Like the chicken and the egg

Like the chicken and the egg, experimentation and conjecture revolve around each other at the heart of the scientific method. In the science of life, however, isolation of variables and repetition of trials have often proven difficult and ethically convoluted. Biological study largely evolved in conjunction with the philosophy of medicine, the natural connection being that an understanding of biological function is crucial in repairing dysfunction. Regardless of whether theory or practice arose first, “good” medicine may arguably be characterized by conservative practice. Ironically, however, most medical advances arise from happen stance, or from isolated extenuating circumstance, and after wide spread dissemination and adoption are they more thoroughly investigated; surgery for instance. Amputations, weapon removal, cataract couching, denture fixation, and even basic reconstructive surgery are documented early in the first millennia BC. Homer describes many surgical practices in his depictions of the Trojan War, but still attributed infection and disease to the uncontrollable will of the Gods. The complexity behind why of two people, with apparently similar health (or as the case may be, ailment), one turns out fine whereas the other might fall into sickness or die was beyond the philosophy and instruments of the time (and in fact wasn’t even fully understood until the 1850’s with the founding of epidemiology by John Snow). Without the proper physiochemical and biomolecular tools, and live imaging techniques of the modern century, an in depth holistic understanding of biological function was unattainable. Instead, experiments presented themselves as anatomical dissections to determine what all, and where all, everything is. Naturally, theory developed in response and vivisections subsequently arose and developed to test what all everything does, a task still hardly dented in the modern age.  

Without the instruments or methods for developing philosophy, ancient medicine progressed through widespread dissemination of practices, often between remote destinations, proven to be tried and true. Good examples are rhinoplasty, in which skin from the forehead is used to replace a nose, and cataract couching, in which the crystalline deposit blocking vision is moved out of the way, where first described in Hindu medical texts mid-millennia BC, and subsequently where included, described in generally similar terms, in the medical encyclopedia composed by Celsus (~300 AD). Shared nuances, such as specifying which hand is best for certain parts of the procedure, construction of instruments, and important help to include for expediting the process are too great for coincidence, and indicate they didn’t arise separately. Doctors tackling the issue of ‘experimenting’ with new procedures was first documented in Alexandria (~300 BC), with Herophilus and Eristatus practicing procedures on criminals sentenced to death by first inflicting than repairing ailments. Although the logic being many would benefit from the suffering of few, the practice may still seem ostensibly analogues to the atrocities of Nazi medical experimentation. The two, however, couldn’t possibly more apart, and in their separate ways each illustrate the general consensus of ‘good’ medicine being typified by a cautious and conservative approach. Permission to perform the first criminal vivisections was a city wide affair, and surprisingly controversial considering the era, and the subjects being dead men walking anyways. Though a relatively rare occurrence, the hands on experience was invaluable for training doctors, and garnished major contributions to understanding biological function. On the other hand, the reckless abandonment of human life displayed in Nazi medical experimentation, often focused on testing the bounds of human tolerance for extreme conditions, actually afforded very little relevant and no scientifically useful information despite the massive number of trials and variety of subjects implicated.        

The ethics of justified medical experimentation, however, historically only apply to human subjects and very little regard has been paid to animals. The amount of animals that die each month from experimentation is roughly equal to the number of lives lost in the Holocaust (~6-10 million), and arguably from far more gruesome means. The difference, however, is that the information is unattainable by any other means, and has proven essential for treating human diseases and developing less invasive techniques. One may argue that the ends justify the means or that animals lack the agency to comprehend their circumstance. Ironically however, the more we learn the more it seems that in fact our and animal psyches are not all that different, and that barring inherited genetic disorders, the cause of ailment is based on environmental circumstance (including contact with other organisms) and lifestyle, and that there are no ‘magic-bullet’ cures, just good old fashioned healthy living. Further, a huge body of evidence is accumulating suggesting regular use of most drugs (inherently always developed through animal testing) actually have severe health repercussions. Unlike the chicken and egg problem, which has been solved through the theory of evolution (the egg must have came first, and was a mutant laid by an almost chicken), the tragic comedy of medical experimentation may have no answer, and the harder we look the more it seems we’ve had the solution all along.      

