Stuart Newman: The Virosphere And Non-Linear Evolution

Article – Suzan Mazur

It was Stuart Newman who was the first of the Altenberg 16 scientists I discussed developments with following the Extended Synthesis symposium in 2008 at Konrad Lorenz Institute, a meeting I was barred from attending for having gotten out in front of …

Stuart Newman: The Virosphere And Non-Linear Evolution

By Suzan Mazur

(Photo by Jura Newman)

It was Stuart Newman who was the first of the Altenberg 16 scientists I discussed developments with following the Extended Synthesis symposium in 2008 at Konrad Lorenz Institute, a meeting I was barred from attending for having gotten out in front of the event with a series of stories and an e-book — showcased on these pages — in which I interviewed evolutionary thinkers who had also not been invited to Altenberg. And over the last half dozen or so years, I’ve had many rich, off-the-record (if such a thing still exists) phone conversations with Stuart Newman about everything from ancient art to deep politics to origin of life and life in general.

However, it was Werner Callebaut, the Belgian philosopher of science who died last November, who initially sent me KLI’s letter of invitation and working program for Altenberg and so was ultimately responsible for the media attention “the Woodstock of evolution” generated. In addition to Werner Callebaut’s affiliation with Hasselt University where he was a professor, he was scientific manager of KLI, and editor-in-chief of the institute’s journal Biological Theory — a role Stuart Newman, a KLI external professor, has now assumed as well following the loss of his friend and colleague.

Werner Callebaut 1952-2014

Several weeks ago I asked Stuart Newman – whose principal professional role is as a cell biologist and professor of anatomy at New York Medical College — if he would comment on the current excitement over the virosphere and non-linear approach to evolution. He is not a virologist but graciously stepped outside his immediate area of investigation, which is limb development, to address my questions. Newman, of course, is also known for his essays and activism on ethical issues related to science. Our interview follows.

Suzan Mazur: Some scientists say we need a whole new language to reflect the reality of non-linear evolution. What are your thoughts?

Stuart Newman: Non-linear means that you can’t look at straight lines of descent anymore because viruses and other entities are coming in at all stages of evolution. Classically this — horizontal transfer — has been considered a rare thing. With the new understanding of what viruses can do, the non-linear approach becomes much more prominent.

The idea is that when you look at the early history of life and the origin of the cell, you really can’t track linearly from primitive form through changes in the genome to later forms because entities are now understood to be coming in laterally from other forms. It’s new thinking and I have no disagreement with it.

Suzan Mazur: That idea of horizontal transfer has gotten a little twisted since that 1970s paper of Carl Woese in which Nigel Goldenfeld — Woese’s long-time collaborator — says the reference was to collective, communal life with massive endosymbiosis “meaning organisms were very porous and could crash into each other and absorb each other on a massive scale and that’s how cellular functions were transmitted.”

Stuart Newman: Organisms are clearly more than their nucleic acid, RNA and DNA. A virus, for example, has an RNA or DNA but also a capsid. It has proteins that organize into a shell around the informational molecules. If you want to understand how that capsid becomes organized, you have to look at the properties of the proteins, their physical properties. You can’t just look at the information in the genome and say I understand everything about the organism.

Suzan Mazur: But many scientists are saying we can no longer ignore the virosphere, which is ubiquitous. Some say that a viroid-like entity may have been the first replicon on Earth.

Stuart Newman: It’s not enough to say the cell got that way because of the cooperation of many, many virus-like entities over time. The physical structure, the shape, the mechanisms of division, etc., are things that are emergent properties once the materials are in place.

Life organizes materials, packages nucleic acid. Communities of these virus-like structures give rise to prokaryotes and eukaryotes.

Nucleic acid specifies some of the materials; some of the materials are gobbled up from the external world. And then you have a material object with a certain shape and form and developmental direction.

Suzan Mazur: Virologists are not saying life is just nucleic acid. Viruses are seen as organisms that comprise about 10% of the human genome. We also have the microbiota. The emerging thinking is that life is relational. Symbiotic. It can’t be thought of anymore as A, B, C, D, etc.

The thinking is that viruses as active organisms can enter a cell membrane, for example, manipulate its protein receptors and then proceed to make copies.

Stuart Newman: They manipulate proteins because they’re carrying genetic information into the cell, they arrange for new proteins to be made that the cell didn’t make before.

It’s important to recognize that there are physical interactions among proteins and interaction of proteins with the external environment. Proteins have shape and if a virus is alive, and I’ll concede that you can call a virus alive [emphasis added], it is because its proteins have certain organizational properties.

Suzan Mazur: Some viruses – known as defective viruses — don’t have proteins, and viroids don’t have proteins.

How does your research fit into this non-linear approach to evolution?

Stuart Newman: There are non-linear physical processes that lead to jumps in the arrangement or form of cells, for example.

Suzan Mazur: So if 10% of our genome is virus, could this be related to the saltational jumps you refer to in physical biology terms?

