How much should we worry about bionanotechnology?

We should be very worried indeed about bionanotechnology, according to Alan Goldstein, a biomaterials scientist from Alfred University, who has written a long article called I Nanobot on this theme in the online magazine According to this article, we are stumbling into creating a new form of life, which is, naturally, out of our control. “And Prometheus has returned. His new screen name is nanobiotechnology.” I think that some very serious ethical issues will be raised by bionanotechnology and synthetic biology as they develop. But this article is not a good start to the discussion; when you cut through Goldstein’s overwrought and overheated writing, quite a lot of what he says is just wrong.

Goldstein makes a few interesting and worthwhile points. Life isn’t just about information, you have to have metabolism too. A virus isn’t truly alive, because it consists only of information – it has to borrow a metabolism from the host it parasitises to reproduce. And our familiarity with one form of life – our form, based on DNA for information storage, proteins for metabolic function, and RNA to intercede between information and metabolism – means that we’re too unimaginative about conceiving entirely alien types of life. But the examples he gives of potentially novel, man-made forms of life reveal some very deep misconceptions about how life itself, at its most abstract, works.

I don’t think Goldstein really understands the distinction between equilibrium self-assembly, by which lipid molecules form vesicles, for example, and the fundamentally out-of-equilibrium character of the self-organisation characteristic of living things. I am literally not the same person I was when I was twenty; living organisms are constantly turning over the molecules they are made from; the patterns persist, but the molecules that make up the pattern are constantly changing. So his notion that if we make an anti-cancer drug delivery device with an antibody that targets a certain molecule on a cell wall, then that device will stay stuck there through the lifetime of the organism, and if it finds its way to a germ cell it will be passed down from generation to generation like a retrovirus, is completely implausible. The molecule that it’s stuck to will soon be turned over, the device itself will be similarly transient. It’s because the device lacks a way to store the information that would be needed to continually regenerate itself that it can’t be considered in any sensible way living.

If rogue, powered vesicles lodging in our sperm and egg cells aren’t scary enough, Goldstein next invokes the possibility of the meddling with the spark of life itself – electricity. But the moment we close that nano-switch and allow electron current to flow between living and nonliving matter, we open the nano-door to new forms of living chemistry — shattering the “carbon barrier.” This is, without doubt, the most momentous scientific development since the invention of nuclear weapons.” This sounds serious, but it seems to be founded on a misconception of how biology uses electricity. Our cells burn sugar, Goldstein says, which “yields high-energy electrons that are the anima of the living state. “ Again, this is highly misleading. The energy currency of biology isn’t electricity, it’s chemistry – specifically it’s the energy containing molecule ATP. And when electrical signals are transmitted, through our nerves, or to make our heart work, it isn’t electrons that are moving, it’s ions. Goldstein makes a big deal out of the idea of a Biomolecule-to-Material interface between a nanofabricated pacemaker and the biological pacemaker cells of the heart. “A nanofabricated pacemaker with a true BTM interface will feed electrons from an implanted nanoscale device directly into electron-conducting biomolecules that are naturally embedded in the membrane of the pacemaker cells. There will be no noise across this type of interface. Electrons will only flow if the living and nonliving materials are hard-wired together. In this sense, the system can be said to have functional self-awareness: Each side of the BTM interface has an operational knowledge of the other.” This sounds like a profound and disturbing blurring of the line between the artificial and the biological. The only trouble is, it’s based on a simple error. Pacemaker cells don’t have electron-conducting biomolecules embedded in their membranes; the membrane potentials are set up and relaxed by the flow of ions through ion channels. There can be no direct interface of the kind that Goldstein describes. Of course, we can and do make artificial interfaces between organisms and artefacts – the artificial pacemakers that Goldstein mentions are one example, and cochlear implants are another. The increasing use of this kind of interface between artefacts and human beings does already raise ethical and philosophical issues, but discussion of these isn’t helped by this kind of mysticism built on misconception.

