Prospects of medical diagnostics
Opinions of post-science experts on new methods of diagnosing diseases
In the "Point of View" format, Post-Science introduces readers to the opinions of our experts on current problems of society, education and science. In the new issue, we asked our authors to express their point of view on the prospects for the development of medical diagnostic methods.
"Individual monitoring using microchips
may lead to a revolutionary breakthrough in diagnosis and treatment"Diagnosis in the medical sense involves a set of rules, methods, solutions that ultimately allow us to come to a conclusion about the presence or probability of the presence of a particular disease.
Functional diagnostics is a specific and well-defined section of medical diagnostics. Assessing the prospects and development of functional diagnostics in recent years, I would like to note that there are both skeptics and optimists. Skeptics say that since the basis of functional diagnostics is clinical physiology, that is, the analysis of regulatory processes occurring in the human body and indicating the presence of the disease, and clinical physiology itself has not undergone major changes in recent years, functional diagnostics is currently undergoing a stabilization phase without waiting for revolutionary breakthroughs.
Optimists reason quite the opposite. They say that the accumulation of technological innovations and data obtained recently leads to qualitative and quantitative changes that open up new horizons in this area.
There is no doubt that with the development of modern technologies, we are able to detect earlier and earlier changes in regulation associated with the disease. But I would like to draw attention not to quantitative, but to qualitative trends in functional diagnostics. Traditionally, the subject of study was the processes in the body that occur either in a state of relative rest, or with an artificially created "substantial" load, that is, in fact, it was a "provocative" functional diagnosis. The first successful attempt to switch to "observational" functional diagnostics can be recognized as the creation in the 60s of the XX century of equipment for continuous monitoring of ECG (N. Holter) and blood pressure (A. Ninman) in conditions of "real life activity".
50 years of distrust, skepticism, pessimism, recognition and improvement have passed, and these methods have become indispensable in the detection and treatment of cardiac arrhythmias and conduction disorders and arterial hypertension. Now we understand that the hypertension that has traditionally been detected at a doctor's appointment is only 40-60% of the "iceberg" of actual hypertension. Some of it turned out to be false hypertension – "white coat hypertension". And very alarming night hypertension, as well as hypertension, which manifests itself only in the workplace, has become available for detection and correction only when using modern devices that automatically measure pressure every 15-30 minutes.
Moreover, there is already equipment in the form of bracelets for monitoring blood pressure every second in conditions of "real emotional and physical" stresses. In 2014, for the first time in the USA, a system implanted into the pulmonary artery for continuous measurement and transmission of data on pressure in the small circulatory circle at home to the monitoring center was allowed for clinical use. This technological breakthrough has led to tangible results in the observation and treatment of patients with low heart performance. Great efforts in creating implantable devices that allow monitoring an increasingly wide range of indicators of the cardiovascular system have been noted by companies producing implantable pacemakers.
Practically, it can be stated that "the genie has escaped from the bottle" and we are on the verge of creating an "observational functional diagnostics" based on implanted microchips. Optimists dream of safe microchips that will be implanted into a person "with a warning" and work for a long time, collecting the necessary information that will identify the earliest adverse functional changes. That is, functional diagnostics will be aimed at identifying and correcting conditions preceding the disease. This direction – individual monitoring using microchips – can lead to a revolutionary breakthrough in diagnosis and treatment.
Anatoly Rogoza,
Doctor of Biological Sciences, Professor, Head of the Department of New Diagnostic Methods of the Russian Cardiological Research and Production Complex of the Ministry of Health of the Russian Federation.
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"Decision-making in diagnostics is left to the person,
but the help provided by technology becomes significant"Recently, there has been not only the emergence of new diagnostic methods, but also, surprisingly, the revival of methods that until recently seemed outdated.
Moreover, these approaches acquire a completely different role in diagnostics than it was before.
As one example, we can mention the introduction of new methods of microscopic analysis. The decline in the role and relevance of these methods was determined by the small accuracy of microscopic methods, but to a greater extent by the high cost. Blood smear analysis is expensive, an automatic analyzer performs the analysis both faster and cheaper. The introduction of automated sample preparation systems, automatic photographing of drugs, the development of decision support systems and much more have made microscopic methods both more accurate and cheaper. Already, robotic systems have been installed in some clinics that allow automatic photographing of a large number of drugs. The role of the diagnostician is reduced to the analysis of the obtained images. Image recognition systems are next in line. It is clear that the decision-making remains with the person, but the help provided by technology becomes significant.
Plus, new microscopy methods are gradually moving from research laboratories to the clinic. These are not only new devices, but also new experimental approaches. We are talking primarily about systems related to the use of fluorescent proteins, which have long been used for research purposes or in screening systems. The latter quickly develops into diagnostic applications.
Another interesting example is the development of flow cytofluorimetry methods. This method analyzes the presence of certain proteins on the cell surface, which is very important, for example, for the differential diagnosis of leukemias and lymphomas. Tumor cells are distinguished by a rather specific set of proteins on their surface, identifying which, you can make a diagnosis. The problem is that it is necessary to identify quite a lot of markers. Previously, it was possible to identify two, rarely more, markers at the same time. If there are a lot of tumor cells, then there is no problem. But if there are few tumor cells, then it is almost impossible to recognize them among the numerous normal ones. Now approaches are being implemented when eight markers are identified simultaneously. Some of them are used to identify the tumor population, and some are used to characterize the properties of tumor cells.
