“We received a grant of €19M from the Netherlands Science Foundation last summer for our synthetic cell development project. The award went to 15 working groups—15 groups working in this area is substantial. We will probably appoint 30-80 PhD students. But some of our labs also have national grants and so the 15 groups could each include 10 to 20 researchers.
The 15 PIs have already individually been working on aspects of synthetic cell development. But for the first time there is proper funding for tackling larger scale problems.”—University of Groningen biochemist Bert Poolman, in conversation with me in 2017
The Netherlands is a small country of 17 million people. With a GDP of roughly $850B, it is 18th in world economies. Not counting the narco economy, that is—estimated at $3.4B—money Dutch police report is being laundered in real estate, travel, hospitality and other industries. Nevertheless, it is a model state with a GDP per capita of $50,000, 5% living below poverty and with AAA Fitch and S&P ratings. A year or so ago the Dutch government, responding to public interest in origins of life, allocated €2.5M ($2.9M) to establish an Origins of Life Center and €19M ($22M) for a synthetic cell development program.
Scientists in the Netherlands have now tapped some of the €19M to organize the country’s “1st International Symposium on Building a Synthetic Cell.” The bottom-up meeting takes place August 28-29 at Delft University of Technology, where 32 speakers take the stage to present their perspectives. Half are Dutch, half from assorted countries. Two philosophers are in the mix, two chivalrous knights, and lots of fresh faces.
The symposium’s chair is Marileen Dogterom, a Delft University biophysicist who also chairs Delft’s bionanoscience department besides running the Dogterom lab, which looks at cytoskeleton “assembly, force generation and organization.” Dogterom is a professor at Leiden Institute of Physics as well. She is a winner of the 2018 Spinoza Prize, the Netherlands’ highest scientific award (€2.5M).
‘The cytoskeleton is a dynamic polymer system, it is constantly changing shape. So it is different than for example a human skeleton. The microtubules (tubular proteins that form the cytoskeleton, ed.) generate forces by growing and shrinking. The same microtubules also help with cell polarization, making a cell’s front look different from its back. A cell needs this for example to be able to walk. So the cytoskeleton also has to do with the spatial organization of the cell.”
It’s interesting that the conference is taking place at Delft, which is also home to a neutron and positron research center. Delft is part of LENS (League of Advanced European Neutron Sources), a consortium of countries using neutron scattering to probe and measure matter, including inside living cells—with the most sophisticated facility in Sweden (46% complete).
But the questions: Why build a synthetic cell? and What is life? continue to reverberate.
The late Carl Woese, who was awarded the Leeuwenhoek Medal by the Royal Netherlands Academy of Arts and Sciences (1992), opposed the idea of making a synthetic cell, telling me in a 2012 interview weeks before he died that he thought the push for a synthetic cell was all about “Power” and scientists “thinking they’re God.”
Indeed, the Germans have appointed Peter Dabrock—who chairs the German Ethics Council (a government advisory group)—to oversee “challenges at the interface of science and society,” including synthetic cell development. However, as a Protestant theologian, Dabrock’s appointment has generated criticism.
Stanford University biochemical engineer Drew Endy at the recent National Science Foundation synthetic cell gathering in Alexandria, Virginia questioned whether making a synthetic cell wasn’t simply giving a name to what scientists have already been working on for years. Endy was a presence not only at the Alexandria synthetic cell meeting, but at the Bavaria synthetic cell conference last summer in Ringberg Castle and is a speaker at Delft as well. Coincidentally, he has an honorary doctorate from Delft. He’s also on Esquire magazine’s list of “The 75 most influential people of the 21st century.”
The Dutch conference promo never actually defines life. It does, however, address why the country has decided to build a synthetic cell. It repeats the mantra that the initiative is all about trying to understand how life works, adding that part of the plan is to “gain insight” into what the conditions were that first enabled life to emerge on Earth, which may also be relevant elsewhere in the universe. Plus the Dutch, like most invested parties, have an interest in seeing spinoffs from the research.
Motive-wise, nothing really new here. What is new is the Dutch drive to get the job done. To show they mean business, they’ve invited some pretty serious scientists to the Delft discussions.
Among the big name presenters from the Netherlands is University of Groningen biochemist Bert Poolman. Poolman is a principal investigator in the Dutch synthetic cell initiative and was introduced to me last October while I was in North Holland by Jan-Willem Mantel, coordinator of the Dutch Origins Center. My interviews with both Poolman and Mantel are posted at HuffPost.
Another key speaker is Christophe Danelon at Delft, who has been working on a minimal cell for some years. The Danelon Group wants to “reconstitute four cellular modules”:
— DNA replication
— vesicle growth through lipid biosynthesis
— compartment division
— regulatory genetic circuits
Of considerable note among the Dutch presenters is Cees Dekker, who in 2014 was decorated by King Willem-Alexander for his “pioneering work of great social relevance”: Knight of the Order of the Netherlands Lion. Cees Dekker is a physicist at Delft whose research interests include the biophysics of DNA and synthetic cells.
