Mechanobiology/Atomic Biology Nexus: Natural Selection “Dispose[d] Of”

“The Invisible Revealed” exhibition, Nov. 12, 2021-March 6, 2022, MAAS Powerhouse Museum, Australia. Original artifacts to be displayed next to tomographic visuals that reveal “structural secrets.” Above figure featured in show: Mahasiddha Catrapa, Tibet (1400-1599).

“[A]t the scale of biological organelles below 100 nanometers many phenomena have characteristic energies that converge there. For instance, energies related to an electron confined to a box several nanometers in size.  Thermal energy.  Mechanical energy.  And chemical energy.  Especially those bonds that are prevalent within the molecules of life. They all converge in magnitude at that spatial scale.  There is cross-talk.  This means you have the link between mechanics and thermodynamics and the link between thermodynamics and quantum mechanics and they all mix there in the region between 10 nanometers and 100 nanometers.  It’s that area, in particular, of mechanobiology that’s going to be extremely interesting and challenging because of the mixing of these scales.”— Bogdan Dragnea, 2018 conversation with me

Anthropologist Maurice Bloch has suggested that human imagination arose 40,000 to 50,000 years ago during the upper Paleolithic revolution, that humans largely live in their reflective imagination, and that human “pretend play” is now evident as early as age six. But Bloch—who says imagination in the brain is “separate from perceived stimulus”—has not assigned a numbers range for other animals or for plants, fungi, microbes, or viruses. Perhaps the experts gathering June 28-29 online under the banner of the Linnean Society to discuss living systems will.

The work of many of these experts presenting at Linnean’s virtual meeting has been supported by the John Templeton Foundation, which likes to fund projects relating to science and religion (the latter arose 5,000 years ago, according to Bloch), as well as “science of purpose” projects.

Santa Fe Institute Distinguished Professor Geoffrey West once explained the Templeton controversy over sponsorship of science: 

The controversy surrounds the original setup of the [Templeton] foundation.  One would see that the wishes of Sir John Templeton that would deal with questions of religion and God and so forth would be honored”.

JTF has in recent years funded an $11M Extended Evolutionary Synthesis project involving 49 scientists at eight institutions in the US, UK and Sweden with seven of those Templeton-funded scientists (including its Project Leader and Project Co-Leader) presenting at the 2016 Royal Society evolution summit in London.  Three other Royal Society meeting presenters were non-funded participants of the EES project.

In 2015, in an attempt to insinuate its divine message into science, Templeton co-sponsored a two-year project with a $1.7M grant awarded to the Center of Theological Inquiry, a religious think tank in Princeton for the investigation of how the world’s religions might respond to the discovery of life on other planets; NASA’s Astrobiology Program kicked in 5% of its annual budget ($1.108M) to the project!

On the agenda for the Linnean virtual meeting are such issues as whether teleology is a sin, teleophobia, and the resuscitation of natural selection (partial list).

But microbiologist Carl Woese argued 17 years ago in “A New Biology for a New Century” that it was time to put the organism back into its environment and feel the flow:

Our task now is to resynthesize biology; put the organism back into its environment; connect it again to its evolutionary past; and let us feel that complex flow that is organism, evolution, and environment united. The time has come for biology to enter the nonlinear world.

It would follow then that imagination cannot be separate from outside stimulus.  Moreover, cytogeneticist Antonio Lima-de-Faria says this in his recent paper:

Three properties are of special importance because they do not start at the organism level but appear before DNA and the cell emerged in evolution.  Vision, regeneration and luminescence are already evident in crystals and minerals. The ability to direct light to specific sites is present in crystals.  The phenomenon is called double-refraction. . . .This means that vision is anchored in the mineral world.”    

Importantly, life science outside said Linnean Society zoom conference is “rapidly expanding” into atomic biology in its exploration of biological structure and function.  (See lists at story end.) 

The most powerful facility for this (neutron, electron science) is ESS, the European Spallation Source now nearing completion at Lund University, Sweden. And Lund University’s Antonio Lima-de-Faria—who celebrates his 100th birthday on July 4—says further in his recent paper, the “current theory” of evolution (that would be Darwinian natural selection) is thus effectively “dispose[d] of:

Physics led the way in the creation of Molecular Biology by employing X-ray crystallography of the atomic structure of protein and DNA.  Now it is physics again, by using large accelerators of electrons and neutrons, that is transforming molecular biology into Atomic Biology.

