CELL INTELLIGENCE

MINDSET

MAIN HYPOTHESIS

APPROACH

For the past 2 decades I have applied essentially two lines of reasoning to examine whether cells are intelligent. They can be summarized in the following statements:

First a disclaimer. My work over the past 2 decades did not intend to join the ongoing efforts of philosophers, logicians and computer scientists to find a universal definition of intelligence. On the contrary, it did not question the common assumption that everybody can tell a mindless, mechanical gadget from an intelligent machine, and proceeded to ask which of the two categories apply to a living cell. Clearly, there are many different levels of intelligence, but I believe that most people consider a machine mechanical and mindless if its actions either do not seem to respond to signals or else always show the same set of reactions. On the other hand, we expect an intelligent machine to responds to signals in a large variety of ways, especially if the signals are unforeseeable, and if its responses offer solutions to problems which were transmitted by the signals. Usually, this means that the intelligent machine contains at least 2 different machines, one which it mindless and carries out some mechanical labor while the other collects and processes signals and controls the action of the first.

Therefore, I went ahead using the following operational definition of an intelligent cell. An intelligent cell contains a compartment which is capable of collecting and integrating a variety of physically different and unforeseeable signals as the basis of problem-solving decisions.

The prevailing wisdom of modern biology has it that cells are immensely complex, but rigidly operating chemical machines that derive their operating instructions internally from their genes and externally from chemicals and electrical signals emitted rigidly by other cells. Unable to believe that any machine can be designed that contains an instruction library which anticipates all the mishaps and glitches of a billion years of evolution without crashing over and over again, I began more than 2 decades ago to search for signs that the cell was actually a 'smart' machine. In other words, I looked for experimental evidence that cells contained a signal integration system that allowed them to sense, weigh and process huge numbers of signals from outside and inside their bodies and to make decisions on their own.

One of the reasons for my disbelief was the sheer size of the organisms that cells built out of themselves. Organism like us are 30,000 times larger in length and and we are not the biggest. Keep in mind that the cells of a gnat are not smaller than the cells of a whale. The whale just contains a lot more cells. How could they build such a huge range of organisms without the ability to override any permanent instructions in order to solve unforeseeable problems on its own?

Anybody who ever built anything bigger than himself knows what frightening surprises it can bring to exceed the dimensions of actions and objects with which we are familiar. The Sears Tower in Chicago is 'only' 300 times larger than the body of its architects. Ask the architects and construction companies who solved the legions of surprise technical problems whether an architect rigidly programmed to respond mechanically could have built it! Then try to build something 30,000 times larger, i.e. a building which is 25 miles tall with a rigid and mechanically operating robot!

Under what circumstances would a cell reveal that it is 'intelligent'? I thought that the best place to start searching was the field of cell movement. A moving cell has to operate its own body in sophisticated ways and, in addition, may have to navigate in space and time while dealing with numerous unforeseeable events, such as encounters with other cells and other objects that its genome could not possibly have anticipated.

I think that cell motility, indeed, revealed cell intelligence. This website highlights some of the experiments and offers the images and the arguments that support the claim of cell intelligence. The left side of the screen guides the visitor to the various topics, subheadings, images, bibliography and a platform of discussion that reflects responses of visitors to my e-mail address.

1.If cells are intelligent, molecules and their genes would be the 'collaborators' or even 'slaves' , but not the 'masters' of the life functions of cells.

We have all accepted this in the case of organisms. For example, consider the function of an organism like me to make sounds with his throat. Everybody takes it for granted that there is no gene that programmed the words that I speak, but that the information processing speech center in my brain makes the molecules in my throat act and interact when I speak them. Yet, when it comes to cells we tend to believe the opposite: Daily, biologists claim to have found new genes and molecules that act and interact to produce this or the other cell function. If cells are intelligent we would have to rethink all the cause-and-effect chains from genes to molecules to cell function that we believe today to be true.

2. If cells are intelligent, medical treatment may involve 'talking to cells [See ref 17] rather than to flood the organism with pharmaceuticals as we do today.

If cells are intelligent, they are capable of integrating physically different signals (mechanical, electrical, chemical, temperature, pH, etc.) before they generate a response. Integration of physically different signals is only possible if each is first transduced into a common, unifying type of signal. The unifying signals are then integrated and subsequently re-transduced into the response action. For example, all the different kinds of signals that we integrate in our brain are first transduced into unifying electrical pulses, called action potentials, before we integrate them. Finally, we return the same kind of signal, namely electrical response pulses from our brain to the e.g. muscles which re-transduce them into mechanical actions.

