Brain-2005-Hubel y Wiesel SUPER

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brilliance; and with that kind of intuitive brilliance fancy

methodology was unnecessary. Before Hubel and Wieselstarted their work, most believed that the visual cortex

would be activated by light, as such. Failure to achieve results

with diffuse light stimulation was a trigger for the construction

of more sophisticated apparatus. In Germany, Richard Jung

and his colleagues spent much time and effort constructing

elaborate machines to activate the cells with diffuse light.

Jung was later to recount that he might have discovered the

orientation-selective cells during his 5 years work on the

visual cortex if he had used a stick instead of the quantifying

machine. Hubel and Wiesel had themselves used a now

outmoded approach to stimulate the visual system, when

that chance insertion of a slide into the projector elicited a

wild response from a cell. Their concern from then on wasto simplify themachinery andmake the cells a gooddeal easier

to study.For them,justas importantas stubbornness, ingetting

results, was almost certainly the simplicity, the looseness, of

our methods of stimulation. The incredible crudeness of our

firstslide projectors . . . andour refusal to wastetime bothering

withmeasuring intensities, rates of movement andso on . . . all

worked in our favor. The term loose is curiously out of

place, given how much valuable information was obtained

with it, and how little from sophisticated stimuli. From then

on they seemed to have developed a lasting contempt for fancy

machinery, Hubel once boasting that the best use they could

make of their computer was to heat the laboratory. How could

one avoid this disdain when papers, published as late as 1977,

using sophisticated methodology and advanced computer

analysis, did not improve much on the precision with which

the properties of cells were described, and provided no

new insights whatsoever? How can one admire the detailedand tedious measurement of the orientational preferences of

cells that arenot orientation-selective, as some have tried to do

with the directionally selective cells of V5?

There is perhaps a little overmodesty in the description of

their work as being hypothesis-free,or what many would today

describe pejoratively as a sort of fishing expedition. Even if

true, this was a major fishing expedition with an ineluctable

and beautifully exploited logic; and the catch was astonishing.

It is no wonder that every chance was seized avidly. Once

orientation-selective cells were discovered (by chance) in

the visual cortex of an animal (the cat) which has two eyes

and a retinotopically organized primary visual cortex, the rest

followed easily, or so this collection of papers makes it seem.The succession of questions can be summarized as follows:

How many orientations are represented within any given

retinotopically defined position of the visual field? How are

cells responding to different orientations organized with

respect to one another? Are all orientations represented for

each eye? How are the orientation columns and the ocular

dominance columns organized with respect to each other?

What is the overall organization of the two sets of columns

in the context of the topographic map within V1? Given that

visual deprivation early in life leads to lifelong blindnessa

topic widely discussedsincethe time of John Locke butput ona

scientific and clinical basis by the publication of Marius von

Sendens bookSpace and Sight(1962)it was natural to wantto study the effects of visual deprivation on the specificity of

visual cells in the cortex. Here, two eyes were better than one,

since it was possible to deprive one eye, or both, or neither. It

would,of course, bestretching thingstoo much to claim that the

decision to work on a two-eyed animal was taken by chance

but, even if this accident is allowed, they still usedthe two eyes

in a most imaginative way. Buriedwithin this setof questionsis

some kind of implicit hypothesis. And the authors were well

aware, right from the start, that their undertaking was a major

one and that they were on to some striking findings. Why else,

astheytellus, wouldthey project to writea book asearly asthe

1960s, well before their work came to maturity? Why else,

too, would they have been so aware of potential competitors,jealously guarding their results and projected experiments?

It is likely that their apprenticeship prepared Hubel and

Wiesel, if not for the accidents and lucky breaks, then at

least for how to proceed once the significance of the accident

had been appreciated. The biographical sketches detail their

brilliant intellectual surroundings. The catalogue of names is a

veritable aristocratic roll call: Bernard Katz, William Rushton,

E. D. Adrian, John Eccles, Alan Hodgkin, Andrew Huxley,

Edwin Land, Michael Fuortes and Francis Crick. Indeed they

regard themselves as the scientific great-grandsons of Charles

David H. Hubel

Torsten N. Wiesel

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Sherrington, a lineage of which the latter would no doubt

have approved. No room here for the more modest in ability,

who might nevertheless come up with an interesting question

or two. Towering above all in inspiration to them was Steve

Kuffler, thegrandmaestro of neurobiologyin the1950sand the

1960s, who had surrounded himself with brilliant investigat-

ors. Clearly, the atmosphere at Johns Hopkins, and later atHarvard Medical School, was highly congenial and deeply

