Several ethical issues can arise during the development of any novel therapeutic. The development of genetic and cellular therapies share many ethical issues with other types of therapy, such as prosthetics, drugs, organ transplantation, and protein replacement. In addition, there are ethical issues unique to gene and cell therapy. In all cases, scientists, clinicians, regulatory committees, and concerned citizens take an active role in addressing these issues.
Balancing risk and benefit to the patient is important to any developing therapeutic. This is complicated by the fact that most gene therapy trials are Phase I trials, which means that safety of the vector and delivery mode are being evaluated and no direct benefit to the participant is expected. To assess potential benefit, regulatory committees often request that investigators administer a range of doses of the agent for the initial patients to determine whether higher doses do have adverse effects—even during Phase II/III trials. Thus, the dosage tested in a particular patient may be insufficient to induce a therapeutic response or may be so high as to cause toxicity.
High costs associated with gene and cell therapy raise the ethical question of whether these treatments will only be utilized by the wealthy. Biotechnology companies such as Novartis, which developed the leukemia treatment Kymriah, are aware of this and are developing programs to provide financial help to patients in the USA who are uninsured or underinsured. Another factor to consider is that gene and cell therapies are designed to be curative, and so the cost of therapy can be weighed against that of lifetime treatment. In the long-term, costs will likely be reduced by optimized production of cell and gene therapies and the development of therapies that do not need to be tailored to the individual. In the meantime, patient groups, clinicians, regulators and manufacturers all have a role to play in addressing the issue of cost.
Contamination of the human genome with novel DNA sequences is a concern that may be considered in two ways. First, there is the issue of accidental contamination of the genome while conducting gene or cell therapy on somatic (adult) cells. To minimize the possibility of this, all vectors are tested to make sure they do not enter the germ line in experimental animals, and sperm from human males in clinical studies are tested to make sure the gene has not inserted in the genome. Second, there is the issue of intentional manipulation of the germline to alleviate disease. As new gene editing technologies have now made this much easier, there is currently much debate between scientists, clinicians, patient groups, and regulators regarding the ethics of editing, or not editing the human genome.
Use of embryonic stem cells, or human fetal tissue, as a source of stem cells remains an ethical issue. The development of stem cells from other sources such as iPSCs has somewhat reduced the dependence on ESCs.