Wednesday, June 21, 2006

Who’s afraid of nanoparticles?

Lots of people, it seems. They have the potential to become the new DDT or dioxins or hormone mimics, the invisible ingredients of our environment and our synthetic products that are suspected of wreaking biochemical havoc. I don’t say the notion is ridiculous, but we need to keep it in proportion. The Royal Society/RAE report on the hazards and ethics of nanotechnology did a good job of giving some perspective on the concerns: we shouldn’t take it for granted that nanoparticles are safe (even if their bulkier counterparts are), but neither are we totally ignorant about exposure to such particles, and it is unlikely that we can make many generalizations about their health risks. Certainly, we need legislation to stop these tiny grains from slipping through current health & safety regulations.

My recent article on the damaging effects that titania nanoparticles apparently have on mouse microglia, the defensive cells of the brain, will probably be welcomed as ammunition by those who want a moratorium on all nanoparticle research. It does not give grounds for that – this research is a long way from establishing actual neurotoxocity – but it does give pause for thought about nanoparticle sun creams. I rather suspect this stuff is not going to be a major hazard, but we can’t be sure of that, and I confess that I’ll prefer to avoid them this summer.

For various mundane reasons, some comments by the EPA researchers involved in this work didn’t make it into the article. But they help to put the implications in perspective, and so I’m posting them here:
Responses from Dr. Bellina Veronesi
Question: Apart from sun creams, which consumer products that involve contact with the human body currently use titania nanoparticles?
Answer: Cosmetics, prosthetics (artificial joints, for example)
Question: You mention toothpaste and cosmetics - do you know of specific examples of these?
Answer: Most product labels would probably not note if a given chemical concentration was in the “nano” range. Often times, the titanium oxide is listed in the ingredients, but is not identified as "nano-." More specific information might be considered to be confidential business information (CBI) and not available.
Question: I'm finding it hard to see from the paper exactly how long the production of ROS tended to continue for after the microglia were exposed.
Answer: Over a 120 minute period, which was the extent of our measurements.
Question: It seems that the worry is not about the response per se, but that it is sustained.
Answer: The concern from the neurobiology/neurotoxicology point of view is that a cell type (the microglia), whose job it is to react to offending foreign stimuli in the brain by releasing free radicals (ROS), is doing just that in response to nanosize Titanium dioxide. If those free radicals are not neutralized by anti-oxidants present in the brain (Vitamin C, Vitamin E, super oxide dismutase), they can damage neurons.
But remember, these measurements were made in isolated microglia, so we can't yet say if it is neurotoxic. Rather, the next step would be to examine the consequences of ROS release in a more complex culture system consisting of mixtures of brain cells, including microglia and neurons. Based on those findings, we would then test in animals.
Question: What do we know about how such nanoparticles might get transported around the body? Can you say anything about the chances of them reaching the brain?
Answer: Experts such as Dr. Wolfgang Kreyling (GSF Institute for Inhalation Biology (Munich)) have shown that nanosize particles, such as TiO2, can leave the lungs of exposed animals and distribute to other organs. However, it is still undetermined whether TiO2 can cross the blood brain barrier and enter the brain.
Question: Can you say anything about whether the concentrations you studied might be realistic in terms of exposure levels?
Answer: It is not “good science” to extrapolate in vitro data to whole animal/human response. There are many obligatory steps/test models that must be tested first. Similarly, our study was not designed to assess whether the test concentrations used in the cell culture studies have relevance to those found in consumer products.
Question: How worrying are the results at this point, given that they are not in vivo studies?
Answer: This was a carefully designed study that followed a format prescribed in the nanoparticle scientific literature ((Nel et al., Science 2006) That format entails moving from cell culture to animal testing in a tiered fashion. We are examining further the possibility that TiO2 may be neurotoxic in culture. If these results prove positive, we will adhere to the format and next test in more complex culture models that use neurons or dissociated whole brain to determine. Results of these studies will determine if animal studies should be pursued.
Question: What are the major uncertainties about how the findings might translate to humans, and what are the next steps?
Answer: This study exposed TiO2 to isolated, brain cells taken from a mouse. Within the confines of this model, it would be speculative to say what the effects would occur in human cells, let alone a human being. Such a prediction requires an extremely lengthy course of testing, involving successively more complicated experimental models. As I noted in my previous answer, we will follow a format that allows for such sequential research.
Question: How do you feel about the fact that titania nanoparticles are currently in use in consumer products? Would you want to use such products yourself?
Answer: Nano-size TiO2 has been in commercial use/multiple routes of human exposure for several years, providing great benefits without incident. Numerous already published studies give TiO2 (nanosize, larger size) a clean bill of health.
The uniqueness of this study is that we are looking at the response of cells with very high resolution, state-of-the-art measurements. Again, this is the initial stage of a very lengthy experimental process the findings of which will provide better insight and guidance related to the use of such products.

