[Help] Petition to end laboratory testing on animals.

[Baldseagull]

So would you conclude that the animals are “well cared for” right up until the experiments begin? What if these experiments happened on a daily basis? Is the overall care adequate if you are causing pain and suffering on a regular basis?

Adequate is probably a fair word to use. The side effect of some experiments is some pain and suffering, I don't believe pain and suffering is the aim of the experiment, except perhaps in research around pain relief, just as some soreness after surgery on humans is not the aim of cutting someone open.

We didn't really know what the pancreas did till someone cut one out of a dog to see if it could get by without it, it did for a while but became diabetic and died, a clue for the cause and treatment of diabetes, that was not expected from the experiment.
Someone else then discovered that you couldn't take all the products of a pancreas and successfully dose a diabetic dog with them, it turns out that the digestive enzymes the pancreas produces in one part, destroys the insulin it creates in another part.
Insulin was then isolated from the pancreas of a pig and used to treat diabetes in humans, and insulin derived from pigs has treated human diabetics, for about a hundred years. I believe there is a vegan alternative in use now, but some years ago, the Vegan head of PETA at the time was a diabetic, she advocated the ending of all exploitation of animals, in any way, but still dosed herself with pig derived insulin. Her justification was that by a few pigs deaths, she could continue the fight to save the lives and suffering of all animals.

 

[Harry Wilson's tackle]

Of course I dismissed his point. If you’re causing pain to a sentient being they are not “better cared for” than their technician counterparts. Attempting to bring other human rights issues into the situation, again, is not a justifiable excuse to cause animals pain and suffering. It comes across as a way to attempt to dilute the main issue here which is animal rights and animal welfare.

I see your point in regards to it being “the only way”, and whilst I in no way pretend to be an expert, but a quick Google lead me to a research paper from the Yale School of Medicine and several British universities titled “Where Is the Evidence That Animal Research Benefits Humans?” that evaluated the claim that major medical advances are attributed to experiments on animals and concluded that it was not supported by any evidence. It concluded that most experiments on animals are not relevant to human health, they do not contribute meaningfully to medical advances, and many are undertaken simply out of curiosity and do not even pretend to hold promise for curing illnesses. I would be genuinely interested to know your thoughts on this.

First some quick clarifications then I will address your very interesting question. I haven't seen a single example of 'causing pain' in research in my lab or any other lab in my institute. Almost all work is done in anaesthetized animals (which are killed at the end of the experiment while still under anaesthetic). Have you ever had a general anaesthetic? There is no pain. Yes, animals are killed but the 'pain' angle is false. If you argue that it is simply wrong to kill any animal (whether for research or food) and you back this up by being vegan, using no medicine, wearing no leather (there are some other things that were developed via animal research but this will suffice) I will absolutely respect your position. But putting 'causing pain' at the top of your list weakens your position.

Second, everyone who works in research that I know is concerned about animal welfare. None of us are interested in animal rights, however. I suspect this is the true place where our views digress (unless you are one of those who refuse to take any medicines or other treatments, and forbid your family likewise, and I don't regard you as mad). We owe our fellow creatures an obligation to treat them well, But they have no 'rights'. With rights come responsibilities. I appreciate this reasoning has been countered with arguments about 'the right to lead a life unmolested by human activity' but that right does not even extend to humans. Anyway, rights is a red herring.

OK you have asked a specific and important question. Yes, I do think a great deal of animal research is wasteful and should not have been done. Animal research is not a black and white issue. I object to a vast amount of it, on the grounds that basic requirements for design and analysis are not met, and non-randomized studies and non-blinded data collection and analysis leads to false findings. I am a vigorous and noisy advocate against shit research, and the perverse incentives of rewarding people for raising grant funding and publishing in high JIF journals, much to the annoyance of some. But I can't develop my drug without animal research. The knowledge base I have accumulated on how best to generate reliable information about drug activity, insight into mechanisms, ability to detect potential adversity (and I'm not talking about 'pain' here) is based on decades of painstaking and carefully considered animal research. I stand by it. All of it.

But what do we do about the poor quality research that leads nowhere? First of all, I will preface my comments with this. Just because I, as someone with nearly 40 years' experience, has an idea, it does not mean it is correct. What I do is construct a simple hypothesis and test it. More often than not the data will show my idea was wrong. This is the scientific method of attempting to falsify a hypothesis. In the end, when you have an idea that is correct it becomes impossible to disprove it and we can then take it to the next stage. In my case 'does targeting X receptor change Y to ameliorate disease Z' is a testable hypothesis, but it involves a lot of work, showing that the drug that targets X is specific and selective, that the change in X is linked to the change in Y and the change in Y is linked to benefit on Z. And that's just the start. Most research fails because somewhere along the line these connections are not made. Molecular selectivity is the main issue and that is not apparent till the drug is put through repeat dose tox studies. That means conscious animals. But less than 0.01% of drugs get that far, and most that do are not toxic. The law demads these tests, by the way.

