1. Introduction

Historical vistas create an important link in the globally continuous line of progress and evolution of world civilizations, especially in the history of science. George Alfred Leon Sarton, a Belgian-American chemist and historian wrote, “We shall not be able to understand our science of to-day, if we do not succeed in penetrating its genesis and its evolution……..and if we do not understand our science of today we will not be able to add to it.” According to Al Razi, the scholar who attains complete knowledge of the achievement of those who came before him will be able to add original contributions to it. History of medicine is continuous and uninterrupted and gives the medicine of today by a joint global contribution of the whole world. It can be divided into following six phases ^[1].

1. Creation of Adam (Peace Be Upon Him) and prehistory.
2. Ancient civilizations: Assuro-Babylonian, Ancient Egyptian, Indian, Persian, and Far Eastern.
3. Greco-Roman and Alexandrian.
4. Greco-Arabic or Greco-Islamic medicine (7^th to 16^th century the Golden age of Arab Islamic civilization): In Europe, this period is usually referred to as the Dark Ages, in which the great era of the Greco-Roman medicine came to an end and no progress in medical science was made until the Renaissance.
5. Renaissance (14^th to 17^th century): It is regarded as the cultural bridge between the middle ages and modern history.
6. Western civilization: It comprises of Industrial revolution (18^th to 19^th centuries) and Modern day civilization (20^th century).

Urolithiasis is a major global health problem with complex pathophysiology, multifactorial etiology and high recurrence rate. It is one of the oldest diseases of modern era which has increased in both the developed and the developing countries during the past decades. In 1901 English archeologist E Smith found a bladder stone from a 5000 year old mummy dated back to 4800BC in El Amrah, Egypt. The medical texts of Asutu in Mesopotamia, between 3200 BC and 1200 BC are the earliest literature, for describing symptoms and prescribing treatments to dissolve the calculus ^[2]. Ancient Mesopotamia were using opium (Papave somniferum L.) and cannabis (Cannabis sativa L.) in case of pain and bleeding caused by kidney or bladder stones ^[3]. In Ancient Greek periods, Hippocrates (460 BC to 370 BC) in his famous book Oath of Medical Ethics for Physicians quoted “I will not cut for calculus, even for the patients in whom the disease is manifest; I will leave this operation to be performed by practitioners.” This statement, suggested surgery as one of the way of urolithiasis management ^[2]. Hippocrates in his book internal affections wrote, “From the kidneys these four diseases arise. In the first one, the patient suffers the following: a sharp pain attacks his kidneys, loin, flank, and his testicle on the same side as the kidney; he urinates frequently, and drips urine a little at a time; together with the urine, sand, too, is passed, and when the sand discharges through the urethra, it provides violent pain in it. When the patient has finished urinating, the pain stops; later, though, he labors under the same distress again. When he is passing urine, he rubs his penis because of pain. Many physicians that do not understand the diseases, when they see the sand, think the patient is suffering from stones of the bladder, which he is not, but rather from the stones of the kidneys………….. When the case is such, clean the patient downwards with scammony juice (obtained by incision of the living root of Convolvulus scammonia L.) or the root itself, first applying vapor-baths to the whole body. On the following day, clean downwards with juice from white chick-peas (Cicer arietinum L.) to the amount of two choes (6.55Liters); add salt and give this drink” ^[4]. Aristotle (382-322 BCE) in his book Problems wrote about the actions of drugs affected urination, “Why are sweet-smelling seeds and plants diuretic? It is because they are warm and easily absorbed, and such things are diuretic? For the internal heat digests quickly and the smell is not corporeal, since even the strong-smelling plants like garlic (Allium sativum L.), which by their heat cure diuretic, produce more excretions. Sweet smelling seeds are also hot” ^[4]. Greek Dioscorides in his book De Materia Medica (50-70 AD) and Pliny the Elder (an ancient Roman naturalist) in Naturalis Historis (70-79 AD) have shared number of medicinal plants used against urolithiasis along their mode of action.

