What Is Life? The Physical Aspect of the Living Cell  is a 1944 science book written for the lay reader by the physicist  Erwin Schrödinger .  The book was based on a course of public lectures delivered by Schrödinger in February   1943, under the auspices of the  Dublin Institute for Advanced Studies , where he was Director of Theoretical Physics, at  Trinity College, Dublin .  The lectures attracted an audience of about 400, who were warned "that the subject-matter was a difficult one and that the lectures could not be termed popular, even though the physicist’s most dreaded weapon, mathematical deduction, would hardly be utilized." [ 1 ]   Schrödinger's lecture focused on one important question: "how can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?" [ 1 ]


In the book, Schrödinger introduced the idea of an "aperiodic solid" that contained genetic information in its configuration of  covalent chemical bonds . In the 1940s, this idea stimulated enthusiasm for discovering the chemical basis of  genetic   inheritance . Although the existence of some form of hereditary information had been hypothesized since 1869, its role in reproduction and its helical shape were still unknown at the time of Schrödinger's lecture. In 1953,  James D. Watson  and  Francis Crick  jointly proposed the  double helix  structure of  deoxyribonucleic acid  (DNA) on the basis of, amongst other theoretical insights,  X-ray diffraction  experiments conducted by  Rosalind Franklin . They both credited Schrödinger's book with presenting an early theoretical description of how the storage of genetic information would work, and each independently acknowledged the book as a source of inspiration for their initial researches. [ 2 ] [ 3 ]


The book, published in 1944, is based on lectures delivered under the auspices of the  Dublin Institute for Advanced Studies  at  Trinity College, Dublin  in February 1943, attended by  Éamon de Valera  and his  cabinet . [ 4 ]  At that time, although DNA was known to be a constituent of cell nuclei, it had not yet been identified with certainty as the molecular basis of inheritance, and the concept of a "heredity molecule" was strictly theoretical, with various candidates. One of the most successful branches of physics at this time was  statistical physics . Schrödinger himself is one of the founding fathers of  quantum mechanics , a theory which posits a statistical focus for understanding the natural world at subatomic scale.


Max Delbrück 's thinking about the physical basis of life was an important influence on Schrödinger. [ 5 ]  However, long before the publication of  What is Life? , the American geneticist  Hermann J. Muller , who would later win a Nobel Prize in 1946, had in his 1922 article "Variation due to Change in the Individual Gene" [ 6 ]  already laid out all the basic properties of the "heredity molecule" (not yet known to be DNA) which Schrödinger re-derived in 1944 "from first principles" in  What is Life?  (including the "aperiodicity" of the molecule), properties which Muller specified and refined additionally in his 1929 article "The Gene As The Basis of Life" [ 7 ]  and during the 1930s. [ 8 ]   Muller himself wrote in a 1960 letter to a journalist [ citation needed ]  regarding  What Is Life?  that whatever the book got right about the "hereditary molecule" had already been published before 1944 and that Schrödinger's were only the wrong speculations; Muller also named two famous geneticists, including Delbrück, who knew every relevant pre-1944 publication and had been in contact with Schrödinger before 1944. DNA as the molecule of heredity became foremost only after  Oswald Avery 's bacterial-transformation experiments published in 1944; before those experiments, proteins were considered the most likely candidates. DNA was confirmed as the molecule in question by the
 Hershey–Chase experiment  conducted in 1952.


In Chapter I, Schrödinger explains that most physical laws on a large scale are due to  chaos  on a small scale. He calls this principle "order-from-disorder". As an example he mentions  diffusion , which can be modeled as a highly ordered process, but which is nevertheless caused by  random movement  of atoms or molecules. As the number of atoms is reduced, the behaviour of a system becomes increasingly random. He states that life greatly depends on order and that a naïve physicist may assume that the master code of a living organism has to consist of a large number of atoms.


In Chapter II and III, he summarizes what was known at the time about the hereditary mechanism. Most importantly, he elaborates on the role  mutations  play in biological  evolution . He concludes that the carrier of hereditary information has to be both small in size and permanent in time, contradicting the naïve physicist's expectation. This contradiction cannot be resolved by  classical physics .


In Chapter IV, Schrödinger presents  molecules , which are indeed stable even if they consist of only a few atoms, as the solution. Even though molecules had long been known to exist, their stability could not be explained by  classical physics  due to the discrete nature of quantum mechanics. Furthermore, mutations are directly linked to  quantum leaps .


He continues to explain, in chapter V, that true  solids , which are also permanent, are composed of highly ordered  crystals . The stability of molecules and crystals is due to the same principles, and a molecule might be called "the germ of a solid". On the other hand, an  amorphous solid , without crystalline structure, should be regarded as a  liquid  with a very high  viscosity . Schrödinger writes that the heredity material is likely to be a molecule, which unlike a crystal does not repeat itself. He calls this an "aperiodic crystal". Its aperiodic nature allows it to encode an almost infinite number of possibilities with a small number of atoms. He finally compares this picture with the known facts and finds it in accordance with them.


In Chapter VI, Schrödinger states:


...living matter, while not eluding the "laws of physics" as established up to date, is likely to involve "other laws of physics" hitherto unknown, which however, once they have been revealed, will form just as integral a part of science as the former.


He anticipates that this statement will be open to misconception and tries to clarify it. The main principle involved with "order-from-disorder" is the  second law of thermodynamics , according to which  entropy  only increases in a  closed system  (such as the universe). Schrödinger explains that living matter evades the decay to  thermodynamical equilibrium  by homeostatically maintaining  negative entropy  in an  open system .


In Chapter VII, he maintains that "order-from-order" is not absolutely new to physics; in fact, it is even simpler and more plausible. But nature follows "order-from-disorder", with such exceptions as the predictable movement of the  celestial bodies  and the behaviour of mechanical devices such as clocks. Even those are influenced by thermal and frictional forces. The degree to which a system functions mechanically or randomly depends on the temperature. If sufficiently heated, a clock melts into a puddle of randomly moving molecules. Conversely, if the temperature approaches  absolute zero , any system behaves more and more mechanically. Some systems, such as clocks, approach this mechanical behaviour even at room temperature.


Schrödinger concludes this chapter and the book with  philosophical  speculations on  determinism ,  free will , and the mystery of human  consciousness . He attempts to "see whether we cannot draw the correct non-contradictory conclusion from the following two premises: (1) My body functions as a pure mechanism according to Laws of Nature; and (2) Yet I know, by incontrovertible direct experience, that I am directing its motions, of which I foresee the effects, that may be fateful and all-important, in which case I feel and take full responsibility for them. The only possible inference from these two facts is, I think, that I – I in the widest meaning of the word, that is to say, every conscious mind that has ever said or felt 'I' – am the person, if any, who controls the 'motion of the atoms' according to the Laws of Nature". Schrödinger then states that this insight is not new and that the  Upanishads  considered this insight of " ATMAN  =  BRAHMAN " to "represent quintessence of deepest insights into the happenings of the world." Schrödinger rejects the idea that the source of consciousness should perish with the body because he finds the idea "distasteful". He also rejects the idea that there are multiple immortal souls that can exist without the body because he believes that consciousness is nevertheless highly dependent on the body. Schrödinger writes that, to reconcile the two premises,


"The only possible alternative is simply to keep to the immediate experience that consciousness is a singular of which the plural is unknown; that there is only one thing and that what seems to be a plurality is merely a series of different aspects of this one thing…:


Any intuitions that consciousness is plural, he says, are illusions. Schrödinger is sympathetic to the  Hindu  concept of  Brahman , by which each individual's consciousness is only a manifestation of a  unitary consciousness  pervading the  universe  — which corresponds to the Hindu concept of God. Schrödinger concludes that "...'I' am the person, if any, who controls the 'motion of the atoms' according to the Laws of Nature." However, he also qualifies the conclusion as "necessarily subjective" in its "philosophical implications". In the final paragraph, he points out that what is meant by "I" is not the collection of experienced events but "namely the canvas upon which they are collected." If a hypnotist succeeds in blotting out all earlier reminiscences, he writes, there would be no loss of personal existence — "Nor will there ever be." [ 9 ]


In a world governed by the  second law of thermodynamics , all  isolated systems  are expected to approach a state of maximum disorder or  entropy : an irreversible state of  thermodynamic equilibrium , where  free energy  is no longer available to do  work . It has been argued that, since life approaches and maintains a highly ordered state, it violates the aforementioned second law, implying that there is a paradox. However, since the  biosphere  is not an isolated system, there is no paradox. The increase of order inside an organism is more than paid for by an increase in disorder outside this organism by the loss of heat into the environment. By this mechanism, the second law is obeyed, and life maintains a highly ordered state, which it sustains by causing a net increase in disorder in the Universe. In order to increase the complexity on Earth—as life does—free energy is needed, and in this case is provided by the Sun. [ 10 ] [ 11 ]


Lynette Deborah White  (5 July 1967 – 14 February 1988) was murdered in  Cardiff , Wales.  South Wales Police  issued a  photofit  image of a bloodstained, white male seen in the vicinity at the time of the murder but were unable to trace the man.


In November 1988, the police charged five men with White's murder, although none of the  scientific evidence  discovered at the crime scene could be linked to them. In November 1990, following what was then the longest murder trial in British history, three of the men were found guilty and sentenced to  life imprisonment .


In December 1992, the convictions were ruled unsafe and  quashed  by the  Court of Appeal  after it was decided that the police investigating the murder had acted improperly. The wrongful conviction of the three men has been called one of the most egregious  miscarriages of justice  in recent times. The police insisted that the men had been released purely on a  legal technicality , that they would be seeking no other suspects, and resisted calls for the case to be reopened.


In January 2002, new  DNA technology  enabled forensic scientists led by  Angela Gallop  to obtain a reliable crime scene DNA profile. The extracted profile led police to the real killer, Jeffrey Gafoor, who confessed to White's murder and was sentenced to life imprisonment. Gafoor received a shorter minimum tariff (the length of time before a prisoner may be considered for parole) than had been given to the wrongfully convicted men, due to the reduction for a guilty plea, highlighting a controversial feature of the sentencing guidelines.


In 2004, the  Independent Police Complaints Commission  (IPCC) began a review of the conduct of the police during the original inquiry. Over the next 12 months around 30 people were arrested in connection with the investigation, 19 of whom were serving or retired police officers. In 2007, three of the prosecution witnesses who gave evidence at the original murder trial were convicted of  perjury  and sentenced to 18 months imprisonment.


In 2011, eight former police officers were charged with conspiring to  pervert the course of justice . Their subsequent trial was the largest  police corruption  trial in British criminal history. A further four police officers were due to be tried on the same charges in 2012. In November 2011, the trial collapsed when the defence claimed that copies of files which they said they should have seen had instead been destroyed. As a result, the judge ruled that the defendants could not receive a fair trial and they were acquitted. In January 2012, the missing documents were found, still in the original box in which they had been sent to South Wales Police by the IPCC.