Separate from all this is the poor quality research that was never intended to go anywhere. The research factory labs in China are now churning out mountains of data shwing that X changes Y and Y changes Z but rarely do they show that Z benefits a disease. I get to referee papers like this every week. I can't remember ever accepting one for publication (n=3, not blinded, not randomized, western blots that are technical replicates not biological....). But the work will be published in another journal. The authors will move on to something else. Most of this stuff is done quickly using cultured cells. The animal work that is included is a waste of animals (it is all mice; I haven't seen a paper of this sort that uses rats let alone rabbits or dogs).

So yes, the majority of world reseach now is done in China, uses mice, and is crap and wrong. False positives abound due to wishful thinking and in some cases deliberate fabrication. This work has no impact on the progress of knowledge and almost allof it is ignored.

Now, if you turn to higher species, rabbits and dogs, there use is negligible. Why? Nobody would spend £1000 on a dog to test a drug, and perhaps a million pounds to complete a dog study, unless they already had a mountain of data to show the drug is potentially useful, and because dogs are a logical and necessary species for that last bit of work before FIH (first in human) studies. I have never used dogs for one scientific reason (they are proven to be not predictive in my research area for reasons that are well understood), one practical reason (I don't have a drug I would want to test in a higher species) and one ethical reason (I don't believe there is any scientific justification for using dogs in research; and with that there is no justification for using a species that is a domestic pet). That said a colleague who worked on a brain disease used primates for work just prior to human studies because no other animal species has the necessary equivalents of the parts of the human brain relevant to his area. It is that or just give up on people with Parkinson's and related conditions. I don't like it but I can't condemn it.

Most animal research, of course, does not immediately benefit humans, if you define benefit as the emergence of a drug. If you measure my work by requiring that every time I go into the lab I create a new drug, then you can argue my work does not benefit humans. But that is a distortion of how ideas are generated and tested. The new drug I am working on would never have been conceived if it were not for perhaps 10000 separate pieces of research over the last 100 years involving perhaps 1,000,000 animals, that prvided a knowlege base on how the disease manifests, its pathogenic signature, the components that may be druggable, the species that best mimick what happens in humans, the underlying physiology, the type of targeting that is possible, the characteristics of drug effects on different aspects pf the pathophysiology etc. You literally cannot make this stuff up and to generate a knowledge base is excruciatingly challenging.

Finally, an individual has to ask themself whether their question is big enought to demand an answer, then persuade the Home Office (yes, they judge in the UK) that the means justifies the end. There is far too much trivial research going on, mostly using mice (or zebra fish, the new go to model) and mostly in China, and I'd like to see an end to it, but this means requiring better standards on design and analysis, not attempting to legislate the likes of me into oblivion.

I'll call it a day, now. If you have any more questions, PM me.

 

[midnight_rendezvous]

Adequate is probably a fair word to use. The side effect of some experiments is some pain and suffering, I don't believe pain and suffering is the aim of the experiment, except perhaps in research around pain relief, just as some soreness after surgery on humans is not the aim of cutting someone open.

We didn't really know what the pancreas did till someone cut one out of a dog to see if it could get by without it, it did for a while but became diabetic and died, a clue for the cause and treatment of diabetes, that was not expected from the experiment.
Someone else then discovered that you couldn't take all the products of a pancreas and successfully dose a diabetic dog with them, it turns out that the digestive enzymes the pancreas produces in one part, destroys the insulin it creates in another part.
Insulin was then isolated from the pancreas of a pig and used to treat diabetes in humans, and insulin derived from pigs has treated human diabetics, for about a hundred years. I believe there is a vegan alternative in use now, but some years ago, the Vegan head of PETA at the time was a diabetic, she advocated the ending of all exploitation of animals, in any way, but still dosed herself with pig derived insulin. Her justification was that by a few pigs deaths, she could continue the fight to save the lives and suffering of all animals.

I fully accept that I have, in all likelihood, benefited in some way because of animal testing. There’s no denying it but that doesn’t mean I need to continue to contribute to animal suffering moving forwards. Animal suffering in the name of science should be challenged and I firmly believe that a more humane approach is needed, especially when there is so much doubt about the scientific validity of applying the results from research on animals to humans.

 

[midnight_rendezvous]

First some quick clarifications then I will address your very interesting question. I haven't seen a single example of 'causing pain' in research in my lab or any other lab in my institute. Almost all work is done in anaesthetized animals (which are killed at the end of the experiment while still under anaesthetic). Have you ever had a general anaesthetic? There is no pain. Yes, animals are killed but the 'pain' angle is false. If you argue that it is simply wrong to kill any animal (whether for research or food) and you back this up by being vegan, using no medicine, wearing no leather (there are some other things that were developed via animal research but this will suffice) I will absolutely respect your position. But putting 'causing pain' at the top of your list weakens your position.

