The precise information that is conveyed between nerve cells remains unknown. Networks of nerve cells grown on silicon chips, using a polyester as a guide, may bring us closer to translating the elusive neural language

Curtis, Adam

English

Enlighten: Publications

albeit in a different way, by modulating 
ryanodine receptors in blood vessels. If so,
the absence of FKBP12.6 would lead to an
increase in blood pressure, requiring the
heart to pump more forcefully. And the 
predicted outcome of more forceful cardiac
contraction in the face of lasting high blood
pressure is enlargement of the heart. Indeed,
Xin et al. found that male, but not female,
FKBP12.6-null mice had high blood pres-
sure1. This is consistent with the idea that
cardiac hypertrophy in the males is a sec-
ondary consequence of elevated blood pres-
sure, and that oestrogen opposes the effects
of a lack of FKBP12.6 on blood pressure.
There are other possibilities, however.
The increases in intracellular calcium levels
seen in FKBP12.6-deficient animals might
lead directly to an increase in the activity of
the calcium-dependent transcription factor
NFAT. Alternatively, because FKBP12 and
FKBP12.6 not only regulate calcium release
through ryanodine receptors but are also
important components of the calcineurin
protein complex, which regulates NFAT
activity, it is possible that disruption of
FKBP12 or FKBP12.6 in the heart or blood
vessels leads to the activation of NFAT
through effects on calcineurin. The activa-
tion of NFAT by either of these two mecha-
nisms might induce a gene programme
that causes an increase in blood pressure or 
cardiac hypertrophy. It is conceivable that
oestrogen decreases the expression or activi-
ty of NFAT or its target genes in the blood
vessels or hearts of females. Whatever the
answer, an understanding of the molecular
mechanisms at work will no doubt be crucial
to comprehending gender-based differences
in cardiovascular function. n
Mark T. Nelson and Gerald M. Herrera are in the
Department of Pharmacology, University of
Vermont, Given Medical Building, Burlington,
Vermont 05405-0068, USA.
e-mail: mtnelson@zoo.uvm.edu
1. Xin, H.-B. et al. Nature 416, 334–337 (2002).
2. Shou, W. et al. Nature 391, 489–492 (1998).
3. Molkentin, J. D. et al. Cell 93, 215–228 (1998).
4. Graef, I. A., Chen, F., Chen, L., Kuo, A. & Crabtree, G. R. Cell
105, 863–875 (2001).
5. Stevenson, A. S., Gomez, M. F., Hill-Eubanks, D. C. &
Nelson, M. T. J. Biol. Chem. 276, 15018–15024 (2001).
6. Marks, A. R. Physiol. Rev. 76, 631–649 (1996).
7. Mendelsohn, M. E. & Karas, R. H. N. Engl. J. Med. 340,
1801–1811 (1999).
8. Wellman, G. C., Bonev, A. D., Nelson, M. T. & Brayden, J. E.
Circ. Res. 79, 1024–1030 (1996).
9. Geary, G. G. et al. J. Appl. Physiol. 91, 2391–2399 (2001).
10.Zhu, Y. et al. Science 295, 505–508 (2002).
Work on growing neuronal networks has
been in progress for several years, although
previous experiments paid insufficient
attention to preventing the neurites from
moving or becoming rearranged in the cul-
tures; this can happen through the mechani-
cal forces generated by the cells themselves.
But secure, long-term positioning of neu-
rites (on a scale of days to weeks) has been
achieved2, with lines of neurons immobi-
lized using the protein laminin. Maher et al.3
have also grown cells in deep pits, and
recorded data from them. An alternative to
network growing has also been tried. In
an earlier, seminal experiment, Syed and 
collegues4 reconstructed neuronal circuits
by delicate hand surgery and managed
to rebuild a working circuit. But they did
not explore modified circuits or the effects
of changes in the message.
Now Merz and Fromherz1 have built on
the results of such experiments, and have
obtained well-defined, if very small, stable
networks of cultured neurons from the
pond snail Lymnaea stagnalis. Using micro-
fabrication techniques, they etched a series
of pits and grooves in a polyester surface on
a silicon substrate (Fig. 1a). The design traps
the cell bodies but allows neurites to grow
along the grooves. Merz and Fromherz
managed to identify pairs of nerve cells that
had formed connections and to record elec-
trical signals from them. They did this by
injecting current into one neuron and
showing that a voltage change occurred in
the neighbouring cell, indicating that elec-
trical synapses had formed. Moreover, the
electrical events observed in the networks
were as expected, proving that the behav-
iour of the neurons was not being apprecia-
bly affected by the chemistry or structure of
the polyester–silicon growth material. 