Modern Medicine and Lessons from Antiquity

A new era of computer aided drug discovery and medicinal simulation is upon us, replacing the paradigm of test and try again. For Millennium, man relied on nature to provide beneficial compounds such as natural herbs, opiates for anesthesia, or penicillin and related compounds as natural antibiotics. Bread with blue mold was a staple of medieval folk medicine for treating infected wounds, but the common underlying thread of good medicine seems to be relying on tried and true remedies, and new discoveries face trial by fire. The last fifty years or so, however, have been marked by explosive advances in medical technology and associated methodology. Most notably the computer has been at the heart of all advances. It has enabled data analysis in days what previously could not accomplished in lifetimes, entire medical histories can be assessed and compared, it has allowed analysis of physical data revealing the structure and function of cellular machinery at approaching an atomic resolution, and it has allowed for the construction of exceedingly complex models for interpreting the data we collect. They are shifting the paradigm of drug discovery. Generally speaking, what's traditionally been done is chemists take a chemical compound known to have a specific mechanism of action, they design thousands of variants on it, test them on rodents then non-rodent mammalian models, take the top competitors, and more thoroughly investigate the pharmacokinetic properties of the drug, its toxicity, absorption and excretion. The most promising compounds then move onto clinical trials in volunteers, their effects are traced for a couple decades, and statistical analysis is applied to determine whether the drug had a marked positive influence. Successes have generally been shots in the dark, and even so they almost always have serious side effects and everyone reacts differently to them anyways. Computers aid in the individualization of medical approaches. With medicine becoming more and more of an industry, its becoming easier to overlook individual concerns, an advanced enough computer program, in a sense however could potentially act as an individual doctor.
The doctors of Antiquity laid the foundation for a theoretical approach to medicine, conjecturing possibilities and using the minimal means they had for testing them. Modern advances however yield more information than were able to analyze, and people are often too caught up on finding a "magic bullet" cure, when increasingly its becoming evident the Greek holistic view is indeed the truth. Although these tools may provide means for analyzing problems, they are still far off from designing treatments for all individuals, and then even more so there isn't the industrial infrastructure anyways to produce it all. I think the greatest medical advance will be when individuals start utilizing all the information available to them and start living preventatively instead of letting others postulate solutions.

Ben J Bibliography

     

1) Anita Guerrini. Experimenting with Humans and Animals; From Galen to Animal Rights Johns Hopkins University Press, Baltimore (2003)

Summary             A broad overview of experimental and medical development from the 3^rd BCE until modern day, including understanding anatomy through vivisection and disease as microscopic molecular disorders and their application to surgery and vaccination is discussed.

3) Maud Gleason. Shock and Awe: the performance dimension of Galen's anatomy demonstrations (2007) Princeton/Stanford Working papers in classics
Summary            Galen's dissection demonstrations are described with a focus on the performance aspects used by Galen to enhance his reputation. Some more notorious stories including his dissection and resuscitation of an Ape are recalled, and the tools and techniques used are described.

2) Peter James and Nick Thorpe. Ancient Inventions (1994) Random House publishing group, NY.

Summary             I focused on descriptions of the tools and techniques employed for ancient techniques including couching of cataracts, reconstructive surgery, and denture construction and fixation.

      3) JR Kirkup. The history and evolution of surgical instruments II:Origins: function: carriage: manufacture Annals of the Royal College of Surgeons of England (1982) vol. 64

Summary             An overview of instrumental development from primitive substitutions of shell or bone for teeth, and shaping of metal rods into simple surgical tools, and developments leading to more complicated fabrications. 

4)  John Stewart Milne. Surgical Instruments in Greek and Roman Times. Claredon Press: Oxford, 1907. 

Summary             Complementing resource for comparing an early 20^th CE dissertation on ancient surgical instruments to the late 20^th CE reference above.

5) John Michalczyk. In the Shadow of the Reich: Nazi Medicine (1997)

Summary             This documentary describes the rise of the Nazi regime. The steps leading up to the implementation of their "final solution" are presented, starting with mandatory sterilization for the mentally retarded modeled after preceding American legislation,  the concept of "social hygiene" and purification, the role of doctors in ghettos, and the inhumane "science" of death camps.

6) J Horner, FD Minifie. Research Ethics I: Responsible Conduct of Research (RCR)—Historical and Contemporary Issues Pertaining to Human and Animal Experimentation Journal of Speech, Language, and Hearing Research; Vol. 54, S303–S329 (2011)

Summary              The chronological  order of major legislation and developments in research ethics, largely in the last two centuries, are cataloged in this article supplement.

7) Steven Johnson. The Ghost Map. Riverhead Books: NY (2006)

Summary           The 1850's cholera outbreak in London is described and the mentality of major figures and ideas of its cause are outlined. Most notably, John Snow's medical methodology involving large scale cataloging of lifestyles surrounding affected versus unaffected individuals, tracing the outbreak back to a sewage contaminated pump, and discovery of microscopic infectious agents is presented. 

8) S Mukhopadhyay, GC Layek. Analysis of blood flow through a modelled artery with an aneurysm Applied Mathematics and Computation Volume 217, Issue 16, 15 (2011) 6792-6801  

Abstract                The intention of the present work is to carry out a systematic analysis of flow features in a tube, modelled as artery, having a local aneurysm in presence of haematocrit…. the numerical illustrations presented in this paper provide an effective measure to estimate the combined influence of haematocrit and aneurysm on flow characteristics.      

