Saturday, March 21, 2015

Intriguing Work By Professor Roger Kamm on "Emergent Behavior"

I just recently found some very intriguing research- ongoing, by Professor Roger Kamm at MIT, in what is described as the field of “Emergent behavior of integrated cellular systems.” On a somewhat related note: I have posted here- a number of articles on determinism but more importantly, the empirical applications of determinism from a theoretical point of view and what is very interesting about Dr. Kamm’s research is that it highlights this very question about the nature of causality and does so in a very real world problem area, the possible manufacture of “living machines.”
Emergent behavior is described as essentially the way in which individual cells form higher functioning organs. This field of engineering turns upon the basic premise that a “top down manufacturing” coupled with intrinsic, natural processes, (for example those found in cells themselves), can lead potentially to new, artificial cells which might be directed to all sorts of activities, including making new medicines, treating diseases and even making mimic organs.
Many probably will recall the announcement by Craig Venter of the self named, Craig Venter Institute (JCVI), a few years ago, (2008) of the world’s first “synthetic cell.” http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/overview/
Venter was approaching the problem as a geneticist who has sequenced very large genomes. If one can know the genetic code then, like synthetic chemistry, it should be possible to design organisms from the bottom up. But I believe this illustrates more key differences than the similarities.
One of the things, I believe, that differentiates Kamm’s work from Venter’s is that Kamm is proposing to venture into multicellularity. But I believe the other main difference is that he is attempting to show that cells might achieve, with proper engineering, some artificial property and this might be “emergent.” And that is the fascinating part. What is it that makes a cell property “natural” and another cell property, or behavior, unnatural or “emergent.”
In Dr Kamm’s abstract (which I am attempting to obtain the transcript of) entitled “Emergent Behaviors of Cellular Systems: Lessons In Making Biological Machines” he states the following:
Recent advances in synthetic biology, developmental biology and tissue engineering, have raised the prospect of building living, multi-cellular machines.
Kamm is undoubtedly referring to advances in bio-engineering that have led to very advanced applications like artificial skin grafts, used for grafting in burn victims, in which human skin cells are essentially tricked into populating artificial lattices, and their immunological signatures attenuated to reduce potential for rejection. In a multicellular “machine” an organ mimic might help to produce insulin in a diabetic patient, or some kind of artificial lung graft might help produce proteins that could help alleviate breathing disorders. There would be virtually all kinds of possibilities from such a finding.
These theses, however, assume a kind of biological determinism. That, in theory pre-determined states of a biological system can determine a final state, that would be the principal behind this sort of engineering…in the same way that an actual machine is pre-designed blue print fashion, in another computer via CAD and/or software engineering.
And on this point I believe it is highly experimental, and I’m not quite convinced of what this might entail. Is it robotic or is it just an alternative form of life? So those questions definitely relate to biological and also possible genetic determinism. Kamm highlights this issue: “…The process of building a living machine, however, necessarily deviates from current top-down manufacturing procedures in ways that are both limiting and enabling.” The impetus for artificial cell machines is probably to a large extent due to recent advances in stem cells. Stem cells or pluripotent cells PC’s” to be technical, are actually thought of for this very purpose, as cells which are not pre-destined to become skin, liver, or brain etc., but in theory, can become what the medical practitioner triggers them to be. Kamm would take it a large step further, even from where tissue engineering is attempting to go now, by looking at integrating various cells to work in a collective whole which he believes is much more powerful (the analogue he uses is to “organoids” or clusters of PC which show collective behavior).
Clearly living machines are still at a very basic level currently, and still far from applications, but these raise intriguing questions. Kamm’s idea’s of, for example “co-locating” various multicellular components, in order to assemble working structures, is not vastly unlike what Venter achieved with a single cell, the co location of single, cellular components; a core of genetic material (nucleus) transplanted into a receptive, empty cell membrane. In theory it appears possible, the issue is how these might be “enabling but also limiting” and this issue of it being enabled but at the same time potentially inherently limited, is directly related to potential implications of biological determinism.