White had left school without any qualifications and had been sexually abused for money since she was 14 years old. [ 1 ] [ 2 ]  Tim Rogers, a  BBC Wales  journalist, interviewed White a few weeks before her murder as part of an investigation into  child prostitution . Rogers said that White was "probably the most visible prostitute working in Cardiff at the time." [ 3 ]  Acquaintances said that "she would be the first girl out at lunchtime, and the last one left at night", even working on Christmas Day. [ 4 ]  Described by friends as "pretty and popular", White earned around £100 each night. [ 1 ]  She told Rogers that she had been drugged and taken to  Bristol  by a gang of men who forced her into prostitution and that even after eventually making her way back to Cardiff she had found herself trapped in "a continual spiral of prostitution." [ 3 ]


By 1988 she was working every day to pay for her boyfriend Stephen "Pineapple" Miller's  cocaine  addiction. [ 4 ]  Miller, who was also her  pimp , took at least £60-£90 each day from White, who was his only source of income. [ 5 ] [ 6 ] [ 7 ]  Each day he would drive her to where she worked,  Riverside, Cardiff , before meeting with her at the "North Star" club in the evenings to collect her earnings. [ 5 ] [ 8 ] [ 9 ]  The two lived together at a flat in Dorset Street, Cardiff. [ 1 ] [ 10 ] [ 11 ]


White went missing five days before her murder and made no contact with Miller or any of her friends or known associates. [ 11 ]  Neither her whereabouts during this period nor the reason for her disappearance have ever been ascertained. [ 12 ]  She was due to be called as a witness for the prosecution in two forthcoming trials, and it was later conjectured that she was deliberately "lying low" to avoid giving evidence. [ 13 ] [ 14 ] [ 15 ]  The first trial ( R. v Francine Cordle ) involved an allegation of attempted murder and the second ( R. v Robert Gent & Eric Marasco ) involved an allegation of attempting to procure the services of a 13-year-old girl for prostitution. [ 13 ] [ 16 ]  When White disappeared, the police began actively searching for her, and a judge issued a  warrant for her arrest  to ensure that she attended the first trial, which was listed to commence at  Cardiff Crown Court  on 15 February 1988. [ 17 ]


Earlier in February 1988, another prostitute, Leanne Vilday, had loaned White the keys to the flat in James Street, where she was later murdered, for the purpose of taking clients there for sex. [ 18 ]  After White disappeared, Vilday was unable to get into the flat herself without the keys and on the evening of 14 February she asked taxi driver Eddie Dimond, who knew both women, to take her to the address. There Vilday was able to get another occupant to drop a spare set of keys from a window to open the main door of the building but was still unable to enter her own flat. [ 11 ]


Dimond and Vilday then drove to  Butetown Police Station  to report the situation and their concerns about White's disappearance. They returned to James Street with  PS  William Bisgood,  PC  Simon Johnson and PC Anthony Prosser, who were expecting to serve the arrest warrant on White and then take her into police custody. On arrival, Vilday and Dimond remained outside while the police forced entry and at 9.17 pm found White's body inside. [ 17 ]  PC Johnson later testified that he was aware that White was a "missing witness" in a court case and that officers had been looking for her. PC Prosser said, "We had been looking for her all weekend." He said he discovered White lying on her back on the floor of a bedroom in the flat, having suffered "massive injuries." [ 10 ]


White's throat had been cut from the right ear across the front and around to the left side of the neck, exposing the bones of the spine. There were multiple stab wounds to her chest and breasts, and other wounds to her face, stomach, arms, wrists and inner thighs, as well as  defensive wounds  on her hands. [ 18 ] [ 19 ]   Bernard Knight , the  pathologist  who conducted White's autopsy, described it as "a mutilating attack with sexual overtones" and identified a total of 69 wounds. Although she had been stabbed seven times in the heart he concluded that it was the throat injury which had killed her. He said: "It would require considerable force because the skin, muscles, larynx and voice box had been cut right down to the neckbone."


Speculating on how the wound could have been inflicted, he said it was a normal reflex for a person to keep their head down in such a situation, and her head may have been forcibly held back for the knife wound to be inflicted. One of the two T-shirts Lynette was wearing was "absolutely lacerated. It looked like a  colander ." Knight believed the murder weapon was at least five inches long. [ 18 ] [ 20 ]  He determined that she had died between midnight and 4   am. Her wristwatch had stopped at 1:45   am, leading the police to conclude that this was the most likely time of death. [ 5 ] [ 18 ] [ 21 ]


White's body was discovered between the foot of the bed – the room's only furniture – and the window, still clothed but with one shoe off. There was heavy bloodstaining to the base of the bed, the carpet and the walls of the room. There was very little blood on the mattress, where an opened but unused  condom  was found. [ 18 ]  Forensic examination found 150 different sets of finger and palm prints in the flat.  Azoospermic   semen  was present both in White's vagina and underwear, which pathologists determined had been deposited there within six hours of her death. [ 5 ] [ 18 ]  Some of the blood found on White's clothing, including her exposed sock, was found to be from a male with the  blood type  AB. [ 22 ]


The subsequent murder inquiry was led by  Detective Chief Superintendent  (DCS) John Williams, the head of South Wales Police's  Criminal Investigation Department  (CID). [ 23 ]  Appeals for information led to several potential witnesses independently describing a white male, approximately 5'8"–5'10", aged in his mid-30s, with dark hair and a "dishevelled" appearance. He was seen in a distressed state in the vicinity of the James Street flat in the early hours of 14 February, appeared to have cut himself on the hand, and had blood on his clothing. [ 24 ] [ 25 ]


An  E-FIT  of the suspect was compiled and on 17 March 1988 DCS Williams appeared on the  BBC  television programme  Crimewatch UK , where he stated that the police believed this man was responsible for White's murder. [ 26 ]  Williams said: "This man almost certainly had the blood of the deceased on him." [ 27 ] [ 28 ] [ 29 ]


On 25 February the police detained an individual who bore a striking resemblance to the e-fit but he was released the following day after providing an alibi corroborated by a third party. The suspect seen outside the flat has never been positively identified. [ 16 ]


Francine Cordle, whom White had been due to testify against, and Cordle's mother, Peggy Farrugia, were also initially considered suspects, but the discovery of the blood on White's clothing allowed the police to eliminate them from their inquiries.


Stephen Miller was questioned at the beginning of the inquiry, having been picked up by the police early on 15 February, but after giving a statement detailing his whereabouts during the crucial period, he was released without charge and the police announced that he had been ruled out of their investigations. [ 16 ]  When Miller was first taken in by the police for questioning he was still wearing the clothes that he had been wearing at the time of the murder. These were dirty and unwashed – the police even joked with Miller during his initial interview that he should sit in the opposite corner of the room due to the smell of his clothing – but there were no traces of blood found on them. His car was also forensically examined with no result, and his blood type did not match that found on White's clothing. Another witness, David Orton, also gave a statement to the police detailing his movements with Miller during the time of the murder, completely corroborating Miller's alibi. [ 16 ]


On 20 April 1988 DC Geoff Thomas put together a list of 12 people of interest, based on their previous criminal activities. One of the men, whose identity has never been publicly revealed and was referred to only as 'Mr X', was a convicted sex offender and  paedophile  who lived around twenty minutes driving distance from James Street, was known to use prostitutes, and was a frequent visitor to Cardiff. [ 30 ]  He had a history of  mental illness  and had been classified as a " psychopath " by his doctor. [ 31 ] [ 32 ] [ 33 ]  When interviewed by the police, he admitted that he had in the past paid White for sex, and was unable to account for his movements or provide an alibi for the period of the murder. [ 22 ]  Crucially for the investigating officers, Mr. X was of blood type AB. [ 34 ]


Mr. X was interviewed by Detective Constable Paul Fish, who believed that, had he been pressed, he would have confessed to White's murder. It was decided however to adopt a "softly-softly" approach until they had DNA results from the crimescene. [ 22 ]  On 19 October 1988 Detective Inspector Graham Mouncher placed Mr. X under surveillance for three days to identify his routines and associates. The policemen's main concern was that Mr. X would voluntarily commit himself to a mental institution if he became aware of the surveillance but by 25 October DI Mouncher was so convinced that he was the killer that he requested further surveillance. This took place between 27 and 30 October 1988. On 7 November 1988 Detective Chief Inspector Adrian Morgan informed DCS Williams that Mr. X was now the  prime suspect . [ 22 ]


On 9 November 1988 the results of the DNA analysis eliminated Mr. X from the investigation.


Although their prime suspect had been eliminated from the inquiry, the police had collected thousands of statements through interviews and door-to-door enquiries. After the collapse of their case against Mr. X the police now returned to these. Among them were statements from Paul Atkins and Mark Grommek, two associates of Mr. X. Grommek was the tenant of the flat immediately above that where White was murdered. [ 35 ]  Both Atkins and Grommek were homosexual and had previous convictions for  petty crimes , which made them, in the view of Satish Sekar, "susceptible to police pressure." [ 36 ]


Both men gave alibis for their whereabouts at the time of the murder, but under pressure from the police Atkins eventually gave a statement on 26 April in which he first said that Grommek had killed White, and then confessed to killing her himself. [ 37 ]


Detective Chief Inspector John Ludlow recorded that Atkins first stated that Grommek had gone to the flat to have sex with White and after hearing a scream, Atkins went downstairs and saw Grommek exiting the flat covered in blood and carrying a blood stained knife. Atkins later said he had met White himself in the Custom House pub and went back to the flat to have sex with her. [ 38 ]  He then "wrestled her to the floor, sat astride her and stabbed her." [ 39 ]  As the statement contained "four completely different accounts in the one document" it was not treated seriously. [ 36 ]


Yusef Abdullahi had been questioned as part of the routine door-to-door enquiries. At the time of the murder he had been working on board the ship  MV   Coral Sea , some 8 miles (13 km) away in  Barry Docks . [ 40 ]  Although he did not realise this at the time, his  common-law  wife Jackie Harris was having an affair with Geoff Smith, a South Wales police officer attached to the Vice Squad. His common-law brother-in-law, Ronnie Williams, was also a  police informant . [ 41 ]  Williams began passing information to the police in March 1988, much of it unreliable, including a claim that White had been stabbed in the  Casablanca  club in Butetown before being moved to the flat in James Street. Initially he claimed that Abdullahi knew the identity of the killer and was concealing this information but later he began to implicate him more directly with the murder, and claimed that Abdullahi had been able to leave work at the  Coral Sea  on the night of the murder without his colleagues being aware. It was well known by their associates and the police that Abdullahi and Williams "detested each other." [ 31 ]  On 19 May 1988 Detective Inspector Richard Powell took a formal statement from Abdullahi in which he gave details of his work on the  Coral Sea . [ 40 ]


