Monograph of Dr. rer. nat. Andreas Heinrich Malczan
This brain theory consists of a number of hypotheses, which are listed below.
Humans are vertebrates, their brains evolved from the brains of vertebrates.
Vertebrates are chordates, their nervous system must have evolved from the nervous system of chordates.
Chordates are bilateral segmented animals, so their nervous system must have evolved from the nervous system of bilateral segmented animals.
In the simplest segmented bilateria, the body (with the exception of the head or tail segment) consists of (almost) identical segments.
The simplest segmented bilateria must have emerged from unsegmented bilateria. This happened via the intermediate stage of colony formation. In asexual reproduction, which alternated with sexual reproduction, the offspring were produced by budding. If the daughter creatures produced by budding were not separated, a colony of two, later three and ultimately many identical individual creatures was formed. Each individual represented a segment of the future segmented living being. With the development of a division of labour between the interconnected segments, which could also lead to the specialisation of elements, true segmented animals emerged. In these, the failure to separate the daughter creatures formed by budding was genetically manifested. A segmented being also developed in the sexual reproduction path. This is how the segmented bilateria came into being.
The nervous system of the segmented bilateria developed from the nervous system of the unsegmented bilateria, which now formed the segments of the new, segmented creature.
The special characteristic of these creatures was a specialisation of cells that came together to form organs. The concentration of special nerve cells led to the emergence of neuronal organs, which we call neuronal centres.
The nervous system of the unsegmented Bilateria, whose lineage leads to the vertebrates and ultimately to humans, was a centralised nervous system, which was also symmetrical. There were three types of neuronal centres on each half of the body.
In the motor centre were the motor neurons, which controlled the muscles of the respective half of the body with their axons.
The sensory centre contained the neurons that received input from receptors in this half of the body and contacted it with their axons to the motor neurons of the motor centre.
In the middle value centre there were neurons that served to control important life processes. They received control signals from the sensory and motor centres, but also had an activating effect on them.
The bilateral sensory and motor centres as well as the mean centres are the result of the spatial concentration of cells with the same task into organs and thus represent the archetypes of neuronal organs.
Each neural centre of one half of the body had an inhibitory effect on the analogous neural centre of the contralateral half of the body, so that the signals that were stronger on one half of the body prevailed (contralateral inhibition). This was caused by inhibitory interneurons.
Already in the unsegmented animal, whose lineage led to vertebrates and humans, there were four classes of projection neurons, which we later find in the human brain. In the sensory centre of each half of the body, class 3 neurons projected to the ipsilateral motor centre, where class 5 neurons were located, projecting to motor targets. In both the sensory and motor centres of each half of the body, class 6 mean neurons integrated arousal and projected to the ipsilateral mean centre, so that control of vital functions was also dependent on sensory and motor arousal. Each midpoint centre projected activatingly into both the sensory and motor centres of the same half of the body by exciting class 1 neurons in these centres and these activated the neurons there. Each neuronal centre projected by means of class 2 neurons into a side-switch nucleus, which in turn projected excitatoryly into the contralateral similar centre, but terminated there at inhibitory interneurons. Thus, contralateral sensory, motor and mean inhibition were realised. Both halves of the body were in neuronal competition with each other.
Thus, four classes of projection neurons already existed in the original unsegmented bilateria, whose lineage led to the vertebrates.
During the transition from unsegmented to segmented bilateria, there were interactions between neighbouring segments, and sometimes also between all segments. The common intestine served to absorb nutrients, a common blood circulation served to supply all segments with nutrients and oxygen and to remove metabolic residues and carbon dioxide. There was also a neuronal signal exchange between the segments.
Initially, the axons of receptors not only ended in the sensory centre of their own segment, but increasingly also crossed the segment boundary to the two directly adjacent neighbouring segments and ended there in the sensory centre. This is still observed today even in vertebrates. The dermatomes of humans also cross the segment boundaries, so that the dermatomes of the different segments overlap in each case. This is a relic from grey prehistoric times. The non-segmental signals reached the class 3 neurons via the receptor axons and were passed on by these to the motor centre. However, they did not find any motor targets there, so they also crossed the segment boundaries and returned to the original segment.