In an attempt to find an abstract definition of life, Goldstein revives a hoary old error about the relationship between the second law of thermodynamics and life: “The second law of thermodynamics tells us that all natural systems move spontaneously toward maximum entropy. By literally assembling itself from thin air, biological life appears to be the lone exception to this law. “ As I spent several lectures explaining to my first year physics students last semester, what the second law of thermodynamics says is that isolated systems tend to maximum entropy. Systems that can exchange energy with their surroundings are bound only by the weaker constraint that as they change, the total entropy of the universe must not decrease. If a lake freezes, the entropy of the water decreases, but as the ice forms it expels heat which raises the entropy of its surroundings by at least as much as its own entropy decreases. Biology is no different, trading local decreases of entropy for global increases. Goldstein does at least concede this point, noting that “geodes are not alive”, but he then goes on to say that “nanomachines could even be designed to use self-assembly to replicate”. This statement, at least, is half-true; self-assembly is one of the most important design principles used by biology and it’s increasingly being exploited in nanotechnology too. But self-assembly is not, in itself, biology – it’s a tool used by biology. A system that is organised purely by equilibrium self-assembly is moving towards thermodynamic equilibrium, and things that are at equilibrium are dead.

The problem at the heart of this article is that in insisting that life is not about DNA, but metabolism, Goldstein has thrown the baby out with the bathwater. Life isn’t just about information, but it needs information in order to be able to replicate, and most centrally, it needs some way of storing information in order to evolve. It’s true that that information could be carried in other vehicles than DNA, and it need not necessarily be encoded by a sequence of monomers in a macromolecule. I believe that it might in principle be possible in the future to build an artificial system that does fulfill some general definition of life. I agree that this would constitute a dramatic scientific development that would have far-reaching implications that should be discussed well in advance. But I don’t think it’s doing anyone a service to overstate the significance of the developments in nanobiotechnology that we are seeing at the moment, and I think that scientists commenting on these issues do have some obligation to maintain some standards of scientific accuracy.

20 thoughts on “How much should we worry about bionanotechnology?”

  1. Richard,

    I was waiting to read a good rebuttal of the Goldstein article and this one is as good as any. In my opinion, too many people underestimate biology. Eric Drexler does it, Alan Goldstein does it. The body is complex, consisting of regulatory networks, metabolic pathways, and behind all this a plethora of genetic information that we do not understand yet.

    We do need to be aware of potential consequences. I am convinced that within 2 decades many people will have devices implanted in their bodies, mostly for diagnostics and monitoring of insulin levels, etc. Therapeutics that target are genetic makeup (or at least deliver RNAi) are not far away either and the consequences could be bad, but no one should allow fear of what might happen to cloud the quest for the good that would happen if things worked.

    What I fear is that every time the word “bot” is associated with nanotechnology, the connotations are almost always negative. I am not the worlds biggest fan of molecular manufacturing in the short term, but there has to be a way to get better information out there, and a lot of it.

  2. If passivated nanodiamondoids don’t play nice enough to permit the stable construction of even a basic library of parts geometries, a nice backup plan is that functionalized diamond surfaces can be be used as sensors to catch pathogens, both natural and synthetic.

  3. Thanks for the kind words, Deepak and Zelah. I could have written a lot more, but I had to get some work done! I agree very strongly with Deepak’s comment about the propensity to underestimate biology. What I find particularly striking about Goldstein’s article is the way in which he muddles metaphor and reality; this is a common and very regrettable feature of too much writing about biology. On the other hand, and here again I agree with you, there really are things in the pipeline with potential consequences that we should worry about, but we do need to focus on what’s real or plausible.

    Phillip, it should indeed be possible to graft all kinds of functionality onto diamond. The questions to ask are, what advantages would diamond have over other surfaces, and perhaps more particularly how would you couple the sensor to an actuator of some sort – something that triggered some action having detected a target.

  4. This Tokyo group has a much better biosensor idea than mine:
    and another similiar boron-doped diamond sensor platform:
    The above are solution phase though. I think the fact that different hydrogen surface coverages can be metastable at room temperature will make diamonds versatile for many template geometries.

    Diamond’s hardness makes it a low mass low volume low wear solution, as does diamond’s chemical inertness (in the absence of a 2X1 carbon surface reconstruct). Its high themal conductivity should make it an accurate sensor. Big electro-chem window and biocompatibility are obviously good for this application.

    In the not too distant future I think it will be possible to bring the whole sensor apparatus to the pathogen. Combine a nanodiamond electrode whose surface is functionalized so that it will “stick” to a targeted microbe surface structure in a way that completes a circuit, along with an integrating a quantum dot.
    For the near future, have a diamond LED depression shining on a CCD. Functionalize a surface ring surrounding the LED, so that a microbe will bind to it. This will block the LED, and the ommision will be noticed when the CCD data is fed into a computer. I don’t know how to go about going in for a closer look to verify the captured microbe is the baddie you are looking for. I also don’t know the specific surface chemistry involved in the functionalized sensor ring, or the procedure involved. If I could do that, I’d be a Phillionaire!!

