How We Go from Animal Model to Clinical Trial

[♩INTRO] When we talk about cool new research here
on SciShow, you might hear us say something like: “This study was done on
rats. And rats aren’t people.” It’s nothing against them personally. Animal studies allow scientists to test new
treatments in living, breathing organisms before they try them out in people, which helps spot complications or potential
pitfalls. But animals aren’t mini humans, so what happens in a mouse may not happen
the same way in a person. And that means two things. For one, it means we can’t always assume
a cure in mice will be effective in human patients. But it also means that safely going from animal
to human trials is a lot more complicated than you might think. Before any animals even get involved, pharmaceutical
researchers run a bunch of what are called in vitro tests, basically anything done in dishes and tubes
rather than animals. What they’re doing has to have a lot of
potential since, as you can imagine, the use of animals in research can be unsettling
for a lot of people. Many countries have formal institutions in
place which try to limit the use of animals for cases where they’re really
needed, and they have regulations which specifically ensure these animals are
treated in a humane way. Now, a lot of medical research is conducted
in rodents. That’s because rodents are small, easy to
breed, and relatively cheap to care for in large
numbers. And rodents have enough similarity to humans
in a lot of areas, including genetics, behavior, and biology,
that they can help scientists suss out whether a drug has real potential. Also, we can breed them to be optimized for
research. Large numbers of rats can have almost identical
genomes, for example, allowing for more uniform and reliable results. And scientists know how to manipulate their
genomes to get what we call knockout specimens: ones that lack specific
genes. This lets them dig deeper into what a treatment
is actually doing to the body, which helps minimize any surprises that might
happen when a drug is given to humans instead. You might think it’s strange that so many
trials are done in mice or rats when we’d get the most reliable information
from animals that are closer relatives, especially other
primates. But while primates are the right choice in
some cases, there are ethical and logistical concerns with conducting research
on them, and for the most part, rodents are pretty good substitutes. Besides, testing a drug in primates doesn’t
guarantee a smooth transition to human trials, because the only animals with
all the right cells and proteins to perfectly predict what happens in a human
body are, well, humans. That’s why, even when a drug has passed
animal tests with flying colors, researchers build in a number of safety measures
to minimize the risk of adverse reactions in people. It’s considered important to use as little
of the drug as possible, for example. That usually means starting with the smallest
amount that seemed to work in animals, called the minimum anticipated biological
effect level, or MABEL. If that doesn’t cause any problems, but
doesn’t work, either, then researchers can dial up the dosage. They also lay out exactly what their definition
of “working” is ahead of time. These are what are called primary and secondary
outcomes. If they’re too lofty or unfocused, like if there are dozens of things the drug
could do, then you’re likely to perceive a benefit
that isn’t really there. This is what’s called multiplicity in a
trial, and it arises because the statistics used to determine whether something has made an
impact or not have a certain margin of error. On the flip side, if your trial outcomes are
too narrow or impossible to obtain, you might not realize a drug is actually doing
something good. And at the same time as they’re determining
primary and secondary outcomes, researchers also set guidelines for adverse
event outcomes, basically, what reactions mean it’s time
to call it quits, and what reactions, though perhaps unpleasant to experience, aren’t
really that big a deal. The good news is that they already have an
idea what might happen from those preclinical animal experiments. But they also have to make plans for things
that come out of left field. So, they make guidelines to determine how
to react if things go wrong, which take into account everything from the
number of participants affected to the severity of their reactions. Of course, it doesn’t help matters if companies
are overzealous about their hopeful cures. In many cases, when a failed clinical trial
makes headlines, investigators later discover corners that
were cut along the way. But sometimes, researchers do everything right
and the worst still happens. Take the 2006 trial for TeGenero, an antibody that researchers hoped would be
the next cure for a set of autoimmune diseases. For the first human test, 6 of the otherwise
healthy participants were given 1/500th the dose used during primate
trials, but within an hour, all experienced severe inflammatory reactions
requiring hospitalization. The drug was supposed to activate certain
cells in the immune system, so in a sense, it was doing its job, it just
did it a little too well. The human cells the drug targeted turned out
to be way more sensitive than any of the animals tried. And that kind of uniquely human reaction to
a drug is really hard to predict. Nowadays, trials build in a lot more safety
measures than they did a couple decades ago, like taking more time between
dosing each participant to see if something bad happens. And they can take advantage of newer technologies
like computer models that can better predict how human proteins
interact with potential drugs. But researchers and regulators are still working
on ways to make the clinical testing process even safer. And a big part of that is making better protocols
for working with animals. That’s because, despite all the amazing
things we can do with computers, bodies are really complicated. So we still need animal testing to see how
things work in real living things. So even though rats aren’t people, we still
need their help to keep people safe. Thanks for watching this episode of SciShow! If you enjoyed learning more about the importance
of animals in research, you might like our episode about 5 times researchers
gave animals drugs and what we learned from those experiments. [♩OUTRO]