Stuart Newman: A virus can import the capacity to make new proteins into complex organisms. When that happens, you have to ask, what do the proteins do? The first thing ever known that proteins did was that they were catalysts, enzymes, and they catalyzed chemical reactions. Nobody disputes that.

But when you get to morphogenesis, when you get to multicellular organisms and how they build complex structures like ourselves, that’s not performed simply by catalysis. It’s not chemical reactions that does that. The proteins involved, which I refer to as the interaction toolkit proteins, mobilize physical processes – adhesion, diffusion and lateral inhibition — that were not relevant on the scale of the single cell, and they create form.

Suzan Mazur: There is also the idea about cell-cell adhesion happening by the manipulation of cell membranes by viruses. František Baluška has told me the following: “They [viruses] manipulate adjacent cells to form cell-cell adhesions (known as viral synapses) to spread from cell-to-cell. Synapses in very early evolution may have been induced by repetitive viral infections.”

A virus is an active agent. It can enter an animal cell membrane and manipulate the cell’s protein receptors. Once inside it starts to make copies. Viroids are associated with plants, they can attach to the plant leaf and can enter a plant cell if a plant is injured. Once inside they do the same kind of thing as viruses, i.e., make copies.

Stuart Newman: Cells attach to each other by cell surface proteins and receptors. So that’s right. Receptors are involved. If a virus manipulates a receptor, then it’s really still the receptor that is mediating the attachment.

Suzan Mazur: But it’s the virus that originates the attachment.

Stuart Newman: We know what mediates the attachment to cells. Viruses can bring in new proteins that change the strength of the adhesion or they introduce new molecules like nucleic acids that influence the avidity of preexisting cell surface proteins that create adhesive interactions. But if you’re going to tell me that the virus is doing it through some will that it has – I can’t go along with that.

Suzan Mazur: I am not saying that. I’d suggest you have a dialogue with the virus experts.

Stuart Newman: I’ve read some of the literature. The thing is even though they emphasize viruses doing new things – when you get to the point of how cells are attaching to each other – I’m not disagreeing that viruses can influence it, but the mechanism of attachment is still proteins adhering to proteins. And viruses specify proteins. So there’s no contradiction, I’m just looking at the physical mechanism. Even the virus people can’t deny that viruses act in the physical world. A virus may be an organism, may capture this or do that, but it can only influence morphogenesis by modulating the physical forces that are creating form in the organism.

You and I have had previous conversations about animal morphogenesis, and I mentioned that it is dependent on the cells to crawl past one another and to rearrange by changing their position and that makes a blob of animal cell, makes it like a liquid because its subunits can change position. And if you put pressure on it, there’s a readjustment.

I’ve written a couple of papers on plant evolution with some colleagues who are plant developmental biologists. We’ve worked together on extending the physico-genetic “dynamical patterning module” framework to encompass plants.

In plants because of the cell wall, the tissues are solid, more like bricks. You don’t have the same physics. So the physics of liquids, which is very relevant to animal morphogenesis is not relevant to plant morphogenesis. On the other hand, plants are not inert the way you might think if their cells are solid and stuck to each other, because they have channels between their cells. So plants can convey signals, such as auxins, very rapidly and at great distances through cells. This makes them very different. They’re more like nerves.

Suzan Mazur: What is the goal of your research regarding morphogenesis?

Stuart Newman: There was a whole history of life that preceded multicellular organisms. The viruses, the communication between different forms of life, including viruses and prokaryotes leading to the kind of endosymbiotic communal arrangements that Lynn Margulis talked about such as eukaryotic cells. Then eukaryotic cells evolved for maybe a billion years after that, until cells began to be sticky and formed clumps rather than being isolated, perhaps because something changed in the physical environment on Earth.

Suzan Mazur: This idea of cell adhesion, did this start with Gerald Edelman and his CAMs?

Stuart Newman: There was a whole field of CAMs. Gerald Edelman kind of appropriated the field. He made important contributions, but renamed a lot of the molecules to make it seem like the whole concept was original with him.

There was Johannes Holtfreter from the 1940s and 50s – his work was extremely important in cell adhesion and morphogenesis. There was also Paul Weiss, similarly important in these areas during that period. H.V. Wilson worked on adhesion in marine sponges even earlier, at the beginning of the 20th century. Wilson dissociated the sponge by forcing them through a sieve and reconstituted them. They spontaneously reformed all the internal structures that sponges have. Wilson even found that cells of different varieties of sponges recognized and adhered to their own kind in mixtures There’s been a lot of cell adhesion research for many years.

One of my teachers at the University of Chicago, named Aron Moscona was a major figure in that field, as well as Malcolm Steinberg, whose ideas on the role of physics in development I’ve drawn from for my own work.

As far as the history of life is concerned, multicellular organisms only began about 700 million years ago. All of the genes and pathways that had appeared up until that point evolved without anything to do with multicellularity. Multicellularity didn’t yet exist.

Suzan Mazur: I once asked Jim Shapiro when multicellularity happened. He said “At the first cell division.” And Lynn Margulis commented: “But they all use the word “multicellular” when they really mean “animal” – since there are no unicellular animals, and since multicellularity, genuine multicellularity, details of multicellularity are known in protists, bacteria and all the major groups of life.”

