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North Carolina universities go beyond organ-on-a-chip

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The researchers in the North Carolina universities involved in this project have high hopes according to an Oct. 9, 2015 news item on Nanowerk,

A team of researchers from the University of North Carolina at Chapel Hill and NC State University has received a $5.3 million, five-year Transformative Research (R01) Award from the National Institutes of Health (NIH) to create fully functioning versions of the human gut that fit on a chip the size of a dime.

Such “organs-on-a-chip” have become vital for biomedical research, as researchers seek alternatives to animal models for drug discovery and testing. The new grant will fund a technology that represents a major step forward for the field, overcoming limitations that have mired other efforts.

The technology will use primary cells derived directly from human biopsies, which are known to provide more relevant results than the immortalized cell lines used in current approaches. In addition, the device will sculpt these cells into the sophisticated architecture of the gut, rather than the disorganized ball of cells that are created in other miniature organ systems.

“We are building a device that goes far beyond the organ-on-a-chip,” said Nancy L. Allbritton, MD, PhD, professor and chair of the UNC-NC State joint department of biomedical engineering and one of four principle investigators on the NIH grant. “We call it a ‘simulacrum,’ [emphasis mine] a term used in science fiction to describe a duplicate. The idea is to create something that is indistinguishable from your own gut.”

I’ve come across the term ‘simulacrum’ in relation to philosophy so it’s a bit of a surprise to find it in a news release about an organ-on-a-chip where it seems to have been redefined somewhat. Here’s more from the Simulacrum entry on Wikipedia (Note: Links have been removed),

A simulacrum (plural: simulacra from Latin: simulacrum, which means “likeness, similarity”), is a representation or imitation of a person or thing.[1] The word was first recorded in the English language in the late 16th century, used to describe a representation, such as a statue or a painting, especially of a god. By the late 19th century, it had gathered a secondary association of inferiority: an image without the substance or qualities of the original.[2] Philosopher Fredric Jameson offers photorealism as an example of artistic simulacrum, where a painting is sometimes created by copying a photograph that is itself a copy of the real.[3] Other art forms that play with simulacra include trompe-l’œil,[4] pop art, Italian neorealism, and French New Wave.[3]

Philosophy

The simulacrum has long been of interest to philosophers. In his Sophist, Plato speaks of two kinds of image making. The first is a faithful reproduction, attempted to copy precisely the original. The second is intentionally distorted in order to make the copy appear correct to viewers. He gives the example of Greek statuary, which was crafted larger on the top than on the bottom so that viewers on the ground would see it correctly. If they could view it in scale, they would realize it was malformed. This example from the visual arts serves as a metaphor for the philosophical arts and the tendency of some philosophers to distort truth so that it appears accurate unless viewed from the proper angle.[5] Nietzsche addresses the concept of simulacrum (but does not use the term) in the Twilight of the Idols, suggesting that most philosophers, by ignoring the reliable input of their senses and resorting to the constructs of language and reason, arrive at a distorted copy of reality.[6]

Postmodernist French social theorist Jean Baudrillard argues that a simulacrum is not a copy of the real, but becomes truth in its own right: the hyperreal. Where Plato saw two types of representation—faithful and intentionally distorted (simulacrum)—Baudrillard sees four: (1) basic reflection of reality; (2) perversion of reality; (3) pretence of reality (where there is no model); and (4) simulacrum, which “bears no relation to any reality whatsoever”.[7] In Baudrillard’s concept, like Nietzsche’s, simulacra are perceived as negative, but another modern philosopher who addressed the topic, Gilles Deleuze, takes a different view, seeing simulacra as the avenue by which an accepted ideal or “privileged position” could be “challenged and overturned”.[8] Deleuze defines simulacra as “those systems in which different relates to different by means of difference itself. What is essential is that we find in these systems no prior identity, no internal resemblance”.[9]

Getting back to the proposed research, an Oct. (?), 2015 University of North Carolina news release, which originated the news item, describes the proposed work in more detail,

Allbritton is an expert at microfabrication and microengineering. Also on the team are intestinal stem cell expert Scott T. Magness, associate professor of medicine, biomedical engineering, and cell and molecular physiology in the UNC School of Medicine; microbiome expert Scott Bultman, associate professor of genetics in the UNC School of Medicine; and bioinformatics expert Shawn Gomez, associate professor of biomedical engineering in UNC’s College of Arts and Sciences and NC State.