In the United States, Oak Ridge National Laboratory is the key neutron scattering facility.  To further illuminate, I am republishing my 2018 Q&A with ORNL scientist, John Katsaras.  The story appears at length in my book, Darwin Overthrown:  Hello Mechanobiology.

JOHN KATSARAS

Suzan Mazur:  Neutron scattering has been around for a while, why all the excitement now?  The Europeans have formed LENS (League of Advanced European Neutron Sources), and Sweden is building the next generation spallation source with apparently unprecedented brightness at Lund University (48% complete). Oak Ridge National Laboratory is expanding its facilities.  There are also upcoming conferences on neutrons and biology. Why all the excitement?

John Katsaras: Neutron scattering is comprised of many different techniques, each requiring its own approach—one can say that about other techniques, such as microscopies.  As far as biology is concerned or soft materials, the real excitement is that you can probe these materials at the nanoscale.  We’ve shown here at ORNL that you can probe cells when they’re living with nanoscopic resolution.

Currently there are no other techniques that can accurately probe living materials at the nanoscale.  There’s a lot of debate about that.  To the best of my knowledge, neutron is the only one, as we’ve demonstrated here.  

Moreover, there are very few techniques period that can probe soft materials on the nanoscale in a disordered state. When you crystallize things, there are scattering techniques that can be used, for example, electrons and x-rays.  But when material is not crystallized, neutrons have a distinct advantage.

Neutrons also come in different flavors. You can look at static structure. You can also look at dynamic structure.  In static structure you are studying the time averaged structure. In the case of dynamic structure, by definition things are moving around and you are capturing snapshots of the structure.  So with neutrons you can  study a range of things from—collective motion—molecules moving together in some synchrony, or individually. [emphasis added]

Suzan Mazur:  Thank you.  Cytogeneticist Antonio Lima-de-Faria from Lund University, where they’re building the European Spallation Source, refers to “enormous accelerators of electrons and neutrons elucidate[ing] DNA’s own evolution—determination of exact position and movement of atoms.”  Do you agree with that?

John Katsaras:  I agree in the sense that you can observe how DNA’s structure evolves in real time as a function of changes in temperature, pH or ion content, for example.  Depending on the timescales, which can range from fractions of a second to hours, these kinetic measurements can be done with X-ray and neutrons, although neutrons are better able to capture the slower kinetics due to their lower flux compared to X-rays.

Suzan Mazur:  Lima-de-Faria has also said neutrons can probe matter including biomatter enabling measurements of structure from micrometers to one-hundred thousandth of a micrometer plus motion from milliseconds to ten-million-millionths of a millisecond.  Do you agree with that?

John Katsaras:  Basically yes.  You can look at things from the micron scale, which  corresponds to optical techniques that provide complementary data.  And then you go to angstroms with neutron crystallography.  Neutrons can be understood similar to X-rays in crystallography, where you obtain atomic positions with angstrom resolution, corresponding to 1 x 10 to the minus 10 meters.  So, yes you can.  And the dynamic information with that can be accessed with neutron ranges from the picosecond to the hundreds of nanoseconds.

Suzan Mazur:  Is every structure and function the immediate product of a molecular cascade originating in atomic and electronic events?

John Katsaras:  That’s a good question.  I don’t know how to answer it.  Of course structure has a role in how function is expressed.  One such case is the so-called raft hypothesis in membranes, for example.  Something we’ve been investigating here at Oak Ridge. 

Suzan Mazur:  That was actually my next question.  Your team at Oak Ridge has done the “first ever direct nanoscale examination of a living membrane.” What can we now see that we couldn’t see without these advanced measurements and instruments?

John Katsaras: But it’s not necessarily the instruments that make the difference.  It’s the approach to the problem.  Sometimes there’s an overemphasis on hardware.  The best hardware doesn’t always lead to the best science. Of course you need access to the very best instruments you can find.  But if you don’t have the right questions and if you don’t have the right sample, it will result in a poor or mediocre experiment.  What’s needed most is a great experiment. In the membranes experiment we did here we engineered the bacteria so we could visualize its membrane, using neutron scattering. 