To record and stimulate electrical signals
in their neuronal network, Merz and
Fromherz used conventional intracellular
news and views
274 NATURE | VOL 416 | 21 MARCH 2002 | www.nature.com
Within a nerve cell, or neuron, differ-ences in electrical potential encodeinformation, and messages can be
passed on to other neurons through connec-
tions  that may be chemical or electrical. But,
like nineteenth-century linguists contem-
plating the hieroglyphs of the Rosetta Stone,
we have only vague clues as to the symbolism
and language, let alone the grammar or 
syntax, of neural messages. We will never
dig up a neurobiological Rosetta Stone — but
we might be able to synthesize our own. In
a notable paper in Advanced Materials, Merz
and Fromherz1 have taken us at least one stage
towards this goal, and their work brings with
it the promise of further discoveries. 
To decipher the neural code, the aim is to
grow networks of neurons in culture, with
each neuron connected to others through
synapses that form at the ends of the neuron’s
tendril-like extensions, or neurites. We need
to reproduce the connectivity that is seen
anatomically in nervous systems and which,
when destroyed, leads to loss of correct func-
tion. We suspect that the message passing
across a synapse carries instructions for how
the information should be processed and
possibly also routed, and in many cases we
know what the correct (or at least normal)
input and output are. What we would like to
test are the effects of different connectivities
and input messages on the neuronal output. 
Materials science
Breaking the neural code
Adam Curtis
The precise information that is conveyed between nerve cells remains
unknown. Networks of nerve cells grown on silicon chips, using a polyester
as a guide, may bring us closer to translating the elusive neural language.
Figure 1 Artificially grown networks of neurons
could be the key to deciphering the intricate
code of neural messages. a, Merz and Fromherz1
etched pits and grooves in a polyester–silicon
material to control the growth of neurites into
a functioning network; pits 70–80 mm in
diameter match the size of the pond-snail
neurons used in the experiment, and grooves
up to 15 mm wide and 30 mm deep confine and
guide the neurites into forming synaptic
connections between neurons. b, Following a
pattern suggested by Wilkinson6, Sandison et
al.5 grew this neuronal network in grooves in
silica — although the difficulty of confining
the growth within the structure is apparent.
a,
M
. M
E
R
Z
 &
 P
. F
R
O
M
H
E
R
Z
 /
 b
, A
. C
U
R
T
IS
  
© 2002 Macmillan Magazines Ltd
glass microelectrodes, although their earlier
work had used extracellular electrodes,
based on field-effect transistors to amplify
the weak electrical signals. Extracellular elec-
trodes have an advantage over the intracellu-
lar kind because trapping neurons with fixed
electrodes, or piercing them with a micro-
electrode, can kill them. In fact, my own
group has recently invented a manipulable
extracellular electrode array5 that can be
rapidly moved from site to site. The electrode
patterns can be matched to that of the net-
work under test, although the array’s extra-
cellular position does reduce the magnitude
of the signal that can be extracted.
The growth technique of Merz and
Fromherz, when combined with advances
in electrode design, should open the way to
investigating how connectivity and patterns
of connection modify neural processing. In
other words, it should be possible to test the
consequences of specific changes in connec-
tivity or in the electrically injected message
on the output. Furthermore, as Merz and
Fromherz1 point out, their system should
allow the role of subthreshold signals to be
assessed — these are events that do not lead
directly to transmission of a neural message,
but which may influence the electrical
potentials of nerve cells. 
With the tools in place, the outstanding
question is how a neuronal network could be
designed. There are two sensible approaches:
first, to try to mimic what is already found
in nature; and second, to formally develop
logically designed networks. Judith Wilkin-
son (quoted in ref. 6) has applied graph and
tiling theory to design networks that should
be able to propagate and compare messages
(Fig. 1b). These are probably the only in vitro
systems that feature branching networks that
are just like those in real nervous systems.
Such logically designed networks are just
now being realized. 
