Open letter to diabetics

Natalia López Moratalla.
Professor of Biochemistry and Molecular Biology, University of Navarra.
Published in ABC de Madrid, 29 September 2002.

A few weeks ago I received the manifesto of the association de Diabéticos Navarros ¿Por qué no avanzar en la cura de la diabetes y otras enfermedades? aimed at raising awareness among citizens and political forces of the importance of scientists to continue researching. I am fully aware of this. I am well aware that diabetes ( subject I) is a tough disease, it is common and it starts at an early age. The beta islet cells of the pancreas, the ones that produce insulin, are gradually but very effectively destroyed because the cells of the body's defence system against foreign substances go berserk and attack their own. I am investigating precisely the destructive machinery of these cells in this and other autoimmune diseases in an attempt to stop them.

As they say in the manifesto, Prof. Bernat Soria's team proposes obtaining pluripotent stem cells obtained from embryos left over from in vitro fertilisation, which are potentially capable of being transformed into insulin-producing cells and, therefore, potentially capable of providing this hormone to the organism by regenerating the islets of the pancreas once transplanted into the patient. From the perspective of this therapeutic possibility, they call for laws to authorise the importation of embryo-derived cell lines, the use of frozen embryos and therapeutic cloning. And, at final, as they rightly say, they want to proceed with the financing with public funds of the research applied to the treatment of these diseases. It is a commendable effort to cure diabetes, but unfortunately it is giving rise to hopes that are currently more wishful thinking than reality.

I ask you to read carefully, and without prejudice, my proposal to be more ambitious. I think you have the right (and society as a whole has the right) to "demand" creativity, rigour, and also freedom from impositions marked by interests unrelated to science itself. It is a whole challenge to cure without destroying, to cure without damaging as much or more other organs or systems of the patient; to cure without introducing the risk of tumours. In other words, to cure.

It is well known that in the case of autoimmune diseases such as diabetes subject I it is not enough to transplant new cells into the pancreas or new pancreatic islets into the patient; if the aggressiveness of the "killer" immune system cells is not corrected sooner or later, which is always in the short term deadline for a young patient, the transplanted cells (from donor islets, his own stem cells, or from an embryo, or a clone) will be destroyed like those of his pancreas, and the disease will resurface. It is very important that Denise Faustman has already found an important core topic , and in doing so, she has put in place a method that works; she published it on 19 July in the journal Harvard University. They have alleviated the very root of the disease not only by "immunosuppressing" the patient's immune system, but also by removing the destructive cells in the islets of the damaged pancreas. The surprise, what they did not expect, is that with this system there is no need for the always difficult transplants. It was already known in 2000 that the pancreas also has stem cells, the adult ones, and that these can differentiate into insulin-producing ones (Nature Medicine 6, 278-288). Well, these Harvard researchers have found that it is these stem cells that are capable of regenerating the pancreas, if the harmful cells are removed.

This opens up the horizon of research therapeutics in a spectacular, desired, sought after and dreamed of way. Dr. Soria has recently recognised, in the heart of the academic community, that it was not within reach to safely master embryonic cells so that they produce insulin. Moreover, the problem of rejection (which some call secondary because they are unaware of the complexity of the autoimmune response) has not been technically solved. Nor is cell reprogramming for therapeutic cloning technically solved. Nor has it been resolved whether embryonic stem cells from embryos left over from assisted fertilisation clinics will inherit the numerous genetic defects and malformations observed in embryos produced in vitro.

But the horizon has opened up again in two very clear ways. One route is through the patient's own stem cells (pluripotent or more mature); a hormone has been obtained that stimulates the cells to produce insulin, and liver cells cultured in a medium containing glucose have been converted into nothing less than insulin-producing cells. But it's not just positive news for the disease we're talking about. We can now produce stem cells from embryonic subject without destroying embryos. In these months of 2002, the most serious problem of pluripotent stem cell technologies has been solved. On the one hand, Cibelli's team at business ACT has obtained cells with the characteristics of monkey embryonic stem cells only by activating the oocytes without fertilising them (Science 295, p. 819): the cells are derived from a single cell assembly, not an embryo, although it is often called a "parthenogenetic embryo". On the other hand, Oslo has succeeded in transforming cells without cloning the patient (Nature Biotechnology). These are new techniques that need to be validated, but they give a message that is worth listening to: scientific progress does not (at least not exclusively) involve the use of human embryos, nor cloning. There is a whole range of promises that are also better promises.

To make discussion fair, it cannot be disregarded that there are indeed alternatives: one promote the production of insulin induced by the newly known new hormone; another to exploit the potential of the patient's own stem cells; and another to obtain embryonic stem cells without the need to destroy embryos. There is more science.