sleep then and now, 1805-2005 (RSM presentation 22 April 2005, Sleep and genetics meeting)

This site documents the Royal Society of Medicine's Sleep Medicine sections contribution to the Royal Society of Medicine's bicentenary. Complaints etc to Dr C Idzikowski.

22nd April - bicentenary talk (presented at the Sleep and Genetics meeting)


Writing this presentation on 'Sleep then and now - 1805-2005' turned out to be quite complicated, least of all because the writer (Chris Idzikowski) may not actually be present! Whilst the initial thought was simply to compare sleep in 1805 with 2005, meaning how people slept then (1805) compared to how they sleep now (2005), the comparison almost immediately extended itself to what scientists and medical practitioners thought about sleep then and now, and of course how the Royal Society of Medicine (RSM) regarded sleep then and now. Also as the talk was being given at a genetics meeting it was deemed appropriate to put a genetics slant to the talk. Furthermore it seemed reasonable to mark the bicentenial (1805-2005) of the Royal Society of Medicine ((RSM))with a little more than a talk, so a flier for the library has also been written (identifying some of the Fellows and Presidents who have particularly contributed to thinking about sleep and sleep disorders practice) as well as setting up a website which contains material relating to the subject.

So this talk will cover the following topics.

  • Sleep and society 1805-2005
  • Sleep and science and medicine 1805-2005
  • Sleep and genetics and chronobiology
  • Sleep 1805-2005: a roadmap of the website
  • Sleep and the Royal Society of Medicine Library 'card'.

Brief RSM History

The Royal Society of Medicine (RSM) evolved from numerous London-based medical societies. It's founding arose when many members of the Medical Society of London abandoned this organisation to form the Medical and Chirurgical Society in 1805. The Medical Society of London had originally formed in 1773 to share experiences and promote the then three primary divisions of medicie: physicians, surgeons and apothecaries....

Founding groups (1907)

From 1805 many other medical societies formed as well as the Medical and Chirurgical Society and these were amalgamated in 1907 to form the Royal Society of Medicine.

  • Society of Anaesthetists, 1893-1908
  • British Balneological and Climatology Society, 1895-1909
  • Clinical Society of London, 1868-1907
  • Dermatological Society of London, 1882-1907
  • Dermatological Society of Great Britain and Ireland, 1894-1907
  • Society for the Study of Diseases in Children, 1900-1908
  • British Electrotherapeutic Society, 1901-1907
  • Epidemiological Society of London, 1850-1907
  • British Gynaecological Society, 1884-1907
  • British Laryngological, Rhinological and Otological Association, 1888-1907
  • Laryngological Society of London, 1893-1907
  • Neurological Society, 1886-1907
  • Obstetrical Society of London, 1858-1907
  • Odontological Society of Great Britain, 1856-1907
  • Pathological Society of London, 1846-1907
  • Therapeutical Society, 1902-1907


  • Accident and Emergency Medicine 1987
  • Anaesthesia 1908
  • Balneological and Climatological 1909-1931
  • Cardiothoracic 1991
  • Clinicalb1907
  • Clinical Forensic & Legal Medicine 1988
  • Clinical Immunology and Allergy 1965
  • Clinical Neurosciences (formerly Neurology) 1997
  • Coloproctology (formerly Proctology 1913-1983) 1913
  • Comparative Medicine 1923
  • Dermatology 1907
  • Electro-Therapeutics (see also Radiology & Physical Medicine) 1907-1931
  • Endocrinology 1946
  • Epidemiology & Public Health
  • (Epidemiology 1907-1913; Epidemiology & State Medicine 1913 - 1952; Epidemiology & Preventative Medicine 1952-1974; Epidemiology & Community Medicine 1974-1990) 1907
  • Experimental Medicine & Therapeutics (see Therapeutics & Pharmacology 1907-1943 - joined Medicine to form Medicine, Experimental Medicine & Therapeutics 1973-1987) 1943-1973
  • General Practice with Primary Health Care (formerly known as General Practice 1950-2003) 1950
  • Geriatrics & Gerontology 1991
  • History of Medicine 1912
  • Hypnosis & Psychosomatic Medicine (preciously Mental & Dental Hypnosis 1978-1987) 1988
  • Larynology & Rhinology (formerly section of Larynology 1907-1993) 1907
  • Library (Scientific Research) (became Pharmaceutical Medicine & Research) 1956-1994
  • Measurement in Medicine 1963-2000
  • Medicine (became Medicine, Experimental Medicine & Therapeutics until abolished in 1987) 1907-1973
  • Medical Education 1966-1982
  • Medicine, Experimental Medicine & Therapeutics (see also Medicine Section & Therapeutics and Pharmacological section) 1973-1987
  • Nephrology 1994
  • Neurology (became Clinical Neurosciences 1977) 1907-1997
  • Obstetrics and Gynaecology 1907
  • Occupational Medicine 1964
  • Odontology 1907
  • Oncology 1970
  • Open 1974
  • Ophthalmology 1912
  • Orthopaedics 1913
  • Otology-incl. Otosclerosis Committee 1907
  • Paediatrics and Child Health (previously known as Study of Disease 1908-1946; Paediatrics 1946-1999) 1908
  • Pathology 1907
  • Pharmaceutical Medicine & Research (previously Library - Scientific Research) 1994
  • Plastic Surgery 1967
  • Proctology (see Coloproctology) 1913-1983
  • Psychiatry 1912
  • Radiology 1931
  • Respiratory Medicine 1991
  • Rheumatology & Rehabilitation 1931
  • Sports Medicine 1994
  • Surgery 1907
  • Therapeutics & Pharmacology (Experimental Medicine & Therapeutics) 1907-1943
  • Transplantation 1994
  • Tropical Medicine Section 1912-1936
  • United Services (Previously known as War Section 1919-1929) 1929
  • Urology Section 1920
  • War Section (then United Services) 1919-1929


