Most diseases have cellular origins. The majority can be traced to simple biochemical imbalances that can often be corrected by drugs. The cells return to a near-normal state and the patient feels better. Some complex diseases start with gene changes that prevent a particular protein being expressed or change the protein structure in such a way that its function is altered or ineffective. Even with the checks and balances of internal repair or cell suicide, some gene changes escape and, when involved in the fundamental cell processes, they can have a devastating effect on cell growth or function. Increased growth caused by gene changes leads to the slippery slope of cancer where these ‘out of control’ cells further change their genetics and develop the ability for limitless division and, in some cases, gain the ability to invade other tissues. In simple terms, treating such diseases requires that the errant cells are removed, corrected, or even better replaced. Many other diseases are not directly life threatening but cannot be corrected by drug treatment because of their complex biochemical nature. The ideal solution would be to treat the disease at its root by replacing the faulty cells. This process is called cellular therapy and can be divided into different forms. The most familiar is the transplantation of mature functional cells, as in a blood transfusion, and stem cells as in bone marrow transplants. We still await a standard therapy for the introduction of modified human or animal cells that replace a required substance, such as insulin-producing cells for diabetics.
Many quote the Swiss physician and alchemist Philippus Aureolus Paracelsus as the first person to describe the concept of cell therapy in his book D er grossen Wundartzney (‘Great Surgery Book’) published in 1536 in which he wrote: ‘the heart heals the heart, lung heals the lung, spleen heals the spleen; like cures like’. This remark came from his theory that eating healthy animal organs would rebuild and revitalize the particular ageing or faulty organ—more of a nutritionist doctrine than one of a modern cellular therapist. As long ago as 1667, Jean-Baptiste Denis, working in the royal laboratory of Louis XIV, attempted to transfuse blood from a calf into a mentally ill patient. The first recorded non-blood transfusion occurred in 1912 when German physicians tried to treat children suffering from under-active thyroid with transplanted thyroid cells. In 1931, a Swiss clinician Paul Niehans became the ‘father of cell therapy’ by accident when he introduced minced bovine thyroid tissue into a rapidly deteriorating patient who had experienced severe damage to his thyroid glands during surgery. The patient recovered and lived for a further 30 years. Niehans became renowned for his cellular treatments, and his patients included members of various Royal families, Pope Pius XII, politicians, and famous film stars. His name and some treatments, especially skin and beauty processes, live on at the Paul Niehans Clinic founded in Switzerland by his daughter. The 20th century is littered with stories of so-called cellular therapies. John Brinkley, known as the ‘goat gland doctor’, reportedly did 16,000 operations in which he implanted men with tissue from the testicles of young goats, asserting that this procedure was effective against impotence and could cure conditions ranging from acne to insanity. His licence was revoked on the grounds of immorality and unprofessional conduct. James Wilson promoted the use of bovine connective tissue cells. He claimed that such cellular preparations taken by mouth ‘have the ability to migrate to any tissue in need of repair and, once at the site, take on the characteristics of the healthy cell it associates with’. Other attempts along similar lines caused hundreds of deaths by violent immune reactions to bacterial or viral infections including two men who died of gas gangrene following injections of foetal sheep cells. Other, even more questionable embryonic cell transplant therapies were pioneered by Niehans in Switzerland. In the 1970s, his student Wolfram Kuhnau set up a clinic in Mexico, where there were no regulations, using embryonic blue shark cells purchased off local fishermen and with a dubious number of live cells, to ‘treat’ patients for a wide range of diseases. As a result of this ‘quackery’ and the bad press it received, it is no wonder that there was a high degree of scepticism about cell-based therapies as we approached the 21st century.