LAUGHING GAS, ETHER, AND SURGICAL ANESTHESIA

12 May

Despite  the  wealth  of  soporific  agents  available  in  nature’s  medical garden,  the  remarkable products   of  the  eighteenth-century  chemical

revolution eventually eclipsed the ancient anodynes. Joseph Priestly (1733–1804), British theologian,  educator,  writer, and political theorist, is best known  as the discoverer of oxygen, but  as Sir Humphry Davy (1778–1829) said of this indefatigable chemist, ‘‘no single person ever dis- covered so many new and curious substances.’’ Most curious of all was the gas known as nitrous oxide, or laughing gas. As he was in the habit of testing the effect of new gases on himself, Priestley might have discovered the anesthetic  properties  of laughing  gas if his research  had  not  been interrupted by the political and religious conflicts that forced him to emi- grate to America in 1794.

The ingenious discoveries of the first pneumatic  chemists provided new opportunities for quacks and charlatans. Conscientious  experimen- talists  could  not  compete  with charlatans promising  miraculous  cures for asthma,  catarrh, consumption, and cancer through  the inhalation of oxygen, hydrogen, and other ‘‘factitious airs.’’ Some physicians, however, attempted to find legitimate medical uses for the new gases. Fascinated by pneumatic   chemistry,   Thomas   Beddoes   (1760–1808)  persuaded   his friends Thomas  Wedgwood  (1771–1805) and  James Watt  (1736–1819) to help him establish the Pneumatic Institute, a hospital in which the inha- lation of factitious  airs was used in the treatment of lung disease. Many scientists, including Humphry Davy, were intrigued  by his work. While suffering from toothache in 1795, Davy began inhaling nitrous oxide. In addition to feeling giddy, relaxed, and cheerful, Davy noted that the pain caused by his wisdom teeth had almost disappeared. Soon after the exhil- aration wore off, the pain returned,  worse than ever. Nevertheless, Davy suggested that nitrous  oxide might be useful during surgical operations. Davy’s associate, Michael Faraday (1791–1867), discovered the soporific effect of ether vapor during experiments on various gases. In comparing the effects of ether and nitrous oxide, Faraday found that both chemicals produced  similar responses. Most subjects found  inhalation of ether or nitrous oxide very pleasant,  but, occasionally, people who inhaled ether or nitrous oxide experienced frightening and bizarre effects, such as loss of sensations,  prolonged  lethargy,  hallucinations, and  fainting.  Other eighteenth-century chemists recommended ether for fits, headaches, gout, rheumatism,  asthma, deafness, whooping cough, and other disorders.

Even the valiant  attempts  of Henry  Hill Hickman  (1801–1830) to validate the safety and efficacy of inhalation anesthesia  failed to arouse the interest of the medical profession. Unlike many pioneers of anesthe- sia, Hickman  did not simply sniff at various chemicals. Dogs and mice placed in a sealed glass vessel were subjected to various test gases until they were in a state  of ‘‘suspended animation.’’  In this state,  animals were insensitive to pain, but were at risk of circulatory  collapse during surgery. Unsuccessful in his attempts  to call attention to surgical anesthesia,  Hickman  apparently succumbed  to an overwhelming  sense of failure and committed  suicide.

The story  of the development  of surgical anesthesia  in the 1840s involves a most unlikely cast of characters  more suited to farce than his- torical  drama.  Moreover,  the major  events took  place not  in the pres- tigious medical colleges and  hospitals  of Europe,  but  at the periphery of the medical and scientific world. The chief characters  were peripatetic professors,  show-business  chemists, and dentists,  who at the time were regarded  as closer to  quacks  than  to  doctors.  Bitter  priority  disputes consumed  and  even destroyed  the  lives of several of the  participants in  the  discovery  of  surgical  anesthesia.   The  cast  of  characters   in- cludes Horace  Wells (1815–1848) and William Thomas  Green  Morton (1819–1868), dentists  who  had  shared  a successful partnership before Wells recognized the anesthetic properties  of nitrous  oxide and Morton demonstrated the value of ether. Charles Thomas  Jackson  (1805–1880), chemist and  physician,  later  claimed that  he rather  than  Morton  dis- covered  ether  anesthesia.  While  the  priority  battle  between  Morton and Jackson raged in New England, Georgia physician Crawford Williamson  Long (1815–1878) announced that  he had discovered ether anesthesia  before Morton.

During  the nineteenth  century,  medicine shows and philosophical

lectures by self-appointed professors  brought  edification  and entertain- ment   to   the   citizens   of   cities   and   towns   throughout   America.

‘‘Professors of chemistry’’ enlivened lectures on the amazing properties of newly discovered gases by breathing  fire with hydrogen  and encour- aging  volunteers  to  make  fools  of  themselves  after  inhaling  nitrous oxide. Students  of dentistry,  medicine,  and  chemistry  did not  have to wait for the itinerant  professors; they could enjoy ‘‘laughing gas parties’’ and  ‘‘ether  frolics’’ whenever  they  wished.  Indeed,  the  ‘‘champagne effect’’ of  these  substances   was  so  well  known  that   when  Jackson attempted to claim priority,  Morton’s  defenders  noted  that  one could hardly find a school or community  in America where the boys and girls had not inhaled  these drugs.

