Cyto-Toxicity and dosage

Ryan_m_b

It really depends on the drug. Ideally you want to be as close as possible with genetics to a human but you also want to be as close as possible in proteomics. Some species are less related genetically but are better at simulating specific systems or tissues. Other species such as drosophila have only 50% genetic similarity and 70% protein (if i remember that correctly, its been a long while since ive worked in a drosophila lab!) but are useful for development and genetic studies. They're also quite good because they breed in large numbers and through generations very quickly.

Drug testing is a very wide field, it's not really as simple as "test the closest to human". If we had humans that we tested on theres a lot of work we couldnt do, such as how genetic diseases progress across generations unless you want to go to the expense and time of breeding thousands of people for hundreds of years.

I wish we didnt have to test on animals but there is no alternative at the moment. Hopefully over the next several decades our progress with tissue engineering and regenerative medicine will provide us with fully formed in vitro tissues/organs to test on instead.

Jennifer100

What are the reasons to not test drugs on cats instead of dogs? Don't dogs and cats have around the same amount of genetic difference to humans?

(Although obviously there's a lot of variables like what drug is involved)

Which is better; cats or dogs (If you're taking into account specifically the proteomics of cats versus the proteomics of dogs)

Ryan_m_b

I'm not entirely sure however I do know that cats are primarily used in neuroscience research whilst dogs are more used for drug testing. As you point out the variables of what you are trying to test make a difference, also note that genetic difference is far from being the sole contributor.

As we have already conducted decades of research on cats and dogs (and drosophila/mice/rats for that matter) we already have a detailed understanding of how their biology matches/differs from ours and have designed standardised protocols for dealing with them. If we were to switch to another animal it would take further decades of research to get to a point where the use of said animal rivals that of a cat or dog.

A quick search didn't give me any indication that the proteome of dogs and cats has been fully mapped. Even if it had depending on what you want to test would decide what you wanted to use. If drug X affects the Shapes system# and that system is both inherit in dogs and cats then your choice of what to use changes to include costs, ease of access, systemic effects etc etc etc

I'm afraid there is no simple answer to your question, we can't make a list of "best animals to use" and rank them. What animal to use depends on what you are testing (does it even have to be an animal? What about plants/bacteria/cell culture?), what animal models currently exist and a multitude of other concerns.

#(--> = activates --| = stops) Square --> Circle --> Triangle --| Circle

Jennifer100

how much better is a rabbit to test (to determine potential toxicity of a drug on humans) on than a rat? In terms of its genetic similarity to humans and how much worse is a rabbit to test (to determine potential toxicity) on than a cat or a dog? in terms of its genetic similarity to humans (in regards to just genetic similarity to humans; I know that theres other variables involved in animal testing)
because for example I read this

http://wiki.answers.com/Q/Are_rabbit..._rodent_family
Contrary to popular belief rabbits are not part of the rodent family although they look very similar. They are part of the Lagomorph family, which are more closely related to horses due to similar methods on how their digestive systems function.

Read more: http://wiki.answers.com/Q/Are_rabbit...#ixzz1IFKO1opJ

Ryan_m_b

I'm sorry but I'm going to have to quote my previous answer to answer this question

May I ask why you are asking? No offence but it seems like you are reeling off one question after the other without reading the answers

Jennifer100

Is there no alternative to testing drugs/compounds etc on animals that is just as good as testing drugs/compounds etc on animals? because I read this on wikipedia


there is no alternative to testing drugs compounds etc thats as good as testing drugs compounds etc on animals right? Since I read this on wikipedia

http://en.wikipedia.org/wiki/Alterna...animal_testing

Two major alternatives to*in vivo*animal testing are*in vitro*cell culture techniques and*in silico*computer simulation.**Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems.[2]*Other alternatives, not subject to this criticism, involve the use of humans for skin irritancy tests and donated human blood for pyrogenicity studies.

Ryan_m_b

It depends on what you are testing but the answer is essentially no, there is no current replacement for animals. Cell culture does not represent the workings of an organism well as they do not create interacting 3d, representative models. However there is a drive to improve our ability to grow human tissues and organs in vitro for testing but we are a long way from being able to do that.

Whenever someone mentions in silico I cringe at their lack of understanding. We can't even simulate how proteins fold with much accuracy or speed, to simulate the entire human body (you would need to do it atom by atom) would require computing power far in excess of anything of our wildest dreams. A bigger problem of that is that any computer simulation that realistic would be able to feel pain, have emotions and thoughts. You've moved the ethical problem from in vivo organisms to in silico

Jennifer100

If you order what is most genetically similiar to humans in this way

Rats Less so than rabbits, rabbits less so than cats and dogs, cats and dogs less so than primates...


where would intelligent parrots, dolphins etc go? Approx? Would they be between cats & dogs & Primates?

Ryan_m_b

"Intelligence" isn't a measure of how genetically close something is to humans. Cats, dogs, primates and rodents are all more similar to us than birds because they are mammals like us. Dolphins are also mammals so they would be closer to us than birds but as our common ancestor was so long ago we are closer to cats, dogs, primates and rodents (who we diverged from far more recently)

When you ask how genetically similar something is you are essentially asking "how long ago did our evolutionary lineages diverge"

Jennifer100

What animals are closer to humans genetically than dogs cats and pigs but less close to humans than primates; and what animals are closer to humans genetically than dogs cats pigs and primates?

Ryan_m_b

Google "mammalian phylogeny". You can find all sorts of diagrams showing the relatedness of organisms, heres two I found that may help you

http://whozoo.org/mammals/mammalianphylo.htm

http://bit.ly/h0xKAC

Jennifer100

because collies have such a notoriously permeable blood/brain barrier; how much worse is it to test the toxicity of a drug on collies and/or dogs with some collie in them, than it is to test on other breeds? (just looking for opinions/approxiamete info)

Ryan_m_b

It depends on what you are testing for. If you want to test a drug and it kills the collie due to CNS toxicity then you would want to account for how the drug may behave differently in other animals.

Jennifer100

I noticed from reading that:

Beagles have a blood brain barrier that is closer to humans than collies
Collies have a notoriously permeable blood brain barrier
So in that regard beagles are better for testing than collies

But what are the upsides and downsides of testing on dogs that are:

jack russel terrier
Huskey
Australian Shepherd
Heeler

and dogs that are a mix of those? For example do huskies also have a notoriously permeable blood brain barrier?

Jennifer100

Do you mean that, if the effect of a compound is sensitive to modifications of the compound and/or components of the compound; that as the dose of compound rises, the available compound for treating what you're trying to treat has an inverse relationship to dosage given orally. and that as a result, if you need to have a very HIGH level maintained, you'd need to buffer it, or administer it through other means.

Or were you just referring to a specific drug when you said that and not answering my question, specifically, about what a compound (or components of a compound) being sensitive to modifications meant thanks