Piet Mondrian’s ‘Red Tree’ (1908-10) opens Dr. Lawrence Steinman’s talk about solving the problem of multiple sclerosis

In these thumbnail images, Mondrian’s trees grow steadily more impressionistic — or from the Steinman perspective, ‘molecular’

There’s a new biography of the polio vaccine hero, Dr. Jonas Salk, only months after the fêting and nomination for innumerable awards of a biopic about the computer pioneer, Alan Turing, and a film about the theoretical physicist Stephen Hawking. Once, there was not much more than portraits like these — and occasionally, a decent novel set among the petri dishes — to give non-scientists an inkling of how the mind of a scientific research star works. This was always intensely frustrating. No matter how gifted the writer or lifelike the cinematic conjuring, if what you crave is a feel for the mental acrobatics, the cerebral gambolling and sensibility involved, you leave the table as hungry as after you saw Shakespeare in Love or The Agony and the Ecstasy, and they failed to make you any wiser about the mind of the Bard or Michelangelo, respectively.

Creativity at the coalface — in art or science — is close to impossible to demonstrate from the outside, looking in.

In science, though, something wonderful has been happening. The evolution of media used in scholarship and every other intellectual realm from chiefly text-centred communication to including images wholesale, has some of the most inventive scientists deploying post-Gutenberg tools to open small doors to their minds to the rest of us.

An unanticipated encounter in Silicon Valley, the other day, with a friend and former student of Dr. Lawrence Steinman, led to a lively conversation in praise of the rare gifts for inspiring and elucidating of this quietly distinguished neuroscientist, molecular biologist and immunologist — who could never be accused of the avid self-promotion that, according to his biographer Charlotte DeCroes Jacobs, destroyed Dr. Salk’s reputation with fellow-scientists. For eight years, from 2003, Dr. Steinman coordinated immunology research across all departments at Stanford University. On more than one occasion, he and his research team have come tantalisingly close to discovering what causes multiple sclerosis, and devising a cure for this inflammatory disease of the brain and spinal cord — the nervous system — which is being diagnosed in growing numbers of people.

Four years ago, Dr. Steinman interwove a report on some of his research team’s latest findings about MS with a captivating appreciation of studies of trees by the Dutch painter, Piet Mondrian (1872-1944) — part of the De Stijl movement in abstract art — at a ceremony at which he was presented with the Charcot Prize.

The Charcot is awarded every two years by the Multiple Sclerosis International Federation to a scientist who has made exceptional progress in working out what causes this condition, and devising treatments for MS patients. Turning to art to aid enlightenment was apt because Jean-Martin Charcot — the French 19th-century scientist considered the founder of modern neurology — was a tremendous enthusiast for the use of drawings and photographs to demystify anatomy. But Dr. Steinman was actually primed for joining visual art to science by David Hubel and Torsten Wiesel — co-winners of the 1981 Nobel prize for physiology or medicine — whom he credits with introducing him, in his student days, to ‘the neurophysiology of perception of art in the brain’.

Here are quick sketches from parts of that Mondrian-inspired lecture — ‘Piet Mondrian’s trees and the evolution in understanding multiple sclerosis’ — with reproductions from the series, starting with ‘Red Tree’. We will not pretend that this is anything other than a ferociously technical paper only comprehensible impressionistically by a non-expert. All we want to say is that it offers tiny, enticing glimmers of the way the mind of one scientist works.

This was Dr. Steinman’s opening:

[W]e pose four questions that are relevant to our understanding of multiple sclerosis (MS). For each, we shall look at the evolution of Piet Mondrian’s paintings of a solitary tree. As we follow the evolution in these paintings from representational to Cubist, we see that our understanding of MS is also a mere process, and that we have a long way to go before it is “complete.”