If cells have an integrative system, it must also use unifying signals which it links and gates by genetically inherited, cell-specific logical rules before it responds. (Of course, the unknown cellular unifying signals will not be electrical signals like action potentials. Cells are far too small for that. ) In other words, if the cells are intelligent they must use some kind of language which we can learn to imitate.

All diseases are ultimately healed by cells. Doctors 'merely', aid the cells of their patients to do their job. Just imagine, the powerful medicine doctors might practice in the future if they can literally 'tell' cells in their own language what they want them to do! For example, cancer cells might be 'told' to stop growing or at least may be 'summoned' to a certain place on the skin where surgeons can easily scoop them out. Cells at the wound of a lost limb or eye may be 'told' to regrow it. They did it once. If we learn the right 'language' maybe, they can do it again.

3. If cells are intelligent, an organism would be the ecology of a huge population of intelligent individuals.

We tend to believe today that our bodies are highly organized buildings composed of cells which we consider to be dumb miniature machines. Even neurons are treated as complex, yet rather dumb signal switching gadgets. However, if each cell has a certain intelligence to make decisions on its own we would have to reconsider this concept, too. In this case, we would have to look at the structures and functions of our bodies as the result of the interaction of a huge population of intelligent individuals. Possibly, we would have to learn to look at our bodies much the way we consider the complex structures and actions of cities and nations as the result of the actions and interactions of huge numbers of individual people. And 'huge' hardly does justice to the number of cells that make up an organism. For example, one human body has more cells than there would be people on 1000 planet Earths. Also, of course, every cell is a much less intelligent part of a body than a human is part of a city or nation. Still, many of our rather mechanical explanations of body functions would have to be re-examined.

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We believe that the following cellular compartments are essential for the intelligent control of cell movement [See ref 10]

Plasma membrane and cortex.. They correspond to the 'skin' and the 'musculatur' of a cell. One can break this part into small, autonomously moving units, called 'microplasts'. [See ref 8].Their very autonomy implies that cells contain some kind of control system which prevents the autonomous units from moving randomly and independently of each other. Otherwise the cell body would presumably go into uncontrolled convulsions or else freeze up altogether.

Bulk cytoplasm:Mitochondria, other organelles and intermediate filaments. This compartment comprises the actual cell body excluding the nucleus. It corresponds to the 'guts and inerds' of the cell body. Its main cytoskeletal component are the intermediate filaments, although microtubules travers this compartment everywhere. It contains the organelles, such as lysosomes and mitochondria.

Nucleus. From the point of view of the 'intelligent cell' the nucleus is the main library. It contains the blueprints and instructions that have evolved over one billion years of evolution, which tell the cell how to operate, how to rebuild itself (including its 'nerves' and 'brain') after every cell division, and how to act and interact with other cells as they build and maintain an organism.

But there is more. Its gene control systems handles huge numbers of signals that arise from within the nucleus and from its outside word, the cytoplasm. It seems to be structured as a hierarchy of levels of genomic instructions. Starting with genes which constitute the most basic level, transposons may belong to a meta-level in the sense that they represent instructions for genes. There may be a meta-meta-level of 'itinerons' that determine the destinations of transposons, and so forth. In short, the nucleus, far from being a 'dumb' library of the intelligent cell, is clearly an intelligent system in its own rights. We may be seeing here the first glimpse that intelligence is a fractal property: Intelligent ecologies contain intelligent populations,which contain intelligent organisms, which contain intelligent cells, which contain intelligent compartments, which contain...and so forth.

Centrosphere: Centrioles and radial array of microtubules. From the point of view of the 'intelligent cell' the centrosphere is the 'brain' of the cell. Analogous to our own bodies, it projects the 'eyes' in the form of a pair of centrioles. Likewise, its 'nerves' correspond to the radial array of microtubules connecting the centrosphere unbranchingly with the cellular 'musculature' contained in the cortex.

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Why cell movement may appear to be random.

For many years people have believed that cell migration is random, and many still do. There are understandable reasons for this belief. For example, the complex shape changes of migrating cells are quite confusing in the short run. In order to recognize the non-randomness of cell migration much longer observation times are required. Long periods of live cell observation in turn require keeping the cells alive and moving inside a temperature controlled, sealed observation chamber under the glaring lights of a microscope. Often, researchers placed too many cells in the microscope field, which added the complexities of cell-to-cell collisions to the situation. Finally, it is always tempting to call something 'random' even if it is merely 'unpredictable' by the knowledge of the time.

