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Book Review: How does the body react to medical nanodevices?
Nanomedicine, Volume IIA: Biocompatibility, the second volume in Robert A. Freitas, Jr.'s Nanomedicine series, has been published just in time to provide an authoritative scientific foundation to address the growing concerns about the biocompatibility of nanotechnology in the environmental and medical communities.
Originally published in Foresight
Update August 31, 2003. Published on KurzweilAI.net November
18, 2003.
For the last 4 years, Robert Freitas has been teasing us with brief
extracts from his forthcoming Nanomedicine,
Volume IIA, in his quarterly nanomedicine articles for Foresight
Update. The second installment of this famous series is
in press and should be out by September 2003. A full online version
will appear in the months to come, though an outline is available
now at Robert's nanomedicine site http://www.nanomedicine.com/NMIIA.htm.
There are now four books in the Nanomedicine trilogy—what
began as a single chapter in Volume II has grown into a book: Volume
IIA. This is hardly surprising when we consider how critical biocompatibility
is to the safety, effectiveness, and utility of medical nanorobotic
devices, and the magnitude and complexity of the subject matter.
In his usual thorough fashion, Freitas gives us an overview of
essentially the entire field of biocompatibility as it relates to
medical nanorobots and the materials that might be used in their
construction. While the target audience is "biomedical engineers,
biocompatibility engineers, medical systems engineers, research
physiologists, clinical laboratory analysts, and other technical
and professional people who are seriously interested in the future
of medical technology" this volume comes at a timely juncture:
published concerns about the biocompatibility of nanotechnology
are growing in the environmental community, and a solid foundation
on which to base the discussion is greatly welcomed. This new book
provides a technical tour-de-force and a treasure trove of facts,
ideas, and recent research results, with an extensive 1400-entry
glossary and over 6100 literature citations in the reference list,
representing 8000 man-hours of effort by the author. This book
should be the starting point for anyone planning a serious research
program in medical nanorobot design.
Perhaps the best way to give the reader an overview of what Nanomedicine
Volume IIA is all about is to quote a few words from Freitas
describing just part of this Magnum Opus:
"Compatibility" most broadly refers to the suitability
of two distinct systems or classes of things to be mixed or taken
together without unfavorable results. More specifically, the safety,
effectiveness, and utility of medical nanorobotic devices will critically
depend upon their biocompatibility with human organs, tissues, cells,
and biochemical systems. Classical biocompatibility has often focused
on the immunological and thrombogenic reactions of the body to foreign
substances placed within it. In this Volume, we broaden the definition
of nanomedical biocompatibility to include all of the mechanical,
physiological, immunological, cytological, and biochemical responses
of the human body to the introduction of medical nanodevices, whether
"particulate" or "bulk" in form. That is, medical
nanodevices may include large doses of independent micron-sized
individual nanorobots, or alternatively may include macroscale nanoorgans
(nanorobotic organs) assembled either as solid objects or built
up from trillions of smaller artificial cells or docked nanorobots
inside the body. We also discuss the effects on the nanorobot of
being placed inside the human body.
In most cases, the biocompatibility of nanomedical devices may
be regarded as a problem of equivalent difficulty to finding biocompatible
surfaces for implants and prostheses that will only be present in
vivo for a relatively short time. That's because fast-acting medical
nanorobots will usually be removed from the body after their diagnostic
or therapeutic purpose is complete. In these instances, special
surface coatings along with arrays of active presentation semaphores
may suffice. At the other extreme, very long-lived prostheses are
already feasible with macroscale implants such as artificial knee
joints, pins, and metal plates that are embedded in bone. As our
control of material properties extends more completely into the
molecular realm, surface characteristics can be modulated and reprogrammed,
hopefully permitting long-term biocompatibility to be achieved.
In some cases, nanoorgans may be coated with an adherent layer of
immune-compatible natural or engineered cells in order to blend
in and integrate thoroughly with their surroundings. Today (in
2002), the broad outlines of the general solutions to nanodevice
biocompatibility are already apparent. However, data on the long-term
effects of implants is at best incomplete and many important aspects
of nanomedical biocompatibility are still unresolved—and will
remain unresolved until an active experimental program is undertaken
to systematically investigate them.
Since a common building material for medical nanorobots is likely
to be diamond or diamondoid substances, the first and most obvious
question is whether diamondoid devices or their components are likely
to be hazardous to the human body. Chapter 15.1 briefly explores
the potential for crude mechanical damage to human tissues caused
by the ingestion or inhalation of diamond or related particles.
