The Ethics of Animal use in Research

so i’m doing my phd

here at queen’s and i look at the

interactions in between the nervous

system

and the immune system after spinal cord

injury

how those interactions result in the

development of chronic pain

and how we can potentially alter those

interactions

to provide patients with pain relief in

my work

i use a mouse model of spinal cord

injury that does a really good job at

mimicking the human model of spinal cord

injury

although i usually don’t tell people i

just met that last part

because although we owe almost all of

our medical

modern advancements to the use of

laboratory animals

their topic in research can be an

uncomfortable one for many people

and some are completely against their

use altogether

so in february of 2019 an article was

published in the queen’s journal

titled the curtain on animal research at

queen’s lifts and inch

i felt like it was a really negative

depiction

of animal use and research and it

suggested in a lot of ways that

scientists were

stuck in a rut and refused to adapt as

technology moved

forward and indeed if you look online

a lot of the journalism out there is

about how

we have advanced past the use of needing

animals

and a lot of people who do support

animal research don’t like to be too

vocal and talk about it

because in the past themselves or their

families have been harmed or threatened

so i decided in march of 2019 to write

kind of a

response piece to this and i titled it

a letter from a queen’s researcher

animal testing is unfairly judged

at the time i published the article

anonymously

and although i got a bunch of different

friends from a variety of different

backgrounds to read it over

and we had some really insightful

discussions about it i was a little bit

nervous about how people would receive

it

some liked it and others weren’t such of

a

big fan a lot of people thought again

technology has advanced we don’t need

animals in research anymore

some thought that animal research was

cruel and pointless and others thought

that

it just wasn’t right for us to subject

animals to this use

when there’s alternatives

so i think that even though animal

research is one of those uncomfortable

topics it’s a little bit

one of those ethically gray areas it’s

important for us to talk about it

because how can all of you make an

informed stance

on it if you are only given one side of

the story

and i think in a time where there’s

increased public and patient engagement

in research

this is becoming ever more important

so let’s begin by talking about the

legislation behind annual research

so if you are a researcher or a

university

in canada and you would like to use

animals in any capacity

this does include animal testing but it

also includes

animal observation or if you’re using

them to train professionals like

training veterinarians or veterinary

technicians you must obtain

a certification of good animal practice

from the canadian animal care committee

and

this committee gives its certification

out and every three years it must be

renewed

and how it gets renewed is that the

canadian animal care committee will come

to the

institution on a surprise visit so

there’s no tweaking things beforehand

and they will inspect every room and

they’ll look at all the products being

used

and potentially any animals on study

and each university also has their own

animal care committee

but this committee is primarily

concerned with

the protocols and procedures that will

be happening on site or in direct

affiliation with the university

and animal care committees are composed

of a variety of different peoples from

different

backgrounds there are researchers who do

use animals in their work

as well as laboratory technicians who

deal with the day-to-day care of animals

and the university’s head veterinarian

but there’s also researchers

who don’t use animals in their work at

all or commit

community members who have no

affiliation

to the university these protocols are

approved based on the three r’s of

animal research

which are reduction replacement and

refinement

reduction is reducing the number of

animals you would need in your study

and also being able to justify why you

need the animal numbers that you do

replacement can be either replacing your

laboratory animal with an inanimate

system like a computational modeling

system

or it could be replacing your animal

with a less sentient version

and sentience has to do with how

organisms can perceive and process the

environment around them

so an example of this is replacing maybe

a laboratory rat

with a snail or a fish or an insect

and refinement has to do with altering

the process itself