Phagokinetic tracks

Many years ago I found a new technique that allows cells to migrate in the controlled, protected and and dark environment of their normal culture incubator for days and weeks, while the experimenter can still observe their movement. This is possible because the technique, called phagokinetic tracks works like a cloud chamber in which the cells leave tracks of their movements in a carpet of tiny gold particles on their substratum. The phagokinetic tracks can be viewed by scanning electron microscopy like in the illustration above, but it is more convenient to use darkfield light microscopy like in all the illustrations below.

The related tracks of sister cells

Not only are the tracks of sister cells related, but the shapes and internal architecture of their bodies (i.e. their cytoskeleton) appear as symmetrical or identical as their tracks are [See ref 1, ref 2 ]. This suggests that the programs that determine the future movements of the cells are implemented by building and re-building the inner architecture of the cells [See ref 3 ]. .

Significance for cell intelligence:

If cells are able to program directional changes at certain times in their life cycle they must be able to measure angles and time durations. This implication is strengthened by their ability to override these programs in sophisticated ways if they collide with other cells, encounter guiding lines or participate in group migration.

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Colliding cells seem to rebound like colliding billiard balls

Rebounding must be reprogramming

Note: the fast moving cells in the experiments described here are always fibroblasts. Most epthelial cells migrate very little, and if they collide with other epithelial cells they remain together.

Significance for cell intelligence:

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Guidance is not chemical in nature

Cells are not forced mechanically to accept guidance

Significance for cell intelligence:

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Anything that changes from a fast road to a slow one without thinking must obey a 'law of refraction'.

Cells do not obey a 'law of refraction'.

Significance for cell intelligence:

However, if the troop maintains its direction upon changing into the field, and even turns and follows the curb, we know that the mechanical forces of traction do not explain the action of the soldiers now or earlier when they followed the road. Instead, we can infer that they were driven by an interplay between endogenous instructions and exogenous signals that were processed by their signal integration systems. I think, the same logic applies to cells that do not obey laws of refraction. In the case of the soldiers we know that their actions are dictated by their brain. In the case of cells, I suppose, we have to conclude that they have one.

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Cells do not lose guidance at intersections between 'roads'. Instead, they examine their options

Significance for cell intelligence:

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Cells can migrate in groups

Group migration is not a tug-of-war

However, this explanation cannot apply in the case of migrating PtK1 groups. Obviously, if cells in a group pull in opposite directions, they will slow each other down. Thus, the group can never move faster than its members migrating alone. In contrast, PtK1 cell groups are faster than their members.

There is another important difference. The direction of a group in a tug-of-war would fluctuate soemwhat randomly depending on the superimposition of opposing forces from one moment to the other. As shown in the live cell sequence below, that is not the case for PtK1 groups, either.

Significance for cell intelligence:

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The co-ordinated shape changes of migrating cells

When whole animal cells move, different parts of their bodies carry out different movements. For example, the so-called leading front may ruffle while the trailing end, the so-called tail retracts. When a cell makes a turn, it simply produces a new pseudopodium into the new direction. The figure below shows the typical example of a mouse fibroblast that undergoes dramatic and concerted shape changes as it turns a tail into a front and vice versa. In this way it makes a turn without actually rotating its body as a whole.

How can cells move different parts of their bodies differently? The answer came when we found ways to isolate viable fragments from the periphery of cells which we called 'microplasts'. They were able to move independently. By controlling the actions of each such domain the cells can control the movements of different parts of their body. But, of course, it means that the cells must have a central control system to do that. [See ref 8]

Microplasts

Significance for cell intelligence

a. The cell must contain a motor control system that controls the movments of its entire body. It determines when and where its numerous motile domains are allowed to carry out any of their built-in movements. Otherwise, these domains (i.e. cortex domains from which the microplasts were formed) would exercise their autonomy and render the cell incapable of any directional, purposeful movement.

b. The inability of microplasts to restore or create directionality of their movement suggests, that directionality of movement is the product of a higher level of control. Since the directionality of movement responds to obstacles and other unforeseeable events in the path of a moving cell this high level control appears 'intelligent' (i.e. signal integrative and decision-making).

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Eyes map the directions of signal sources in a one-to-one fashion.

The best possible design for a cellular 'eye' would look like a pair of centrioles

Centrioles are able to map the direction of light sources in a one-to-one fashion.

1. absorbs or deflects light of certain wavelengths,
2. carries a photoreceptor at its base (see red spots in the figure below)
3. the lumen of the centriole is opaque for the light.

If the first centriole measures the 'longitude' of the source, the second is oriented perpendicular to the first in order to measure the 'latitude'.