inspiring. Clearly, too, the focus was on the problem rather

than on thoughtless measurement. Hubel recounts how he was

once advised by Kuffler to stick in some quantification, so as

to soothe the scientific conscience of the mindless measurers,

making the paper seem more scientific and therefore better

suited for publication. He laments that their work would be

unpublishable today, since referees, under the guise of a

scientific rigour that is both coarse and imperceptive, would

demand a host of detailed measurements. In one paper, they

write of the long time taken to produce a graph using a com-

puter, adding: We concluded that for both speed and for pre-

cision it is hard to beat judgments based on the human ear.Certainly [the curves] could not have been obtained with com-

puter averaging methods before the authors reached the age

of mandatory retirement. It is difficult to deny that their work

would have suffered greatly if they had been working in the

present era of white-coated, rubber-gloved and dispassionate

scientific honesty, one that, distrustful of human judgement,

confides all measurements to a computer that supposedly

does not suffer from human bias. Yet it is also interesting

and instructive to compare the results that Hubel and Wiesel

obtained when they judgedthe response specificitiesof cells by

ear (itself not a negligible measuring device) with the host of

papers that make generous use of the apparently neutral

computer-generated orientationselectivity index, the colourselectivity index, and many other indices. After a quarter of a

century of rigorous application, the latter have revealed noth-

ing or little that is interesting or new. The authors themselves

make the point, perhaps unwittingly, in the commentaries that

follow each paper. Advances there have been, they seem to be

saying, but nothing to compare with the original discoveries.

It is, no doubt, this poverty of results, compared to the rich-

ness of the original findings, that has led DavidHubel to regard

modern technologies, and the mathematical pitchforks asso-

ciated with them, with such disdain. The Epilogue of the book

has him wandering sadly through the debris left by the much-

vaunted computational approach which, one cannot but agree,

has contributed little that is of importance to understandinghow the brain works. He disapproves, as indeed do I, of linear

systems analysis and apparently shares my horror for the

current craze for multiplexing, the belief that few if any

cells in the visual brain are highly specialized and that most

of them aremultipurpose. He hasnothing but praisefor thefact

that the major textbook of molecular biology, The Molecular

Biology of the Gene, contains noequationsand that no one has

tried to fit a protein molecule to a Gabor function. Before

anyone dismisses these views too hastily, it is worth con-

sidering how much information the crude techniques used

by Hubel and Wiesel gave, and how little, by contrast, these

fancy approaches have provided. The evidence is all there in

this book.

How did such a collaboration last for so many years and

why did it eventually end? The first question is relatively easy

to answer. One successful set of experiments led to another,

generating an unstoppable momentum. Both authors wereintoxicated enough by their results to persevere with one

experiment and then plan and push on with the next. Several

factors aided them in this. Steve Kuffler was evidently some

kind of Lorenzo de Medici, content to see brilliant work

progress in his department, dispensing advice in an avuncular

way and not anxious, as so many are today, to add his name

to the papers and thus get hiscut of the glory. The relationships

established in the laboratory were evidently friendly enough

for the authors to say nothing more than that they were some-

times mixed with resentments and varieties of complexes.

Crucially, both were spared the curse of administration

one that so many academics, in spite of their protestations,

love. After one year administering the Physiology Departmentat Harvard, Hubel had had more than he could take when

the installation of a pencil sharpener necessitated at least

two elaborate meetings. They were also working at a time

when cats were even more plentiful than monkeys and not

much more expensive. Editors were more relaxed and referees

kinder. Nor were the grant-giving committees quite as for-

bidding as today. The authors state that their kind of work

could notbe done today.Sadly,theyare right.Theirlaboratory,

small in size and shared with others, encouraged continual

dialogue and discussionone of the characteristics of great

laboratories such as the Laboratory of Molecular Biology in

Cambridge, UK, or the Bell Laboratories, USA. One gets the

impression that there wasalsoa feelingof self-sufficiency. Oneof the authors great strengthsbut in the longer term also a

weaknesswas their understandable indifference to work

done by others, perhaps encouraged by Steve Kufflers oft-

repeated question: Do you want to be a consumer or a produ-

cer?For example, even in this book, andafterso many years of

discussion, they still believe, erroneously, that I mapped area

V5 of theowl monkeyin 1980, thus gettingboth thespeciesand

the date wrong, though I should be grateful that they got my

name right! They arenot even aware of where V5 is,describing

it as lying in the anterior lunate sulcus, whereas it is actually

located some distance away, in the posterior bank of the

superior temporal sulcus. This is surprising, since V5 is now

one of the most studied visual areas after V1 and is comingclose to surpassing the latter. But all this presumably matters

little to David Hubel and Torsten Wiesel, since the work was

not undertaken by them! It is said that on one occasion, when

asked whether he intended to respond to criticisms made of

theirworkinapaper,Hubelrepliedthat,todoso,hewouldhave

to read the paper, which was more than he was prepared to do.