Cees Dekker, with Delft biophysicist Nynke Dekker—another symposium speaker—co-founded the university’s bionanoscience department (they are not otherwise related).
Nynke Dekker’s lab is investigating the “key cellular process of nucleic acid replication from a biophysical perspective in viral, bacterial, and eukaryotic systems.”
Wilhelm TS Huck is both a presenter and a Delft conference organizer. Huck was decorated by King Willem-Alexander earlier this year with the civilian order of chivalry: Knight of the Order of the Netherlands Lion. He is a professor of physical organic chemistry at the Institute for Molecules and Materials, Radboud University Nijmegen. Huck has been developing “artificial cells on the basis of tiny droplets the size of a picolitre.”
In 2016, Huck was awarded the Spinoza Prize. He’s also a member of the Simons Foundation Collaboration on Origins of Life (project: “the influence of molecular structure on dynamics of complex reaction networks”). In addition, Huck serves as vice president of the scientific advisory board of MaxSynBio—the Max Planck program on synthetic cell development.
According to physicist Eberhard Bodenschatz, director of Max Panck Institute for Dynamics and Self-Organization, Gottingen, who addressed the NSF synthetic cell meeting in May—the Dutch and Max Planck synthetic cell initiatives are very similar, except that the Dutch have now added a genome to their synthetic cell scheme and the Germans have not. The Germans want to see how far self-organization will take them.
“Extraordinary professor” Pieter Rein ten Wolde, from AMOLF (Dutch Foundation for Fundamental Research on Matter), will also share highlights of his research at the Delft gathering. His Biochemical Network group at AMOLF is looking to “unravel the design principles” of biochemical networks through database analyses, theory and computer simulation. PR ten Wolde thinks cellular copy operation can be mapped onto a computational copy operation. On his web page he points out that cyanobacteria clock components have to be synthesized every cell cycle.
Ten Wolde would like to “develop minimal models of the cell cycle.” He thinks these “can be exploited in the design of synthetic cells that need to grow and divide.”
Another symposium presenter from Holland who I interviewed last October while in Groningen, is engineer-turned-systems biologist Matthias Heinemann. Heinemann describes the Dutch synthetic cell initiative this way:
“A lot of biology has to do with control mechanisms, with oscillation, with feedback, and these are all things engineers know how to deal with. An engineer actually does biotechnology, and biotechnology is to some extent metabolism. Some think metabolism came early in evolution. This is what I’m investigating now, metabolism.
If you look at this map of chemical reactions, which take place in every single cell—1,000 to 1,500 chemical reactions. This map that anyone during their biochemistry studies has had to suffer through. This is our field of research now.
In trying to understand how life first came about, we look at how food molecules are taken up in existing cells and then processed. How energy is extracted. How new cells are synthesized. We’re trying to learn what the principles are behind this network. What in evolutionary terms governs this network. Nothing makes sense without evolution. . . .
What I mentioned earlier—metabolism could be responsible for introducing some cell dynamics and these dynamics could then lead to a growth and division cycle. We’re studying this with existing cells but in the effort together with Bert Poolman we also will try to mimic this in a synthetic system. As we build the synthetic cell, we’ll try to introduce oscillations to get the cell to split. It’s a two-way approach. Dissecting and studying existing cells—how they do it—and trying to rebuild this in a synthetic cell.”
Tom de Greef, a professor of synthetic biology at Holland’s Eindhoven University of Technology will conduct a masterclass at the symposium titled: “Engineering Bioinspired Molecular Networks and Synthetic Cells.”
The de Greef research group is working on “bottom-up construction of basic cellular functions from well-characterized biological components, and the development of novel biological computing devices that can enhance signal-processing capabilities of natural and synthetic cells.”
Radboud University presenter Carla Rita Palmerino is a philosopher and science historian on the faculty of philosophy, theology and religious studies.
Ramboud philosopher Hub Zwart is also scheduled to speak. He’s the author of 10 books and founder of ISIS (Institute for Science, Innovation and Society). His interest is in how scientific research challenges our understanding of life and “the place of human beings” in it.
Others Dutch speakers include: John van der Oost (“a pioneer of the CRISPR revolution”)—as well as Arnold Driessen, Bela Mulder, Gijs Wuite (researching physics of life processes), Sander Tans, and Siewert-Jan Marrink.
On the international side—the committee was wise to invite as a keynote speaker NCBI-NIH’s Eugene Koonin. Koonin is a mesmerizing personality with an H-index of 190 (that’s higher than Charles Darwin’s). In 2002, Koonin and NCBI colleague Kira Makarova identified the genetic region now known as CRISPR-Cas.
(By the way, Delft conference organizers refer to every international speaker as a “keynote speaker.”)
Koonin has demonstrated the ability to unite various tribes of evolutionary science and articulate a way forward. And he has set the record straight on natural selection, even if his co-author(s) may be stuck in selfish Dawkins-speak.