      9) John Cullis, John Hudson and Philip Jones A Different Rationale for Redistribution: Pursuit of  Happiness in the European Union Journal of Happiness Studies Volume 12, 2, (2011) 323-341

Abstract                This paper considers the role of redistribution in the light of recent research findings on self reported happiness. The analysis and empirical work reported here tries to relate this to a representative actor ‘homo realitus’ and the ‘pursuit of happiness’ rather than the traditional ‘homo economicus’. Econometrically estimating the determinants of happiness in the European Union (EU) using Eurobarometer data and the construction of an ‘Index of Happiness’ facilitates policy simulations. Such simulations find that in terms of average happiness there is little advantage to redistributing income within a country, but more from redistributing income between countries. The importance for happiness of relative income, average standard of living, marital status and age are confirmed. The theoretical rationale for redistribution is also examined.

10) Y Ohno, et al.   High-Performance Drug Discovery: Computational Screening by Combining Docking and Molecular Dynamics Simulations (2001) Public Library of Science http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2746282

 Abstract           Virtual compound screening using molecular docking is widely used in the discovery of new lead compounds for drug design. However, this method is not completely reliable and therefore unsatisfactory. In this study, we used massive molecular dynamics simulations of protein-ligand conformations obtained by molecular docking in order to improve the enrichment performance of molecular docking. Our screening approach employed the molecular mechanics/Poisson-Boltzmann and surface area method to estimate the binding free energies....This result indicates that the application of molecular dynamics simulations to virtual screening for lead discovery is both effective and practical. However, further optimization of the computational protocols is required for screening various target proteins.

11) KL Steinmetz, EG Spack. The basics of preclinical drug development for neurodegenerative disease indications (2007) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2697630   
Abstract             Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties...

12)  Kuntz. Structure-based strategies for drug design and discovery (1992) Science 257 pg 1078-82   

13) Rebecca White. Drugs and nutrition: how side effects can influence nutritional intake (2010) Proceedings of the Nutrition Society, 69, 558-564
  Abstract             There are many factors that can influence nutritional intake. Food availability, physical capability, appetite, presence of gastrointestinal symptoms and perception of food are examples. Drug therapy can negatively influence nutritional intake through their effect on these factors, predominantly due to side effects. This review aims to give a brief overview of each of these factors and how drug therapy can affect them.  




 Selected Excerpts from Primary Sources

Galen On The Natural Faculties 1.15

Here let us forget the absurdities of Asclepiades, and, in company with those who are persuaded that the urine does pass through the kidneys, let us consider what is the character of this function. For, most assuredly, either the urine is conveyed by its own motion to the kidneys, considering this the better course (as do we when we go off to market!¹), or, if this be impossible, then some other reason for its conveyance must be found. What, then, is this? If we are not going to grant the kidneys a faculty for attracting this particular quality,² as Hippocrates held, we shall discover no other reason. For, surely everyone sees that either the kidneys must attract the urine, or the veins must propel it.

 Celsus De Medicina Book 1, Prooemium

Homer stated, however, not that they gave any aid in the pestilence or in the various sorts of diseases, but only that they relieved wounds by the knife and by medicaments. Hence it appears that by them those parts only of the Art were attempted, and that they were the oldest.[p. 5] From the same authority, indeed, it can be learned that diseases were then ascribed to the anger of the immortal gods, and from them help used to be sought; and it is probable that with no aids against bad health, none the less health was generally good because of good habits, which neither indolence nor luxury had vitiated: since it is these two which have afflicted the bodies of men, first in Greece, and later amongst us; and hence this complex Art of Medicine, not needed in former times

At first the science of healing was held to be part of philosophy, so that treatment of disease and contemplation of the nature of things began through the same authorities; clearly because healing was needed especially by those whose bodily strength had been weakened by restless thinking and night-watching. Hence we find that many who professed philosophy became expert in medicine, the most celebrated being Pythagoras, Empedocles and Democritus. But it was, as some believe, a pupil of the last, Hippocrates of Cos, a man first and foremost worthy to be remembered, notable both for professional skill and for eloquence, who separated this branch of learning from the study of philosophy. After him[p. 7] Diocles of Carystus, next Praxagoras and Chrysippus, then Herophilus and Erasistratus, so practised this art that they made advances even towards various methods of treatment.

he Art of Medicine was divided into three parts: one being that which cures through diet, another through medicaments, and the third by hand. The Greeks termed the first Διαιτητικήν, the second Φαρμακευτικήν, the third Χειρουργίαν.