to ensure the model organism is

minimized in the amount of discomfort

and pain it experiences

and the animal care committee each

person must be

okay with the protocol that gets

approved so it’s not a situation where

one person can just be overpowered by

everyone else on the committee

so another common comment i commonly get

is that technology has advanced to a

point where we just don’t need animals

anymore

and don’t get me wrong there’s been some

phenomenal advancements with

computational modeling

and cell and tissue culturing techniques

and but the issue is if we want to

create therapeutics for human use

we are not yet at a point where animals

and their products can be completely cut

out of the research process

without it greatly hindering things

another amazing advancement that’s been

happening

is that scientific groups and

communities have moved towards sharing

their large data sets

as well as creating public databases for

people to use free of cost

so let’s say for example there’s a group

out there

who’s particularly interested in gene

changes that happen

in immune cells after spinal cord injury

perhaps they obtain some blood samples

from spinal cord injury patients

and they run an analysis on it and they

get a huge amount of data

when they’re ready to publish their

findings in a scientific journal

they have to release the entirety of the

data set

to the public for anyone to use i could

for then i could download this data set

maybe i run a different analysis

and pick out a couple different gene

targets

i could then move to a different public

database

one of which is called imgen and see

what the gene expression levels

are in up to 85 different immune cells

could then head back to my lab and use

cultured cell lines to see

if i alter the gene expression of this

immune cell how does that activity of

the cell change

some labs even have the equipment to 3d

print

small organs so we can see how the organ

as a total will change

but of course all of these techniques do

a great job at reducing the number of

organisms we need because before we even

move into a disease model

we might have already eliminated a

couple targets of interest

or maybe we have a better idea of the

disease mechanism itself

but the issue is cells in a petri dish

lack the overall organ architecture

which in some diseases can be super

important

and a 3d printed organ lacks the

interactions that happen

with other organs we are not just a

collection

of a bunch of organisms or a bunch of

organs really close together

all our organs communicate with one

another and the circulatory and immune

system play a huge role

another issue is that each one of our

cells

contains the exact same copy of dna

and this means that different cell types

could express the same genes or produce

the same proteins

so that’s sometimes why when there are

new drugs or new therapeutics you see

off-targeted effects that you didn’t

originally think would happen

another important thing to consider is

causation force versus correlation

so what do i mean by this maybe you took

some blood samples

from patients with and without chronic

low back pain

and maybe in your chronic low back pain

population you saw an increased level of

a certain protein

you cannot assume that that increase of

protein

is what’s causing people’s pain and it’s

not ethical to then medicate your

patients to lower that protein level

which then kind of brings us to a

trickier criticism of animal research

which is how can you say that the life

of a human

is more important than the life of an

animal

so going back to the three r’s of animal

research

sentience which is in the replacement

are

can refer to the ability of an organism

to sense the environment around it and

process it

and it’s a very delicate balance of

using the least sentient organism

possible

but still being able to get clinically

relevant data

so science has to a certain extent

created a hierarchy

of organism life

and even though there are differences

between humans and animals

animals are still contributing massively

to the biomedical science process

for example a recent development out of

the university of calgary

it has been that they found that if you

give ms patients or multiple sclerosis

patients

minocycline which is a common acne

medication

after their first ms event they will

reduce by half

the rate that they could go on to

develop chronic ms

and this is a huge finding for canada

because in canada we have one of the

highest rates of ms in the world

so this finding has done a great job of

improving the quality of life of

thousands of people

and would not have been possible without

the mouse model of multiple sclerosis

and also if you’re a diabetic who’s ever

