be replicated
Endpoints
As the authors point out, endpoints in cancer research can be less quantitative compared to say statin research where cholesterol level is the endpoint. In cancer studies sometimes tumor size is an endpoint. As an imaging person, my field very frequently frowns on this, as a drug can cause tumor swelling, i.e., increase in size, while actually causing tumor cell death. Not everyone has access to expensive imaging equipment or the skills to utilize many imaging modalities. So a lot of cancer drug researchers rely on caliper measurements of the tumor even though most would acknowledge that a tumor is rarely a perfect sphere where one only needs to measure the diameter.
Cutting edge
The authors suggest that some of the irreproducible results could be due to publications that were cutting edge, i.e., a researcher found something completely new or unexpected and published quickly. Also some technology might not be available to Amgen that was used in one of the publications. For example oxygen imaging is available in maybe 3-4 labs in the world.
Competition
Although this may sound terrible to the general public, there have been cases where researchers have omitted a key ingredient or step on a method in order to keep a competitive advantage.
Narrow scope
Begley and Ellis state that the robustness of some results were checked. For example, a publication might get phenomenal results with a particular tumor cell-line or model. When Amgen tried to broaden the scope, e.g., trying a different cell-line or model, the “narrow” promising results turned out to be less robust.
Statistics
Another issue is improper statistics. Quite often scientist haven’t had enough statistical training or do not consult a statistician and therefore use an incorrect method or interpretation.
Conclusion
Interestingly, Begley mentions that the results do not use enough predictive biomarkers (an area of focus for my research which I hope to contribute a solution). The authors’ suggestion to try to show tumor models where there is a negative result is often not possible when a grant funds a particular cancer or model. I totally agree about the selective presentation aspect of their paper. Unfortunately, I don’t think it is uncommon for a publication to have a figure that is stated to be “representative” of all the data, when in fact it was carefully selected as the best example. As some commenters on the online version of this Nature article state, it’s interesting that Begley and Ellis do not list the publications they tried to replicate, thereby limiting the possibility to replicated their article. Transparency?
Edit: I want to be clear that I don’t condone some of these reasons for the lack of reproducible publications. I want to emphasize that there are some reasons why a drug company might not be able to replicate a publication and therefore, there is no need for Reuters or Yahoo news to say the sky is falling for scientist.