Can a biological ‘machine’ be made and if so, does this require that key functions in it are pre-determined? It would seem to be a new paradigm for how an organism might grow.
Here is an excerpt from the Research.gov site for the National Science Foundation’s Center For Emergent Behaviors of Integrated Cellular Systems which Dr. Kamm is Program Director (found here). https://www.research.gov/research-portal/appmanager/base/desktop?_nfpb=true&_windowLabel=assetSummary_1&_urlType=action&wlpassetSummary_1_id=%2FresearchGov%2FResearchAsset%2FPublicAffairs%2FCenterforEmergentBehaviorsofIntegratedCellularSystems.html&wlpassetSummary_1_action=selectAssetDetail
 “The Center for Emergent Behaviors of Integrated Cellular Systems (EBICS), based at MIT, seeks to understand cells and their environment, and how these cells work together to incorporate biochemical and mechanical cues to perform a wide variety of functions. The center’s approach for constructing biological machines is similar to the engineering techniques employed in making non-biological machines. Many Center staff members are engineers, and they think like engineers, building machines up from individual parts.
The research could have dramatic applications in industry, medicine, energy and the environment, among others. Biological robots in an assembly line, for example, could repair themselves and adapt to optimize their performance; new “organs” could be designed and implanted, with the ability to sense drug or glucose levels in the bloodstream, and respond appropriately by turning on or off drug secretion; organisms could swim to an oil spill, and consume the damaging substance, replicate if needed, then swim home to the host ship for processing; smart plant-based machines could release the correct amount of controlled energy to produce heat, light or mechanical work.
Creating living systems with important new roles raises ethical issues that center scientists work to address. “Will these machines be endowed with the capability to self-repair, adapt, and self-replicate?” says Center director Roger Kamm. “If so, they become indistinguishable from natural organisms and need to be considered in a similar light. If stem cells are used, from what source may they be taken? What protections and regulations need to be in place?
What strikes me is how these “machines” would interact with other biological organisms. If we are to imagine, swimming biological robots that clean up oil spills, and then return to the ship for example, how would they do against a natural open ocean super predator, like a whale, or smaller fish? How would these machines fight off bacterial attack in open water? Bacteria attack virtually any substance known. I came across a proposal (in a grant) recently in which bacteria are being fed paint stripper as food, that would be dichloromethane. And bacteria it turns out, feed off of crude oil and have been doing so for probably as long as it has been oozing up from the Gulf of Mexico. So it seems that many of these problems of the “biological machines” described by this group, would in theory, be virtually identical to those faced by natural organisms.
Should we be concerned about potential ethical issues? When you think about it, our world is chaulk full of non-natural functioning, living systems or environs. For example, we don’t have the very natural plagues that would be expected to naturally be present in a non-vaccinated society. Or of rampant illnesses spread because we lack molecularly engineered anti-biotics or anti-viral vaccines. We live in a biologically engineered society, which is to a large extent, a society inherited and built, from the ancient practices of designing the environment we live in, not limited to the selective breeding of livestock and food crops to produce higher yields, nor the physical structures and systems that surround us.
Deliberate cross breeding of plants was likely done tens of thousands of years ago, (I would guess at the outset of agriculture) though the original engineers obviously lacked the sophisticated tools of today. Yes, there are issues with GMO”s particularly to free market, and the potential risks of proteins made from engineered crops or other products should be evaluated. People should have the right to access natural organic sources. However, these aims are not incongruent with better technologies that might lead to new, and unexpected breakthroughs in medicine. These are some radical ideas directed toward unmet and unsolved medical challenges, (artificial organs, cancer) so perhaps out-of the box thinking is not only justified, but required. I look at most of our more advanced health advancements, and see that these are directly resultant of more knowledge about science, not less. It should be noted that organ mimics referred to by Kamm, might in fact replace animal testing altogether. So I believe we will deal with the ethical limitations of the engineering as the advancements come about, and their potential benefits or risks can be evaluated, not before.




Author notes:
[Material from "The Crisis Equation" blog]MKK

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