taken insulin

or maybe an advil or an aspirin or you

went in for a routine surgery

and had to was prescribed antibiotics or

painkillers

you have animal research to thank

because of that

and the reality is scientists at this

time are just using the best models that

they have available

if a non-animal model was to come along

that was as good as or better than the

animal models that we currently use

science would move to adapt to use that

one

but at this point we don’t have those

models available for a lot of diseases

and at the end of the day it’s okay if

you’re uncomfortable with animal

research

it’s a very uncomfortable topic but

supporting animal research doesn’t need

to be an all or nothing approach

you can support the use of animals in

biomedical research

but maybe you don’t support their use in

cosmetic research

or you can read a scientific journal

article and be really critical

about the methods that they used or the

conclusions that they drew from their

study

but making generalized blanket

statements like

all animal research is barbaric and

unnecessary

is simply untrue so why do i

use animals in my work so like i

mentioned i study chronic pain that

develops after a spinal cord injury

and in the province of ontario 11 people

each week

will suffer from a spinal cord injury

and for each one of these patients it

will take them approximately two to

three years

to stabilize and when they do finally

stabilize

they are often faced with a whole host

of medical complications

even though the trauma itself is to the

central nervous system

many different body systems can be

affected

for example heart rate breathing blood

pressure the digestive system the

urinary tract system

movement the musculoskeletal system and

mental health can all be affected

and for sixty to eighty percent of these

patients they will go on to develop

chronic pain

and at this point doctors don’t really

have a lot of effective treatments to

offer this population

and of the treatments that they do have

available many of them

do not lower the patient’s pain to a

rate where they can

live a healthy productive life that they

would like to live

so through the use of computational

modeling

cell and tissue culturing techniques

microbiome analysis

and a new mouse model of spinal cord

injury that i developed

that more accurately mimics a human

spinal cord injury

i hope to go on to help develop better

therapeutics to offer these patients

some pain relief

and at the end of the day i know my

research will be difficult

and it will of course have limitations

to it but i know that people would not

be able to live the quality of life that

they currently do

without the irreplaceable contribution

of many laboratory animals over the

years

thank you

you

所以我

正在皇后大学攻读博士学位,我研究脊髓损伤后

神经系统和免疫系统之间的相互作用,

这些相互作用如何导致

慢性疼痛的发展,

以及我们如何可能改变这些

相互作用

以提供给患者 在

我的工作中缓解疼痛,

我使用了一种脊髓损伤小鼠模型

,它在模仿人类脊髓损伤模型方面做得非常好,

尽管我通常不告诉人们我

刚刚遇到了最后一部分,

因为尽管我们几乎欠所有人 在

我们

使用实验动物的医学现代进步中,

它们在研究中的主题

对许多人来说可能是一个不舒服的主题

,有些人完全反对使用它们,

因此在 2019 年 2 月,一篇

题为《动物研究的帷幕》的文章在女王杂志上发表 在

Queen’s Lifts and inch

我觉得这是

对动物使用和研究的负面描述,它

在很多方面都暗示了这一点

随着技术的

进步,

科学家们

陷入了困境,拒绝适应 ‘不喜欢

大声谈论它,

因为过去他们自己或他们的

家人受到伤害或威胁,

所以我决定在 2019 年 3 月写

一篇对此的回应,并将其命名

为女王研究员的一封信

在我匿名发表这篇文章时,动物试验受到了不公平的评价

,尽管我有一群

来自不同

背景的不同朋友来阅读它

,我们对此进行了一些非常有见地的

讨论,但我

对人们如何看待它有点紧张 会收到的

有些人喜欢,有些人不是很

喜欢很多人再次认为

技术已经进步,我们不再需要

研究动物

有些人认为 在动物研究中是

残酷和毫无意义的,其他人

认为,

当有替代品时,我们让动物接受这种用途是不合适的,

所以我认为即使动物

研究是那些令人不安的

话题

之一,它在道德上也有点像其中之一 灰色地带

讨论它对我们来说很重要,

因为如果您只了解故事的一方面,那么你们所有人如何才能就此做出明智的立场

,我认为在

公众和患者

参与研究

的时代越来越多,这正在成为 越来越重要,

所以让我们从讨论

年度研究背后的立法开始,

如果您是加拿大的研究人员或

大学

,并且您想

以任何身份使用动物,

这确实包括动物试验,但

也包括

动物观察,或者如果您 重新使用

它们来培训专业人员,例如

培训兽医或兽医

技术人员,您必须从加拿大获得

良好动物实践

的认证 ian 动物护理委员会

该委员会颁发

证书,每三年必须

更新一次

,更新的方式是

加拿大动物护理委员会将突然

访问该

机构,因此

事先没有任何调整

,他们将检查 每个房间,

他们会查看所有正在使用的产品

,可能还有任何正在研究的动物

,每所大学也有自己的

动物护理委员会,

但该委员会主要

关注

将在现场或直接

附属机构发生的协议和程序 大学

和动物护理委员会

由来自

不同

背景

的各种不同人组成

但也有研究

人员在他们的工作中根本不使用动物

或致力于

社区 与大学无关的成员

这些协议是

基于动物研究的三个 r 批准的

您进行

替换的数字可以是用计算建模系统等

无生命系统替换您的实验动物,

也可以是

用较少感知的版本替换您的动物,

而感知与

生物体如何感知和处理

周围环境有关,

所以 这方面的一个例子是

用蜗牛或鱼或昆虫代替实验室老鼠

,改进与

改变过程本身有关,

以确保模型生物体

的不适

和疼痛最小化

,动物护理委员会 每个

人都必须

对获得批准的协议感到满意,

所以这不是一种

情况 没有人可以被

委员会中的其他人压倒

所以我通常得到的另一个常见评论

是技术已经发展到

我们不再需要动物

并且不要误会我的地步计算已经取得了一些

惊人的进步

建模

以及细胞和组织培养技术

,但问题是,如果我们想

创造供人类使用的治疗方法,

我们还没有达到

可以将动物及其产品完全

排除在研究过程之外

而不会大大阻碍事情的

另一个惊人进展 正在

发生的事情

是,科学团体和

社区已经开始共享

他们的大型数据集

,并创建公共数据库供

人们免费使用,

所以假设有一个团体

对免疫系统中发生的基因变化特别感兴趣

脊髓损伤后的细胞

也许他们从脊髓损伤患者那里获得了一些血液样本

他们对其进行分析,

当他们准备在科学期刊上发表他们的发现时,他们会获得大量数据,

他们必须向公众发布整个

数据集

,以供任何人使用

,那时我可以 可以下载这个数据集,

也许我运行一个不同的分析

并挑选出几个不同的基因

目标

,然后我可以转移到一个不同的公共

数据库

,其中一个叫做 imgen,查看

多达 85 个不同免疫细胞中的基因表达水平是多少?