The impetus for the “organ-on-chip” movement comes largely from the failings of the pharmaceutical industry. For just a single drug to go through the discovery, testing, and approval process can take as many as 15 years and as much as $5 billion dollars. Animal models are expensive to work with and often don’t respond to drugs and diseases the same way humans do. Human cells grown in flat sheets on Petri dishes are also a poor proxy. Three-dimensional “organoids” are an improvement, but these hollow balls are made of a mishmash of cells that doesn’t accurately mimic the structure and function of the real organ.

Basically, the human gut is a 30-foot long hollow tube made up of a continuous single-layer of specialized cells. Regenerative stem cells reside deep inside millions of small pits or “crypts” along the tube, and mature differentiated cells are linked to the pits and live further out toward the surface. The gut also contains trillions of microbes, which are estimated to outnumber human cells by ten to one. These diverse microbial communities – collectively known as the microbiota – process toxins and pharmaceuticals, stimulate immunity, and even release hormones to impact behavior.

To create a dime-sized version of this complex microenvironment, the UNC-NC State team borrowed fabrication technologies from the electronics and microfluidics world. The device is composed of a polymer base containing an array of imprinted or shaped “hydrogels,” a mesh of molecules that can absorb water like a sponge. These hydrogels are specifically engineered to provide the structural support and biochemical cues for growing cells from the gut. Plugged into the device will be various kinds of plumbing that bring in chemicals, fluids, and gases to provide cues that tell the cells how and where to differentiate and grow. For example, the researchers will engineer a steep oxygen gradient into the device that will enable oxygen-loving human cells and anaerobic microbes to coexist in close proximity.

“The underlying concept – to simply grow a piece of human tissue in a dish – doesn’t seem that groundbreaking,” said Magness. “We have been doing that for a long time with cancer cells, but those efforts do not replicate human physiology. Using native stem cells from the small intestine or colon, we can now develop gut tissue layers in a dish that contains stem cells and all the differentiated cells of the gut. That is the thing stem cell biologists and engineers have been shooting for, to make real tissue behave properly in a dish to create better models for drug screening and cell-based therapies. With this work, we made a big leap toward that goal.”

Right now, the team has a working prototype that can physically and chemically guide mouse intestinal stem cells into the appropriate structure and function of the gut. For several years, Magness has been isolating and banking human stem cells from samples from patients undergoing routine colonoscopies at UNC Hospitals.

As part of the grant, he will work with the rest of the team to apply these stem cells to the new device and create “simulacra” that are representative of each patient’s individual gut. The approach will enable researchers to explore in a personalized way how both the human and microbial cells of the gut behave during healthy and diseased states.

“Having a system like this will advance microbiota research tremendously,” said Bultman. “Right now microbiota studies involve taking samples, doing sequencing, and then compiling an inventory of all the microbes in the disease cases and healthy controls. These studies just draw associations, so it is difficult to glean cause and effect. This device will enable us to probe the microbiota, and gain a better understanding of whether changes in these microbial communities are the cause or the consequence of disease.”

I wish them good luck with their work and to end on another interesting note, the concept of organs-on-a-chip won a design award. From a June 22, 2015 article by Oliver Wainwright for the Guardian (Note: Links have been removed),

Meet the Lung-on-a-chip, a simulation of the biological processes inside the human lung, developed by the Wyss Institute for Biologically Inspired Engineering at Harvard University – and now crowned Design of the Year by London’s Design Museum.

Lined with living human cells, the “organs-on-chips” mimic the tissue structures and mechanical motions of human organs, promising to accelerate drug discovery, decrease development costs and potentially usher in a future of personalised medicine.

“This is the epitome of design innovation,” says Paola Antonelli, design curator at New York’s Museum of Modern Art [MOMA], who nominated the project for the award and recently acquired organs-on-chips for MoMA’s permanent collection. “Removing some of the pitfalls of human and animal testing means, theoretically, that drug trials could be conducted faster and their viable results disseminated more quickly.”

