Any experimental therapy that is intended to be used regularly in people must necessarily pass through a series of preclinical phases, design and validation in cellular and animal models, in research laboratories, followed by the corresponding clinical phases of the tests, in hospitals, to verify your safety and effectiveness. The development of a therapy recapitulates the four fundamental principles of bioethics: beneficence (doing good), non-maleficence (not doing evil), autonomy (taking into account individual freedom, through obtaining informed consent from the patient) and justice (anyone should be able to benefit from the therapy). These ethical foundations are also picked up in some way in the Hippocratic oath in Medicine.
We tend to think that a good therapy is one that is more effective but, in reality, any therapy before being effective must be, above all, safe. It should not aggravate the condition of the patient to be treated or cause additional alterations to their health. The majority of preclinical trials and the first phases of clinical trials have the task of guaranteeing the safety, the non-toxicity of the therapy, in order to maximize the benefits, minimizing their associated risks.
Naturally, the exception to all the above is the compassionate use of experimental therapies, when the deterioration of the patient's health is irreversible and there are no treatments that can stop the foreseeable fatal outcome. These are exceptional cases that must be authorized as such by the Spanish Agency for Medicines and Health Products (AEMPS) and by the corresponding Research Ethics Committee with medicines (CEIm) of the hospital, in charge of ensuring the health and safety of patients , after evaluating the cases individually and independently. Of course, the AEMPS and the CEIm must also authorize the rest of the clinical trials with non-compassionate experimental therapies.
The logical pressure of patients, naturally interested in having therapies tested and approved as soon as possible, must be carefully managed
I think it's important to remember these truisms these days in which possible experimental therapies appear regularly in the media. At the end of November we met the possible first case of genetic editing in human embryos, implanted and apparently gestated at term, in order to obtain children immune to infection by the HIV virus of AIDS. This experiment, which seems to have been carried out in China, will not have achieved the desired goal, but will have transferred to the twin girls a genetic variability and a series of unnecessary risks to their health that will determine the medical supervision for the rest of their lives. It must be said clearly: it is not safe to inactivate the gene CCR5 in embryos through genetic editing to ensure that the resulting baby can not be infected by the HIV virus. It is neither recommended nor necessary nor is it the best medical option to be able to have a child free of viruses from parents who carry it. There are other valid medical alternatives, much less risky.
Almost simultaneously to the previous case we have known a new experimental therapy to treat patients with congenital Leber type 10 amaurosis, caused by mutations in the gene CEP290. This innovative therapy, based on genetic editing through CRISPR, will be used experimentally in one of the two eyes of a limited number of patients with this degenerative disease, which is the most common cause of congenital infantile blindness. But neither is it still entirely safe. The editing procedure may cause additional mutations to those that are intended to be corrected, or leave the gene intact or, in a limited percentage of cells of the retina, perform the expected genetic correction. On the other hand, the eye is a privileged organ, relatively isolated from the rest of the body, so projected subretinal injections should not produce alterations beyond the eye itself.
The logical pressure of patients, naturally interested in having therapies tested and approved as soon as possible, must be carefully managed. This is why patients should not decide to activate a therapy, however they wish to volunteer, although they will always decide whether or not to accept the treatment, once authorized. They are the AEMPS and the CEIm who should assess all the aspects and possible consequences of a new therapy, before authorizing it.
Obviously there always has to be a first time. And it is possible that in the first patients treated the risk assumed is much greater. But we should retain the concept of security as the director of the entire process, only avoidable in very exceptional situations. For example, when there is a risk of death and there are no alternatives, and as long as the compassionate use of the therapy is approved by the competent authorities.
Lluís Montoliu He is a researcher at the National Center for Biotechnology (CNB-CSIC) and the Center for Biomedical Research in the Network of Rare Diseases (CIBERER-ISCIII).