books and arts A troubled pilgrim’s progress The compelling personal journey of a founding father of cellular immunology.

Science as Autobiography: The kinds of antibody are synthesized naturally, Troubled Life of Niels Jerne without previous exposure to foreign anti- by Thomas Söderqvist gens, and that their diversity is due to a Yale University Press: 2003. 400 pp. random process. The antigen, rather than $40, £27.50 being involved in moulding the antibody, Gustav J. V. Nossal is only a catalyst. David Talmage and Frank Macfarlane Burnet refined the theory, pro- The central puzzle of the immune system posing that the natural antibody is a surface is how it can react specifically to virtually receptor on white blood cells known as any microbe or foreign molecule. How is it lymphocytes, with the antigen needing only possible, with a large but limited number of to encounter the ‘right’ cell to stimulate the genes, to produce billions of different sorts immune response and increase the number of antibody? Before revealing the answer, of appropriate cells. This clonal-selection we must pay tribute to Niels Kaj Jerne theory turned out to be correct. Regarding (1911–94), the Danish-born immunologist the antigen as playing a selective rather than who unquestionably deserves the credit for an instructive role was a true paradigm shift. creating a theoretical framework within Jerne made two other profound contri- which the matter could be pursued. butions. He devised a simple and elegant The steps along the path are elegantly technique (known as the haemolytic plaque described in this biography by Thomas technique) for determining the number of Söderqvist, first published in Danish in 1998 antibody-forming cells. This added a vital and recently revised and translated into Source of inspiration? Niels Jerne’s personal life quantitative element to cellular immunol- English.But if the reader is expecting a typical may have contributed to his scientific work. ogy, and facilitated the development of scientific biography, in which the research of hybridoma technology for producing a famous person is catalogued and explained, a couple of years. At 22, he decided to study monoclonal antibodies — antibodies with a rude shock awaits. After more than ten medicine in Copenhagen, but again could predetermined exquisite specificity. Jerne years of meticulous examination of Jerne’s not commit himself to it. He failed in a job shared the 1984 Nobel prize with its inven- extensive papers,and 160 hours of interviews with a publishing house, then worked for tors, Georges Köhler and César Milstein. He with him, Söderqvist presents a thought- his father for three years — helping him to was also the founding director of the Basel provoking, surprisingly frank account of find better ways of curing bacon. Only at Institute for Immunology which, within a Jerne’s personal life and philosophy. the age of 28 did he begin to study medicine decade, he made into a Mecca of European The controversial justification for this seriously, graduating eight years later, and immunology and a cauldron of intellectual approach is Söderqvist’s belief that the starting research at the State Serum Institute ferment. It must have been a source of great source of Jerne’s creativity lay in his personal in Copenhagen. satisfaction to Jerne that it was at this experiences; that his scientific work was an At 23, Jerne had married his first wife, institute that the nature of the generator of inseparable part of his life as a whole. Thus, Tjek Wahl,a German art student who estab- random antibody diversity was discovered Söderqvist embarks on what he terms new lished a successful painting career and bore by Susumo Tonegawa, leading to another biographical territory, namely existential him two sons. Marriage problems began Nobel prize. Each antibody-forming cell biography. As a result, we are given both an seven years later, when Jerne had a two-year develops from a unique recombination authoritative presentation of Jerne’s scien- affair with a physician whose erotic arts event that assembles functional antibody tific achievements and a penetrating survey included sado-masochism. Although Tjek genes from a pre-existing array of minigenes. of this troubled pilgrim’s progress. knew of this and of two other brief liaisons, The combinatorial element of antibody- Jerne’s parents were Danish, but lived she was unable to accept it when Niels started gene production thereby creates the huge successively in England, Germany and the an affair with her close friend Adda. number of different end products. Netherlands.The young Niels became fluent As Tjek’s own infidelities became clear, Jerne also deserves credit for setting up in