This article is concerned with a profound and ongoing change in the scientific understanding of the mammalian brain in general and the human brain in particular. Its focus is on the increasing appreciation of the ‘plasticity’ of the adult brain. In this context the title of my article assumes a particular significance: in contrast to the traditional scientific approach to the mature brain as stable and fixed, it outlines the argument that the changes in scientific comprehension of the brain mean that the human brain is now understood as plastic and hence changeable. In the following, the emergence of this plastic adult brain is now understood as traced in the advent of the field of adult neurogenesis. For this purpose I will describe the processes through which the formation and functional integration of novel neurons in the adult brain have turned from negated to valued scientific findings, and have become the concern of a burgeoning field in the neurosciences.Footnote ¹ I put forward the argument that the emergence of the field of adult neurogenesis towards the end of the twentieth century can be understood as the creation of a novel thought collective. As such it forms part and parcel of a fundamental change in thought styles ongoing within the neurosciences. According to Fleck, a thought style: ‘is the entirety of intellectual preparedness or readiness for one particular way of seeing and acting and no other’ (1979: 64). As Nikolas Rose puts it:

In the following, I will discuss how a transformation in thought style has taken place that is marked by the transition between two divergent understandings of plasticity. The first is a ‘traditional’ and still very influential one, which considers plasticity above all as a developmental quality and assumes a largely stable adult brain, whose plasticity is mainly a result of functional change within a structurally stable network. It is being replaced by a ‘novel’ understanding of plasticity. This conceives of a much higher degree of malleability of the nervous system in general, and hence the possibility for extensive functional and structural changes during all phases of life. Against this background, the article investigates the research on adult neurogenesis: this specific field of analysis provides an entrée into the complex questions of plasticity as a central and highly interwoven concept in contemporary neuroscientific research.Footnote ²

I will further discuss the way in which the development of the field of adult neurogenesis has been shaped by the necessity to distinguish between the primate and the human brain, which are considered as the most advanced organs to be found in the living world. The human brain has a complexity which is without match in the animal kingdom. In the traditional thought style, the human brain possesses an intricate structural and functional complexity whose individual characteristics are mainly acquired during childhood and adolescence. Its particular configuration, once developed, remains formative throughout life. As a consequence, the particular configuration of the human brain not only identifies, but also distinguishes the individual as a member of the human species. This notion of a human brain occupying a separate category within brain evolution has been very persistent throughout the twentieth century up to the present, and has been decisive in shaping the development of the field of adult neurogenesis.

As part of the transformation of thought style ongoing in the neurosciences, this understanding of the adult human brain as complex and hence immutable but is increasingly being put into doubt. As a consequence, the conception of an unchangeable human brain is being replaced by that of a plastic human brain, which continues to be malleable throughout life. This novel brain provides ample opportunity for transformation. Conceivably, the individual of the present and that same individual in the future may differ in ways that reflect the altered constitution of the individual brain. Such a plastic brain lends itself much more readily to therapeutic intervention than a largely stable adult brain. The latter cannot be expected to change its function, much less its structure, to a large degree in response to therapeutic intervention. Thus, I will argue that, in the case of research on adult neurogenesis, this difference represents not just another opening of the neurosciences towards novel therapeutic approaches, but has also played a decisive role in promoting a transformation in thought styles.

The dogma: the adult brain contains a constant number of neurons

Within neurobiological research, the generation of neuronal cells during early development and the subsequent elimination of superfluous cells are considered central processes in the sculpting of the central and the peripheral nervous system. As part of developmental plasticity, these phenomena have been studied extensively. However, until the 1990s, the predominant scientific understanding was that in mammals the capacity for neuronal renewal is terminated with the completion of early postnatal development. The characterization of the adult brain, as a network consisting of a constant number of neurons, has been very firm. It persisted for almost the entire twentieth century with little successful challenge. Accordingly, it has been repeatedly labelled as a ‘dogma’ by neuroscientists (e.g. Ihrie and Alvarez-Buylla, Reference Ihrie and Alvarez-Buylla2008). The choice of this term seems to underscore the dominance of this view in the scientific perception of the mammalian brain. Interestingly, this so-called dogma is not confined to science but has become so commonplace in Western culture that almost everyone has been aware that the choice of an exuberant lifestyle might have irrevocable repercussions, as one has to go about life relying on fewer and fewer neurons. Now there is hope: a brain which at least partially regenerates itself and might be amenable to therapeutic measures based on cellular regeneration seems to be a possibility. In the following I will highlight some of the stages on the way to this regenerative brain.

