s a feminist in a family with Victo-rian mores and as a Jew and free-thinker in MussoliniÕs Italy, Rita

Levi-Montalcini has encountered variousforms of oppression many times in herlife. Yet the neurobiologist, whose tenac-ity and preciseness are immediately ap-parent in her light, steel-blue eyes andelegant black-and-white attire, embracesthe forces that shaped her.ÒIf I had not been discrim-inated against or had not suÝered persecution, I wouldnever have received the No-bel Prize,Ó she declares.

Poised on the edge of acouch in her apartment inRome that she shares withher twin sister, Paola, Levi-Montalcini recalls the long,determined struggle that cul-minated in joining the smallgroup of women Nobelistsin 1986. She won the prizefor elucidating a substanceessential to the survival ofnerve cells. Her discovery ofnerve growth factor led to anew understanding of thedevelopment and diÝerenti-ation of the nervous system.Today it and other similarfactors are the subject of in-tense investigation becauseof their potential to revivedamaged neurons, especial-ly those harmed in such dis-eases as AlzheimerÕs.

The journey from Turin,where she was born in 1909,to this serene and impecca-ble Roman living room ladenwith plants and with the etch-ings and sculptures of Pao-la, a well-known artist, test-ed Levi-MontalciniÕs mettlefrom her earliest years. ÒItwas a very patriarchal society, and I sim-ply resented, from early childhood, thatwomen were reared in such a way thateverything was decided by the man,Óshe proclaims. Initially, she wanted to bea philosopher but soon decided she wasnot logically minded enough. When hergoverness, to whom she was devoted,died of cancer, she chose to become adoctor. There only remained the smallmatter of getting her father, an engi-

neer, to grant permission and of mak-ing up for the time she had lost in agirlsÕ high school, where graduation ledto marriage, not to the university. ThatÒannoyed me so much that I decided tonever do as my mother did. And it wasa very good decisionÑat that time, Icould never have done anything in par-ticular if I had married.Ó Levi-Montalci-

ni pauses, leans forward and asks in-tensely, ÒAre you married?Ó She sighswith relief at the answer. ÒGood,Ó shesays, smiling.

After she received her fatherÕs grudg-ing consent, Levi-Montalcini studied forthe entrance examination and then en-rolled in the Turin School of Medicineat the age of 21. Drawn to a famous, ec-centric teacher, Giuseppe Levi, she de-cided to become an intern at the Insti-

tute of Anatomy. There Levi-Montalcinibecame adept at histology, in particu-lar at staining nerve cells.

Since Levi was curious about aspectsof the nervous system, he assigned hisstudent a Herculean labor: to Þgureout how the convolutions of the humanbrain are formed. In addition to theoverwhelming undertaking of Þndinghuman fetuses in a country where abor-tion was illegal, Òthe assignment was an impossible task to give your student

or an established scientist,ÓLevi-Montalcini explains, hervoice hardening. ÒIt was a re-ally stupid question, which IcouldnÕt solve and no onecould solve.Ó

She abandoned the proj-ectÑafter a series of un-pleasant forays for subjectmatterÑand with LeviÕs per-mission began to study thedevelopment of the nervoussystem in chick embryos.Several years later she wasforced to stop that work aswell. Mussolini had declaredhis dictatorship by 1925 andsince then anti-Semitism hadgrown in Italy. By 1936, hos-tility was openly apparent,and in 1939, Levi-Montalciniwithdrew from the universi-ty, worried about the safetyof her non-Jewish colleagueswho would be taking a riskby letting her study.

Levi-Montalcini acceptedan invitation to conduct herresearch at a neurological in-stitute in Belgium. But, fear-ing for her family, she soonreturned to TurinÑjust be-fore Mussolini and Hitlerforged their alliance. Unde-terred, Levi-Montalcini con-tinued her research: ÒI im-mediately found a way toestablish a laboratory in my

bedroom.Ó In the years that followed,bombs fell repeatedly, and again andagain she would lug her microscopeand slides to safety in the basement.