Neuronal signal exchange between segments was perfected when two new types of projection neurons evolved, to which we assign neuron class 4 and 5. In the segmented Bilateria, whose lineage leads to the vertebrates, neurons of class 4 took over the signal transport from one segment to the neighbouring segment on the head side. Each receptor excited not only a class 3 projection neuron, which projected to the ipsilateral motor centre of that segment, but also an additional class 4 projection neuron, whose axon crossed the segment boundary and excited its own class 3 neuron in the neighbouring head-side segment and (in the course of evolution) also a projection neuron of the new class 4, which in turn projected to the next head-side segment. Thus, in each sensory centre of each segment there was the complete input of its own receptors (intrinsic input) as well as the input of all receptors of all tail-side segments (extrinsic input). The head segment had the input of all ipsilateral receptors from all segments - a brain could emerge there.
The ascending foreign input reached the motor centre of the segment via class 3 neurons, but did not find any motor targets there, because it originated from lower-lying segments where corresponding receptors controlled the associated motor neurons. Therefore, the extraneous input was fed via class 5 projection neurons in descending order to the segment where the motor targets were located.
Thus, on each half of the body, a nervous system emerged that resembled a rope ladder. On the sensory side, the sensory centres formed the sensory ganglia (clusters of cells), while on the motor side, the motor centres formed the motor ganglia. The sensory ladder spar was formed by the axons of class 3 neurons, the motor ladder spar consisted of the axons of class 5 neurons. The axons of class 3 neurons formed the horizontal commissures. The cell clusters (ganglia) represent neuronal organs.
These rope ladders of the left and right halves of the body were connected to each other via cross commissures in each segment, because each sensory and motor centre projected inhibitoryly into the contralateral one - with the interposition of lateral alternating neurons.
The analogous linkages of the mean centres - also these projected into the neighbouring segments and into the contralateral mean centres of the same segment are almost not visible in this tetraneural (four-stranded) nervous system because the mean systems (initially) consisted of very few neurons.
In the course of evolution, a lateral neighbour inhibition developed - possibly already in the unsegmented bilateria involved. The class 6 median neurons possessed a larger dendrite tree, with which they combined the excitation of a motor or sensory centre and projected it excitatoryly into the associated median centre. It is possible that some of them formed an inhibitory transmitter in the course of evolution. The inhibitory neurotransmitter GABA is formed by decarboxylation of glutamate, which is an excitatory neurotransmitter. So inhibitory neurons could have formed. They sucked up the excitation of the surroundings and inhibited the very first neuron they reached with their short axon. Thus, lateral neighbour inhibition could have developed, which served to amplify the contrast between the neuronal signals. Strong neuronal signals inhibited the weaker ones. Initially, this lateral inhibition served to enhance the contrast between the signals within each neuronal centre.
Lateral neighbour inhibition became established in all segments of the segmented Bilateria, whose lineage led to vertebrates and humans. Since there was signal exchange between the left and right sides of the body, contralateral inhibition also occurred at the segmental level. The left and right sides of the body were in neuronal competition with each other in each segment.
However, there was also a vertical exchange of signals between the segments - on the sensory side ascending via class 4 neurons and on the motor side descending via class 5 neurons. Therefore, the different segments of the body were also in neuronal competition with each other. This competition was present on the sensory side and involved sensory signals - both intrinsic signals and extrinsic signals. Between the neurons of class 3, this neuronal competition was caused by inhibitory interneurons. The same was true for the motor side, where class 5 neurons excited inhibitory interneurons that caused neighbour inhibition. All body segments were in neuronal competition with each other.
This neuronal competition between the segments led to specialisation in a longer evolutionary process. Since the activity of all organs was ultimately neurally controlled (both in terms of input and output), their signals competed with and suppressed each other because of the signal exchange in each segment. The strongest competition took place in the head-side segments, where the signals from the whole body arrived. The signals from the tail-side segments were suppressed more than in the head-side segments. This led to an undersupply of neuronal control signals there, resulting in (gradual) neuronal atrophy, a slow regression. After many millions of years, there was no longer every organ in every segment, but only every type of organ in a few segments. Many important organs eventually remained only in one segment (usually bilaterally) or - if this was not enough to sustain life - in a few directly adjacent segments. However, the organs were not preserved in the head segments, but in the lower-lying segments. In the head segments, the receptor signals of the olfactory, gustatory, visual and vestibular receptors were predominant and won the neuronal competition with the control organs of the different organs, so that these also atrophied in the head segments.