Wednesday, June 14, 2006

To boldly go…?

My Nature article on NASA’s manned spaceflight program has drawn some flak, as I suspected it might. That’s good – it is only by compelling people to voice their arguments for such a goal, rather than taking its validity as a self-evident truth, that we can assess them. And how woeful they can seem. Certainly, I find it depressing when people suggest that the only way the human race can survive is to get off the planet as soon as possible. I’m struck also at the difference in attitude between the US and the rest of the world – it really does seem as though the national narrative of frontiers and pioneers in the States shapes so much of public thinking in a way that just doesn’t resonate elsewhere. I don’t want to be too critical of that – it’s surely driven some of the great American achievements of modern times. But I do wonder whether it has led to distortions of history all the way from Columbus’s voyage to the Apollo missions – for example, a failure to appreciate how much commerce and military dominance have played a part in such events. That's certainly brought out in the gobsmacking article by Michael Lembeck mentioned by one of the correspondents - read it and weep. I've responded to that on the Nature site.

Brian Enke makes a new point, however: that manned spaceflight is needed to keep the public on board. I took this up with Brian, and we've had what I think is a productive exchange (certainly more so than some of the stuff posted on the Nature weblog). Here it is:

Dear Brian,
Your comment on the Nature weblog raises an interesting point that I'd not heard put before: that a manned space program is necessary to keep the public on board in funding space science. As a pragmatic expedient, I could accept that. If the only way public funding of space science can be sustained is to provide the public with the justification that ultimately the aim is to get us ‘out there’, then so be it. But that would be a sad state of affairs, and one that I'd find somewhat intellectually dishonest. It may be that some space researchers do indeed feel this is the appropriate end goal, but I suspect that just as many would argue that it is right to fund intellectual inquiry into the universe and our place in it just as it is right to fund any other kind of basic 'big' science, or indeed to fund research on history or linguistics or to give money to the arts. High-energy physics does not need to appeal to any great mission beyond that of finding out about the world. Space science poses equally grand questions, and these ought to be justification enough. Certainly, I find it highly disingenuous to argue (as some have done, though you have not) that manned spaceflight is warranted for economic reasons such as space mining and tourism. I take the point that, in the current climate, science has to be able to 'sell itself', but I'd prefer that we can be as honest as possible about why it is being done.

I'm not against manned spaceflight per se. Indeed, I think we need it for good space science: the Hubble repair showed just why it is valuable to be able to put people into low-Earth orbit. And if we could put a person on Mars tomorrow, I'd be hugely excited. I simply don't see the latter as such a priority that it needs so much of NASA's budget channelled in that direction. This is really the point: the science is suffering, and at the expense of a politically motivated program. I agree that it would be wonderful for NASA to be given enough money to do all things well (I can't say I'd consider the money well spent that would go on a manned mission to the moon or Mars, but I'd rather that than have it spent on defence). But this isn't going to happen, it seems. With limited resources, it seems a tragedy to have to devote so much of them to what is basically a PR exercise.

The international scientific community owes NASA a huge debt of gratitude for the fantastic things it has done. But it does seem to me that Mike Griffin is now having to practice some realpolitik that goes against his inclinations, and that seems a shame.
Best wishes,

Hi Phil -
Thanks for the comments - it's always exciting to have a good dialogue on these issues. Most of the time, people end up stomping around, posturing, blind to any alternative viewpoints, and ultimately frustrated for that very reason.

I was simply pointing out how things are, motivationally, rather than how they "should be" (if anyone could ever possibly agree on that). I hear your words, respect your opinion, and agree with most of it... but I personally don't have a problem with science being MORE than a mere intellectual pursuit. If science can lead to something tangible, so much the better. That's how you tie into real funding... make a business case for the science. Otherwise, we're left over with the dregs - mere stipends that keep a program alive but lacking inspiration and excitement. Off my philosophy box... ;)

Here's a major point for you to consider quite carefully. You refer to "the NASA budget" below, as is common... but what exactly IS "the NASA budget". You can take the stipend view - our government doles out X amount of dollars to create Y number of high-tech jobs, and what comes out of it really doesn't matter. In that sad state of affairs, one science job equals one engineering job, more or less... and one science dollar equals one human exploration dollar. Again, what is accomplished doesn't matter - it's all a line-item in the federal budget - a happy-pill to placate the masses. OR you can take (IMHO) a far more progressive view - the NASA budget is a combination of individual programs, each of which has meaning and stands strongly on its own merits. Sounds much more honest, right? But watch out - here's the trap - in that progressive view, taking a dollar away from human spaceflight doesn't necessarily add a dollar to space science research. They are individual programs - and the budgets must (eventually) be justified individually. Taking a dollar from human spaceflight eliminates a dollar from the federal deficit. That's it, period.