Despite the progress reported by workers
such as Merz and Fromherz, we should still
proceed cautiously — for instance, we do not
even know whether there are (or aren’t) sev-
eral types of neural coding, or language, in a
single animal. But, as in other code-breaking
efforts, there will probably be a long period
of data collection — revealing more and
more of the neurobiological Rosetta Stone
— until we have enough information to start
interpreting the neural code. n
Adam Curtis is at the Centre for Cell Engineering,
IBLS, Joseph Black Building, University of Glasgow,
Glasgow G12 8QQ, UK. 
e-mail: a.curtis@bio.gla.ac.uk
1. Merz, M. & Fromherz, P. Adv. Mater. 14, 141–144 (2002).
2. Lauer, L., Klein, C. & Offenhauesser, A. Biomaterials 22,
1925–1932 (2001).
3. Maher, M. P. et al. Cell. Eng. 37, 110–118 (1999).
4. Syed, N. I., Bulloch, A. G. M. & Lukowiak, K. Science 250,
282–285 (1990).
5. Sandison, M., Curtis, A. S. G. & Wilkinson, C. D. W.
J. Neurosci. Methods 114, 63–71 (2002).
6. Wilkinson, C. D. W. & Curtis, A. S. G. Physics World 12,
45–48 (1999).
On page 291 of this issue, Segal and col-leagues (Reeves et al.)1 cast new andunexpected light on one of the corner-
stones of the immune system. Their observa-
tions overturn the established wisdom that
has guided the study of phagocytosis and
pose questions about the role of reactive 
oxygen species in destroying invading
pathogens. 
It is 120 years since Elie Metchnikoff dis-
covered phagocytes — cells that engulf and
devour bacteria and other invaders of the
bloodstream. This ‘innate immunological
response’ is the body’s first line of defence
against such violations, and it depends pre-
dominantly on the most abundant class of
phagocytic cells, the most numerous white
cells in the blood, the neutrophils. Sufferers
from the rare, hereditary chronic granulo-
matous disease (CGD), whose neutrophils
are defective, die from bacterial and fungal
infections if they are not treated. (Metch-
nikoff  later came to believe that, with the
passage of the years, phagocytic cells become
incontinent, rampage through our tissues,
gnaw at our vitals and cause the catastrophe
that we recognize as ageing.)
Neutrophils surge towards the site of an
infection and engulf bacteria by a well-char-
acterized process (opsonization) that
requires blood serum proteins. They then
destroy the involuntary guest trapped within
a phagocytic vacuole. The cytoplasm of 
the neutrophil is rich in granules (whence 
its original description as a granulocyte),
which, on activation, discharge their con-
tents inside the phagocytic vacuole. 
The picture of the killing process that has
dominated thinking over the past 40 years is
that the lethal agents are the highly reactive
news and views
Traditional optical experiments,
such as splitting rays of light
into various colours with a
prism, have had the attraction
of being visible to the naked
eye. Modern methods of
confining light within
microscopic structures, and
tailoring its interaction with
matter on atomic scales, are
taking optics into the quantum
realm. Making the results
visible is not straightforward.
But a beautiful example comes
from C. Chicanne et al.
(Physical Review Letters 88,
097402; 2002), who have
designed a way of taking
snapshots of intricate light
interference patterns in tiny
photonic structures. One of
their snapshots is shown here. 
The images are
reminiscent of the ‘quantum
corrals’ for electrons, first
created by Donald Eigler and
colleagues in 1993, and
produced with the scanning
tunnelling microscope (STM).
This instrument probes
surfaces with a sharp needle,
which can also be used to
move loose atoms around on a
metallic surface and position
them into a closed loop. The
electrons confined within these
corrals interfere with one
another and produce beautiful
patterns, which the STM
images make manifest. These
experiments have been highly
instructive for illustrating the
quantum-mechanical principle
that electrons can behave as
waves.
Chicanne et al. now
present an optical analogue of
the quantum corral. Light has
wave properties, of course, but
interpreting the interference
effects is not straightforward
within a radius around a light
source that is comparable to
the wavelength of the light
itself. To study this zone,
Chicanne et al. made use of
a relative of the STM, the
scanning near-field optical
microscope. Here, the surface
probe is an optical fibre tapered
to a sharp end that also
illuminates the sample. 
Much as in the
experiments by Eigler and
colleagues, Chicanne et al. first
created corrals by carefully
positioning particles of gold in
a loop, in this example in the
shape of a stadium. The optical
corral is then imaged by
scanning the fibre over the
surface while collecting light
transmitted though the
transparent sample. The result
is images of light interference
patterns in a microscopic
structure. The principles
involved will help direct future
observations, and tailored
distribution, of light at atomic
dimensions.