Neuronal competition also led to a slow remodelling of the neuronal organisation. Many receptors initially delivered approximately the same signals in each segment (brightness receptors, taste receptors, verstibular receptors). We call them dependent receptors. These were also in neuronal competition with each other in each segment. The tail-side receptors suffered most from this. In the course of evolution, they were reduced in these segments (neuronal atrophy) and ultimately degenerated. In the end, only one head segment gained dominance for each dependent signal type, its receptor type remained and led to the fact that this sensory modality was only detected in this head segment. Here, a segment could certainly perceive several signal types, but each of them now had a master segment to which it was assigned.
The vestibular sensors took a special path. Initially, each segment on each side of the body had a statocyst in which a statoconium rolled around and irritated the hair cells, but neuronal competition meant that these statocysts only remained in one segment. The statocyste of the remaining segments gradually regressed. The small opening, through which a grain of sand initially entered and acted as a statoconium, enlarged. The grain of sand fell out and the water could enter the cavity. Now the hair cells no longer reacted to the earth's gravitational field, but to the water flow. The cavities became channel-like and developed into the lateral line system, an important long-distance locating sense. It is the relic left behind by the vestibular organs originally present in each body segment.
The independent receptors, which (statistically speaking) had a different signal strength in each segment, remained in all segments. The dependent ones, on the other hand, remained only in the head segments, and there only in one segment at a time. We assign the independent receptors to the trunk senses, while the dependent receptors are attributed to the head senses. The large signal strength of the dependent receptors in the head segments led to the suppression of the control signals of the various organs in the head segments due to the neuronal competition of all signals with each other, so that these were degenerated due to decreasing signal strength and ultimately atrophied.
A special feature developed in the vestibular sense, which initially served not so much for orientation in the gravitational field, but primarily for locomotion. Here, the special structure required a change of sides of the signals already in the unsegmented animals, such as the polyps. This change of sides was preserved in the segmented animals, so that below the segment that possessed the vestibular organs, a signal crossing formed. Signals above this vestibular segment also used this signal crossing, so that specifically the visual signals also crossed to the contralateral side before they descended to control the motor system. The signal crossing consisted of a sensory and a motor part.
The resulting nervous system of those segmented bilaterians whose lineage led to the vertebrates consisted of a tetraneural nervous system, which was also segmented and consisted of the head segments and the trunk segments. In each segment there was a floor of the nervous system consisting of the sensory and motor ganglia, between which commissures and cross commissures ensured horizontal signal transport, while the connectives ensured signal transport from one segment to the next. Sensory signals propagated headward, were conducted to the ipsilateral motor nucleus (ganglion) in each floor and there switched to descending projecting neurons so that they could trigger the motor responses in the target segments. There was lateral inhibition in all nuclei for contrast enhancement, neuronal competition between the left and right sides, and likewise all segments of one half of the body were in neuronal competition with each other.
The first segment specialised in sensor technology. In the second segment, the thalamic floor was created. In the third segment, the tectum opticum developed. In the fourth segment, the torus semicircularis formed. In the fifth segment, a crossing floor was formed so that the vestibular signals could switch to the opposite side to control contralateral muscles in order to establish the standard position of the body. The sixth segment contained another pair of eyes. The seventh segment formed the input and output floor of the head segments, received the trunk signals and controlled the trunk muscles.
The motor output nucleus of the seventh floor was the nucleus ruber. It realised the contralateral inhibition of the counterpart muscles at brainstem level by being output not only to the ipsilateral trunk muscles, but also simultaneously to a lateral alternating nucleus, which projected excitatoryly into the contralateral nucleus ruber and terminated there at inhibitory interneurons. Thus, a point-to-point connection was established between the two output nuclei that realised contralateral inhibition at the brainstem level. The side-changing nucleus of this floor was also bilateral and formed the nucleus olivaris, which projected excitatory into the contralateral nucleus ruber and activated inhibitory interneurons there for inhibition.
Those inhibitory interneurons of the nucleus ruber that were excited by the contralateral nucleus olivaris separated and formed their own nucleus in the course of evolution, which we call the nucleus Purkinje. It switches the output of the nucleus olivaris to the inhibitory transmitter GABA and projects inhibitory into the nucleus ruber to realise contralateral inhibition at the brainstem level. The nucleus purkinje gave rise to the cerebellar cortex of vertebrates.