Leanne Vilday had also been placed under pressure during her interviews, particularly as it was she who had initially raised the alarm with the police, who felt she may be concealing information. She was a single parent, a lesbian, a drug addict, and a prostitute. The police were visiting her daily, leading to her being asked to leave the flat she shared with her friend, Angela Psaila, who was also a prostitute. She began lodging with another couple, who also complained that the police were calling round to speak with Vilday on an almost daily basis. [ 36 ]


On 19 May 1988, while drunk, Vilday eventually named Miller and Yusef Abdullahi as the killers in front of several other prostitutes. That evening she was questioned by PS David Hathaway and agreed that she had named the two men while drunk, but said this was a false accusation as a result of "drunken rambling" and that she had heard the names from DI Powell when he had questioned her earlier in the day. [ 40 ]  She was then asked by the police if she would agree to be  hypnotised , and a session with a hypnotherapist was scheduled. [ 42 ]


Violet Elizabeth Perriam was a secretary at a Cardiff yacht club. On 10 November 1988, the day after Mr. X was cleared of any involvement, Perriam gave a statement to the police that she had been driving home from the club and had passed 7 James Street at around 1.30 am on the night that White was murdered. [ 43 ]  She claimed that she saw four "excited" black males outside the building, "arguing and gesticulating," and recognised two of them as John Actie and Rashid Omar, who was of mixed-race. [ 44 ] [ 45 ]


John Actie had earlier responded to the door-to-door enquiries and told the police that on the night of the murder he had gone to the  Casablanca  club at around midnight, and had left there at around 3.30 am. John Actie was the cousin of Leanne Vilday's boyfriend, Ronnie Actie. Perriam's statement was the "breakthrough" needed by the police and her allegation that she saw John Actie and others "at or near the scene of the murder" allowed the investigation to take a new direction after it had reached an impasse following the elimination of Mr. X. [ 7 ] [ 46 ]


Angela Psaila lived in a flat at St Clare's Court,  Butetown , which had an unrestricted view of the front of 7 James Street. Described later as "one of the most vulnerable members of Cardiff society", Psaila had an IQ of just 55, indicating mild mental retardation. [ 47 ] [ 48 ] [ 49 ]  Armed with Perriam's statement placing the group of black men outside the flat at the time of the murder, the police questioned Psaila on 17 November 1988 and insisted that she was somehow connected with the crime. In the first of two statements taken that day, Psaila claimed that Miller visited her at about 1   am on 14 February looking for White. Two and a half hours later she gave another statement claiming that she saw Miller, John and Ronnie Actie, Abdullahi, Tony Paris and Tony Brace (a doorman from the North Star club) outside 7 James Street. She also claimed to have heard screams from the flat and to have seen Ronnie Actie talking up to someone in the window of Grommek's flat before being let into the building. [ 50 ]  As part of the 2021 three-part BBC documentary  A Killing in Tiger Bay  the supposed screaming was reconstructed, using an actress in White's former flat and sensitive sound recording equipment placed at Psaila's former flat. Even with no background noise, the screams were barely audible. [ 51 ]


The same day, Grommek and Atkins gave new statements to the police saying that they had also seen a group of men outside the flat, including Ronnie Actie and Abdullahi. [ 50 ]  During his first interview, in the morning, Grommek had stated that he knew nothing about the murder but by the afternoon he had given a very detailed account of the circumstances surrounding the crime. [ 52 ]  Grommek also said that he had opened the door to the building to let Ronnie Actie in, and both he and Atkins now claimed that they too had heard screams that night. [ 50 ]


Psaila gave a new statement to the police on 6 December 1988. In this account, she had been present at St Clare's Court with Leanne Vilday and on hearing the screams the two had gone to 7 James Street. In what Sekar called "a most remarkable coincidence", Vilday, Grommek and Atkins all decided independently to go to the police that day and give new accounts of the murder. Vilday said that on hearing the screams she had gone to the flat and found White dead inside. In the room were Miller, Abdullahi, Ronnie Actie, Tony Miller (Stephen Miller's brother) and an unnamed man of mixed-race. Grommek and Atkins gave statements which corroborated this new version of events. Psaila and Vilday were then taken into  protective custody . [ 53 ]


On 7 December 1988, the police arrested Stephen and Tony Miller, Yusef Abdullahi, Ronnie Actie, Rashid Omar and Martin Tucker. John Actie and Tony Paris were arrested on 9 December. No forensic evidence had been found to link any of the men with the crime scene. [ 14 ] [ 54 ]


The police were notified on 10 December that Psaila's blood type was AB, the same as that found on White's sock and trousers. They reinterviewed her the following day, insisting that it was her blood that was found on White. Psaila gave a new version of events, this time claiming that she and Vilday had been present when White was murdered, and had taken part in the killing. She named Stephen and Tony Miller, Ronnie and John Actie, Tony Paris and Abdullahi as the other killers, and said Vilday had been responsible for cutting White's throat.


Vilday then gave a new statement on the same day, naming Stephen Miller, Ronnie and John Actie, Abdullahi and Paris as the killers, and saying that she and Psaila had both been forced to cut one of White's wrists to ensure their complicity and silence.


Over a period of four days, Stephen Miller was interviewed on 19 occasions for a total of 13 hours; he was denied access to a solicitor for the first two interviews. Miller, who had a  mental age  of 11, confessed to the killing after making 307 denials. [ 55 ]  Miller also implicated the other men. [ 56 ] [ 57 ]


The trial commenced at  Swansea Crown Court  on 5 October 1989, but was interrupted on 26 February 1990 – after 82 days of evidence – by the sudden death of the judge, Mr Justice McNeill, from a heart attack. [ 19 ] [ 58 ] [ 59 ] [ 60 ]  The subsequent retrial, also held at Swansea, commenced on 14 May 1990 before Mr Justice Leonard. [ 61 ]  It was at the time the longest murder trial in British legal history, lasting 197 days. [ 24 ] [ 62 ]  On 22 November 1990, three of the five accused were found guilty of White's murder. [ 19 ] [ 32 ]  Tony Paris, Yusef Abdullahi and Stephen Miller – who became known as the "Cardiff Three" – were each sentenced to  life imprisonment . [ 54 ] [ 63 ] [ 64 ]  Cousins Ronnie and John Actie were acquitted of the murder; both had spent two years in custody. 17 years later, in September 2007, Ronnie was found dead in his back garden; police said there were no suspicious circumstances. [ 65 ]


Evidence concerning the unreliability of the taped police confession of Stephen Miller was given by Icelandic-British academic, forensic psychologist and former detective  Gísli Guðjónsson . [ 51 ]


In early 1991 a number of journalists began to question the safety of the convictions and commercial television broadcaster  Channel 4  transmitted their own investigation of the case in "Butetown: The Bridge And The Boys", part of their  Black Bag  magazine and documentary series aimed at Black and Asian viewers. [ 66 ] [ 67 ]  In May 1991 two of the convicted men were granted leave to appeal their convictions, but the third, Stephen Miller, was refused. [ 68 ]   Satish Sekar , an  investigative journalist  specialising in crime and justice issues, had tracked down two witnesses not called at the trial who could provide an  alibi  for Miller's whereabouts at the time of the murder. Miller asked him if he would organise a new legal team to prepare his appeal. Sekar persuaded renowned solicitor  Gareth Peirce  to take on the case and handle the renewed application to appeal, and Peirce instructed  Michael Mansfield   QC  to represent Miller in court. [ 69 ]


A public campaign to overturn the convictions, started by families and friends of the three men, began to receive high-profile support, including that of American community leader  Al Sharpton , and  Gerry Conlon , a recently exonerated member of the " Guildford Four ". [ 70 ]  Further television documentaries followed in 1992, including "Unsafe Convictions" as part of the  BBC  documentary series  Panorama [ 29 ] [ 71 ]  and in 2021 the three-part BBC documentary  A Killing in Tiger Bay , which included first-hand accounts from Miller, Paris and John Actie, as well as from some of the defence team and expert witness  Gísli Guðjónsson . [ 51 ]


Their appeal was heard over four days in December 1992 and ended after the  Court of Appeal  listened to an audio recording of Stephen Miller's police interrogation. Mansfield argued that the trial judge "was wrong to admit the evidence of Mr Miller's police interviews contained on the tapes because it was tainted by the officers' 'oppressive' conduct." The interviews were, he said, "not a search for the truth but a police attempt to achieve—by any means short of violence—a concurrence between Mr Miller's account and Ms Vilday's." [ 72 ]


In his judgement,  Lord Taylor  said that the police had "bullied and hectored" Miller during a "travesty of an interview" and that  "short of physical violence, it is hard to conceive of a more hostile and intimidating approach by officers to a suspect." The truthfulness of Miller's admission was, according to Taylor, "irrelevant" as the nature of the questioning "required the interview to be rejected as evidence." [ 73 ]  He ordered copies of the recording to be sent to the  Director of Public Prosecutions  and the Chairman of the  Royal Commission on Criminal Justice  as an "example of what we hope we shall never hear again in this court". [ 74 ]  All three men had their convictions declared "unsafe and unsatisfactory" and were released. [ 24 ]


Yusef Abdullahi was treated for  posttraumatic stress disorder  after his release from prison and campaigned on behalf of other victims of miscarriages of justice and for the reopening of the investigation into White's murder. In 1996 he said: "Until it happens to you, no-one can have any idea what it's like to be convicted for a murder you didn't commit. We've been really messed up by what we've been through. We needed counselling, but no-one offered us any help. Being inside really did my head in." He died of a  perforated ulcer  in January 2011, aged 49. [ 75 ] [ 76 ]


In September 2000, the case was reopened. Forensic scientists led by  Angela Gallop  discovered fresh evidence, including a small trace of blood on the cellophane wrapper from a cigarette packet and a further ten traces of the same blood underneath several layers of paint on a  skirting board  at the crime scene. [ 77 ] [ 78 ]  The killer was dubbed "Cellophane Man" by scientists and detectives. [ 79 ]  No match was found in the  United Kingdom National DNA Database .