In spite of the hardshipÑor perhaps,as Levi-Montalcini sees it, because ofthe adversityÑit was during this timethat she laid the groundwork for her lat-er investigation of nerve growth factor.ÒYou never know what is good, what isbad in life,Ó she muses. ÒI mean, in my

Finding the Good in the Bad

PROFILE: RITALEVI-MONTALCINI

NOBEL LAUREATE Rita Levi-Montalcini conducted neurobiolog-ical research as bombs fell on her town during World War II.

32 SCIENTIFIC AMERICAN January 1993

AP

Wor

ldw

ide

Pho

tos

Copyright 1992 Scientific American, Inc.

case, it was my good chance.Ó Levi-Mon-talcini and her family left Turin in 1942for the surrounding hills and success-fully survived the war in hiding. By con-vincing farmers that she needed eggs forher children (whom she did not have),Levi-Montalcini studied how embryon-ic nerve tissue diÝerentiates into spe-cialized types. The prevailing theory, de-veloped by renowned biologist ViktorHamburger of Washington University,held that the diÝerentiation, or special-ization, of nerve cells depends in largepart on their destination. In his experi-ments, Hamburger removed developinglimbs in chick embryos to see how suchexcision would aÝect the later growthand diÝerentiation of the nerve cellsdestined for that region of the embryo.

Hamburger observed that the centersof embryonic nerve cells near and in the developing spinal columnÑwherethe cells start their journey out to othertissuesÑwere much smaller when he ex-cised the limb buds. He suggested thatsome inductive or organizing factor,probably contained in the limb, couldno longer call out to the nerve cells.Therefore, they neither specialized norgrew away from the developing spinalcord into the region of the absent limb.

After conducting experiments direct-ed at the same question, Levi-Montal-cini reached a diÝerent conclusion. Shefound that fewer nerve cells grew intothe area where the limb bud had beeneliminated, but she proposed that somekind of nutrient, important for the sur-vival of nerve cells and normally pro-duced by the limb, was missing. Hertheory diÝered from HamburgerÕs viewbecause Levi-Montalcini proposed thatnerve cell diÝerentiation did take placedespite the removal of the limb but thatthe cells soon died because they did notreceive some sustaining, trophic factor.The limb did not contribute to diÝeren-tiation, that is, it did not contain an organizing factor; rather it producedsomething that nourished already spe-cialized nerve cells.

A paper of hers on this topic waspublished in a Belgian journal and wasread by Hamburger, who invited her toSt. Louis in 1946. Hamburger wantedto work with Levi-Montalcini on theproblem of nerve cell diÝerentiationÑand, indeed, later came to agree withher interpretation. Although she initial-ly accepted a semester-long researchposition at Washington, Levi-Montalciniremained until 1961. She is now profes-sor emeritus at Washington but spendsmost of her time in her native country.

Levi-Montalcini recalls being unsureof the future of her research after shearrived in the U.S. One afternoon, a series of observations, as well as the

presentation of a challenge, gave her a renewed sense of purpose. At thattime, neurobiologists thought diÝerenc-es in the number and function of vari-ous nerve cells were mostly the conse-quence of proliferative processes.

But Levi-Montalcini was about to dis-cover that the developing nervous sys-tem, at least in parts, uses a strategy dif-ferent from the one previously assumed.She had prepared a series of tissue slides

of chick embryo spinal cords in diÝer-ent stages of development. By looking at the succession of slides, she was able to observe the migration of nerve cells early in development to their Þnal po-sitions alongside the spinal column.There, for the Þrst time, she saw thelater elimination, or pruning back, ofsome of them. ÒI put on a Bach cantatabecause I was so terribly happy. I hadrealized that there was still so much tobe discovered,Ó says Levi-Montalcini, herdelight vividly clear.

