What do scientists do?

Those scientists. What do they want to do now?

They want to dig an enormous donut-shaped hole in Texas at a cost of hundreds of millions of dollars.
They want to breed millions of deformed fruitflies.
They want to send a chunk of machinery into space to look at microwaves.
They want to infect apes with a lethal virus.
They want to fill an abandoned mineshaft in South Dakota with purified water.
They want to drill holes in monkeys' skulls and stick wires into their brains.

And they get paid for this? I can't believe it. Tell me again.

They want to find out why things have mass.
They want to understand evolution.
They want to find out the age of the Universe and what it's made of.
They want a cure or a vaccine for AIDS.
They want to look at invisible particles from the centre of the Sun.
They want to understand the brain.

Oh. Well, was all of that nasty, expensive stuff really necessary?

Good question.

Science usually involves doing some pretty stupid things, over and over and over again. At the end of it, if you're lucky, you're not one bit richer or more comfortable or better-fed or more popular, but you may have a bit of knowledge that you didn't have before. If you're really lucky, the result may stand up to scrutiny from your fellow-scientists and be published and become part of the body of publicly available knowledge. By however small an amount, the world will have been changed.

If it's good science, the knowledge is worth having, despite all the stupid things you had to do to get it. If it's not worth having, it's bad science and a waste of time, money and other things besides.

Sometimes you don't know for certain whether your experiment will result in anything. You have to go to a funding agency and persuade them that the cost, the number of dead monkeys or traumatized rats, the volume of displaced Texan subsoil is worth it for only the chance of getting a bit of knowledge. What argues on your side is the durability of good science: once the results are out, they are out for all the world to see and use and refer to and build on. Of course, if it was pointless crap to begin with, it'll remain pointless&hellip

In my field (theoretical physics) we have it easy. Nothing's going to get wasted except some pieces of chalk and an unspecified number of CPU cycles. On the other hand, we're not going to come up with a cure for cancer either. So the big bucks go elsewhere, and we're pretty free to play around with whatever we like as long as not too much money goes on office furniture and trips to pleasant conference locations.

Judging Science

In the life sciences stakes are much higher, but the questions are the same.

Motivation: What problem is to be solved? What can the research accomplish?
Means and Method: What are the costs? What does it require us to do?
Theory: How can the method achieve the desired result? Will the method achieve the result? Why choose that particular method?

It's a fancy version of "Do the ends justify the means?". But in science, unlike in Soviet Russia, the answer is usually no. Most research proposals are rejected.

In order to pass judgement on a piece of research, these are the questions I need to ask. If I don't have some idea about the answers, then (unless the means are absolutely illegal, immoral or abhorrent) I can't make a judgement. You can't judge an experiment without looking at it as a whole.

Rats' Paws and Pains

Now to the rats. The "rat paw test" is a commonly used way to evaluate analgesics -- painkillers -- or other types of medication, such as anti-inflammatory drugs. For me, that's a pretty sound motivation: we want painkillers that work. Now to the method. You do something nasty to a rat's paw which induces some degree of pain. For example,

A dilute solution of formaldehyde and saline is injected under the skin of a rat's paw, inducing pain that lasts for about 90 minutes. The rat licks its paw repeatedly, which is a sign of moderate pain (a pain rating of 3). Then after a while, the animal holds the paw in the air (a rating of 2), steps on it gingerly (a rating of 1) and finally walks normally (a rating of 0).
(from the "MadSci library"). Or, from the Japanese Journal of Pharmacology:
In the tail-immersion test, the rat's tail was immersed in warm water at 47°C (117°F), and the latency to a nociceptive response was measured. In the scald-pain test, the right hind foot was scalded by immersion into hot water at 57°C (135°F). Two hours later, additional thermal stimulus was applied to the same foot, and the latency to a nociceptive response was measured.
Or, from the NIH website,
Researchers had tried to reproduce the symptoms of neuropathic pain in animals, but without success. At NIDR, they injected the hind paws of rats with solutions causing brief inflammation, such as Freund's adjuvant or capsaicin, then tested them for hyperalgesia and allodynia by placing them on warmed surfaces and timing the "withdrawal latency" - the time before the rat lifted the affected paw. An improved method, developed by Kenneth Hargreaves of the NAB, was to place the rat in a glass box and direct a pinpoint radiant heat stimulus at the inflamed paw. An attached photoelectric cell measured the withdrawal latency in fractions of seconds.

This is done both with and without administration of the analgesic to see whether there is a difference. To give you some idea of the temperatures involved in the "tail immersion" and "scald-pain" tests, your typical cup of drive-through coffee will be at 60°C (140°F); the coffee in the McDonalds coffee case was at about 82°C (180°F).