In January 2002, after the development of the  Second Generation Multiplex Plus  (SGM+) test, forensic scientists, led by Professor  Angela Gallop ,  were finally able to obtain a reliable crime scene DNA profile. [ 80 ]  Hopes were also raised of solving the case when in the same year South Wales Police were able to positively identify a historical  Port Talbot  serial killer,  Joe Kappen , using the pioneering approach of  familial DNA searching . [ 81 ]  He had been unmasked as the killer after forensic samples from three 1973 murder victims were found to match his living son, and detectives on the White case hoped techniques could be used in their case. [ 81 ]


Using this process of familial searching, a partial match was eventually made with the profile of a 14-year-old youth who was known to the police but who had not been born at the time of the murder of White. This led to the arrest on 28 February 2003 of Jeffrey Gafoor, who was the youth's uncle. [ 79 ] [ 82 ]  Gafoor was prosecuted for the murder in July 2003. On 4 July 2003, at  Cardiff Crown Court , he pleaded guilty to White's murder and the judge,  Mr Justice Royce , sentenced him to life imprisonment, with a minimum tariff of twelve years and eight months. [ 19 ] [ 80 ]


In November 2004, the IPCC announced that it would supervise a reinvestigation by the South Wales Police into the original police inquiry. [ 83 ]  On 13 April 2005, five retired police officers were arrested in connection with offences of  false imprisonment ,  conspiring to pervert the course of justice  and  misconduct in public office . [ 77 ] [ 84 ]  Four more retired police officers were arrested in connection with their roles in the original murder investigation on 21 April 2005. [ 85 ]  Along with the officers, a further 13 people were arrested in connection with evidence and information that they had provided in 1988 which had incriminated the three convicted men. [ 86 ]  On 19 May 2005, three serving police officers – a  Detective Constable , a  Constable  and a  Detective Sergeant  – were arrested. [ 87 ]  As the investigation continued, over 30 arrests had been made by November 2005, 19 of whom were serving or retired police officers, including one  Inspector . [ 88 ] [ 89 ]


In February 2007, four witnesses who gave evidence at the original murder trial were charged with  perjury . [ 35 ]  In December 2008, three of the accused – Angela Psaila, Leanne Vilday and Mark Grommek – were found guilty of committing perjury and each sentenced to 18 months imprisonment. The fourth, Paul Atkins, was deemed "unfit to stand trial." [ 60 ]  Mr Justice Maddison, sentencing, said: "It's been submitted on your behalf, accepted by the prosecution, and I accept it myself... you were seriously hounded, bullied, threatened, abused and manipulated by the police during a period of several months leading up to late 1988, as a result of which you felt compelled to agree to false accounts they suggested to you." However, perjury was "an offence which strikes at the heart of the system of the administration of justice." [ 90 ]


In March 2009, the Special Crime Division of the  Crown Prosecution Service  (CPS) announced that there was "sufficient evidence" to prosecute three serving officers and ten former officers involved in the original investigation with conspiracy to pervert the course of justice. [ 60 ]  Two further witnesses in the original trial, Violet Perriam and Ian Massey, were also charged with perjury. [ 91 ]  In July 2011 the trial ( R v Mouncher and Others )—the largest police corruption trial in British criminal history—of Chief Inspectors Graham Mouncher and Richard Powell, Inspector Thomas Page, Detectives Michael Daniels, Paul Jennings, Paul Stephen, Peter Greenwood and John Seaford, and Violet Perriam and Ian Massey, commenced at Swansea Crown Court. [ 92 ]  Massey was a convicted  armed robber  incarcerated at  HM Prison Cardiff  at the same time as Tony Paris and John Actie. He agreed to act as a police informant against the men in return for "representations made by the police" to his forthcoming Parole Board hearing, and gave evidence at their trial that Paris had confessed to White's murder in his presence. [ 93 ] [ 94 ]


During the trial, "concerns had been almost continually raised" by defence counsel relating to alleged non-disclosure by the prosecution of relevant documents. [ 95 ]  On 28 November 2011,  Mr Justice Sweeney  ordered the prosecution to produce to him a number of specific documents requested by the defence. Four of the documents were "found to be missing from their expected location" and an initial investigation by the police concluded that the documents had been destroyed in 2010 on the instructions of Detective Chief Superintendent Christopher Coutts. As a result, Nicholas Dean QC, leading counsel for the prosecution, informed the court, on 1 December 2011, that "the prosecution can no longer sustain a position maintaining that the court and the defendants can have the required confidence in the disclosure process, the confidence that my Lord has referred to with all its importance to our criminal justice system. In those circumstances I formally offer no further evidence and will invite my Lord to direct the jury to return not guilty verdicts." [ 96 ]


The decision was made at the highest level, by  Keir Starmer , at the time the Director of Public Prosecutions, Head of the  Crown Prosecution Service  and the most senior public prosecutor in England and Wales. [ 97 ]  The trial collapsed and South Wales Police immediately announced referral to the IPCC for further investigation. [ 98 ]  Starmer said: "Prosecutions will stand or fall on the quality of disclosure, and failings can leave the court with no choice but to acquit defendants who have a case to answer." [ 99 ]  On 17 January 2012, the missing documents were found in the office of DCS Coutts, still in the original box in which they had been sent from the IPCC. [ 100 ] [ 101 ] [ 102 ]


Sekar responded to the acquittals by saying: "It is a very, very sad day for justice, as it suggests you cannot ever prosecute police officers successfully if you can't do it in a case like this." [ 103 ]   Tom Mangold , the BBC journalist and broadcaster who covered the case for  Panorama  in 1992 and 2012, called it "the biggest scandal in the history of British justice." [ 104 ]  Mangold also noted: "If the 13 accused Cardiff detectives had been found guilty, presumably all their previous cases — hundreds — would have had to be reopened and re-examined. Instead, they are now considering suing the South Wales Police." [ 57 ]  By the time the trial collapsed, all of the police officers charged had been allowed to retire. [ 105 ]


In February 2015, then  Home Secretary   Theresa May  announced that an investigation into the collapse of the police corruption trial would be carried out, led by Richard Horwell QC. [ 106 ]  May, who rejected calls for a full  public inquiry , said: "There are still unresolved questions surrounding the reasons why no-one was found responsible for this appalling miscarriage of justice." [ 106 ]  The inquiry was expected to present its findings in the summer of 2015 but this was delayed by the civil actions brought by former officers against South Wales Police. [ 107 ]


Following the collapse of the corruption trial, eight former police officers and seven others sued South Wales Police for damage to their reputations. [ 108 ]  The action alleged malicious prosecution, false imprisonment and misfeasance in public office by South Wales Police. [ 109 ]  On 14 June 2016,  Mr Justice Wyn Williams  ruled that the force "was within its rights to investigate the officers" and dismissed the case. [ 110 ]  He said: "I find it very difficult to understand how the accounts emerged as they did if no police officer was instrumental in what occurred. I have reached the clear conclusion that reasonable grounds existed from the start of LW3 [the inquiry into police corruption] to suspect that the untruthful accounts which the core four [Psaila, Vilday, Grommek and Atkins] gave about the involvement of the original defendants in Lynette's murder were brought about by criminal conduct on the part of police officers involved in LW1 [the original murder investigation]. In my judgment, it was permissible for LW3 officers to suspect that officers who had been part of LW1 had engaged in a conspiracy to mould and manipulate evidence." Furthermore, the explanation given by Chief Superintendent Thomas Page regarding documents that he had burned in his garden prior to his arrest, was, according to the judge, "open to considerable doubt". [ 110 ]


Other (active) UK cold cases where the offender's DNA is known:


Citations


Bibliography


Carl Richard Woese  ( / w oʊ z /   WOHZ ; [ 3 ]  July 15, 1928 – December 30, 2012) was an American  microbiologist  and  biophysicist . Woese is famous for defining the  Archaea  (a new  domain  of life) in 1977 through a pioneering  phylogenetic   taxonomy  of  16S ribosomal RNA , a technique that has revolutionized microbiology. [ 4 ] [ 5 ] [ 6 ] [ 7 ]  He also originated the  RNA world hypothesis  in 1967, although not by that name. [ 8 ]  Woese held the  Stanley O. Ikenberry  Chair and was professor of microbiology at the  University of Illinois Urbana–Champaign . [ 9 ] [ 10 ] [ 11 ]


Woese was born in Syracuse, New York on July 15, 1928. His family was  German American . Woese attended  Deerfield Academy  in  Massachusetts . He received a bachelor's degree in  mathematics  and  physics  from  Amherst College  in 1950. During his time at Amherst, Woese took only one biology course ( Biochemistry , in his senior year) and had "no scientific interest in plants and animals" until advised by  William M. Fairbank , then an assistant professor of physics at Amherst, to pursue  biophysics  at  Yale . [ 12 ]


In 1953, he completed a  PhD  in  biophysics  at  Yale University , where his doctoral research focused on the inactivation of  viruses  by heat and  ionizing radiation . [ 13 ] [ 14 ]  He studied medicine at the  University of Rochester  for two years. [ 14 ]  Then he became a postdoctoral researcher in biophysics at Yale University investigating bacterial spores. [ 15 ]  From 1960 to 1963, he worked as a biophysicist at the  General Electric Research Laboratory  in  Schenectady, New York . [ 13 ] [ 16 ]  In 1964, Woese joined the microbiology faculty of the University of Illinois Urbana–Champaign, where he focused on Archaea, genomics, and  molecular evolution  as his areas of expertise. [ 11 ] [ 13 ] [ 16 ]  He became a professor at the University of Illinois Urbana–Champaign's  Carl R. Woese Institute for Genomic Biology , which was renamed in his honor in 2015, after his death. [ 16 ]


Woese died on December 30, 2012, following complications from  pancreatic cancer , leaving as survivors his wife Gabriella and a son and daughter. [ 17 ] [ 18 ] [ 19 ]


Woese turned his attention to the  genetic code  while setting up his lab at  General Electric 's  Knolls Laboratory  in the fall of 1960. [ 14 ]  Interest among physicists and molecular biologists had begun to coalesce around deciphering the correspondence between the twenty  amino acids  and the four letter alphabet of  nucleic acid bases  in the decade following  James D. Watson ,  Francis Crick , and  Rosalind Franklin 's discovery of the structure of DNA in 1953. [ 1 ]  Woese published a series of papers on the topic. In one, he deduced a correspondence table between what was then known as "soluble RNA" and DNA based upon their respective  base pair  ratios. [ 20 ]  He then re-evaluated experimental data associated with the hypothesis that viruses used one base, rather than a triplet, to encode each amino acid, and suggested 18 codons, correctly predicting one for  proline . [ 14 ] [ 21 ]  Other work established the mechanistic basis of protein translation, but in Woese's view, largely overlooked the genetic code's evolutionary origins as an afterthought. [ 1 ]


In 1962, Woese spent several months as a visiting researcher at the  Pasteur Institute  in  Paris , a locus of intense activity on the molecular biology of gene expression and gene regulation. [ 14 ]  While in Paris, he met  Sol Spiegelman , who invited Woese to visit the  University of Illinois  after hearing his research goals; at this visit Spiegelman offered Woese a position with immediate  tenure  beginning in the fall of 1964. [ 14 ]  With the freedom to patiently pursue more speculative threads of inquiry outside the mainstream of biological research, Woese began to consider the genetic code in evolutionary terms, asking how the codon assignments and their translation into an amino acid sequence might have evolved. [ 14 ] [ 22 ]