Apollonius and Glaucias, and somewhat later Heraclides of Tarentum, and other men of no small note, who in accordance with what they professed called themselves Empirici (or Experimentalists)

For they believe it impossible for one who is ignorant of the origin of diseases to learn how to treat them suitably. They say that it does not admit of doubt that there is need for differences in treatment, if, as certain of the professors of philosophy have stated, some excess, or some deficiency, among the four elements, creates adverse health; or, if all the fault is in the humours, as was the view of Herophilus; or in the breath, according to Hippocrates; or if blood is transfused into those blood-vessels which are fitted for pneuma, and excites inflammation[p. 11] which the Greeks term φλεγμόνην, and that inflammation effects such a disturbance as there is in fever, which was taught by Erasistratus; or if little bodies by being brought to a standstill in passing through invisible pores block the passage, as Asclepiades contended — his will be the right way of treatment, who has not failed to see the primary origin of the cause

Some following Erasistratus hold that in the belly the food is ground up; others, following Plistonicus, a pupil of Praxagoras, that it putrefies; others believe with Hippocrates, that food is cooked up by heat. In addition there are the followers of Asclepiades, who propound that all such notions are vain and superfluous, that there is no concoction at all, but that material is transmitted through the body, crude as swallowed

the Art of Medicine was not a discovery following upon reasoning, but after the discovery of the remedy, the reason for it was sought out

More rarely, yet now and again, a disease itself is new. That this does not happen is manifestly untrue, for in our time a lady, from whose genitals flesh had prolapsed and become gangrenous, died in the course of a few hours, whilst practitioners of the highest standing found out neither the class of malady nor a remedy. I conclude that they attempted nothing because no one was willing to risk a conjecture of his own in the case of a distinguished personage, for fear that he might seem to have killed, if he did not save her;[p. 29] yet it is probable that something might possibly have been thought of, had no such timidity prevailed, and perchance this might have been successful had one but tried it.

Themison, contend that there is no cause whatever, the knowledge of which has any bearing on treatment: they hold that it is sufficient to observe certain general characteristics of diseases; that of these there are three classes, one a constriction, another a flux, the third a mixture. For the sick at one time excrete too little, at another time too much; again, from one part too little, from another too much

But if Erasistratus had been sufficiently versed in the study of the nature of things, as those practitioners rashly claim themselves to be, he would have known also that nothing is due to one cause alone, but that which is taken to be the cause is that which seems to have had the most influence

Erasistratus himself, who says that fever is produced by blood transfused into the arteries, and that this happens in an over-replete body, failed to discover why, of two equally replete persons, one should lapse into disease, and the other remain free from anything dangerous

Hippocrates, said that in healing it was necessary to take note both of common and of particular characteristics.

Cassius, the most ingenious practitioner of our generation, recently dead, in a case suffering from fever and great thirst, when he learnt that the man had begun to feel oppressed after intoxication,[p. 39] administered cold water, by which draught, when by the admixture he had broken the force of the wine, he forthwith dispersed the fever by means of a sleep and a sweat.

Hippocrates Nutriment, introduction

A later Heraclitean, whether a professional doctor or not is uncertain, applied the theory of perpetual change to the assimilation of food by a living organism, and Nutriment is the result.

Apparently nutritive food is supposed to be dissolved in moisture, and thus to be carried to every part of the body, assimilating itself to bone, flesh, and so

Air (breath) also is regarded as food, passing through the arteries from the heart, while the blood passes through the veins from the liver. But the function of blood is not understood ; blood is, like milk, "what is left over" (πλεονας1μός2) when nourishment has taken place. Neither is the function of the heart understood, and its relation to the lungs is never mentioned.

Hippocrates De morbo sacro

The brain of man, as in all other animals, is double, and a thin membrane (meninx)divides it through the middle, and therefore the pain is not always in the same part of the head; for sometimes it is situated on either side, and sometimes the whole is affected; and veins run toward it from all parts of the body, many of which are small, but two are thick, the one from the liver, and the other from the spleen. And it is thus with regard to the one from the liver: a portion of it runs downward through the parts on the side, near the kidneys and the psoas muscles, to the inner part of the thigh, and extends to the foot. It is called vena cava. The other runs upward by the right veins and the lungs, and divides into branches for the heart and the right arm. The remaining part of it rises upward across the clavicle to the right side of the neck, and is superficial so as to be seen; near the ear it is concealed, and there it divides; its thickest, largest, and most hollow part ends in the brain; another small vein goes to the right ear, another to the right eye, and another to the nostril. Such are the distributions of the hepatic vein. And a vein from the spleen is distributed on the left side, upward and downward, like that from the liver, but more slender and feeble.