At the beginning of the twentieth century the view took root of an adult mammalian brain as a largely fixed network consisting of a constant number of neurons (Kempermann 2006: 22–49). The origin of this view is to be found in the anatomical investigations by a large number of researchers, among them William His, Camillo Golgi and, last but not least, by a very dominant figure in early neuroscience, Ramon y Cajal. The anatomical investigations conducted by these researchers were based on sections of brain tissue chemically processed and stained to reveal its cellular structure. Apparently the interpretations deduced from static microscopic images condensed into a view of a fixed network, consisting of a stable number of neurons only allowing for synaptic changes, as discussed below. This transformation seems epitomized by a frequently cited quote from Ramon y Cajal (1928: 750): ‘Once development has ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed and immutable: everything may die, nothing may be regenerated.’ This passage is to be found at the end of a report on a very extensive and carefully conducted analysis of different types of lesions and their consequences for the formation of the nervous system of higher vertebrates.Footnote ³ The author also ascribes the seemingly complete absence of regeneration he had observed to the fact that neurons, as highly differentiated cells, have forfeited their capability to proliferate in exchange for a gain of specific cellular functions. In view of the fact that a replacement of lost neurons via stem cells only became conceivable in the 1990s, this understanding has played an important role in the development of the field of adult neurogenesis. However, in spite of his failure to observe regenerative events, in the following paragraph Cajal (1928: 750) expresses hope that attempts at regeneration might be successful in the future: ‘it is for the science of the future to change if possible this harsh decree’. It is important to understand how a view of a mature brain harbouring a constant number of neurons could become so dominant, all the more as this influential neuroscientist and Nobel laureate, who contributed significantly to the concepts of plasticity, was aware of the limitations of the first empirical investigations.Footnote ⁴

During the same period, it becomes possible to discern two foundations of the framework that has dominated the understanding of plasticity of the brain for much of the twentieth century. First, neuronal networks are composed of single neuronal cells which are connected to each other in a discontinuous fashion, a view founded mainly on the work by Cajal. Second, the information is conveyed between neuronal cells via specific contact points called synapses, a concept introduced by Sir Charles Sherrington. In this framework the establishment of neuronal networks is, in the first instance, a result of development. Hence, modifications of the neuronal network can only take place at the contact points between cells. In this context the fully developed brain is understood as an intricate and largely fixed network of billions of cells, which exert specific functions within different parts of the brain. This understanding proved central for concepts of learning and memory. The ability of the developed brain to record memory, to learn new tasks or simply to deal with changing environments, has been explained by the modulation of the interconnections between its different cellular components. If the brain is to acquire novel information then it does so via the modification of these contact points: synaptic efficacy and strength will ultimately determine where information is conveyed and stored in the brain. This understanding has been theoretically and empirically reinforced during much of the twentieth century (for a discussion of the concept and its historical evolution, see Berlucchi and Buchtel, Reference Berlucchi and Buchtel2009).

Accordingly, during much of the twentieth century, the biological mechanisms underlying plasticity have been understood and described in terms of changes of connectivity, so called ‘functional plasticity’. The strengthening or weakening of existing synapses between individual neurons have been thought to explain the capacity of the mature brain to change its functionality in response to novel demands. However, particularly during the past three decades, the concept of the adult mammalian brain as a largely fixed neuronal network has been increasingly cast into doubt. An increasing amount of evidence has been provided for its ‘structural plasticity’, which implies that not only might the function of existing connections be changed, but that during the entire lifespan connections might be formed and reformed at different levels, affecting different brain structures, to an extent which has not become apparent before. In this context, the generation and functional integration of novel neurons, which has been described as a novel form of structural plasticity occurring throughout the adult life, stands out as a particularly significant finding. The birth and functional integration of new neurons in the mature nervous system has been described ‘as the most extreme cases of neuroplasticity in the adult brain’ (Gage et al., Reference Gage, Kempermann and Song2008: xi). In order to discuss how this novel understanding of the adult brain came to be formed, I will present a brief overview of the development of the research into adult neurogenesis covering a period from the mid twentieth century to the present. In doing so, I will highlight some of the important developments that will allow us to make a first appraisal of the factors which have played a dominant role in shaping a distinct shift in neurobiological research. Reference will be made to research into the vertebrate brain, with an emphasis on the mammalian brain and in particular on the human brain.Footnote ⁵

The beginning of adult neurogenesis, important findings are rejected

In the 1950s, for the first time, a sensitive method for the detection of dividing cells in living tissue became available to researchers in biology (Hughes et al., Reference Hughes, Bond, Brecher, Cronkite, Painter and Quastler1958).Footnote ⁶ With the help of radioactively labelled nucleotides, namely tritiated thymidine, it became possible to directly demonstrate the synthesis of DNA accompanying the generation of novel cells in developing, as well as mature, brain tissue. Before the advent of radioactive tracer molecules, researchers were limited to the direct detection of cells undergoing mitosis, a much less sensitive approach, which did not permit investigation of the dynamics of the processes observed. However, there had been a number of earlier publications reporting the phenomenon (Gross, Reference Gross2000). A few researchers employed the novel labelling method, not only for the investigation of the developing organism—they also reported the occurrence of dividing cells at several sites in the mature mammalian brain. The most notable of these researchers were Joseph Altman and Gopal Das. The first publication by Altman on the subject of adult neurogenesis carries the tentative title: ‘Are new neurons formed in the brains of adult mammals?’ (1962). It was published in the journal Science and followed up by a series of extensive anatomical investigations based on the application of tritiated thymidine. These studies confirmed the existence of neurogenesis in the hippocampus of the adult mammalian brain. Altman and Das also addressed the decisive question of the origin of novel neurons and suggested the existence of undifferentiated precursor cells migrating and giving rise to differentiated neurons at several sites in the mature brain. These analyses were all published in prestigious journals of the field (e.g. Altman, Reference Altman1963, Reference Altman1969; Altman and Das, Reference Altman and Das1965a, Reference Altman and Das1965b, Reference Altman and Das1967).

Gerd Kempermann, one of the prominent actors in the contemporary field of adult neurogenesis comments on the work of Altman and Das (1965a) as follows:

However, in spite of the successful passage through peer review of the empirical data and the authors’ interpretation of it as proof of the process of adult neurogenesis, these studies did not gain general acceptance. The validity of the empirical findings was put into doubt, because of methodological limitations. One important criticism was the ambiguity that remained about the precise localization of the radioactive labelling and the identity of the labelled cells. Given the spatial resolution of the analysis at light microscopic level, the issue of whether the labelled cells were neurons or the other main cellular components, the glial cells, could not be resolved in an unambiguous manner. The proofs provided did not satisfy the requirements of the field for the acceptance of such anomalous findings. As a consequence, these first reports on adult neurogenesis were not recognized as a significant contribution to the understanding of the brain, but repudiated as irrelevant by important actors in the field of nervous system development. Charles Gross quotes Paul Weiss, a well known neuroscientist who, in reference to a comprehensive study by Altman, wrote that ‘sporadic residual straggler neurons have been reported’ (Gross, Reference Gross2000). From an analytical point of view, it appears that the predominant thought style at the time did not allow the significance of these novel findings to be recognized by the majority of those within this research community. They had no other option but to categorize them as irrelevant. As a consequence, Altman discontinued publishing research on adult neurogenesis in the 1970s. These circumstances lend themselves well to a description along the lines of Fleck’s concept of the thought style, since, in Fleck’s terms: ‘In the history of knowledge, no formal relation of logic exists between conceptions and evidence. Evidence conforms to conceptions just as often as conceptions conform to evidence’ (1979: 28).

However, the studies by Altman were followed up by Shirley Bayer and Michael Kaplan and their co-workers (e.g. Bayer, Reference Bayer1985; Bayer et al., Reference Bayer, Yackel and Puri1982; Kaplan, Reference Kaplan1981; Kaplan and Hinds, Reference Kaplan and Hinds1977; Kaplan et al., Reference Kaplan, McNelly and Hinds1985). Michael Kaplan and James Hinds developed an improved detection method based on electron microscopy. This enabled the analysis of the cells labelled with tritiated thymidine at much higher resolution. This made it possible to pinpoint cellular characteristics identifying individual cells as newly formed neurons. Consequently, their publication in Science on the application of this novel method for the analysis of the adult rat brain ends with a very optimistic statement: ‘Now we have confirmed that growth and plasticity, including neurogenesis and synaptogenesis, can also occur in the mature, unoperated, mammalian brain.’ In spite of the fact that this work and the other analyses were, once more, published prominently, the resistance of the thought community could not be overcome. Interestingly, the repudiation was based once more on a critique of the methodology employed. ‘Those may look like neurons in New Mexico’, Michael Kaplan remembers Pasko Rakic (a central actor and eminent researcher on the formation of the brain) saying on the occasion of a meeting, ‘but they don’t in New Haven’ (in Lehrer, Reference Lehrer2006). The extensive engagement with the subject of adult neurogenesis proved detrimental to the research career of Kaplan, who abandoned the field to practise medicine (Kaplan, Reference Kaplan2001).

One can conclude that the period from the 1960s to the 1980s was dominated by the conception of an adult mammalian brain with a constant number of neurons. Anomalies brought to light by methodological progress, which cast doubt on the predominant thought style based on the cellular immutability of the adult brain, were repeatedly categorized as insufficiently robust, and hence this evidence was not considered to be a challenge to that belief. This seems to correspond to what Fleck has discussed as characteristic of a thought collective—an insistence on maintaining a certain type of thought style, either by ignoring, concealing or investing a great deal of effort in categorizing novel evidence as not contradictory to the dominant understanding (Fleck, Reference Fleck1979: 27–38). During the same period, glial cells, comprising different types of highly differentiated, so-called support cells of the nervous systems, were also found to possess the capacity for life-long multiplication (e.g. Kaplan and Hinds, Reference Kaplan and Hinds1980). This work was readily accepted in the field, as Kaplan (2001) discusses in his review. In contrast, the most widely read neurobiological textbook of 2000 still makes no mention of adult neurogenesis (Kandel et al., Reference Kandel, Schwartz and Jessell2000). Until recently, glial cells have been considered primarily to have a nourishing and stabilizing function, which serves to support the neurons. Seemingly, their capability to replicate was thought to be in accordance with their function as supporting cells, as it did not seem directly to affect the formation of the neuronal network.

Adult neurogenesis becomes a fact, but birds’ brains are different

In spite of the continued failures of the phenomenon of neurogenesis in the adult mammalian nervous system to gain acceptance, in the 1980s, for the first time, the research of Fernando Nottebohm's laboratory began to affect the dominant thought style of cellular immutability of the vertebrate brain. Building on a very elaborate experimental system, which allowed Nottebohm and his co-workers to link behaviour and brain physiology in songbirds, the annually recurrent acquisition of novel songs by male canaries could be connected to the seasonal generation and function of novel neurons. (Nottebohm, Reference Nottebohm2004). Most tellingly, the initial adherence to, and subsequent abolition of, the predominant thought style can be traced within the publications of this laboratory. The first descriptions of a brain volume change associated with seasonal song-learning in male songbirds were still framed in terms of a model of plasticity primarily based on synaptic change; although the researchers envisioned structural changes at the level of the synapse, they still could not imagine the addition of novel neurons in the brain: ‘According to this hypothesis the plastic substrate for vocal learning is renewed once yearly, a growing, then shedding of synapses, much the way trees grow leaves in the spring and shed them in the fall’ (Nottebohm, Reference Nottebohm1981: 1370). In spite of this initial interpretation, a few years later comprehensive empirical evidence had been generated, which proved that the novel neurons were being generated in a season-dependent fashion, in the areas of the bird brain involved in song-learning. Central to this demonstration was that Nottebohm and his co-workers could not only provide proof that these novel cells were indeed neuronal in nature, but also, and much more importantly, that they exerted specific functions in the investigated behaviour. Consequently, emboldened by the empirical evidence Goldman and Nottebohm announced a fundamental transformation in the understanding of adult brain plasticity: ‘Regardless of its behavioral significance, the ventricular zone neurogenesis we have observed is both provocative and reassuring of the plasticity that might reside in adult nervous systems’ (Goldman and Nottebohm, Reference Goldman and Nottebohm1983: 2394). A decisive step had been taken towards changing ‘the harsh decree’ that Cajal had deplored. Not unexpectedly, Nottebohm claimed evolution to be on his side: ‘From all we know of nervous systems, we get the impression that principles of function are widespread across taxonomic phyla’ (in Kolata, Reference Kolata1984: 1325). With this argument he referred to a widely held belief in biological science. The notion that important physiological mechanisms are evolutionarily conserved throughout the animal kingdom is a constitutive assumption which underlies a vast spectrum of empirical approaches. It represents a central justification for an increasing number of animal models. The assumption of evolutionary conservatism allows researchers to generalize from phenomena observed in so-called model organisms in relation to species which are considered to occupy a higher level in the evolutionary hierarchy, including humans.

Undoubtedly, the work by Nottebohm and his colleagues signified an important step towards the development of a concept of structural plasticity based on neuronal renewal. In contrast to earlier studies performed on mammalian species, it turned adult neurogenesis into a physiologically explicable phenomenon, as it connected its occurrence to a complex behaviour in birds. It has also been pointed out that Nottebohm—in contrast to his predecessors Altman and Kaplan, who were in an early phase of their academic career when they published their controversial evidence—was already a distinguished and established scientist (Gross, Reference Gross2000). Thus methodological critique of the experimental approach did not suffice to repudiate this novel work. Evidence had been provided not only for the existence of adult neurogenesis, but also for its function. This particular constellation of arguments finally allowed a central view on brain evolution to become apparent. This was that the human brain occupies a distinct place in evolution, one that cannot be explained in terms of continuous development and improvement of physiological functions already present in vertebrate species, such as birds, occupying much lower ranks within the evolutionary tree. On the contrary, only a sudden acceleration of evolution, separating primates and in particular the human species from lower vertebrates and the rest of the animal kingdom, can explain the emergence of such a highly complex organ as the human brain (for a discussion on the topic see Bradbury, Reference Bradbury2005).

As will be discussed in the following section, immanent in this understanding has been the idea that the unequalled degree of functional and hence anatomical complexity of the human brain also presupposes its cellular immutability. Within this thought style, the absence of adult neurogenesis constitutes a hallmark of the evolution of the human brain. As I will argue, this particular understanding of brain evolution has played a decisive role in the developments analysed here. It has largely determined the scientific relevance ascribed to these early findings, as well as to later findings on neurogenesis. The assumption of evolutionary discontinuity deprived the argument of evolutionary conservatism provided by Nottebohm of its central justification. In the view predominant within the neuroscience community of this period, the evidence gathered in song birds did not in any way prove the existence—or the relevance—of this phenomenon in those species with the most advanced brain structures, namely primates, including humans. The initial reception of his work can be summarized in the following remark quoted by Michael Specter: ‘Old Fernando found a cute thing about birds’ (2001: p45). From an analytical point of view what was decisive was that, although in biological research the concept of evolutionary continuity was deeply entrenched, the existing style of thought was still resisting transformation. In Fleck’s terms, the findings of Nottebohm’s group were treated as a ‘supplement’ to the existing thought style.Footnote ⁷

The mammalian brain is plastic, but not the primate brain

In 1984 a conference of the New York Academy of Science with the optimistic title ‘Hope for a New Neurology’ brought together a number of researchers concerned with regenerative phenomena, their occurrence in the adult nervous system of vertebrates and their possible therapeutic value (Nottebohm, Reference Nottebohm1984). In the proceedings of this conference a number of groups reported on the phenomenon of adult neurogenesis in different vertebrate species. However, the contribution by one of the participants, Pasko Rakic, a very well known expert on cortical development, stands out, as it discusses not the presence but the absence of a regenerative capacity, namely the lack of adult neurogenesis in the primate brain. It also presents an explanation for why neurogenesis could not exist, which alludes to the understanding that the complexity of the most highly developed brains is based on their adult immutability: ‘The addition of new “naïve” neurons into existing circuits would interfere with the retention of acquired experience and learned behavior that is evolutionarily the most significant advantage of all primate species including human’ (Rakic, Reference Rakic and Nottebohm1985a: 208). These conclusions were reformulated and extended in a widely cited publication with the title ‘Limits of neurogenesis in primates’ (Rakic, Reference Rakic1985b) in the journal Science:

These two publications can be considered as a rather timely and poignant reply to the progress in research on adult neurogenesis and related plasticity paradigms in several vertebrate species, including birds and mammals. They can also be interpreted as a pre-emptive strike to preserve a secure and separate place in neuroscience for the most highly developed brains, emphasizing their synaptic rather than their structural plasticity. This empirical work seemingly banished adult neurogenesis once and for all from the realm of the mature human brain. It is interesting to note that, at this point, the traditional thought style proved so dominant that work based on negative evidence, namely the absence of a proof for neurogenesis in the primate brain, could be published in a prestigious journal and was received as a relevant argument.