Dentists  were  probably   more  highly  motivated   than  any  other

practitioners to discover novel and powerful anesthetics. Until the excruciating  pain of a rotting  tooth  exceeded the anticipated agony of extraction,  the victim of toothache was unlikely to submit to the services of a dentist.  Throughout history,  dentists  claimed  to  possess potions that   would   remove   bad   teeth   and   eliminate   pain.   Ancient   tooth- dressings included everything from honey and opium to sour apples, powdered  beetles,  and  even rattlesnake venom  in  vinegar.  Kissing  a donkey,  biting  off the  head  of a mouse,  inserting  a live louse in the bad  tooth,  and  applications  of powdered  crow dung  were among  the most peculiar treatments for toothache.

In France, dentistry evolved as an area of specialization in surgery.

Textbooks  written  by and  for surgeons  typically included  descriptions of  the  teeth,  diseases  of  the  teeth  and  gums,  tooth   extraction,   the

construction of  artificial  teeth,  materials  for  filling  teeth,  and  other methods  of treating  disorders  of the teeth and gums. Although  the sta- tus  of  those  who  only  pulled  teeth  was  lower  than  that  of  barber- surgeons,  even  master  surgeons  performed   dental  procedures.   Texts devoted  to dentistry  had  been published  in the sixteenth  century,  but Le chirurgien dentiste (1728), a comprehensive,  two-volume  treatise  by surgeon-dentist Pierre Fauchard (1678–1761), is considered a landmark in the history of dentistry. Surgeons who treated  the dental problems of eighteenth  century  French  aristocrats enjoyed considerable  prestige.

Chapin  Aaron  Harris  (1806–1860), a founder  of American  den-

tistry, began the study of medicine, surgery, and dentistry as apprentice to  his  brother. In  1833, Harris  passed  an  examination   administered by  the  Maryland State  Medical  Board  and  was  awarded  the  M.D. Although  Harris  began his career as a doctor,  he decided to specialize in dentistry  and  spent  many  years  as an  itinerant  practitioner before he received a license to practice dentistry from the Medical and Chirur- gical Faculty  of Maryland and  settled  in Baltimore.  Harris  published many articles and books  about  dentistry,  including  The Dental Art: A Practical  Treatise  on Dental Surgery, Principles and Practice  of Dental Surgery,  and  Dictionary  of  Dental  Science:  Bibliography,  Biography and Medical  Terminology.  Harris  was a cofounder  of the  first  dental school  in the world,  the Baltimore  College of Dental  Surgery  (1840), and  established  the first national  dental  society, the American  Society of Dental  Surgeons.

As  nineteenth-century  American   dentists   introduced   improved dental  appliances  and  instruments, their  professional   and  economic advancement was limited  by the fears of prospective  patients  and  the disdain  of the medical profession.  These obstacles were especially gall- ing to men like Horace  Wells and his business partner  William Morton. Wells and Morton had developed improved sets of false teeth and dental solder, but potential  customers  were reluctant  to accept their ‘‘money- back-if-not-satisfied’’  deal because it required  extraction  of all remain- ing teeth  and  roots.  Thus,  Wells and  Morton were keenly interested in any agent that  could reliably achieve painless dentistry.

On December  10, 1844, Wells attended  a lecture by Dr.  Gardner

Quincy Colton, during which the remarkable properties of nitrous oxide were demonstrated. Wells was struck  by the fact that,  while under  the influence of laughing  gas, a volunteer  remained  in a state  of euphoria even though  he fell off the stage and injured his leg. Wells asked Colton to bring laughing gas to his office for an experiment. The next morning, Colton  administered the gas to Wells and John  M. Riggs, a dental stu- dent,  extracted  a  tooth.  When  Wells regained  consciousness,  he was elated to realize that he had not experienced any pain during the operation. Within a month,  Wells had used nitrous oxide on over a dozen patients. At Morton’s  request,  Dr. John  Collins Warren  (1778–1856), Professor

Surgical anesthesia at Massachusetts

Surgical anesthesia at Massachusetts  General Hospital,  1846.

of Anatomy  at  Harvard Medical  School,  allowed  Wells to  address  a class in surgery. However,  Warren’s  skeptical  attitude  toward  painless dentistry was evident in his introductory remarks.  ‘‘There’s a gentleman here,’’ Warren  warned  his students,  ‘‘who pretends  he has  something which will destroy  pain in surgical operations.’’  When the medical stu- dent who ‘‘volunteered’’ to have a tooth  extracted  groaned  during  the operation, Wells and Morton were ridiculed and humiliated  by the hos- tile audience.  Ironically,  the patient  later  admitted  that  he had  felt no pain.