Second, everyone who works in research that I know is concerned about animal welfare. None of us are interested in animal rights, however. I suspect this is the true place where our views digress (unless you are one of those who refuse to take any medicines or other treatments, and forbid your family likewise, and I don't regard you as mad). We owe our fellow creatures an obligation to treat them well, But they have no 'rights'. With rights come responsibilities. I appreciate this reasoning has been countered with arguments about 'the right to lead a life unmolested by human activity' but that right does not even extend to humans. Anyway, rights is a red herring.

OK you have asked a specific and important question. Yes, I do think a great deal of animal research is wasteful and should not have been done. Animal research is not a black and white issue. I object to a vast amount of it, on the grounds that basic requirements for design and analysis are not met, and non-randomized studies and non-blinded data collection and analysis leads to false findings. I am a vigorous and noisy advocate against shit research, and the perverse incentives of rewarding people for raising grant funding and publishing in high JIF journals, much to the annoyance of some. But I can't develop my drug without animal research. The knowledge base I have accumulated on how best to generate reliable information about drug activity, insight into mechanisms, ability to detect potential adversity (and I'm not talking about 'pain' here) is based on decades of painstaking and carefully considered animal research. I stand by it. All of it.

But what do we do about the poor quality research that leads nowhere? First of all, I will preface my comments with this. Just because I, as someone with nearly 40 years' experience, has an idea, it does not mean it is correct. What I do is construct a simple hypothesis and test it. More often than not the data will show my idea was wrong. This is the scientific method of attempting to falsify a hypothesis. In the end, when you have an idea that is correct it becomes impossible to disprove it and we can then take it to the next stage. In my case 'does targeting X receptor change Y to ameliorate disease Z' is a testable hypothesis, but it involves a lot of work, showing that the drug that targets X is specific and selective, that the change in X is linked to the change in Y and the change in Y is linked to benefit on Z. And that's just the start. Most research fails because somewhere along the line these connections are not made. Molecular selectivity is the main issue and that is not apparent till the drug is put through repeat dose tox studies. That means conscious animals. But less than 0.01% of drugs get that far, and most that do are not toxic. The law demads these tests, by the way.

Separate from all this is the poor quality research that was never intended to go anywhere. The research factory labs in China are now churning out mountains of data shwing that X changes Y and Y changes Z but rarely do they show that Z benefits a disease. I get to referee papers like this every week. I can't remember ever accepting one for publication (n=3, not blinded, not randomized, western blots that are technical replicates not biological....). But the work will be published in another journal. The authors will move on to something else. Most of this stuff is done quickly using cultured cells. The animal work that is included is a waste of animals (it is all mice; I haven't seen a paper of this sort that uses rats let alone rabbits or dogs).

So yes, the majority of world reseach now is done in China, uses mice, and is crap and wrong. False positives abound due to wishful thinking and in some cases deliberate fabrication. This work has no impact on the progress of knowledge and almost allof it is ignored.

Now, if you turn to higher species, rabbits and dogs, there use is negligible. Why? Nobody would spend £1000 on a dog to test a drug, and perhaps a million pounds to complete a dog study, unless they already had a mountain of data to show the drug is potentially useful, and because dogs are a logical and necessary species for that last bit of work before FIH (first in human) studies. I have never used dogs for one scientific reason (they are proven to be not predictive in my research area for reasons that are well understood), one practical reason (I don't have a drug I would want to test in a higher species) and one ethical reason (I don't believe there is any scientific justification for using dogs in research; and with that there is no justification for using a species that is a domestic pet). That said a colleague who worked on a brain disease used primates for work just prior to human studies because no other animal species has the necessary equivalents of the parts of the human brain relevant to his area. It is that or just give up on people with Parkinson's and related conditions. I don't like it but I can't condemn it.

Most animal research, of course, does not immediately benefit humans, if you define benefit as the emergence of a drug. If you measure my work by requiring that every time I go into the lab I create a new drug, then you can argue my work does not benefit humans. But that is a distortion of how ideas are generated and tested. The new drug I am working on would never have been conceived if it were not for perhaps 10000 separate pieces of research over the last 100 years involving perhaps 1,000,000 animals, that prvided a knowlege base on how the disease manifests, its pathogenic signature, the components that may be druggable, the species that best mimick what happens in humans, the underlying physiology, the type of targeting that is possible, the characteristics of drug effects on different aspects pf the pathophysiology etc. You literally cannot make this stuff up and to generate a knowledge base is excruciatingly challenging.

Finally, an individual has to ask themself whether their question is big enought to demand an answer, then persuade the Home Office (yes, they judge in the UK) that the means justifies the end. There is far too much trivial research going on, mostly using mice (or zebra fish, the new go to model) and mostly in China, and I'd like to see an end to it, but this means requiring better standards on design and analysis, not attempting to legislate the likes of me into oblivion.

I'll call it a day, now. If you have any more questions, PM me.

I thank you for your very detailed reply. I shall consider the points you have made and certainly take you up on your offer of DM if I have any follow up. However, if you believe that animals don’t have rights it is very unlikely, almost impossible, that we will ever see to eye on this and I have no wish to waste your time or my own. Enjoy your Thursday!

