>> [inaudible conversations] my name is candace i work with some of the events in the store welcome.

i have the couple of things to go over before we get started. rerecording the event this evening and the c-span is here no interruptions would be excellent. the author will speak first then we will open to questions we do have a microphone over here. please use that as we can hear you and at the end please full up your chairs before you get into the signing line. i am happy to welcome richard harris and his book rigor mortis. some cost of dollar amounts in human value he chose the science of the top research institutions are in urgent

need of repair form from drugs to would be advanced due to failure or dramatic testing errors sloppy science could be potentially fatal. the co-founder says signs of the best way to build the knowledge but mr. harris reminds us is also humans subject to the publish or perish reverse incentives. adding to these tensions is a gripping tale of what some call a crisis. read this book 81 to see how biomedical research is reviving itself. reporting for the npr desk with his initial focus on climate change and

biomedical research. a three-time winner of the american association advancement of science journalism award and co-founder of the d.c. science writers association. this is his first book, a richard harris. [applause] >> five. >> thank you very much and for coming out i do appreciate it. so to talk about the book i'm interested in hearing your questions as she mentioned i have been at npr 31 years and to cover just about everything. after a long stretch of covering climate change in the 1990's and 2000's my boss said how about going back to biomedical research? i said i'd better brushup so one of the first things i

did look at the nih budget i was startled to discover it had been undergoing severe gyrations from 2003 since 1998 which seemed like good news for biomedical research but after 2003 the dollars flattened out in the spending power a decreased by 20 percent so i thought this is not a good formula for things to be happening. fifty% increase of academic labs for biomedical research and basically congress said we have done enough that is not a good thing to be happening -- happening. so sure the there after i came across a paper published in the journal nature that looked at what

was coming out of these academic labs the main researcher was that a amgen and head of research and what back to review studies that was published in scientific journals and discovered that when they originally came across he thought if these were good results this is how pharmaceutical companies work these days they rely on the academic science. he said i could not get them the first time so let's try it again so the second cycle they tried to replicate. fifty-three studies even recruited the help of scientists and of those he

could only get six to replicate that is 11% that is a a pretty grim statistic he said a lot of science coming out of academic labs are not reproducible in the was a concern than a few months before his study was published a second study was done from germany so this is now known as the reproduce ability crisis. i think it is a conservative is a new surprising thing that had not been around before. actually a lot of these have persisted for a long while but what has happened they are becoming acutely aware that this is an issue and be concerned about the need to address.

i am not the only person thinking about these things there reza survey how many people believe there is a reproduce ability crisis? more than half of the scientist said yes. another 40 percent said there is a slight crisis i not sure what that is but 90 percent acknowledges is a very serious issue. so like my book i was aware i was stepping into world level lot of concerns and my first thought is people won't talk about this it is uncomfortable they don't want to hang up their dirty laundry you be surprised how many said yes this is a concern. talk to me and talk about what is wrong and what to do. so i had incredible access

to nobel laureates and others who said yes let's see what we can do so the title "rigor mortis" i think the rigor of science has not died it definitely need some help and the subtitle is over the top when you read the book but it does draw the eye to the fact they are issues that have an impact for people who consume to say there is a bunch of health problems out there helpless to a understand and find ways to treat them there are 7,000 diseases out there there's only treatments for 500 and they're not very successful so i set out to talk to a bunch of people and heard a lot of different things not

just the bad news but what is starting to generate interest of how to fix these problems so by the time you're done with the bookie were not totally depressed you do have a sense that people are in engaged. so first about the bad news news, what we know is science is hard we should not expect 100 percent protection if everything they publishes correct my answer would be were not trying hard enough. so there should be a failure rate absolutely. that is not a cause of concern about what i've focused on is the fact a lot of the failures are avoidable there are things that are happening in the

laboratory of eating the wrong direction never to perfection the you can reduce the unforced errors and accelerate the progress my initial title was science fiction. [laughter] because it was slowing down. if we could reduce science fiction. >> so i will talk about four different categories one is bad enough that they don't plan their experiments with as much care as they could the also made bacon -- bad assumptions of the animal models and they assume they were from the animal supplies to human beings and very often that is not the case or is misleading.