In  1848,  when  he  evaluated  the  anesthesia  controversy,   Henry

J. Bigelow (1818–1890) argued  that  Wells had not satisfied the criteria for surgical anesthesia.  Surgeons  needed  an anesthetic  agent  that  was inevitable, complete, and safe. Behaviors elicited by nitrous  oxide inha- lation  were unpredictable and  suggestion  played  an important role in determining  the  effect of the  gas. Those  who  inhaled  for  amusement almost  always  became  exhilarated;   those  well  prepared   for  surgery became drowsy and lost consciousness.  During  the priority  battle  that followed the acceptance  of inhalation anesthesia,  Morton complained that  he was the only person involved in the discovery who had suffered a ‘‘pecuniary loss.’’ His colleague Horace  Wells, however, paid a higher price for his part in the controversy;  he lost his sanity and his life. Fail- ing to find professional  recognition,  Wells resorted  to sniffing ether and chloroform to  cope  with  depression.  Less  than  four  years  after  his humiliating  experience  at  Massachusetts General  Hospital,  Wells was arrested  for  allegedly accosting  a young  woman  and  throwing  some- thing,  which might have been acid, ether,  or chloroform, at her. Two days  later,  Wells was  found  dead  in  his  cell, with  an  empty  vial  of

chloroform, a penknife, a razor,  and a suicide note. Thus, Wells would never know  that  nitrous  oxide, mixed with oxygen, would  become an important anesthetic  agent in dentistry.

Only a short  time after  Wells’s dismal performance reassured  the

Boston  Brahmins  that  a mere dentist  could  not  teach  them  the secret of painless  surgery,  Morton convinced  the  same  elite physicians  that inhalation  anesthesia   was  ‘‘no  humbug.’’  Like  nitrous   oxide,  ether had been used for recreational  purposes.  Moreover,  during its long his- tory as a chemical oddity, several investigators  came tantalizingly  close to discovering its anesthetic properties.  The honor  of being first to syn- thesize ether has been attributed to several Renaissance  alchemists, but the  nature  of  these  alchemical  preparations is obscure.  The  starting materials  (sulfuric acid and alcohol) would have been widely available, but careful temperature regulation  is needed to enhance the production of ethyl ether as opposed to other possible reaction products.  Certainly, early preparations of ether  would  have been impure,  and,  as Morton discovered,  purity  was critical  when  ether  was used  as an  anesthetic agent.  Even though  ether had been used as a sedative in the treatment of tuberculosis,  asthma,  and  whooping  cough,  its anesthetic  potential was rarely exploited. Extrapolating from the pleasant  experience of an ether  frolic  to  dental  and  surgical  operations was not  a simple, self- evident  step  before  practitioners deliberately  set forth  on  a quest  for inhalation anesthetics.

According   to   family   tradition,  Morton  graduated  from   the

Baltimore  College  of  Dental  Surgery  in 1842. There  is, however,  no proof  that  Morton ever matriculated at  any  dental  school.  Although dentistry  was hardly  recognized  as  a  profession  at  that  time,  practi- tioners  were working  to improve  the training  and status  of dentists by establishing journals, professional societies, and schools, such as the Baltimore College of Dental Surgery (later the School of Dentistry, University  of Maryland). Whatever  their  education  and  training  may have been, both  Wells and Morton were apparently skillful and inven- tive dentists who specialized in ‘‘mechanical dentistry,’’ or ‘‘plate work.’’ Because of the  suffering  of his patients,  and  their  tendency  to  prefer death to dentistry,  Morton was obsessed with finding a way to mitigate the pain of dental  operations. Like surgeons,  dentists could offer their patients  only  unreliable  soporifics.  Moreover,   the  nausea  caused  by alcohol  and  laudanum was especially dangerous  during  dental  proce- dures because vomiting could lead to suffocation  and death.

Despite  the  financial  success  of  the  Wells–Morton partnership, Morton became  one of Jackson’s  private  pupils  in order  to make  the transition from  dentistry  to  medicine.  In  a  discussion  of  toothache, Jackson  recommended  using ether as ‘‘toothache drops.’’ Jackson  later claimed that he had known about  ether anesthesia since the early 1840s, but  when Morton performed  tooth  extractions  on Jackson’s  wife and

aunt, Jackson merely encouraged  the ladies to be brave. Therefore, dur- ing the priority  battle  over the discovery of anesthesia,  Morton argued that  his former  mentor  had  never thought of going beyond  the appli- cation of liquid ether ‘‘in the same manner that laudanum and other nar- cotics have always been applied to sensitive teeth.’’ Always on the alert for pain-relieving  agents,  Morton consulted  the medical literature  and found that ether had been used as an antispasmodic, anodyne,  and nar- cotic. Noting  that  when ether was applied  to a rotten  tooth,  the gums became numb,  Morton wondered  whether ether could numb the whole body.  Taking  elaborate  precautions to  ensure  secrecy, Morton tested the effects of ether inhalation on various  animals.  Disconcerted  by the variability  of his results,  Morton sought  Jackson’s  advice and  learned that  the ether  sold by pharmacists  was rarely pure  enough  for special uses.

