Comments and reactions to the posts are welcome! Simply click on the "comment" line below each post to see previous comments or on the pencil icon to add a new one!

Basel Declaration



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

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 are im­mense and ar­du­ous:
  • A complete 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.

Clinical value of basic research

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, most of which was not originally performed to cure Parkinson’s disease.  The clinical value of basic research must be measured over the scale of hundreds of years, not quantified over a decade or less.

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 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.

- D.R. Muir

No comments: