Darwin’s Neuroscientist: Gerald M. Edelman, 1929-2014

Image
Dr. Gerald M. Edelman, 1929-2014.

“The brain is wider than the sky.
For, put them side by side,
The one the other will include,
With ease, and you beside.”

Dr. Gerald M. Edelman often used these lines from Emily Dickinson to introduce the deep mysteries of neuroscience and consciousness. Dr. Edelman (it was always ‘Dr.’), who has died in La Jolla, aged 84, was without doubt a scientific great. He was a Nobel laureate at the age of 43, a pioneer in immunology, embryology, molecular biology, and neuroscience, a shrewd political operator, and a Renaissance man of striking erudition who displayed a masterful knowledge of science, music, literature, and the visual arts who at one time could have been a concert violinist. He quoted Woody Allen and Jascha Heifetz as readily as Linus Pauling and Ludwig Wittgenstein, a compelling raconteur who loved telling a good Jewish joke just as much as explaining the principles of neuronal selection. And he was my mentor from the time I arrived as a freshly minted Ph.D. at The Neurosciences Institute in San Diego, back in 2001. His influence in biology and the neurosciences is inestimable. While his loss marks the end of an era, his legacy is sure to continue.

Gerald Maurice Edelman was born in Ozone Park, New York City, in 1929, to parents Edward and Anna. He trained in medicine at the University of Pennsylvania, graduating cum laude in 1954. After an internship at the Massachusetts General Hospital and three years in the US Army Medical Corp in France, Edelman entered the doctoral program at Rockefeller University, New York. Staying at Rockefeller after his Ph.D. he became Associate Dean and Vincent Astor Distinguished Professor, and in 1981 he founded The Neuroscience Institute (NSI). In 1992 the NSI moved lock, stock, and barrel into new purpose-built laboratories in La Jolla, California, where Edelman continued as Director for more than twenty years. A dedicated man, he continued working at the NSI until a week before he died.

In 1972 Edelman won the Nobel Prize in Physiology or Medicine (shared independently with Rodney Porter) for showing how antibodies can recognize an almost infinite range of invading antigens. Edelman’s insight, the principles of which resonate throughout his entire career, was based on variation and selection: antibodies undergo a process of ‘evolution within the body’ in order to match novel antigens. Crucially, he performed definitive experiments on the chemical structure of antibodies to support his idea [1].

Image
Dr. Edelman at Rockefeller University in 1972, explaining his model of gamma globulin.

Edelman then moved into embryology, discovering an important class of proteins known as ‘cell adhesion molecules’ [2]. Though this, too, was a major contribution, it was the biological basis of mind and consciousness – one of the ‘dark areas’ of science, where mystery reigned – that drew his attention for the rest of his long career. Over more than three decades Edelman developed his theory of neuronal group selection, also known as ‘neural Darwinism’, which again took principles of variation and selection, but here applied them to brain development and dynamics [3-7]. The theory is rich and still underappreciated. At its heart is the realization that the brain is very different from a computer: as he put it, brains don’t work with ‘logic and a clock’. Instead, Edelman emphasized the rampantly ‘re-entrant’ connectivity of the brain, with massively parallel bidirectional connections linking most brain regions. Uncovering the implications of re-entry remains a profound challenge today.

Image
The campus of The Neuroscience Institute in La Jolla, California.

Edelman was convinced that scientific breakthroughs require both sharp minds and inspiring environments. The NSI was founded as a monastery of science, supporting a small cadre of experimental and theoretical neuroscientists and enabling them to work on ambitious goals free from the immediate pressures of research funding and paper publication. This at least was the model, and Edelman struggled heroically to maintain its reality in the face of increasing financial pressures and the shifting landscape of academia. That he was able to succeed for so long attests to his political nous and focal determination as well as his intellectual prowess. I remember vividly the ritual lunches that exemplified life at the NSI. The entire scientific staff ate together at noon every day (except Fridays), at tables seemingly designed to hold just enough people so that the only common topic could be neuroscience; Edelman, of course, held court at one table, brainstorming and story-telling in equal measure. The NSI itself is a striking building, housing not only experimental laboratories but also a concert-grade auditorium. Science and art were, for Edelman, two manifestations of a fundamental urge towards creativity and beauty.

Edelman did not always take the easiest path through academic life. Among many rivalries, he enjoyed lively clashes with fellow Nobel laureate Francis Crick who, like Edelman himself, had turned his attention to the brain after resolving a central problem in a different area of biology. Crick once infamously referred to neural Darwinism as ‘neural Edelmanism’ [8], a criticism which nowadays seems less forceful as attention within neurosciences increasingly focuses on neuronal population dynamics (just before his death in 2004, Crick met with Edelman and they put aside any remaining feelings of enmity). In 2003 both men published influential papers setting out their respective ideas on consciousness [9, 10]; these papers put the neuroscience of consciousness at last, and for good, back on the agenda.

The biological basis of consciousness had been central to Edelman’s scientific agenda from the late 1980s. Consciousness had long been considered beyond the reach of science; Edelman was at the forefront its rehabilitation as a serious subject within biology. His approach was from the outset more subtle and sophisticated than those of his contemporaries. Rather than simply looking for ‘neural correlates of consciousness’ – brain areas or types of activity that happen to co-exist with conscious states – Edelman wanted to naturalize phenomenology itself. That is, he tried to establish formal mappings between phenomenological properties of conscious experience and homologous properties of neural dynamics. In short, this meant coming up with explanations rather than mere correlations, the idea being that such an approach would demystify the dualistic schism between ‘mind’ and ‘matter’ first invoked by Descartes. This approach was first outlined in his book The Remembered Present [5] and later amplified in A Universe of Consciousness, a work co-authored with Giulio Tononi [11]. It was this approach to consciousness that first drew me to the NSI and to Edelman, and I was not disappointed. These ideas, and the work they enabled, will continue to shape and define consciousness science for years to come.

My own memories of Edelman revolve entirely around life at the NSI. It was immediately obvious that he was not a distant boss who might leave his minions to get on with their research in isolation. He was generous with his time. I saw him almost every working day, and many discussions lasted long beyond their allotted duration. His dedication to detail sometimes took the breath away. On one occasion, while working on a paper together [12], I had fallen into the habit of giving him a hard copy of my latest effort each Friday evening. One Monday morning I noticed the appearance of a thick sheaf of papers on my desk. Over the weekend Edelman had cut and paste – with scissors and glue, not Microsoft Word – paragraphs, sentences, and individual words, to almost entirely rewrite my tentative text. Needless to say, it was much improved.

The abiding memory of anyone who has spent time with Dr. Edelman is however not the scientific accomplishments, not the achievements encompassed by the NSI, but instead the impression of an uncommon intellect moving more quickly and ranging more widely than seemed possible. The New York Times put it this way in a 2004 profile:

“Out of free-floating riffs, vaudevillian jokes, recollections, citations and patient explanations, out of the excited explosions of example and counterexample, associations develop, mental terrain is reordered, and ever grander patterns emerge.”

Dr. Edelman will long be remembered for his remarkably diverse scientific contributions, his strength of character, erudition, integrity, and humour, and for the warmth and dedication he showed to those fortunate enough to share his vision. He is survived by his wife, Maxine, and three children: David, Eric, and Judith.

Anil Seth
Professor of Cognitive and Computational Neuroscience
Co-Director, Sackler Centre for Consciousness Science
University of Sussex

This article has been republished in Frontiers in Conciousness Research doi: 10.3389/fpsyg.2014.00896

References

1 Edelman, G.M., Benacerraf, B., Ovary, Z., and Poulik, M.D. (1961) Structural differences among antibodies of different specificities. Proc Natl Acad Sci U S A 47, 1751-1758
2 Edelman, G.M. (1983) Cell adhesion molecules. Science 219, 450-457
3 Edelman, G.M. and Gally, J. (2001) Degeneracy and complexity in biological systems. Proc. Natl. Acad. Sci. USA 98, 13763-13768
4 Edelman, G.M. (1993) Neural Darwinism: selection and reentrant signaling in higher brain function. Neuron 10, 115-125.
5 Edelman, G.M. (1989) The remembered present. Basic Books
6 Edelman, G.M. (1987) Neural Darwinism: The Theory of Neuronal Group Selection. Basic Books, Inc.
7 Edelman, G.M. (1978) Group selection and phasic re-entrant signalling: a theory of higher brain function. In The Mindful Brain (Edelman, G.M. and Mountcastle, V.B., eds), MIT Press
8 Crick, F. (1989) Neural edelmanism. Trends Neurosci 12, 240-248
9 Edelman, G.M. (2003) Naturalizing consciousness: a theoretical framework. Proc Natl Acad Sci U S A 100, 5520-5524
10 Crick, F. and Koch, C. (2003) A framework for consciousness. Nature Neuroscience 6, 119-126
11 Edelman, G.M. and Tononi, G. (2000) A universe of consciousness : how matter becomes imagination. Basic Books
12 Seth, A.K., Izhikevich, E.I, Reeke, G.N, and Edelman, G.M. (2006) Theories and measures of consciousness: An extended framework. Proc Natl Acad Sci U S A 103, 10799-804

 

The amoral molecule

Image

The cuddle drug, the trust hormone, the moral molecule: oxytocin (OXT), has been called all these things and more.  You can buy nasal sprays of the stuff online in the promise that some judicious squirting will make people trust you more. In a recent book neuroscientist-cum-economist Paul Zak goes the whole hog, saying that if we only let ourselves be guided by this “moral molecule”, prosperity and social harmony will certainly ensue.