On  September  30, 1846, Morton saturated a  handkerchief with

ether, looked at his watch, and inhaled deeply. He regained conscious- ness about  8 minutes  later  with  no  ill effects other  than  mild exhila- ration,  followed  by headache.  That  evening Morton tested  the  effect of ether  while extracting  a patient’s  firmly rooted  bicuspid.  After  the painless operation, the patient  gave Morton a written testimonial. Convinced  of the validity  of his discovery,  Morton again  approached Dr.  Warren  to  ask  for  an  opportunity to  demonstrate his method  of producing  insensibility  to  pain.  Thinking  that  inhaling  ether  through some  special apparatus might  produce  more  reliable  results  than  the

‘‘rag-and-gag’’ method  previously employed,  Morton sought  the assis- tance of a well-known scientific instrument-maker.

By  October   16,  1846,  the  day  of  the  hospital   demonstration, Morton was in a state of terrible  anxiety and his inhalation apparatus was still unfinished. The patient was already strapped to the table in prep- aration for his ordeal when Morton rushed in with his new inhaler and administered his secret ‘‘Letheon gas.’’ Amazed by the patient’s complete quiet and  tranquility during  the extirpation of a large tumor  from  his mouth  and tongue,  Warren  graciously  announced: ‘‘Gentlemen, this is no humbug.’’ Witnesses later recalled this demonstration as ‘‘the most sublime  scene ever witnessed  in  the  operating-room.’’ The  operation performed  by Warren  at Massachusetts General  Hospital  under  ether anesthesia was seen as the beginning of a new age for the ancient art of surgery.  It also marked  the beginning  of a vicious priority  battle  that found its way into petitions, patent applications, pamphlets, testimonials, and learned articles in professional  journals  and encyclopedias.

According  to Morton, the first intimation of the trouble  to come

was a visit from Jackson  on October  23, 1846. Jackson  had heard  that Morton intended   to  take  out  a  patent   for  surgical  anesthesia   and expected  to  make  a good  deal  of money.  Dentists  routinely  patented their inventions,  but  physicians supposedly  answered  to a higher code

of ethics. However, Jackson  demanded  fees for professional  advice, his name on the patent,  and 10 percent of the net profits. Shortly after pre- senting  his demands  to  Morton, Jackson  sent  a  sealed  report  to  the Academy of Sciences of France  in which he claimed that he had discov- ered ether  anesthesia  and  had  instructed  a certain  dentist  to use ether when extracting teeth. Jackson’s sealed report  was his insurance policy; if ether  proved  to be dangerous, his report  could  be destroyed,  but  if it was successful, he intended  to  use it to  claim priority.  As soon  as the success of ether anesthesia  seemed assured,  Jackson  presented  him- self as its sole discoverer and denounced  Morton as a ‘‘stooge’’ acting under his direction.  When Jackson  spoke to the Massachusetts Medical Society, most of his audience accepted the claims of the eminent physi- cian, chemist, and geologist against  his rival, the ‘‘quack dentist.’’ Not everyone was convinced that  Jackson  deserved credit for the discovery. Indeed, Jackson was asked whether he would have accepted the blame if Morton’s  patient  had died. Jackson’s critics saw this as an example of the old adage: success has many fathers,  failure is a bastard.

On  the  grounds  that  the  Massachusetts Medical  Society’s ethics code did not allow doctors to use secret remedies, when Morton offered his services for another  operation, hospital  surgeons refused to employ him until  he revealed  the identity  of Letheon.  They also assured  him that  the  patient  would  die if her  leg was not  amputated, and  would probably  die of shock if the operation was conducted  without  anesthe- sia. It was not easy for Morton to envision the greater good of humanity while his dreams  of fame  and  fortune  evaporated even more  quickly than  ether itself. Opportunities to profit  from his discovery continually eluded  him.  In  1868, shortly  after  consulting  his lawyer about  issues related  to his 20-year conflict with Jackson,  Morton died of a cerebral hemorrhage. An inscription  on Morton’s  tomb, composed by Dr. Jacob Bigelow, honors  him as the inventor  of inhalation anesthesia.  Jackson survived Morton by 12 years, but he did not enjoy a peaceful old age. According  to a story probably  too  good to be true,  after  considerable drinking,  Jackson  wandered  into  the  Mount   Auburn   Cemetery  and was overcome  by a frenzy while reading  the  inscription  on  Morton’s tomb.  Declared  hopelessly  insane,  Jackson  was confined  to  a mental asylum for the rest of his miserable life.

While Wells, Morton, and Jackson were disputing the discovery of

inhalation anesthesia,  Crawford  Long  emerged from  his obscure  exis- tence in rural  Georgia  with testimonials  documenting his own priority claim. Like Wells, Long came to an appreciation of the medical poten- tial of a drug from casual observations of its recreational  uses. When a traveling chemist sparked  local interest in laughing gas, Long had sug- gested that ether would be just as exhilarating. According to Long, sniff- ing ether became a popular  form of entertainment at local social events. After these ether frolics, participants sometimes discovered bruises and

other  injuries  acquired  while ‘‘under  the  influence.’’ Long  concluded that  ether might be used to induce insensitivity to pain during  surgery, but he apparently had more opportunities to stage ether frolics than sur- gical operations. In March  of 1842, Long persuaded  James M. Venable to have a tumor  on his neck surgically removed. Knowing  that Venable was afraid of the knife, but fond of ether, Long suggested that  he sniff ether prior to the operation. It was not until 1849 that  Long published an account  of his discovery in the Southern Medical and Surgical Jour- nal. Technically, Long established his priority,  but as Sir William Osier said: ‘‘In science the credit goes to the man  who convinces the world, not to the man to whom the idea first occurs.’’