finally it is a toxic culture of the system that is built up largely caused by this problem of decreasing funding available for biomedical research in particular. for the ever shrinking pool of money and you put in a grant proposal you have no one at a five chance so you have to support your lab from these grants as the main source of funding so if i have to write 546 grants on average to get funding just for one to keep the lab gullying is the incredible amount of pressure and there isn't much back up if they don't get the agreement is possible they will shut down so this environment invites

people to get into awkward situations so a couple of examples, i mentioned what is commonly used in laboratories petri dishes that grow perpetually the first wusses featured in a wonderful book and a tv movie she was a woman diagnosed with cervical cancer they isolated cells and turned into the world's first immortal souls this was useful to be used in biomedical research but it was also showing that they

grow incredibly rapid if you make a small error before you know, it there spewed throat all of the cells and takeover. they think they are studying liver cancer but ultimately may be-- realize they're studying these alternate cells which is a problem in over the decades that the cells were taking over there is a lot of concern but not much was done so 15 years ago there were some tests that could rapidly identify if it was the author nacelles are the original ones but they're not used as widely as they need to be so this is just one example there is 450 of their examples that are used all the time in biomedical

research labs they have tools to check out but they cost money and inconvenience so the test are not used as often as they need to be. second, the methods sometimes they design experiments that don't have enough power to tell them what is going on so that classic study of live garett disease they have led to a lot of drugs in the lot of failures for treatment. some of them the scientists didn't think the early of what they needed or what they needed to use but it is also true it is quite extensive to do that right that may take dozens of chinese that could easily

cost over $100,000 in many academic scientists don't have that money. so i will call the results a pilot study so they are constrained by resources but on the other hand there are occasions leading to large-scale clinical trials leading to results that are very disappointing we do have a small number of mice and then tens of millions of dollars trying to expand that. so that is just one example that gives you a flavor for what can go wrong. i think yeah other assumption of mouse work if you think it works in mice you could cure cancer and strokes in mice but those

findings don't often translates to human beings. we're not meissen they are not tiny people but the assumption is we are mammals and they are mammals often scientists will say i don't have anything better. but i think we should be more modest in our expectations talking to people that could make better use of the animals or hobbies extract meaning not just your crossing your fingers and finally some words about that culture i will read from page. >> is a little harder to read in but i write for the radio -- three of the year rigo.

starting with a comment from the social scientist if they're working as hard and as long as they can they you are going beyond their own physical limits so what else can you do to get the edge to cross the finish line first? you can cut corners often that is the only option. he works at health partners institute but has documented some of this behavior and scientists rarely admit to out right this behavior but to question bowl practices something changed on a gut feeling for change the results of a study by industry and read this is going on day know that if they don't get the result

that is good then maybe they cannot get their grant or their lab funded. so the pressure is all wrong day have to choose petrie's what is best for science doing what is best for their careers and the people they are supporting. that incentive system is out of whack for science and i talk about that. and some of the things that could be done. so i just want to read a little bit more because i thought he was very thoughtful so boils down to human nature to let go of the notion of what is right and fair people see how others are being as a clue to their own behavior.

i am paraphrasing. if you perceive to have a fair shot you're less likely to bend the rules but if you think justice has been violated then you will say i will cheat also been they are more likely to engage is less than ideal behavior and actually he was on a recent national academy of sciences committee looking at the issue of scientific integrity and they wrestled with this. twenty-five years the first time the academy has gone back to let these issues their perception in 1992 and they're looking at a bad apples that when they reconsider the views of scientific integrity the real problem it isn't just

the bad apple put the barrel and the environment of how they are pressured one scottish scientist says nobody wants to do bad science we all want to understand but the incentives are so out of whack scientists can do what they really want to do so how can we change the system ? align these better so good science follows? there are some difficult solutions but one thing that is simple to do is validate that these are readily available the national institute of health requires