“Greco-Arabic" or "Greco-Islamic" medicine extended from Spain to Central Asia and India. Arab-Islamic physicians and scholars developed a large and complex medical literature exploring and synthesizing the theory and practice of medicine. They introduced many new ideas and upgraded the knowledge about herbs and their therapeutic effects and safety. The Arabs and Muslims appreciated Greco-Roman culture and learning, and translated tens of thousands of scientific and medical texts into Arabic for further study ^[5]. After the end of Greco-Roman times till the Renaissance as stated by John Howard Lidgett Cumpston (1880-1954 AD), the first director-general of the Australian Department of Health, “At the time when the Arabs appeared in the Orient, Greek sciences were in total decadence and the practice of magic reigned supreme ^[1].” In the 7^th century, Islam emerged from the desert of the Arabian Peninsula, conquering the old Egyptian, Persian, Roman, and Near Eastern Empires with Arabic language and added its culture to the heritage of Greece, Rome, Judaism, Christianity, and the Near East. After the 16^th century, Crusades, Mongol invasions, natural disasters, loss of international trade, the capitulations of the Ottoman Empire to Western interests, and the rise of European imperialism contributed to political and economic decline of Islamic world. Bertrand Russell (1872-1970 AD) the British philosopher, mathematician, historian, and social critic wrote, “Islamic science, while admirable in many technical ways, lacked the intellectual energy required for innovation and was chiefly important as a preserver of ancient knowledge and transmitter to medieval Europe ^[6]”. The statement of Bertrand Russell is completely wrong. It has confirmed that Greco-Arabic Muslim scientist were not just preserve, compile or transmit the Greco-Roman medical literature. They critically reviewed the translated heritage of previous civilizations and accepting only what proves to be true ^[1]. The famous statement of Al-Razi is: “I never write about things unless I first examine them myself ^[7]”. He further wrote, “I prayed to God to direct and lead me to the truth in writing this book. It grieves me to oppose and criticize the man, Galen, from whose sea of knowledge I have drawn much. Indeed, he is the Master and I am the disciple. Although this reverence and appreciation will and should not prevent me from doubting, as I did, what is erroneous in his theories. I imagine and feel deeply in my heart that Galen has chosen me to undertake this task, and if he were alive, he would have congratulated me on what I am doing. I say this because Galen’s aim was to seek and find the truth and bring light out of darkness. I wish indeed he were alive to read what I have published ^[8].” Muhadhdhab al-Deen Al-Baghdadi in his book Al Mukhtar Fi Al Tibb wrote, “I will also avoid including anything mentioned which is not proven by experiment as narrated to me by my teacher and through my own experience (obtained) by experimenting and testing ^[9]”. Multidimensional development of Arab–Islamic thought, provided the stimulus for developing the human intellect further, and for bringing about the forces of rationalism and humanism that led to the twelfth century Medieval Renaissance, the fifteenth century Italian Renaissance, and indeed, for sowing the seeds of European Reformation. This multidimensional approach comprised of Greco-Roman medicinal heritage, Prophetic medicines that were derived from Quran and Ahadith and the practical experience of Greco-Arabic Muslim scientists. According to Dickinson, Sarton, Cumston, and Margota, in the East the development of botany, pharmacy, and chemistry and revival of other branches of science was the major contribution of that Greco– Arabic school of medicine ^[1]. Ibn Sina introduced sublingual and intra nasal route of drug administration for faster and easier drug delivery of cardiac drugs and reported in his book Al-Advia Wal Qalbiya ^[10]. Al-Zahrawi packed single doses of drugs in cat-gut parcels, ready for swallowing and drug gradually seeped out of the parcel, known today as capsule ^[11]. These are few examples. However, Greco-Arabic-Islamic medicines influenced Western medical circles to such an extent that it was included in the curriculum of European medical schools for many centuries ^[5]. Unfortunately, many original authentic medical manuscripts written by famous scholars of the Islamic era were plagiarized, authoritatively edited, published the Latinized works of the Islamic scholars under the names of medieval European authors. The famous example for that is Constantinus Africanus, who as stated by Campbell, suppressed the names of the Arabic authors whose works he produced Latin versions of in the eleventh century. The number of primary source studies based on them by historians or medical researchers remained few and were limited to individual efforts. Therefore, it can be focused on this missing-link era ^[1].

In following contents, the contribution of following Greco-Arabic Muslim scientist has shared with special reference of urolithiasis, its diagnosis, management and treatment.