These were his questions for his audience of chiefly fellow-scientists, slightly simplified and re-worded, here:

1. The male/female disparity: why are women developing MS so much more frequently than men?

2. Are there guardian molecules that protect the nervous system in MS?

3. With all the approved drugs, how can we rationally decide which one to use?

4. The Precise Scalpel vs. the Big Hammer for therapy: in the future, will MS be treated chiefly with powerful, heavy-duty drugs aimed at ‘wide swathes of the immune system,’ or with fine discrimination, using treatments tailored to the needs of particular patients?

The parallels Dr. Steinman drew for the path of his MS research are to Mondrian’s going from depicting a tree more or less as most of us perceive one, to finer atomisations of the way we discern a trunk and branches from sets of shapes and correspondences we associate with ‘tree-ness’. Similarly, beginning with viewing people as whole beings – and concentrating on a disease afflicting some of them – Dr. Steinman proceeds to delve into causes of their affliction at the level of fractions, the realm of molecular biology. He advances from considering aspects of MS and its manifestations from the whole-person viewpoint — with symptoms and behaviour obvious to any observer — to exploring causes in microbiology, in an analysis growing steadily more abstract and arcane.

In viewing the disease from the whole-person perspective, he begins by asking …

… why there is an increasing incidence of MS in females. One might argue
that the increase in MS in females must be due to some factor in the environment. It is hard to imagine that females are “evolving” so rapidly that one might attribute this phenomenon to a genetic factor. We suggest the most likely environmental influence is the increased “fat” and increased caloric intake in the female diet. The set of receptors influenced by fats and by sex hormones is of course found in the
remarkable PPAR family.

Though men are also consuming more fat and calories, there is a peculiar — harmful — interplay between fat and female sex hormones.

Next, Dr. Steinman relates how research has been pointing to the behaviour of a particular protein:

We sought to identify molecules that are produced by both neurons and glia, and that serve to protect the brain from inflammatory and degenerative damage. […] The amyloid molecules produced in the brain in response to stress in a variety of pathologies including MS may be imbued with protective properties. These molecules may be actually converted into therapeutics for MS, in both the relapsing–remitting and progressive manifestations of the disease.

Now, Mondrian again, for a consideration of the third question on his list:

In Figure 5, The Flowering Apple Tree, painted in 1912, Mondrian has evolved his depiction of trees to an even more Cubist interpretation. It is a wonder that our brains perceive a “tree” in this representation with only subtle representational cues. But as we acknowledge these subtle cues, the rising verticality of the “trunk” and the characteristic horizontality of the branches, we learn that this is all that we need to convince ourselves, that is, our brains, that this is a “tree.”

… Just as our brains can discern what is a tree and what is not, we therefore ask whether there are rational algorithms to determine which therapeutic is most suitable for any particular patient. As treating neurologists we are blessed with
a situation now where we can choose between multiple orally active drugs as well as injectable drugs for treatment of RRMS. But how can we make rational decisions when choosing among them?

There is no substitute for the fun of reading the paper yourself, making of it whatever you can. That takes real effort if, like those of us at post-Gutenberg.com, your ignorance of molecular biology is a long way south of abysmal. To get hold of a free copy, you will need the help of a good research librarian  — or you can spend $5 on buying one on the PubMed site of the U.S. National Institutes of Health. [ Post-publication note with excellent news:  please see the offer in the comments section below. ]

Of course Mondrian had everything to do with luring us into persisting past our incomprehension and in spite of it, even though we had never encountered his tree pictures until the Charcot lecture found its way to us, serendipitously. Long ago, in childhood, we loved this artist’s geometric paintings in electrifying primary colours.

Steinman colleagues at Stanford, over the years, have included the late Carl Djerassi – the subject of several posts on this blog, not least as an exemplary forerunner of post-Gutenberg Man, about whom it is an understatement to say that he was equally at home in the arts and sciences. At a private celebration of his life in March, we found ourselves sitting next to someone else cleverly harnessing his love of fine art to his mission as a scientist — and he will be the subject of the next entry in this blog.

part 2 is here