people better funded to go out to get the cell lines authenticated to get the grant money. so we will see if that helps to resolve some of these issues that still quite common scientist to make sure the results are more transparent in 2001 the five the sequencing the genome in the cover story of the journal nature and instead of publishing all of the data that represented the human genome they picked out one dozen highlights one of them was the observation that genes were jumping from bacteria directly which was

a totally surprising finding nobody expected bacteria to do that so they published this as part of the lineup of exciting discoveries in the lab they said this is not true it could not be possible but because it was published and made publicly available all the other scientist to figure out what was going on to say guess what? you made a mistake this isn't what is going on it is a misunderstanding and in very short order it was corrected. as were they making a false discovery that would help

and to make it more transparent and this obviously raises competitive issues to the extent that this could happen if you know, the you put this stuff out there in the public domain it is much better to find your own errors. so i think transparency is a powerful way not the entire solution but very helpful as well. clearly there needs more scientific training in 2014

we looked at the best courses and universities to treat methodologies to say who has the best course? we have no answers people learn about these things. while that is a lovely and traditional approach if your mentor is not that hot on methodology so by definition half of the mentors will be below average. that is an issue that people realize and nih has funded a number of courses that good curriculum of methodology that is a very positive effort.

sova hardest problem people have been scratching their head not only recognizes in the world of biomedical research but how do you solve that problem? to have a nice healthy world but if there is that in balance you have to put more money in but it also push people out of science. how basically the biology of diseased and treatments have been cured.

i have not heard a satisfactory solution but trying to sort that out maybe the audience would have answers but it is not all bad news there is room for improvement this comes at a critical junction recognize this is something we just cannot forget about with the will to do something is the most encouraging. thanks for your attention and i am happy to take questions. [applause]

>> you identified four types is the rate of sloppiness the same in university and hospital affiliated biomedical research? or the pharmaceutical labs or who has a better track record?. >> that is an excellent question. there is a strong profit motive to get things right by the time it comes out of big farm it is much more likely to be corrected and academic research. so anybody in pharma knows 90 percent of what we do fails. but we recognize that. put the things that they think work do they work to move forward? those have a

better track record. so here is the results world go run with that so take it to the intermediate web first so let's see if that works so have the time we could get it to work a lot of those don't go any farther and to their credit they say put the brakes on that we don't want to waste of everybody's time they

want more evidence of what will work. >>. >> thanks for your presentation and also the first question. mine is an extension of that. with methodology so then that can lead to the trial several unsuccessful because those trials are so expensive so as far as you're concerned is the

inverse truth is there any way to quantify because you get negative results and things don't follow from their at least in some fraction of cases does that ever happened?. >> that is very hard wood the drug have worked if you tested that properly? but yes it is a major driving force it cost $1 billion to develop the drug but what they're counting is all the experiments that they do that don't work sold a large

percentage of those failed. most of the time they don't succeed in human trial so those could be $100 million trials or more that is clearly part of the driving force of the drug prices. but in terms of the basic science that says if we could improve the success rate everybody would benefit. we waste less money and faster progress. >> but nobody has tried to quantify the inverse? because repetitive stories have not been done. >> they tend not to chase it

down the staten drugs that were developed these very successful drugs to treat high cholesterol many people in this river probably familiar but those studies with mice and rats have that basic biology that they could make a difference they understood on a molecular level so one of the big drug company said forget it a scientist in japan said i am now ready to give a promise so the cali downhaul -- a colleague downhaul was doing research on chicken lo and

behold they worked. that is mild and lesson we should not trust mice to much. but in this case us chickens gave us the answer. >> i have been listening to you for years. >> and my taller or shorter? [laughter] >> you have seen the good farmer - - pharma over the off label markets the fda is very careful with those

small pilot studies they are positive results negative results are suppressed in now that we have the supreme court from the companies will be protected by the first amendment eating something should be done about publication so somebody to get the same results?. >> that is a huge problem no question they've you get the