Whodathunkit? (Tor those unfamiliar with slang written in this form: Who would have thought it?)

The relationship of silver ions & nanoparticles, Nietzsche, and Rice University

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My hat’s off to Mike Williams for introducing Nietzsche into a news item about silver nanoparticles and toxicity. Here’s the line from his July 11, 2012 Rice University news release (Note: I have removed some links),

Their work comes with a Nietzsche-esque warning: Use enough. If you don’t kill them, you make them stronger.

Scientists have long known that silver ions, which flow from nanoparticles when oxidized, are deadly to bacteria. Silver nanoparticles are used just about everywhere, including in cosmetics, socks, food containers, detergents, sprays and a wide range of other products to stop the spread of germs.

But scientists have also suspected silver nanoparticles themselves may be toxic to bacteria, particularly the smallest of them at about 3 nanometers. Not so, according to the Rice team that reported its results this month in the American Chemical Society journal Nano Letters.

This next bit describing the research is an example of what I find so compelling (curiosity and persistence) about science,

To figure that out, the researchers had to strip the particles of their powers. “Our original expectation was that the smaller a particle is, the greater the toxicity,” said Zongming Xiu, a Rice postdoctoral researcher and lead author of the paper. Xiu set out to test nanoparticles, both commercially available and custom-synthesized from 3 to 11 nanometers, to see whether there was a correlation between size and toxicity.

“We could not get consistent results,” he said. “It was very frustrating and really weird.”

Here’s what they did next, what they found, and the implications of their findings,

Xiu decided to test nanoparticle toxicity in an anaerobic environment – that is, sealed inside a chamber with no exposure to oxygen — to control the silver ions’ release. He found that the filtered particles were a lot less toxic to microbes than silver ions.

Working with the lab of Rice chemist Vicki Colvin, the team then synthesized silver nanoparticles inside the anaerobic chamber to eliminate any chance of oxidation. “We found the particles, even up to a concentration of 195 parts per million, were still not toxic to bacteria,” Xiu said. “But for the ionic silver, a concentration of about 15 parts per billion would kill all the bacteria present. That told us the particle is 7,665 times less toxic than the silver ions, indicating a negligible toxicity.”

“The point of that experiment,” Alvarez [Pedro Alvarez, George R. Brown Professor and chair of Rice’s Civil and Environmental Engineering Department] said, “was to show that a lot of people were obtaining data that was confounded by a release of ions, which was occurring during exposure they perhaps weren’t aware of.”

Alvarez suggested the team’s anaerobic method may be used to test many other kinds of metallic nanoparticles for toxicity and could help fine-tune the antibacterial qualities of silver particles. In their tests, the Rice researchers also found evidence of homesis; [e.g..,] E. coli became stimulated by silver ions when they encountered doses too small to kill them.

“Ultimately, we want to control the rate of (ion) release to obtain the desired concentrations that just do the job,” Alvarez said. “You don’t want to overshoot and overload the environment with toxic ions while depleting silver, which is a noble metal, a valuable resource – and a somewhat expensive disinfectant. But you don’t want to undershoot, either.”

He said the finding should shift the debate over the size, shape and coating of silver nanoparticles. [emphasis mine] “Of course they matter,” Alvarez said, “but only indirectly, as far as these variables affect the dissolution rate of the ions. The key determinant of toxicity is the silver ions. So the focus should be on mass-transfer processes and controlled-release mechanisms.”

Interestingly, this is a joint US-UK effort (US Environmental Protection Agency and the U.K. Natural Environment Research Council). H/T to Will Soutter’s July 12, 2012 news item on Azonano for the information about this latest silver nanoparticle research from Rice University. The July 11, 2012 news item on Nanowerk also features information about the silver nanoparticles, ions, and Rice University.

I have mentioned Vicki Colvin’s work previously including this Jan. 28, 2011 posting about a UK/US joint environmental research effort. I have also mentioned Pedro Alvarez a few times including this Aug. 2, 2010 posting about nanomaterials and the construction industry.