  5. Dear Richard:

    It appears we are mutually disappointed by each other’s lack of understanding. You say “The energy currency of biology isn’t electricity, it’s chemistry – specifically it’s the energy containing molecule ATP.” Whereas the energy in ATP is, in fact, the energy of ATP’s relatively high energy electrons, a.k.a. reducing power. ATP doesn’t DO anything in biological systems. It is the transfer of electrons from the high energy bonds in ATP that actually do the useful work. Bioelectrochemistry in living systems is a combination of ionics, electronics, and electrodics. It’s too bad you don’t appear to understand that. Finally, anyone who doubts the importance of the valence bond (which is composed of electrons… not ATP) in biological life processes needs to reconsider their position very carefully.

    As for misunderestimating biology, I’m afraid you have the players reversed. You may not “literally” be the same person you were, but you have many of the same biomolecular components. A normal woman carries her eggs for decades … and that’s just a simple example. Some molecules turn over by the minute but many others have lifetimes of days, months and even years. More to the point, biomolecules incorporated into bionano devices may or may not be accessible to normal turnover systems within the body. That, in fact, is a major point that needs to be addressed in the design of nanobiosafety guidelines. Your self-serving assumption that biomolecular components within nanobiobots will follow the same turnover rules as ‘normal’ biomolecules is exactly the type of ‘inside the box’ thinking that my article is designed to warn against. You may feel secure in that box but, hopefully, there are others who will want to take a look outside.

    I am alo sorry that you misrepresent my position on Entropy since I make it quite clear that the Second Law must be applied to the total system under consideration rather than just the biological life forms within the system.

    I would be happy to engage in a serious discussion with you in an appropriate forum. You sound like a relatively bright guy in need of an education in molecular biology. Rote concepts like, “The energy currency of biology isn’t electricity, it’s chemistry – specifically it’s the energy containing molecule ATP.” are straight out of Biology 101. If you can’t see any more deeply into the mechanisms of life than that, you are certainly not ready to follow my thinking about how nano and bio will interface, much less provide a serious critique of my theories.

  6. Alan, thanks for taking the time to reply to my post. I notice that you do not comment on my suggestion that you are wrong to impy that electron transporting molecules cross the membrane of pace-maker cells, nor do you clarify the crucial difference – glossed over in your piece – between equilibrium self-assembly and non-equlibrium self-organisation and pattern formation. Nor do your address the central philosophical issue about how one can sensibly talk about life without information, as well as metabolism.

    You are of course right to say that I need an education in molecular biology – we all need to learn more. I didn’t do biology 101; I’m a physicist (albeit one who has learnt enough biology to collaborate with some serious molecular biologists, to publish in good, peer reviewed, biological journals and to write a well-received book with a strong biological component). But there’s a lot physics can tell us about the way biology works. One thing it says is that your notion of permanent binding of a molecule to a receptor just can’t be right. For very good reasons, the energy scale of all interactions involved both in self-assembly and molecular recognition events is set by kT, Boltzmann’s constant times temperature, and this means that all such interactions are necessarily temporary. A very good reference for this kind of issue is Phil Nelson’s textbook “Biological physics: energy, information, life”.

    As for your comment about the role of electrons in ATP, well of course you’re right in one sense, that all the physical phenomenon we encounter, apart from radioactivity, fission and fusion, depend only on the electromagnetic force. But at this level the statement is trivial and empty. You were arguing for a special connection between the physics exploited in our semiconductor devices and the processes of life. The difference between the roles of electrons in the two situations is fundamental – semiconductor physics depends on coherent electron transport, a process that to my knowledge is important in only one biological context – the electron harvesting processes that go on in photosynthetic centres. The energy transfer processes that are involved when ATP is hydrolysed in a motor protein, or indeed when it is synthesised by ATP-synthase using energy stored as a hydrogen ion gradient, involving a subtle interplay of Brownian motion and weak interactions, are quite different, with no role at all for coherent electron transport of the kind that underlies the electrical phenomena we are familiar with at the macroscopic scale.