But coming back to the question of structure and function. The way DNA is organized, for example, DNA’s structure is integral to its replication process.

Suzan Mazur: Your membranes research revealed that lipids gathered with others of their type.

John Katsaras:  Right. The cell makes thousands of different types of lipids.  In the plasma membrane, which is the outer membrane of the cell, there are hundreds or, maybe thousands of different lipids.  The question is, why does the cell expend so much energy to make all of these different lipids. 

You could say, well, maybe they have all different physical properties..  As a result, mixtures of lipids may come together to create an environment for a protein enabling the protein to perform its function. 

How does this happen? Are these passive processes driven by thermodynamics or are they active processes where the cell makes these things, puts them in place, and then continues to micromanage them?  This remains an open question. [emphasis added]

Suzan Mazur:  Is the Oak Ridge Spallation Neutron Source (SNS) the only neutron scattering facility in the US?

John Katsaras: Not the only, however Oak Ridge is the largest US facility—both the Spallation Neutron Source and the High Flux Isotope Reactor. There’s also the NCNR [Center for Neutron Research] in Maryland.  A small facility in Missouri [University of Missouri Research Reactor].  And a spallation source similar to SNS at Los Alamos [LANSCE], although I am not sure if it is currently open for civilian research.

Suzan Mazur:  Are you collaborating with Europe on investigations?

John Katsaras: I have a collaborator in Austria, Georg Pabst at the University of Graz.  We’ve been developing an asymmetric membrane with a model system.  Since model systems are much simpler than functional biological membranes, they allow one to get a handle on what’s going on in real systems.

It should be pointed out that  membranes have two bilayer leaflets. In functional  cells these leaflets are chemically different, i.e.,  the leaflets contain different lipids.  The inner or cytoplasmic leaflet differs from the outer leaflet chemically.  One can argue as to why that is. 

When you make model systems you generally mix these lipids and they will always randomly distribute equally in both leaflets.  The chemical makeup of that bilayer will be the same for both leaflets or very close.  There may be some factors that may make the lipid prefer the inner lipid versus the outer bilayer leaflet.  But for the most part, the leaflets are symmetrical. 

We’ve been developing something that is asymmetric, to better mimic the biological membrane.  That’s one of the things our lab is working on with Georg Pabst and his group.  We’re also working with other people here within the United States and Canada (e.g., Fred Heberle, Drew Marquardt and Erwin London).  This has been written up in Nature Protocols, which will be coming out very soon. 

Suzan Mazur:  What does this mean for synthetic cell development?

John Katsaras:  The systems that we work on are created to understand biological membranes.  That’s our focus.  Now, of course, you can use cells to create and encapsulate material.  These are useful in industry and drug delivery.  You can send them to image parts of the body.  So you can develop model membranes with all these different functions. 

Suzan Mazur:  But do you envision down the road being able to see more and more of what is happening inside the cell to determine position, measure, etc.

John Katsaras:  Scientists have done that over many years. You can do electron microscopy, for example, and look at a cell, at 10 angstroms or whatever the sample allows you.  And you can look at the organization of cells at  some resolution.  In most cases, the cells are dead. 

With living systems it becomes much more difficult to study systems with good spatial resolution.  Some of the ways you can do it is optically.  Then it’s a question of resolution. So people are looking at creating model cells.  But as far as I know, they are almost always inert.

The other thing that’s becoming really important is the computational aspect of science, which means you now have data with which you can better understand the structure-function relationship, for instance.   

Suzan Mazur:  But are we closer to understanding the origin of life because of advanced neutron scattering?

John Katsaras:  You can start putting the pieces together regarding big scientific questions about the origin of life, which will lead to a better understanding of what’s going on regarding disease. 

Experiments have been going on for a long time regarding the origins of life.  The techniques themselves are needed but insufficient in understanding the fundamental problem.  In science you have to come up with an idea.  The science is the idea. Technique is part of the story, but in the end, you always have to have a good idea to work from. [emphasis added]

Suzan Mazur: What are the hazards working in the areas of neutron scattering?  The use of deuterium, for instance.