Liesbeth Venema
Quantum optics 
Light corralled 
1mm
Immunology
The Wright stuff
Walter Gratzer
White cells in the bloodstream seek out and destroy invading bacteria. The
explanation for the actual killing mechanism turns out to be wonderfully
more subtle than previously thought.
NATURE | VOL 416 | 21 MARCH 2002 | www.nature.com 275© 2002 Macmillan Magazines Ltd


Materials science: Breaking the neural code

Crossref

Enlighten

albeit in a different way, by modulating ryanodine receptors in blood vessels. If so,the absence of FKBP12.6 would lead to anincrease in blood pressure, requiring theheart to pump more forcefully. And the predicted outcome of more forceful cardiaccontraction in the face of lasting high bloodpressure is enlargement of the heart. Indeed,Xin et al. found that male, but not female,FKBP12.6-null mice had high blood pres-sure1. This is consistent with the idea thatcardiac hypertrophy in the males is a sec-ondary consequence of elevated blood pres-sure, and that oestrogen opposes the effectsof a lack of FKBP12.6 on blood pressure.There are other possibilities, however.The increases in intracellular calcium levelsseen in FKBP12.6-deficient animals mightlead directly to an increase in the activity ofthe calcium-dependent transcription factorNFAT. Alternatively, because FKBP12 andFKBP12.6 not only regulate calcium releasethrough ryanodine receptors but are alsoimportant components of the calcineurinprotein complex, which regulates NFATactivity, it is possible that disruption ofFKBP12 or FKBP12.6 in the heart or bloodvessels leads to the activation of NFATthrough effects on calcineurin. The activa-tion of NFAT by either of these two mecha-nisms might induce a gene programmethat causes an increase in blood pressure or cardiac hypertrophy. It is conceivable thatoestrogen decreases the expression or activi-ty of NFAT or its target genes in the bloodvessels or hearts of females. Whatever theanswer, an understanding of the molecularmechanisms at work will no doubt be crucialto comprehending gender-based differencesin cardiovascular function. nMark T. Nelson and Gerald M. Herrera are in theDepartment of Pharmacology, University ofVermont, Given Medical Building, Burlington,Vermont 05405-0068, USA.e-mail: mtnelson@zoo.uvm.edu1. Xin, H.-B. et al. Nature 416, 334–337 (2002).2. Shou, W. et al. Nature 391, 489–492 (1998).3. Molkentin, J. D. et al. Cell 93, 215–228 (1998).4. Graef, I. A., Chen, F., Chen, L., Kuo, A. & Crabtree, G. R. Cell105, 863–875 (2001).5. Stevenson, A. S., Gomez, M. F., Hill-Eubanks, D. C. &Nelson, M. T. J. Biol. Chem. 276, 15018–15024 (2001).6. Marks, A. R. Physiol. Rev. 76, 631–649 (1996).7. Mendelsohn, M. E. & Karas, R. H. N. Engl. J. Med. 340,1801–1811 (1999).8. Wellman, G. C., Bonev, A. D., Nelson, M. T. & Brayden, J. E.Circ. Res. 79, 1024–1030 (1996).9. Geary, G. G. et al. J. Appl. Physiol. 91, 2391–2399 (2001).10.Zhu, Y. et al. Science 295, 505–508 (2002).Work on growing neuronal networks hasbeen in progress for several years, althoughprevious experiments paid insufficientattention to preventing the neurites frommoving or becoming rearranged in the cul-tures; this can happen through the mechani-cal forces generated by the cells themselves.But secure, long-term positioning of neu-rites (on a scale of days to weeks) has beenachieved2, with lines of neurons immobi-lized using the protein laminin. Maher et al.3have also grown cells in deep pits, andrecorded data from them. An alternative tonetwork growing has also been tried. Inan earlier, seminal experiment, Syed and collegues4 reconstructed neuronal circuitsby delicate hand surgery and managedto rebuild a working circuit. But they didnot explore modified circuits or the effectsof changes in the message.Now Merz and Fromherz1 have built onthe results of such experiments, and haveobtained well-defined, if very small, stablenetworks of cultured neurons from thepond snail Lymnaea stagnalis. Using micro-fabrication techniques, they etched a seriesof pits and grooves in a polyester surface ona silicon substrate (Fig. 1a). The design trapsthe cell bodies but allows neurites to growalong the grooves. Merz and Fromherzmanaged to identify pairs of nerve cells thathad formed connections and to record elec-trical signals from them. They did this byinjecting current into one neuron andshowing that a voltage change occurred inthe neighbouring cell, indicating that elec-trical synapses had formed. Moreover, theelectrical events observed in the networkswere as expected, proving that the behav-iour of the neurons was not being apprecia-bly affected by the chemistry or structure ofthe polyester–silicon growth material. To record and stimulate electrical signalsin their neuronal network, Merz andFromherz used conventional