REPORTS

genitors of the 1918 virus probably switched 5. C. F. Basler et al., Proc. Natl. Acad. Sci. U.S.A. 98, 22. Supplemental material is available at Science Online
hosts from birds to mammals sometime after 2746 (2001). (www.sciencemag.org/cgi/content/full/293/5536/
6. R. G. Webster, Proc. Natl. Acad. Sci. U.S.A. 96, 1164 1842/DC1).
1900 (1, 6), it is likely that the 1918 HA gene (1999). 23. D. C. Wiley, J. J. Skehel, Annu. Rev. Biochem. 56, 365
changed at a rate of 0.4 to 8.0% per year after it 7. J. Lederberg, Proc. Natl. Acad. Sci. U.S.A. 98, 2115 (1987).
was generated. Thus, using the predicted se- (2001). 24. R. E. Shope, J. Exp. Med. 63, 669 (1936).
8. D. Khatchikian, M. Orlich, R. Rott, Nature 340, 156 25. A. B. Beklemishev et al., Mol. Gen. Mikrobiol. Virusol.
quence difference of 0.4% and the likely range (1989). 1, 24 (1993).
of rates, we estimate that the recombination-to- 9. K. Subbarao et al., Science 279, 393 (1998). 26. M. H. Bikour, E. H. Frost, S. Deslandes, B. Talbot, Y.
preservation time was less than 1 year. 10. E. Kilbourne, J. Am. Med. Assoc. 237, 1225 (1977). Elazhary, J. Gen. Virol. 76, 2539 (1995).
The victims from whom the 1918 influenza 11. R. G. Webster, W. J. Bean, O. T. Gorman, T. M. 27. K. Strimmer, A. von Haeseler, Mol. Biol. Evol. 13, 964
Chambers, Y. Kawaoka, Microbiol. Rev. 56, 152 (1996).
sequences were obtained died in the major (1992). 28. M. J. Gibbs, G. F. Weiller, Proc. Natl. Acad. Sci. U.S.A.
“second wave” of the pandemic in late Septem- 12. O. T. Gorman et al., J. Virol. 65, 3704 (1991). 96, 8022 (1999).
ber and October 1918 (2, 3); thus, the 1918 HA 13. J. P. Anderson et al., J. Virol. 74, 10752 (2000). 29. C. Scholtissek, S. Ludwig, W. M. Fitch, Arch. Virol.
14. M. Worobey, A Rambaut, E. C. Holmes, Proc. Natl. 131, 237 (1993).
gene was probably generated in late 1917 or Acad. Sci. U.S.A. 96, 7352 (1999). 30. M. Garcia, J. M. Crawford, J. W. Latimer, E. Rivera-
early 1918. The “first wave” of the pandemic 15. J. S. Pita et al., J. Gen. Virol. 82, 655 (2001). Cruz, M. L. Perdue, J. Gen. Virol. 77, 1493 (1996).
was in early 1918 (2), but the first outbreaks 16. S. Fields, G. Winter, Cell 28, 303 (1982). 31. J. J. Skehel, D. C. Wiley, Annu. Rev. Biochem. 69, 531
may have been in late 1917. Hence, the start of 17. M. Bergmann, A. Garcia-Sastre, P. Palese, J. Virol. 66, (2000).
7576 (1992). 32. K. Tamura, M. Nei, Mol. Biol. Evol. 10, 512 (1993).
the pandemic coincided with a recombination 18. J. D. Thompson, T. J. Gibson, F. Plewniak, F. Jeanmou- 33. We thank G. Ada, B. Blanden, F. Fenner, G. Laver, J.
event that might produce the phenotypic nov- gin, D. G. Higgins, Nucleic Acids Res. 24, 4876 (1997). Trueman, R. Webster, and two unidentified reviewers
19. M. J. Gibbs, J. S. Armstrong, A. J. Gibbs, Bioinformatics for helpful comments, and C. Simeonovic, G. Weiller,

