PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Personalized Medicine: Sweet or Bitter Pill? by Monica G. Marcu, Ph.D., Pharm.D. My first thought when I started to write this article was actually a concern. How can I stay “politically correct”, optimistic enough but still truthful to my beliefs? Have I succeeded? We surely dream about and need personalized medicine, from early ages to our exit, each and every one of us. Maybe all started with the oldest religious scripts, which stated that, while we are part of the same large family, each of us is a unique, wonderful expression of life. Much later, the modern genomic discoveries came to prove it, sure enough, we are overwhelmingly similar and, at the same time, so unique and distinctive… One could expect that individualized medicine should have been a priority from the beginning of modern pharmacology. But what is, after all, and what is the purpose of “personalized medicine”? The aim of personalized treatment is to match the right drug(s) to the right patient, at the right time and, in some cases, even to design and formulate the appropriate treatment for a patient according to her/his genotype. Fundamental to the future development of future medicine is the identification, sequencing and mapping of the human genome—especially the genetic variations—although understanding the complex human proteomics would not hurt at all. There is a lot of hype about genomics as the best way to lead to drug discovery and all the intricate secrets of life. While many scientists are excited about the genes and their encoding of underlying causes of many diseases, I personally remain skeptical. Except for very few genetically inherited diseases, the actual use of genetic information in any particular individual will remain negligible. For many reasons, some obvious already and some less (since we still lack critical means of exploring the in vivo function, over the long-term, of genes and their products in humans), I expect that actually external and environmental factors would play a more significant role in influencing transcription and the post-transcriptional events. One of the main variability factors will prove to be the extraordinary biological flexibility of human bodies and minds—hard to encode and predict by any means. Studies with twins have already shown that one’s environment (e.g., life style, family, beliefs, pollution) is the crucial factor influencing diseases or health. Overview: The groundwork of individualized medicine was laid by a network of scientists, physicians, pharmacists and even politicians and writers. It is about the biology of genes (although we do not know exactly how many, when and how they work and collaborate), their expressed (or not) proteins, the biochemical and molecular targets and their specific drugs. It is about these “hot” concepts: pharmacogenomics, pharmacogenetics and pharmacoproteomics. It is about developing basic technologies of molecular diagnostics, particularly those for single nucleotide polymorphism (SNP) genotyping to reveal a most common form of genetic variation. Once a diagnosis is proposed, an individual therapy follows, as well as a strategy for closely monitoring the results. Hopefully, a cure is the final goal…besides publishing in a high-impact journal. Tools and Sciences: Along these steps, complex biochip/microarray technologies are employed (besides classical syringes and needles, what did you think?) while cutting-edge bioinformatics is called upon to analyze the immense amount of generated data. Automate and Integrate! Already on its way and relying on biochips, pharmacogenomics (i.e., studying the drugs mechanism of action on cells as revealed by gene expression) deals with the application of genomics to drug discovery and development. For diagnosis purpose, biological samples (including biopsies, when necessary) are analyzed using biochips. Previously known (i.e., personal genetic ID) or acquired genetic data and protein functional expression patterns are generated and visualized. Then, an excellent physician-scientist and/or a skilful robot will interpret the results and decide. Any treatment will be, of course, monitored through the promising science of pharmacogenetics, the study of genetic factors that influence drug action, metabolism and consequent prediction of adverse reactions. Finally, pharmacoproteomics, an important contribution to personalized medicine, is needed as a more reliable functional representation of patient-to-patient variation during therapy. It deals with the protein expression patterns. Examples of future personalized therapies for specific conditions are: - genotyping for drug resistance in HIV infection. - personalized therapy of various types of cancers, for different molecular signatures and stages. - personalized therapy for neurological disease: antipsychotics for schizophrenia and antidepressant therapy tailored to biochemical and personality traits. - gene therapies for numerous inherited or acquired diseases. Presently, we encounter personalized medicine in: - biological therapies using a patient’s own cells (i.e., autologous transplantations). - vaccines prepared from individual patients tumor cells (i.e., auto-vaccines). - individualized therapies with monoclonal antibodies directed at specific genetic and immunologic targets (ex vivo gene