intracellularnews and views274 NATURE | VOL 416 | 21 MARCH 2002 | www.nature.comWithin a nerve cell, or neuron, differ-ences in electrical potential encodeinformation, and messages can bepassed on to other neurons through connec-tions  that may be chemical or electrical. But,like nineteenth-century linguists contem-plating the hieroglyphs of the Rosetta Stone,we have only vague clues as to the symbolismand language, let alone the grammar or syntax, of neural messages. We will neverdig up a neurobiological Rosetta Stone — butwe might be able to synthesize our own. Ina notable paper in Advanced Materials, Merzand Fromherz1 have taken us at least one stagetowards this goal, and their work brings withit the promise of further discoveries. To decipher the neural code, the aim is togrow networks of neurons in culture, witheach neuron connected to others throughsynapses that form at the ends of the neuron’stendril-like extensions, or neurites. We needto reproduce the connectivity that is seenanatomically in nervous systems and which,when destroyed, leads to loss of correct func-tion. We suspect that the message passingacross a synapse carries instructions for howthe information should be processed andpossibly also routed, and in many cases weknow what the correct (or at least normal)input and output are. What we would like totest are the effects of different connectivitiesand input messages on the neuronal output. Materials scienceBreaking the neural codeAdam CurtisThe precise information that is conveyed between nerve cells remainsunknown. Networks of nerve cells grown on silicon chips, using a polyesteras a guide, may bring us closer to translating the elusive neural language.Figure 1 Artificially grown networks of neuronscould be the key to deciphering the intricatecode of neural messages. a, Merz and Fromherz1etched pits and grooves in a polyester–siliconmaterial to control the growth of neurites intoa functioning network; pits 70–80 mm indiameter match the size of the pond-snailneurons used in the experiment, and groovesup to 15 mm wide and 30 mm deep confine andguide the neurites into forming synapticconnections between neurons. b, Following apattern suggested by Wilkinson6, Sandison etal.5 grew this neuronal network in grooves insilica — although the difficulty of confiningthe growth within the structure is apparent.a,M. MERZ & P. FROMHERZ / b, A. CURTIS  © 2002 Macmillan Magazines Ltdglass microelectrodes, although their earlierwork had used extracellular electrodes,based on field-effect transistors to amplifythe weak electrical signals. Extracellular elec-trodes have an advantage over the intracellu-lar kind because trapping neurons with fixedelectrodes, or piercing them with a micro-electrode, can kill them. In fact, my owngroup has recently invented a manipulableextracellular electrode array5 that can berapidly moved from site to site. The electrodepatterns can be matched to that of the net-work under test, although the array’s extra-cellular position does reduce the magnitudeof the signal that can be extracted.The growth technique of Merz andFromherz, when combined with advancesin electrode design, should open the way toinvestigating how connectivity and patternsof connection modify neural processing. Inother words, it should be possible to test theconsequences of specific changes in connec-tivity or in the electrically injected messageon the output. Furthermore, as Merz andFromherz1 point out, their system shouldallow the role of subthreshold signals to beassessed — these are events that do not leaddirectly to transmission of a neural message,but which may influence the electricalpotentials of nerve cells. With the tools in place, the outstandingquestion is how a neuronal network could bedesigned. There are two sensible approaches:first, to try to mimic what is already foundin nature; and second, to formally developlogically designed networks. Judith Wilkin-son (quoted in ref. 6) has applied graph andtiling theory to design networks that shouldbe able to propagate and compare messages(Fig. 1b). These are probably the only in vitrosystems that feature branching networks thatare just like those in real nervous systems.Such logically designed networks are justnow being realized. Despite the progress reported by workerssuch as Merz and Fromherz, we should stillproceed cautiously — for instance, we do noteven know whether there are (or aren’t) sev-eral types of neural coding, or language, in asingle animal. But, as in other code-breakingefforts, there will probably be a long periodof data collection — revealing more andmore of the neurobiological Rosetta Stone— until we have enough information to startinterpreting the neural code. nAdam Curtis is at the Centre for Cell Engineering,IBLS, Joseph Black Building, University of Glasgow,Glasgow G12 8QQ, UK. e-mail: a.curtis@bio.gla.ac.uk1. Merz, M. & Fromherz, P. Adv. Mater. 