By the time they parted company in 1980, the authors had

succeeded in charting the anatomy and physiology of area V1

of the brain in greater detail than ever before, and making it

the best understood area of the cerebral cortex. They had used

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almost all techniques available to them; charted ocular

dominance and orientation columns and looked at their ana-

tomy; established with greater precision than ever before the

details of how the fibres from the lateral geniculate nucleus

terminate in the visual cortex; established the concept of the

column in the visual cortex firmly; shown that selectivities are

established at birth and are susceptible during a critical periodafter that; and, above all, with their loose methods had intro-

duced new and very high standards of evidence into cortical

neurobiology which fewhave managed to emulate. Why, then,

did this flourishing scientific collaboration end? Their work

had been mainly on area V1, or area 17, and with so much

achieved it seemed as if V1 was well enough understood, and

theworkthusbegantorunoutofsteam.Indeed,asearlyas1968

they had thought of V1 as sufficiently well characterized that

despite the large areas still unexplored, in broad outline the

function of area 17 isprobably nowrelativelywellunderstood.

It was to areas beyond V1 that one should turn ones attention,

or sotheyimpliedwhenthey wrotein thesame paper Howthis

information [in area17] is used at later stages in the visual pathis far from clear, and represents one of the most tantalizing

problems for the future.

In his autobiographical sketch, Torsten Wiesel writes with

disarming honesty that there may have been a more profound

reason that our partnership came to an end. The additional

demands on our time [came] when we were investigating

the properties of cells of higher visual areas beyond the pri-

mary visual cortex, an exploration that each of us eventually

regarded as a failure . . . The two naturalists, who for so

long had journeyed together with a seemingly inexhaustible

sense of wonder, were unaccustomed to the frustrations that

are the daily bread of so much scientific research . . . what

developed between us, our special bond and private dialogues,took place while we carried out our experiments. When these

explorations stalled, when the wonder faded, so did our col-

laboration. Perhaps it was necessary for each of us to turn to

new partners and questions.

It is indeedthrough the exploration of the highervisual areas

that their concept of hierarchy began to be questioned.

That concept was largely the result of concentrating on

orientation-selective cells and ignoring other categories of

cell. They managed to identify different levels of complexity

in thefunctional properties of orientation-selective cells, andit

is this that led them to the hierarchical concept of visual physi-

ology. Ironically, it was adherence to thishierarchical doctrine

that made them misinterpret, or not interpret, the functions of a

visualareain thecat that isequivalent to area V5 inthe monkey,the ClareBishop area, in an article that they describe as not

one of our favorite papers. Hubel was later to repudiate this

exclusive hierarchical concept implicitly, but never explicitly.

The implicit repudiation came with the work he did with

Margaret Livingstone, which showed that their earlier model

of V1 was incorrect; that there was a functional segregation

within V1,much as hadbeen predictedfrom thedemonstration

of functional specialization among the higher visual areas of

the brain, beyond V1, and which receive their input from V1.

It is a pity that Hubel and Wiesel ignored the concepts of

functional specialization and parallelism, established by work

in the higher visual areas. It is a pity, too, that in gazing into the

future through the past David Hubel (the main author of thecommentaries of this book) has nothing to say about this

functional specializationperhaps because it does not figure

in their collaboration. It is, in my view, a major oversight, but

it is an oversight that one might want to forgive, much as

one would forgive Einstein for reputedly ignoring quantum

mechanics. When one has finished rereading, or reading for

the first time, the extraordinary output that has resulted from

this legendary collaboration, one decides pretty much to

forgive such blemishes. Neuroscience should rejoice that,

during a mere 25 years, its world was enriched not only by

a wealth of knowledge but also by new standards of evidence

and elegance of methodology which have left a permanent

imprint.

Semir Zeki

Laboratory of Neurobiology

University College London

London, UK

doi:10.1093/brain/awh507

Book review 1229

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Brain-2005-Hubel y Wiesel SUPER