BJKlein-- Rob joins ImmInst today to discuss "The Pace and Proliferation of Biological Technologies"
Rob-- If anyone is interested, my homepage is at www.synthesis.cc, and I have posted a draft chapter of my book at www.biologyistechnology.com.
BJKlein-- So the book's title is "Learning to Fly: The past, present, and future of Biological Technology
BJKlein-- ready to dive into questions, Rob?
Rob-- Sure.
BJKlein-- Can you give a trajectory as to how aging may be cured?
BJKlein-- as in what technologies, and when?
Rob-- Hmmm...that's quite question to start with. But here goes. I am not sure we understand what "aging" is, exactly. So curing it will have to wait until we understand it better.
Rob-- We definitely need better tools to characterize biological systems, which is what I spend most of my time working on.
Rob-- Once we have a better sense of what exactly is "going wrong", then we will have a much better chance at fixing it.
BJKlein-- hince, aging is possible to cure?
BJKlein-- or perhaps, you may give us your idea on what aging is?
BJKlein-- eventhough, as you say, it would be premature.
Rob-- Well, all life comes in units of single cells. In complex organisms, many of those cells cooperate to create behavior that is far beyond the capabilties of the individuals.
Rob-- If we assume we get stem cells sorted out, that means we should be able to start replacing cells, or the cooperative units of cells we call tissues and organs.
Rob-- This is all well and good for most of the tissues and organs in our bodies, but I have a feeling we are going to run into problems with this strategy in the brain.
BJKlein-- at is would seem, but there has been some success, i have thought?
BJKlein-- with parkinson's i think
Rob-- We certainly don't understand all of the brain yet, but it is pretty clear that memories and cognition rely on connections between cells within the brain. We may well be able to replace aging neurons in the brain, but I don't know how we are going to copy over connections between old cells to the new ones.
Rob-- There are indeed interesting preliminary results in restoring function in Parkinsons and brain injuries using stem cells.
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Rob-- But the difference between a desperate patient consenting to try an experimental therapy and something that is safe and available for all is quite large.
BJKlein-- what are some of the advancements you have made in thinking about biological technologies?
BJKlein -- what are some of the advancements you have made in thinking about biological technologies?
Rob -- Fundamentally, we don't have the technologies to understand how single cells work. We have to start at this level.
Rob -- This is why I have been focussing my efforts on building molecular and microfluidic gizmos to enable single cell analysis.
BJKlein -- perhaps modeling the systems in computers is the best way to understand?
Rob -- Think of them as test and measurement gear for single cells.
BJKlein -- interesting
Rob -- I am highly skeptical of complex computer models -- it is way too easy to get the result you are looking for, and it is clear that for even the simplest models we don't know enough to make them truly predictive.
BJKlein -- so i take it you do lab work on cells with your 'gizmos'?
Rob -- If only I were that far along.
BJKlein -- heh
Rob -- Along with collaborators from The Molecular Sciences Institute, where I used to be a Research Fellow, I just published in Nature Methods a way of sensitively quantifying proteins and metabolites.
BJKlein -- this is a farther out question, but do you see biology as our end goal.. or do humans become more?
Rob -- But so far that technique only works with relatively large samples -- it isn't so easy to manipulate single cells in the lab. That will require complex microfluidic instruments -- the "lab on a chip".
BJKlein -- 'sensitively quantifying proteins and metabolites' -- can you explain a bit more?
Rob -- That is an interesting question. I don't understand how we will download our brains, because we don't yet know how much computation our brains actually do. That may happen, someday, but we are a long way away. I would be very happy just to keep my biology going for a good long time.
BJKlein -- how long?
Rob -- Hah. If we do in fact get stem cells working in some way, or even figure out how to control differentiation of cells already within tissues, then hundreds of years perhaps. At some point, the cells you have in your body will accumulate a number of mutations, and you have to get rid of them.
* BJKlein nods
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Rob -- Stem cells should do the trick here, but at some point you run into the problem that you have to play this game in the brain. And as I already suggested, you may not stay "you" when cortical neurons are replaced.
BJKlein -- for the record.. a question i like to ask all guests.. what do you think happens after death?
Rob -- Nothing.
Rob -- There is no evidence that anything happens, so why invent something to make ourselves feel better?
BJKlein -- thus your wish to live hundreds of years?