1. Abu Bakr Mohammad Ibn Zakariya Al-Razi (Rhazes, 864–930 AD) --- Al-Hawi fi al-Tibb (Comprehensive Book on Medicine).
2. Abubakr Al-Akawayni Al-Bokhari (?–983 AD) --- Hidayat al-Mutallimin fi-al-Tibb (Learner’s Guide to Medicine).
3. Abul Qasim Khalaf Ibn al-Abbas Al-Zahrawi (Abulcasis, 936–1013 AD) --- Kitab Al-Tasrif (The Method of Medicine).

2. Al-Razi

Al-Razi in his book named Al-Hawi fi al-Tibb (part 7, book I) precisely explained the anatomy, physiology and pathophysiology of urinary tract diseases, specially the diagnosis and management of urolithiasis ^[2]. He stated, “……….Kidneys can have stones and their pain resembles this pain of colon and these two must be differentiated. Pain in the loins, sediment in urine, passage of stone or black urine passed with pain several months before denotes stone pain. If there is nausea or the pain follows a meal or is located in the abdomen and more to the front than the back, then it is more likely to be colonic pain. The site of the pain is important: in abdominal colic, the pain is more generalized and tends to be anterior, while in kidney stones, the pain is more limited and tends to be in the back……….. Among these symptoms are a simple abdominal irritation, tingling pain in the pelvic area, and pricking sensation in the urethra. Occasionally, the pain can extend to the inguinal as the renal calculus passes through the ureter and moves towards the bladder……… the darkness of urine, deposition of calculus materials in the urine, feelings of heaviness and discomfort in the abdomen, and stretching sensations in this area while lying are the symptoms which can indicate the formation of calculus……… The urine stops either because the kidney lacks it and the sign of this is the stoppage of urine and no heavy pains in the back and not in the loin, ureter, and bladder, any discomfort and not at the bladder neck, any cause of obstruction as we will show and together with this, the abdomen is lax and in the body, there is swelling and dropsy or profuse sweating. Or urine is within the kidney which is obstructed, and in it, the lesion which is swelling or stone or clots of blood or pus. Common to all of them is the pain in the lumbar region with emptiness of the bladder. But if it be a stone, the signs of the stone would appear before that. And if it be a hot swelling, with the pain, there is some throbbing. And if it be diseases in the kidney, then it is only heaviness. And if it be a solid swelling, the urine does not stop suddenly but gradually and with heaviness only. And if it be clots of blood or pus, then it would be preceded by ulcer. And if the urine is stopped because of the urinary passages from the kidney, the bladder will be empty and the pain in the ureter along its course with pricking and stitching as the ureteric pain is continuous and pricking, after this, use the previous criteria as in the kidney. ………..and the differentiation between kidney calculi and renal obstruction or pyelonephritis is that; with inflammation, (there are) mixed fevers, rigors, and polyuria with frequency; with obstruction, (there is) oliguria and the urine is clear and with stones, the urine is either clear or not and with sandy sedimentation.………..Do not lie long on your back. Avoid cheese, milk derivatives, especially fresh cheese, hard-boiled eggs, unleavened bread. Use diuretics— cucumbers (Cucumis sativus L.), melons (Cucumis melo L.), figs (Ficus carica L.), grapes (Vitis vinifera L.), and crystal — clear water from natural sources. ………… Sedatives for renal colic attacks are useful and after the pain had subsided, a number of herbal remedies including wormwood (Artemisia absinthium L.), birthwort (Aristolochia clementis Alain.), and pepper (Piper nigrum L.) to help calculi’s expulsion. Juice of radish leaves (Raphanus sativus L.), caper (Capparis spinosa L.), Prunus mahaleb L., water of soaked chick peas (Cicer arietinum L.) and bitter almonds (Prunus amygdalus var. amara (DC.) Focke.) are effective for breaking the calculi. This recommendation of “diet, hydration, and diuresis” is what is currently advised for patients with urinary calculi………During such times (having kidney calculus), the frequency of bathing and the number of times that one enters Khazineh (A big bathtub full of hot water) should be increased, prescriptions should be followed and medications should be used. If such orders be followed consistently, the patients will not feel the pain and before its complete formation, calculus will be broken into small pieces and pain will not be intensified…………After getting out of bath or Khazineh, the patient should be ordered to move and jump around incessantly and for a long duration of time. Having done this, the patient should enter Khazineh again and stay there till the time he feels that the pain has been displaced and it is running down the inguinal”. Al-Razi for the first time introduced preoperative preparation of the patient by an enema and meatotomy for impacted urethral calculi. He wrote, “Because stools in the rectum may render palpating for and locating of bladder stones difficult or impossible, it is essential that the patient should be given an enema beforehand. When the bowel empty out its content, feeling the stone and also abdominal palpation (suprapubic abdominal palpation) becomes easier……………If a stone is impacted in the tip of the urethra be aware not to force it out by pushing as this causes laceration and subsequent severe pains and infections, but incise the end of the penis and remove the stone”. He further stated, “Urine mirrored the circulation in the urinary system”. He observes physical characteristics of urine and draw clinical decisions from its appearance in those days, when new laboratory analyses for urine examination were not available. He used to scrutinize urine for color, consistency, deposits, taste, clarity, touch, etc, and classified each finding into various subdivisions and specified the underlying cause and significance of each. Al-Razi believed that pain becomes worse when the calculi are passing through the ureters; otherwise, patients just “feel heaviness in the flanks”. Differential diagnoses between colitis and renal colic and between kidney and bladder calculi were very clearly made by him ^[7][12]. The contribution of Al-Razi in the field of medicine and surgery for the management and treatment of urolithiasis is highlighted in Table 1, Table 2 and Table 3.