然后回到我的实验室,使用

培养的细胞系,

看看我是否改变了这种免疫细胞的基因

表达 总数会发生变化,

但当然所有这些技术

在减少我们需要的生物数量方面做得很好,

因为在我们

进入疾病模型之前,

我们可能已经消除了

几个目标 兴趣,

或者我们对疾病机制本身有更好的了解,

但问题是培养皿中的细胞

缺乏整体器官结构

,这在某些疾病中可能非常

重要,

而 3D 打印的器官缺乏

与我们其他器官发生的相互作用 不仅仅是

一堆有机体或一堆器官的集合,它们

真的很紧密地结合在一起,

我们所有的器官都相互交流

,循环系统和免疫

系统发挥着巨大的作用

另一个问题是我们的每个

细胞都

包含完全相同的 dna 副本

这意味着不同的细胞类型

可以表达相同的基因或

产生相同的蛋白质,

所以有时当有

新药或新疗法时,你会

看到你最初认为不会发生的脱靶效应,

另一个需要考虑的重要事情是

因果关系与相关性

所以我的意思是什么也许你

从患有和不患有慢性

腰背的患者身上采集了一些血液样本 疼痛

,也许在您的慢性腰痛

人群中,您看到某种蛋白质水平升高,

您不能假设蛋白质的增加

是导致人们疼痛的

原因,然后用药物治疗您的

患者降低蛋白质

水平是不道德的 给我们带来了

对动物研究的一个更棘手的批评,

那就是你怎么能说人类

的生命比动物的生命更重要,

所以回到动物研究的三个

r 的替换

可以参考的

有机体感知周围环境并对其进行

处理的能力

,这是一个非常微妙的平衡,即

使用尽可能少的感知有机体,

但仍然能够获得临床

相关数据,

因此科学在一定程度上

创造了有机体生命的层次结构

和 即使

人类和动物之间存在差异,例如

动物仍然为

生物医学科学进程

做出了巨大贡献 卡尔加里大学最近的一项发展

是,他们发现,如果您

在第一次 ms 事件后给 ms 患者或多发性硬化症患者服用米诺环素,这是一种常见的痤疮药物,他们将

减少一半

的速度,他们可以继续

发展慢性 MS

,这对加拿大来说是一个巨大的发现,

因为在加拿大,我们拥有

世界上 MS 发病率最高的国家之一,

因此这一发现在

改善成千上万人的生活质量方面做得很好

而且不会 如果没有

多发性硬化症的小鼠模型,

并且如果您是糖尿病患者,曾经

服用过胰岛素,

也可能是 advil 或阿司匹林,或者您

进行了常规手术

并且不得不服用抗生素或

止痛药,

那么您要感谢动物研究,

因为

现实情况是,科学家们

此时只是在使用他们现有的最好的模型,

如果要出现一个非动物模型,

那就是一样好或赌注 不是

我们目前使用科学的动物模型

会适应使用那个模型,

但目前我们没有这些

模型可用于治疗很多疾病

,归根结底,如果

你不满意也没关系 动物

研究

这是一个非常不舒服的话题,但

支持动物研究

不需要是全有或全无的方法

您可以支持在

生物医学研究中使用动物,

但也许您不支持在化妆品研究中使用它们,

或者您可以阅读科学 期刊

文章,并对

他们使用的方法或

他们从研究中得出的结论持批评态度,

但是像所有动物研究一样做出笼统的概括性

陈述

是野蛮和

不必要的,

这根本是不真实的,所以我为什么要

在工作中使用动物,就像我

提到的那样 我研究

脊髓损伤后出现的慢性疼痛

,在安大略省,每周有 11 人

会遭受脊髓损伤

,每人 这些患者

大约需要两到

三年的时间

才能稳定下来,当他们最终

稳定下来时,

他们通常会面临

一大堆医疗并发症,

即使创伤本身是对中枢神经系统的创伤,

许多不同的身体系统也会受到

影响

,例如 心率 呼吸

血压 消化系统

泌尿道系统

运动 肌肉骨骼系统和

心理健康都会受到影响

,这些患者中有 60% 到 80%

将继续发展为

慢性疼痛

,此时医生并没有

为这一人群

提供的许多有效治疗方法以及他们确实可用的治疗方法中的

许多

都不能将患者的疼痛

降低到他们可以通过使用计算来过

上他们希望过的健康的生产性生活的速度

建模

细胞和组织培养技术

微生物组分析

和脊髓损伤小鼠新模型

我开发

了更准确地模拟人类

脊髓

损伤的帽子

对此,但我知道,如果没有许多实验动物多年来不可替代的贡献,人们

将无法过上他们目前的生活质量,

谢谢