Downloaded from www.sciencemag.org on January 11, 2015

elty required to trigger a pandemic. This coin-
16, 573 (2000). and the ANU Division of Botany and Zoology for
cidence suggests a causal link.
20. E. C. Holmes, M. Worobey, A. Rambaut, Mol. Biol. their support of this unfunded research.
Recombination, like point mutation and Evol. 16, 405 (1999).
reassortment, produces novel virus variants 21. D. H. Huson, Bioinformatics 14, 68 (1998). 12 April 2001; accepted 18 June 2001
and can result in increased virulence (13–15).
Because the HA gene is the major virulence
determinant (3–11), recombination in this
gene may have similarly altered the 1918 Control of Octopus Arm
virus. The parental H1 HA genes would have
been progressively altered by point mutation Extension by a Peripheral Motor
after their divergence; we estimate that they
differed at up to 30 amino acid positions at
the time of the recombination, and that the
Program
1918 HA differed from each of its parents at German Sumbre,1 Yoram Gutfreund,1* Graziano Fiorito,2
about half as many positions. Recombination Tamar Flash,3 Binyamin Hochner1†
may have altered the antigenicity of the HA
so that the immunity of those who had sur- For goal-directed arm movements, the nervous system generates a sequence
vived earlier infections was ineffective. Sim- of motor commands that bring the arm toward the target. Control of the
ilarly, the membrane-fusion or receptor-bind- octopus arm is especially complex because the arm can be moved in any
ing function of the HA protein may have direction, with a virtually infinite number of degrees of freedom. Here we
changed (3, 31), and this may have given the show that arm extensions can be evoked mechanically or electrically in arms
1918 virus an unusual tissue specificity, such whose connection with the brain has been severed. These extensions show
that it spread from the upper respiratory tract kinematic features that are almost identical to normal behavior, suggesting
to the lungs. Experiments comparing recon- that the basic motor program for voluntary movement is embedded within
structed 1918 and parental HA proteins may the neural circuitry of the arm itself. Such peripheral motor programs
distinguish between these possibilities. represent considerable simplification in the motor control of this highly
Our analysis suggests that the two paren- redundant appendage.
tal lineages were probably mammal-adapted
and capable of mammal-to-mammal trans- In directed voluntary movements, the ner- (2, 3), by vectorial summation and superpo-
mission, and yet they did not generate a vous system generates a sequence of motor sition of basic movement primitives (4, 5),
pandemic. It is possible that the recombina- commands producing the forces and veloci- and by the use of a flexible combination of
tion event triggered the pandemic not only by ties that efficiently bring the limb to the target muscle synergies (6). However, flexible
altering HA structure or function, but also by (1). In articulated appendages, the control of structures introduce a further dimension of
permitting the virus to outcompete these par- goal-directed movements appears to be sim- complexity.
ents or to be the first of these H1-subtype plified by the planning of optimal trajectories The octopus arm can move in any direc-
influenzas to switch hosts from some other tion, using a virtually infinite number of
mammal into humans. degrees of freedom. This high maneuver-
1
Department of Neurobiology and Interdisciplinary ability results from octopus arms behaving
Center for Neuronal Computation, Institute of Life
References and Notes Sciences, Hebrew University, Jerusalem 91904, Israel. like a muscular hydrostat, because they are
1. J. K. Taubenberger, A. H. Reid, T. G. Fanning, Virology 2
Laboratorio di Neurobiologia, Stazione Zoologica di almost entirely constructed of densely
274, 241 (2000). Napoli “A. Dohrn,” Naples 80121, Italy. 3Department packed muscle fibers along their transverse,
2. A. W. Crosby, America’s Forgotten Plague: The Influ- of Computer Science and Applied Mathematics, Weiz-
enza of 1918 (Cambridge Univ. Press, New York,
longitudinal, and oblique axes (7 ). These
mann Institute of Science, Rehovot 76100, Israel.
1989). flexible arms are controlled by an elaborate
3. A. H. Reid, T. G. Fanning, J. V. Hultin, J. K. Tauben- *Present address: Department of Neurobiology, Stan- peripheral nervous system containing
berger, Proc. Natl. Acad. Sci. U.S.A. 96, 1651 (1999). ford University School of Medicine Stanford, CA
94305, USA.
⬃5 ⫻ 107 neurons distributed along each
4. A. H. Reid, T. G. Fanning, T. A. Janczewski, J. K.
Taubenberger, Proc. Natl. Acad. Sci. U.S.A. 97, 6786 †To whom correspondence should be addressed: arm. Only ⬃4 ⫻ 105 of these are motor
(2000). E-mail: [email protected] neurons (8), which innervate the intrinsic

