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Keith A. Malformations of the human body from a new point of view: 1. Brain and Spinal Cord - 2. Face and Mouth. (1932) Br. Med. J.

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This 1932 paper by Keith are two presentations in his series of six Hunterian Lectures given in 1932 and is an historic description of abnormalities in human development.



See also Keith A. Malformations of the human body from a new point of view: 1. Brain and Spinal Cord - 2. Face and Mouth. (1932) Br. Med. J.

Keith A. Malformations of the human body from a new point of view: 3. Umbilicus - 4. Testes. (1932) Br. Med. J. .

Keith A. Malformations of the human body from a new point of view: 5. Bladder Exstrophy - 6. Perineum. (1932) Br. Med. J. .


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MALFORMATIONS OF THE HUMAN BODY FROM A NEW POINT or VIEW

SIR ARTHUR KEITH’S HUNTERIAN TLECTIIJRES

The following are the first two of a series of six abstracts of Hunterian Lectures delivered in January at the Royal College of Surgeons of England Sir Arthur Keith, F .R.S., Conservator of the Museum.

I.—MALFORMATIONS OF THE BRAIN AND SPINAL CORD

i In the earlier stages of development, operations which are in many respects comparable to those performed by surgeons are carried out automatically by the tissues of the human embryo. Pre—natal surgery might be described as knifeless, bloodless, and surgeonless. When prep-natal operations fail—and modern_research is throwing much light on whythey sometimes fail—children are born with defects which may be so grave that life isvimpossible. But even the lesser defects tax the ingenuity of the modern surgeon. , I , _ . C .

_ The greatest "of these developmental operations carried out in the embryo relate to the enclosure of the entire nervoussystem of the human body. Thanks to the combined labours of embryologists, we are now able to follow the rapid sequence of events ' which brings about the enclosure of brain and spinal cord from forehead to rump_. Although the human brain is by far the most complex structure known to us, it and the spinal cord are in reality a greatly transformed wide strip of skin which runs along the back of the embryo. ..,It,.is a remarkable fact that, although the brain is only needed after birth, yet it is the first of all bodily structures to become differentiated, appearing even before the heart has become functional, and when the embryo is less than one-twenty-fifth of an

inch long. In this early period the skin of thelback is being modified to form nerve ‘plates.

. Medical menlhave becomelsofamiliar with the details of the operation which encloses the nervous system that they are apt to forget the merits of Nature as a surgeon.‘ Two conditions are necessary in everyday surgery: the parts which are to unite must be brought into apposition -_—that condition is dependent on the surgeon. Theother condition is that the parts so broughtgtogetherpmust have the power to unite by healing ; this power is inherent in all living tissues, particularly -in those of the embryo. When the embryo enters the fourth week of development the margins of the nerve plate along the back begin to rise up, so that first a trough is ‘ formed and then a tube. The folded margins of the tubebegin to come‘ in‘ contact at the region of the neck ; edge‘ becomes healed‘ to edge, just as in a wound, except that there is noscar, left to mark the site. From the neck» thepprocess of union spreads forwards and backwards. In less than a

week» it has reached the site of the forehead, and in less '

than two weeks it has reached the lower ‘region of the trunk. ' In less than two weeks the whole of man’s central nervous system becomes submerged in an orderly manner, and the line of submergence is obliterated by a covering of skin—a major operation in plastic surgery is successfully and automatically carried out.» .4 . .. —

_But Nature’s operation may fail completely ; the child then comes into the world with the brain and spinal cord exposed on the head and back as flat plates. More frequently the failure is partial—the lower part of the spinal cord being left exposed——constituting the defect known as spina bifida. We are coming to a knowledge as to why an operation——usually carried out with the utmost success by Nature, or by powers inherent in the tissues—does

MALFORMATIONS OF THE BRAIN AND SPINAL CORD

' ——to injurious influences.


sometimes fail. Spina bifida. can be produced experimentally in the developing eggs of fish and frog by subjecting them——when the neural plates arebeing enclosed By such means any ‘wound can‘ be kept open. ‘ j V ’ p ‘ C '