John Katsaras:  It’s not hazardous at all because deuterium is not radioactive, it’s stable, an isotope of hydrogen.  As long as you don’t drink it.  And even if you drank some of it, nothing would happen to you.  Just don’t drink too much.

Suzan Mazur:  Do you see the US moving more into neutron science the way the Europeans are?

John Katsaras:  Well we are.  SNS is a great example.  ESS  in Sweden will be more powerful but America is planning a second target station that  will be very competitive.

Suzan Mazur:  Where will that be, the second target station?

John Katsaras:  We don’t know.  There are ongoing discussions.  If it does come to fruition, it will be tailored to look at biological materials and soft materials.  If it does happen, then I would very much like to have that machine because its characteristics will be effectively maximized for the type of science I’m interested in.

[Note:  John Katsaras has emailed the following update: 

“[The second target station] STS will be next door to the first target station (FTS) and would be ideally suited for studies of Advanced Materials, which include quantum phenomena, engineered materials, soft matter, and biological materials (for further information please visit:

https://neutrons.ornl.gov/sts

and the corresponding STS fact sheet:

https://neutrons.ornl.gov/sites/default/files/STS%20Brochure%2011×17%20%202018.pdf ).”]

Suzan Mazur:  How long have you been working in neutron science.

John Katsaras:  I’ve been involved with membranes research my entire career.  I began as a graduate student in 1984.  I’ve worked in neutron scattering since 1994, starting at the Chalk River Laboratories in Canada.  Those are very similar labs to Oak Ridge.  They were developed during World War II and the Canadians had the heavy water reactor concept, which they developed in the 40s and 50s.  The first really big reactor in Canada built was called NRX—National Research Experimental.  Canada then developed the National Research Universal reactor.

Suzan Mazur:  You’ve seen quite a lot.  Do you expect to continue with your research for some years to come?

John Katsaras: Well, I haven’t stopped.  I’ve been at it since 1984 and I don’t plan to stop anytime soon.  One of the reasons I came to the United States was to make sure my career could continue.  Canada’s NRU reactor was shut down this year.  That I knew was going to happen because the reactor became operational in 1957.  The writing was on the wall as far as its longevity was concerned.  Its lifespan was clearly coming to an end.  That would be it.  I moved to Oak Ridge in 2010.

Suzan Mazur:  You were born in Canada?

John Katsaras:  I was born in Greece.  On the island of Rhodes.  My mother and I emigrated to Montreal when I was two years old and I came to the US when I was 52.  It’s been a very good place to live and work, and ORNL has experienced a revitalization of its facilities over the last 15-20 years. 

Suzan Mazur: What do you expect from the research in the way of applications?

John Katsaras:  I don’t think of science that way.  Putting applications before science is like putting the cart before the horse.   It’s important to address basic questions. From those answers all kinds of possibilities emerge.  We’re too preoccupied now with technology and outcomes.  Discovery happens when you least expect it.  A lot of practical applications often emerge when you’re not trying to make practical applications. 

Successful breakthroughs happen because you have some of the brightest people researching, scientists who are allowed to think and work on basic problems that are of tremendous interest.  It’s been proven over and over, that this is the best way to do science. 

Even with the atom bomb, for example.  The basic physics aspect of creating an atom bomb had been worked out.  The building of the bomb was the real problem.  It was an engineering problem. Then, of course, the politics of day came into play, because billions of dollars had to be found to create a device.

Suzan Mazur:  Is there a final point you’d like to make?

John Katsaras:  Any country that wants to be at the cutting edge of science has got to have excellent basic research.  The United States has hugely invested in basic research over the years, and as such continues to attract the best scientists.  Once you have such an investment in basic research, important technology flows.

Suzan Mazur:  What kind of budget does Oak Ridge have?

John Katsaras:  Its annual operating budget is about $1.6 billion dollars. 

Suzan Mazur:  That’s quite a substantial amount.

John Katsaras:  And now you have China coming into the frame.  It has put an enormous amount of money into basic science and is attracting a lot of Western talent.

Suzan Mazur: China is building a spallation neutron source in Dongguan.

John Katsaras: Just outside of Hong Kong. 

Suzan Mazur:  Do you get back to Greece?

John Katsaras:  Once a year to visit my mother.  I travel to Canada quite a bit.

