More than a century ago the re-nowned Spanish neurobiologistSantiago Ram�n y Cajal discov-

ered the growth cone, Òthat fantasticending of the growing axon.Ó His Þndpartially explained one of the most fun-damental and dynamic events in embry-onic development. These Òliving batter-ing rams,Ó as he observed, sprout fromnerve cells and forge ahead toward se-lect tissues. Hence, he suggested thatthese structures enable young neuronsto wire the synaptic links that form anadult nervous system. Until recently,though, no one had Þgured out how thegrowth cones know where to go.

Cajal himself, it turns out, had theright idea. He proposed that the targettissues might release certain diÝusiblechemicals that, like a trail of breadcrumbs, could lure the advancing axonsfrom afar. Following this path, a teamled by Marc Tessier-Lavigne of the Uni-versity of California at San Franciscoand the Howard Hughes Medical Insti-tute identiÞed two such chemotropicproteins. It has christened them netrin-1 and netrin-2, after the Sanskrit netr,

meaning Òone who guides.ÓBoth proteins promote and orient the

growth of so-called commissural axonsin the developing spinal cord of chick-ens and rodents. These axons branchfrom nerve cells in the dorsal spinalcord and travel around itscircumference to tissuesin the front known as theßoor plate. From there,they turn toward the brain.Studies done in vitro haveshown that a collection ofßoor-plate cells can elicitaxonal outgrowth of thiskind from dorsal spinal-cord explants. Neverthe-less, because the ßoorplate is so small, workershad been unable to isolateits active ingredients.

Tessier-Lavigne and hiscolleagues managed toavoid that problem alto-gether. They compared theßoor plateÕs allure withthat of more accessibletissues and found that thecell membranes in a devel-

oping chick brain could also draw com-missural axons at a distance. The teampuriÞed the netrins from some 25,000chick brains. To conÞrm that theseproteins were indeed the spinal cordÕschemical bait, the group introducednetrin-1 RNA into a line of mammaliancells. These custom-made cells then pro-duced netrin-1 and attracted axons asßoor-plate cells would.

Although both netrin-1 and netrin-2were present in the chick membrane,ßoor-plate cells make only netrin-1.ÒThe netrin-1 transcript is expressed athigh levels in the ßoor plate,Ó Tessier-Lavigne says, Òwhereas netrin-2 is ex-pressed at lower levels over the ventraltwo thirds of the spinal cord.Ó He spec-ulates that this distribution might ex-plain the path commissural axons typ-ically take. Because higher levels ofnetrin-1 linger near the ßoor plate, theoutgrowing axons most likely travel to-ward an ever increasing amount of net-rin to reach their destination.

As further evidence that the netrinsgovern this growth, the same patternof circumferential migration seems tooccur in other species. The researchershave discovered that the netrins resem-ble unc-6, a protein that guides thegrowth of certain axons in a nematode.And Corey S. GoodmanÕs laboratory atthe University of California at Berkeley

have been, it cannot have been large.ÓThe Bell CurveÕs most egregious fail-

ing, however, may be its bleak assess-ment of educational eÝorts to improvethe intellectual performance of childrenfrom deprived backgrounds. Herrnsteinand Murray cast a jaundiced eye overHead Start and other eÝorts for at-riskyoungstersÑprojects that have beenclaimed to produce long-lasting gains inIQ, a possibility that would not squarewell with biological determinism. Herrn-stein and Murray downplay such results,noting that such interventions are tooexpensive to be widely used. The onlyone they are enthusiastic about is adop-tion, which, paradoxically, they acceptas having a positive eÝect on IQ. ÒTheirtreatment of intervention wouldnÕt beaccepted by an academic journalÑitÕsthat bad,Ó exclaims Richard Nisbett, apsychology professor at the Universityof Michigan. ÒIÕm distressed by the ex-tent to which people assume [Murray]is playing by the rules.Ó

Jencks is also unhappy with the bookÕsconclusions about education. ÒHerrn-stein and Murray are saying Head StartdidnÕt have a profound eÝect. But thatdoesnÕt tell us that we couldnÕt do a lotbetter if we had a diÝerent society,Ó hesays. ÒIn Japan, for example, childrenlearn more math than they do in theU.S. because everybody there agreesmath is important.Ó

Scarr, who accepts a substantial rolefor heredity in individual IQ diÝerenc-es, insists that eÝorts to boost intellec-tual functioning in disadvantaged youthcan deliver results. ÒThereÕs no questionthat rescuing children from desperatelyawful circumstances will improve theirperformance,Ó she notes.