    I look forward to offering a critique of your theories as you develop them. In the meantime you have the advantage, because my views about how nano- and bio- will interface are laid out at some length in my book. I do, in fact, agree with you that this interface will offer some serious ethical challenges. I also agree with you that thinking about these issues is difficult, unfamiliar and non-intuitive. That doesn’t excuse us from the need to keep an anchor of scientific accuracy.

  7. -“A virus isn’t truly alive, because it consists only of information – it has to borrow a metabolism from the host it parasitises to reproduce. ”
    If a bacteria isn’t alive, then what is? Isn’t that exactly what complex life forms are build upon? it is just a compilation of information. without the environment, it is obvious to say we would not be here. We are the parasite. Just like they are. Every move they make is just because they respond, for whatever reason, to their environment. Don’t We? So you say, ‘we think’. yes we do. but our bains are themselves composed of information. the ones of our past. Now, it makes you think how much different we are to a bacteria…or even a photon. Entropy always rises, yes…but the only reason life seems to be the only exeption is because we only see the present. The future…will always bring more entropy….even if certain instances in the present don’t.
    i’m tired.
    what u think?

  8. Eric, I’m not entirely sure what you’re getting at here. Bacteria certainly are alive, because they do have their own metabolism, given supplies of essential chemicals from the environment they can replicate themselves. Viruses don’t just need to get food and energy from their environment, they need to borrow the mechanisms for self-replication as well. So, fundamentally, we aren’t that different from bacteria, but we are from viruses.

  9. Phillip, those were an interesting pair of papers. They’re using the electrical properties of diamond – in the first example, using thin diamond films as the channel of an FET which is gated by surface adsorption of target species – rather than its optical properties.

  10. Yeah, the papers utilized FETs, not LEDs. But diamonds will make good LEDs and this property can be used for biosensor applications. This patent is where I got the idea while looking to see if MNT power systems would scale (with diamond solar panels):
    And here is an abstract describing an all diamond LED:

    I’m hyping diamond properties, but I have good things to say about the versatility of nanogold and CNTs as well.

  11. Phillip, I’m not sure that a diamond LED is what you want for a biosensor application – because it has a wide band gap it emits in the UV (your Science ref quotes 235 nm). The absorption coefficient of water rises very steeply as you get into the UV (I’d need to look up an absorption spectrum to see precisely how far up the slope 235 nm is). The other issue in principle with basing a sensor on an LED is that the operation of LEDs is fundamentally something that happens in the bulk of a material. The chemfet principle works so well at the nanoscale because you can confine the conduction to a region very close to a surface, which is thus very sensitive to adsorbed species. If you want an optical property that is very sensitive to the surface, then plasmon spectra in metals are the place to look. This is what underlies the amazing sensitivity of surface enhanced Raman scattering, for example. I’ve just got a very interesting preprint from a friend (a compatriot of yours, at Waterloo) showing this sort of principle being used to detect, not just the presence of a protein, but changes in its conformation, at the surface of gold nanoparticles.

  12. Dear Richard:

    As I said, I would be happy to go point-for-point with you in some forum that provides a significant readership. Blogs, like opinions, are available to (almost) everyone and read by almost no one… so I won’t do any further posting here. It is too bad that you don’t get my point about the unifying role of chemical bonding in nanobiotechnology. You say, “semiconductor physics depends on coherent electron transport.” But I say electron transport is the symptom, so to speak. It is the physical chemistry necessary to fabricate the semiconductor that is the key enabling technology. The explicit goal of nanobiotechnology is to integrate the chemistries of living and nonliving systems. If you think you know what that means, I think you are seriously deluded. A simple, almost trivial example of nanobio being used to ‘direct’ electron transport would be a semiconductor that transfers electrons to a redox enzyme immobilized via nanofabrication. And while you should certainly be proud of having a book out, I have published tens of thousands of words in my articles on nanobio and related topics so I don’t think my specific views are much more difficult to find than yours. Perhaps you have published a few diagrams of your vision of the nano-bio interface but, frankly, the literature (both peer reviewed and otherwise) is replete with such things as well as a few actual prototypes. The guidelines in my most recent article are based on science not speculation. And, while they certainly will need to be refined, the general principles are quite sound.

  13. Alan, I’m glad at least that you have moved your argument away from simply asserting my ignorance of biology, but I’m disappointed that you are still unprepared to respond to my criticisms in any kind of specific way. Of course, if you find a forum for a head-to-head debate I’ll be very happy to take part. It’s possible, though, that you underestimate the readership of this (and other) blogs – this site has received more than 30,000 visits so far this month.