www.sciencemag.org SCIENCE VOL 293 7 SEPTEMBER 2001 1845

 REPORTS
muscles of the arm and locally control mus- composed of ⬃300 interconnected ganglia the ganglia (Fig. 1B). The axons in the
cle action (9). This peripheral nervous sys- and two cerebrobrachial (axonal) tracts of tracts carry sensory and motor information
tem is organized as an axial nerve cord ⬃30,000 nerve fibers running dorsally to to and from the highly developed central-
ized brain (10).
The octopus reduces the complexity of
controlling this flexible appendage by us-
ing highly stereotypical movements.
Reaching movements consist of a bend
propagating along the arm toward the tip
(Fig. 1D) in a highly stereotypical and in-
variant way (11). The level of muscle ac-
tivity [measured with an electromyogram
(EMG)] shows a positive correlation with
kinematic variables, and the EMG level
measured during the initial stages of the
movement predicts the bend’s peak propa-
gation velocity attained later during the
movement. These predictive relations sug-
gest that feed-forward motor commands
play an important role in the motor program
for arm extension (12).
Here we show that arm extensions can
be elicited in denervated arms by electrical
stimulation of the arm axial nerve cord or
by tactile stimulation of the skin, suggest-
ing that a major part of this voluntary
movement is controlled by a pattern gener-
ator that is confined to the arm’s neuromus-
cular system.
A short train of electrical stimulation to
the dorsal part of the denervated nerve cord
(13) evoked movements that involved the
entire arm. Forty-six percent of these
movements were characterized by a bend
traveling forward along the arm (14 ). In 20
of these extensions, the movement occurred
after the termination of the stimuli, indicat-
ing that the movement was indeed triggered
by the stimulation and is not directly driven
by the stimuli (Fig. 1C). In the remaining
30 movements, the movement started be-
fore the end of the stimulation train. The
average overlap between the stimulation
train and the acceleration phase of the
movements was only 19%. Because kine-
matic analysis showed no differences be-
tween the two types of movements, both
were combined for further analysis. Arm
extensions were evoked by stimulation of
the dorsal part of the axial nerve cord that
contains the axonal tracts from the brain
(Fig. 1B). In contrast, stimulation of the
muscles within the same area or the gangli-
onic part of the cord (Fig. 1B) (10) evoked
only local muscular contractions.
The evoked bend propagation resembled
stereotypical arm extensions in freely be-
having animals (11) (Fig. 1, D and E). As in
Fig. 1. Natural and evoked arm extensions are qualitatively similar. (A) A decerebrated preparation natural behavior, a dorsally oriented bend
was fixed to the experimental platform (green arrow, stimulating electrode; red arrow, area where propagated along the arm, causing the suck-
the axial nerve cord was transacted and stimulated). (B) The arrangement of the intrinsic arm ers to point in the direction of the movement.
muscles and an enlarged portion of the axial nerve cord showing the stimulating site. (C) A stimulus
train (red trace) is superimposed on the velocity profile of an evoked arm extension (black dots).
As the bend propagated, the part of the arm
The acceleration phase begins after the stimulus ends. (D) A freely behaving octopus reaching proximal to the bend remained extended.
toward a target. (E) Electrically evoked bend propagation in the denervated arm of a decerebrated Movements resembling normal arm exten-
animal ( yellow arrows indicate the bend point). sions could also be initiated in amputated

