Ralph Steinman Nobel Prize for Medicine 2011 for dendritic immune signalling cell-biology, is shape sensing involved?

Do you have a hero? I have a bunch, especially in the medical field for people overcoming great obstacles to promote breakthrough knowledge, like this year’s Medicine Nobel Laureate-Ralph Steinman.

Notice how when Steinman first started publishing his first dendritic cell-biology observations in 1973 that a new type of immune cell could be found from peering into a microscope image, ‘the early criticism was relentless,’ yet why is this so ? Where is the openness in science to grasp wonderful ideas,where is the camaraderie of support from his peers?

Nature is not easy to understand, you would think that good science would be embraced by a researcher’s peers but just the opposite appears to be the norm, ‘that the journey was even possible was down to his forceful personality, energy and focus.’

Here’s another observation, ‘Steinman soon characterized pathways for the engulfing of molecules by cells (endocytosis) and, with Cohn, proposed the involvement of membrane recycling in this process.’ Sounds to me like a lot of shape sensing going on here, hearing terms like, engulfing- recycling membranes, boy, those processes sure involve shape changes.

The mysterious accessory cells stuck to glass, so Steinman — inspired by his cell-biology colleagues’ emphasis on microscopy — decided to examine glass-adherent spleen cells using phase contrast, live imaging and electron-microscopy techniques.’ If spleen cells are sticking to glass they are distorting themselves, spreading out, getting flatter which is definitely a tensegrity process, but nothing is mentioned from that context, hmmmm?

What he saw under the lens was a new type of immune cell that had branching, rapidly changing projections.’ That is more shape changes happening all along these rapidly changing projections. Just at the leading edge of any cell process projection are processes that we don’t really have a clue yet as to what is doing their guiding.

‘He brought in numerous scientists from other fields, and loved to collaborate.’ His attitude is perhaps one of the most critical reasons for his tenacity toward success, he cared and helped others to join the journey too. Wow, that’s how we go to Mars with spirit like that!

‘That the journey was even possible was down to his forceful personality, energy and focus.’

This is where I feel blessed that we are capable of being on a similar trajectory with our own concussion, brain pull, brain rotation project.

‘And he was equally passionate about making the leap from the bench to the bedside.’

That is our guiding concern, we want to observe these subtle signals within the brain in order to be able to extract their information to diagnose a brain concussion, something that is still a dream. But again the words of my colleague at the University of Ottawa, Director of Neurology, Dr Antoine (Tony) Hakim, ring in my head, ‘Mike if you guys can diagnose a concussion using heart data, that would be massive.’ Thank you so much Tony for saying that. There are still a ton of obstacles in our way, but somehow we will persevere, we will see to work making the difference.

All of us has our own hard fought struggle, our own journey. Getting toward a concussion diagnosis is our particular road that we are on. So please hold the criticism, we are after a truth of Nature, just like Ralph Steinman lived. Please read on

‘Nature | Obituary

Ralph Steinman (1943–2011)

Nature
478,
460
(27 October 2011)
doi:10.1038/478460a
Published online
26 October 2011

Immunologist and cheerleader for dendritic-cell biology.

Ralph Steinman changed the world of immunology when he discovered dendritic cells, but it took the field a long time to recognize the importance of his discovery. The idea that a new type of immune cell could be found in 1973 — in the era of molecular cell biology — simply by looking down a microscope seemed far-fetched. The early criticism was relentless. Steinman’s road to the Nobel Prize in Physiology or Medicine — awarded (unusually) just days after his death — was full of obstacles. That the journey was even possible was down to his forceful personality, energy and focus.

Steinman was born in 1943 in Sherbrook, Quebec, Canada, as the second son in a family of Jewish immigrants originating in Moldavia and Poland. The Steinmans owned Mozart’s, a general store selling everything from appliances to clothing. His parents wanted him to study religion and take over the family business, but summers working in the store reinforced Steinman’s desire to do something else. His love of science led him to McGill University in Montreal, Canada, then to Harvard Medical School in Boston, Massachusetts, where in the late 1960s he heard lectures by Kurt Bloch on the initiation of immunity and studied Peter Medawar’s work on tolerance and Frank Mcfarlane Burnet’s ideas on clonal selection.

ROCKEFELLER UNIV.

Although Steinman did a residency in internal medicine at Massachusetts General Hospital in Boston, he was drawn to basic research. In 1970, he joined Zanvil Cohn and James Hirsch’s laboratory at Rockefeller University in New York to work on the initiation of immune responses. Cohn and Hirsch were focusing on macrophages, but Steinman was also influenced by his campus neighbours: Christian de Duve, George Palade, Philip Siekevitz, David Sabatini and Günter Blobel were inventing modern cell biology a few floors above. Steinman soon characterized pathways for the engulfing of molecules by cells (endocytosis) and, with Cohn, proposed the involvement of membrane recycling in this process.

At that time, in the early 1970s, immunologists were developing culture systems to help study the cellular basis of immunity. An early finding was that, in addition to B and T lymphocytes, antibody responses required another type of cell, dubbed an ‘accessory cell’. The mysterious accessory cells stuck to glass, so Steinman — inspired by his cell-biology colleagues’ emphasis on microscopy — decided to examine glass-adherent spleen cells using phase contrast, live imaging and electron-microscopy techniques.

“As a basic scientist he recognized the enormous challenge of taking a discovery from the laboratory to the patient.”

What he saw under the lens was a new type of immune cell that had branching, rapidly changing projections. Three experiments (on two of which, one of us, MCN, was involved) then convinced Steinman that these ‘dendritic’ cells were the missing accessory cells: they could induce T-cell division and initiate killer-T-cell responses to antigens, and were biochemically distinct from macrophages.

For decades, Steinman was the consensus leader of, and the most enthusiastic cheerleader for, the field of dendritic-cell biology. He brought in numerous scientists from other fields, and loved to collaborate. With Wesley van Voorhis, he showed that dendritic cells exist in the blood of humans. With Kayo Inaba, he established, among other things, that when loaded with antigen, dendritic cells could induce anti-tumour immunity in mice. With Gerald Schuler, he saw that dendritic cells could be activated by pathogens to initiate immunity.

Steinman was generous and much loved by his colleagues. Even when he was terribly ill, he spent the little time he had left ensuring that his students and fellows would land on their feet after he passed.

He was passionate about his work as editor of the Journal of Experimental Medicine, a responsibility that he enjoyed for more than 40 years. His focus on publishing outstanding science had a profound influence on his field.

And he was equally passionate about making the leap from the bench to the bedside. In recent years, he tried to use dendritic cells to develop vaccines. As a basic scientist he recognized the enormous challenge of taking a discovery from the laboratory to the patient. But he relished the task because of its importance in treating infectious diseases and cancer. Steinman’s passion continued even when it was him in the bed, receiving dendritic-cell therapy of his own design.

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About cerebrovortex

Montreal Grandmother, Agnes Kent was saved by Raul Wallenberg from certain death, when he provided papers for her and her Mom to escape away from the Nazis. Today when asked what that escape meant, she replied,"Remind people, that while statesmen and whole countries remained silent and did nothing, a single individual chose to act, with ramifications that proved enormous. Similar choices confront us today. Write that simple truth she said, it can never be repeated often enough because the world keeps forgetting it."
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