 

[Harry Wilson's tackle]

I'm afraid I'm going to reject the premise and the analogy. You can only score a goal by making an attempt on goal, there is no other way. But a medical student can train to become a surgeon without ever practising on animals. You can develop drugs without testing them on animals - or more to the point, testing them on animals appears to be unnecessary in the overwhelming number of cases. 95% of drugs proved safe and effective in animals are not safe or effective in humans. So what was the point of the animal tests? Moreover, considering how damaging aspirin is to a wide range of species, would it ever get to human trials if it was invented today?

" A survey of 4,451 experimental cancer drugs developed between 2003 and 2011 found that more than 93 percent failed." You can't just pass that off glibly as "early stage work done badly on drugs .... which were published owing to the general ignorance in the sector on what constitutes good design and analysis." Over 4,000 experimental cancer drugs studied with poor study design and general ignorance amongst researchers? Nature gets a vast number of retractions of studies testing drugs on animals? Wow! If this is the case then this sector needs a radical overhaul and a major review of how it is funded. We've all give money to cancer research charities - is this what happens to it, a repetitive cycle of badly-conducted research? This doesn't defend the argument to continue animal trials in any way shape or form.

So Nature gets retractions, but meanwhile BMJ published a review in 2014 demonstrating that animal research provides little benefit at great cost, concluding that "the conduct, reporting, and synthesis of much animal research continues to be inadequate; that the current situation is unethical since animals and humans participate in research that cannot produce reliable results; there is insufficient systematic evidence for the clinical benefits of animal research and greater rigour and accountability is needed to ensure best use of public funds."

I get that someone inventing a completely new drug would be loathe to stick it in a person without having any idea of what it might do to them. But if the researcher is that unclear about the effects, just sticking it in a stressed-out caged rabbit, at big doses and often with no pain relief, isn't exactly a 'good experimental design'. That just sounds like cutting corners. Given the large amount of animal research being undertaken, some findings will extrapolate to humans just by chance. Modern, human-relevant non-animal tests are the way forward, but is the problem that they are expensive? Has pharmaceutical research become more about the bottom-line? From the outside it looks like one of the few fields of scientific research driven by corporations rather than academics.

The football analogy is more along the lines of kicking the ball at your own goal, to prove the ball can indeed go in a net, before making an attempt on the oppositions goal. It doesn't help you win the match.

Let me stop you, there. Most drugs in development fail. To say that animal research is therefore not necessary is false logic. All drugs that work and are used therapeutically have been tested in animals. No new drug discovered in the last 50 years, to my knowledge, was introduced to humans without any animal research. Even digitalis, which was a plant extract whose benefit was discovered by Withering hundreds of years ago without animal experiments, eventually fell out of use due to formulation issues and its adverse effects, and it required animal research to put that right (and in any case digitalis is now largely superseded by better drugs, developed via animal research).

My analogy (for what its worth - just a bit of fun and hardly worth a whole reply) is therefore correct. Most attempts on goal fail to result in a goal. The Albion are particular experts at this. The solution is not to stop attempting to score.

Show me a better more efficient way of making drugs that does not require use of animals (that means showing thay are safe as well as effective) then I'll shake your hand. Lots of people propose hypothetical ways to do this but none have been shown to work. Like the perpetual motion machine, animal-free research will work if you keep poking it (with injections of real animal data) perhaps.

For the answers to most of your other points see my reply above to another poster. The reproducibility crisis is something I have published about, and it is due to nonrandomized nonblinded studies, publication bias and other human foibles. It has nothing to do with animal models being misleading.

There really are people who won't take any medicines because they were all developed using animal research. That is entirely inconsistent with your contention that animal research is not necessary. We'd all rather not do it, and if we didn't need to we wouldn't. I just wish we could do it better. Spurious arguments that animal research never works, and the unstated implication that some other mythical method does, doesn't help in this regard. It is simply false.

 

[Harry Wilson's tackle]

I thank you for your very detailed reply. I shall consider the points you have made and certainly take you up on your offer of DM if I have any follow up. However, if you believe that animals don’t have rights it is very unlikely, almost impossible, that we will ever see to eye on this and I have no wish to waste your time or my own. Enjoy your Thursday!

We probably differ in our understanding of the conecpt of rights. I am no Roger Scruton, by the way, and my notion of responsibilities (that we humans have towards other creatures) diplores the Scruton logic that any creature that cannot enter a social contract with a human is fit to be exploited.

All the best

 

[Justice]

They do this because we as a race do not give a **** about animals. Most on here would probably describe themselves as an 'animal lover', which is a bit rich given they probably eat animals every day.

So you can’t love your pet dog and enjoy a Sunday roast Your confusing animal lover with pet lover to different things.

I love my dog, enjoy a Sunday roast and would happily kill rodents at the first sign of infestation.