The primitive vestibular sense - called palaeovestibular sense - provided correction signals in case of deviations from the standard position of the body in water. Due to the low friction, the body continued to oscillate after reaching the standard position, which in turn caused correction signals. Thus, the body oscillated back and forth, and a resulting propulsive component caused forward movement in the water. Fins increased the efficiency of the propulsive component. Thus, the vestibular sense served primarily for forward movement.
The paleovestibular sense was maximum coded. A grain of sand rolled to the lowest point in the statocyst where it excited the hair cells there. The hair cell with the maximum excitation delivered the motor correction signal to the contralateral muscles of the trunk. The change of sides was made possible by the crossing floor.
The vestibular sense was technically improved in the course of evolution. A gelatinous mass protected the hair cells from abrasion. Self-generated statoconia were formed on this mass, replacing the grain of sand. The hair cells now resembled leaf springs, which were firmly clamped at one end and lined the stytocyste cavity. The hair cell that was at the lowest point was now the least excited, just as a vertically positioned leaf spring has the least bending. The vestibular signal was now minimum coded. We call this type of vestibular sense the neovestibular sense.
The minimum-coded vestibular signals were unsuitable for motor control. They had to be converted into maximum-coded ones. The Purkinje nucleus did this by relatively inhibiting the output of the neighbouring mean nucleus - the nucleus reticularis. Thus, the signal strength was reversed and the output was maximum-encoded again. The neurons of the nucleus reticularis that realised this signal inversion split off in the course of evolution and formed a neuron nucleus called the nucleus fastegii, which became a cerebellar nucleus. The part of the Purkinje nucleus that processed vestibular signals became the vestibulocerebellum. It was used for signal inversion of the vestibular signals so that they could cause motor responses as maximum-encoded signals.
The spinal trunk signals of the muscle sensors were treated in the same way as the vestibular signals in the course of evolution. They not only served to control the trunk muscles, but were delivered to the opposite side via the nucleus olivaris, switched there to GABA in the purkinje nucleus and inhibited the mean value signals delivered by the nucleus reticularis in the purkinje nucleus. This inverted them. Thus, the contralateral inhibition of the motor counterparts at the brainstem level was replaced by the inverse excitation (co-activation). The part of the Purkinje nucleus that inverted the spinal trunk signals became the spinocerebellum, and the responsible cerebellar nucleus became the nucleus interpositus, which consists of the nucleus emboliformis and the nucleus globosus. The main task of the spinocerebellum at this time was the inverse excitation of the motor counterparts.
The output of the developing cerebellum not only reached the nucleus ruber to cause the inverse excitation of the motor counterparts there, but also reached the head via class 4 neurons and formed its own ladder in the cord ladder system. This gave rise to the frontal cortex in the course of evolution. This is why we call the cortical ladder with the cerebellum signals the frontal turning loop. Class 4 neurons passed the signals to class 3 neurons, which projected to the motor side of the frontal reversal loop in class 5 neurons. The latter controlled the associated motor neurons in descending order.
Due to the development of different types of receptors and the large increase in the number of receptors of each receptor type, both the number of horizontally projecting class 3 and 2 commissural neurons and the number of vertically projecting class 4 and 5 connective neurons increased in the cord ladder nervous system. The vertical axons formed broad axon bundles that united to form a neural tube, in the middle of which a fluid-filled cavity, the ventricular cavity, was formed. In sectional view, the neural tube again provides the original cord ladder systems, as their original structure was preserved.
In the neural tube, due to the topological arrangement of the neurons and axons, a body model of the signal-providing receptors of all the segments located on the tail side was created in each segment for each modality. These input models were spatially located as layers stacked in half-cylinder shapes. Via class 3 neurons, they projected into motor body models, which also consisted of class 5 neurons arranged in half-cylinders. In this way, each modality was able to take effect motorically. The body models on the top floor represented all the segments of the body; in vertebrates, the cortex emerged from them. This was also divided into four lobes by splitting the modalities into four modal loops.