De morbis popularibus, on the epidemics Phthisis: dwindling or wasting away, tuberculosis

IN THASUS, about the autumn equinox, and under the Pleiades, the rains were abundant, constant, and soft, with southerly winds; the winter southerly, the northerly winds faint, droughts; on the whole, the winter having the character of spring. The spring was southerly, cool, rains small in quantity. Summer, for the most part, cloudy, no rain, the Etesian winds, rare and small, blew in an irregular manner. The whole constitution of the season being thus inclined to the southerly, and with droughts early in the spring, from the preceding opposite and northerly state, ardent fevers occurred in a few instances, and these very mild, being rarely attended with hemorrhage, and never proving fatal. Swellings appeared about the ears, in many on either side, and in the greatest number on both sides, being unaccompanied by fever so as not to confine the patient to bed; in all cases they disappeared without giving trouble, neither did any of them come to suppuration, as is common in swellings from other causes. They were of a lax, large, diffused character, without inflammation or pain, and they went away without any critical sign. They seized children, adults, and mostly those who were engaged in the exercises of the palestra and gymnasium, but seldom attacked women. Many had dry coughs without expectoration, and accompanied with hoarseness of voice. In some instances earlier, and in others later, inflammations with pain seized sometimes one of [p. 101]the testicles, and sometimes both; some of these cases were accompanied with fever and some not; the greater part of these were attended with much suffering. In other respects they were free of disease, so as not to require medical assistance.

Early in the beginning of spring, and through the summer, and towards winter, many of those who had been long gradually declining, took to bed with symptoms of phthisis; in many cases formerly of a doubtful character the disease then became confirmed; in these the constitution inclined to the phthisical. Many, and, in fact, the most of them, died; and of those confined to bed, I do not know if a single individual survived for any considerable time….The urine was thin, colorless, unconcocted, or thick, with a deficient sediment, not settling favorably, but casting down a crude and unseasonable sediment.

n the course of the summer and autumn many fevers of the [p. 102]continual type, but not violent; they attacked persons who had been long indisposed, but who were otherwise not in an uncomfortable state.

Nazi Eugenics and "medical" experimentation

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From Cures to Causal reasoning

             Experimentation is integral for improving modern medical practice. The ability to treat a medical disorder lays in both understanding how things ought to function, and isolating the variables of disorder. Ancient Greek and Roman conceptualization of medical causation largely arose between the 8^th and 3^rd century BC, and by the 2^nd century CE had evolved into an essentially modern medical philosophy. Many common medical practices, including medicaments and surgical practices arose significantly earlier even dating back to 3000 BC in Egypt; the cradle of medicine. I will be discussing which Greek philosophers and what initiated these changes, how they developed, and the impacts they had. In particular, the generally conservative nature of medical progression and the typical feature of tweaking tried and true methods rather than developing new ones.  Common medical instruments are portrayed below, most of which had functions and application that remained essentially static throughout the medical enlightenment and the form and function of their modern counterparts remain practically unchanged. Celsus comments on the conservative nature of medicine in De Medicina;
  
More rarely, yet now and again, a disease itself is new. That this does not happen is manifestly untrue, for in our time a lady, from whose genitals flesh had prolapsed and become gangrenous, died in the course of a few hours, whilst practitioners of the highest standing found out neither the class of malady nor a remedy. I conclude that they attempted nothing because no one was willing to risk a conjecture of his own in the case of a distinguished personage, for fear that he might seem to have killed, if he did not save her;[p. 29] yet it is probable that something might possibly have been thought of, had no such timidity prevailed, and perchance this might have been successful had one but tried it.

Ancient Greek and Roman Medical Instruments

Michael Lahanas

http://www.mlahanas.de/Greeks/MedicalInstruments.htm

 Hooks, bone drills, and catheters

 

Vaginal speculum, scalpels, and forceps

Many medical practices from antiquity have been done away with, bloodletting being a notable example, but also more obscure practices such as the Hippocratic bench for spine alignment depicted below.

 

Medical practices such as splint setting and surgery itself, such as amputations and even more complicated procedures such as rhinoplasty and removal of cataracts were all common practice and and had a well established history despite the lack of a philosophical understanding of the underlying biological mechanisms. In the book Ancient Inventions Peter James and Nick Thorpe discuss the similarity of surgical practices throughout this development of medical philosophy and even in their common applications today. Nearly identical techniques for rhinoplasty and cataract removal appeared in Hindu texts nearly half a millennium earlier than in Greek and Roman medical treatises, suggesting the borrowing of procedures across cultures. Very similar basic tools and procedures had been applied for nearly three millennia up until the last hundred or so years. Medical experimentation on humans, such as the Nazis during WWII, have largely been atrocities due to the invasiveness and often sadism of procedures. Medical practice in general has actually been largely conservative.