There are varying degrees of potential mechanical injury and these
are probably ultimately dose-dependent. It will be part of any
medical nanorobot research project to determine the actual amount
of diamondoid particulate matter necessary to cause clinically significant
injury.
A great deal of preliminary information is already available on
the biocompatibility of various materials that are likely to find
extensive use in medical nanorobots. Chapter 15.3 includes a review
of the experimental literature describing the known overall biocompatibility
of diamond, carbon fullerenes and nanotubes, nondiamondoid carbon,
fluorinated carbon (e.g., Teflon), sapphire and alumina, and a few
other possible nanomedical materials such as DNA and dendrimers—in
both bulk and particulate forms.
One of the more interesting issues is that medical nanorobots might
be consumed by the body's defenders, the white cells. Thus, nanorobots
will have to dodge, pacify, or escape from their embrace. As Freitas
observes: "... all nanorobots that are of a size capable of
ingestion by phagocytic cells must incorporate physical mechanisms
and operational protocols for avoiding and escaping from phagocytes.
The basic strategy is first to avoid phagocytic contact, recognition,
or binding and activation, and secondly, if this fails, then to
inhibit phagocytic engulfment or enclosure and scission of the phagosome.
If trapped, the medical nanorobot can induce exocytosis of the phagosomal
vacuole in which it is lodged or inhibit both phagolysosomal fusion
and phagosome metabolism. In rare circumstances, it may be necessary
to kill the phagocyte or to blockade the entire phagocytic system.
Of course, the most direct approach for a fully-functional medical
nanorobot is to employ its motility mechanisms to locomote out of,
or away from, the phagocytic cell that is attempting to engulf it.
This may involve reverse cytopenetration, which must be done cautiously
(e.g., the rapid exit of nonenveloped viruses from cells can be
cytotoxic). It is possible that frustrated phagocytosis may induce
a localized compensatory granulomatous reaction. Medical nanorobots
therefore may also need to employ simple but active defensive strategies
to forestall granuloma formation."
And, as always, Freitas is famous not just for his thorough coverage
of the field, but also for the historical side lights that enliven
his text. Pounded diamond dust, for example, was used by assassins
through the ages—an observation that inspired Freitas to investigate
the issue more directly by examining pounded diamonds with a scanning
electron microscope (SEM) and confirming that "even a single
hammer blow produced numerous particles of a wide variety of sizes
(0.1-100 micron), many possessing sharp ragged 'fishhook' edges,
deep angular concavities, serrations, irregular holes, and other
interesting features." No doubt of greater concern to his
wife was his earlier report (http://www.nanomedicine.com/NMI/9.5.1.htm#p3)
of self-experimentation with (albeit uncrushed) diamond powder,
finding that "even irregularly-shaped diamondoid particles
~3 microns and smaller apparently roll smoothly out of the way when
ground between the teeth, whereas particles larger than ~3 microns
cannot roll sufficiently and retain a sensible grittiness."
This excellent volume provides us with yet another authoritative
analysis of issues that are critical to the development of nanomedicine—and
again makes clear that, while there is much to do there are no insurmountable
obstacles nor fundamental barriers that stand in our way.</p>
<p>To end with a question: do you expect to be alive in thirty years?
If so—and most people do—then the development of nanomedicine
within that time frame will benefit you directly. The medical nanorobots
we are talking about could save your <a href="javascript:loadBrain('Life')" onMouseOver="playBrain('Life')" onMouseOut="stopBrain()" class="thought">life</a>, the lives of your loved
ones and the lives of your friends. This is possible and even likely,
but not inevitable. How long it takes to develop this life saving
technology depends on what we do—it is not happening according
to some cosmic plan, with a date engraved in stone that neither
you nor I can change—but rather it will take as long as we
let it take. Yes, thirty years is a long time. Yes, most people
have a hard time <a href="javascript:loadBrain('Thinking')" onMouseOver="playBrain('Thinking')" onMouseOut="stopBrain()" class="thought">thinking</a> about the next year, let alone the next
decade, let alone a few decades hence. But if we don't act today,
then we might one day wake up in a future where we are old and infirm
and the promise of nanomedicine is still just that: a promise. To
paraphrase a famous slogan: think long term, act short term.</p>
<p><i>© 2003 <a href="http://www.foresight.org/index.html" target="_blank">Foresight
Institute</a>. Reprinted with permission.</i></p>
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