Would the puritan animal lover not deal with a rat infestation? You can’t pick and choose.

 

[Kalimantan Gull]

Let me stop you, there. Most drugs in development fail. To say that animal research is therefore not necessary is false logic. All drugs that work and are used therapeutically have been tested in animals. No new drug discovered in the last 50 years, to my knowledge, was introduced to humans without any animal research. Even digitalis, which was a plant extract whose benefit was discovered by Withering hundreds of years ago without animal experiments, eventually fell out of use due to formulation issues and its adverse effects, and it required animal research to put that right (and in any case digitalis is now largely superseded by better drugs, developed via animal research).

My analogy (for what its worth - just a bit of fun and hardly worth a whole reply) is therefore correct. Most attempts on goal fail to result in a goal. The Albion are particular experts at this. The solution is not to stop attempting to score.

Show me a better more efficient way of making drugs that does not require use of animals (that means showing thay are safe as well as effective) then I'll shake your hand. Lots of people propose hypothetical ways to do this but none have been shown to work. Like the perpetual motion machine, animal-free research will work if you keep poking it (with injections of real animal data) perhaps.

For the answers to most of your other points see my reply above to another poster. The reproducibility crisis is something I have published about, and it is due to nonrandomized nonblinded studies, publication bias and other human foibles. It has nothing to do with animal models being misleading.

There really are people who won't take any medicines because they were all developed using animal research. That is entirely inconsistent with your contention that animal research is not necessary. We'd all rather not do it, and if we didn't need to we wouldn't. I just wish we could do it better. Spurious arguments that animal research never works, and the unstated implication that some other mythical method does, doesn't help in this regard. It is simply false.

You wrote a long and detailed reply above, and as a scientist myself, I get it. You're doing experiments and this is the way they've been done for years. In my (very different) field, the same thing persists, people still use the old methods when new methods become available, become closed to doing this differently (true in all walks of life), perhaps there is more comfort and trust in the old ways. In my original post I listed a long list of suggested alternatives - I know little of these - but I assume from the way they are presented that they show clear promise, and all the stories we read about AI systems, stem cell research, growing organs in labs, cadaver research etc etc suggests that if we can't eradicate animal research entirely we can certainly make great strides. The best subjects for human drug research are humans, so the development of synthetic humans must be the aim.

Most drugs in development fail - yep, sure. But its why they are failing that is the key to this argument. If they are developed based on a reasonable hypothesis but fail to produce a response in animals, then that is a genuine failure that is to be expected. But if they do produce a response that fails to be replicated in humans - if the aim is to produce a drug solely for humans - then the animal research was a waste of time. Indeed the very act of finding positive results will have led to more rounds of animal experimentation that was always destined to lead nowhere. Ditto for proving something was safe in animals that turned out not to be safe in humans. Its not research that has failed, it is research that was pointless - but carried our because of regulatory requirements. There seems to be a clear scientific argument that we would save huge amounts of time, money, animal suffering and patient suffering by sticking the developed drugs (or drug component) in humans and bypassing the 'testing' phase in animals (not necessarily the development phase). Obviously a human subject will keel over somewhere at some point, so that's the counter-argument, but its one based in legalities more than science

I don't like the 'keep on attempting to score' analogy, I really don't. It suggests lots of blindly throwing darts about, producing any old chemical compound and sticking it in mice to see what happens. Private companies drive pharmaceutical research and the feeling is they prefer to test 10,000 experimental drugs cheaply rather than 1,000 drugs more rigorously and ethically, to then let the profits roll in when they hit the jackpot. But the gathering evidence seems to be that this is proving unproductive (a bit like Brighton's quest to solve the goals problem)

Finally, if you are completely humane then your organisation is probably not the target of the opening post, and I am sympathetic to any dedicated researcher's aims, making scientific advances is to be lauded and not easy in the slightest. At the same time, its unclear from your post if your research is truly necessary. All fields of research piece together thousands of studies on seemingly irrelevant or unconnected things over long periods of time to develop grand theories and breakthroughs. But it is also true that the same conclusion would have been reached with only half as many studies. When it comes to research with ethical questions attached, it is not so straightforward to say that a seemingly irrelevant piece of research led to a grand breakthrough, there has to be more justification to do it than that. Overall, though, I am painfully aware that I am simplifying a subject I know little of too much, that there is far more nuance, and that you are being given a bad name by the cowboy researchers elsewhere. I also don't think you should have to answer for this industry - scientific problems and moral problems don't need to be conflated and everyone everywhere has ethical issues to grapple with their work and research - I know I do.

 

[Harry Wilson's tackle]

You wrote a long and detailed reply above, and as a scientist myself, I get it. You're doing experiments and this is the way they've been done for years. In my (very different) field, the same thing persists, people still use the old methods when new methods become available, become closed to doing this differently (true in all walks of life), perhaps there is more comfort and trust in the old ways. In my original post I listed a long list of suggested alternatives - I know little of these - but I assume from the way they are presented that they show clear promise, and all the stories we read about AI systems, stem cell research, growing organs in labs, cadaver research etc etc suggests that if we can't eradicate animal research entirely we can certainly make great strides. The best subjects for human drug research are humans, so the development of synthetic humans must be the aim.