  • Angiology (Became Vascular Medicine Section) 1986-2002
  • Black & Ethnic Minority Health 2000
  • Catastrophes & Conflict 1999
  • Clinical Haemorheology (amalgamated with Angiology 1997) 1982-1997
  • Clinical Pharmacology & Therapeutics (amalgamated with Section of Pharmaceutical Medicine & Research) 1987-1997
  • Communication in Health Care (formerly Medical Communications) 1986
  • Computers in Medicine 1990-1996
  • Food & Health 1984
  • Learning Disability (formerly Mental Retardation 1983-1993) 1993
  • Lipids in Clinical Medicine 1983
  • Maternity & the Newborn 1982
  • Medical Care of Catastrophes (became Catastrophes & Conflict 1999) 1998-1999
  • Medical Communication (became Communication in Healthcare 2000) 1983-2000
  • Mental Retardation (became Learning Disability 1993) 1983-1993
  • Palliative Care 1996
  • Quality in Healthcare 1991
  • Sexual Health & Reproductive Medicine (formerly Sexual Medicine & Family Planning) 2000
  • Sexual Medicine & Family Planning (became Sexual Health & Reproductive Medicine 2000) 1986-2000
  • Sleep & Its Disorders (became Sleep Medicine 2002) 1999-2002
  • Telemedicine (became Telemedicine & eHealth 2001) 1997-2001
  • Vascular Medicine (formerly Angiology) 2002
  • Venous 1983

The British Medical Journal - Sleeplessness, Page 719, 1894

The subject of sleeplessness is once more under public discussion. The hurry and excitement of modern life is quite correctly held to be responsible for much of the insomnia of which we hear: and most of the articles and letters are full of good advice to live more quietly and of platitudes concerning the harmfulness of rush and worry. The pity of it is that so many people are unable to follow this good advice and are obliged to lead a life of anxiety and high tension. Hence the search for some sovereign panacea that will cure the evil. Many are the remedies suggested: hot baths, cold baths. hot drinks, cold drinks, long walks (some say on bare foot) before retiring to rest, and so forth. Some recommend the well-known plan of steady and monotonous counting, while others advise the more difficult feat of thinking about nothing. There can, however, be no doubt that different remedies suit different cases. Where a holiday and complete change of employment and surroundings is impossible, we would advise what the sufferer finds to be most soothing to his temperament. Some will find this in a long walk, while others will only be excited by the undue exercise; some may find a hot bath, others a cold bath beneficial; some are lulled by tobacco, others by novel reading; others still by a glass of grog. To be read off to sleep by a gentle voice is, perhaps, the pleasantest way of all. We know some who are lulled by very simple measures, such as brushing the hair, or the application of a cooling lotion to the temples. Others have apparently to adopt more heroic measures if we may judge from their letters. We give a quotation from one of these, culled from the Glasgow Herald:
Soap your head with the ordinary yellow soap; rub it into the roots of the hair until your head is just lather all over, tie it up in a napkin, go to bed, and wash it out in the morning. Do this for a fortnight. Take no tea after 6 P.M. I did this, and have never been troubled with sleeplessness since. I have lost sleep on an occasion since, but one or two nights of the soap cure put it all right. I have conversed with medical men, hut I have had no explanation from any of them All that I am careful about is that it cured me.
We cannot help thinking that some of our sleepless readers would prefer the disease to the cure. But if any should like to try it, may we advise that they should first, at any rate, follow that part of the advice which relates to the tea, and leave the soap part as a last resource.
Editor BMJ, 1894.