In spite of these and other efforts to defend the existing thought style, the 1990s were marked by reports of neurogenesis in the adult mammalian brain. The research by Elisabeth Gould and Heather Cameron in the laboratory of Bruce McEwen is of central importance in this context (e.g. Cameron et al., Reference Cameron, Woolley, McEwen and Gould1993; Gould et al., Reference Gould, Cameron, Daniels, Woolley and McEwen1992). It led to the rediscovery of neurogenesis in the adult hippocampus of rats and formed the basis for a number of functional studies. These demonstrated the negative regulation of adult hippocampal neurogenesis by stress and specific hormones in different mammalian species, including primates (e.g. Gould et al., Reference Gould, McEwen, Tanapat, Galea and Fuchs1997, Reference Gould, Tanapat, McEwen, Flügge and Fuchs1998). Decisive, in terms of the concerns of the present argument, is the fact that these novel results were not only published in renowned journals of the field, but also that this work was backed by Bruce McEwen, Eberhard Fuchs and Charles Gross, all very well-established scientists.Footnote ⁸ Subsequent studies profited from methodological progress in the identification and labelling of newly generated cells. The adaptation of a non-radioactive DNA labelling agent (BrDu) greatly facilitated the identification of newly generated cells in the nervous system. In addition, the application of BrDu could be combined with the use of cell type specific marker molecules. The combination of these labelling techniques with novel microscopic methods allowed researchers to identify novel cells as neurons with much greater ease and precision. This methodological progress can be regarded as one explanation for the rapid growth of the field of adult neurogenesis since the 1990s.

However, even more influential for the development of the field of adult neurogenesis was the discovery of neural stem cells in the adult mammalian nervous system, which coincided with the renaissance of research on adult neurogenesis in the mammalian brain (e.g. Reynolds and Weiss, Reference Reynolds and Weiss1992; Richards et al., 1992). These two initially independent research venues proved reciprocally reinforcing, as the identification of neural stem cells provided a conceptual framework for neuronal renewal which had been missing in the previous view of the nervous system. The isolation and cultivation of neuronal stem cells in vitro allowed researchers to propose the presence of such undifferentiated cells also in vivo, i.e. in brain tissue. Only then did it become possible to conclusively overcome one of the tenets formulated by Cajal, namely the inability of differentiated neurons to multiply. It was not differentiated neurons, which are considered incapable of cell division, that provided for neuronal renewal. Rather, it was stem cells and progenitor cells, which are located in specific parts of the brain and can migrate long distances to their final destination, which came to be seen as the source of regeneration. As a consequence the brain became the newest member of the family of organs which distinguish themselves through the presence of stem cells.

Another indication that the 1990s provided a more favourable climate for the research on adult neurogenesis than the preceding decades is the fact that the initial work by Cameron, Gould and their colleagues initiated a cascade of studies into adult neurogenesis in different mammalian species. The procession of this research and its domain-specific reception continued to reflect the efforts initiated by Rakic’s early publication on the primate brain, namely to reserve a separate place in brain evolution for the primate brain. What might be described as a ‘neurobiological line of defence’, which had been drawn around the human as the most advanced mammalian species in evolutionary terms, and its closest relatives the non-human primates, becomes apparent in two different categorizations: either the brains of evolutionarily less advanced species (like birds) are described as being more prone to structural plasticity, or the evolutionarily most advanced brain regions are regarded as less tolerant to structural plasticity (like the neocortex). A review of the advances in the field of adult neurogenesis published in the journal Science reveals the cautious approach of researchers within the neurosciences to this novel field. Novel empirical evidence in favour of adult neurogenesis in different primate species continues to be distinguished and weighed against the evolutionary position of the respective species, i.e. their relatedness to the human species (Barinaga, Reference Barinaga1998). The persistent influence of the existing thought style and of one of its most vocal proponents becomes evident in a quote from well-known neuroscientist Fred Gage, who is cited in this review: ‘ “The idea that they can extrapolate on to humans is blocked in part” by Rakic’s results, says Salk’s Gage’ (Barinaga, Reference Barinaga1998: 2042).

Thus an important part of the progress in adult neurogenesis research continued to be understood and debated within the evolutionary categories discussed earlier. The neocortex, as the most ‘human’ part of the brain, is seemingly not expected to display a similar degree of structural plasticity to the evolutionarily more ‘primitive’ parts of the brain, such as the olfactory bulb. In this style of thought, evidence provided for the occurrence of neurogenesis in the primate cortex (Gould et al., Reference Gould, Reeves, Graziano and Gross1999) was promptly put into doubt by a study, based on the same methodology, documenting the absence of neurogenesis in the same structure (Kornack and Rakic, Reference Kornack and Rakic2001). A comment on a more recent study, which reports the absence of adult neurogenesis in the human cortex, carries the title ‘Stable neuron numbers from cradle to grave’ (Nowakowski, Reference Nowakowski2006). The author argues for a stable number of neurons, in a very similar manner to Rakic 22 years earlier:

In spite of the ongoing controversy, some prominent members of the neuroscience community, such as the Nobel laureate Eric Kandel, in reference to the research on adult neurogenesis, declared a ‘paradigm shift’. Kandel commented on the reception of the work on adult neurogenesis as follows: ‘The scientific community can easily believe something it is 50 percent ready to absorb, but not something that comes out of the left field. But here we are prepared for it’ (in Wade, Reference Wade1999). In so doing, Kandel and others assume the role of conscious advocates of scientific change. They employ the notion of a paradigm shift as a metaphor for change and innovation, as has been discussed for various other scientific contexts by Maasen and Weingart (2000: 135–175). It is noteworthy, too, that Charles Gross, who was an actor as well as a chronicler, and an advocate of a paradigm shift in research on structural plasticity, refers to a historic attempt to link humanness to certain neurobiological properties (Gross, Reference Gross2000). He likens the attempt to designate the absence of adult neurogenesis as uniquely human to another effort to render the human brain anatomically distinct. Shortly after the publication of Darwin’s seminal work, the famous anatomist Richard Owen declared the existence of the ‘hippocampus minor’, an organ unique to the human brain. In a widely publicized controversy with T.H. Huxley, a defender of evolution, Owen finally had to admit, that he had fabricated the evidence, a hippocampus minor had never existed (Gross, Reference Gross1998: 136–178). As Darwin’s work put human uniqueness in question, so apparently does the contemporary research on adult neurogenesis.

The human brain, the last bastion of immutability is lost—a gain for therapy!

In 1998 an international study which was led by the laboratory of Fred Gage proved that the diverse efforts to categorize the primate and the human brain as not structurally plastic were ineffectual. The analysis on post mortem human brains of Swedish patients, who had received DNA-labelling agents marked a watershed in the understanding of adult neurogenesis. It demonstrated the existence of ongoing neurogenesis in the adult human brain, notably in the hippocampus, even in the brain of advanced age (Eriksson et al., Reference Eriksson, Perfilieva, Björk-Eriksson, Alborn, Nordborg and Peterson1998). This work was essentially a resumption of earlier unsuccessful attempts by Kaplan’s group in the 1980s to extend the analysis of adult neurogenesis to the mature human brain (Kaplan, Reference Kaplan2001). This was portrayed as a groundbreaking study, which gave adult neurogenesis the ultimate cachet: as a property of the human brain (Blakeslee, Reference Blakeslee2000). From the perspective of the present analysis, it appears to be an ingenious move by a very visible scientist: Gage is not only a very prominent member of the neuroscience community, but has also been repeatedly and successfully engaged in the public discourse on biomedicine. This 1998 publication not only placed Gage’s laboratory at the forefront of a novel thought collective exploring adult neurogenesis. It also ratified the transformation in thought styles, as the concept of structural plasticity in the adult brain had, for the first time, been demonstrated to be a universal property of the nervous system, present in all species.Footnote ⁹ The vitality of the expanding thought collective centred on the exploration of adult neurogenesis is reflected in the growing number of research reports at the annual meeting of the American Society for Neuroscience. This conference, probably the most important annual event in the neurosciences, is a very large gathering of about 25,000 scientists from around the world. Amongst the abstracts submitted for the conference in 2000, 13 used the keyword ‘adult neurogenesis’; by 2008 this number had grown to 312.

Fred Gage was a very dominant actor, in possession of a sufficient amount of scientific capital to take the crucial step towards ‘humanizing’ adult neurogenesis.Footnote ¹⁰ This proof of the generation and integration of novel neurons in the adult human hippocampus, a major component of the human brain involved in learning and memory, immediately opened up unprecedented possibilities for therapeutic intervention. It triggered an exploration of the role of adult neurogenesis in neurodegenerative diseases, as well as psychiatric disorders such as depression which are known to affect the hippocampus (Grote and Hannan, Reference Grote and Hannan2007). One outcome of this engagement was the founding of Brain Cells Incorporated (BCI), a company focusing on the identification of small therapeutic compounds which stimulate neurogenesis and could serve as novel treatments for mood disorders. BCI thereby targets one of the most important pharmaceutical markets. The company has also assembled some very prominent members of the neuroscience community on its scientific advisory board, amongst them Gage and Kandel. Kandel co-founded Neurogenix, which merged with BCI in 2004. The argument is put forward, that with the extension of research on adult neurogenesis to include the human species, a therapeutic discourse has become very prominent.