For much of the 20th century, prokaryotes were regarded as a single group of organisms and classified based on their  biochemistry ,  morphology  and  metabolism . In a highly influential 1962 paper,  Roger Stanier  and  C. B. van Niel  first established the division of cellular organization into  prokaryotes  and  eukaryotes , defining prokaryotes as those organisms lacking a  cell nucleus . [ 23 ] [ 24 ]  Adapted from  Édouard Chatton 's generalization, Stanier and Van Niel's concept was quickly accepted as the most important distinction among organisms; yet they were nevertheless skeptical of microbiologists' attempts to construct a natural  phylogenetic  classification of bacteria. [ 25 ]  However, it became generally assumed that all life shared a common prokaryotic (implied by the  Greek  root πρό (pro-), before, in front of) ancestor. [ 24 ] [ 26 ]


In 1977, Woese and  George E. Fox  experimentally disproved this universally held hypothesis about the basic structure of the  tree of life . [ 27 ]  Woese and Fox discovered a kind of microbial life which they called the “archaebacteria” ( Archaea ). [ 6 ]  They reported that the archaebacteria comprised "a third kingdom" of life as distinct from bacteria as plants and animals. [ 6 ]  Having defined Archaea as a new "urkingdom" (later  domain ) which were neither bacteria nor eukaryotes, Woese redrew the  taxonomic  tree. His  three-domain system , based on phylogenetic relationships rather than obvious morphological similarities, divided life into 23 main divisions, incorporated within three domains:  Bacteria ,  Archaea , and  Eucarya . [ 4 ]


Acceptance of the validity of Woese's phylogenetically valid classification was a slow process. Prominent biologists including  Salvador Luria  and  Ernst Mayr  objected to his division of the prokaryotes. [ 28 ] [ 29 ]  Not all criticism of him was restricted to the scientific level. A decade of labor-intensive  oligonucleotide  cataloging left him with a reputation as "a crank," and Woese would go on to be dubbed as "Microbiology's Scarred Revolutionary" by a news article printed in the journal  Science . [ 7 ]  The growing body of supporting data led the  scientific community  to accept the Archaea by the mid-1980s. [ 14 ]  Today, few scientists cling to the idea of a unified Prokarya.


Woese's work on Archaea is also significant in its implications for the search for life on other planets. Before the discovery by Woese and Fox, scientists thought that Archaea were extreme organisms that evolved from the microorganisms more familiar to us. Now, most believe they are ancient, and may have robust evolutionary connections to the first organisms on Earth. [ 30 ]  Organisms similar to those archaea that exist in extreme environments may have developed on other planets, some of which harbor conditions conducive to  extremophile  life. [ 31 ]


Notably, Woese's elucidation of the  tree of life  shows the overwhelming diversity of microbial lineages: single-celled organisms represent the vast majority of the biosphere's genetic, metabolic, and ecologic niche diversity. [ 32 ]  As microbes are crucial for many  biogeochemical cycles  and to the continued function of the biosphere, Woese's efforts to clarify the evolution and diversity of microbes provided an invaluable service to  ecologists  and  conservationists . It was a major contribution to the theory of  evolution  and to our knowledge of the history of life. [ 1 ]


Woese wrote, "My evolutionary concerns center on the bacteria and the archaea, whose evolutions cover most of the planet's 4.5-billion-year history. Using ribosomal RNA sequence as an evolutionary measure, my laboratory has reconstructed the phylogeny of both groups, and thereby provided a phylogenetically valid system of classification for prokaryotes. The discovery of the archaea was in fact a product of these studies". [ 13 ]


Woese also speculated about an era of rapid evolution in which considerable  horizontal gene transfer  occurred between organisms. [ 27 ] [ 33 ]  First described by Woese and Fox in a 1977 paper and explored further with microbiologist  Jane Gibson  in a 1980 paper, these organisms, or  progenotes , were imagined as protocells with very low complexity due to their error-prone translation apparatus ("noisy genetic transmission channel"), which produced high mutation rates that limited the specificity of cellular interaction and the size of the genome. [ 34 ] [ 35 ]  This early translation apparatus would have produced a group of structurally similar, functionally equivalent proteins, rather than a single protein. [ 27 ]  Furthermore, because of this reduced specificity, all cellular components were susceptible to horizontal gene transfer, and rapid evolution occurred at the level of the ecosystem. [ 33 ] [ 36 ]


The transition to modern cells (the " Darwinian Threshold ") occurred when organisms evolved translation mechanisms with modern levels of fidelity: improved performance allowed cellular organization to reach a level of complexity and connectedness that made genes from other organisms much less able to displace an individual's own genes. [ 33 ]


In later years, Woese's work concentrated on genomic analysis to elucidate the significance of horizontal gene transfer (HGT) for evolution. [ 37 ]  He worked on detailed analyses of the phylogenies of the aminoacyl-tRNA synthetases and on the effect of horizontal gene transfer on the distribution of those key enzymes among organisms. [ 38 ]  The goal of the research was to explain how the primary cell types (the archaeal, eubacterial, and eukaryotic) evolved from an ancestral state in the  RNA world . [ 13 ]


Woese shared his thoughts on the past, present, and future of biology in  Current Biology : [ 12 ]


The "important questions" that 21st century biology faces all stem from a single question, the nature and generation of  biological organization . . . . Yes, Darwin is back, but in the company of . . . scientists who can see much further into the depths of biology than was possible heretofore. It is no longer a "10,000 species of birds" view of evolution—evolution seen as a procession of forms. The concern is now with the process of evolution itself. [ 12 ]


I see the question of biological organization taking two prominent directions today. The first is the evolution of (proteinaceous) cellular organization, which includes sub-questions such as the evolution of the translation apparatus and the genetic code, and the origin and nature of the hierarchies of control that fine-tune and precisely interrelate the panoply of cellular processes that constitute cells. It also includes the question of the number of different basic cell types that exist on earth today: did all modern cells come from a single ancestral cellular organization? [ 12 ]


The second major direction involves the nature of the global ecosystem. . . . Bacteria are the major organisms on this planet—in numbers, in total mass, in importance to the global balances. Thus, it is  microbial ecology  that . . . is most in need of development, both in terms of facts needed to understand it, and in terms of the framework in which to interpret them. [ 12 ]


Woese considered biology to have an "all-important" role in society. In his view, biology should serve a broader purpose than the pursuit of "an engineered environment": [ 12 ]


What was formally recognized in physics needs now to be recognized in biology: science serves a dual function. On the one hand it is society's servant, attacking the applied problems posed by society. On the other hand, it functions as society's teacher, helping the latter to understand its world and itself. It is the latter function that is effectively missing today. [ 12 ]


Woese was a  MacArthur Fellow  in 1984, was made a member of the  National Academy of Sciences  in 1988, received the  Leeuwenhoek Medal  (microbiology's highest honor) in 1992, the  Selman A. Waksman Award in Microbiology  in 1995 from the  National Academy of Sciences , [ 39 ]  and was a  National Medal of Science  recipient in 2000. In 2003, he received the  Crafoord Prize  from the  Royal Swedish Academy of Sciences  "for his discovery of a third domain of life". [ 40 ] [ 41 ]   He was elected to the  American Philosophical Society  in 2004. [ 42 ]  In 2006, he was made a  foreign member of the Royal Society . [ 11 ]


Many microbial species, such as  Pyrococcus woesei , [ 43 ]   Methanobrevibacter woesei , [ 44 ]  and  Conexibacter woesei , [ 45 ]  are named in his honor.


Microbiologist Justin Sonnenburg of  Stanford University  said "The 1977 paper is one of the most influential in microbiology and arguably, all of biology. It ranks with the works of  Watson  and  Crick  and Darwin, providing an evolutionary framework for the incredible diversity of the microbial world". [ 1 ]


With regard to Woese's work on horizontal gene transfer as a primary evolutionary process, Professor  Norman R. Pace  of the  University of Colorado at Boulder  said, "I think Woese has done more for biology  writ large  than any biologist in history, including  Darwin ... There's a lot more to learn, and he's been interpreting the emerging story brilliantly". [ 46 ]


Sewall Green Wright   FRS (For) [ 3 ]
ForHonorary  FRSE  (December 21, 1889 – March 3, 1988) was an American  geneticist  known for his influential work on  evolutionary theory  and also for his work on  path analysis . He was a founder of  population genetics  alongside  Ronald Fisher  and  J. B. S. Haldane , which was a major step in the development of the  modern synthesis  combining  genetics  with  evolution . He discovered the  inbreeding coefficient  and methods of computing it in  pedigree animals . He extended this work to  populations , [ 4 ]  computing the amount of  inbreeding  between members of populations as a result of random  genetic drift , and along with Fisher he pioneered methods for computing the distribution of  gene frequencies  among populations as a result of the interaction of  natural selection ,  mutation , migration and genetic drift. Wright also made major contributions to  mammalian  and biochemical genetics. [ 5 ] [ 6 ] [ 7 ]


Sewall Wright was born in  Melrose, Massachusetts , to  Philip Green Wright  and Elizabeth Quincy Sewall Wright. His parents were first cousins, [ 8 ]  an interesting fact in light of Wright's later research on  inbreeding . The family moved three years later after Philip accepted a teaching job at  Lombard College , a  Universalist  college in Galesburg, Illinois.


As a child, Wright helped his father and brother print and publish an early book of poems by his father's student  Carl Sandburg . At the age of seven, in 1897, he wrote his first "book", entitled  Wonders of Nature , [ 5 ]  and he published his last paper in 1988: [ 9 ]  he can be claimed, therefore, to be the scientist with the longest career of science writing. Wright's astonishing maturity at the age of seven may be judged from the following excerpt quoted in the obituary: [ 5 ]


Have you ever examined the gizzard of a fowl? The gizzard of a fowl is a deep red colar with blu at the top. First on the outside is a very thick muscle. Under this is a white and fleecy layer. Holding very tight to the other. I expect you know that chickens eat sand. The next two layers are rough and rumply. These layers hold the sand. They grind the food. One night when we had company we had chicken-pie. Our Aunt Polly cut open the gizzard, and in it we found a lot of grain, and some corn.


He was the oldest of three gifted brothers—the others being the  aeronautical engineer   Theodore Paul Wright  and the  political scientist   Quincy Wright . From an early age Wright had a love and talent for  mathematics  and  biology . Wright attended  Galesburg High School  and graduated in 1906. He then enrolled in  Lombard College  where his father taught, to study  mathematics . He was influenced greatly by Professor  Wilhelmine Key , one of the first women to receive a  Ph.D.  in  biology . [ 10 ] [ 11 ] [ 12 ]  Wright received his Ph.D. from  Harvard University , where he worked at the  Bussey Institute  with the pioneering mammalian geneticist  William Ernest Castle  investigating the inheritance of coat colors in  mammals . He worked for the  U.S. Department of Agriculture  until 1925, when he joined the Department of Zoology at the  University of Chicago . He remained there until his retirement in 1955, when he moved to the  University of Wisconsin–Madison . He received many honors in his long career, including the  National Medal of Science  (1966), the  Balzan Prize  (1984), and the  Darwin Medal  of the  Royal Society  (1980). He was a member of the  National Academy of Sciences , [ 13 ]  the  American Philosophical Society , [ 14 ]  the  American Academy of Arts and Sciences , [ 15 ]  and a  Foreign Member of the Royal Society . [ 3 ]  The  American Mathematical Society  selected him as the Josiah Willards Gibbs lecturer for 1941. [ 16 ] [ 17 ]  For his work on genetics of evolutionary processes, Wright was awarded the  Daniel Giraud Elliot Medal  from the National Academy of Sciences in 1945. [ 18 ]


He died in  Madison, Wisconsin , on March 3, 1988.