1846 7 SEPTEMBER 2001 VOL 293 SCIENCE www.sciencemag.org

 REPORTS
arms by electrical stimulation of the nerve then letting the stick collide with a solid arm before, or together with, the command
cord or by tactile stimulation of the skin or barrier. A bend was formed and propagated for arm extension.
suckers. along the arm (Fig. 3A), emphasizing the Because the extensions evoked in dener-
Bend propagations were more readily ini- role of passive interactions with the water vated octopus arms were qualitatively and
tiated when a bend was manually created in shaping the movement (12). However, kinematically identical to natural arm ex-
before stimulation (n ⫽ 50 movements, 16 the velocity profiles were monotonically tensions, there appears to be an underlying
arms). However, such bend propagation decelerating (Fig. 3B), unlike the bell- motor program embedded in the neuromus-
could also be initiated in fully relaxed arms shaped velocity profiles of evoked or nat- cular system of the arm, which does not
(n ⫽ 6, four arms). Here the stimuli triggered ural arm extensions (Fig. 2, C and D). require continuous central control. This
the initial phase of bend formation, followed Furthermore, EMGs recorded during the finding is consistent with the remarkable
by the arm extension. All these observations evoked movements (Fig. 3, C and D; n ⫽ 7, autonomy of the arm local reflexes (15–17 )
show that the nervous system of the arm does three arms) reveal an active propagation of and with the elaborate nervous system in
not just drive local reflexes (15–17) but con- muscle activity as in natural arm extensions each arm, which is connected to the brain
trols complex movements involving the en- (12). by a relatively small number of nerve fibers
tire arm. In 23 experiments in which extensions (8, 10).
Kinematic analysis allowed quantitative could be repeatedly evoked, the initial pos- The division between the central and
comparison between the evoked and natural ture of the arm was changed manually peripheral levels of the octopus motor con-
movements (14 ). In both tactile (n ⫽ 6, while the electrode location and stimulus trol system resembles the hierarchical or-
four arms) and electrically evoked move- parameters remained constant. Movements ganization of motor control systems in oth-
ments (n ⫽ 50, 16 arms), the bend point evoked from similar initial arm postures er invertebrates and vertebrates, even
(the point of maximal curvature) propagat- tended to have similar paths (Fig. 4). Like- though in the octopus it uniquely serves as
ed within a single plane (18), generally wise, different starting postures resulted in an important component in a goal-directed
along a lightly curved path (Fig. 2, A and different final paths (15 experiments). Aim- voluntary movement rather than in rhyth-
B). The coefficient of determination for ing in arm extension thus appears to in- mical or reflexive behaviors (20–22). We
movement within a single plane was highly volve adjusting the initial posture of the do not yet know whether this is a predom-
significant (average R2 ⫽ 0.96 ⫾ 0.06); the
P value was always smaller than 10⫺8 (F Fig. 2. Comparison
test). The average SE ⫽ 0.34 ⫾ 0.39 cm, between the velocity
and the average distance traveled by the profiles of natural arm
bend point was 12.5 ⫾ 4.7 cm. The low SE, extensions (black) and
in comparison to the distance traveled, con- evoked movements in
the denervated arms
firms that the bends propagate within a (red). (A and B) The
single plane. This result is similar to that evoked arm exten-
obtained in freely behaving octopuses (11). sions lie within a sin-
Velocity profiles were derived by calcu- gle plane. (A) The
lating the tangential velocities of the bend paths of 56 evoked
point and plotting these against time (19). extensions mapped
into the best-fit plane.
The velocity profiles of the evoked move- (B) The same arm ex-
ments closely resembled those of arm ex- tension paths rotated
tensions in freely behaving animals (11) by 90°. Note the dif-
(Fig. 2, C and D), both having bell-shaped ference in path vari-
velocity profiles and a similar maximal ve- ability between (A)
locity range (7 to 60 cm/s and 9 to 61 cm/s, and (B). (C and D) Ve-
locity profiles of nat-
respectively). ural and evoked
Normalizing and superimposing the ve- movements. (E and F)
locity profiles according to their maximal Velocity profiles nor-
speed and duration and the bend propaga- malized according to
tion distance (11) revealed a robust invari- their peak velocity,
ance (Fig. 2, E and F) and showed that the duration, and propa-
gated distance and
evoked movements were almost kinemati- aligned at the peak
cally identical to the movements of freely (n ⫽ 56 in both cas-
behaving octopuses (Fig. 2G). The varianc- es). (G) The average
es of the velocity profiles of the evoked and normalized velocity
natural movements were also similar, with profiles [calculated
lower variance during the acceleration from (E) and (F)] of
the natural and
phase of the movements (Fig. 2H). evoked movements
To determine whether the evoked exten- are similar. (H) Super-
sion is generated passively by a whiplike position of the vari-
moving wave or by an active propagation ances calculated from
of muscle contraction, we analyzed the ki- (E) and (F) reveals
nematics of passive bend propagations and similar behavior.
recorded muscle activities (recorded with
an EMG) during the evoked movements.
Passive bend propagations were produced
by dragging a dead arm behind a stick and