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80 Responses

  1. Vic Philip says:


  2. themanhimself3 says:


  3. X6yy17 says:

    Can u pin this comment pls

  4. teflonravager says:


  5. Zero Rebellion says:

    Wow i am so early it is my first time i am second

  6. ArchEnema 67 says:

    My favorite animal model is Jessica Rabbit.

  7. nattygsbord says:

    I think Josef Fritzl and such people could be used instead of testing on animals.

  8. PaleGhost69 says:

    We really should just stick to human trials and give people adequate compensation for any troubles. Oh wait, that's right. We can't give people healthcare in this country!

  9. Strange Hardware says:

    She seriously doesn't have a narrator's voice. The downward, raspy inflection at the end of every sentence she says is so distracting.

  10. SlyPearTree says:

    What if it does not work in animals but would have in humans?

  11. Chuck U Farley says:

    I did a couple clinical trials when I was younger people worry about side effects but I had none.
    I did a couple clinical trials when I was younger people worry about side effects but I had none.
    I did a couple clinical trials when I was younger people worry about side effects but I had none.
    I did a couple clinical trials when I was younger people worry about side effects but I had none.

  12. darkangel21892 says:

    You should've mention how cruelly free products still use animal testing during the development process. They can use the label because the final product that is released to the public isn't tested on animals like prior formulations of that same product were

  13. Michael says:

    instead of testing on animals we should use people in that are in prison with life sentences and/or on death row. Let them contribute to society

  14. Marantz 5006 says:

    Test should be done on murderers, rapist and pedos!

  15. Master Therion says:

    1:40 Those mice are called "knock out" because they are so attractive to researchers as animal models.
    "Wow, look at that model, she's a knock out."

  16. Michael Fregoso says:

    I'm curious if there were a drug that could save human lives but was deadly to every other animal would we ever be able to discover it?

  17. Michael Fregoso says:

    Also what is the ethical difference between experimenting on one animal versus another if neither is worthy of personhood?

  18. Bentley Angeldekao says:

    Animal are not people
    It’s nothing personal

    Darn it I thought you had personal beef with mice

  19. Xpert2021 says:

    We should just test them out on pedophiles. Ezpz

  20. SteveVi0lence says:

    I love sci show!

  21. Gitana Maldita says:

    Let those animals being treated in a human way.

    Poor animals…being treated as humans treat themselves.

  22. Zachary Laid Finding Freedom says:

    Pigs are closely related to humans, hence the swine flu.

  23. English killer make talent says:

    What's the Time in your country ???
    In my country 5:42 am??

  24. Peanut366 says:

    This host…you really need to learn to stop upspeaking, everything sounding like a question is like nails on a chalk board?

  25. Havioc Darkmoon says:

    I doubt I will get the answer her but why do a lot of drugs on the market right now seem to have more side effects the the drug it self. I’m manly talking about the ones a see on tv some of the possable side effects seem worse then what the drug is trying to do, so how to they get approval with all the side effects

  26. All Videos says:

    Animal testing is lit

  27. Jon Boshears says:

    They should use chomos for science experiments

  28. Christian O. Holz says:

    great informative and detailed presentation!

  29. Ace Lightning says:

    I remember an old joke from Saturday Night Live's "Weekend Update"
    …and this just in: "White mice cause cancer!"