Behind this outlandish and rather ridiculous claim lies some fascinating science. The story starts with the discovery that injecting female virgin rats with OXT triggers maternal instincts, and that these same instincts in mother rats are suppressed when OXT is blocked.  Then came the finding of different levels of OXT receptors in two closely related species of vole. The male prairie vole, having high levels, is monogamous and helps look after its little vole-lets.  Male meadow voles, with many fewer receptors, are aggressive loners who move from one female to the next without regard for their offspring. What’s more, genetically manipulating meadow voles to express OXT receptors turns them into monogamous prairie-vole-a-likes. These early rodent studies showed that OXT plays an important and previously unsuspected role in social behaviour.

Studies of oxytocin and social cognition really took off about ten years ago when Paul Zak, Ernst Fehr, and colleagues began manipulating OXT levels in human volunteers while they played a variety of economic and ‘moral’ games in the laboratory.  These studies showed that OXT, usually administered by a few intranasal puffs, could make people more trusting, generous, cooperative, and empathetic.

For example, in the so-called ‘ultimatum game’ one player (the proposer) is given £10 and offers a proportion of it to a second player (the responder) who has to decide whether or not to accept. If the responder accepts, both players get their share; if not, neither gets anything.  Since these are one-off encounters, rational analysis says that the responder should accept any non zero proposal, since something is better than nothing.  In practice what happens is that offers below about £3 are often rejected, presumably because the desire to punish ‘unfair’ offers outweighs the allure of a small reward. Strikingly, a few whiffs of OXT makes donor players more generous, by almost 50% in some cases. And the same thing happens in other similar situations, like the ‘trust game’: OXT seems to make people more cooperative and pro-social.

Even more exciting are recent findings that OXT can help reduce negative experiences and promote social interactions in conditions like autism and schizophrenia.  In part this could be due to OXTs general ability to reduce anxiety, but there’s likely more to the story than this.  It could also be that OXT enhances the ability to ‘read’ emotional expressions, perhaps by increasing their salience.  Although clinical trials have so far been inconclusive there is at least some hope for new OXT-based pharmacological treatments (though not cures) for these sometimes devastating conditions.

These discoveries are eye-opening and apparently very hopeful. What’s not to like?

Image

The main thing not to like is the idea that there could be such a simple relationship between socially-conditioned phenomena like trust and morality, and the machinations of single molecule.  The evolutionary biologist Leslie Orgel said it well with his ‘third rule’: “Biology is more complicated than you imagine, even when you take Orgel’s third rule into account”.  Sure enough, the emerging scientific story says things are far from simple.

Carsten de Dreu of the University of Amsterdam has published a series of important studies showing that whether oxytocin has a prosocial effect, or an antisocial effect, seems to depend critically on who the interactions are between. In one study, OXT was found to increase generosity within a participant’s ingroup (i.e., among participants judged as similar) but to actually decrease it for interactions with outgroup members.  Another study produced even more dramatic results: here, OXT infusion led volunteers to adopt more derogatory attitudes to outgroup members, even when ingroup and outgroup compositions were determined arbitrarily. OXT can even increase social conformity, as shown in a recent study in which volunteers were divided into two groups and had to judge the attractiveness of arbitrary shapes.

All this should make us look very suspiciously on claims that OXT is any kind of ‘moral molecule’ as some might suggest.  So where do we go from here? A crucial next step is to try to understand how the complex interplay between OXT and behaviour is mediated by the brain. Work in this area has already begun: the research on autism, for example, has shown that OXT infusion leads to autistic brains better differentiating between emotional and non-emotional stimuli.  This work complements emerging social neuroscience studies showing how social stereotypes can affect even very basic perceptual processes. In one example, current studies in our lab are indicating that outgroup faces (e.g., Moroccans for Caucasian Dutch subjects) are literally harder to see than ingroup faces.

Neuroscience has come in for a lot of recent criticism for reductionist ‘explanations’ in which complex cognitive phenomena are identified with activity in this-or-that brain region.  Following this pattern, talk of ‘moral molecules’ is, like crime in multi-storey car-parks, wrong on so many levels. There are no moral molecules, only moral people (and maybe moral societies).  But let’s not allow this kind of over-reaching to blind us to the progress being made when sufficient attention is paid to the complex hierarchical interactions linking molecules to minds.  Neuroscience is wonderfully exciting and has enormous potential for human betterment.  It’s just not the whole story.

This piece is based on a talk given at Brighton’s Catalyst Club as part of the 2014 Brighton Science Festival.