Most drugs in development fail - yep, sure. But its why they are failing that is the key to this argument. If they are developed based on a reasonable hypothesis but fail to produce a response in animals, then that is a genuine failure that is to be expected. But if they do produce a response that fails to be replicated in humans - if the aim is to produce a drug solely for humans - then the animal research was a waste of time. Indeed the very act of finding positive results will have led to more rounds of animal experimentation that was always destined to lead nowhere. Ditto for proving something was safe in animals that turned out not to be safe in humans. Its not research that has failed, it is research that was pointless - but carried our because of regulatory requirements. There seems to be a clear scientific argument that we would save huge amounts of time, money, animal suffering and patient suffering by sticking the developed drugs (or drug component) in humans and bypassing the 'testing' phase in animals (not necessarily the development phase). Obviously a human subject will keel over somewhere at some point, so that's the counter-argument, but its one based in legalities more than science

I don't like the 'keep on attempting to score' analogy, I really don't. It suggests lots of blindly throwing darts about, producing any old chemical compound and sticking it in mice to see what happens. Private companies drive pharmaceutical research and the feeling is they prefer to test 10,000 experimental drugs cheaply rather than 1,000 drugs more rigorously and ethically, to then let the profits roll in when they hit the jackpot. But the gathering evidence seems to be that this is proving unproductive (a bit like Brighton's quest to solve the goals problem)

Finally, if you are completely humane then your organisation is probably not the target of the opening post, and I am sympathetic to any dedicated researcher's aims, making scientific advances is to be lauded and not easy in the slightest. At the same time, its unclear from your post if your research is truly necessary. All fields of research piece together thousands of studies on seemingly irrelevant or unconnected things over long periods of time to develop grand theories and breakthroughs. But it is also true that the same conclusion would have been reached with only half as many studies. When it comes to research with ethical questions attached, it is not so straightforward to say that a seemingly irrelevant piece of research led to a grand breakthrough, there has to be more justification to do it than that. Overall, though, I am painfully aware that I am simplifying a subject I know little of too much, that there is far more nuance, and that you are being given a bad name by the cowboy researchers elsewhere. I also don't think you should have to answer for this industry - scientific problems and moral problems don't need to be conflated and everyone everywhere has ethical issues to grapple with their work and research - I know I do.

Thanks for the thoughtful post. I should correct a couple of misconceptions. We don't invent drugs, know they work, and are then forced to do lots of animal experiments because of regulatory requirements. We have regulatory requirements so that when a case is made to take a drug into humns (FIH studies) there is a reasonable expectation the drug is safe. Safety pharmacology has meant that drugs like terfenadine that cause a rare but lethal syndrom that was not picked up till after millions had taken it, no longer get into humans. I have strong links with this aspect of drug discovery and it works brilliantly.

You seem to misunderstand my analogy. When people take a drug into humans they imagine it will work, based on lots of animal data. Just like a football team works the ball towards the goal. Expecting a goal with every attack is naive. But this does no mean the team are simply raking wild punts from all over the pitch whenever they get the ball. Have a read up on 'attrition' and the reasons for it.

The problem isn't even that the efficacy studies are misleading and drugs fail in humans due to false efficacy findings in animals. Efficacy failure was once due to underdosing in humans to avoid the adverse effects that had been identified in animal studies. Absolute stupidity, and entirely due to the medics who drive clinical research. Too many medics have a poor grasp of pharmacology, and a poor understanding of animal models of disease. Some of the decisions I have seen taken over clinical development, patient selection and dose selection have been so poor it beggars belief.

These days getting a drug into man is incredibly hard. The costs are unimaginable. My drug has a very risky entry level human trial possibility that is high risk. To take the drug to its intended larger human target population will require a trial that will cost a billion pounds (£1,000,000,000). The changes of it being done are slim to none. And yet my drug could save 50,000 lives a year in the UK. This is the sharp end of drug reseach, and financial threat is a major cause of attrition, even with a drug hat would have worked.

So clinical work is done more frequently with cheaper interventions (often devices) that have a very high chance of providing small but real benefit in a small population of patients.