  30. Osmosis Jones says:

    Is observing life spans and behavior and rethilats of cells. In petry dish different from cells in a body

  31. Cuddly Cactus says:

    Seriously, we need to stop animal testing for anything intended for use in HUMANS.
    I watched a video awhile ago about testing being conducted in a lab on human cells, this was a new type of testing method they developed using human cells in the lab. It definitely looks promising. And the one problem with using rodents for human RX testing is that for (mostly) anything involving female reproductive issues or rather menstruation problems, rodents do not have a period! Instead of shedding the lining of the uterus they actually reabsorb it. (And as a female, I am definitely jealous!)

    And I really really wish they would just stop testing things like shampoo & make up on animals!!! I always look at the label to make sure any products I buy we not tested on animals, there's a little hopping bunny logo to look for to make it easier. It's just so pointless to subject animals to this type of testing, do a little digging online and find out more, it's truly awful & needs to be banned!!

  32. Daein Ballard says:

    They need genetically engineer rat/mouse models that are as close to humans as possible on a molecular level. As you pointed out one stray protein or enzyme may throw the whole thing off. You used examples of drugs but this can also happen the other way around. For instance Safrole; a common flavoring in drinks and foods before the 1960s. A study in rats found that it causes cancer, in rats… So it was banned by the FDA. This is why Rootbeer doesn't taste like Rootbeer anymore and after the band Rootbeer became way less popular since the flavoring needed to be removed. Anyway some thirty years later another study was done in and it found that rat livers have break down pathways for safrole that human livers don't. The result was significantly higher risk for cancer in rats that didn't exist in humans. Of course Safrole is still banned because "better safe than sorry" right?

  33. Quantum Proton says:

    I vote to use paedophiles who are rotting in prison.

  34. dbd978 says:

    please fix audio it's annoying!

  35. Everything Science says:

    Very good video! How far away do you think we are from making high quality, artificial human tissue so we can do these in vivo measurements on (fake) real human cells?

  36. tothedirtwhenidie says:

    she makes me click

  37. Mike Bennett says:

    With the number of clinical trials going on, this video illustrates the number of potential risks for the volunteers. Thank you. Excellent content.

  38. - says:

    There are lots of monsters on death-row that would make excellent model organisms. May as well get some good from them. ¬_¬

  39. Trevor Orchard says:

    Always respect the science boys and girls (rats and mice) for their continued huge contribution to humans.

  40. Veronika says:

    Thank you so much for an awesome video on lab animals and their importance!!! I work for a company that makes heart valves and I was an animal husbandry technician, now I’m a surgical technician in the same department (working with lab animals). I love my job! And I love giving the animals a high quality of care while helping advance important heart valve research

  41. Hsuman Of Magnanimous Intent says:

    when i think Mabel
    grappling hook!!

  42. LeatherNeck 1833 says:

    Cue the PETA frenzy!

  43. Angie Baby says:

    Scishow is the first channel i ever subbed to… I dont even know how long ago… So long lol

  44. Melias Clarkson says:

    But rats are people imo! They're just not human.

  45. 0ctoroo says:

    I'm in 2nd year of B. Pharm. And this is very useful information.
    Thank you SciShow?

  46. Azi Poor says:

    It's just my my idea, Olivia Gordon speaks better than Hank Green, I like him he's awesome but he's speaking very very fast.

  47. nattygsbord says:

    Why not do testing on cucumbers if we share 98% common DNA with them?

  48. Waylen Edge says:

    Wow she is fugly!

  49. huldu says:

    Why not just use convicted criminals in prison for trials? They've made the choice to be a criminal and therefor should not be considered a part of our society.

  50. breaking beast says:

    So, we know mosquitos are rare species that IF exterminated wouldn't damage eco system. So instead of using CRISPR to kill them why not use it to spread cures, stremgthen their immune system…

  51. P DaPhuuLz says:

    Cats are people too!

  52. Rick Harold says:


  53. Pierre Abbat says:

    I've been reading about the effect of vitamin C on uric acid and blood sugar. Some articles mentioned rat studies. That doesn't make sense. If you're going to test vitamin C doses on rodents, they should be guinea pigs, which don't make vitamin C.

  54. Nick Voelker says:

    You forgot the most import step: Secure funding. Most research dies at the animal testing phase simply because of a lack of funding to progress onto human trials. Step one really should be selecting an area of research where you can demonstrate that there's a potential for huge profits in the future. i.e. obesity research gets about $20 billion in funding annually. Not sure what they're researching though, not a whole lot of mystery in that area.

