Darwin had cataloged and described all of the species collected on his Beagle trip except one: a barnacle. Darwin felt that he should establish himself as an expert on one species before daring to make generalizations about all of them. His growing friendship with Joseph Hooker reinforced this feeling. Hooker was a botanical expert who, in one of his letters to Darwin, included a comment which Darwin took to mean that those who speculated about species and evolution– including himself–should be more careful. And Darwin himself remained anxious about the consequences of his theory of evolution by natural selection. Even though he had great confidence in it, he worried for his reputation and for the survival of his theory if he published it without being able to support it with irrefutable evidence. Finally, it turned out that barnacles, far from being boring, were actually an incredibly strange an interesting species to study.

Darwin named his barnacle 'Anthrobalanus' to indicate that it seemed strangely articulated–that is, it had joints. This fell in line with a discovery that had been made less than twenty years prior, that the barnacles were actually crustaceans (like shrimp and crabs) and not mollusks (like clams). Starting with Anthrobalanus, Darwin conducted a series of microscopic studies of barnacles that, in the end, would occupy him for eight long years.

Darwin did not spend eight years on a single species. As soon as he started studying one species, he realized that he would have difficulty describing its unique features unless he had some sense of what the whole family of barnacles was like. So he started requesting to borrow the samples of other species. What started as a trickle soon turned into a flood, and Darwin found himself inundated with offers of specimens from conchologists and private collectors. He realized that there was no definitive work on barnacles; in fact, the whole field of barnacle classification was a mess. Darwin decided that he could be the one to clean up that mess, so he dived headfirst into a full-scale study of barnacles, including not only current species but also those that had been discovered in fossil beds.

Darwin's friendship with Hooker grew. Hooker became Darwin's main resource regarding evolution, a topic that remained his true love even while he was in the midst of his barnacle research. Hooker's botanical expertise was a useful anchor for Darwin's speculations on the origins of species. Any time he had a question about plant distribution or varieties, Hooker could be depended on to find an answer, if there was one. He invited Hooker to spend time at Down, where the two would go on walks around the grounds before Darwin, sick as ever, returned to his room to rest.

In January 1847, at the end of one of these week-long visits, Darwin gave Hooker a copy of the sketch on evolution by natural selection that he had started in 1842 and expanded in 1844. It was now 231 manuscript pages long. Hooker's response was what Darwin was looking for: he was not yet convinced, but he found it well-reasoned. But his real usefulness was in pointing out the details that Darwin had overlooked, the places where his argument could be most easily challenged. Hooker's comments, then and later, would help Darwin shore up his argument for the day when he was finally ready to take it to the public.

Over the course of 1847, Darwin's illness, still mysterious, worsened; he started suffering again from frequent vomiting and weakness, as he had for years, but now he was also fainting and seeing spots in front of his eyes. In 1849 he had had enough of traditional medicine; it had no clue about his illness and did little to help him. He was skeptical of alternative therapies like mesmerism, but hydropathy–treating illness with hot, cold, and high- pressure water–had some appeal. He spent March of 1849 at a hydropathic spa run by Dr. James Gully. Originally planning to spend six weeks there with his family in a rented house, he ended up spending sixteen weeks. The therapy included whole-body treatments of hot and cold water, showers, vigorous rubbing, and lots of rest. By the end of it he felt like a new man.

He continued the hydropathic treatments at a slower pace after returning to Down. During the rest of 1849, he used his newfound health to continue his research on living barnacles. In 1850 he moved on to the fossil barnacles, the last bit of work before he could bring the chapter of his life on barnacles to a close. He continued to build and maintain a strong financial position. His mind was on barnacles, but his money was on railroads, American and British industry, and farmland, all of which provided generous returns. In April, tragedy struck: Annie, his oldest and favorite daughter, fell ill, and only a few weeks later, on April 23, she was dead. Combined with the death of Charles's father only six months before, in April 1849, this was an enormous shock. Charles's health plummeted, and his Christian faith, which had been in doubtful condition for years, finally died. Over the next few years, with his spirits and health in poor condition, he struggled to wrap up what eventually turned into four large volumes on barnacles. It was not until 1854 that he was finally able to turn his thoughts over entirely to the issue of the origin of species, and issue that had been plaguing him since his journey on the Beagle twenty years before.