Cellular 'vision' can only make sense for near infrared wavelengths

1. UV, or gamma-rays because they would be mutagenic.
2. Visible light, because inside the body of large animals like whales, there is no visible light (But there is, of course, infrared light equivalent to the the body temperature).
3. Infrared light with wavelength above 10 [µm], because the black body radiation peaks there and makes everything glow with the same high intensity.
4. Infrared light with wavelength above 1.5 [µm], because cells live in water and water absorbs this light heavily.

Problems: angular resolution,diffraction, absorption, and signal-to-noise ratio

Diffraction: How can a blade of 70 [nm] width cast a shadow for near-infrared light that has a much larger wavelength of 800 [nm]? Should light of 10 times the wavelength not simply diffract around the blade? Yes, and no. If the photoreceptor is placed right behind the blade, there will still be a shadow even if the wavelength of the light has a much larger wavelength. However, if the photreceptors would move away from the blade, the amplitude of the diffracted light would rise rapidly and reach it. This little known fact about diffraction can easily be verified with a metal plate playing the role of the shielding blade, and a small transistor radio that plays the role of a photoreceptor. AM stations transmit at frequencies of 100 kHz corresponding to wavelengths of 300 [m] which are much larger than the metal plate and the transistor radio. Still, one can locate the station by pressing the radio against the back of the plate while turning the plate into different directions.

Absorption: How can a blade of only 20-30 [nm] thickness absorb or reflect enough light to cast a shadow? It can if it is metallic, i.e. if it had a high electrical conductivity. For example, a layer of 10 [nm] gold, aluminum or copper is quite opaque, because it reflects incident light very efficiently. Therefore, it will be important for the above theory to test whether centriolar blades or any other microtubular arrays have high electrical conductivity. Human technology has produced already a number of organic polymers with high electrical conductivity. Maybe, nature knows the same trick.

Signal-to-noise ratio: No matter what specific light sources the cellular 'eye' is supposed to detect its near-infrared wavelength is also a component of the black body radiation that is emitted everywhere by virtue of the ambient temperature. Therefore, the ratio between the signal and the background noise must be very unfavorable for the signal detection. In similar situations human engineers resort to a very effective method. They modulate the signal intensity with specific pulsation frequencies which allow the detectors to ignore the background noise as it does not pulsate with a regular frequency. Therefore, we expect the cellular near-infrared light sources to pulsate.

As pointed out in the Appendix, pulsating sources are also required if cells have to distinguish between 2 sources that are located in the same sector of size AR=360°/N (N=number of blades= number of photoreceptors)..

Significance for cell intelligence:

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Experimental setup to test the hypothesis that cells can 'see' near-infrared light sources.

The cells were kept in a live cell chamber with careful temperature and pH control. In order to be able to see the cells in the microscope the entire chamber was illuminated with low intensity, visible light of 600 [nm]. The behavior of the test cell was recorded by video and infrared sensitive CCD cameras.

Note: In the recordings shown here and in other sections the phase contrast images of the beads appear white. The irradiated bead is surrounded by a halo of light because the camera is looking directly into the infrared beam. The scattered intensity received by the cells is approximately 1/1000th of the intensity seen by the camera.

Extension of surface projections towards the pulsating light sources.

Absence of heat effects:No convective currents near light spot.

Absence of chemotactic gradient:Particle pick-up in spite of medium stream towards the particle.

Significance for cell intelligence:

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Cells reach out to a second light source while exposed to the high intensity of the first that they reached

In order to distinguish between these possibilities we offered the cells 2 light spots of equal intensity. If the attraction of the test cells was merely phototactic they would either steer exactly between the light spots while being attracted with equal strength to both. Alternatively, should they ever stray off the midline they would experience increasing intensity from the closer light spot and approach it while ignoring the other which appears the weaker the closer the cell approaches the first. In contrast, we recorded many video sequences which showed that the cells were able to extend first to one and subsequently to the other. The following 2 live cell recordings show examples of this finding.

Significance for cell intelligence:

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Cells cannot reach out to a light source if their center is illuminated with the same light (center-irradiation).

Cells remain able to reach out to a light source if a spot next to their center is illuminated with the same light (peripheral irradiation).

Centrosomal location of the cellular 'eye' (exclusion of nucleus as 'eye'): Cells can still reach out to a light source after enucleation.

Centrosomal location of the cellular 'eye' (exclusion of the Golgi apparatus as 'eye'): Cells can still to reach out to a light source after destruction of their Golgi-apparatus.

Significance for cell intelligence:

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What could be the biological function of cellular infrared 'vision'?

Therefore, we suspect that the infrared 'vision' of cells plays a role in development.