Wright married Louise Lane Williams (1895–1975) in 1921. [ 19 ] [ 20 ]  They had three children: Richard, Robert, and Elizabeth. [ 21 ] [ 22 ]


Sewall Wright worshipped as a  Unitarian . [ 23 ] [ 24 ]


His papers on  inbreeding , [ 4 ] [ 25 ]   mating systems , [ 26 ]  and  genetic drift [ 27 ]  make him a principal founder of  theoretical population genetics , along with  R. A. Fisher  and  J. B. S. Haldane . Their theoretical work is the origin of the  modern evolutionary synthesis  or neo-Darwinian synthesis. [ 28 ]  Wright was the inventor/discoverer of the  inbreeding coefficient  and  F-statistics , standard tools in population genetics. He was the chief developer of the mathematical theory of  genetic drift , [ 27 ]  which is sometimes known as the Sewall Wright effect, [ 29 ]  cumulative stochastic changes in  gene frequencies  that arise from random births, deaths, and Mendelian segregations in reproduction.  In this work he also introduced the concept of  effective population size . Wright was convinced that the interaction of  genetic drift  and the other evolutionary forces was important in the process of adaptation. He described the relationship between genotype or phenotype and  fitness  as  fitness surfaces  or  evolutionary landscapes . On these landscapes mean population fitness was the height, plotted against horizontal axes representing the  allele frequencies  or the average phenotypes of the population.  Natural selection  would lead to a population climbing the nearest peak, while  genetic drift  would cause random wandering. He did not accept Fisher's genetic theory of dominance, [ 30 ]  but instead considered it to arise from biochemical considerations. [ 31 ] [ 32 ]  Although set aside for many years, his interpretation is at the basis of modern ideas of dominance. [ 33 ] [ 34 ]


Wright's explanation for  stasis  was that organisms come to occupy  adaptive peaks . [ 35 ]  In order to evolve to another, higher peak, the species would first have to pass through a valley of maladaptive intermediate stages. This could happen by  genetic drift [ 27 ]  if the population is small enough. If a species was divided into small populations, some could find higher peaks. If there was some  gene flow  between the populations, these adaptations could spread to the rest of the species. This was Wright's  shifting balance theory  of evolution. There has been much skepticism among evolutionary biologists as to whether these rather delicate conditions hold often in natural populations. Wright had a long-standing and bitter debate about this with  R. A. Fisher , who felt that most populations in nature were too large for these effects of genetic drift to be important.


Wright's statistical method of  path analysis , [ 4 ] [ 36 ]  which he invented in 1921 and which was one of the first methods using a  graphical model , is still widely used in social science. He was a hugely influential reviewer of manuscripts, [ 3 ]  as one of the most frequent reviewers for  Genetics .


Wright strongly influenced  Jay Lush , who was the most influential figure in introducing  quantitative genetics  into  animal  and  plant breeding . From 1915 to 1925 Wright was employed by the Animal Husbandry Division of the U.S. Bureau of Animal Husbandry. His main project was to investigate the inbreeding that had occurred in the artificial selection that resulted in the leading breeds of livestock used in American beef production. He also performed experiments with 80,000 guinea pigs in the study of physiological genetics. Furthermore he analyzed characters of some 40,000 guinea pigs in 23 strains of brother-sister matings against a random-bred stock. (Wright 1922a-c). The concentrated study of these two groups of mammals eventually led to the Shifting Balance Theory and the concept of "surfaces of selective value" in 1932. [ 9 ]


He did major work on the genetics of  guinea pigs , [ 37 ] [ 38 ]  and many of his students became influential in the development of mammalian genetics. He appreciated as early as 1917 that genes acted by controlling  enzymes . An anecdote about Wright, disclaimed by Wright himself, describes a lecture during which Wright tucked an unruly guinea pig under his armpit, where he usually held a chalkboard eraser: according to the anecdote, at the conclusion of the lecture, Wright absent-mindedly began to erase the blackboard using the guinea pig. [ citation needed ]


The creation of the  statistical   coefficient of determination  has been attributed to Sewall Wright and was first published in 1921. [ 39 ]
This metric is commonly employed to evaluate  regression analyses  in  computational statistics  and  machine learning .


Wright was one of the few geneticists of his time to venture into  philosophy . He found a union of concept in  Charles Hartshorne , who became a lifelong friend and philosophical collaborator. Wright endorsed a form of  panpsychism . He believed that the birth of the consciousness was not due to a mysterious property of increasing complexity, but rather an inherent property, therefore implying these properties were in the most elementary particles. [ 40 ]


Wright and Fisher, along with J.B.S. Haldane, were the key figures in the  modern synthesis  that brought genetics and evolution together. Their work was essential to the contributions of  Dobzhansky ,  Mayr ,  Simpson ,  Julian Huxley , and  Stebbins . The modern synthesis was the most important development in evolutionary biology after  Darwin . Wright also had a major effect on the development of mammalian genetics and biochemical genetics.


Judea Pearl  and Dana Mackenzie's  The Book of Why  (2018) describes the contribution of Wright's work on path analysis and delays in its acceptance by several technical disciplines (specifically statistics and formal causal analysis). [ 41 ]


OpenMx  has as its icon a representation of Wright's piebald  guinea pig .


Karl Günter Zimmer  (12 July 1911 – 29 February 1988) was a  German   nuclear chemist  who is best known for his work in understanding the  ionizing radiation  on  Deoxyribonucleic acid  (DNA) and did fundamental work on radiation biology. : 209  [ 1 ]


In 1935, he published the major work,  Über die Natur der Genmutation und der Genstruktur , with  Timofeev-Resovskij , and  Max Delbrück ; it was considered to be a major advance in understanding the nature of gene mutation and gene structure. [ 2 ] [ 3 ]


From 1945–1955, Zimmer was one of many German nuclear scientists in the former  Soviet program of nuclear weapons  but left  Russia  to eventually settle in  Germany . [ 4 ]


There is little or no information available about his early life but it is known that Zimmer obtained his  doctorate  in 1934 with a thesis on  photochemistry  from the sources provided by  University of Tennessee . [ 2 ] [ 5 ]


Early on, Zimmer worked as an advisor in radiotherapeutic physics in a  radiological  hospital and as an employee of  Auergesellschaft AG  in Berlin. [ 2 ]  However, he completed most of his theoretical work at the  Kaiser-Wilhelm Gesellschaft's   Institut für Hirnforschung  (lit.  Kaiser Wilhelm Institute for Brain Research  (KWIH) [ 6 ] ) in Berlin-Buch. [ 6 ]   Zimmer worked in  Nikolay Timofeev-Resovskij 's genetics department at the KWIH. [ 7 ] [ 8 ]  Timofeev-Resovskij, a  Russian  national with  Soviet citizenship , worked in Germany starting in 1924, and he stayed even after  Adolf Hitler 's party came to power in 1933. [ 9 ] [ 10 ]  Very early in Zimmer's career, in 1935, he published the major work,  Über die Natur der Genmutation und der Genstruktur , with Timofeev-Resovskij, and  Max Delbrück ; it was considered to be a major advance in understanding the nature of gene mutation and gene structure. [ 11 ]  At  Auergesellschaft , Zimmer collaborated with  Nikolaus Riehl , director of scientific research at the works. [ 12 ]


At the close of World War II, Russia had special search teams operating in Austria and Germany, especially in Berlin, to identify and "requisition" equipment, materiel, intellectual property, and personnel useful to the  Soviet program of nuclear weapons . [ 13 ]  The exploitation teams were under the  Russian Alsos  and they were headed by  Lavrenij Beria's  deputy, Colonel General A. P. Zavenyagin. These teams were composed of scientific staff members, in  NKVD  officer's uniforms, from the bomb project's only laboratory,  Laboratory No. 2 , in Moscow. [ 13 ]  In mid-May 1945, the Russian physicists  Georgy Flerov  and  Lev Artsimovich , in NKVD colonel's uniforms, identified Zimmer and compelled him to take them to the location of Riehl and his staff, who had evacuated their  Auergesellschaft  facilities and were west of Berlin, hoping to be in an area occupied by the American or British military forces. Riehl was detained at the search team's facility in Berlin-Friedrichshagen for a week. This sojourn in Berlin turned into 10 years in the former Soviet Union for Riehl and his staff, including their families, were flown to Moscow on 9 July 1945. Riehl was to head up a uranium production group at Plant No. 12 in  Ehlektrostal'  (Электросталь [ 14 ] ). [ 15 ] [ 16 ]


From 1945 to 1950, Riehl was in charge of uranium production at Plant No. 12 in  Ehlektrostal' . When Riehl learned that  Hans-Joachim Born  and Karl Zimmer were being held in  Krasnogorsk , in the main PoW camp for Germans with scientific degrees, Riehl arranged though Zavenyagin to have them sent to Ehlektrostal'.  Alexander Catsch  was also sent there. At Ehlektrostal', Riehl had a hard time incorporating Born, Catsch, and Zimmer into his tasking on uranium production, as Born was a radiochemist, Catsch was a physician and radiation biologist, and Zimmer was a physicist and radiation biologist. [ 17 ] [ 18 ] [ 19 ]


After the detonation of the Russian uranium bomb, uranium production was going smoothly and Riehl's oversight was no longer necessary at Plant No. 12. Riehl then went, in 1950, to head an institute in Sungul', where he stayed until 1952. Essentially the remaining personnel in his group were assigned elsewhere, with the exception of H. E. Ortmann, A. Baroni (PoW), and Herbert Schmitz (PoW), who went with Riehl. However, Riehl had already sent Born, Catsch, and Zimmer to the institute in December 1947. The institute in Sungul' was responsible for the handling, treatment, and use of radioactive products generated in reactors, as well as radiation biology, dosimetry, and radiochemistry. The institute was known as  Laboratory B , and it was overseen by the 9th Chief Directorate of the  NKVD  ( MVD  after 1946), the same organization which oversaw the  Russian Alsos  operation. The scientific staff of Laboratory B – a  ShARAShKA  – was both Soviet and German, the former being mostly political prisoners or exiles, although some of the service staff were criminals. [ 20 ] [ 21 ]  (Laboratory V, in  Obninsk , headed by  Heinz Pose , was also a sharashka and working on the Soviet atomic bomb project. Other notable Germans at the facility were Werner Czulius, Hans Jürgen von Oertzen,  Ernst Rexer , and Carl Friedrich Weiss. [ 22 ] )