Rhinoplasty was first practiced in India, with procedures in Hindu texts dating to ~300 BC, a leaf shaped flap of skin was removed from the forehead, twisted over and stitched on over bamboo or metal tubes to keep the nasal passages open during recovery. Essentially the same procedures are used today in skin grafting, except skin is generally taken from behind the ear. Procedure for cataract displacement described by Celsus. The approximate size of the needle is depicted to the right. Other methods were also implemented in which the cataract was actually broken apart and removed with the needle and a very fine hook. Circumcision was practiced in Eqypt as early as 2600 BC, fine copper and bronze scalpels were used and have been found in tombs.

Though practices stayed relativity constant ideas were constantly fluctuating. The 2^nd century Greek philosopher Celsus largely summarized Greek and Roman advances over this time period in his medical encyclopedia De Medicina, in the Prooemium the developing beliefs of the philosophers involved are detailed;

At first the science of healing was held to be part of philosophy, so that treatment of disease and contemplation of the nature of things began through the same authorities; clearly because healing was needed especially by those whose bodily strength had been weakened by restless thinking and night-watching.

Art of Medicine was divided into three parts: one being that which cures through diet( Διαιτητικήν), another through medicaments(Φαρμακευτικήν), and the third by hand(Χειρουργίαν).

Homer (Greek ~850 BC, Trojan war 1190-1180 BC) stated, however, not that they gave any aid in the pestilence or in the various sorts of diseases, but only that they relieved wounds by the knife and by medicaments…diseases were then ascribed to the anger of the immortal gods, and from them help used to be sought

many who professed philosophy became expert in medicine, the most celebrated being Pythagoras (Ionian Greek philosopher 570-495 BC), Empedocles (490-430 BC, Greek, cosmogenic theory of the four classical elements) and Democritus (460-370 BC, Greek, formulated atomic theory of the cosmos with his mentor Leucippus). But it was, as some believe, a pupil of the last, Hippocrates of Cos (460-370 BC, Greek,  father of western medicine), a man first and foremost worthy to be remembered, notable both for professional skill and for eloquence, who separated this branch of learning from the study of philosophy. After him Diocles of Carystus (4^th BC, importance of diet, wrote treatises in Attic opposed to customary Ionic), next Praxagoras (born ~340 BC, insisted on 11 humors, distinguished arteries and veins) and Chrysippus (279-206 BC, Greek, stoic, determinist, organic unity of the universe; correlation and mutual interdependence between all its parts) then Herophilus (335-280 BC, Greek, pupil of praxagoras, discovered sensory and motor nerves, cofounder of the medical school of Alexandria) and Erasistratus (304-250 BC, Greek, cofounder of medical school of Alexandria, discovered the role of the heart) so practised this art that they made advances even towards various methods of treatment. Apollonius and Glaucias, and somewhat later Heraclides of Tarentum (2^nd BC, Greek, extensively quoted by Galen, only wrote what he himself found to be right; Empirici or Experimentalists) They believe it impossible for one who is ignorant of the origin of diseases to learn how to treat them suitably.

On adverse health:

Herophilus; all the fault is in the humours

Hippocrates; or in the breath

Erasistratus; blood is transfused into those blood-vessels which are fitted for pneuma, and excites inflammation which the Greeks term φλεγμόνην, and that inflammation effects such a disturbance as there is in fever

Asclepiades; little bodies by being brought to a standstill in passing through invisible pores block the passage

On Digestion:

 Erasistratus held that in the belly the food is ground up

Plistonicus, a pupil of Praxagoras, that it putrefies

Hippocrates, that food is cooked up by heat.

Asclepiades, who propound that all such notions are vain and superfluous, that there is no concoction at all, but that material is transmitted through the body, crude as swallowed

On Causation and Treatment

Themison, (1^st BC, founder of the Methodic school of medicine) contend that there is no cause whatever, the knowledge of which has any bearing on treatment: they hold that it is sufficient to observe certain general characteristics of diseases;

if Erasistratus had been sufficiently versed in the study of the nature of things, as those practitioners rashly claim themselves to be, he would have known also that nothing is due to one cause alone,

Erasistratus himself, who says that fever is produced by blood transfused into the arteries, and that this happens in an over-replete body, failed to discover why, of two equally replete persons, one should lapse into disease, and the other remain free

Hippocrates said that in healing it was necessary to take note both of common and of particular characteristics.

Cassius, the most ingenious practitioner of our generation, recently dead, in a case suffering from fever and great thirst, when he learnt that the man had begun to feel oppressed after intoxication,[p. 39] administered cold water, by which draught, when by the admixture he had broken the force of the wine, he forthwith dispersed the fever by means of a sleep and a sweat.

       Submission to the uncontrollable will of the Gods, however, began losing favor with the implementation of Hippocratic medicine. Hippocrates was one of the earliest Greek philosophers to start contemplating the functions of biological processes in attempting to apply medical practices. In his treatise Nutriment he largely postulates on the mechanisms of digestion; 

Apparently nutritive food is supposed to be dissolved in moisture, and thus to be carried to every part of the body, assimilating itself to bone, flesh, and so

Air (breath) also is regarded as food, passing through the arteries from the heart, while the blood passes through the veins from the liver. But the function of blood is not understood ; blood is, like milk, "what is left over" (πλεονας1μός2) when nourishment has taken place.