Over the next several years, Levi-Mon-talcini focused on searching for the mys-terious trophic factor that she had intu-ited during the war. A former studentof HamburgerÕs had fortuitously noticedthat a certain mouse tumor cell lineÑcalled sarcoma 180Ñcaused more nervecells to grow. When Levi-Montalcini in-corporated the tumor cells into devel-oping chicks, she observed the same ef-fect. Something in the tumor caused thediÝerentiation of the nerve cells to ac-celerate; it also caused the creation ofexcessive numbers of nerve Þbers.

Levi-Montalcini started trying to iso-late the trophic factor and began to col-laborate with biochemist Stanley Cohen,then at Washington and now at the Van-derbilt University School of Medicine.They found that the partially puriÞedfactor contained both protein and nucle-ic acid. By adding enzymes from snakevenomÑwhich breaks down these com-poundsÑin hopes of determining whichcomponent contained the biological ac-tivity, the two discovered that the ven-om itself contained the factor.

This Þnding (described in detail in herautobiography, In Praise of Imperfection)led to the realization that nerve growthfactor is produced in salivary glands inmice, providing a new, easy source forstudies of the material. By designing anantiserum, Levi-Montalcini and Cohenwere able to chart the role of the factor.

It became clear that it is essential to thediÝerentiation and health of nerve cells.

In 1986 Levi-Montalcini and Cohenshared the Nobel Prize for this achieve-ment. When the phone rang in Romewith the news, she was pages from theend of Agatha ChristieÕs Evil under the

Sun. ÒAt the moment that I was Þndingout about the criminal, they told methat I was awarded the Nobel,Ó shelaughs, getting up to retrieve the bookfrom the hallway. She points to a hand-written note on the second-to-lastpageÑbeÞtting a neuroscientist, her ed-ition has a skull on the coverÑwhereshe had marked Òcall from StockholmÓand the time. ÒSo I was very happy aboutit, but I wanted much more to knowthe end of the story,Ó she admits.

Although she says her popularity in-terferes with her life, Levi-Montalcini hasused the Nobel to extend her work intoareas that concern her. She is presidentof the Italian Multiple Sclerosis Associ-ation and is a member of the PontiÞcalAcademy of Sciences; she was the Þrstwoman to be elected to the academy. ÒIcan do things that are very, very impor-tant, which I would never have been ableto do if I did not receive it,Ó she says. ÒIthas given me the possibility of helpinga lot of people.Ó And she helps whomev-er she can. The phone rings incessantlyin her apartment. ÒPeople ask for medi-cal help,Ó she explains, after answeringeach call and graciously talking with theparents or other relatives of someone ill.ÒBut sometimes there is nothing to do.Ó

In addition, Levi-Montalcini and hersister recently started their own project:a foundation that will provide mentors,counseling and grants to teenagers de-ciding what Þeld, whether it be art orscience, to enter. For several hours ev-ery week, she receives young students inher laboratory at the Institute of Neuro-biology at the National Research Councilin Rome and talks with them about theirinterests and her experiments. ÒTheonly way to help is to give young peoplea chance for the future. Because we can-not Þght the MaÞa, we cannot Þght cor-ruption without giving an alternative toyoung people,Ó she says.

Levi-MontalciniÕs research at the insti-tute, which she founded in the 1960s,has also taken a new turn. She is study-ing the role of nerve growth factor inthe immune and endocrine systems.ÒThe neotrophic factor was just the tipof the iceberg,Ó she notes. ÒSo even nowI am doing something entirely diÝer-ent. Just in the same spirit as when Iwas a young person. And this is verypleasing to me,Ó she says, laughing. ÒImean, at my old age, I could have nomore capacity. And I believe I still haveplenty.Ó ÑMarguerite Holloway

ÒI simply resented. . . thatwomen were reared insuch a way that everythingwas decided by the man.Ó

36 SCIENTIFIC AMERICAN January 1993 Copyright 1992 Scientific American, Inc.