Despite warnings from the Philadelphia  Medical Examiner that the

physicians  of  Boston  would  soon  constitute   one  fraternity   with  the quacks,  ether  anesthesia  quickly  spread  from  Massachusetts to  Paris and  London. Although  anesthesia  was certainly  an  important factor in the surgical revolution,  more  subtle  and  complex factors  were also involved. Indeed, given the increased use of the knife that accompanied the decline of humoralism  and  the rise of morbid  anatomy  during  the period  from about  1700 to the 1830s, the rapid  acceptance  of anesthe- sia might have been the result  of the increasing  role of surgery rather than the reverse. Potentially  useful anesthetic agents had obviously been available  before  the  1840s. In  any  case, with  the  rapid  dissemination of surgical anesthesia  advances  in the art  were inevitable; so too  were iatrogenic   accidents  and  deaths.   Anesthesia   so  transformed  the  art of surgery  that  Henry  J.  Bigelow urged  reform  of the  curriculum  at Harvard Medical School to inculcate humanity  and sensitivity back into medical  students.  Within  two  years  of  Morton’s  first  public  demon- stration   of  inhalation  anesthesia,   ether,   nitrous   oxide,  chloroform, and  other  anesthetic  agents  were widely used  in dentistry,  obstetrics, and surgery. Physicians also prescribed these powerful anesthetic agents for convulsions,  asthma,  whooping  cough,  menstrual  cramps,  vaginis- mus, neuralgia,  insomnia,  and insanity.

Inspired  by  his  successful  use  of  ether,  James  Young  Simpson

(1811–1879), Professor  of Midwifery  at  Edinburgh and  one  of  Scot- land’s leading surgeons and obstetricians, initiated a search for an anes- thetic  without  ether’s disadvantages. Using  himself and  his friends  as guinea  pigs, Simpson  began  a systematic,  but  dangerous  search  for a volatile anesthetic agent with a better aroma and more rapid action than ether.  Having  asked  for  advice  from  chemists  and  sniffed  his  way through  samples of acetone, benzene, benzoin, and a variety of organic solvents,  Simpson  tested  chloroform. This dense, colorless liquid  pro- duced  a sense of euphoria  as well as loss of consciousness.  Within  a week, Simpson’s patients were enjoying the benefits of chloroform anal- gesia. Chloroform easier to  administer  than  ether,  but  it also seemed to  be more  dangerous. Indeed,  it was fortunate that  the  principle  of

surgical  anesthesia  had  been  established  with  ether,  because  the  rela- tively high mortality  rate  with chloroform might  have inhibited  deve- lopment   of  this  branch   of  the  healing  art.   Emphasizing   the  more unpleasant aspects  of using ether,  Simpson  noted  that  it irritates  the respiratory tract  and is highly inflammable,  which would be very dan- gerous  to  anyone  operating  by  candlelight.  In  1868, chemists  found that  chloral  hydrate,  which  was used  in the  synthesis  of chloroform, also  acted   as  a  soporific   agent.   Instead   of  releasing   chloroform, however,  chloral  hydrate   formed  trichloroethanol in  the  liver.  Che- mists  synthesized  more  useful  analogues   of  chloral   hydrate   in  the

1870s and 1880s.

The safety of anesthesia  was not  the only point  of contention, as demonstrated by the ferocity of the attack  on the use of anesthetics  in obstetrics.  Clergymen, doctors,  and assorted  amateur  moralists  argued that  pain had a God-given,  and therefore  holy role to play in the lives of men, and  especially in the lives of women.  Midwives had  been put to  death  for  the  blasphemous, sinful,  unnatural crime  of  attempting to  alleviate  the  pains  of  childbirth.   Clergymen  denounced   Simpson and commanded  women to endure the pains of childbirth  with patience and fortitude.  Did the Bible not say that  Eve was condemned  to bring forth  children  in sorrow? Obstetricians warned  women that  labor  con- tractions  were identical  to  labor  pains.  Therefore,  without  pain  there would be no contractions and normal  delivery could not occur. Suffer- ing  was  inherent   in  female  physiology   and   labor   pains   enhanced woman’s capacity for tenderness,  femininity,  and maternal  feelings.