Rob -- I would like to live as long as possible, because I want to find out what happens. I am tremendously curious to see how we solve problems, whether we manage to get off this rock and explore the universe, whether we are alone (can't be!), and whether we are on the right track with physics or just stumbling along through intellectual toddlerhood.
BJKlein -- re: brain game, true.. somewhat.. but I think it's more a problem to degree.. and not all or nothing.. thus as we get better at it.. the more likely we are to preserve more of 'us' in our brain
Eliezer -- Rob, when you say "Can't be!", do you mean that it seems extremely improbable, or that it would devastate you to discover that this was the case?
BJKlein -- excellent.. hope to see the future with you.
Rob -- Maybe. It is now clear that cells are constantly be physically remodeled at the microsopic level, constantly growing and editing connections between each other. How do you define the state of a cell in order to copy it?
BJKlein -- i think you need to define it as good as possible.. but there will always be some degree of error
Rob -- Nature is however it is. We can only discover what is out there. I find it highly unlikely that we are alone. It is *possible*, of course, but I can't believe this corner of the unverise is particularly special.
Eliezer -- In terms of the causal effect it has on other cells, which in turned can be defined as the degree to which any observable variable in the target cell correlates with the state of the origin cell.
Eliezer -- In other words, if a variable in the origin cell has no effect on any variables in target cells, we presume that variable does not participate in information processing.
BJKlein -- are you talking brain, eli?
Eliezer -- BJ: yah, neurons
Rob -- To push the question of cell state all the way into statistical physics, how many degrees of freedom does it take to define the state of the cell? How much error in measuring each can you tolerate? What happens if the errors compound non-linearly, so that you get a catastrophic failure?
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Eliezer -- Heisenberg limits, but if your measuring instrument can measure better than the thermal error at 300 Kelvin, I call that good enough.
BJKlein -- would depend on each cell type
Eliezer -- Presuming that your measuring errors are as random as thermal errors. Systematic errors would be bad.
Rob -- These are the sorts of questions that you have to answer if you are going to measure the system adequately to copy it. No Heisenberg required -- we can measure very little classically at this point.
BJKlein -- Rob, do you think it possible to emulate a brain in a computer.. via scan?
Rob -- By that I mean we have access to only a few of the parameters necessary to predict or reproduce the behavior of neurons. We know this is true because nobody has built a brain yet.
Rob -- It may be possible to emulate a brain in a computer, and this has been a favorite past time of physicists and engineers for decades. But there are precious few examples where anyone has demonstrated a model that behaves like a real neuron, or collection of neurons.
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BJKlein -- do you talk with friends about how long you wish to live?
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BJKlein -- I see you have a number of inventions, one being "Spectroscopic Protein Identification"
Rob -- Hmmm...not so much. Most humans are at the whim of the enivronment still, or their genetic heritage, and we don't seem to have much control over that yet.
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BJKlein -- is most of your work theoretical in nature?
Rob -- Yes, that one is extremely challenging. The idea was to augment proteins in a way that one could identify them from physical parameters, rather than relying on more traditional immunochemistry methods.
BJKlein -- so you actually augmented proteins?
Rob -- Most of my work is at the lab bench, where I happen to be right now. I was fortunate to have time both at Princeton and at TMSI to sit and think about theoretical problems, and it became clear that there was no way to measure most of things I wanted to model. So I think mostly about how to measure things in the lab.
BJKlein -- have a publisher for the book yet?
Rob -- We chemically modifed proteins to make them easier to detect and identify. This strategy works, to an extent, but the chemistry is really hard, and pushing things down to measuring just a few copies of a protein is really hard. So I switched directions, and the "Tadpoles" resulted, which were mentioned in the NY Times last Friday.
Rob -- No publisher yet. There was some interest a couple of years ago when I wrote the first draft. But I only just started looking again, after taking several years to mostly work in the lab, during which time I completely changed the tone of the text.
BJKlein -- do you think it possible to create smarter-than-human intelligence on computers?
BJKlein -- "The first paper describing sensitive, parallel quantitation of "just about anything" using Tadpoles is now published."
BJKlein --
http://synthesis.typ...les_unleas.htmlRob -- Probably. Humans have a finite number of neurons, with a probably finite number of connections between them. Once we figure out what the algorithm is, I don't see why we couldn't build silicon versions that are much smarter and faster.
BJKlein -- do you have worries about such computers taking over us?
Rob -- The Terminator will only be a problem if someone programs it that way.
Rob -- Less tritely, I don't think there is any reason for animosity between carbon and silicon. For one thing, we will be interested in different resources. Lots of animals share the same ecosystem, and they live happily together because they eat different things.
