“As Aristotle and every serious theorist of human nature has understood, human beings are by nature cultural animals…”[1]
It is interesting to paraphrase F. Fukuyama: the individual is born of a genetic union and evolution has developed the intelligence, and social and cultural capabilities of the species. Genetics is, however, the cause of many diseases. The inevitability, whether it be predictable or purely random, of genetic diseases is now being overturned by gene therapy. This therapy raises questions especially as we have moved from tragic impotence to direct intervention in just a few decades. The transition has been fast and brutal, the first results are in and there are new risks.
Correct or rewrite
Gene therapy is an experimental technique that uses genes to treat or prevent a disease. This incredible odyssey began with the discovery of DNA by Miescher in 1869, the double helix by Watson and Crick in 1953, then continued with the sequencing of the human genome in February 2001, and recently the discovery of CRISPR. Indeed, without excessive simplification, it can be said that living organisms have perfected their genome over the course of their evolution. Consequently, there are often several genes for the same function and conversely several functions for the same gene.
Many techniques can be used to modify the genetic abnormality that causes a disease. It is possible to decrease or switch off the expression of a gene without altering the genetic capital of the individual. To approach it from another angle, you can increase the activity of a gene that supplements the deficient gene. Or you can modify the genetic capital by using a vector that will insert a gene into the genome of cells of various tissues — most often a virus. Finally, it has become possible to rewrite the genetic code, thanks to CRISPR-Cas9, a system derived from bacteria, which suppresses or replaces one gene with another on the DNA at a specific location.
Globalisation and the three global zones of human gene therapy
In Europe there is a myriad of legislation on gene therapy. 24 European countries, including France, prohibit any intervention on the germline (the cells that combine with those of the other sex to create an embryo). The Council of Europe is calling for a ban on genetic engineering for the germline or to modify the genome of future generations. However, the United Kingdom has recently authorised a modification of the germline via mitochondrial donation.
The United States has a complex regulatory system that makes it very difficult to modify the germline, but does not prohibit it. There are also funding restrictions on embryo research that could have a major effect on the underlying basic science necessary to reach the regulatory approval stage.
And then the third world is simply not regulated. Some countries have not considered this possibility, while others have only ambiguous recommendations or regulations (China, India, Russia, Japan…).
Looking at the clinical trials reported up to 2015, the United States undertook 66.81% of gene therapy clinical trials; all other countries have modest percentages: 9.45% in the United Kingdom; 3.95% in Germany; and about 2% each in Switzerland, France, China and Japan.
The risks of gene therapy
Like any effective therapy, gene therapy presents risks.
The case of Jesse Gelsinger is an example of this; at the age of 18, he was controlling his genetic metabolic disorder with diet and medication. He entered a clinical trial at the University of Pennsylvania in 1999 to test a virus vector of a normal gene for the deficient enzyme. The result was disastrous. Gelsinger suffered a chain reaction that the tests had not predicted – jaundice, a blood clotting disorder, kidney failure, lung failure and brain death. Several mistakes were made when he was included in the trial, but his case remains a high-profile warning of these new risks.
Another example is Spinal Muscular Atrophy (SMA), which is one of the most deadly genetic diseases in infants. The motor neuron degenerates making muscular function impossible and consequently affecting movement, posture and breathing. The advent of Spinraza changed the prognosis of this disease by increasing the production of the protein necessary for the survival of motor neurons without altering the diseased gene. At the same time, AveXis applied to the FDA for approval of a new way of treating SMA, this time using gene therapy. The treatment, Zolgensma, raises questions. The clinical trials of Zolgensma focused on very small groups for short periods of time. The phase 1 trial of Avexis was conducted with only 15 infants; the phase 3 trial increased it by 20 infants. This technique entails two types of risks: the introduction of new genetic material and the vector virus. The replacement of one gene by another from the outside could affect functions other than those for which the gene is replaced, as demonstrated by the tragic experience of Gelsinger — a hypothesis that should alert regulators.
Calculating the risks
The various protagonists of gene therapy agree on one fact: the evidence for efficacy in the trials is strong because the results are quick and easy to measure, but the long-term consequences, individual or at species level, are unprecedented. When a gene therapy, whatever it is, gives children a chance of survival, the equation is simple. When it comes to non-fatal or already treatable genetic conditions, the benefit and risk assessment is difficult. Is it better to continue gene therapy that does not replace the gene but improves the patient’s condition, or is it reasonable to choose a more radical therapy with harder to identify risks? In this debate transparency and peer-reviewed scientific publications are paramount. But patients and especially parents, in the case of children, seem to me to have an essential role to play. Some gene therapies will be failures, others will survive. It is rational that patients should be protected as much as possible, but the most serious cases should be able to access innovative treatments sooner rather than later.
Authorisations for gene therapy are multiplying, which is why the classical pharmaco-economic model has to take the unique nature of this therapy into account. It’s about slowing down clinical use whenever there is major uncertainty, and being even more efficient at the point where benefit and risk are in the balance.