Ideas becoming knowledge: interview with Dr. Rainer Becker (part 1 of 2)

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ETA Mar. 11, 2013: I was notified by Rainer Becker that his participation was cancelled and the organizers took the project in another direction. Consequently, much of what follows is no longer relevant. However, the discussion about knowledge and ideas and Becker’s theorists may be of some interest.

I’m very pleased to publish this interview (part 1 today) with Dr. Rainer Becker on a topic (how an idea becomes knowledge in the field of science) that has long interested me. First, some information about the research project and Dr. Becker from the April 22, 2010 news item on Nanowerk,

How do sensational ideas become commonly accepted knowledge? How does a hypothesis turn into certainty? What are the ways and words that bring results of scientific experiments into textbooks and people’s minds, how are they “transferred” into these domains? Science philosopher Dr. Rainer Becker has recently started dealing with such questions. Over the next three years, Becker will accompany the work of Professor Dr. Frank Rösl’s department at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), which studies cancer-causing viruses. He is one of three scientists in an interdisciplinary joint project which is funded by the German Ministry of Education and Research (BMBF) with a total sum of approximately € 790,000.

…

Becker’s mission in Heidelberg is part of a research project entitled “Transfer knowledge – knowledge transfer. About the past and present of the transfer between life sciences and humanities.” The project is carried out by DKFZ jointly with the Center for Literary and Cultural Studies (Zentrum für Literatur- und Kulturforschung, ZfL) in Berlin. Project leaders are Professor Dr. Frank Rösl of DKFZ and Dr. Falko Schmieder of ZfL. It comprises three individual projects in which forms of knowledge transfer related to three different constellations of science history are studied in a cultural-scientific approach.

Dr. Becker’s project,

The third and final project, which is pursued by Rainer Becker at DKFZ, deals with the question of the relevance of current knowledge concepts such as the one that understands and experimentally studies cancer as a consequence of viral infections.

“I am pleased that we will explore the relevance of tumor virology across disciplinary borders and I hope we will gain fundamental insights into how scientific discourses develop and how they are ultimately accepted in scientific thought collectives,” said departmental head Frank Rösl about the relevance of the current project.

This is not Dr. Becker’s first such project, his doctoral thesis touched on some of the same themes of how scientific discourse develops,

Rainer Becker wrote his doctoral thesis while he was employed at the Institute of Philosophy of Darmstadt Technical University. There he made parallel studies of the social history of the computer and the “universal science” of cybernetics. Back then he already chose a topic that transcends borders between humanities and natural sciences. “While I was working on my doctoral thesis, I explored the question of ‘transfers’ – namely between technology, natural sciences and philosophy in the 1940s: The development of computers and cybernetics would not have been possible without prior conceptual and metaphorical ‘transfers’ between life sciences and technical sciences.”

In his future project, the philosopher will study in real time, so to speak, how natural science data are being obtained, processed and communicated. As a “researcher of science”, he will observe the laboratory work from the perspective of the humanities and cultural science, he will do research in archives and will interview scientists. It is for good reason that the project is located at DKFZ, because this is the place where findings from basic biological research become relevant for medicine and the public. Thus, the Nobel Prize-winning discovery by DKFZ’s former Scientific Director, Professor Harald zur Hausen, that particular viruses cause cervical cancer has led to a vaccine against this type of cancer.

Now for the interview:

1. First, congratulations on receiving funding for such a fascinating line of query. When does the project start and what is the period of time during which it will run?

A: Indeed, the funding delighted all of us. My sub-project in Heidelberg started in late October 2009, it will be supported for 3 years.

2. Will you be working alone or will you be working with an interdisciplinary team?

A: Currently I am doing my study in Heidelberg on my own, getting assisted locally by one of the project leaders, a biologist highly interested in interdisciplinary work: Prof. Frank Roesl, head of the department where I am doing my research. The other project leader, Dr. Falko Schmieder and two other science philosophers support me in Berlin, at the Center for Literary and Cultural Research (ZfL). Like me, both of them work on their own sub-projects while getting support by Dr. Schmieder: he does ensure the convergence of the sub-projects. We discuss the topics during our regular meetings – but also via email, skype, wikis for sharing documents etc.