  14. Alan, I’m not sure about readership, but in terms technical quality of content this blog is among nanotechology’s highest.

    Richard, I think the wide bandgap benefits of diamond outweight the defiencies it brings. A wide bandgap makes it an accurate biosensor. That is necessary to cap false positives. But I’ll post again in a week or two a more detailed blueprint. The specific application I had in mind was a ventillation shaft sensor for microbes. It is operating in an air environment, not water.

  15. To next month’s 30,000 readers:

    Like many people I try my best to keep my word and it was not my intention to post here again. However, I feel I must direct your attention to the Physics Web site at . The article is titled “The future of nanotechnology” and authorship is attributed to Richrd Jones. In this article is the following statement, “We should also stop worrying about grey goo, because it is going to be very hard to produce more highly optimized nano-scale organisms than nature has already achieved.”

    This statement is so stunningly flagrant in its disregard for the potential of nanobiotechnology to create bioweapons of unimaginable capacities that it borders on complete irresponsibility. Richard, if this is indeed an accurate representation of your position then the readers who visit this site certanly do not need me to assess your knowledge of biology.

  16. We don’t even pretend to be scientists.

    But we know a thing or two about the psychology and sociology of the scientific community.

    Isn’t it interesting that, when industry puts out ridiculous hype about the wonders of nanotechnology, the scientists are mute?

    But, when somone, even a fellow scientist, questions the wisdom of nanotechnology, the poor fellow is demonized as “unscientific”?

    Where is the criticism of the unscientific nano-hype from the scientific community? Or would such unseemly criticism jeopardize your grants?

  17. Welcome back, Alan. I’m glad you’ve taken the trouble to do some reading. Do you really think that we are on the verge of being able to make wholly synthetic, self-replicating objects that are able to sustain themselves from environmental sources of energy and chemicals inputs? Do you further believe that these self-replicating objects will easily be made more effective – more fit – than the bacteria that have evolved to fill this role over millions of years? This is what is being argued here, not whether or not bionanotechnology has the potential to raise ethical, environmental or philosophical dangers. We already stressed that there were such potential issues in the report I co-wrote (Social and economic challenges of nanotechnology), published by the UK government in 2003. I think we are many, many decades away even from being able to make the crudest self-replicating device, let alone an efficient one. I’ve written a brief assessment of some of the routes towards biomimetic nanotechnology and some of the barriers in the way in this article in Journal of Polymer Science, Polymer Physics Edition – I posted a draft of this piece here for those without a subscription to the journal.

    If you do want to debate this issue seriously, I’d be interested to hear your views about how, quickly, scientists would overcome those huge gaps in their capabilities. What would the information storage and replication system be? What would you use as an analogue of ATP as an energy storage and transduction molecule? How would you solve the protein folding problem and design molecules capable of allostery? In each of these three central issues, I don’t believe that there is a glimmer of a solution that does not involve co-opting existing biological structures.

    I also note that, three replies on, the technical criticisms I made of your original article remain unanswered and unaddressed.

    T.H.O.N.G. – I’m not demonising Goldstein – I’m just pointing out where I think he’s in error, and giving him the opportunity to defend his point of view. But your point about the lack of criticism of unscientific nano-hype isn’t entirely without foundation. I can’t speak for the rest of the scientific community, but I’ve done my best to say what I think. Among the growing list of people who aren’t speaking to me is Nathan Tinker, of the Nanobusiness Alliance, who I criticized for unscientific nano-hype here. I’ve just received the galley proofs for a piece I wrote for Nature, which will be published in a couple of weeks, that I suspect is going to ruffle some more feathers – I’ll post this when it’s in print. We will see whether my grants survive!

  18. With respect to the Grey Goo concept:

    1. How many molecular reaction take place spontaneously every second in earths biosphere.

    2. How much biological material exists on earth that can interact to form larger or smaller biologically active components

    3. Given the age of the earth why doesn’t Grey Goo exist already?

    The Grey Goo concept seems to suggest we will invent some agressive biologically active molecue which has not been created in earth history?

    Or did I miss something?

  19. We appreciate your even-handedness on the issue, Dr. Jones. Our remarks were addressed more to others in the scientific community.

    We too are on the Nanobusiness Alliance’s blacklist — our first intervention in nanotechnology occurred at an event co-sponsored by the N.A. We consider you good company, ‘though you might well object to that.

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