exciting result you publish if you don't you don't then nobody knows about it. this is not a perfect system the people have been concerned about that they address that that if you have a drug your developing you are supposed to register that at a critical live site this is what i going to do i will post results at this time so the fda expects that to be done before you gesture drug and they are supposed to report their results that is a difficult situation but to go to that database they have not even

reported this year by law that is a red flag. delhi should know there is data about their that should be informative. some people are talking about doing this registration idea. and that is another solution knocking around. but others say that could help resolve these problems and then to say here are my results have a new hypothesis it turns out what i wasn't looking for but the people present them in the literature but you could

avoid that pitfall that is another difficult problem. >> your focus was on biomedicine are there any different considerations with those rates or failure to replicate. >> debt of think anybody knows about that. so as a very general principle is easy to measure things in that makes them harder to get those results.

so with the general malaise in the system and then still have results but my favorite counter example is using that giant accelerator we want to get this right so go to a completely different -- detectors so we have taken the care of front but did you think ahead but also to the physical sciences as well that is not very strong

because that touches on the personal lives. >> one suggestion in terms of how do you make way? may be forced retirement at 65 you are out the door. then my friends say he is a type top in the world didn't know what i want to do with that problem remains to be seen some the desire to have something absolutely true has to be in competition with the funding the brokers so when you have a series of

agreements -- grants that competition is at the point this would have to raise the dead. there is a tremendous desire to show your best to suspect it will only get worse and will not get better it will be a very tough road but to have the success rate in fund-raising i am not that optimistic but the nih has thought about getting people to retire sooner with incentives if this is your

last one he will make it easier to get it. me via 65 your time is up but this is a problem because of the funding crunch the average age of the first grant to support the individual laboratory is in the mid-40s so the really not yet ready to retire a 65. maybe you have done some productive work first but forced retirement isn't pleasant especially if they are productive. so to be hitting on all cylinders. >> this is a great book you did a great job of how this has evolved in one of the

questions i keep thinking about it shows how oh complicated the issues are but one of the things that are the most fundamental but i see this all the time so that if the publication i don't want to say culpability of a science journalist for the publications to having set the tone this is unjust churro the journals of are the worst offenders because

they say that sets the standard so all must call have day criteria as opposed to simply good solid work to draw at a? conclusions but to be very careful of preliminary results but that perversion is what has changed how they look as finance. >> it is a huge issue for sure.

>> there is some hand-wringing about this even the scientists themselves a couple of researchers who said let's get the language in the scientific papers to be unprecedented a 15,000 percent increase. so as they start to think of how they might change the criteria, if there is a checklist and there has been

some suggestions the data should be published the important thing is to recognize what a good science has done and to celebrate that. >> i talked to the executive editor who basically said she feels the universities are putting her in a position if he tried to decide who was a good scientist how many papers have a published in she says taipei -- betting setter interesting but the dean's are overwhelmed with the applications so they formed that out angeles do the same thing.

i look at the top journals because i will let the world the journals do that filtering. >> data is the important responsibility and it turns out many do not stand the test of time but it came out that the exciting studies in the media after not to pan out because we don't read those journals the remember that steady about parkinson's disease? that turns out not to be true we don't see the original study or the follow-up study so with eight to see what type of effort they could make to

turn this around. that part of the world is messed up. >> hi dad. [laughter] i was just curious over the course of talking to people not to spoil the ending is some solution they were working at they've met at a crossroads that this is a good place to start but the one that's sticks in my head

and he is a psychologist from the university of virginia when it was time for his review set to send me every paper you have written but they said we don't care. send me everything you have published in then they realized the when they got to the university when it is time for the review so focused on a couple of strong ideas not

productivity at large those are the sorts of things that move science forward if more deans could pick up that would make a difference not the overall solution but a change of mindset thinking about what is the best science, i do remember that as a live bull moment -- a light bulb moment. good question. [applause]