I suggest, that this therapeutic discourse has separated itself from a primarily discipline-specific discourse. This division enables the scientific community to cope with divergent social demands in the development of their research agenda. On the one hand, a scientific development that seems to amount to a significant threat to an existing thought style has to be carefully managed. On the other hand, the therapeutic demands and economic interests of a burgeoning neuro-biotech industry have to be met. Within the scientific discourse this has led to ongoing attempts to assign a proper place to neuronal renewal, as an interesting, albeit not dominating principle of the physiology of the adult mammalian brain. In this context, neuronal renewal has been described, as confined to certain regions of the adult brain designated as ‘neurogenic’.Footnote ¹¹ In contrast, within the therapeutic discourse on adult neurogenesis, the scientific community signals to society at large its readiness to exploit the therapeutic potential of this novel type of plasticity, which might not only provide a remedy for a number of diseases and damages to the brain, but is also ‘suggesting the potential for a “a self healing brain” ’ (Society for Neuroscience, 2007). Interestingly, in scientific publications these two emerging discourses seem readily to intermingle without directly competing with one another. Reflections on the as yet unknown physiological role of structural plasticity are found alongside affirmations of its therapeutic potential. Within one and the same publication, the need for further research to properly assess the extent and physiological role of neurogenesis is proclaimed, while expectations for its therapeutic application are raised. In spite of the remaining uncertainties as to the functional role of adult neurogenesis, the intention to harness its regenerative powers is repeated as a truism, a mantra, not to be forgotten: ‘The demonstration of active neurogenesis in adult humans not only shows the unforeseen regenerative capacity of the mature central nervous system, but also raises hopes for repairing the damaged adult central nervous system after injury or degenerative neurological disease’ (Ming and Song, Reference Ming and Song2005).

Conclusions

Based on this analysis of the evolution of the field of adult neurogenesis, we can observe a transformation in thought style is occurring in the neurosciences. Within this change, the perception of the human brain has played a central role. The neuroscience community has been confronted with a profound dilemma in rendering the human brain changeable. It had to abolish a long cherished view of a complex and hence immutable adult human brain in favour of a life-long changeable brain. As a consequence, neuroscience has once more to confront the fact that, in biological terms, i.e. in terms of the brain’s structural plasticity, humans might not be as unique as imagined. The concept of a life-long changeable human brain confronts neuroscientists with the great difficulty of describing complexity not only as the apex of a highly interactive developmental phase, but also as the result of a life-long plasticity.

Emily Martin and others have discussed the way that the necessity for life-long learning and flexibility have been dominant themes in Western society since the beginning of the 1970s (Martin, Reference Martin1995, Reference Martin2007). As Martin points out:

An individual whose mature brain continues to be plastic should possess the potential and the capacity to submit itself to continuous (re)adaptation. In light of this, and in spite of the obstacles described above, one might be surprised by the resistance of the neurosciences to adopting the idea of a more plastic human brain. One might then ask why the neuroscientific thought style which favoured concepts of structural plasticity did not gain ascendance earlier, in spite of the empirical evidence favouring a more plastic adult brain. This would have allowed neuroscience to begin to think in terms of a human brain whose constitution corresponded to the need of the members of contemporary Western society to cope with the life-long challenge of reinventing themselves.

Without providing a direct answer, one might conclude that rendering the human brain plastic has made it more amenable to therapy and that this might have constituted a decisive facilitator at the end of the 1990s. This was not present in the 1980s, when the first proposal to investigate neurogenesis in the adult human brain failed to gain acceptance. Pursuing this argument, we could argue that the transformation of thought style was facilitated by the close proximity between today’s biological research and medical applications. As a consequence, biological research has not only become a central carrier, but is also shaped by what I have termed—in the context of the discourse on human embryonic stem cells—the therapeutic promise (Rubin, Reference Rubin2008).

Indeed, a thought style conceptualising a plastic human brain integrates well with those styles of thought which Nikolas Rose (2007:186–223) has described as defining the ‘neurochemical self’ in contemporary society. It builds upon and reinforces the view of the brain as an organ whose adequately managed functions form the organic basis of our identity and of our well-being, a perception which is becoming ever more plausible in contemporary society (Maasen, Reference Maasen2007). Undoubtedly, structural plasticity adds a further therapeutic dimension to the existing neuroscientific catalogue, implying that not only the function of synaptic connections might be modulated by the administration of proper treatments, but also their very existence might be amenable to therapeutic measures. As discussed above, this vision is at the centre of a potentially very large pharmaceutical market for a novel generation of antidepressants. In spite of these economic hopes, however, Martin has noted that, to a large extent, the concepts of structural plasticity, as discussed here, have yet to leave the laboratory (Martin, Reference Martin2007: footnote 36: 291). It therefore remains an open question whether the neurochemical self will also take on the obligation of being plastic.