Laboratory B was known under another cover name [ 23 ]  as  Объект 0211  (Ob'ekt 0211, Object 0211), as well as Object B. [ 24 ] [ 25 ] [ 26 ] [ 27 ]  (In 1955, Laboratory B was closed. Some of its personnel were transferred elsewhere, but most of them were assimilated into a new, second nuclear weapons institute, Scientific Research Institute-1011, NII-1011, today known as the Russian Federal Nuclear Center All-Russian Scientific Research Institute of Technical Physics, RFYaTs–VNIITF. NII-1011 had the designation  предприятие п/я 0215 , i.e., enterprise post office box 0215 and  Объект 0215 ; the latter designation has also been used in reference to Laboratory B after its closure and assimilation into NII-1011. [ 28 ] [ 29 ] [ 30 ] [ 13 ] )


One of the political prisoners in Laboratory B was Riehls' colleague from the KWIH,  N. V. Timofeev-Resovskij , who, as a Soviet citizen, was arrested by the Soviet forces in Berlin at the conclusion of the war, and he was sentenced to 10 years in the  Gulag . In 1947, Timofeev-Resovskij was rescued out of a harsh Gulag prison camp, nursed back to health, and sent to Sungul' to complete his sentence, but still make a contribution to the Soviet atomic bomb project. At Laboratory B, Timofeev-Resovskij headed a biophysics research department, in which Born, Catsch, and Zimmer were able to conduct work similar to that which they had done in Germany, and all three became section heads in Timofeev-Resovskij's department. [ 20 ] [ 21 ] [ 13 ]


Before being rejoined in the Soviet Union, Zimmer, Timofeev-Resovskij, and Riehl had collaborated on the biological effects of ionizing radiation. [ 12 ]  Also, Zimmer and Timofeev-Resovskij had put together a manuscript which was a comprehensive summary of their work and that of others on radiation-induced gene mutation and related areas; the book,  Das Trefferprinzip in der Biologie , was published in Germany while they were in the Soviet Union. [ 31 ]  In 1948, due to  Lysenkoism , there were grave consequences for the institute in Sungul' in general and for Zimmer and Timofeev-Resovskij in particular. The book was put on a forbidden list and the laboratory was not allowed to conduct research on its topics. Since the book represented many years of Zimmer's life's work, he was rather downcast by the circumstances. [ 32 ]


In preparation for release from the Soviet Union, it was standard practice to put personnel into quarantine for a few years if they worked on projects related to the Soviet atomic bomb project, as was the case for Zimmer. Additionally, in 1954, the Deutsche Demokratische Republik (DDR, German Democratic Republic) and the Soviet Union prepared a list of scientists they wished to keep in the DDR, due to their having worked on projects related to the Soviet atomic bomb project; this list was known as the "A-list". On this A-list were the names of 18 scientists. Nine, possibly 10, of the names were associated with the Riehl group which worked at Plant No. 12 in Ehlektrostal'. Born, Catsch, Riehl, and Zimmer were on the list. [ 33 ] [ 34 ] [ 35 ]


Upon Zimmer's release from the Soviet Union in 1955, he eventually went to  West Germany  under legal circumstances, where he worked at the  Kernforschungszentrum Karlsruhe  (Karlsruhe Nuclear Research Center), founded in 1956 and later known as the  Forschungszentrum Karlsruhe . [ 36 ]


He became director of the  Instituts für Strahlenbiologie  (IStB, Institute for Radiation Biology). [ 2 ] [ 37 ]


The following was published in  Kernphysikalische Forschungsberichte  ( Research Reports in Nuclear Physics ), an internal publication of the German  Uranverein . Reports in this publication were classified Top Secret, they had very limited distribution, and the authors were not allowed to keep copies. The reports were confiscated under the Allied  Operation Alsos  and sent to the  United States Atomic Energy Commission  for evaluation. In 1971, the reports were declassified and returned to Germany. The reports are available at the  Karlsruhe Nuclear Research Center  and the  American Institute of Physics . [ 38 ] [ 39 ]


The majority of these literature citations have been garnered by searching on variations of the author's name on  Google ,  Google Scholar , and the  Energy Citations Database , and use of a bibliography of  N. V. Timofeev-Resovskij  provided by the Laboratory of Radiation Biology of the  JINR , Dubna.


A  chromosome  is a  package  of  DNA  containing part or all of the  genetic material  of an  organism . In most chromosomes, the very long thin DNA fibers are coated with  nucleosome -forming packaging  proteins ; in  eukaryotic  cells, the most important of these proteins are the  histones . Aided by  chaperone proteins , the histones bind to and  condense  the DNA molecule to maintain its integrity. [ 1 ] [ 2 ]  These eukaryotic chromosomes display a complex  three-dimensional structure  that has a significant role in  transcriptional regulation . [ 3 ]


Normally, chromosomes are visible under a  light microscope  only during the  metaphase  of  cell division , where all chromosomes are aligned in the center of the cell in their condensed form. [ 4 ]  Before this stage occurs, each chromosome is duplicated ( S phase ), and the two copies are joined by a  centromere —resulting in either an X-shaped structure if the centromere is located equatorially, or a two-armed structure if the centromere is located distally; the joined copies are called ' sister chromatids '. During  metaphase , the duplicated structure (called a 'metaphase chromosome') is highly condensed and thus easiest to distinguish and study. [ 5 ]  In animal cells, chromosomes reach their highest compaction level in  anaphase  during  chromosome segregation . [ 6 ]


Chromosomal  recombination  during  meiosis  and subsequent  sexual reproduction  plays a crucial role in  genetic diversity . If these structures are manipulated incorrectly, through processes known as  chromosomal instability  and  translocation , the cell may undergo  mitotic catastrophe . This will usually cause the cell to initiate  apoptosis , leading to its own  death , but the process is occasionally hampered by cell mutations that result in the progression of  cancer .


The term 'chromosome' is sometimes used in a wider sense to refer to the individualized portions of  chromatin  in cells, which may or may not be visible under light microscopy. In a narrower sense, 'chromosome' can be used to refer to the individualized portions of chromatin during cell division, which are visible under light microscopy due to high condensation.


The word  chromosome  ( / ˈ k r oʊ m ə ˌ s oʊ m ,   - ˌ z oʊ m / ) [ 7 ] [ 8 ]  comes from the  Greek  words  χρῶμα  ( chroma , "colour") and  σῶμα  ( soma , "body"), describing the strong  staining  produced by particular  dyes . [ 9 ]  The term was coined by the German anatomist  Heinrich Wilhelm Waldeyer , [ 10 ]  referring to the term ' chromatin ', which was introduced by  Walther Flemming .


Some of the early  karyological  terms have become outdated. [ 11 ] [ 12 ]  For example, 'chromatin' (Flemming 1880) and 'chromosom' (Waldeyer 1888) both ascribe color to a non-colored state. [ 13 ]


Otto Bütschli  was the first scientist to recognize the structures now known as chromosomes. [ 14 ]


In a series of experiments beginning in the mid-1880s,  Theodor Boveri  gave definitive contributions to elucidating that chromosomes are the  vectors  of  heredity , with two notions that became known as 'chromosome continuity' and 'chromosome individuality'. [ 15 ]


Wilhelm Roux  suggested that every chromosome carries a different  genetic configuration , and Boveri was able to test and confirm this hypothesis. Aided by the rediscovery at the start of the 1900s of  Gregor Mendel 's earlier experimental work, Boveri identified the connection between the rules of inheritance and the behaviour of the chromosomes. Two generations of American  cytologists  were influenced by Boveri:  Edmund Beecher Wilson ,  Nettie Stevens ,  Walter Sutton  and  Theophilus Painter  (Wilson, Stevens, and Painter actually worked with him). [ 16 ]


In his famous textbook,  The Cell in Development and Heredity , Wilson linked together the independent work of Boveri and Sutton (both around 1902) by naming the chromosome theory of inheritance the ' Boveri–Sutton chromosome theory ' (sometimes known as the 'Sutton–Boveri chromosome theory'). [ 17 ]   Ernst Mayr  remarks that the theory was hotly contested by some famous geneticists, including  William Bateson ,  Wilhelm Johannsen ,  Richard Goldschmidt  and  T.H. Morgan , all of a rather dogmatic mindset. Eventually, absolute proof came from chromosome maps in Morgan's own laboratory. [ 18 ]


The number of human chromosomes was published by Painter in 1923. By inspection through a microscope, he counted 24 pairs of chromosomes, giving 48 in total. His error was copied by others, and it was not until 1956 that the true number (46) was determined by Indonesian-born  cytogeneticist   Joe Hin Tjio . [ 19 ]


The  prokaryotes  –  bacteria  and  archaea  – typically have a single  circular chromosome . [ 20 ]  The chromosomes of most bacteria (also called  genophores ), can range in size from only 130,000  base pairs  in the  endosymbiotic  bacteria  Candidatus Hodgkinia cicadicola [ 21 ]  and  Candidatus Tremblaya princeps , [ 22 ]  to more than 14,000,000 base pairs in the soil-dwelling bacterium  Sorangium cellulosum . [ 23 ]


Some bacteria have more than one chromosome. For instance,  Spirochaetes  such as  Borrelia burgdorferi  (causing  Lyme disease ), contain a single  linear  chromosome. [ 24 ]   Vibrios  typically carry two chromosomes of very different size. Genomes of the genus  Burkholderia  carry one, two, or three chromosomes. [ 25 ]


Prokaryotic chromosomes have less sequence-based structure than eukaryotes. Bacteria typically have a one-point (the  origin of replication ) from which replication starts, whereas some archaea contain multiple replication origins. [ 26 ]  The genes in prokaryotes are often organized in  operons  and do not usually contain  introns , unlike eukaryotes.


Prokaryotes  do not possess nuclei. Instead, their DNA is organized into a structure called the  nucleoid . [ 27 ] [ 28 ]  The nucleoid is a distinct structure and occupies a defined region of the bacterial cell. This structure is, however, dynamic and is maintained and remodeled by the actions of a range of histone-like proteins, which associate with the bacterial chromosome. [ 29 ]  In  archaea , the DNA in chromosomes is even more organized, with the DNA packaged within structures similar to eukaryotic nucleosomes. [ 30 ] [ 31 ]


Certain bacteria also contain  plasmids  or other  extrachromosomal DNA . These are circular structures in the  cytoplasm  that contain cellular DNA and play a role in  horizontal gene transfer . [ 5 ]  In prokaryotes and viruses, [ 32 ]  the DNA is often densely packed and organized; in the case of archaea, by homology to eukaryotic histones, and in the case of bacteria, by  histone-like  proteins.


Bacterial chromosomes tend to be tethered to the  plasma membrane  of the bacteria. In molecular biology application, this allows for its isolation from plasmid DNA by centrifugation of lysed bacteria and pelleting of the membranes (and the attached DNA).