Danish, English, German and Dutch, Niels believed divorce to be the only option. an immunology unit within the World never feeling rooted anywhere. He gradually But after ten years of marriage, Tjek could Health Organization to promote research assumed the mantle of an élitist, epicurean, not bear this thought and committed sui- and teaching in developing countries. But deeply cultured European intellectual. A cide. Jerne never forgave himself. In time he his network theory of immune responses ‘bookworm’ from a very young age, he married Adda, who was soon reduced to the proved less successful, and his impatience steeped himself in Kierkegaard, Bergson, role of stepmother and housekeeper. In his with experimental details lessened the Nietzsche, Proust and Gide. Paradoxically, mid-forties, Jerne began an affair with a 19- impact that he might otherwise have had he felt himself to be insecure, alienated and year-old girl who (after divorce from Adda) on the development of immunology as the a misfit while at the same time enjoying became his third wife. Add in a relationship science reached maturity. As Söderqvist conversation, longing for the sublime and, with an American woman who bore his third remarks: “Jerne never took satisfaction convinced of his superior gifts,eager to make child, and one sees the complexity of this from small discoveries — in this respect he an impression on the world. man’s private life. resembled an artist more than a biomedical He took a long time to find his métier. Jerne’s first major scientific achievement researcher — and he struggled to formulate After school, he worked in business in Rot- was in formulating the natural-selection theories of great breadth, wishing to impose terdam, then moved to Leiden to study theory of antibody formation, published in his own worldview and his personality on mathematics and physics,dropping out after 1955.He postulated that millions of different nature.” Later in life, Jerne complained that

NATURE | VOL 424 | 17 JULY 2003 | www.nature.com/nature © 2003 Nature Publishing Group 253 books and arts immunology was becoming too complicated or connection to the text. The neurological and technical. His dismissal of the reduc- illustrations are small, ‘arty’ graphics of the tionist approach to the discipline prevented computer-generated variety, a technique him from appreciating the amazing discov- that has too easily enabled images of the eries made in immunology during the last brain,each postage-stamp-sized,to multiply 15 years of his life. on obscure and complicated backgrounds. Is Söderqvist successful in his attempt at Again, the repetition of style makes these existential biography? The answer must be brain images interchangeable. What’s actu- hedged in uncertainty. Did Jerne use the ally being illustrated is not only hard to see, experiences of his inner life, his understand- but is poorly explained, despite lengthy ing of himself, to construct the natural- captions, albeit of variable fidelity. The selection theory? It seems far-fetched, but caption of figure 9, for example, implying who has the right to be dogmatic about the that the right and left visual fields map onto wellsprings of human creativity? Where the primary visual cortex of the same hemi- Söderqvist has undoubtedly succeeded is in sphere, could be written off as a schoolboy revealing the startling personal journey of howler, were it not that the accompanying one of the twentieth century’s great biologi- text confirms that the authors really have cal thinkers, and in sketching the milieu “Once more unto the breach”: Shakespeare’s misinterpreted the experiment illustrated, within which cellular immunology came of Henry V used mental imagery to rally his troops. which shows the distribution of cortical age. This serious work of scholarship will visual areas and not, as they state, the well- be devoured both by immunologists and by information about the benefits of brain known ‘ocular dominance columns’ of the a wide general readership. I research. The most visible and successful of primary visual cortex, which are beyond the Gustav J. V. Nossal is in the Department of the initiatives is Brain Awareness Week, a spatial resolution of the scanners used. Pathology, University of Melbourne, popular event held annually in many centres The neurological material is restricted Victoria 3010, Australia. worldwide. It provides an invaluable forum mainly to functional imaging of the human for members of the public to meet patient- brain, principally the “folded surface of the support organizations and local brain scien- brain (called the cortex) … where neurons are tists, who usually cover a wide breadth of found”.Unfortunately, the different