3. Abubakr Al-Akawayni Al-Bokhari

In Hidayat al-Mutallimin fi-al-Tibb about urolithiasis and its management he stated, “Now I mention the chapter on urine obstruction, which could be from the kidney or from the bladder also, or ureters, or penile duct (urethra), and the one that is from the urethra could be due to the stone, tissue overgrowth, inflammation, blood clot, or pus. Now I describe them one by one. But urine obstruction when it is from the ureters, manifests in (a way) that the bladder is empty and devoid of urine, and there is heaviness in the back. And if the obstruction is in the penis, its sign is that the bladder is full, and also, if the stone is in the bladder. And if the stone is in the kidney, the bladder is empty. Remember these rules for not making mistakes. And when the bladder is full, on palpation it appears like an inflated bag, and the pain is severe, the bladder is stretched, and this pain may extend to the scrotum. The (obstruction) of the urethra, may be due to the stone, which I have already mentioned its treatment, or from (granulation) tissue grown within the urethra following its ulceration, or from a wart like the one that appears on the skin, and its treatment is difficult. Its sign is that the urine flows scanty, (but) as time passes, the urine decreases until it completely ceases. For treatment, put (the patient) in water tub and use softener pomades (pomades made with fatty ingredients to hold the drug) and rub the oil of Cruciferae (Brassica spp.) until urine starts to come out and the duct (ureter) becomes dilated. When (the obstruction) is not at the ureters but in the urethra, it could be cured with the ‘‘Mabowleh’’, which is a hollow pin made of silver or gold or brass over the head of which are many holes resembling a lance …………..It is possible for the urinary obstruction to be due to a stone lodged at the bladder outlet. Its sign is that when the patient lies down on their back, and elevates the feet and wags them, the stone is dislodged and the urine comes out. Its treatment is with those agents that bring the stone out of the bladder, which I will mention in the chapter on the bladder stone. It is possible for urine retention to be secondary to the bladder weakness when its expulsive force is decreased, the sign of which is that if you put your hand on (the bladder) and compress it, the urine comes out ………….. Again when the bladder is full, avoid using the diuretic agents as it brings death. Again, when the stone is in the bladder this is more common in children, while in the elderly it occurs in the kidney, the signs are that the urine is white and of a fair appearance and when (the patient) wants to urinate, penile erection occurs, and in such a child the penis is mostly erect. He scratches the base of the penis. The pain is so severe and occasionally, the (penile) base may be pulled off from the extensive scratching. When the bladder is full, the patient lie on his back and elevate his legs and shakes them, urine comes out. And this stone has several types: one type is soft and is removed with medications, and another is hard and is not removed with medications. For one month, treat (the patient) with medicines, may be (the stone) is abated, unless (the patient) develops hectic fever and dies. If so, and you treated for one month, (but the stone) does not come out, now you must handle (it) with iron and apply those things that bring the stone out as I mentioned previously…………..Beware that when the stone enlarges in the kidney it hinders the urine, causes intolerable pain, and may lead to mental confusion from pain. Each occasion of the pain is called an episode (the pain is intermittent). During the episode of pain, the patient should sit in a tub of warm water in which the leaves of