Because the main focus of the project is historical, both of the other sub-projects work –like me in the past – in a more historical way: they try to elucidate the current situation in the Heidelberg lab of 2010 – molecular biological work on supposedly tumourgenic viruses – by working in archives, on in part comparable fields, but different time scales: (a) Dr. Birgit Griesecke – mainly doing studies on Ludwig Fleck – is working on the 1930s, (b) PD Dr. Peter Berz – researching contexts esp. around Jacques Monod – is working on the 1970s. Both help me to understand the current scientific situation in the corresponding historical context.

We also try to get additional funding options for one or two other researchers (e.g. sociologists, communication scientists) supporting our work in a interdisciplinary way.

3. Are there any theorists that have influenced how you are approaching this project?

A: The whole project is closely related to the work of the Polish bacteriologist and sociologist of science Ludwig Fleck. Its main theoretical references point to him – by as well trying to ‘refresh’ his approaches in ways more adequate to the current scientific situation: not only everything that happened after the ‘linguistic turn’ and all the concerns on ‘media’, but also dealing with questions on the significance of ‘things’ in the labs around 2010. This confrontation of Fleck with the present research raises several questions, for example:

Do apparatuses reflect or even materialize special sorts of scientific ‘thought-styles’?

Do specific ‘thought-collectives’ gather or even get constituted around special lab equipments to what extent do they form prior styles of thinking – what kind of ‘migration-background’ has each ‘thing’ with what implications and what styles of local adoption?

What exactly is the correlation between assemblages of things, humans, animals, discourses and what Mary Douglas coined ‘worlds of thought’ – and their inhabitants / participants?

What is their contribution to the specific local – and the same time globally connected – scientific way of worldmaking (in the field of cancer research)?

What political implications potentially are embedded in all that fields – from specific ways of problematisation to its effects?

My own theoretical background was mainly influenced by the philosophical tradition of structuralism and so called ‘post-structuralism’, especially Michel Foucault – so phenomenological traditions also interest me. Foucault, Gilles Deleuze, J.-F. Lyotard, M. Serres and M. de Certeau framed my more traditional approaches to political philosophy on the one hand (from Plato, Hobbes, Kant, Nietzsche, Weber, Arendt to the early/middle Frankfurt School, French Postmodernist to current debates on ‘radical democratic’-thinkers as well as philosophical experiments like tiqqun) but on the same time on the other hand to different fields of knowledge, esp. concerning the relation technology – art – bios (I wrote my dissertation on a ‘coevolutionary’ history of the ‚universal machine’/ computers and ‘first’ cybernetics in connection to what Foucault termed ‘biopower’ – coming from Canguilhem and handing this concept over to E. Fox-Keller, I. Hacking, D. Haraway and L. Kay).

In my field, a biological laboratory dealing with viruses and cancer, Michel Serres’ thoughts on different phenomena of ‘inbetween’/’3rds’ as well as Foucault’s spatial approaches in their connection to knowledge/power (heterotopia, taxonomy/order, diagrams like ‘panoptism’) currently form reflections of my experiences more and more – as well as my contention with prominent ‘first wave’ researchers in the field of science/laboratory studies, e.g. B. Latour (esp. the ‘early’), K. Knorr-Cetina, H.J. Rheinberger (esp. beyond his Heidegger-References), P. Rabinow (both theoretical and practical work) and D. Haraway (esp. ‘when species meet’), flanked by what could be coined a wide field of ethnology in the broadest sense (C. Lèvi-Strauss, M. Douglas, C. Geertz, E. Goffman): ethnology of the own, western culture interested me since my first contacts with poststructuralism/Nietzsche. In that range, scientific and everyday practices and their relation to ‘strangeness’ of the field (for the lab-practitioners, for me) more and more comes to focus (think of the concept of ‘problematisation’) – and also theorist of  ‘practice’ keep framing my attention (A. Pickering, K. Sunder-Rajan, M. de Certeau). I hope the projects (my colleagues and mine) will contribute something at least in that latter field.

4. The description in the press release for how you plan to go about your project reminded me of Bruno Latour’s Laboratory Life where he described the creation of a ‘scientific fact’. Obviously you won’t be repeating that work, so I’m wondering if you could describe your process and goals in more detail.

see (3)

Tomorrow: more details about the project and how the research will be disseminated.