Scarr also points out that ameliorat-ing a childÕs environment may reducesocial problems, regardless of its eÝecton IQ. ÒThe low-IQ group deserves a lotmore support than it is getting,Ó she ar-gues. ÒOther societies manage not tohave the same levels of social ills as wedo.Ó Edward F. Zigler, a prominent edu-cational psychologist at Yale University,asserts that Òin terms of everyday so-cial competence, we have overwhelm-ing evidence that high-quality early ed-ucation is beneÞcial.Ó

Therein lies the fatal ßaw in Herrn-stein and MurrayÕs harsh reasoning.Even though boosting IQ scores may bediÛcult and expensive, providing edu-cation can help individuals in otherways. That fact, not IQ scores, is whatpolicy should be concerned with. The

Bell CurveÕs Þxation on IQ as the beststatistical predictor of a lifeÕs fortunesis a myopic one. Science does not denythe beneÞts of a nurturing environmentand a helping hand. ÑTim Beardsley

SCIENTIFIC AMERICAN January 1995 17

The Great AttractorsChemical guides direct young neurons to their Þnal destinations

BATTERING RAMSÑorgrowth cones from com-missural axonsÑare luredtoward ßoor-plate cells bychemical cues.

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recently isolated a netrin gene in thefruit ßy Drosophila. ÒThis shows astrong conservation of biological func-tions between species,Ó Tessier-Lavignenotes.

The researchers studying worms, ßiesand vertebrates plan to collaborate ex-tensively. They are now testing wheth-er netrins and unc-6 function equallywell in vertebrate and invertebrate sys-tems. ÒAside from axonal projections,unc-6 controls the circumferential mi-grations of cells in worms,Ó Tessier-La-vigne adds. ÒSo cell migrations in verte-brate embryos might use netrins asguidance cues.Ó

Such analogies may help the groupanswer other questions as well. The sci-entists have uncovered a slightly small-er protein, dubbed NSA for netrin-syn-ergizing activity, that seems to inßu-ence netrin potency. Perhaps NSA, likecertain proteins in other signaling path-ways, mediates how well the netrinsbind to their receptors. ÒWe really wantto know if NSA is an essential cofactoror not,Ó Tessier-Lavigne states. Also, thenetrins tend to adhere to cell surfacesfor reasons as yet unknown.

What is known is that these novel pro-teins are probably just two words in anentire language of chemical instruc-

tions that direct embryonic develop-ment. Neurobiologists hope to discoverchemicals that can ward oÝ outgrowingaxons and thus prevent them from mak-ing faulty connections. Perhaps otherkinds of cues exist as well. At any rate,Tessier-Lavigne predicts that progresswill be swift because similar chemicalwords seem to speak of the same bio-logical functions in diÝerent species.ÒNow we can go back and forth be-tween diÝerent systems and share ourinsights,Ó he says. For a while, it seemsthe netrins will bring scientists togeth-er as surely as they connect searchingaxons. ÑKristin Leutwyler

Socializing with Non-Naked Mole Rats

Big and hairy, the Damaraland mole rat is not as re-nowned as its hairless cousin. Nevertheless, this specieshas proved just as intriguing as the naked mole rat of zooand cartoon fame. Both forms of mole rat are eusocial—that is, they live in groups in which only a queen and sev-eral males reproduce, whereas the rest of the colony coop-erates to care for the young. This behavior—like that oftermites and ants—is found in very few mammals, and ithas remained a puzzle of natural selection.

By comparing Damaraland and naked mole rats, Jen-nifer U. M. Jarvis and Nigel C. Bennett of the University ofCape Town and others have begun to determine the char-acteristics that appear central to the evolution of eusocial-ity—and hair is clearly not one of them. “The Damaralandis important because it does not have many of the charac-teristics of the naked mole rat,” notes Paul W. Sherman ofCornell University. So it “tells us something that we did notknow.” The degree of genetic relatedness between mem-

bers of a colony, for instance, does not appear as crucialto eusociality as some had believed. In the case of nakedmole rats, siblings raise one another because the survivalof a sister or brother is virtual cloning. A Damaraland col-ony, however, appears much more genetically diverse.Once a queen dies, these mole rats wait to reproduce untilanother female is introduced from somewhere else—atleast in the laboratory.

Instead ecological determinants seem more significantto eusociality. Both Damaraland and naked mole rats livein arid regions where the food supply, underground tu-bers, is sparse and rainfall unpredictable. Cooperative liv-ing ensures finding these precious resources—solitary an-imals would be unable to tunnel extensively enough to lo-cate adequate sustenance. The other, noneusocial formsof mole rats live in regions where food is more readilyavailable. In other words, the more patchy the food, themore the cooperation. —Marguerite Holloway

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