14, 141–144 (2002).2. Lauer, L., Klein, C. & Offenhauesser, A. Biomaterials 22,1925–1932 (2001).3. Maher, M. P. et al. Cell. Eng. 37, 110–118 (1999).4. Syed, N. I., Bulloch, A. G. M. & Lukowiak, K. Science 250,282–285 (1990).5. Sandison, M., Curtis, A. S. G. & Wilkinson, C. D. W.J. Neurosci. Methods 114, 63–71 (2002).6. Wilkinson, C. D. W. & Curtis, A. S. G. Physics World 12,45–48 (1999).On page 291 of this issue, Segal and col-leagues (Reeves et al.)1 cast new andunexpected light on one of the corner-stones of the immune system. Their observa-tions overturn the established wisdom thathas guided the study of phagocytosis andpose questions about the role of reactive oxygen species in destroying invadingpathogens. It is 120 years since Elie Metchnikoff dis-covered phagocytes — cells that engulf anddevour bacteria and other invaders of thebloodstream. This ‘innate immunologicalresponse’ is the body’s first line of defenceagainst such violations, and it depends pre-dominantly on the most abundant class ofphagocytic cells, the most numerous whitecells in the blood, the neutrophils. Sufferersfrom the rare, hereditary chronic granulo-matous disease (CGD), whose neutrophilsare defective, die from bacterial and fungalinfections if they are not treated. (Metch-nikoff  later came to believe that, with thepassage of the years, phagocytic cells becomeincontinent, rampage through our tissues,gnaw at our vitals and cause the catastrophethat we recognize as ageing.)Neutrophils surge towards the site of aninfection and engulf bacteria by a well-char-acterized process (opsonization) thatrequires blood serum proteins. They thendestroy the involuntary guest trapped withina phagocytic vacuole. The cytoplasm of the neutrophil is rich in granules (whence its original description as a granulocyte),which, on activation, discharge their con-tents inside the phagocytic vacuole. The picture of the killing process that hasdominated thinking over the past 40 years isthat the lethal agents are the highly reactivenews and viewsTraditional optical experiments,such as splitting rays of lightinto various colours with aprism, have had the attractionof being visible to the nakedeye. Modern methods ofconfining light withinmicroscopic structures, andtailoring its interaction withmatter on atomic scales, aretaking optics into the quantumrealm. Making the resultsvisible is not straightforward.But a beautiful example comesfrom C. Chicanne et al.(Physical Review Letters 88,097402; 2002), who havedesigned a way of takingsnapshots of intricate lightinterference patterns in tinyphotonic structures. One oftheir snapshots is shown here. The images arereminiscent of the ‘quantumcorrals’ for electrons, firstcreated by Donald Eigler andcolleagues in 1993, andproduced with the scanningtunnelling microscope (STM).This instrument probessurfaces with a sharp needle,which can also be used tomove loose atoms around on ametallic surface and positionthem into a closed loop. Theelectrons confined within thesecorrals interfere with oneanother and produce beautifulpatterns, which the STMimages make manifest. Theseexperiments have been highlyinstructive for illustrating thequantum-mechanical principlethat electrons can behave aswaves.Chicanne et al. nowpresent an optical analogue ofthe quantum corral. Light haswave properties, of course, butinterpreting the interferenceeffects is not straightforwardwithin a radius around a lightsource that is comparable tothe wavelength of the lightitself. To study this zone,Chicanne et al. made use ofa relative of the STM, thescanning near-field opticalmicroscope. Here, the surfaceprobe is an optical fibre taperedto a sharp end that alsoilluminates the sample. Much as in theexperiments by Eigler andcolleagues, Chicanne et al. firstcreated corrals by carefullypositioning particles of gold ina loop, in this example in theshape of a stadium. The opticalcorral is then imaged byscanning the fibre over thesurface while collecting lighttransmitted though thetransparent sample. The resultis images of light interferencepatterns in a microscopicstructure. The principlesinvolved will help direct futureobservations, and tailoreddistribution, of light at atomicdimensions.Liesbeth VenemaQuantum optics Light corralled 1mmImmunologyThe Wright stuffWalter GratzerWhite cells in the bloodstream seek out and destroy invading bacteria. Theexplanation for the actual killing mechanism turns out to be wonderfullymore subtle than previously thought.NATURE | VOL 416 | 21 MARCH 2002 | www.nature.com 275© 2002 Macmillan Magazines Ltd

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