Sleep research and medicine wiki

Introduced concept 22 April - this as best example http://en.wikipedia.org/wiki/Main_Page

early medical practice

British Medical Journal, 1892 - 1 "Sir, for several weeks I have been attending a case of chronic cardiac disease .. complicated with congestion of the lungs. My patient, who has always been a man of most temperate habits, suffers from a very distressing sleeplessness which does not yield to any remedy which a consultant and myself have been able to prescribe. Chloral, bromides of potassium and ammonium, ether, cannabis Indica, and various combinations of the same drugs have been found wanting; and more frequently than not my patient cannot find sleep. Hypodermic injections of morphia are of little service. If any of your readers will have the kindness to communicate what they have found reliable in similar cases, they will greatly oblige, your faithfully, ...."

British Medical Journal, 1892 - 2 "Sir, - if your correspondent, .., would advise his patient, who has been unable to procure sleep from all sorts of narcotics prescribed, to try the effects of a pint bottle of Guinness's extra stout; or if he objects to malt liquor, half a bottle of good sound claret with his dinner, and followed, before going to bed, with two glasses of good Scotch whiskey and water, I think the patient will enjoy a most refreshing sleep, and the trial of which, for a night or two, cannot possibly do him much harm. - Yours truly .... " "

British Medical Journal, Dec 16 1892 - 3 Ask Chris for the punch line?

Genetics and sleep

Signaling Mechanism - Animal Model
acetylcholine beta-2 nicotinic receptor, subunit, null mutant mice
Anandamide/oleamide Fatty acid amide hydrolase, null mutant mice
Dopamine Dopamine transporter, null mutant mice
  • GABA alpha-1 GABA-A receptor subunit, null mutant mice
  • alpha-2 GABA-A receptor subunit, null mutant mice
  • alpha-3 GABA-A receptor subunit, null mutant mice
  • beta-3 GABA-A receptor subunit, null mutant mice
  • Histamine Histidine decarboxylase, null mutant mice
  • Histamine H1 receptor, null mutant mice
  • Histamine H3 receptor, null mutant mice
Hypocretin (orexin)
  • Hypocretin (orexin) Preprohypocretin, null mutant mice
  • Hypocretin (Hcrt) cell, knockout mice
  • Hypocretin cell, knockout rat Hcrt receptor 1 (HcrtR1), null mutant mice
  • Hcrt receptor 2 (HcrtR2), null mutant mice
  • HcrtR1/HcrtR2 double, null mutant mice
Noradrenaline Dopamine beta-hydroxylase (DBH), null mutant mice
Noradrenaline/Hypocretin DBH/Hcrt double, null mutant mice
  • Serotonin 5-HT1A receptor, null mutant mice
  • 5-HT1B receptor, null mutant mice
  • 5-HT2C receptor, null mutant mice
  • Serotonin transporter, null mutant mice
  • Synaptic vesicle release Rab3a, null mutant mice
  • RIM1 alpha-, null mutant mice

Signaling Molecule Animal Model Reference Adenosine
  • Adenosine A1 receptor, null mutant mice
  • Adenosine A2a receptor, null mutant mice
Interleukin-1 (IL-1) IL-1 type I receptor, null mutant (IL-1RI knockout) mice
Interleukin-6 (IL-6) IL-6, null mutant (IL-6 knockout) mice
Interleukin-10 IL-10, null mutant mice (IL-10)
Interferon type I IFN type I receptor, null receptor (IFN-RI) mutant (IFN-RI knockout) mice
  • Nitric oxide Neuronal nitric oxide synthase (nNOS), null mutant mice
  • Inducible (i)NOS, null mutant mice
  • Prostaglandin D2 (PGD2) Transgenic PGD synthase (PGDS) overexpressing mice
  • Lipocalin-type PGDS, null mutant mice
  • DP receptor, null mutant mice
  • Tumor necrosis factor (TNF) TNF 55 kDa receptor, null mutant (TNFR1-KO) mice
  • TNFR2, null mutant (TNFR2KO) mice
  • TNF and lymphotoxin-alpha double, null mutant mice
Growth hormone (GH) and GH- Dwarf (dw/dw) rats (nonfunctional GHRH receptor)
  • GH releasing hormone (GHRH) Dwarf (lit/lit) mice (nonfunctional GHRH receptor) excess GH production mice
  • GH andinsulin-like growth factor-I (IGF-I), null mutant mice
From Wisor JP; Kilduff TS. Molecular genetic advances in sleep research and their relevance to sleep medicine. SLEEP 2005;28(3):357- 367.