www.sciencemag.org SCIENCE VOL 293 7 SEPTEMBER 2001 1847

 REPORTS
Fig. 3. Evoked move-
ments differ from pas-
sive extensionlike move-
ments. (A) A sequence
showing an extension-
like movement generat-
ed by whipping a dead
octopus arm. (B) Veloc-
ity profiles of 12 passive
extensions showing de-
celerating velocity pro-
files, in marked contrast
to the evoked or natural
arm extensions (Fig. 2,
C and D). (C) A se-
quence showing evoked
extension in an ampu-
tated arm during which
an EMG was recorded
with a stainless steel
electrode inserted
though the dorsal mus-
cles and held in place
with a bead glued on
each side of the arm
(arrow) [see (12) for de- Fig. 4. Similar initial postures generate similar
tails]. (D) Velocity pro- bend paths (when the electrode position and
file and EMG of the stimulus parameters are kept constant). (A1
movement in (C). The through A3) Three pairs of similar starting pos-
numbers mark when tures, just before stimulation. (B) The evoked
the images in (C) paths are shown in pairs in different colors as in
were taken. Activity (A1) through (A3). The 3D paths are shifted to
reaching the record- the same starting coordinates.
ing electrode during
the stimulation train video cameras set ⬃90° apart and were recorded
(horizontal line) prob- simultaneously with the stimulus train on a video
ably results from fast- recorder. The three-dimensional (3D) spatial posi-
propagating activity tion of the bend point (the point of maximum
along the axonal curvature) was determined with the direct linear
tracts. There is a burst transformation method [see (11)]. Out of the many
evoked movements (such as local contraction,
of activity just before stiffening, waving, etc.), only in ⬃10% (n ⫽ 116)
the bend point reaches the electrode (arrow), followed by tonic activity when the arm is was a bend observed and its movement analyzed.
extended. Only those movements in which the bend was
found to propagate were studied (n ⫽ 63). Fifty-six
movements (89%) had a bell-shaped velocity pro-
file and were compared to natural movements.
inantly feed-forward control mechanism 6. E. Bizzi, M. C. Tresch, P. Saltiel, A. d’Avella, Nature
15. M. J. Wells, J. Exp. Biol. 36, 590 (1959).
Rev. Neurosci. 1, 101 (2000).
(12) or involves a distributed control sys- 16. C. H. F. Rowell, J. Exp. Biol. 40, 257 (1963).
7. W. Kier, K. Smith, Zool. J. Linn. Soc. 83, 307 (1985). 17. J. S. Altman, Nature 229, 204 (1971).
tem based on local reflexes, as in other 8. J. Z. Young, Proc. R. Soc. London Ser. B 162, 47 18. The plane of motion was determined by rotating the
animals (23, 24 ). (1965). 3D coordinates of the paths in space and subjectively
In this control scheme, the arm neuronal 9. H. Matzner, Y. Gutfreund, B. Hochner, J. Neuro- determining the best plane containing the bend point
networks produce the neuronal activation physiol. 83, 1315 (2000). movement. The path was then transformed into a
10. P. Graziadei, in The Anatomy of the Nervous System coordinate system where the selected plane lay at
patterns prescribing all of the spatiotempo- of Octopus vulgaris, J. Z. Young, Ed. (Clarendon, 45° to the zy plane. The fit to a single plane was
ral details of the basic movement patterns, Oxford, 1971), pp. 45–59. estimated by the coefficient of determination (R2 ) of
suggesting that the higher central levels 11. Y. Gutfreund et al., J. Neurosci. 16, 7297 (1996). the regression analysis.
12. Y. Gutfreund, T. Flash, G. Fiorito, B. Hochner, J. Neu- 19. Time derivatives of the 3D position coordinates of
(that is, the brain) send global commands to the bend point were calculated in order to obtain the
rosci. 18, 5976 (1998).
the arm neuronal network to activate and 13. To obtain the denervated arm preparation, Octo- tangential velocity in the direction of motion (11).
scale the program variables. This division pus vulgaris from the Bay of Naples were anesthe- 20. M. L. Shick, G. N. Orlovsky, Physiol. Rev. 56, 465
tized in a mixture of 2% ethanol in seawater (as (1976).
of labor between the central and peripheral 21. Y. I. Arshavsky, T. G. Deliagina, G. N. Orlovsky, Curr.
was also done before each operation) and then
nervous systems and the use of a propagat- Opin. Neurobiol. 7, 781 (1997).
“decerebrated” by removal of the supraesophageal
ing wave with a limited number of degrees brain mass [B. B. Boycott, J. Z. Young, Symp. Soc. 22. F. Delcomyn, Science 210, 492 (1980).
of freedom greatly simplify the movement Exp. Biol. 4, 432 (1950)] to produce a subdued 23. W. B. Kristan et al., in Biomechanics and Neural
preparation (Fig. 1A). After a recovery period of Control of Posture and Movement, J. Winters, P. E.
control of flexible arms. Crago, Eds. (Springer-Verlag, New York, 2000), pp.
⬃24 hours, the nerve cord of one of the arms was
exposed and transected. We also used acutely 206 –218.
amputated arms. The preparations were sub- 24. H. J. Chiel, R. D. Beer, Trends Neurosci. 20, 553
References and Notes merged in circulating aerated seawater at ⬃20°C. (1997).
1. J. M. Hollerbach, in Visual Cognition and Action, The proximal part of the denervated arm was fixed 25. Supported by the U.S. Office of Naval Research and
D. N. Osherson, S. M. Kosslyn, J. M. Hollerbach, Eds. to a platform; the distal part hung freely. Tactile the Israel Science Foundation. We thank E. Bizzi and
(MIT Press, Cambridge, MA, 1990), pp. 151–182. stimulation was applied to the suckers or skin of Y. Yarom for advice and critical readings of this
2. T. Flash, N. Hogan, J. Neurosci. 5, 1688 (1985). the arm. Electrical stimulation (at 40 to 90 Hz for manuscript; J. Kien for suggestions and editorial as-
3. C. Harris, D. Wolpert, Nature 20, 780 (1998). 200 to 500 ms) was applied through a Teflon- sistance; and A. De Santis, A. Packard, and Y. Yekutieli
coated silver bipolar electrode placed on the dorsal for their help.
4. T. Flash, E. Henis, J. Cogn. Neurosci. 3, 220 (1991).
5. F. A. Mussa-Ivaldi, Curr. Opin. Neurobiol. 9, 713 part of the exposed axial nerve cord (Fig. 1B).
(1999). 14. The evoked arm responses were filmed with two 22 March 2001; accepted 11 July 2001