There is an additional reason for this conjecture. Animal cell migration is very slow and animal development occurs simultaneously everywhere in the embryo. What, if a migrating cell makes a mistake and ends up in the wrong place? It cannot stop the development everywhere else, turn back the developmental clock and start from scratch. Therefore, it seems good engineering to provide the migrating cells with the means to 'look ahead' towards their spatial goals.

How far should a cell look ahead? In a developing embryo any spatial goal is a moving target. If it takes a cell 6-10 hours to reach this goal, it would probably no longer exist because development may have changed the area around the goal too much. Since an animal cell needs about 1.5 hours to cross its own diameter of appr. 20 µm its spatial goals should be no further away than 4-6 cell diameters or 80-120 µm. Indeed, our experiments showed that the cells ignored microscopic light sources that were further away than about 60 µm [ ref 13. ].

Cells detect each other at a distance.

Cells react to each other across a film of glass.

Significance for cell intelligence:

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Another line of arguments to support microtubules as good candidates for cellular 'nerves' comes from experiments that interfere with microtubules: If anti-microtubular drugs are given to the cell it can still move all parts of its body, but the remarkable coordination of the typical shape changes is lost. This led to the following question. Are any signals, indeed, propagated along the microtubules to the cell cortex in response to pulsating near-infrared light? If so, how can they be detected?

Experimental strategies to identify changes of microtubules during a putative signal transmission.

Signal transmission is unlikely to drastically change the microtubule structure.

Signal transmission may alter the effectiveness of anti-microtubular drugs.

Disassembly of cytoplasmic asters ('DCA') of CV1 cells.

Therefore, I wrote a program to measure the microtubules in a cell while they were disassembled by the anti-microtubular drug nocodazole. The figure below shows a typical example of the way the program turns the fluorescent patterns of microtubules (panel a) into a set of labeled pixels (panel b) that can be counted.

Significance for cell intelligence:

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The possible role of heme-related molecules in the reception and emission of near infrared light

Chlorophylls and cytochromes as models for the absorbers and emittors of near infrared light.

Heme proteins may also serve as models for the unknown emitter substances of the pulsating infrared light because there is no principal reason why the quantum-mechanical absorption mechanism could not also be an emission mechanism. For example, I have shown recently that bacteriochlorophyll is able to fluoresce in the near infrared range [See ref 18]. As mentioned above,mitochondria contain practically all the heme proteins of tissue cells. Therefore, they appear to be excellent candidates for near infrared emitters of cells. It is also likely that they would emit the light in pulses whenever they discharge a load of ATP molecules that they have synthesized in the course of their normal function, namely oxidative phosphorylation.

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Cellular eyes cannot use lenses to locate light sources.

Cellular eyes cannot compare signal intensities to locate light sources.

There is a further problem. Due to the ubiquitous and violent thermal fluctuations the world of cells is extremely noisy in every respect. Whatever concentrations or intensities a cell on a trial-and-error run may wish to compare from place to place, they are all very unreliable. To be sure, a mathematical average over the signal strength could eliminate the fluctuations, however, in practical terms it would not work.Imagine yourself in a howling hurricane trying to average the strength of coffee aroma in the air order to find your cup!

The ideal eye has no directional preference.

'Blinds' can accomplish the one-to-one mapping of source directions

Each 'blind' must be curved

In order to work in 3 dimensions, the design has to be a cylinder

In order to map longitude and latitude of a source we need 2 cylinders perpendicular to each other.

Pitched blinds achieve continuous angular resolution.

Unfortunately, one cannot increase the number N at will in order to achieve finer and finer resolution because each blind has to have a certain minimal thickness in order to absorb or reflect the signal. But there is a much more elegant way to refine the resolution to such a degree that it is practically continuous: One may pitch the blinds as shown in the figure below.

Back to the drawing board?

It is true, 2 sources can reach receptors on the same blind, but at different positions on the cylinder axis. Pitch or no pitch, any receptors at a specific position on the axis of the cylinder can still be reached by only one of the sources.

A problem arises, though, if the 2 sources are located in the same sector, and some of the receptors of the same blind are irradiated by both at the same time. Obviously, in this case the cell cannot tell the sources apart unless they differ in at least one characteristic. It would be rather simple to distinguish between different sources if their emission would pulsate at a specific frequencies. In this case the cell could compute the location of either source by relating only receptors that receive the same pulsation frequency.

Pulsating source intensities would also offer a solution to the problem of increasing the signal-to-noise ratio that is particularly important in the thermally very noisy world of cells. Indeed, the experiments show, that cells are able to detect pulsating near-infrared light sources but not sources with constant intensity.