Now, back to the animal waste....as I said there is a huge amount of work, funded in the UK by charities like the BHF and Cancer UK. If you can manage to blag some money off them, you will have to have a plausible story. Your work will almost certainly not be on a drug, but a drug target, with a focus on explaining mechanisms of dosease. This is what 'good research' supposedly looks like now. If you have a drug or a drug idea you can apply to MRC or BHF for translational money, but this requires complex arrangements over IP between the funder and the university. In my case my college claimed there was no IP opportunity for my drug and refused to pay to get an opinion, and would not support my application for funds. I managed to pay for research using my war chest of money (that my college has recently taken from me, claiming what is mine is theirs). On the strength of my data, my colleagues (a small company that has developed drugs for cancer) paid (costs now running into tens of thousands) to prepare a patent, and it has been granted! We have a patent when my college told me none was possible. To take the drug forward will be extremely complicated (far too complicated than I am inclined to explain here). The point being that even for an unmet need the complexity to take animal data and use it to make a product is almost overwhelming. Dropping the animal bit and using unvalidated approaches such as AI, a human cell shell grown in the lab, etc., won't help. The only data that counts is data from a human trial and all the animal studies or AI or whatever you want will do is inform the decision of the investors to pay for a clinical study or not. I cannot ever see data from an animal model of the disease being replaced by modeling or a human cell shell in this regard.

None of this has anything to do with the well-funded data factories that produce mountains of information on 'mechanisms' (the main type of work done in the UK and US these days) the most eye-catching of which get published in Nature and much of which is false and gets retracted. None of this has anything to do with the state funded data factories in China that generate mountains of crap, mostly using cultured cells, that is mostly false and meaningless.

A mate of mine who is the science director of a major research charity is so disillusioned with the difficulty in being able to develop a career as a medical researcher that his advice to promising students is don't do a PhD - get out and change your career. It is so hard to do anything worthwhile. It is hard to fund any research these days in the UK. Those who are best at getting funding are often the low grade psychopath type happy to write proposal after proposal till something clicks, then manipluate their data to maximise its publication viability. People talk about 'winning' grants. I have no time for any of this shit (one of the benefits, and also hazards, of being on the 'spectrum' - lol!).

And yet, despite all the poor research, the data factories, the shithousery that only humans can invent, I still don't see an alternative to animal research. By all means attempt to validate new approaches. I saw a paper on a 'human' organ (I won't say which or it will reveal my research area) that had been grown on a micro frame, a few years ago. The paper was in Science or Nature. The problem was the organ was not functional. It also lacked the complex structures that define the mechanisms that go wrong in diseases of that organ. This won't even replace the equivalent organ from a mouse in research. Perhaps in ten years time someone will invent another bit of technology that will take this on. I am in favour and expect to see the work funded (if well founded). But till then we can't simply give up. Do animal reseach, better, that's what I say.

And get rid of the perverse incentives, the publish or perish culture. In safety pharmacology all companies collaborate. They have a common goal - to ensure their drugs are safe and anything they can learn from each other is useful. The co-operation is global and unprecedented. If only we could replicate this in Discovery, we would be able to use far fewer animals in a far more efficient fashion. In academia people should not be judged on the publish or perish basis. Most of us discover nothing in our lives of any real merit. Jim Black invented cimetidine and propranolol. Yet he jumped ship to ICI becase he couldn't get promoted in academia because he didn't publish much. This was in the late 50s! We still laud those with hight h factors. A chap at UC had an h factor of over 200, but he essentially made one (esoteric) discovery and milked it. He was actually a good bloke, but many aren't. My institute is a great place - it isn't a mad house like Stamford or Oxford where staff actually sabotage one another's research, nor is it full of second rate minds like most of the red brick unis and former polys I have had the displeasure to interact with, so I have found my perfect perch. But much of the rest of what is out there is wasteful and crappy.

I have argued we need to reform before the public cotton on to the poor work and start asking 'where has all our money gone'? I know of one charity that has charity shops on every high street that has pissed tens of millions up the wall ever year, and has funded nothing that has generated a new drug. I could go on and on about how his has happened but....human beings again; self serving, perverse incentives etc.

 

[amexer]

These people that are trying to invent drugs for our health are not testing animals for fun. Nothings a perfect but as long as it is done as humanely as possible

 

[amexer]

Thanks for the thoughtful post. I should correct a couple of misconceptions. We don't invent drugs, know they work, and are then forced to do lots of animal experiments because of regulatory requirements. We have regulatory requirements so that when a case is made to take a drug into humns (FIH studies) there is a reasonable expectation the drug is safe. Safety pharmacology has meant that drugs like terfenadine that cause a rare but lethal syndrom that was not picked up till after millions had taken it, no longer get into humans. I have strong links with this aspect of drug discovery and it works brilliantly.

You seem to misunderstand my analogy. When people take a drug into humans they imagine it will work, based on lots of animal data. Just like a football team works the ball towards the goal. Expecting a goal with every attack is naive. But this does no mean the team are simply raking wild punts from all over the pitch whenever they get the ball. Have a read up on 'attrition' and the reasons for it.

The problem isn't even that the efficacy studies are misleading and drugs fail in humans due to false efficacy findings in animals. Efficacy failure was once due to underdosing in humans to avoid the adverse effects that had been identified in animal studies. Absolute stupidity, and entirely due to the medics who drive clinical research. Too many medics have a poor grasp of pharmacology, and a poor understanding of animal models of disease. Some of the decisions I have seen taken over clinical development, patient selection and dose selection have been so poor it beggars belief.