These paraphrases on sections from Nutriment demonstrate both an application of intuition, and a profound lack of information on many of the bodies function. Food, both the soluble and insoluble, indeed must be dissolved in moisture before being carried to the rest of the body. Solvation is the medical term for breaking up large aggregations of lipids into tiny lipid droplets, which can then be packaged with soluble lipoproteins for transport to the rest of the body through the blood. The roll of blood as that “moistening” medium, however, apparently went overlooked. More important than philosophical conjecture, he was also one of the first to compile detailed descriptions of the circumstances of diseases, and there variations. In De morbis popularibus, on the epidemics he comments on many factors surrounding a tuberculosis epidemic, then known as phthisis (Greek for dwindling or wasting away);

IN THASUS, about the autumn equinox, and under the Pleiades, the rains were abundant, constant, and soft, with southerly winds; the winter southerly, the northerly winds faint, droughts; on the whole, the winter having the character of spring. The spring was southerly, cool, rains small in quantity. Summer, for the most part, cloudy, no rain, the Etesian winds, rare and small, blew in an irregular manner. The whole constitution of the season being thus inclined to the southerly, and with droughts early in the spring, from the preceding opposite and northerly state, ardent fevers occurred in a few instances, and these very mild, being rarely attended with hemorrhage, and never proving fatal 

They were of a lax, large, diffused character, without inflammation or pain, and they went away without any critical sign

Many had dry coughs without expectoration, and accompanied with hoarseness of voice. In some instances earlier, and in others later, inflammations with pain seized sometimes one of [p. 101]the testicles, and sometimes both; some of these cases were accompanied with fever and some not

The urine was thin, colorless, unconcocted, or thick, with a deficient sediment, not settling favorably, but casting down a crude and unseasonable sediment.

In the course of the summer and autumn many fevers of the [p. 102]continual type, but not violent; they attacked persons who had been long indisposed, but who were otherwise not in an uncomfortable state.

Within these passages, the beginning of widespread medical categorization and compilation begins to be evident. Both the spectrum of conditions and their chronology is taken into account. Large scale data collection of this sort, however, didn’t prove particularly enlightening  until the 1850’s with the invent of epidemiology. John Snow is attributed as the farther of epidemiology for his role in understanding the underlying reasons for the 1854 cholera outbreak in England. He assembled huge amounts of data on the eating, drinking, and hygiene habits of both sick and healthy individuals during the epidemic, ultimately tracing the outbreak back to a contaminated well. The Book Ghost Map by Steve Johnson describes the context surrounding this paradigm shift. Previously, miasma theories, derived from the greek term for pollution, were most commonly accepted. The notion of disease being transmitted through polluted air dates back to Hippocrates who was obsessed with air quality.

His treatise On Air, Water, and Places begins : “whoever wishes to investigate medicine properly, should proceed thus: in the first place to consider the seasons fo the year, and what effects each of them produces for they are not all alike, but differ much from themselves in regard to their changes. Then the winds, the hot and the cold, especially such as are common to all countries, and then such as are peculiar to each locality.”

In 1853 miasma theories were still eminently compatible with religious traditions. Henry Whitehead, a man of the cross, attributed the Golden Square outbreak to God’s will. Even the revolutionist Victorians also clung to miasmic theory. Belief in miasmic theory likely largely resulted from authors' visceral disgust with the smells of the city. No science or statistics of time, however, suggested smell alone was killing London’s people.

John Snow’s detailed rigorous analysis of the water companies and the transmission routes of the Horsleydown outbreak couldn’t compete with a whif of the air in Bermondsey district which wreaked with the stench of decaying corpses. Telescopes and Microscopes had been around for 200 years but the idea of microbes causing disease was still unheard of. Instead theories such as Thomas Sydenham’s internal-constitution theory of the epidemic, an eccentric hybrid of weather forecasting and medieval humorology, were common. He posited that Certain atmospheric conditions encouraged specific types of disease, and predisposition to infection lay in the sufferers themselves. Eventually, however, John Snow's Veronoi diagram, shown below, illustrated the pump as the primary suspect for the outbreak.

Black bars represent deaths, and the grey line represents the border where walking distance to Broad Street pump is closer than other pumps.