.The formation of the. ‘eye also entails‘ two operations carried out by developmental surgery. They are minor operations compared with that which segregates the brain from the embryonic skin. Although they failmuch less frequently than that" connected with theicentral nervous system, they are much more instructive from asurgical point of view, for it was while experimenting with the rudiments of the eye that‘ embryologists discovered some of the secrets of developmental surgery. An eye arises by part of the embryonic tube growing out sideways as a pocket to form the retina. VVhen the closed end of the neural or retinal pocket comeseagainst the skin of the embryonic head, the area of skin" so touched begins to behave curiously. It grows inwards in the form of a

pocket,’ which abuts’ against the nerve pocket‘ or out i growth. Both pockets become shut off——the one from the

embryonic skin to form the lens of the eye, the other from the neutral tube to form the sensitive lining of the eyeball. So perfectis the healing at the point where the

lens pocket becomes detached from the skin that not a,

Indeed, that part of the skin becomes the VVhen the first stages of eye

trace is left. clear cornea of the eye.

formation are ‘completed, one side of the eyeball still

remains open ; this fissure is closed by aprocess similar to that which unites the two sidesof a wound, Sometimes union of the fissure of the eyeball is imperfect, giving rise to the defect known as coloboma.

It was in connexion with the development of the eye

_ that embryologists made the first of a series of discoveries

which "are letting us’ into some of Nature’s surgical secrets. It was found that the brain pocket which grows out.to form the retina is a “T master tissue ”—-‘one possessing’ almost magical qualities. If it is prevented..from coming in contact’ with the embryonic skin, or is cut away before it reaches the skin, then the lens-forming area of skin remains quiescent, and no lens pocket is ‘formed. But if the neural pocket be detached, and then be embedded beneath any area of skin of the embryo, then the overlying skin at once begins to‘ form a pocket and a lens.’ The neural pocket possesses this magical power because of a growth—controlling substance formed within it. Magic of a similar kind is known to everyone who has studied the formation of "gallson plants and trees. Lately Professor Spemann of Freiburg discovered that a certain small area of tissue on the back of the very young embryo has these magical or morphogenetic

qualities to a much more wonderful degree than even the

retinal pocket. I Ifa graft is taken of this central tissue,

and if it be implanted ‘on the side of the embryo, then _. the surrounding tissue, which in ordinary course would »have become part of» the body wall, now begins to form

a nerve plate and- a new embryo. The key tojsome of

Nature’s secret surgical processes, carried out as routine

proceeding in building. up the embryonic body, will be foundin a knowledgeof her morphogenic substances. In the matter of repair Nature is still the master. surgeon.

. The elaborate lining of the internal ear, which provides the essential machinery of hearing, begins as an area of exposed skin on the side ‘of the head of the embryo. Through a series of growth and healing processes the area becomeslsubmerged in the form of a pocket, the mouth healinglover and leaving no trace of the original opening. The lecturer knew of no instance in man where the auditory pocket had failed to close, yet in certain fishes it remained open. This was one of the minor discoveries made by John Hunter, founder of the Museum of the ‘Royal College of Surgeons.


Although the surgeon’s immediate interests were confined to making good Nature's failures, he could not help speculating on how the elaborate operations just described had come into being. It was quite evident that no kind of vertebrate animal could have lived with its nervous system spread out as open medullary plates on head and back, exposed to every injury. To find such a stage of evolution one has to turn to the lowest of invertebrate forms of life, where the nerve system is still essentially a part of the skin. The elaborate growth and extension of the nerve system seen in the vertebrate animal became possible only when provision had been made for the earlier stages of development being gone through in positions of shelter and nurture. With the elaboration of intrauterine life all forms of developmental extensions and elaborations became possible. When we see a human child born with its nerve plates still exposed

from head to sacrum, we are in reality witnessing a reversion to a stage of evolution which our ancestors went through long before the coal measures were laid down.

Ii.——Malformations Of The Face And Mouth

Nature, in carrying out her evolutionary projects, has resorted to operations nearly akin to those carried out by modern surgeons. In the formation of the face of all animals which suckle their young two such operations are carried out. Even as late as the seventh week the human foetus has no roof to its mouth ; the mouth—the chewing and sucking chamber—is continuous with the nasal and breath chamber. By the beginning of the third month a fleshy shelf has grown out from each side of the mouth ; the edges of these shelves, coming into apposition along the middle line of the roof of the mouth, unite together by a process similar to that seen in the healing of a wound. The operation proceeds automatically, and is finished in the space of ten days. If it fails, then the condition of cleft palate results, and the surgeon has to make good Nature's failure. Cleft palate interferes with sucking, mastication, and speech. Many of the lion cubs formerly born in the Zoological Gardens, London, suffered rom cleft palate. By altering the diet of the lionesses—— as suggested by Sir John Bland-Sutton——giving them a plentiful supply of vitamins and better surroundings, the occurrence of these defects has been prevented.