Significance for cell intelligence:

• Centrioles are built as a pair of cylinders perpendicular to each other.
• In cross-section they have slanting blades.
• The angle of the blades is such that the backward elongation of each blade intersects the foot of the previous one.
• Each blade is slightly curved.
• Each blade is pitched .

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1. Albrecht-Buehler, G.: Daughter 3T3 cells: Are they mirror images of each other? J. Cell Biol. 72: 595-603, 1977

2. Albrecht-Buehler, G.: The phagokinetic tracks of 3T3 cells. Cell 11:395-404, 1977

3. Albrecht-Buehler, G.: The phagokinetic tracks of 3T3 cells: Parallels between the orientation of track segments and of cellular structures which contain actin or tubulin. Cell 12:333-339, 1977

4. Albrecht-Buehler, G.: The tracks of moving cells. Scientific American 238:68-76, 1978

5. Albrecht-Buehler, G.: The angular distribution of directional changes of guided 3T3 cells. J. Cell Biol. 80:53-60, 1979

6. Albrecht-Buehler, G. and Bushnell, A.: The orientation of centrioles in migrating 3T3 cells. Exp. Cell Res. 120: 111-118, 1979

7. Albrecht-Buehler, G.: Group locomotion of PtKl cells. Exp. Cell Res. 122:402-407, 1979

8. Albrecht-Buehler, G.: The autonomous movements of cytoplasmic fragments. Proc. Natl. Acad. Sci. U.S.A. 77: 6639-6644, 1980

9. Albrecht-Buehler, G.: Does the geomentric design of centrioles imply their function? Cell Motility 1: 237-265, 1981

10. Albrecht-Buehler, G. Is Cytoplasm Intelligent too? In: Muscle and Cell Motility VI (ed. J. Shay) p. 1-21 (1985).

11. Albrecht-Buehler, G. In defense of non-molecular' cell biology. International Review of Cytology 120:191-241 (1990)

12. Albrecht-Buehler, G. The iris diaphragm Model of centriole and basal body formation. Cell Motiltiy and the Cytoskeleton17:187-213 (1990)

13. Albrecht-Buehler, G. Surface extensions of 3T3 cells towards distant infrared sources. J. Cell Biol. (1991)114:493-502

14. Albrecht-Buehler, G. (1992) Speculation about the function and formation of centrioles and basal bodies. In:The Centrosome (ed. V.I. Kalnins) Academic Press, pp 69-102

15. Albrecht-Buehler, G. A rudimentary form of cellular 'vision'(1992) Proc. Natl. Acad. Sci. USA 89:8288-8292

16. Albrecht-Buehler, G. The cellular infrared detector appears to be contained in the centrosome. Cell Motiltiy and the Cytoskeleton 27:262-271 (1994)

17. Albrecht-Buehler, G. Changes of cell behavior by near-infrared signals. Cell Motiltiy and the Cytoskeleton 32:299-304 (1995).

18. Albrecht-Buehler, G., Autofluorescence of live purple bacteria in the near infrared. (1997) Experimental Cell Research 236:43-50

19. Albrecht-Buehler, G. Phagokinetic Track Assay of Cell locomotion in Tissue Culture, In 'Cells: A Laboratory Manual' Vol. 2, Cold Spring Harbor, NY (1997) 77.1-77.10

20. Albrecht-Buehler, G. (1998) Altered drug resistance of microtubules in cells exposed to infrared light pulses:Are Microtubules the 'Nerves' of Cells? Cell Motility and the Cytoskeleton (in press)

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3T3 cells Fibroblasts from a Swiss mouse embryo isolated more than 30 years ago by Howard Green and George Todaro and ever since kept growing in tissue culture as a permanent cell line.

centrioles Centrioles are a pair of small cylinders (0.5 µm x 0.2 µm) oriented perpendicular to each other and located inside the centrosphere adjacent to the nucleus. During mitosis cells place them at the spindle poles. Therefore, only eukaryotic cells may have centrioles. They are found predominantly in animal cells, while most plant cells do not have centrioles. However, both plant and animal cells can make them de novo if they differentiate into migrating cells. For example, human cells have no centrioles during early embryonic development. The fertilized human egg has no centrioles and continues to divide until gastrulation begins and with it the massive migration of cells from the mesoderm. At that point every cell equips itself with a pair of centrioles. Therefore, the frequently copied statement from textbooks that centrioles organize mitotic spindles is wrong: Plant cells and early human cells have perfect mitotic spindles, but no centrioles. We believe that centrioles are the 'eyes' of cells [See ref 9,ref 14,ref 16]

centrosome Discovered and named by early cytologists as an organelle-free spherical area near the nucleus of a cell. It is associated with the Golgi apparatus and contains the pair of centrioles in animal cells. In interphase cells the microtubules radiate unbranchingly from the centrosome to the cell cortex. In dividing cells the centrosome organizes the spindle poles from which the spindle microtubules radiate unbranchingly to the chromosomes. Fertilization requires the passing on of centrioles to the zygote. It is one of the most mysterious parts of the cell. Daniel Mazia considers centrosomes "the bearer of information about the cell morphology". We would like to go further and consider the centrosome as the 'brain' of the cell.