1848 7 SEPTEMBER 2001 VOL 293 SCIENCE www.sciencemag.org

 Control of Octopus Arm Extension by a Peripheral Motor Program
German Sumbre et al.
Science 293, 1845 (2001);
DOI: 10.1126/science.1060976

This copy is for your personal, non-commercial use only.

If you wish to distribute this article to others, you can order high-quality copies for your
colleagues, clients, or customers by clicking here.

Downloaded from www.sciencemag.org on January 11, 2015

Permission to republish or repurpose articles or portions of articles can be obtained by
following the guidelines here.

The following resources related to this article are available online at

www.sciencemag.org (this information is current as of January 11, 2015 ):

Updated information and services, including high-resolution figures, can be found in the online
version of this article at:
http://www.sciencemag.org/content/293/5536/1845.full.html
This article cites 17 articles, 9 of which can be accessed free:
http://www.sciencemag.org/content/293/5536/1845.full.html#ref-list-1
This article has been cited by 35 article(s) on the ISI Web of Science
This article has been cited by 14 articles hosted by HighWire Press; see:
http://www.sciencemag.org/content/293/5536/1845.full.html#related-urls
This article appears in the following subject collections:
Psychology
http://www.sciencemag.org/cgi/collection/psychology

Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the
American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright
2001 by the American Association for the Advancement of Science; all rights reserved. The title Science is a
registered trademark of AAAS.