 Despite the relatively conservative nature of medical practice many regulations on research ethics have only rather recently been imposed. Jennifer Horner outlines these advances in her paper Research Ethics I: Responsible Conduct of Research (RCR)—Historical and Contemporary Issues Pertaining to Human and Animal Experimentation 

Modern medicine, however, has seemingly moved away from this conservative nature with new experimental drugs on the market almost daily with very little research on their lasting and indirect effects. Rather than the long standing model concisely put by Celsus in which;

 the Art of Medicine was not a discovery following upon reasoning, but after the discovery of the remedy, the reason for it was sought out.

Modern man has begun attempting reason as a means for discovering a remedy. 

The Joy of Anesthesia

Opium occupies a special role in the history of Anesthetics. Homer's epics contain the first references to opium as a drug "which quiets all pains and quarrels." The Greek medical Philosopher Galen (130-200AD) later commented on opium; (It) resists poison and venomous bites, cures chronic headache, vertigo, deafness, epilepsy, apoplexy, dimness of sight, loss of voice, asthma, coughs of all kinds, spitting of blood, tightness of breath, colic, the iliac poison, jaundice, hardness of the spleen, stone, urinary complaints, fevers, dropsies, leprosies, and the troubles to which women are subject, melancholy and all pestilences (Republished: Scott, Scott, J.M. The White Poppy. New York: Funk & Wagnells, 1969; 5, 46-82, 109-125). The clinical usage of opium was not widely implemented, however, due to a keen general awareness of the dangers associated with over use.

 

 Ether was one of the first "modern" anesthetics discovered, synthesized in 1275 by the Spanish chemist Raymundus Lullius. Its medical potential wasn't realized until much later when anesthesia broke onto the medical scene in the late 1700s with the help of chemists such as Joseph Priestly, who first synthesized nitrous oxide in 1772, and sir Humphrey Davy who recognized the potential of "laughing gas" in 1799. He first experimented with animals then himself, above Priestly is depicted administering NO to Davy in a sort of exhibition party. Not all forays into anesthetic research, however, ended so enthusiastically. Depicted below is the purported result of accidentally spilling a bottle of chloroform. Supposedly the Edinburgh professor James Simpson's wife walked in on him and colleagues all passed out as such.

The use of anesthetics has been present throughout the current era, its widespread acceptance and even daily use, however, has only skyrocketed in the last couple hundred years. Addiction to drugs has always been around, but the daily consumption of weak pain killers has become exceedingly common only recently. Though championing heart health, the effects of 2 Advil, Aleve, or Tylenol a day have no long standing history. Relatively few drugs were known and discovered up until the 18th century, they were all largely well characterized and generally wariness was associated with their use. Now, people are so often looking for a magic bullet as a cure that they overlook an ignorance of long-term effects and try anything. Perhaps some wisdom in the caution of the ancients may prove essential in humanities ever accelerating push into medical science.

The Discovery and Invention of Anesthesia by Adam Blatner M.D.

http://www.blatner.com/adam/consctransf/historyofmedicine/4-anesthesia/hxanesthes.html
                                 Drugs and Narcotics in History by Roy Porter
http://books.google.com/books?id=I1YxRwBn5poC&pg=PA4&lpg=PA4&dq=ancient+greek+roman+opium&source=bl&ots=kFr64bhnwL&sig=a6NCL66f7xVeHSwFNxbZpKxOiZc&hl=en&ei=08RZTZjvNYOB8ga6odWqBw&sa=X&oi=book_result&ct=result&resnum=7&ved=0CEUQ6AEwBg#v=onepage&q=ancient%20greek%20roman%20opium&f=false

Champions of the Dogmatist Ethic

In the wake of Alexander the Great’s crumbling empire, new ideas distinct from the ancient Greek practices were gaining acceptance. Herophilus and Erasistratus championed the “Dogmatist” medical ethic in 280 BCE Alexandria, and for the first time were granted permission by the king to perform a vivisection on a condemned criminal for purely scientific reasons. The Empirics, however, opposed dissection and vivisection saying they aren’t necessarily representative of dealing with an actual patient, and that instead of spending time theorizing, doctor’s should be focused on the needs of actual patients. In the 1^st CE the roman historian Cornelius Celsus portrays the debate in his medical encyclopedia De Medicina. Celsus portrays the criminal's

vivisection as a means for the surgeon the familiarize himself with common wounds in battle. The "wound-man" portrayed on the right is from De Medicini and portrays common injuries obtained in battle and was used as a reference for implementing wounds and practicing surgery. Celsus apparently approves of the act saying "nor is it, as most people say, cruel that in the execution of criminals, and but a few of them, we should seek remedies for innocent people of future ages." Though debatably brutish, the practice of human vivisection apparently played important roles in the evolution of human medical understanding. In Herophilus's treatise On Anatomy he was the first to distinguish nerves and further the difference between sensory and motor nerves, that the brain rather than the heart was the center of the nervous system, that perceiving pain depended on both brain and nerves, and revealed the presence of optical nerves and retina.