cabbage (Brassica oleracea L.), leaves of marsh-mallow (Althaea officinalis L.), chamomile (Anthemis nobilis L.), dwarf yellow (Astragalus hamosus L.), fenugreek (Trigonella foenum-graecum L.), flaxseed (Linum usitatissimum L.), seed of mingwort (Artemisia absinthium L.), and starthistle (Centaurea calcitrapa L.) have been brewed. And after getting out of the water tub, the back (of the patient) should be massaged gently with the oil of wallflower (Cheiranthus × cheiri L.), and then he should jump (up and down) on one foot, or ride a horse trotting in place, or climb fast down a ladder until the stone comes out of there………….If the stone lodges in the penis, its sign is that of penile pain. If so, (the penis) must be sucked with the mouth to expel (the stone), or (the patient must) put the penis in the warm water and massage it to expel (the stone) and even have marsh-mallow (Althaea officinalis L.) decoction and violet oil (essential oil extracted from the flowers of Viola odorata L.) instilled in the urethra and milked outward to expel the stone. If the stone is large or lodged transversely and cannot be expelled then an incision (of the urethra) has to be made to extract the stone. And again those single medicines (used) for the extraction of stone are that I mention: Jews’ stone (Lapis Judaicus) grinded in clean water and three Deram-Sang (37.5 gram) of it consumed, root of cumin (Cuminum cyminum L.), scholopendriun (Asplenium scolopendrium L.), seeds of caper (Capparis spinosa L.), capillaire (Adimantum capillusveneris L.), round cypress (Cyperus rotundus), root of starthistle (Centaurea calcitrapa L.), caraway (Cuminum carvi L.), seeds of melon (Cucumis melo L.), seeds of cucumber (Cucumis sativus L.), seeds of pentaphyllum (Gynostemma pentaphyllum (Thunb.) Makino.), and beetroot (Beta vulgaris L.) concentrate; these drugs are the first line (medications). And ground pine (Teucrium chamaepitys L.), dittany (Marrubium pseudodictamnus L.), herb ivy (Ajuga iva (L.) Schreb.), decoction of black pea (Lathyrus niger (L.) Bernh.), asparagus root (Asparagus officinalis L.), Indian Djatrah (?), crown of the root of agrimony (Agrimonia eupatoria L.), seeds of radish (Raphanus sativus L.), and ………… these drugs are stronger, and the strongest of them is beetle (Cantharidae), but care should be taken as it could lead to bladder ulceration. Now that I gave the guidelines (for treatment), I proceed to pay attention to stone prevention. As it is known that the etiologies of stone are concentrated materials, natural heat, and obstruction in the ducts, I have to mention, briefly highly concentrated foods like... fresh fruit, and cow and camel meats,…………. and everything that is concentrated should be avoided, particularly fresh cheese..…….And also the use of those drugs that dilate the urinaryduct like the seed of melon(Cucumis melo L.), cucumber (Cucumis sativus L.), white cucumber (Cucumis anguria L.), seeds of marsh-mallow (Althaea officinalis L.), seeds of sweet squash (Cucurbita maxima Duchesne.), and………….. is recommended ^[12][13].

4. Al-Zahrawi 

He shared a number of specially designed practically applied surgical equipments (Table 3) for urolithiasis management, which provided the basis to develop modern surgical equipments later on.

Table 1. Compound formulations used by Ibn Sina for urolithiasis management.

Keys: Hydromel= drink made with water mixed with yeast and honey; Oxymel =mixture of honey and vinegar; Litholytic= agent which dissolves or break stones; Lithotriptic= agent which causes binding inhibition among particles to form stones and stop further stone growth.

Table 2. Animal and mineral drugs used by Ibn Sina and Al-Antaki for urolithiasis management.

Table 3. Historical glimpses of surgical management for renal stones.