Genetics of normal and pathological sleep in humans . Sleep Medicine Reviews, Volume 9, Issue 2, April 2005, Pages 91-100 Y. Dauvilliers, S. Maret and Mehdi Tafti

High similarity in sleep habits in twins (e.g. Heath et al in 1800 mz (1103 same sex) found that genetic differences account for 33% variance in sleep quality and 40% in sleep pattern).

A.C. Heath et al., Evidence for genetic influences on sleep disturbance and sleep pattern in twins. Sleep 13 (1990), pp. 318-335.

Also EEG records similar in 85% mzs.

Narcolepsy - Predisposing allele is DQB1*0602, an allele found in up to 95% of narcoleptics BUT COMPLEX. For example, DQB1*0301 increases susceptibility, whereas alleles such as DQB1*0601 and DQB1*0501 are protective. Familial forms of narcolepsy with several subjects affected over several generations are rare, making mapping studies through linkage analysis very difficult.
In a natural canine model of narcolepsy for which the transmission is autosomal recessive with complete penetrance, mutations of the gene encoding the type 2 hypocretin/orexin receptor were found to be responsible for the disease.

Sleep paralysis - (inability to move when falling asleep or at awakening) is experienced by 17-80% of narcolepsy patients, but can also occur in an isolated form. Isolated sleep paralysis is highly families with an autosomal dominant mode of transmission and not associated with the HLA-DQB1*0602. The prevalence of sleep paralysis is high (5-62%), but greatly varies among ethnic groups with the highest incidence in African-Americans and in association with panic disorder.

OSA Chromosome 2p and 19p suggested.

InsomniaMcCarren et al. [68.] used an insomnia questionnaire in 2825 Vietnam era veteran male twins and found higher concordance rates in MZ than in DZ twins for all sleep problems independent of combat experiences.
Molecular studies of primary insomnias are very rare but in a single patient with chronic insomnia, a mis-sense mutation was found in the gene encoding the GABA-A beta3 subunit
Another recent study looking for an association between the CLOCK gene polymorphisms and insomnia in mood disorders revealed a higher recurrence of initial, middle, and early insomnia in patients with homozygous (CC) CLOCK genotype.

FFI is a very rare disease characterized by severe insomnia, dysautonomia, and motor disturbances rapidly leading to death.73 FFI is the first sleep disorder for which a gene mutation has been identified, a point mutation (codon 178) in the prion protein gene (PRP) on chromosome 20 and rarely a mutation on codon 200.[74.] The same mutations are found in certain forms of dementia of the Creutzfeldt-Jakob type, but the polymorphic codon 129 appears to determine fatal insomnia phenotype expression versus Creutzfeldt-Jakob.

Sleepwalking an association between sleepwalking and HLA DQB1*0501 notably in the familial forms.
RBD A single genetic study was published to date, reporting an association between this REM sleep parasomnia and HLA-DQ1 (DQB1*05 and 06).

Primary nocturnal enuresis nocturnal enuresis is inherited through an autosomal dominant mode of transmission with high penetrance (90%). [85.] Four gene loci on chromosome 8q, 13q, 12q, and 22q11 associated with nocturnal enuresis have been identified but the existence of others is presumed

Circadian rhythm sleep disorders A PER2 gene mutation (serine→glycine) on chromosome 2q was found to be responsible for phase advance syndrome in a large kindred with autosomal dominant transmission and high penetrance.
In delayed sleep phase syndrome appears associated with HLA DR1[97.] and PER3 gene polymorphism.
An association was also found between the melatonin receptor 1a (MEL1A) gene polymorphism and the absence of 24-hour sleep–wake rhythm synchronization.

Two different groups carried out genetic linkage studies in large kindred of patients affected by restless legs syndrome. A significant linkage was found on the long arm of chromosome 12 in one study (maximum Lod SCORE=3.59) 107 and on chromosome 14 in the second one (maximum Lod SCORE=3.23). [108.] One main candidate gene within the region on chromosome 12q is the neurotensin gene, an important modulator of the dopaminergic transmission.

An association between Kleine-Levin syndrome and HLA DQB1*0201. [110.] This study suggests the involvement of a potential auto-immune a

Genetics of normal and pathological sleep in humans . Sleep Medicine Reviews, Volume 9, Issue 2, April 2005, Pages 91-100 Y. Dauvilliers, S. Maret and Mehdi Tafti