Musings of a Cancer Doctor
Wide-ranging views and perspective from George W. Sledge, Jr., MD
Tuesday, February 18, 2014
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My favorite movie of 2013 will not win an Oscar. Entitled “A Boy and His Atom,” it is directed and produced by IBM scientists, and is a totally charming short celebrating nanotechnology. You actually view individual atoms being moved around. Not big on plot, but delightful nevertheless, it can be seen on YouTube at: http://www.youtube.com/watch?v=oSCX78-8-q0

 

Nanotechnology is one of those unfulfilled promises, made years ago, that is just so compelling that we keep giving it second (and third, and fourth, and fifth) chances. It has to come true at some point. Just what that point is, and just how it will manifest itself, is uncertain, but virtually all agree that something will come of it.

 

What do we even mean by nanotechnology? A few years ago albumen-bound paclitaxel was introduced to the world as the first nanotechnology drug. If slapping some egg white on Taxol is nanotechnology, then I’m the King of Siam: really quite ridiculous, but “Abraxane is nano” has had an astonishingly long run. “Doxil is nano” as well: fat droplets = nanotechnology. I’m not convinced that putting a drug in a different wrapper really qualifies, but what do I know?

 

Part of the problem is definitional. The Google definition (“the branch of technology that deals with dimensions and tolerances of less than 100 nanometers, esp. the manipulation of individual atoms and molecules.”) is fine, but basically only tells you that really small stuff is nanotech. What does “manipulation” mean? My fingers aren’t 100 nanometers.

 

I think of nanotech in the way that Nobel laureate Richard Feynman did. His foundational talk, titled “There’s Plenty of Room at the Bottom,” was presented in 1959, and still delights. In it he speaks of “a very wild idea, it would be interesting in surgery if you could swallow the surgeon. You put the mechanical surgeon inside the blood vessel and it goes into the heart and ‘looks’ around. (Of course the information has to be fed out.) It finds out which valve is the faulty one and takes a little knife and slices it out. Other small machines might be permanently incorporated in the body to assist some inadequately-functioning organ.”

 

Feynman went even further: “But I am not afraid to consider the final question as to whether, ultimately – in the great future – we can arrange the atoms the way we want; the very atoms, all the way down!” The great future was well within the lifetime of some in his audience, witness to the escalating speed of technology. Witness “A Boy and His Atom.”

 

That’s what I think of when I think of nanotechnology: really little machines. “Swallowing the surgeon” eventually became the concept of nanobots injected to fix molecular defects. The futurist Ray Kurzwell speaks of an era (he predicts 2030) when we are loaded with billions of these tiny machines, which communicate with the Cloud, and are endowed with what he calls “a measure of intelligence.” They will put medical oncologists (and many other specialists) out of business through preventative maintenance. In theory, I suppose, I may live long enough to benefit from these nanobots while still drawing on my pre-nanobot medical pension. Sweet!

 

Kurzweil takes something like 150 nutritional supplements per day in hopes of delaying his death long enough for the nanos to render him immortal, which suggests he either knows a great deal more or a great deal less than I do about nutritional supplements. He recently went to work at Google, which is beginning to get into the immortality biz. You can see Kurzweil interviewed by the Wall Street Journal here: http://blogs.wsj.com/cio/2014/02/04/googles-ray-kurzweil-envisions-new-era-of-search/

 

The best way to know that something is real in medicine, rather than some pipe dream, is when there’s a medical journal devoted to it. And, of course there is: it’s called Cancer Nanotechnology. I went and looked at its table of contents. The first article I espied was “Pharmacokinetics and biodistribution of negatively charged pectin nanoparticles encapsulating paclitaxel.” You know pectin: the agent you add to jam or jelly to help them thicken. Pectin. Really? Nanotechnology? Maybe I am the King of Siam.

After medical journals, your next best bet in seeing whether something is real is to measure government response. The NCI’s Nanotechnology Characterization Laboratory performs nanomaterial safety and toxicity testing in vitro and in vivo. To date it has evaluated over 250 potential nanomedicines, several of which are making their way to the clinic.

 

One likes to think of nanotech as essentially benign. But the long-term safety of nanomedicines is one of the great imponderables: there just haven’t been any studies. When I was an intern, a cardiology fellow shared some folk wisdom with my team: “If you haven’t had any complications, you haven’t done enough procedures.” True then, true now. My bet is that we’ll discover some new side effects.

 

And it’s not just nanotech side effects at the individual level that technologists worry about. Consider the “Gray Goo” scenario much beloved by nanotech Cassandras and science fiction authors. In the Gray Goo scenario, originally described by the nanotechnologist Eric Drexler, self-replicating von Neumann machines consume all of the matter on Earth while dividing uncontrollably. All that’s left of us and everything else is a large ball of Gray Goo. Yuck.

 

Realistic? Maybe yes, maybe no. If it is, get me out of here: some idiot dictator will release it by intent, or some lab tech by mistake. The Feds certainly take it seriously: the Department of Defense had a $426.1 million nanotechnology budget in 2012. The nanotech budget was less in 2013, but that may be sequestration.

 

The National Nanotechnology Initiative website says the “DOD considers nanotechnology to have potential to contribute to the warfighting capabilities of the nation… The DOD also invests in nanotechnology for advanced energetic materials, photocatalytic coatings, active microelectronic devices, and a wide array of other promising technologies.” I don’t worry about photocatalytic coatings (Pectin, anyone? Egg white on your drone?) But “active microelectronic devices” and  “other promising technologies” are probably what we need to look out for.

 

Back to medicine. One of the cooler new technologies, just firing up but already attracting attention, are ADARs (adenosine deaminases acting on RNA). ADARs allow one to edit RNA transcripts, correcting mutations at the transcript level. A recent paper (Montiel-Gonzalez et al. PNAS 2013; 110: 18285-90) showed the potential of this technology to correct a mutation causing cystic fibrosis. It’s early days yet (cell line works, not yet at the organism level), but a star-struck molecular biologist writing in the New England Journal of Medicine referred to the approach as “an RNA-repairing nanomachine within the limits of current technology.”

 

So maybe we’re not all that far off from the day when nanotech will correct all our inherited defects. I certainly have my share, and I’ve accumulated a few others along the way. Ultimately, of course, what constitutes an inherited defect will represent a novel problem of definition. Is your nose too small? There’s an ADAR for that!  (Note to my readers: nose = a family-friendly euphemism). I see a thriving industry targeting professional athletes and Hollywood actors, and soon all the rest of us. We’ll all look like Brad Pitt and Angelina Jolie, all run like Jesse Owens, and all live forever.

 

Yeah, right. And egg white and pectin are nanotech.

About the Author

George W. Sledge, Jr., MD
GEORGE W. SLEDGE, JR., MD, is Chief of Oncology at Stanford University. His OT writing was recognized with an APEX Award for Publication Excellence in the category of “Regular Departments & Columns.”