Stuart Newman: Multiple cells existed when the first cell divided, but not multicellularity, which refers to kinds of organisms in which the cells have some interaction or communication with one another that are more than just transient. I’m not one of the “they” who use “multicellular” to just mean “animal.” In fact, I can’t think of a single biologist who would exclude plants, fungi, and some protists such as the cellular slime mold Dictyostelium discoideum, from this designation.

One important thing about evolution is that there is no theory of everything for how things evolved. It happens in stages. There’s a phase where things are viruses and viroids and prokaryotes and eukaryotes. If you try to understand the eukaryotic cell simply on the basis of virus biology, you can’t get very far because something new happened when this cooperation took place. You had a new entity. The scientific issues with that new entity, the eukaryotic cell were very, very different from all the components that went into making it. So when new things happen you have new scientific questions.

What I’ve been concerned with is what happened when eukaryotic cells became social. They did this a number of different times, independently. Slime molds, for example, are amoebas that are transiently social as they build multicellular structures. They build little slugs which crawl around. But then they disperse and they become amoebas again. They’re called social amoebas. They have certain regularities and certain signals that mediate their morphogenesis. The single-celled opisthokonts — the ancestors of the fungi and the animals — split into two branches at some point and each lineage evolved multicellular forms – mushrooms and animals. Later the multicellular plants arose from an entirely separate eukaryotic lineage.

I’m curious about what happened when the holozoans – the non-fungi branch of the opisthokonts — became multicellular. In these multicellular holozoans there were genes that existed before that specified proteins that existed before and they became recruited to perform completely new, multicellular tasks.

So you put things together and new properties emerge. You don’t even have to have much genetic evolution to get those new properties.

Suzan Mazur: What kind of “genes” are you talking about? This whole concept of gene is in flux.

Stuart Newman: I fully agree that terms like genetic program and blueprint are wrong. I’ve been writing about this for more than 30 years. But “gene” as I use it refers to a nucleic acid sequence that specifies a protein sequence. I don’t think you will find any biologists who disagree with this usage.

Suzan Mazur: Do you think we’ll know definitively anytime in the near future about what happened regarding body plans?

Stuart Newman: There are certain things that are very puzzling about it. For example, if you have a simple cluster of cells, it doesn’t form a body. It’s just a mass of cells. There is a protein called Wnt that is present in all the animal systems we know about and is essential for turning a cluster of cells into a complex body. It’s present in sponges. It’s present in hydra. It’s present even in placozoa, which is the simplest animal form – it’s like a sandwich of cell layers. They all have Wnt.

Most of the interaction toolkit proteins were present in the single-cell ancestors of animals: cadherins (which mediate cell-cell attachment in animals) were there before, for example. Sometimes proteins have come in by horizontal gene transfer from viruses, bacteria or fungi. The multifunctional proteins known as galectins may be an example of this.

But with regard to Wnt, it’s not clear where it came from. Because if you look at the single cell cousins of the animals, they don’t have any Wnt. They have part of the pathway that Wnt activates but they don’t have Wnt itself. When we look at all the viral genomes, all the bacterial genomes in the hope of finding what the origin of Wnt is — who brought it in? How did it come in? So far it’s not been found. So maybe there’s some virus or cell type that’s gone extinct that brought Wnt, a distinguishing component of animal development, into the genome..

Concerning the role of horizontal or lateral transfer, since evolution occurs in stages and at each stage there are new phenomena that emerge, it may be that some of these novelties arise when a new gene or pathway is brought in laterally by a virus. We know from developmental biology that changes in form, some rather abrupt, take place when new proteins appear that can mobilize physical forces that cause cells to rearrange. Presumably that’s how many morphological novelties arose during evolution as well.

So then you say, here are these entities, viruses, that have been found to be more prominent on contributing to the genealogy of complex organisms than previously thought. You have to ask: do we throw away the whole paradigm from developmental biology of cells rearranging and tissue masses separating, hollowing out, segmenting? Or do we say that the effect of the new thing was to modulate the mechanisms we already understand to drive morphogenesis?

Suzan Mazur: It depends on what the new thing is. This may be one of those punctuated moments. Eugene Koonin has told me that he thinks “a paradigm shift in evolutionary biology is actually happening or has happened.” Luis Villarreal says that “if living systems work by these processes that are consortial and complex, then our very language and logic are a problem in terms of how we apply it to understand what’s going on.”

Suzan Mazur is the author of two books, The Origin of Life Circus: A How to Make Life Extravaganza and The Altenberg 16: An Exposé of the Evolution Industry. Her reports have appeared in the Financial Times, The Economist, Forbes, Newsday, Philadelphia Inquirer, Archaeology, Astrobiology, Connoisseur, Omni and other publications, as well as on PBS, CBC and MBC. She has been a guest on McLaughlin, Charlie Rose and various Fox Television News programs. Email:

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