Said Koonin in our 2017 conversation about “The New Evolutionary Biology” (also posted at HuffPost):
“Perhaps making all these parallels between natural selection and artificial selection, the way Darwin does in his book, could be somewhat dangerous because in artificial selection there is someone who is selecting, even if unconsciously. In that respect, the evolutionary process is very different in nature where nothing is there to actually select. . . . No one in the mainstream scientific community now takes selection literally.”
Chemist John Sutherland, Medical Research Council Laboratory of Molecular Biology in the UK, is another of the high profile international speakers. Sutherland co-chairs the Simons Collaboration on Origins of Life and is probably best known for winning Harry Lonsdale’s Origin of Life Challenge in 2012 along with University College London chemist Matt Powner.
Eors Szathmary, a Hungarian biologist from Eotvos Lorand University, will share his insights as well. Szathmary was one of the organizers of COOL EDGE 2013— the origins of life conference at CERN (which not even Ganesh was able to rescue)—and one of the “Altenberg 16.” Szathmary collaborated with John Maynard Smith on two books: The Major Transitions in Evolution; and The Origins of Life..
Michael Jewett is a biochemical engineer and keynote speaker from Northwestern University. The focus of the Jewett lab is “designing, constructing, and modifying biological systems involved in protein synthesis and metabolism” using cell-free systems.
Developmental biologist Kate Adamala is a presenter from the University of Minnesota. Her protobiology lab is “building tools for studying and controlling biology using synthetic cells and protein engineering technologies.”
Several presenters are from various Max Planck Institutes in Germany.
Petra Schwille is a biophysicist at MPI for Biochemistry, Martinsried (near Munich) working in cellular and molecular biophysics. She describes her lab’s research on bottom-up minimal systems this way:
“Our ambition is to quantitatively understand living systems on the scale of individually active and interactive molecules such as proteins, lipids and nucleic acids. We primarily employ single molecule fluorescence microscopy and spectroscopy, supplemented by force microscopy to achieve resolution far below the diffraction limit.”
The research interests of presenter Joachim Spatz, director of MPI for Medical Research in Heidelberg, include cellular biophysics, materials science, cell biology, interface science and physics of soft matter.
Tobias Erb is a speaker from MPI, Marburg (Max Planck Institute for Terrestrial Microbiology). He is director and head of the department of biochemistry and synthetic metabolism there. The focus of the Erb lab is “understanding and applying fundamental design principles of metabolism.” Studying metabolism in the living cell to “build novel, synthetic metabolism in a bottom-up fashion.”
Cell and developmental biologist Mohan Balasubramanian is a keynote speaker from the UK’s University of Warwick. He is currently investigating cytokinetic actomyosin ring structure, assembly and function, with funding from the Royal Society.
Balasubramanian described his research philosophy in an interview last year with Nida Siddiqui:
“I think research is about enjoying the process not waiting for the results. You can tell from talking to some people that they enjoy the process and if you do the process properly, you will get something.”
And he voiced these concerns:
“There is a big shift in how science is being done, nowadays it’s a lot of collaborative science. When I started my Ph.D., it was very common to pick any of the top journals and find papers that have only 2 authors. There is a first author and the senior author. There were even papers that had one author. This was all possible those days. But if you look at papers now there are too many authors. The problem with that is it takes thirty human years to finish a project and there is a team of people and four joint first authors and a senior author. There aren’t going to be enough jobs. The way science has evolved requires large teams to accomplish the jobs and many of them may not make it because to accommodate that many successful postdocs you need to quadruple the intake. It is only natural since people have to earn a living and have a good quality life. Other options, like an industry job, is becoming more and more common.”
An important talk at Delft representing the rapidly growing mechanobiology movement will be Allen Liu’s. Liu is a mechanical and biomedical engineer at the University of Michigan. The Liu Lab’s interests are “mechanobiology and mechanotransduction, bottom-up synthetic biology, droplet microfluidics, systems biology of endocytosis and cell migration.”
Keynote Hagan Bayley is from the University of Oxford, where he is a professor of chemical biology. He also heads the Bayley Group at Oxford, whose research interests include: fundamental properties of ion channels and pores, single molecule chemistry and catalysis, printed tissues and tissue-like materials, among others. Bayley was one of the organizers of the 2017 synthetic cell meeting at Ringberg Castle.
Yannick Rondelez, a presenter from France’s National Center for Scientific Research (CNRS/ESPCI) is investigating information processing chemical systems, in vitro. Rondelez describes cellular computing this way:
“The dynamical and information-processing properties of living cells, i.e., their ability to make decisions, sense their environment, maintain their integrity, memorize bits of information, interact, coordinate, etc. is indeed encapsulated in the topology and dynamics of their molecular networks.”
It’s a large group and a landmark meeting, one whose proceedings should be live streamed over the Internet—like last February’s Mechanics of Morphogenesis conference at Princeton—or at a minimum, talks videotaped and posted online as the NSF synthetic cell gathering’s organizers were smart to do to garner public support.