Suzan Mazur: Do you have interesting hobbies outside the lab?

John Katsaras:  I play a lot of hockey.  I fish.  I love history, including science history.  I cycle and am a big collector of European racing bikes from the 50s and 60s, but I’m also interested in the ones Schwinn made at its Chicago factory.  

The bicycle is still the most efficient human-powered machine.  Roads were actually built for bicycles, not cars.

Neutron Science Facilities Worldwide:

Oak Ridge Neutron Facilities (SNS/HFIR)

NIST Center for Neutron Research, Maryland

Los Alamos Neutron Science Center (LANSCE)

University of Missouri Research Reactor Center

European Spallation Source, Lund University, Sweden

ISIS Neutron and Muon Source, UK

Institut Laue-Langevin (ILL), France

Laboratoire Leon Brillouin, France  

Helmholtz-Zentrum Berlin, Germany

Jülich Centre for Neutron Science (JCNS), Germany

FRM II, Munich, Germany

Budapest Neutron Centre, Hungary

Swiss Spallation Neutron Source, Paul Scherrer Institut

Frank Laboratory of Neutron Physics, Dubna, Russia

China Spallation Neutron Source, Dongguan, China

Bhabha Atomic Research Centre, Mumbai, India

Japan Proton Accelerator Research Complex (J-PARC)

JAEA Research Reactors, Japan

High Flux Advanced Neutron Application Reactor, South Korea

Australian Centre for Neutron Scattering (ACNS)

Relevant Conferences:

9th Workshop on Neutron Scattering Applications in Structural Biology, Oak Ridge National Laboratory, Tennessee, US, June 11-15, 2018

American Conference on Neutron Scattering, University of Maryland, College Park, US, June 24-28, 2018

Membranes Beyond,” International Workshop on Status and Perspectives in Research on Membrane Structures and Interaction, McMaster University, Hamilton, Ontario, Canada, July 2-4, 2018

15th International Surface X-ray and Neutron Scattering Conference, Pohang Accelerator Lab, Pohang, South Korea, July 15-19, 2018

Neutrons and Biology Conference, Carqueriranne, France, Sept. 16-19, 2018

High Brilliance Workshop, Cologne, Germany, Oct. 4-5, 2018

ISIS Large Scale Structures User Meeting, Abingdon, UK, November 1-2, 2018

Gordon Research Conference on Neutron Scattering, Hong Kong, China, May 5-10, 2019

European Conference on Neutron Scattering 2019 (ECNS), Saint Petersburg, Russia, July 1-5, 2019

MLZ [online] Conference 2021, Neutrons for Life Sciences, June 8-June 11, 2021, exploring:  (1) protein structure, function and dynamics, (2) biological membranes, surfaces and interfaces, (3) biological processes, (4) neutron and complementary methods in biology, (5) life sciences with neutrons in Russia, (6) neutrons in the fight against virus diseases, (7) drug design and delivery.

International Conference on Neutron Scattering 2021, sponsored by Argentine Neutron Techniques Association, Buenos Aires, Argentina, July 4-8, 2021 (meeing rescheduled to August 2022 — “largest international platform for sharing and exchanging the latest advances in neutron scattering science”, featuring these topics: (1) soft matter, (2) biology and biology interfaces, (3) magnetism and thin films, (4) solid state chemistry, (5) life sciences, (6) energy  and engineering materials, (7) functional materials. (8) industrial applications, (9) cultural heritage and archaeometry, (10) neutron physics, (11) neutron sources and facilities).

23rd National School on Neutron and X-ray Scattering (virtual/Zoom), conducted by Argonne National Laboratory and Oak Ridge National Laboratory, United States, July 12-30, 2021

Dynamics of Electrons in Atomic and Molecular Nanoclusters, Enrice (Sicily), Italy, Aug. 25-31, 2021

X-ray and Neutron Science International Student Summer Programme 2021, European Photon Neutron Science Campus, Grenoble, France, Sept. 3-Oct. 2, 2021.

Italian Crystal Growth, Torino, Italy, Dec. 16-17, 2021 (Honoring crystallography pioneer, Raymond Kern. Focus:  crystal growth in biology, crystal growth for environment and health, etc.)

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