therapy involves the genetic modification of patients’ own cells in vitro, prior to their reimplantation in the patient’s body.) Benefits of Personalized Medicine The impact on the long run should be significant, especially for preventive strategies such as vaccines and for genotyping hereditary, predisposition markers to diseases. Finding out that one has a higher chance of developing liver problems, for instance, would reinforce a healthy diet and life style, alcohol avoidance and periodic liver monitoring. Early molecular diagnosis and individualized immunotherapy or chemotherapy are probably the best hope when cancerous cells are present. Immunologically, personalized self-molecules/medicines are better tolerated than other therapies. Tissue engineering—coercing own cells to rebuild damaged tissues—is another example of a potential benefit. Stem cell therapies offer hope for many diseases, although it could take a while until we understand the embryogenesis and apply that knowledge. Other potential benefits of individualized medicine: - Identify early the patients who respond to certain drug treatments or metabolize drugs faster/slower than normal - Develop drugs targeted for specific genetic groups - Accurate dosage according to the patient’s genotype - Cheaper drug development - Facilitate drug approval and introduction to the market An increase in the safety and efficacy of treatments, by tailoring them to individuals, has obvious benefits in financial terms. One third of hospitalizations are due to or related to drug therapies today. Some therapies are not correct, some are not specific enough, some are administered too late or too early. For patients and physicians, refined diagnosis, the presence of a personal molecular health profile and the choice of an individualized therapy represent a true revolution in medicine. And there is already information showing that personalized medicine will be cost-effective in the healthcare systems. Bitter pill? The promise of personalized medicine reminds me in many ways about the wonderful predictions regarding the robots’ impact on our daily lives. Remember? The futuristic visionaries thought that robots and machines would be our greatest allies, replacing many of us at work, that we will have time to enjoy life while computers perform our job duties and even clean and shop for us. That prediction proved to be so wrong; instead of reducing our workload, we are engulfed by more and more duties JUST BECAUSE of the speed and expectations brought forth by machines and computers. Similarly, I suspect, we will encounter many more difficult and challenging economical, ethical and social problems in the future, especially in light of people relying more and more on drugs instead of themselves to regain health. It is not strange (to me) that the more polluted our planet becomes, the more sick we all (plants, animals, birds and insects) are. The more drugs and sophisticated diagnosis procedures we employ, the less time and art physicians spend on patients (who are more and more troubled by asthma, cancer, obesity and depression). The epidemiological studies (and traces of common sense) have shown the impact of natural and social environment on human health, in all diseases studied. Comprehensive changes in diet and lifestyle can often prevent or reverse the progression of severe, life-threatening diseases without the need for expensive and potentially dangerous drugs. “Better medicines” offer the bitter illusion of an omnipotent pill or medical procedure to cure us, no matter how much we abuse or neglect our bodies and souls. That hope is simply impossible to realize in the end. On a less philosophical note, the ethical issues raised by accumulating personal genomic and proteomic data are serious. While some talk about carrying a DNA ID or a personalized CD, others fear the loss of privacy and potentially tragic discriminations. Some people simply do not wish to know about their genetic predispositions, which, more often than not could prove to be inaccurate. In the end, who has the right to access this data, who controls what and how? The economical issues against are at least as strong as those forces in favor of personalized medicine. Already, the cost of medical care and insurance has skyrocketed and continue to grow without end in sight. Millions do not have medical insurance and cannot afford basic and simple medical procedures. How are we going to handle, then, the access of some to expensive genetic tests and treatments? Tough questions. While you look for the answers, allow me to get some flax seeds and oranges—my weapons against cell oxidation. Then I have to run, I mean really have to run—for my health! ### Monica Marcu is a pharmacologist at the National Cancer Institute Center for Bioinformatics/Kevric Co. (N.C.I.C.B. - OC/CIPS). Her primary research focuses on understanding cellular stress in cancer and signal transduction pathways. She is a member of the 2003-2004 Steering Committee for The Science Advisory Board. Interested in finding out more about personalized medicine. Please read the following Perspectives: Beyond Biomedicine: Renegotiating the Sick Role for Postmodern Conditions Excerpts from “Ethical Issues in Pharmacogenetics” ### << Previous Next >> [ View All Perspectives ] |
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