centrosphere(see centrosome)

cortex A dense layer of contractile proteins (actin, myosin, etc.) right underneath the plasma membrane. It executes changes of cell shape and generates the major types of motile surface projections (pseudopodia) such as filopodia, lamellipoia, and blebs.

cytoskeleton A network of 3 types of protein polymers, namely the microtubules, the intermediate filaments and the microfilaments. It also contains numerous proteins that are associated with the fibrous polymers. They nucleate, bundle, cap and link the fibers with each other, with cell organelles and the plasma membrane. It is the mechanical and functional framework for every known cellular function.

cytoplasmic asters The radial array of microtubules of interphase cells with the centrosome at its center. The cytoplasmic asters are distinct from the mitotic asters that radiate from the spindle poles of a dividing cell. In the context of our research we mean specifically radial arrays of microtubules that were regenerated after an anti-microtubular drug had disassembled the original array of microtubules.

emergence The phenomenon that the whole may be more than the sum of its parts ('1+1>2'). For example, flight is an emergent property of all the mechanical parts of an airplane: None of the parts can fly, but the whole of the parts can. Applying this concept to 'intelligence' one may claim that intelligence is an emergent property: ....the level of cell intelligence emerges from the intelligence of cell compartments.The level of organism intelligence emerges from intelligent cells. The level of intelligence displayed by entire populations emerges from intelligent organisms. The level of intelligence of an ecology emerges from the intelligence of its populations... and so forth.

fractal The structural property of an object that consists of self-similar parts. In other words, the parts are smaller copies of the object. So are the parts of the parts, and so forth ad infinitum.

intermediate filaments One of the 3 cytoskeletal fiber types. They have a diameter of 10 nm and are composed of a large family of proteins. A subset of intermediate filaments are also known a keratin fibers which give skin and hair their mechanical strength.

lysosomes Organelles that contain lytic enzymes. They represent the 'digestive' system of cells.

microplast Microplasts are fragments of cells that remain alive for many hours.They come in various sizes. The smallest contain about 2% of a cell volume and consist mostly of cortex surrounded by a plasma membrane. Their movements are autonomous, but restricted to the universally observed shape changes such as spreading, attaching, ruffling, blebbing, waving of filopodia etc. Unlike whole cells they cannot move their entire body to another location after they were forced to round up and respread. This procedure destroys all directional properties that might have been left in their bodies from their parental cell. Microplasts cannot restore or create directionality of movement.

microtubules One of the 3 cytoskeletal fibers. They have a diameter of 24 nm and appear to be hollow tubes, although there are cases where they are filled with an unknown substance.They are composed of two proteins and appear prominently in mitotic spindles. In interphase, they form cytoplasmic asters. The blades of centrioles are composed of microtubules. Our research suggests that they are the 'nerves' of the cells.

mitochondria The 'power supplies' of cells. I believe, they also represent pulsating near infrared light sources because they contain the vast majority of porphyrin (heme-)containing proteins in tissue cells, namely the cytochromes. In phase contrast microscopy they appear as squiggly lines. They 'swim' in a snake-like fashion autonomously through the cytoplasm. They divide autonomously because they are the only cellular compartment with its own DNA. However, that DNA is not a complete genome. Another part of their genome, however, is contained in the cell's nucleus requiring a remarkable level of co-operation between the two.

nucleus From the point of view of the 'intelligent cell' the nucleus is the main library. It contains the blueprints and instructions that have evolved over one billion years of evolution, which tell the cell how to operate, how to rebuild itself (including its 'nerves' and 'brain') after every cell division, and how to act and interact with other cells as they build and maintain an organism. Topologically speaking, the nucleus is located outside the cell because there is a closed surface between it and the cytoplasm. This surface is not entirely closed, though, because it is pierced by so-called nuclear pore complexes.

