My good friend and blogfather, Orac, posted something yesterday about animal testing

in medical laboratories. I've been meaning to write something about that for a while; now

seems like a good time.

I'm not someone who thinks that being cruel to animals is no big deal. I have known

some people like that, but thankfully they're very rare, and none of them

were scientists whose work involves doing animal testing in real laboratories.

But animal testing isn't about pointless cruelty. It's about understanding things that we

simply cannot learn about in any other way. It's extremely important to minimize the

cruelty we inflict on the subjects of animal tests: there's no benefit in torturing an animal;

there's no good reason to inflict unnecessary pain on any living thing. When we

can study something without using animals, we should. When we must use animals

in scientific study, we should be as kind to them as we possibly can. But the fact remains that in many cases, animal studies are necessary.

I don't want to get into a long discussion of the ethics of it here; that's a discussion

which has been had hundreds of times in plenty of other places, and there's really no sense

repeating it yet again. But there is one thing I can contribute to this discussion. One of the

constant refrains of animal-rights protesters arguing against animal testing is: "Animal

testing isn't necessary. We can use computer simulations instead."

As a computer scientist who's spent some time studying simulation, I feel qualified

to comment on that aspect of this argument.

The simplest answer to that is the old programmers mantra: "Garbage in, Garbage out".

To be a tad more precise, like any other computer program, a simulation can only do what

you tell it to. If you don't already know how something works, you can't simulate it. If you

think you know how something works but you made a tiny, miniscule error, then the

simulation can diverge dramatically from reality.

Simulations are an incredibly useful technique. They can be used in several different ways:

If we know how something works, we can simulate it, and do experiments simply by

changing parameters to the code. This can allow us to perform experiments that

would be impossible in the real world, or to run multiple experiments much faster

than we could, in a more controlled fashion, than we could in the

real world. For example, we can run orbital simulations of our solar system which

are astonishingly precise, and which allow us to try scenarios that would be impossible

to test in the real world. If we don't know how something works, but we have a theory, we can test it

by implementing a simulation according to our theory, and comparing the results of

the simulation to observed real-world results. If our simulation closely matches what

we observe in the real world, it's a great piece of supporting evidence. If it doesn't,

it means we got it wrong. For example, people have been running massive simulations of

the experiments that hope to produce the Higgs boson, which allows them to make

predictions about how they'll be able to recognize it if their experiments manage to

create one. If we know part of how something works, we can build simulations give us a way

of experimenting specifically on that part without the added complexity of

a complete system. For example, we can study specific parts of cellular metabolism:

we know the basic chemistry of how a mitochondria produces energy for the cell. We

can focus our attention on simulations of that specific process, without dealing

with all of the details of cellular metabolism.

It might sound like I'm saying that simulations can't surprise us - because they

can only produce things that we already know. That's not the case - accurate simulations can be extremely surprising. The most common cause of that is a phenomenon called

emergence. Emergent phenomena are things where some thing behaves one way at one scale,

but changes dramatically when you put together huge numbers of those things and look

at them at a different scale.

The best example of emergent phenomena is our macro-scale universe. When we look at

the world, things seem concrete and predictable. When you watch a baseball game,

you can see the baseball fly from the hand of the pitcher to the bat, and it's obvious

that you can precisely describe both the position and the velocity of the baseball when it's

in flight. But the baseball is made up of a huge number of particles which do not behave in such well-mannered ways. They're unpredictable, erratic. Their behavior can't

be described precisely, only probabilistically. And yet, when we put together quadrillions of quadrillions of unpredictable, probabilistic particles, we get something concrete, comprehensible, and extremely predictable.

Simulations can (and frequently do) surprise us due to emergence. We

may understand the how some thing works, without understanding what's going to happen when we

splice together a billion of them. (Simulations can produce surprises due to things

other than emergence; the reason that I stress that one is that it's the one I've experienced.)

But getting back to the topic at hand: when it comes to animal testing, most of the

time, we can't use simulations - because we don't understand enough to be able to

do an accurate simulation. We can't simulate what we don't know. And when it comes to

medicine, there's an awful lot that we don't know.

A few examples: we know that a lot of non-coding DNA has function doing various things

like regulating coding DNA. We don't know all of the functions of non-coding DNA. Of the non-coding regions we basically understand, we don't understand how they all work. Getting

away from DNA, the basic day-to-day functioning of our cells includes tons of

processes that we simply don't understand. There's so much going on in a single cell

that we don't understand yet, that we don't have a chance of producing a dead-on accurate simulation of it.

And to try to simulate more than a single cell is even harder - because the cells of

our body have an extremely complicated set of interdependencies and interactions. To do a simulated drug test, we need to simulate both the intra- and inter-cellular processes that would be affected by that drug. And the fact is, we don't.

To throw out another example: as I've mentioned before, I have clinical depression.

I manage it by taking a selective serotonin reuptake inhibitor called "zoloft". For me,

and for many other people with depression, SSRIs are almost miracle drugs - they

completely eliminate the symptoms of depression. But: We don't know why zoloft works.

It was designed under a theory - the "serotonin theory" - that thought that depression was

caused by an inadequate supply of serotonin in synapses of the brain; zoloft was

designed specifically to target the cellular mechanisms by which serotonin is

removed from those synapses. But that theory has, largely, been discredited. It appears

that the mechanism that zoloft was designed to target is not the mechanism

by which it works! Why? No one is sure, but a lot of people are doing a lot of work to try to understand it.

For the people trying to understand that, in order to develop better treatments

for depression, simulations are no good - because we don't know the mechanism by which

the drugs work. We know that they do, but we don't know why or how.

When it comes to other things, we're in a similar situation. Will a new antibiotic work? Maybe. Maybe not. How do we know? We need to test it. We start with tests in cell cultures. But lots of drugs that work in cell culture don't work in a living creature. There are numerous chemicals that kill HIV in cell culture, but don't work in an infected animal. There are tons of chemotheraputic agents that kill cancer in culture, but that don't work in

an animal or a person. We can't do tests of those using simulations, because we simply

don't know enough about the underlying mechanisms. And if we don't understand a process

or mechanism, we can't simulate it.

Life is still very mysterious to us. There's so much about living things and the

basic physical and chemical processes that occur inside of them that we don't understand. Those mysteries are what we try to study with science, in order to develop more understanding. Simulations can be a useful tool in the process of exploring. But it can't replace observations and experiments with real living things. There's still no substitute

for reality.