BJKlein -- getting back to Bio Tech advancement..
BJKlein -- you think "the only way to ensure safety in the long run is to push research and development as fast as possible"
Rob -- While keeping everything wide open, yes.
BJKlein -- what attracted you to this field?
Rob -- We are already living in the time where we can modify biological systems, but we can't do anything about mistakes, or even natural threats. As far as I can tell, we don't have the technologica capability to make a vaccine against the current scary Avian Flu. Gotta fix that.
BJKlein -- heh
BJKlein -- creating new viruses as well..
Rob -- I have always loved biology, and I have always built things. My degrees are in physics, which gives me a different perspective on measurement, technology, and experiments than most people in the field.
BJKlein -- seems you have dreams of space travel.. i on the otherhand, don't seem much excitiment other than earth.. for now at least
Rob -- Yes, new viruses. It is already possible to build genomes that size, as has been demonstrated several times in academic work over the last several years. Fortunately, it is still hard to make anything novel from scratch that works.
Rob -- Drew Endy at MIT is probably the one who will get new viruses working first.
Rob -- Well, we will see how technology for getting into orbit evolves. Rockets are fine, but I think the energy difference between rockets and the space elevator is pretty interesting.
BJKlein -- ya, pretty interesting what nanotech may help us with..
Rob -- Hmmm...I don't know what nanotech means anymore. I would call it "chemistry".
BJKlein -- have you sequenced your dna ?
BJKlein -- right.
Rob -- Sequencing an individual's DNA still costs millions of dollars. If I had that kind of money, I would spend it differently.
BJKlein -- you have my interest... how would you spend it?
ddhewitt -- There is a push for the thousand dollar personal genome.
Rob -- At the present rate of cost reduction, it will be another 15-20 years before we hit the "thousand dollar genome".
ddhewitt -- I respectfully disagree.
BJKlein -- official chat has ended.. but please feel free to stay with us Rob, as long as you wish
Rob -- The numbers are published in my paper in 2003. That doesn't mean new technology won't make things go faster (and I think they will), but if you extend out the current curves that is what you get.
Rob -- I can hang out for a little while longer. Though I have to get back to experiments pretty soon.
Rob -- Nothing like a Sunday night alone in the lab.
BJKlein -- heh, no family?
Rob -- My wife is writing a mid-term in her office.
BJKlein -- have you considered cryonics as a safety net to allow you to see the future?
BJKlein -- my wife is working on law upstairs in our house
BJKlein -- lawyer
Rob -- If anyone had shown that to be a viable way to preserve tissue, and demonstrated recovery of the state of cells and connections in the brain, then I might be more interested. Alas, it seems a bit speculative to me.
BJKlein -- check:
http://www.cryoletter.org pass: life
BJKlein -- at the bottom is new research
BJKlein -- "First paper showing good ultrastructure of vitrified/rewarmed mammalian brains and the reversibility of prolonged warm ischemic injury in dogs without subsequent neurological deficits, and setting forth the present scientific evidence in support of cryonics:"
BJKlein -- I had a chance to interview Charles Platt for the ImmInst Film Project
BJKlein -- a co-writer of the paper
Rob -- At this point, the paper goes on the "to read" stack. I am snowed under at the moment.
BJKlein -- also interview Brian Wowk who is working on a new cryonics procedure called vitrification..
BJKlein -- understand..
BJKlein -- i'm interested in understanding why people do what they do.. at the core..
BJKlein -- for example, for me, i see death as oblivion.. thus i do everything to overcome death
BJKlein -- all my work goes into saving lives
BJKlein -- with as much leveraged technology and intelligence as i can muster ;-)
Rob -- Well, it is certainly likely to be an end to learning, which would be a disapointing turn of events.
BJKlein -- in light of the fact that nothing exists after death.. seems likely
Rob -- Anybody else have questions they would like to ask?
BJKlein -- would you descrive yourself as seeking immortality?
BJKlein -- was a quiet night.. sorry for that.
Rob -- (Not to dismiss yours, Bruce.)
BJKlein -- np
BJKlein -- I should let you get back to the bench.. best of luck to your wife!
Rob -- Yes, back to the bench. Thanks for listening, everybody.
BJKlein -- i'll post archive soon to the web..
BJKlein -- thanks very much for joining us.. as others will likely read later.
Rob -- Good night.
BJKlein -- take care