Thanks to the labours of Dr. Robert Broom amongst the fossil animals preserved in very early geological formations (Permian and Triassic) of South Africa, we know that the evolutionary movement which ended in shutting the month off from the nose began very many millions of years ago. Amongst these South African fossil forms there occur mammal-like reptiles. Dr. Broom and Professor Watson of University College, London, have traced the evolution of the palatal plates from mere side ledges, until they meet in the middle line of the roof of the mouth and form a complete bony palate. The evolution of the palate, which occupied aeons of time, is repeated in the course of ten days in the face of the human foetus.

The appearance of a bony roof in the _mouths of South African mammal-like reptiles was part of a revolutionary movement which overtook the jaws of the ancestors of true mammals. fifty years ago we knew that the lower jaw of mammals had somehow, and at some remote date, become hinged to the base of the skull in a new way, and

that the old hinge—the one which continues to serve in .

reptiles-—became incorporated in the ear. How such a transformation in structure and function took place was an enigma until the discovery of the South African mammallike reptiles. In them several stages of the transformation have been found——the new joint coming into being and

serving for purposes of hearing. In the Museum of the Royal College of Surgeons there are two human lower jaws which reproduce both hinges—the new mammalian and the old reptilian.

If as yet we know little of the growth-controlling mechanisms which make such evolutionary changes possible, we do clearly realize the functional significance of the change. With a bony roof to the mouth and .1 new hinge to the lower jaw, mastication became possible. Mechanical preparation of the food, formerly thrust on the stomach, was taken over by the teeth and jaws. VVith the development of a palate sucking became possible. Nay, it is not unlikely, when we consider how Nature has lavished her inventive resources on behalf of the young, that the primary purpose was to permit the immature young to be suckled.

At a still earlier date another evolutionary operation was carried out in the face of vertebrate animals—one still to be observed in the face of every human foetus during the latter part of the seventh week of development. If this operation fails, then there results the condition known as “'hare-lip ”—-where one or both nostrils communicate by a single or a double cleft with the roof of the mouth. The first stage in establishing an open communication between nose and mouth is still perpetuated in certain fishes ; with the evolution of air-breathing forms this open trough between nose and mouth became covered over. In the course of development the edges came together, and a process of union, similar to that seen in a wound, united their opposing edges. Thus a respiratory passage was established through the nose to the mouth. The surgeon, in carrying out an operation for the repair of “ hare—lip ” in a human infant, is repeating a process which was introduced during the evolution of the lowest and earliest air-breathing vertebrate animals.

“ Hare-lip ” and “ cleft palate,” the commonest maldevelopments of the human face, may be regarded as relapses .pr reversions to states which prevailed in the infancy of vertebrate animals, but there are other defects which cannot be so explained. There is the condition of “ cyclops,” where both eyes, in place of being separated by the bridge of the nose, are fused together to form one eye under the forehead. The degree of fusion varies. The nose may be absent altogether, or it may form a fleshy, proboscis—like structure just over the median eye. The lower jaw may be absent altogether, so that the ears meet

in front of the neck, and the mouth is reduced to a mere‘

pin-hole. VVe have no reason to believe that at any point of man’s long ancestral chain there was ever a form with a median single eye, a proboscis-like nose, a pin-hole mouth, and ears which met where the chin should be. These cyclopean monsters can be produced to order in the developing eggs of fish and newt. brain—the part to which nose and eyes are attached——is the last to be developed in the growth of the embryonic head. If, when this final stage is being reached, the developing embryo be subjected to injurious conditions, then development is arrested before the right and left eye buds and nose buds have separated. It is under such conditions that human cyclopean monsters are produced, and fortunately they never live. They can never have

produced progeny, and yet they occur to-day just as they

did in the time of the ancient Greeks.

.__ —_

-1 ,1

The Department of Scientific and Industrial Research has now issued its report for the year 1930-31. (Cmd. 3989, H.M. Stationery Office, 3s. net.) This is divided into the following main sections: report of the Committee of the Privy Council for Scientific and Industrial Research; report of the Advisory Council; summary of the work of the research organizations of the Department; and information concerning research

the bones of the old hinge being allocated to the ear and 5 associations.

The front part of the’