The letters from these years reveal the main preoccupations of Darwin’s life with a new intensity. The period opens with a family tragedy in the death of Darwin’s oldest and favourite daughter, Anne, and it shows how, weary and mourning his dead child, Darwin persevered with his scientific work, single-mindedly committed to the completion of his barnacle research.  His four-volume study was finally published after eight years of work. Darwin's professional circle was enlarged both by new friendships with noted scientists such as the physiologist Thomas Henry Huxley, and the American botanist Asa Gray, but also by contact with a network of animal breeders, nurserymen, and pigeon-fanciers.

Darwin's study of barnacles, begun in 1844, took him eight years to complete. The correspondence reveals how his interest in a species found during the Beagle voyage developed into an investigation of the comparative anatomy of other cirripedes and finally a comprehensive taxonomical study of the entire group. Despite struggling with a recurrent illness, he continued to write on geologicy, and published notes on the use of microscopes.  Three more children, Elizabeth, Francis, and Leonard, were born during this period, but the death of Darwin's father in 1848 left the family well-provided for.  

The scientific results of the Beagle voyage still dominated Darwin's working life, but he broadened his continuing investigations into the nature and origin of species. Far from being a recluse, Darwin was at the heart of British scientific society, travelling often to London and elsewhere to attend meetings and confer with colleagues, including the man who was to become his closest friend, Joseph Dalton Hooker. Down House was altered and extended to accommodate Darwin’s growing family; and, with his father’s advice, Darwin began a series of judicious financial investments to ensure a comfortable future for all those under his care.

The seven-year period following Darwin's return to England from the Beagle voyage was one of extraordinary activity and productivity in which he became recognised as a naturalist of outstanding ability, as an author and editor, and as a professional man with official responsibilities in several scientific organisations. They are also the years in which he married, started a family, and moved to Down House, Kent, his home for the rest of his life. By 1842 he was ready to write an outline of his species theory, the so-called 'pencil sketch', based on a principle that he called ‘natural selection’. 

The year 1870 is aptly summarised by the brief entry Darwin made in his journal: ‘The whole of the year at work on the Descent of Man & Selection in relation to Sex’.  Descent was the culmination of over three decades of observations and reflections on human ancestry, including the origin of language, mind, morals, and religious temperament. The year was otherwise coloured by controversies, including vigorous objections to the application of natural selection to humans from Wallace and St George Jackson Mivart.

At the start of 1869, Darwin was hard at work making changes and additions for a fifth edition of  Origin. He may have resented the interruption to his work on sexual selection and human evolution, but he spent forty-six days on the task. Much of the remainder of the year was spent researching and revising chapters for  Descent, and gathering additional material on emotional expression. Yet the scope of Darwin’s interests remained extremely broad, many letters throughout the year touching on subjects such as South American geology, barnacle morphology, insectivorous plants, and earthworms, subjects that had exercised Darwin for decades.

The quantity of Darwin’s correspondence increased dramatically in 1868 due largely to his ever-widening research on human evolution and sexual selection.Darwin’s theory of sexual selection as applied to human descent led him to investigate aspects of the structure and behaviour of other animals more extensively, and to further this programme, he re-established links with specialists who had provided assistance. Considerable correspondence was generated by the long-awaited publication of Variation in animals and plants under domestication. Having been advertised by the publisher John Murray as early as 1865, the two-volume work appeared in January 1868.

Charles Darwin’s major achievement in 1867 was the completion of his large work, The variation of animals and plants under domestication (Variation). The importance of Darwin’s network of correspondents becomes vividly apparent in his work on expression in 1867, as he continued to circulate a list of questions on human expression that he may have drawn up in late 1866. His correspondents were asked to copy the list and forward it to those who might best answer the questions, with the result that Darwin began to receive replies from different corners of the world.

The year 1866 began well for Charles Darwin, as his health, after several years of illness, was now considerably improved. In February, Darwin received a request from his publisher, John Murray, for a new edition of  Origin. Darwin got the fourth edition to the printers in July. Much to Darwin’s annoyance, however, publication was delayed by Murray, who judged that it would sell better if released later in the year. Darwin also completed the major part of what was to become Variation. Debate about Darwin’s theory of transmutation continued in 1866, with important commentaries appearing in France, Germany, and Italy.

On receiving a photograph from Charles Darwin, the American botanist Asa Gray wrote on 11 July 1864: ‘the venerable beard gives the look of your having suffered, and … of having grown older’.  Because of poor health, Because of poor health, Darwin corresponded little during the first three months of 1864, dictating nearly all his letters and having scientific papers read to him. In March, his health improved; he consulted William Jenner, physician to Queen Victoria, who prescribed radically different treatment to the five physicians Darwin had consulted in 1863. Darwin exclaimed to his close friend, the botanist Joseph Dalton Hooker: ‘Hurrah! I have been 52 hours without vomiting!!’. He continued his hybridising experiments and finished a couple of botanical papers, resuming work on the manuscript of Variation, the long-awaited sequel to Origin.