Prokaryotic chromosomes and plasmids are, like eukaryotic DNA, generally  supercoiled . The DNA must first be released into its relaxed state for access for  transcription , regulation, and  replication .


Each eukaryotic chromosome consists of a long linear  DNA molecule  associated with  proteins , forming a compact complex of proteins and DNA called  chromatin .  Chromatin contains the vast majority of the DNA in an organism, but a  small amount  inherited maternally can be found in the  mitochondria . It is present in most  cells , with a few exceptions, for example,  red blood cells .


Histones  are responsible for the first and most basic unit of chromosome organization, the  nucleosome .


Eukaryotes  ( cells  with nuclei such as those found in plants, fungi, and animals) possess multiple large linear chromosomes contained in the cell's nucleus. Each chromosome has one  centromere , with one or two arms projecting from the centromere, although, under most circumstances, these arms are not visible as such. In addition, most eukaryotes have a small circular  mitochondrial genome , and some eukaryotes may have additional small circular or linear  cytoplasmic  chromosomes.


In the nuclear chromosomes of eukaryotes, the uncondensed DNA exists in a semi-ordered structure, where it is wrapped around  histones  (structural proteins), forming a composite material called chromatin.


The packaging of DNA into nucleosomes causes a 10 nanometer fibre which may further condense up to 30 nm fibres [ 33 ]  Most of the euchromatin in interphase nuclei appears to be in the form of 30-nm fibers. [ 33 ]  Chromatin structure is the more decondensed state, i.e. the 10-nm conformation allows transcription. [ 33 ]


During  interphase  (the period of the  cell cycle  where the cell is not dividing), two types of chromatin can be distinguished:


In the early stages of  mitosis  or  meiosis  (cell division), the chromatin double helix becomes more and more condensed. They cease to function as accessible genetic material ( transcription  stops) and become a compact transportable form. The loops of thirty-nanometer chromatin fibers are thought to fold upon themselves further to form the compact metaphase chromosomes of mitotic cells. The DNA is thus condensed about ten-thousand-fold. [ 33 ]


The  chromosome scaffold , which is made of proteins such as  condensin ,  TOP2A  and  KIF4 , [ 34 ]  plays an important role in holding the chromatin into compact chromosomes. Loops of thirty-nanometer structure further condense with scaffold into higher order structures. [ 35 ]


This highly compact form makes the individual chromosomes visible, and they form the classic four-arm structure, a pair of sister  chromatids  attached to each other at the  centromere . The shorter arms are called  p arms  (from the French  petit , small) and the longer arms are called  q arms  ( q  follows  p  in the Latin alphabet; q-g "grande"; alternatively it is sometimes said q is short for  queue  meaning tail in French [ 36 ] ). This is the only natural context in which individual chromosomes are visible with an optical  microscope .


Mitotic metaphase chromosomes are best described by a linearly organized longitudinally compressed array of consecutive chromatin loops. [ 37 ]


During mitosis,  microtubules  grow from centrosomes located at opposite ends of the cell and also attach to the centromere at specialized structures called  kinetochores , one of which is present on each sister  chromatid . A special DNA base sequence in the region of the kinetochores provides, along with special proteins, longer-lasting attachment in this region. The microtubules then pull the chromatids apart toward the centrosomes, so that each daughter cell inherits one set of chromatids. Once the cells have divided, the chromatids are uncoiled and DNA can again be transcribed. In spite of their appearance, chromosomes are structurally highly condensed, which enables these giant DNA structures to be contained within a cell nucleus.


Chromosomes in humans can be divided into two types:  autosomes  (body chromosome(s)) and allosome ( sex chromosome (s)). Certain genetic traits are linked to a person's sex and are passed on through the sex chromosomes. The autosomes contain the rest of the genetic hereditary information. All act in the same way during cell division. Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), giving a total of 46 per cell. In addition to these, human cells have many hundreds of copies of the  mitochondrial genome .  Sequencing  of the  human genome  has provided a great deal of information about each of the chromosomes. Below is a table compiling statistics for the chromosomes, based on the  Sanger Institute 's human genome information in the  Vertebrate Genome Annotation (VEGA) database . [ 38 ]  Number of genes is an estimate, as it is in part based on  gene predictions . Total chromosome length is an estimate as well, based on the estimated size of unsequenced  heterochromatin  regions.


Based on the micrographic characteristics of size, position of the  centromere  and sometimes the presence of a  chromosomal satellite , the human chromosomes are classified into the following groups: [ 41 ] [ 42 ]


In general, the  karyotype  is the characteristic chromosome complement of a  eukaryote   species . [ 43 ]  The preparation and study of karyotypes is part of  cytogenetics .


Although the  replication  and  transcription  of  DNA  is highly standardized in eukaryotes, the same cannot be said for their karyotypes, which are often highly variable. There may be variation between species in chromosome number and in detailed organization.
In some cases, there is significant variation within species. Often there is:


Also, variation in karyotype may occur during development from the fertilized egg.


The technique of determining the karyotype is usually called  karyotyping . Cells can be locked part-way through division (in metaphase)  in vitro  (in a reaction vial) with  colchicine . These cells are then stained, photographed, and arranged into a  karyogram , with the set of chromosomes arranged, autosomes in order of length, and sex chromosomes (here X/Y) at the end.


Like many sexually reproducing species, humans have special  gonosomes  (sex chromosomes, in contrast to  autosomes ). These are XX in females and XY in males.


Investigation into the human karyotype took many years to settle the most basic question:  How many chromosomes does a normal  diploid  human cell contain?  In 1912,  Hans von Winiwarter  reported 47 chromosomes in  spermatogonia  and 48 in  oogonia , concluding an  XX/XO   sex determination mechanism . [ 44 ]  In 1922,  Painter  was not certain whether the diploid number of man is 46 or 48, at first favouring 46. [ 45 ]  He revised his opinion later from 46 to 48, and he correctly insisted on humans having an  XX/XY  system. [ 46 ]


New techniques were needed to definitively solve the problem:


It took until 1954 before the human diploid number was confirmed as 46. [ 47 ] [ 48 ]  Considering the techniques of Winiwarter and Painter, their results were quite remarkable. [ 49 ]   Chimpanzees , the closest living relatives to modern humans, have 48 chromosomes as do the other  great apes : in humans two chromosomes fused to form  chromosome 2 .


Chromosomal aberrations are disruptions in the normal chromosomal content of a cell. They can cause genetic conditions in humans, such as  Down syndrome , [ 50 ]  although most aberrations have little to no effect. Some chromosome abnormalities do not cause disease in carriers, such as  translocations , or  chromosomal inversions , although they may lead to a higher chance of bearing a child with a chromosome disorder. [ citation needed ]  Abnormal numbers of chromosomes or chromosome sets, called  aneuploidy , may be lethal or may give rise to genetic disorders. [ 51 ]   Genetic counseling  is offered for families that may carry a chromosome rearrangement.


The gain or loss of DNA from chromosomes can lead to a variety of  genetic disorders . [ 52 ]  Human examples include:


Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. [ 57 ]  In particular, risk of aneuploidy is increased by tobacco smoking, [ 58 ] [ 59 ]  and occupational exposure to benzene, [ 60 ]  insecticides, [ 61 ] [ 62 ]  and perfluorinated compounds. [ 63 ]  Increased aneuploidy is often associated with increased DNA damage in spermatozoa.


The number of chromosomes in  eukaryotes  is highly variable. It is possible for chromosomes to fuse or break and thus evolve into novel karyotypes. Chromosomes can also be fused artificially. For example, when the 16 chromosomes of  yeast  were fused into one giant chromosome, it was found that the cells were still viable with only somewhat reduced growth rates. [ 64 ]


The tables below give the total number of chromosomes (including sex chromosomes) in a cell nucleus for various eukaryotes. Most are  diploid , such as  humans  who have 22 different types of  autosomes —each present as two homologous pairs—and two  sex chromosomes , giving 46 chromosomes in total. Some other organisms have more than two copies of their chromosome types, for example  bread wheat  which is  hexaploid , having six copies of seven different chromosome types for a total of 42 chromosomes.


Normal members of a particular eukaryotic species all have the same number of nuclear chromosomes. Other eukaryotic chromosomes, i.e., mitochondrial and plasmid-like small chromosomes, are much more variable in number, and there may be thousands of copies per cell.


Asexually reproducing  species have one set of chromosomes that are the same in all body cells. However, asexual species can be either haploid or diploid.


Sexually reproducing  species have  somatic cells  (body cells) that are  diploid  [2n], having two sets of chromosomes (23 pairs in humans), one set from the mother and one from the father.  Gametes  (reproductive cells) are  haploid  [n], having one set of chromosomes. Gametes are produced by  meiosis  of a diploid  germline  cell, during which the matching chromosomes of father and mother can exchange small parts of themselves ( crossover ) and thus create new chromosomes that are not inherited solely from either parent. When a male and a female gamete merge during  fertilization , a new diploid organism is formed.


Some animal and plant species are  polyploid  [Xn], having more than two sets of  homologous chromosomes . Important crops such as tobacco or wheat are often polyploid, compared to their ancestral species. Wheat has a haploid number of seven chromosomes, still seen in some  cultivars  as well as the wild progenitors. The more common types of pasta and bread wheat are polyploid, having 28 (tetraploid) and 42 (hexaploid) chromosomes, compared to the 14 (diploid) chromosomes in wild wheat. [ 90 ]


Prokaryote  species generally have one copy of each major chromosome, but most cells can easily survive with multiple copies. [ 91 ]  For example,  Buchnera , a  symbiont  of  aphids  has multiple copies of its chromosome, ranging from 10 to 400 copies per cell. [ 92 ]  However, in some large bacteria, such as  Epulopiscium fishelsoni  up to 100,000 copies of the chromosome can be present. [ 93 ]  Plasmids and plasmid-like small chromosomes are, as in eukaryotes, highly variable in copy number. The number of plasmids in the cell is almost entirely determined by the rate of division of the plasmid – fast division causes high copy number.


A  microchromosome  is a  chromosome  defined for its relatively small size. They are typical components of the  karyotype  of  birds , some  reptiles ,  fish ,  amphibians , and  monotremes . [ 1 ]  As many bird genomes have chromosomes of widely different lengths, the name was meant to distinguish them from the comparatively large  macrochromosomes . [ 2 ]  The distinction referred to the measured size of the chromosome while staining for karyotype, and while there is not a strict definition, chromosomes resembling the large chromosomes of mammals were called  macrochromosomes  (roughly 3 to 6 μm), while the much smaller ones of less than around 0.5 μm were called  microchromosomes . [ 3 ]  In terms of  base pairs , by convention, those of less than 20Mb were called  microchromosomes , those between 20 and 40 Mb are classified as  intermediate chromosomes , and those larger than 40Mb are  macrochromosomes . [ 4 ]  By this definition, all normal chromosomes in  organisms with relatively small genomes (less than 100-200Mb) would be considered microchromosomes.