  55. batmanfanforever08 says:

    Animal testing will always be needed. We mayn't like it, but animal testing will always be needed. I do think we need to treat the animals more humanely, but yes animal testing is still needed.

  56. El_Nacho says:

    I wonder how many drugs werent developed further, because they did not help in mice, but would have worked in humans.

  57. Avery Sax says:

    You make me voracious … :)))

  58. Chad Mojito says:

    Editor messed up the audio! Several syllables at the beginning or end of her lines are blatantly missing or notched. Was this made by an intern using Audacity?

  59. leppie says:

    I hope that machine learning will eventually eleminate the use for animal testing. Edit: Nothing against it, but better if we dont need to.

  60. Gabe K says:

    human trials should be done on heinous convicts, be their only way to truly benefit humanity aside from their deaths.

  61. Igor Karlić says:

    Vegan fanatics are criminals against humanity.

  62. Pa Pinkelman says:

    Rats aren't people.
    But a lot of people…

  63. Fawks Masters says:

    Daaamn, i must be ovulating today, host lookin’ fiiiiiiiiine

  64. Matt McGregor says:

    Never quite understood why it's ethically wrong to experiment on a monkey or ape, but ok to experiment on rats and mice. I understand that the latter breed and produce at a much faster rate, but what's really the difference. Still an animal. Not human.
    Does it really matter if there's similarities with us, and other primates? Still, very much not human.

  65. Ryan McLain says:

    Not really about how to get from A to B…

  66. Laff700 says:

    "Rats aren't people. It's nothing against them personally."

    I don't know, that sounds pretty specist to me. It's accurate to say they aren't humans but that doesn't mean they aren't people.

  67. Buster Beagle says:

    Did someone get some speech coaching? I think so.

  68. Fernando Pires says:

    #t=5m37s "We still need their help to keep people safe". Yeah, the mice must be really glad to help being tested and killed for our needs. Very bad phrasing in this video. If you want to defend animal testing at least admit how unethical and cruel they are.

  69. Existenceisillusion says:

    Yeah, but The Rats of NIMH was a good book

  70. Juzzy Potter says:

    Rats aren't people, but some people sure are rats.

  71. Sagacious Eagle says:

    Any thought on experimenting on prisoners on death sentence?

  72. Thecrazeeespaceman says:

    Rats arent people…. but some people are rats… (mafia accent)

  73. DoctorX17 says:

    folds proteins

  74. Cat Man says:

    If you are looking for interesting topics to make videos about, you may want to focus on some recent research on curing hear loss. This is a problem that affects millions of people, and there are prospects on the way. I hope you take the time to look at the following websites that are reporting on this.

  75. diane toomey says:

    Interesting omission in this video: Drugs that test safe and effective in animals fail in humans about 95% of the time. That's a statistic from the National Institutes of Health:

  76. Iago Silva says:

    0:11 Rats may not be people, but Soylent Green is

  77. douglas steel says:

    I hate the editing of these things, its really distracting and irritating. I'm not sure what chopping transients off words is intended to convey. Urgency? All the time. At least vary it

  78. Jason Gastrich says:

    Rats, cats and baseball bats

  79. Force says:

    John, get this idiot valley girl outta here.

  80. radzewicz says:

    Hi Olivia. Consider some of the gibberish that is being spread over butter vs margarine. What is butter? Butter is a suspension of milk solids in fat. what is margarine? Margarine is a suspension of milk solids in fat. So what's the difference? By law since 1943 (US) butter must contain animal fat, specifically dairy fat. margarine is a more general, generic term and butter is a form of margarine. so margarine can contain any type of fat, including walrus fat, should you so choose. To be realistic, heart-healthy margarines such as Promise or ICBINB are made with plant fats. Plant fats are liquid at room temperature so we call them oils. To make them more solid they are partially hydrogenated. However even after hydrogenation they still contain less than 1/3 the saturated fat of butter. And, like butter, they contain zero trans fat (read the friggin' labels!). So, bottom line, is that heart-healthy margarines are much better for your health than butter and neither is "one molecule away from being a plastic".

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