In the course of evolution, the axons of classes 4 and 5 in the upper two tiers unfolded in such a way that separate turning loops were created for different modality classes. The temporal loop mainly received signals from the hair cell receptors. These served the vestibular system on the one hand and the lateral line sense of the trunk on the other. With the further development of the vestibular system, the sense of hearing developed, whose signals were also evaluated in the temporal loop. Furthermore, the temporal loop received the olfactory signals directly - i.e. without a diversion via the thalamic level - and later also included the developing limbic system. Other sensory trunk senses (electrosensitivity) also supplied the temporal loop. The parietal loop received the signals of the muscle tension receptors of the trunk as well as those of the tendon organs and the signals of other joint position analysing receptors of the trunk. With the development of sensors for the sense of touch and pain, their signals were also evaluated in the parietal loop. Later, the analogue signals of the developing fins or the extremities of the tetrapods were added. The occipital loop received the output of the visual receptors. The output of the cerebellum was fed to the developing frontal loop. The different lobes of the vertebrate brain emerged from the turning loops.
In the neural tube, the bodies of the neurons were located on the inside, while the axons ran on the outside. The strong increase in the number of axons, which moved externally from the nucleus olivaris to the opposite side in order to dock internally in the cerebellum to its Purkinje cells, led to the emergence of a slit-like neural tube opening through which these axons moved inwards. The ventricular fluid exiting through the gap now surrounded the primordial brain from the outside as well. The cerebellum itself enlarged to such an extent that it was forced out of the neural tube interior through the resulting gap and was now attached to the neural tube on the outside.
The Purkinje cells of the early spinocerebellum controlled the contralateral muscles. Therefore, this spinocerebellum was a motor body model of the contralateral side.
The neurons of class 3 found an access to the cerebellum as moss fibres. Their signals represented the ipsilateral body models and originated from the muscle spindles, later also from the tactile and pain receptors. Already at the neural tube level, these signals excited the contralateral motor neurons for the purpose of the creature's self-protection. Since the Purkinje cells represented the contralateral side, they were also excited in the cerebellum by the tactile and pain signals. If an action on the body produced tactile or pain signals, the contralateral muscles were excited and moved the affected part of the body away from the site of the action. The excitation of the Purnkinje cells by the mossy fibres occurred via the interposition of the granule cells, which acted as local interneurons. Thus, the spinocerebellum additionally took over the neural tube's own apparatus and served as self-protection. The Purkinje cells represented the contralateral motor body model, whereas the granule cells represented the ipsilateral sensory body model.
With the increase in receptors, muscles and motor neurons, the nucleus olivaris and the cerebellar cortex began to expand greatly in circumference; folding allowed a greater increase in area. The dendrite trees of the Purkinje cells followed this circumferential expansion and developed broad, spreading dendrite trees that became increasingly flat. The axons of the granule cells, which had to reach as many Purkinje cells as possible, grew in the orthogonal direction.
Signals from the ipsilateral muscle spindles also found access to the cerebellum via the moss fibres. However, they had an inhibitory effect on the Purkinje cells, as these represented the contralateral motor body model. This inhibitory effect was caused by basket and stellate cells, which were excited by these (motor) moss fibres. A strong motor excitation of a muscle thus reduced the excitation of the counterpart in the cerebellum.
In the uppermost floor of the cord ladder system, the cortical floor, which had disintegrated by splitting into four modality floors, the striatum emerged in a longer developmental path. All cortical neurons of class 6 projected into the dopaminergic centre of the seventh floor, the substantia nigra pars compacta. This was immediately adjacent to the nucleus ruber and was also present bilaterally. Like every median nucleus, this projected back to the cortical floor. There, however, this back projection ended at the inhibitory interneurons that served lateral inhibition. These segregated spatially and formed the striatum, or more precisely the striosomes of the striatum. They switched the cortical signals returning from the substantia nigra to the inhibitory transmitter GABA. In the course of evolution, they formed their own projection axons, which terminated in the nucleus ruber precisely at the neurons that also received the associated excitatory cortex signal, and inhibited them. Due to the dopaminergically induced time delay, this neuronal differential circuit was now time-sensitive and could detect movements of objects perceived via a wide variety of modalities. Movements could now be smelled, seen, felt, i.e. detected multimodally and generate movements in the nucleus ruber, since this was the motor output nucleus of the forebrain.
