Participants of an international workshop at Tel Aviv University called for paying attention to bioethics and preventing discrimination, but called for promoting the development of personalized medicines to reduce side effects and increase their effectiveness
Avi Blizovsky
An advisory panel of the US Food and Drug Administration (FDA) recommended in mid-June that a heart failure drug be approved specifically for African-Americans.
In 1997, the Food and Drug Administration did not approve the use of the drug for all patients, after two clinical trials did not show a significant statistical advantage between the subjects who received the drug and the control group. In an experiment done last year, funded by the manufacturer, the NitroMed company, 1,050 patients of African-American origin who suffer from heart failure participated. The results of the experiment were unequivocal: the mortality rate among the subjects who received the drug was 43% lower compared to a control group that received a placebo drug.
Coincidentally, at about the same time, an international workshop was held at the School of Medicine at Tel Aviv University under the title "Personalized Medicine Europe: Health, Genes, and Society." Prof. Gregory Lifshitz, director of the Yoran Institute for Human Genome Research, and Dr. David Gurvitz, director of the laboratory, participated in the organization of the conference. National Institute for Population Genetics of Israel.
One of the participants in the workshop was Felix Pero, co-director of the field of genomics in the FDA's clinical pharmacology and biopharmaceuticals office, who said in response to a question from the science website that 70% of the drugs we take do not reach peak effectiveness and do not fulfill the medical promise behind them.
"We need to rethink the approach to drug development. Our current paradigm is no longer applicable. The big concepts need to be re-examined and therefore it is necessary to create incentives for such a change. We need to create an environment that will allow us to develop a new business approach to drug development. There are already several such drugs on the market today. Quite a few more drugs are in the development stages. However, in the meantime it has not reached the mainstream. ” concludes Fero.
What is the reason?
Perua: "The obstacles are still significant. Pharmaceutical companies prefer to develop drugs whose market includes millions of consumers. As soon as a certain drug is only suitable for a part of the population, and it doesn't matter which part at the moment, it reduces the market. The fact that a drug is no longer suitable for the general public is a perception that needs to be overcome. We need to identify those who respond and those who do not respond to the drug and the correct dosage for the drug, as well as identify who is in greater danger from taking the drug."
According to Perua, until now the pharmaceutical industry has dealt at most with the pharmacokinetic aspect, meaning adjusting quantities. Now it will also be necessary to consider the pharmacodynamic angle - whether or not the drug helps the specific patient. This is the area that needs to be researched the most and will be the most essential to the drug development approach in the future." Talk also means money. For example, if a genetic test shows that certain populations have genes that are activated by the drug Herceptin and cause the drug to have no effect, it will be possible to exclude these people from the sample groups and save the frustrating waiting time at the end of which it is only discovered that these people do not respond to the drug. By the way, such a test can be performed quite easily using biological chips that will be developed for this purpose. In the same way it is possible to determine whether the patient will or will not respond to chemotherapy treatment. If it is found that he does not respond, another alternative is sought and he is prevented from suffering, and the waste of time during which the disease sometimes spreads to the point of no return.
Pero gives as an example the shoe industry that offers a selection of sizes and a selection of colors. When it comes to medicine, the differences between people are not always visible, but the Human Genome Project, in which 3 billion dollars of public money was invested, has produced a way to distinguish these differences. Now the bottleneck is in the pharmaceutical companies. "Just as shoe manufacturers produce shoes in different sizes, so do medicines. Non-personalization makes the pharmaceutical industry ineffective."
In a theoretical example, he shows, for example, that for a certain drug that causes harm to 10% of those who use it, the rate of harm can be lowered if a genetic test is conducted. "If it turns out that ten percent of the population, who are people with certain genetic characteristics, have a 50% risk of developing side effects, 40% of the population has a 12.5% chance, and for the remaining 50%, the medicine helps and has no side effects. By giving the drug only to those for whom it is not accompanied by a side effect at all, and by being able to distinguish this group through genetic tests, it will be possible to lower the injury rate to zero."
In conclusion, Dr. Perua said that it is necessary to educate the doctors, and to introduce the subject of bioethics, as well as the field of personalized medicine, into the medical school curriculum. Likewise, a dialogue must be created with the public, which is beginning to show concerns about the various aspects of genetic research, and in particular cloning and treatment with the help of embryonic stem cells. "It takes courage, a strong will and to make the adapted medicines a reality".
Prof. Gregory Lipbshitz from the Department of Anatomy and Anthropology of the Faculty of Medicine in Tel Aviv and director of the Yoran Institute for Human Genome Research, explains the purpose of the workshop: "Genetic research is now operating in a completely new direction. Up until now and even today we are mainly engaged in the search for genes that create tendencies for various diseases such as heart attacks, bone loss (osteoporosis), diabetes, hypertension and more. It seems clear to us that there are also genes that react differently to the drugs we receive, and therefore we now need to look for another component in the genome that controls the body's physiological responses to the drugs we receive.