But there is more. Its gene control systems handles huge numbers of signals that arise from within the nucleus and from its outside word, the cytoplasm. It seems to be structured as a hierarchy of levels of genomic instructions. Starting with genes which constitute the most basic level, transposons may belong to a meta-level in the sense that they represent instructions for genes. There may be a meta-meta-level of 'itinerons' that determine the destinations of transposons, and so forth.

In short, the nucleus, far from being a 'dumb' library of the intelligent cell, is clearly an intelligent system in its own rights. We may be seeing here the first glimpse that intelligence is a fractal property: Intelligent ecologies contain intelligent populations,which contain intelligent organisms, which contain intelligent cells, which contain intelligent compartments, which contain...and so forth.

plasma membrane The 'skin' of the cell that transmits materials and sensory signals beween the inside of the cell and its outside world.

phagokinetic tracks A biological 'cloud chamber' that allows cells to record their own movements in the form of tracks that they leave in a carpet of tiny gold particles on the substrate. [See examples and ref 1, ref 2, ref 4 ]

pseudopodium A motile and ephemeral surface projection out of the cortex of a cell. Examples are filopodia, lamellipodia and blebs.

ruffle A lamellipodium in the process of folding back onto the cell body from which it extended earlier. Seen from the side, ruffles are straight like pencils that swivel around one end near the substrate.

tail The rear part of a migrating cell which usually has a pointed shape that retracts to the body every so often during locomotion [See example]. Both front and tail of a migrating cell are expressions of its so-called polarity. Polarity, in turn, is the expression of the remarkable ability of a cell to turn its initially undirectional body into a directional (vectorial) shape in and out of itself. Mathematicians would call this turning of a scalar into a vector a violation of the Curie principle which is presumably another hint that cells have information-processing abilities.

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• June 1977 Cover of Cell
• September 1977 Scientific American p102-105, Science and the Citizen: Gold Dust Twins
• January 17, 1979 Newsday Part II/1,3 On the Trail Of Moving Cells
• August 20, 1979 Newsweek p 48,52 In: Secrets of the Human Cell
• January 1981 Hospital Practice 16 p28-37 Are Cancer Cells 'Fittest' in Darwinian Struggle?
• March 1981 Scientific American p 86, Science and the Citizen: The Moving Finger
• July/August 1981 Mosaic p 21-27 The Mystery of Cell Movement
• 1983 Introduction of Molecular Biology of the Cell (1st Edition) (ed. B.Alberts, D.Bray, J.Lewis, M.Raff, K.Roberts and J.D.Watson) p XXXIII-XXXVIII, Garland Publishing, Inc. New York .
• 1990 Cover of Cell Motility and the Cytoskeleton Vol 17/4.
• August 1991 Nature:352 p 665, News and Views: Seeing red.
• November 7, 1992 NewScientist p 14 Cells Open Their 'Eyes' To Infrared
• June 1993 Discover p 64 Cells That Reach Out For the Light
• 1996 Life Itself by Boyce Rensberger (Oxford University Press) p. 56-60

• (1976) Cell Motility (ed. R.D.Goldman, T.Pollard, J.Rosenbaum) Spring Harbor Conferences on Cell Proliferation III, Cold Spring Harbor, NY
• April 1978 Scientific American [See ref 4]
• (1979) The role of intercellular signals: Navigation, Encounter, Outcome. (ed. J. Nicholls) Life Science Research Report 14: 75-96, Verlag Chemie Berlin
• (1982) Natl. Cancer Inst. Monogr. 60, International Symposium on Aging and Cancer (Org. Senator Claude Pepper, Lewis Thomas)
• (1982) Cold Spring Harbor Symposia on Quantitative Biol XLVI, Cold Spring Harbor, NY
• (1984) Cancer Cell 1 (ed. A. Levine, W. Topp, J.D.Watson), Cold Spring Harbor, NY
• (1985) Experimental Biology and Medicine 10, Karger, Basel
• (1985) Muscle and Cell Motility VI (ed. J. Shay), Plenum Press New York
• (1988)Biotechnology and Bioapplications of Colloidal Gold(ed. R. Albrecht, G.M. Hodges), Scanning Microscopy International, Chicago
• (1990) International Review of Cytology Volume 120, Academic Press, San Diego, New York
• (1992) The Centrosome (ed. V.I. Kalnins) Academic Press, San Diego, New York
• (1997) 'Cells: A Laboratory Manual' Cold Spring Harbor, NY

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Over the years I have been continuously supported by various funding agencies. The work presented in Chapter 2 has been supported by grants from the National Institute of Health and the National Science Foundation. The work presented in Chapter 3 has been supported by grants from the Office of Naval Research, the United States Army Research Office and the Airforce Office of Scientific Research.

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