Saddened  by the controversy,  Simpson met his critics on theologi-

cal  as  well as  scientific  grounds.  Using  the  Bible to  substantiate  his work,  Simpson  asserted  that  the  curse  in  Genesis  had  been  revoked by a passage in Deuteronomy that  promised:  ‘‘The Lord  will bless the fruit  of  the  womb  and  the  land.’’ Moreover,  the  word  translated  as

‘‘sorrow’’ in  the  case  of  Eve’s punishment   was  really  the  word  for

‘‘labor,’’ which referred  to both  farming  and  childbirth.  Furthermore, God  established  the  principle  of  anesthesia  when  he  caused  a  deep sleep to fall upon Adam before operating  on his rib. When John  Snow (1813–1858) administered chloroform to Queen Victoria in 1853 during the birth  of her eighth child, the issue of whether a proper  lady would accept  anesthesia  was settled.  When  one of her daughters  gave birth, Queen  Victoria  said:  ‘‘What  a  blessing she had  chloroform.’’  Unlike his American  counterparts, Simpson  died rich in honors  and  respect. He  was  knighted,   appointed  Physician   in  Scotland   to  the  Queen, awarded   an  honorary doctorate by  Oxford  University,  received  the Freedom  of the  City  of Edinburgh, and,  after  his untimely  death  at age 59, academic and commercial activities in Scotland  were suspended to  accommodate one  of the  largest  funerals  ever to  honor  a Scottish doctor.

The priority  battle  in America  became part  of a broader  contro- versy about  which  agent,  ether  or  chloroform, was better,  as well as arguments  about  the relative value of Simpson’s work and that  of the Americans   who   had   discovered   inhalation  anesthesia.   When   the Edinburgh Daily Review called the introduction of chloroform for anes- thesia ‘‘the greatest of all discoveries in modern  times,’’ Bigelow complained  that  Simpson was ignoring  his American  predecessors and claiming too much credit for surgical anesthesia.  In response,  Simpson informed Bigelow that he saw the use of chloroform and ether as anesthetic agents not as great discoveries in themselves, but as steps in a long history that  included  Sir Humphry Davy,  as well as the Greek,  Roman, and medieval surgeons who had used various soporific vapors. For Simpson and his British colleagues, the discovery of chloroform was the climax of a   sweeping   historical   narrative.    Infuriated,  Bigelow  insisted   that it was wrong to call chloroform the ‘‘greatest discovery’’ in any account of  surgical  anesthesia.   Ether  had  been  used  successfully  and  safely for  many  years  before  chloroform  anesthesia   caused  ‘‘hundreds  of cases of disaster and death.’’ According to Bigelow, Simpson’s self- aggrandizing   historical  account  was  nothing  but  ‘‘antiquarian   dust’’ that   was  used  ‘‘to  obscure  the  truth.’’  Bigelow  wanted  the  world, especially the British, to acknowledge the difference between ‘‘the mod- ern discovery of anesthesia  and the less important use of chloroform.’’ Even after Simpson and Bigelow were dead, the controversy  continued. Jacob Bigelow’s son, Dr. Henry J. Bigelow, wanted to make it perfectly clear that  Americans  had  discovered the first surgical anesthetic  agent that  was  ‘‘inevitable, complete, and  safe.’’  That  agent  was ether,  not chloroform.

The  changing  nature  of surgical  practice  must  have  been  rather

painful  to  those  who  had  established  their  reputation through  speed and strength  and now saw surgeons  developing a deliberate  and subtle touch. Practitioners who had struggled to attain the professional detach- ment  (or callousness)  needed  to  operate  in the pre-anesthetic  era  had taken  great pride in their achievements.  Like the librarian  who objects to people taking books from neatly ordered shelves, the master surgeon might  resent  the  trick  that  obviated   the  need  for  his  painstakingly acquired  skills.  Some  doctors   believed  that  inhalation of  anesthetic agents  would  poison  the  blood,  promote  hemorrhages, cause convul- sions, nausea, intoxication, prolonged  stupor,  cerebral excitement, asphyxia,  bronchitis,  pneumonia, inflammation of the brain,  paralysis, insanity, depression, local or systemic infection, miscarriage, or damage to the fetus. Anesthetics  might damage  nerves and muscles or interfere with wound healing. Many sectarians, such as hydropaths, homeopaths, and  naturopaths, opposed  the  use  of  all  powerful,  chemical  agents, including  anesthetics.  Some temperance  advocates  denounced  Demon Anesthesia as well as Demon Rum.

While some practitioners denounced anesthesia as a dangerous  and blasphemous novelty and others  adopted  it without  reservations,  most doctors  cautiously  accepted  it as a mixed blessing that  had to be used selectively. The risks and benefits of anesthesia  had to be evaluated  by a new ‘‘utilitarian calculus’’ that  took into consideration a host of vari- ables, such as age, sex, race, ethnicity, the seriousness of the operation, and  so forth.  The  rapid  spread  of anesthetic  techniques  was unprec- edented  in medical  history,  but  not  all patients  received the blessings of painless surgery,  even for major  limb amputations. Some surgeons justified anesthesia  by arguing  that  pain  itself was dangerous, because it caused shock, depleted  precious  stores of vital energy, and damaged the body.  Moreover,  anesthesia  encouraged  patients  to  accept  opera- tions and allowed surgeons to refine their skills. Advocates  of universal anesthetization accused  doctors  who  insisted  on  the  selective use  of anesthetics of exaggerating potential  risks in order to maintain  exclusive control  over anesthesia.  The American  Medical Association’s Commit- tee on Medical  Science warned  that  chloroform and ether should  only be used by physicians; with respect to anesthesia,  even dentists  should defer to physicians.  To put  this concern  in context,  note  that  doctors also warned  patients  that  bathing  could  prove  fatal  unless prescribed by a physician instead of a hydropath.