These different ways of studying pain are given the name of pain models, because they are used to model the pain that the researchers actually want to know about and reduce: different types of pain in human patients associated with different injuries or surgical procedures.

How can we judge this method, which involves exposing lots of rats to varying degrees of pain, in relation to its goal of reducing pain in human patients? Why choose the rat; what alternative methods could there be? Why choose deliberately to breed rats and inflict pain on them, when there are plenty of injured, scalded and otherwise buggered-about rats roaming the streets?

These are questions that the experimenters have to answer for themselves, but I can hazard a guess as to what some answers might be. We can't study pain without studying an animal that feels pain. We need an animal with a nervous system that processes pain somewhat as humans do. We can't get reliable results without doing lots of experiments the same way, so we need a small animal that breeds quickly. We can't reliably compare one drug with another or with a placebo just using random injured rats from the street. The results would be worthless without good controls.

Of course, they might answer "We use rats because that's the standard practice" or "We use specially-bred lab rats because they're nice and clean and don't get our hands dirty"… neither of which is a good answer. But that's part of judging good science from bad: whether or not there is a good reason for the methods used.

Ethics: Questions and Guidelines

There are of course lots of questions remaining. Is the rat similar enough to the human to make the results useful? Are the pain models really similar enough to the situations where humans experience pain? How much do the rats suffer? Are they permanently scarred? If this is to stand a chance of being good science, we need to think about all of these questions and try to answer them.

In fact, such are the ethical issues that a body called the International Association for the Study of Pain has produced a set of guidelines for pain research in humans and animals. I quote from the guidelines:

Investigators of animals models for chronic pain, as well as those applying acute painful stimuli to animals, should be aware of the problems pertinent to such studies and should make every effort to minimize pain. They should accept a general attitude in which the animal is regarded not as an object for exploitation, but as a living individual.

… The intended experiments on pain in conscious animals (should) be reviewed beforehand by scientists and lay-persons. The potential benefit of such experiments to our understanding of pain mechanisms and pain therapy needs to be shown. The investigator should be aware of the ethical need for a continuing justification of his investigations.

… In studies of acute or chronic pain in animals measures should be taken to provide a reasonable assurance that the animal is exposed to the minimal pain necessary for the purposes of the experiment. An animal presumably experiencing chronic pain should be treated for relief of pain, or should be allowed to self-administer analgesic agents or procedures, as long as this will not interfere with the aim of the investigation.

The full guidelines can be read at www.iasp-pain.org/ethics-a.html .

Sacrifices and Brains

But there's more. Apparently once the above tests have been performed, the rats may be killed (by a method not specified in our source) and the components of their nervous systems (spinal cord, brain etc.) extracted and "analyzed" (again, our source does not specify how).

How can we judge this somewhat gruesome procedure? What is the motivation and theory behind it? Here the situation becomes somewhat hazy. It may have something to do with performing surgery on newborn babies. Do they feel pain the same as adults? What can we do about it? This might be a reasonable motivation.

How can looking at bits of rats' brains help us solve the problems of neonatal surgery? What aspects of the brains are studied? Here I admit defeat. I can't find a source that explains what this might have to do with surgery on newborn babies.

And that is a shame, because without knowing how the stupid, wasteful, nasty method might connect up with the aims of the experiment, I can't begin to judge whether it is a good thing. Will the analysis of thousands of pieces of dead rat lead to less suffering for newborns? If not, it remains simply stupid, wasteful and nasty: no different in effect from the animal sacrifices of the Old Testament. If it will, is it too much to attribute "glee" to the scientists who have reason to believe that they are doing a good thing? Reducing the pain of neonatal surgery should inspire at least some enthusiasm.

Conclusion and Rant

How am I going to judge the injections of formalin, the scaldings, the pinpoint heat stimuli, the veritable genocide and dissection on a grand scale of lab rats?

Am I going to judge it by the "glee" apparently displayed on an experimenter's face? Am I going to judge it by one researcher's use of the word sacrifice and by a religious analogy that begs the question of what the research was for? Am I going to judge it by telling myself that the experimentalists are "coldly determined" and have no "affection and familiarity"? Am I going to judge it by calling the rat a "sacred creature" and "one of God's creatures"? Am I going to judge it by telling myself that the result of the experiment will be to "learn something we should never have forgotten" (whatever that might be)?

Am I going to judge it by telling myself that the researcher is "a good man by public standards", has saved many lives, has done internationally-recognized work?

NO. None of these is a good reason for thinking the experiment to be a good or a bad thing. The only reasons I have are these: What is the experiment for? What sacrifices (of whatever kind) does it require? Will it do what it is claimed? Is it worth it?

wwwsoc.nii.ac.jp/tjps/kyoto/jjp/ TOC00-83(4)/00-83-286.html