Here two problems arose that have very important consequences. First, different people react differently to the same drug. But it turns out that even in the same person, there is a difference in the response of the genes to the drug when it is given in different forms. Different forms of taking the drug cause different reactions in our genome and actually activate different physiological mechanisms, at least partially. We were not aware of this until very recently.
Not long ago, an interesting study was published from a research laboratory at the University of Indianapolis in which the hormone PTH was tested. This hormone causes certain responses of the skeleton in regards to the state of the bone. The researchers wanted to check which physiological genetic mechanisms it activates. There are different types of treatment. There is treatment that is given continuously, and there is treatment that is given with breaks. In the tests they conducted on rats, it turned out that the two treatments activate about 22 genes in common, but in addition each of them activates dozens of specific genes in response to drug treatment. The same drug for the same organism with the same genetic predispositions activates different genetic physiological mechanisms. We do not yet know what the clinical significance of findings of this type is because until recently, there were no technologies that allowed testing the activity of so many genes at once. It's a matter of the last 5 years.
As mentioned, this is in addition to the fact that the same drug with the same characterization of treatment, causes different results in different people. This has been known for a long time. A drug needs to be adjusted. There are, for example, 12-14 types of blood pressure medication. When a person suffering from blood pressure comes to the doctor, he receives a type A drug. If it turns out that it has no effect or causes side effects, you get medicine B and C, and so on. There is of course also a dose but also a type of medicine. It turns out that to a large extent these two phenomena - both the type of reaction and the level of reaction to the same drug, depend on genes. The new methods will allow this fact to be taken into account.
Prof. Lipshitz continues: the genetic reactions to drugs can create both a majority and a minority in the population for whom the particular drug is not suitable. Drug development is a very expensive thing. Will a pharmaceutical company or any company in general, take on all the heavy financial problems that will be associated with the development of a drug intended for a small market in advance because the prevalence of the genes is not equal. Some alleles are more common and some are rarer. In practical terms, it is clear that every pharmaceutical company will focus on the majority, because that is where the market is. What happens to the minority? After all, they also pay health insurance. They also deserve all the rights, but how do you apply it practically? Especially one should pay attention to the fact that in a certain gene we may belong to the majority but in another gene out of the many thousands that exist in the body we will belong to the minority. As mentioned, we cannot choose which disease to get.
Two of the lecturers did refer mainly to the ethical aspect. Prof. Michel Rebel from the Weizmann Institute, who heads the Israeli Council for Bioethics, says that personalized medicines are part of the improvement brought about by modern genetics. It will be possible to identify potential patients before the disease breaks out in them and treat accordingly with preventive treatment or choose a healthy alternative.
This will also open the door to more prenatal testing. It will even be possible to remove one cell from a three-day-old fertilized egg outside the womb, carry out genetic tests using DNA chips, and return only healthy embryos to the body. It will also be possible to conduct more tests before the marriage and thus be better prepared. According to him, Judaism even allows abortion in the case of a fetus that is known in advance to develop into a sick person.
In any case, in these treatments, care must be taken that genomics does not become eugenics. The difference is simple: eugenics is when society decides what is a normal person and what is not. Legitimate medicine is if the individual decides what to do with the test results and not society. It should be remembered that there is no such thing as genetic hygiene - a theory that led to the act of mass extermination carried out by the Nazis who believed in it. There are no ideal gardens. There are simply different genes. Genetics and behavioral sciences is a legitimate field of research such genes contribute 5-10% of the effect - there is no such thing as a gene for violence. Will we improve the IQ in society through genetic filtering or through providing better conditions - education, health, etc. People are much more than their genome pool.” According to him, there is no such thing as a standard human being: "We are all mutants".
Janine Lohnshoff, from the VU Medical Center in Amsterdam called her lecture: "Personalized Medicines - New Aspects, New Dilemmas." According to her, after the misuse of genetics for the purpose of committing crimes against humanity, there is a great fear in the public about the progress.
The research field of medical ethics in the twentieth century is dominated by a paradigm of protection: protection of human dignity, as it is expressed in respect for people and free choice. We are required to accept the difference genetically. The genetic information and genetic traits are different from other information and traits and therefore require special attention and in particular with regard to the protection of the information from viewing by unauthorized persons. Genetic information is part of the spectrum of all medical information and not a category in itself. All medical information should be kept confidential in the best possible way."
Lonshoff also joins the call to introduce bioethics into medical schools.
for further reading
to the TARGET.COM website
FDA Genomics website
Idan the human genome - the moral aspect
https://www.hayadan.org.il/BuildaGate4/general2/data_card.php?Cat=~~~194657068~~~47&SiteName=hayadan