Two cortical projections developed. On the one hand, the cortical midline neurons of layer 6 projected via the tractus tegmentalis to the nucleus ruber and from there via the nucleus olivaris into the climbing fibre system of the cerebellum. This midline area developed into the pontocerebellum. On the other hand, class 5 cortical neurons projected from the same cortex areas via the bridging nuclei and the mossy fibre system into the granule cells of this pontocerebellum. Here, both projection pathways were true to the cluster, the signals from the climbing fibres and those from the granule cells originated from the same cortex cluster and both led to the excitation of the Purkinje cells. Signals from neighbouring clusters had an inhibitory effect on the Purkinje cells with the interposition of basket and star cells, whereby the great length of the parallel fibres enabled the provision of signals from neighbouring clusters. A cortex cluster consisted in each case of a mean neuron and those neurons of class 5 that excited exactly this mean neuron. Output neurons in the dentate nucleus, the cerebellar nucleus of the developing pontocerebellum, only generated a signal if both neurons from the assigned cortex cluster were active and at the same time activity was also present in the neighbouring clusters, i.e. a complex signal was present.
Tetanic excitation of Purkinje cells and pontocerebellar interneurons caused LTP and LTD of synaptic coupling in the presence of granule cell activity. As a result, Purkinje cells were imprinted with an intrinsic signal. If this was present, cerebellum output was significantly stronger. Due to the divergent distribution of the climbing fibre signals to several Purkinje cells, several different complex signals could be learned per cerebellum cluster.
Nerve cells could die. The transmission reliability could be increased by distributing a signal to several nerve cells so that an axon bundle ensured the transmission. With divergent distribution to several, later many, neighbouring neurons, a distance-dependent, exponential signal attenuation occurred.
A pair of motor signals, consisting for example of the muscle spindle signal of a muscle and its motor counterpart, was minimum coded in the divergent signal distribution to a number of output neurons, because the superposition of two strictly concave functions produces a minimum in which the location of the minimum depends on the firing rate of the two input neurons. This minimum-coded signal thus encoded the firing rate ratio of the two input signals, i.e. in principle approximately the joint angle. When this minimum-encoded signal reached the spinocerebellum, it was inverted and maximum-encoded. In the nucleus ruber, the motor output nucleus, the two motor neurons of the two muscles were triggered by these maximum-encoded output neurons, so that the joint angle could be set again. The signal divergence in the nucleus olivaris led to the spatial inflation of this structure, and the lack of space resulted in the formation of folds. Analogous observations were made in the cerebellar cortex. In the nucleus ruber, this signal divergence was reversed by signal convergence. The magnocellular neurons required for this formed the magnocellular nucleus part of the nucleus ruber.
The signal divergence also occurred in the cortex. The class 4 input neurons distributed the input in the area to very many class 3 neurons, which in turn projected to the motor cortex side in class 5 neurons. Thus, there were extreme value coded signals in the cortex as well. In the visual cortex, the magnocellular input of the light-dark signals even produced a maximum-coded signal that encoded the angle of inclination of a straight line.
In contrast to the nucleus ruber, the cortical signal divergence resulted in maximum-encoded signals. This was due to the fact that the signal attenuation occurred in the area, so that the distance was quadratically included in the attenuation. Electrical potential differences of the cell membrane were caused by the charges of ions whose concentration decreased with the square of the distance when the ions had to distribute themselves in the area. The excitation function of a single output neuron was concave. The superposition of several such concave functions led to the appearance of maxima, whose position depended on the parameters of the system.
These cortical, extreme value-encoded signals were also included in the basal ganglion system. Via the dopaminergic diversions via the substantia nigra pars compacta, they reached the matrix of the striatum, whose neurons were permanently excited by the cortical input, and inhibited them. As a result, these signals were inverted. However, they no longer travelled to the nucleus ruber, but upwards to the ventral thalamus. There they inhibited the similar cortex signals from which they had been derived. However, since they had taken a dopaminergic diversions, they represented past signals that inhibited present signals. If nothing had changed in the meantime, there was no output at all, excitation and inhibition eliminated. Only moving objects left a residual signal. Thus, an image of those objects that had moved in the meantime was created in the ventral thalamus. Since the basal ganglia were present in all cortical turning loops and later in all lobes of the brain, moving objects of all modalities were recognised. Movements could therefore be smelled, seen, felt, perceived by the vestibular system, as well as movement recognition, e.g. through the lateral line sense or the electrosensory sense.
Monograph of Dr. rer. nat. Andreas Heinrich Malczan