Many nineteenth century critics of anesthesia sincerely believed that pain was God’s punishment  for human failures and wickedness. William Henry Atkinson, M.D., the first president of the American Dental Association,  contended  that  anesthesia  was a Satanic  plot  to  deprive men of the capacity  to reason  and endure  the pain that  God  intended them  to  experience.  Certainly   doctors   were  influenced  by  religious dogma,  but professional  norms also conditioned  them to be suspicious of  an  innovation   that  challenged  centuries  of  medical  experience  in which  insensitivity  to  pain  (as  in  coma,  shock,   or  brain   damage) was a harbinger  of death. Pain, life, and healing had always been inextricably  linked.

Opponents of the new surgery pounced upon reports of deaths after

anesthesia, ignoring the fact that it was not uncommon for patients to die after operations performed  without  anesthesia.  Some critics feared that anesthetics   gave  doctors   excessive  power  over  patients.   Anesthetic agents could be used to subdue  and tranquilize  uncooperative patients into  unnecessary,  experimental  operations. It  was  even possible  that the relief of pain was an illusion; the patient  might actually suffer pain but be rendered incapable of expressing or recalling the experience. Although many of these fears were obviously exaggerated, further experience proved that anesthetics, like any potent drug, could cause ser- ious side effects: fatal  cardiac  arrhythmias, circulatory  failures  during surgery, postsurgical  pneumonia, vomiting that could cause suffocation or tissue damage,  and more subtle effects on the liver, brain,  fetus, or

newborn infants. As a modern medical specialty, anesthesiology includes the administration of surgical anesthesia,  acute and chronic pain relief, postoperative care, the management of intensive care, respiratory inten- sive care, chronic pain management, resuscitation, and emergency medicine.  Some  departments of anesthesia  have  become  departments of anesthesia and perioperative medicine. Nevertheless, even under opti- mum, fully modern conditions, the dangers of anesthesia should never be underestimated. In  many  cases,  general  anesthesia  may  be  the  most dangerous  part  of an operation.

With  proper   management, inhalation  anesthesia   was  generally

safe, complete,  and  inevitable.  Complete  insensibility,  however,  is not suitable for all operations. Although  some of the drugs and instruments involved  in the  development  of local,  regional,  and  spinal  anesthesia predate Morton’s  demonstration, the development  of special techniques for their use began in earnest after the acceptance of inhalation anesthe- sia. In 1803, Friedrich  Wilhelm Sertu¨ rner (1783–1841) isolated crystals of a powerful analgesic agent from crude opium.  Sertu¨ rner named  this chemical morphine, for Morpheus, the Greek god of dreams. Morphine paste could be introduced  locally with the point of a lancet, or a solution of  morphine  could  be  instilled  into  a  wound.  In  the  1850s, Charles Gabriel Pravaz (1791–1853) and Alexander Wood (1817–1884) indepen- dently  invented  the modern  type of hollow  metal  needle. (The device known  as a hypodermic  syringe in the  United  States  and  England  is called a Pravaz syringe on the Continent.) Injections  of morphine  were generally used for the relief of localized pain, but some surgeons admin- istered morphine  in preparation for surgery under general anesthesia  in the  belief that  it prevented  shock,  delirium,  nausea,  and  lessened the amount  of inhalant  needed. Heroin, a derivative of morphine first synthesized in 1874, was widely marketed  in the 1890s as a pain reliever that  was allegedly safer than  morphine.  After the chemical structure  of morphine  was elucidated  in 1923, many other  derivatives of morphine were tested, but very few had any particular advantages.

The   ancient   Incas   had   successfully   exploited   the   anesthetic

qualities  of the  coca leaf as well as its mood-altering properties,  and their Peruvian  descendants  continued  to use coca leaves to drive away pain,  hunger,  nausea,  fatigue,  and  sorrow.  While  Europeans  quickly took up the native American  custom of smoking tobacco,  they ignored coca leaves until nineteenth-century chemists isolated  interesting  alka- loids,  including  cocaine.  After  reading  a  report  on  the  physiological effects of cocaine,  Sigmund  Freud  (1856–1939) decided  that  the drug might serve as a tonic in the treatment of mental and physical diseases. Using  himself as guinea  pig, Freud  discovered  that  cocaine  banished his depression and increased his energy. Freud urged Carl Koller (1857–1944), a physician who specialized in eye disorders, to try cocaine for the relief of eye diseases such as trachoma and iritis. When a solution

