Basic research with animals as experimental subjects is essential if we hope to understand the brain. The ethical standards to which we hold ourselves and by which we conduct those experiments are a measure of our humanity.

The Basel declaration is a public commitment to seek the highest possible standards for animal research. Scientists must transparently communicate their work to the general public, and state their support for well-conducted basic research. I have signed the basel declaration, and lay out here how I see the relationship between basic and clinical research, and between modelling and experimentation in neuroscience.

Modelling and simulation

All of the analysis and simulations I perform are fundamentally based on data collected from animal experiments. There is no other source for the anatomical and physiological measurements necessary to make models of the neocortex. If we want to understand the workings of the human mind and brain, of course measurements from human brains would be ideal, and our close primate relatives the next best choice. For good ethical reasons, we restrict the type and number of experiments that can be performed on humans, non-human primates and other animals. As a result, most data that underlie cortical models come from mice, rats and cats. As a rule, the data come from basic research — research with no direct clinical application.

The problem with modelling

Every model is based on simplifying assumptions. Any model that assumes something that is known to be false is destined for the trash. But in many cases, experimental measurements required to build an accurate model are either highly variable, or not present. Every model can only be based on current knowledge, which implies that modelling and experimental work exist in a co-dependent cycle: models can make predictions and suggest hypothesis, which must be verified experimentally; the experiments offer improved data with which to improve models.

All neural modellers have an ethical investment and obligation in the animal research their models are based on.

A "perfect" model

Cortical models have been presented as a tool for reducing the number of animal experiments that must be performed. This may well prove to be true, but the requirements for building an exact model that could be used to test and design drugs, as well as to perform basic research, are immense and arduous:

• A comprehensive description of the connections between neurons in the human brain; ideally with a complete understanding of the rules used to form those connections.
• A complete understanding of the physiology of every class of neuron in the brain; ideally with an molecular-level understanding of how that physiology arises.
• A complete understanding of the developmental process of the brain, including all of the molecular and activity-driven cues required to form an adult brain.
• All of the above, for every neurological condition that one would want to treat.

It should be obvious how much experimental work this list entails. Most of the measurements required to fulfil those four points cannot ethically be made in human subjects, but if the list were fulfilled for a particular animal model then that might suffice to drastically reduce the number of animal experiments made. However, the vast amount of research required to reach that point ensures that no person living today will survive to see that goal reached. Modern neuroscience dates back no more than 150 years to the work of Cajal and Golgi. I estimate that at least another 150 years will be required to come close to an understanding of the human brain.

Clinical value of basic research

The path that connects a fundamental research finding with an eventual clinical intervention is long, winding, and obscured along much of its length. Basic research is necessary if we want to understand the mechanisms by which brains work, and exactly how they fail. This understanding makes it easier to propose a clinical treatment that has a chance of success. Without a basic understanding of the working brain, we cannot know why some interventions work and other do not. It is also difficult to judge in advance what the clinical outcome of a basic research result will be.

Deep brain stimulation is a clinical treatment for Parkinson's disease and chronic pain. The technique involves implanting a number of electrodes in the thalamus of a patient (a sub-cortical nucleus involved in gating sensory and motor projections), and delivering periodic electrical stimuli to the neurons there. It is a remarkably effective treatment that dramatically improves the quality of life of affected patients.

Deep brain stimulation is an impressive medical advance delivered by neuroscience, and was only recently approved for regular use in patients. However, the foundations of this clinical treatment are laid on deep strata of basic research:

• Electrophysiology (Galvani and Volta, ca. 1791)
• The electrical function of neurons (Emil du Bois-Reymond, ca. 1848)
• Stereotactic surgery (Sir Victor Horsley and Robert H. Clarke ca. 1908; Ernest A. Spiegel, Henry T. Wycis and Lars Leksell ca. 1947)
• Structure (Willis ca. 1664; Meynert ca. 1872; Vogt and Vogt ca. 1909; Cajal; etc.) and function (Marshall 1941; Moruzzi and Magoun 1949; Aladjalova 1957; etc.) of the thalamus
• The relationship between thalamus and parkinson's disease, and so on.

Several points stand out from this example: firstly, that the current extremely effective clinical treatment of Parkinson's disease by deep brain stimulation relies on a vast collection of basic research results.

Secondly, that the clinical value of basic research must be measured over the scale of hundreds of years, not quantified over a decade or less.

Finally, the overwhelming majority of the experiments covered by the list above were not performed with the goal of finding a treatment for Parkinson's disease sufferers. The conclusion is obviously that basic research is essential for developing clinical treatments, but should not be required to reach a concrete clinical goal, since that goal is long distant and most likely unforeseeable.

Subscribing to an ethical framework

Given that animal experiments must be performed for neuroscience to progress, and given the deep public support for medical advances in neuroscience, how should those experiments be designed and performed? Signing the Basel declaration implies that we will seek and uphold the highest ethical standards of animal care and experimental design, by minimising the number of animals used and imposing as little discomfort and suffering as possible.

We also have an obligation to engage with society, by actively promoting good research and transparently explaining our own. We should promote policy based on sound experimental evidence and not on opinion. But equally, we insist that new laws governing research must be based on facts and democratic discussion. Radical groups that act outside the legal and ethical frameworks that society has agreed upon must be curtailed. Discussion of animal research in the media and politically must be conducted in an impartial manner as part of a balanced dialogue including researchers.

Acknowledgements

Thanks to Daniel Kiper for commenting on an earlier version of this article.