These days getting a drug into man is incredibly hard. The costs are unimaginable. My drug has a very risky entry level human trial possibility that is high risk. To take the drug to its intended larger human target population will require a trial that will cost a billion pounds (£1,000,000,000). The changes of it being done are slim to none. And yet my drug could save 50,000 lives a year in the UK. This is the sharp end of drug reseach, and financial threat is a major cause of attrition, even with a drug hat would have worked.

So clinical work is done more frequently with cheaper interventions (often devices) that have a very high chance of providing small but real benefit in a small population of patients.

Now, back to the animal waste....as I said there is a huge amount of work, funded in the UK by charities like the BHF and Cancer UK. If you can manage to blag some money off them, you will have to have a plausible story. Your work will almost certainly not be on a drug, but a drug target, with a focus on explaining mechanisms of dosease. This is what 'good research' supposedly looks like now. If you have a drug or a drug idea you can apply to MRC or BHF for translational money, but this requires complex arrangements over IP between the funder and the university. In my case my college claimed there was no IP opportunity for my drug and refused to pay to get an opinion, and would not support my application for funds. I managed to pay for research using my war chest of money (that my college has recently taken from me, claiming what is mine is theirs). On the strength of my data, my colleagues (a small company that has developed drugs for cancer) paid (costs now running into tens of thousands) to prepare a patent, and it has been granted! We have a patent when my college told me none was possible. To take the drug forward will be extremely complicated (far too complicated than I am inclined to explain here). The point being that even for an unmet need the complexity to take animal data and use it to make a product is almost overwhelming. Dropping the animal bit and using unvalidated approaches such as AI, a human cell shell grown in the lab, etc., won't help. The only data that counts is data from a human trial and all the animal studies or AI or whatever you want will do is inform the decision of the investors to pay for a clinical study or not. I cannot ever see data from an animal model of the disease being replaced by modeling or a human cell shell in this regard.

None of this has anything to do with the well-funded data factories that produce mountains of information on 'mechanisms' (the main type of work done in the UK and US these days) the most eye-catching of which get published in Nature and much of which is false and gets retracted. None of this has anything to do with the state funded data factories in China that generate mountains of crap, mostly using cultured cells, that is mostly false and meaningless.

A mate of mine who is the science director of a major research charity is so disillusioned with the difficulty in being able to develop a career as a medical researcher that his advice to promising students is don't do a PhD - get out and change your career. It is so hard to do anything worthwhile. It is hard to fund any research these days in the UK. Those who are best at getting funding are often the low grade psychopath type happy to write proposal after proposal till something clicks, then manipluate their data to maximise its publication viability. People talk about 'winning' grants. I have no time for any of this shit (one of the benefits, and also hazards, of being on the 'spectrum' - lol!).

And yet, despite all the poor research, the data factories, the shithousery that only humans can invent, I still don't see an alternative to animal research. By all means attempt to validate new approaches. I saw a paper on a 'human' organ (I won't say which or it will reveal my research area) that had been grown on a micro frame, a few years ago. The paper was in Science or Nature. The problem was the organ was not functional. It also lacked the complex structures that define the mechanisms that go wrong in diseases of that organ. This won't even replace the equivalent organ from a mouse in research. Perhaps in ten years time someone will invent another bit of technology that will take this on. I am in favour and expect to see the work funded (if well founded). But till then we can't simply give up. Do animal reseach, better, that's what I say.

And get rid of the perverse incentives, the publish or perish culture. In safety pharmacology all companies collaborate. They have a common goal - to ensure their drugs are safe and anything they can learn from each other is useful. The co-operation is global and unprecedented. If only we could replicate this in Discovery, we would be able to use far fewer animals in a far more efficient fashion. In academia people should not be judged on the publish or perish basis. Most of us discover nothing in our lives of any real merit. Jim Black invented cimetidine and propranolol. Yet he jumped ship to ICI becase he couldn't get promoted in academia because he didn't publish much. This was in the late 50s! We still laud those with hight h factors. A chap at UC had an h factor of over 200, but he essentially made one (esoteric) discovery and milked it. He was actually a good bloke, but many aren't. My institute is a great place - it isn't a mad house like Stamford or Oxford where staff actually sabotage one another's research, nor is it full of second rate minds like most of the red brick unis and former polys I have had the displeasure to interact with, so I have found my perfect perch. But much of the rest of what is out there is wasteful and crappy.

I have argued we need to reform before the public cotton on to the poor work and start asking 'where has all our money gone'? I know of one charity that has charity shops on every high street that has pissed tens of millions up the wall ever year, and has funded nothing that has generated a new drug. I could go on and on about how his has happened but....human beings again; self serving, perverse incentives etc.

Very interesting from someone on ground floor. You say you are working on something that could save 50k lives. and mention £1b needed to take this to trial.. Matter of interest who supplies the funds for you to take this forward

 

[Motogull]

The scientists should only test on animals when they run out Palace fans.