imaging basic and clinical research. methods — for example, positron-emission Scanning Square and ‘coffee table’ in its aspect, tomography (PET) and functional magnetic there is much that is artful in this book. It is resonance imaging (fMRI) — used in the Shakespeare itself a play in seven ‘acts’. Each act covers various studies referred to in the book are not The Bard on the Brain: different topics, such as “Minds and Brains”, properly explained. There is no doubt that Understanding the Mind Through “Our Inner World”and “The Seventh Age of fMRI has revolutionized cognitive neuro- the Art of Shakespeare and the Man”,and each contains a number of‘scenes’, science. The method, however, does not Science of Brain Imaging whose titles range from the straightforwardly actually detect “the amount of fresh blood by Paul M. Matthews & Jeffery McQuain banal, “The Wonder of the Human Brain”, flow”,but records changes in the levels of the Dana Press: 2003. 192 pp. £24.50 to the dramatic, “Let Me Clutch Thee”, to paramagnetic molecule deoxyhaemoglobin. University of Chicago Press: 2003. 192 pp. $35 the boggling,“Putting an English Tongue in How this blood-oxygen-level-dependent Kevan A. C. Martin a French Brain”. Each scene begins with a signal (the so-called BOLD signal) correlates précis of a plot or subplot from one of the with neural activity has been the subject of Every now and then, an editor will come up plays, which is followed by an excerpt from intense and technically difficult invasive with what seems to them to be a brilliantly a scene and finally a commentary that inter- experiments with animals, but such experi- original wheeze. Here, Jane Nevins of the weaves topics evoked by the excerpt and its ments are vital steps in developing a deeper Dana Press persuaded Paul Matthews, a speculative neurological correlate. With 34 understanding of the basic physiology and neurologist, and Jeffery McQuain, an Eng- such scenes, this unrelenting format does anatomy underlying human brain function. lish scholar, to use Shakespeare’s plays as wear a little thin. Writing anything worth This information would help lay readers a vehicle for describing the brain correlates reading alongside an excerpt from Shake- to understand why the non-invasive tech- of cognitive function. Perhaps she was speare is a challenge, but here even the niques now used in human studies cannot, prompted by the popular success of the shortest sentences can somehow contrive to on their own,“define the brain mechanisms 1998 film Shakespeare in Love, in which the emphasize the difference, as in “Shakespeare responsible for thoughts, emotions, and audience meets the young Shakespeare, has Juliet ponder what defines a ‘Montague’”. disorders that Shakespeare wonderfully then struggling with writer’s block and The subsequent analyses are largely un- described”.The reader is left with the impres- trying to meet a deadline for his new play, revealing: “Shakespeare was a keen observer sion that imaging techniques all produce Romeo and Ethel the Pirate’s Daughter, of human nature”,or “some of his characters multiple images of tiny brains decorated whose plot is suggested to him by his rival, talk to themselves in sonnets”.Unfortunately, with rainbow-coloured blobs of unknown Christopher Marlowe. More significantly, much of the commentary on Shakespeare’s significance. This is a missed opportunity the film conveys the powerful effect of a live text is reminiscent of the cribs one crammed to explain why different techniques of brain theatre performance on an audience. How the night before the English literature imaging are used in the clinical setting, and does theatre weave its magic spell? In the examination in the hope of impressing the how the images are interpreted. film, Phillip Henslowe, director of The Rose teacher with such pearls as “Shakespeare A danger inherent in popular science Theatre, gives his answer: “I don’t know. lived intimately with a rich world of imagi- books is that they try to be popular and so It’s a mystery.” nation, which he communicated to others simplify too much. The lesson we learn from The connection between theatre and the through words and stage action”. the theatre, and from Shakespeare’s plays in brain explored in this book is less mysterious The book’s illustrations are prodigal. The particular, is that complex ideas and emo- when we learn that the remit of the Dana full-page photographs of performances of tions can be effectively communicated to a Alliance for Brain Initiatives is to publicize Shakespeare’s plays appear without context receptive audience, even if the language is

254 © 2003 Nature Publishing Group NATURE | VOL 424 | 17 JULY 2003 | www.nature.com/nature