[1] “Francis Fukuyama, “Biotechnology and the Threat of a Posthuman Future.” The Chronicle of Higher Education (22 March 2002): B7 — B10.”
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You know mitochondrial donation for example can become a great solution for infertile women. There are a great number of such patients who need this therapy. It’s a true fact. Mitochondrial donation is starting its development. And I guess it will have a success. With the help of such program women with serious diseases will receive a unique opportunity to have healthy child. I think it’s great! Just imagine feelings of these women. Now they believe and wait for the day they will be able to use this new procedure. But I know only few states work on this issue. It’s not legal in fact everywhere. What is interesting is that poor countries are first in this field. Ukraine for example. I read in this country mitochondrial donation has been being used already!
While reading about new technologies and modern medical approaches it seems to be fantastic. There are no boundaries. And medicine and science make wonders.Some countries support and develop genetic engineering. While there are those that ban in some way. Anyway everything has been developing. And we just receive a result of this development. We are humans. And we face with various medical challenges. From year to year number of unsolved problems becomes less and less. It seems specialists can treat everything today. It’s good news. Another question is how much it costs. Sometimes it happen many people cannot effort some treatment due to the high price.
1/ Mitochondria. Mitochondrial donation is special gene therapy which aim is to treat symptomatic genetic anomalies in the DNA of our energy factory. It is a good but complex example of the issue I raised in this short paper. Shortly mitochondrial donation is a germline therapy so we have to build the predictability models of its long term consequences.
2/ Price. It will be easier than previously. Indeed those techniques rely first on testing the human genome of adults and/or oocytes which is a fully automated process which price is very affordable. Secondly, the lab techniques are far less complex and expensive than doing an open heart operation. So let the market open a free competition between corporations (which is presently the case not only in one country but in all advanced countries) and prices will lower fastly.
Yes, it’s really revolutionary technique. And this technique will help to fight with infertility. I support such innovations in medicine. And as of donor confidentiality I think it’s right make such donation anonymous as well. It’s the same as eggs donor confidentiality. Infertile patient uses donor eggs in order to conceive child. And they don’t see and know each other. It’s not in all cases but usually just in such way. I think it’s right. Because it can be difficult in some time. And one day donor can decide to fund baby born with the help of her eggs or mitochondria. Thus it can be problems… This method can be great treatment for women who have gone through numerous failed IVF attempts. So, time will show new opportunities of using mitochondrial donation.
I have read about great new achievement of fertility specialists. It’s called mitochondrial donation. Bad work of eggs mitochondria led to infertility. It means having active mito-chondria in eggs woman can get pregnant. This procedure is also called «three parents’ baby». It’s because materials of three persons are used. I even heard that such children have already born! And in future such procedure can become the same simple and common as egg donation today. It’s even better than egg donation. Because such child will be practically 100% of parents’ genes. The very little percent of donor’s DNA can be. And it will be mitochondria DNA. In fact it’s very interesting project. I know that even Ukraine started such procedures in IVF clinics! I guess many women can be calm and safety still. Today we have so many variants and ways to get pregnant in any age and situation.
Yes, it’s really hard to imagine but it seems to be truth as it is written in the internet news! Ukraine has become the first country in the world where a child of three parents was born. Prior to this, the only case of nuclear transfer in unfertilized eggs is known. And currently the procedure for the conception of a child from three parents in Ukraine is not regulated by law as I know. That’s why the eggs were transferred to a clinic in the UK! And as a result this country became the first in the world to officially authorize the conception of a child “from three parents. Ukraine did not hesitate, and carried out the procedure)) I read in the article that the 34 years old Ukrainian woman was successfully fertilized in the UK. She came back to her homeland and gave birth to a healthy baby! And just imagine for fifteen years! this woman struggled with a diagnosis of infertility. Before this case she tried to get pregnant using the IVF method but it didn’t help. I read that she was treated both in Ukrainian and in Israel clinics. And all efforts and procedures didn’t result with successful pregnancy. Therefore the woman agreed to test a new IVF method and won the infertility war)) I hope that this great and unique method of mitochondrial donation also will help me!)
Gene therapy is very exciting theme and it’s always interesting for me to read something like that as I also had some gene mutations. I have primary mitochondrial disease and it’s a genetic condition. As it is known most of mitochondrial diseases are caused just by genetic defects in the mitochondrial DNA. And it’s fact that unfortunately mitochondrial DNA is inherited only from our mother. Thus as you understand it turns out that mother can carry abnormal mitochondria. And therefore she is at risk of passing on the serious disease to her child. It’s even if she herself show only mild or even no symptoms. Thus I know for sure it can be passed from me to my future baby. And of course I can’t risk in such case and I want my child to be healthy. For many years due to the complex nature of these diseases, their diagnosis and therapy have been being very difficult. But I have already read about new great therapy that can help just in such cases. I am talking about mitochondrial donation and its great possibilities! I have been waiting for such great procedure as mitochondrial donation very much))! Now I am thinking of choosing a clinic where to try it. I read that even Ukraine has already conduct such programs and use mitochondrial donation! Thus maybe just this country and this method will help me to become mother)