As we all know, in reality, NASA is a combination of the two approaches... and it IS likely that taking a dollar from human spaceflight will (in the short-term) add a dollar, or 50 cents, or a dime, or whatever to space science. This effect is little more than a local optimization within the government bureaucracy. Long term, it's obvious that everyone at NASA loses, as I pointed out in my initial comments.

There's one other trap in the above paradigm.... or rather a juicy angle for us to exploit. If each program truly stands on its own merits, then a dollar of space science funding equals a dollar of hurricane Katrina relief or Iraq whatever-they're-doing-over-there. Better yet, it's a dollar of Medicare fraud. In this budget-view, there is ZERO reason to take money away from human spaceflight. Bob Park is notorious for preaching a flawed, divisive premise - he wants to fund space science at the explicit expense of the human spaceflight community. Winners vs Losers. I'm going to eat your cake because I like cake, and your piece looks really yummy. Why did he decide to pick on human spaceflight? Did a manned rocket land on his cat or something? Why isn't he on a rampage against Medicare - which wastes nearly twice the entire NASA budget every year funding fraudulent claims?

A robust space industry is either a national priority or it isn't. If space is important, we'll have plenty of funds for space science AND human exploration. If not, we won't. So... I'd rather dedicate my personal efforts toward increasing public awareness of the importance of space science AND exploration. That way, we all win.

- Brian

Dear Brian,
You almost persuade me. That's to say, if NASA budgetting really isn't a simplistic zero-sum game, then I can see the case for why I shouldn't be too concerned if the US administration wants to spend billions on a program that doesn't strike me as having much intrinsic value at this point in time. But it does seem clear that increases in spending on manned spaceflight have taken money from science projects, even if not in a directly zero-sum manner. I do understand and accept your point, however, that providing a vision that captivates the public might in the long term mean that the science gains too.

I suppose I also can't suppress some concern that that vision can lead to snowballing rhetoric that some people take seriously, so that we end up with chaps like the one on the Nature weblog who genuinely believe that humanity is doomed if we don't get on and colonize the moon or Mars quickly. That seems a bit unhealthy.

In any event, thanks very much for your considered response - it has given me something to think about.
With best wishes,

Hi Phil -
I've truly enjoyed our exchange, and I admire your open-mindedness. Perhaps you even want to throw in a mention of my recent science fiction novel, Shadows of Medusa? It turned out to be a fun read, I'm happy to say, and it touches on the theme we've been discussing - that science and human exploration can co-exist (though I take some fictional liberties and digressions, heh heh). If anyone out there wants to order the book, they should go through the website, though... because the full publisher price on Amazon is a total rip-off.

And I agree - there are some reasons for exploring and settling space thrown about occasionally that I don't personally agree with either. Sometimes you have to step back and say, "hmmm... no thanks." But on the other hand, most of the time the people with the opinions strongly believe them, and one has to be extremely cautious and respectful when stepping on people's beliefs. I suppose that's MY belief. :)

In fact, tying that position into the whole government budget and zero-sum game matter... I don't personally believe the government should be spending MY money (there's a charged term you hear all the time) on certain things that I don't see much intrinsic value in. And I reserve the right to complain about it occasionally. But I do have to recognize and accept that for every single government dollar spent, someone out there somewhere feels very strongly that it's being spent well.

So in the end, perhaps "almost" being persuaded by someone is a good thing, if it leads to a healthy dose of tolerance.

Oh, one more parting thought, spurred by what you noted below: "it does seem clear that increases in spending on manned spaceflight have taken money from science projects". Agreed again - it shouldn't be that way in a perfect world, but that's just the way it is. On the other hand, one can find examples of spending in human spaceflight leading directly to increases in science spending. Our LAMP instrument (in my day job, I work at the Southwest Research Institute) is a great example - it will fly on the Lunar Reconnaissance Orbiter, an entire juicy science mission funded/motivated with human exploration dollars. This is beautiful synergy - great science coupled directly with human exploration. Personally, I'd like to see more of that.

- Brian