of cocaine was instilled into  the eye of a frog, Koller  could  touch  the cornea without  eliciting any reaction.  Following successful tests on rab- bits and humans,  Koller announced his discovery at the 1884 Ophthal- mologic  Congress  in  Heidelberg.  Freud   credited  his  colleague  Carl Koller  with discovering  the local anesthetic  properties  of cocaine,  but some scholars think that  Freud  should be considered one of the found- ers of psychopharmacology for his own studies of cocaine. By the end of  the  nineteenth  century,  many  popular  ointments,   snuffs,  supposi- tories,  cigarettes,  cigars,  patent   medicines,  and  beverages  contained cocaine.  The  best known  is Coca-Cola,  a patent  medicine introduced in 1886 as a therapeutic agent  and  general  tonic.  In addition  to  coca leaf extract,  Coca-Cola  contained  an extract  of the kola  nut,  which is high in caffeine. By 1906 when the Pure Food and Drug Law was passed in the United  States, the makers of Coca-Cola  were using decocainized coca leaves, but the caffeine remained.

William  S.  Halsted   (1852–1922),  one  of  New  York’s  leading surgeons,  realized that  Koller had barely begun to exploit the possible range of cocaine anesthesia.  Impressed  with the drug’s effects, Halsted performed  a series of tests on himself, his medical students,  and experi- mental  animals.  Because cocaine constricts  blood  vessels, it seemed to be the  ideal  local  anesthetic  for  surgery  in highly  vascularized  areas. Halsted  developed  a technique  that  he called conduction anesthesia  or nerve  block  anesthesia—a  means  of specifically anesthetizing  various parts  of the  body  by injecting  cocaine  solutions  into  the  appropriate nerves.

When using cocaine, Halsted  enjoyed feelings of increased energy

and creativity,  as well as freedom  from pain and fatigue,  but  when he stopped  taking  cocaine he experienced vertigo, cramps, anxiety, insom- nia, and  hallucinations. When his addiction  to cocaine interfered  with his ability to operate,  Halsted  was sent to an asylum for the mentally ill. He was quite a different person when he emerged a year later, cured of the cocaine habit,  but  addicted  to morphine.  Encouraged and  sup- ported  by his colleagues William Osler (1849–1919) and William Henry Welch (1850–1934), Halsted  continued  his distinguished  career  as the first professor of surgery at Johns Hopkins.  A century later, descriptions of the symptoms  of cocaine abuse included intense anxiety, depression, acute psychosis, paranoid delusions,  auditory  or visual hallucinations, and seizures followed by respiratory or cardiac  arrest.

The history of anesthesia  is closely related to studies of the mean-

ing and mechanism of pain. While scientific understanding of the mech- anism   of   pain   is  far   from   complete,   the   problem   can   now   be reformulated in terms of neuroendocrinology and the discovery of the opiate receptors and the endorphins, the body’s own endogenous morphine-like  substances,  in the 1970s. Given the fact that  opium  and morphine  are not natural constituents  of the nervous system, scientists

reasoned  that  there  must  be opiate  receptors  that  play  a  role  in the control   of  pain   via  some  endogenous   narcotic.   Avram   Goldstein (1919–), one of the pioneers of this field, said that  when thinking  about the effects of morphine  he asked himself ‘‘why would God  have made opiate receptors  unless he had also made an endogenous  morphine-like substance?’’ Just  as enzymes and  substrates  fit together  like locks and keys, so too might natural opiates  interact  with the receptors  on nerve cells that apparently interacted  with morphine  and morphine-like  drugs. In 1973, Solomon  Snyder (1938–) and Candace  Pert (1946–) identified the opiate  receptors  in the brain.  Within  the year, scientists at several other  laboratories confirmed  their  discovery.  By 1975, scientists  had discovered the endogenous opiates, neurotransmitter peptides called endorphins or enkephalins  that  mimic the action  of morphine.  Several families of endorphins were found  in the  brain,  pituitary  gland,  and other tissues. Through  studies of the endorphin system, neurobiologists and  pharmacologists expect to find ways to control  the production of endorphins, develop  safe  endorphin-like  drugs,  and  modulate   acute and chronic pain.

Although  patients  and lay people tend to believe that  the relief of

suffering  is one  of the  primary  goals  of medicine,  pain  and  suffering have received relatively little attention in medical education  and train- ing. Subjective pain, and the cultural  contexts in which patients  experi- ence pain are not necessarily considered aspects of the ‘‘functional impairments’’ and disabilities that fall into the domain of medicine. Pain was traditionally regarded  as a symptom,  rather  than  a diagnosis,  and thus, of little interest  in and of itself. Control  of surgical pain presum- ably raised expectations  that  all forms of pain  could  be controlled  by appropriate analgesics. However, success in the development  of surgical anesthesia  was not  readily  extended  to  the broader  problem  of acute and chronic pain. Since the 1960s, patients  and patient  advocates  have become  increasingly  vocal  about   the  problem   of  pain,  particularly chronic pain, which was not a major concern of surgeons. Chronic pain, in particular, has  been  called  one  of the  most  intractable of modern epidemics.  In  response,   many   hospitals   and   medical  centers   have established  multidisciplinary  pain clinics.

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