Eugene Cheval,
Doctor of Biological Sciences, Senior Researcher at the A.N. Belozersky Research Institute of Physico-Chemical Biology of Moscow State University.
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"The analysis of the results of omix examinations allows
to actually implement the principle of personalized medicine"Over the past two decades, the methods of quantitative and qualitative analysis of the molecular foundations of life have undergone a radical update.
From the detection of individual varieties of molecules in both fundamental and applied biomedical science, they have irrevocably moved on to the detection of entire classes of molecules in their complete or almost complete totality.
Such cumulative methods have received the name omix, from the generalization of the names of the sections of science ending in the suffix "-omika". For example, genomics studies ensembles of genes, i.e. genomes. Transcriptomics – ensembles of matrix RNAs, i.e. transcriptomes. Proteomics – ensembles of proteins, that is, proteomes. Metabolomics – ensembles of metabolic reactions, i.e. metabolomes, and so on.
The use of a variety of omix technologies made possible the long-standing dream of ancient medicine, breathed new life into the clinical paradigm formulated by Galen and Avicenna: "Treat the patient, not the disease."
Analysis of the results of various omix examinations allows finally to implement the above-mentioned principle of personalized medicine and prescribe to a particular patient exactly the treatment method that is most suitable for him.
Nevertheless, it is very difficult to analyze the "raw" results of each of the omix studies for the purposes of personalized medicine due to the large volumes of poorly structured information that these "raw" data represent.
Powerful mathematical and statistical methods available in bioinformatics come to the aid in processing "raw" data. One of the main ways of deep generalization and analysis of omix data is the transition from the description in terms of individual molecules (proteins, RNA, DNA, and so on) to more general characteristics describing signaling pathways, that is, a complex set of interacting genes and their products (proteins) that determines the metabolic and mitotic fate of the cell.
Since such a set of signaling pathways is called a signal, the approach investigating changes in these pathways can be called signaling. Due to the law of large numbers (since signaling pathways contain hundreds of genes and gene products), a significant part of stochastic noise can be overcome at the signal level, which greatly complicates the analysis of systemic changes at the genomic/transcriptomic/proteomic level. The correlation of the results of various genomic/transcriptomic/proteomic studies at the signal level, as a rule, is also higher than at the genomic/transcriptomic/proteomic level.
It is at the signal level that it is possible to find effective predictor markers of the individual effectiveness of many drugs, in particular antitumor drugs, as well as to solve a larger-scale task than personalized medicine – "drug repurposing", that is, the search for those diseases in which various drugs previously created for the treatment of others can be effective diseases. Such reprofiling becomes possible due to the accumulation in the public domain of the results of millions of genomic/transcriptomic/proteomic/metabolomic and so on studies in various pathological conditions.
Nikolai Borisov,
Doctor of Technical Sciences, Burnazyan Federal Medical Biophysical Center.
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"Conduct a genetic analysis, sequence the genome and understand what kind of disease you will have, –
this naive dream, unfortunately, has not been realized"It is very difficult to say in general for all diseases at once which diagnostic methods are needed.
First of all, it is necessary to separate genetic diseases from non-genetic ones. If we talk about autoimmune diseases, then they need to pay attention to antibodies. Some diseases require imaging techniques, such as magnetic resonance imaging or positron emission tomography. If we talk about neuropsychiatric diseases, then only in rare cases there is a certain genetic basis, which is well studied and where genetic diagnosis helps.
To carry out a genetic analysis, to sequence the genome and understand what kind of disease you will have – this naive dream, unfortunately, has not been realized. It turned out that we all have a fairly large number of nucleotide polymorphisms, and when you, for example, get an analysis of the entire genome, you will have a lot of genetic changes, and it will be unclear how you can accurately associate this particular mutation in this particular gene with this particular disease and this symptom. So in most cases, the traditional descriptive diagnosis remains, when the patient comes to the doctor and describes his problems, since, unfortunately, there are no clear markers, for example, for schizophrenia, and psychiatrists have to investigate the symptoms.
In the case of some other diseases, you can more clearly see what is called a biomarker when you measure something and can accurately understand: if a person, for example, has some substance in his blood, it means that he has such a disease. The best example is phenylketonuria, which is determined by the concentration of phenylalanine in the blood. Doctors dream of finding similar biomarkers for many other diseases, but such biomarkers are rare for widespread diseases. And for most psychiatric diseases, no matter how sad it may sound, there are practically no such markers, so the patient still goes to the doctor and complains about his symptoms, and the doctor examines him and sees the manifestation of classic symptoms, or, as it is now fashionable to say, endophenotypes, and makes a diagnosis based on them.
In neurodegenerative diseases, neuroimaging methods can be informative: for example, in Parkinsonism in the late stages, positron emission tomography can record the loss of dopamine neurons, but in the early stages this is impossible, and the most important thing is to diagnose a person's problems before the disease fully develops! What I am talking about applies primarily to neurodegenerative and psychiatric diseases that I deal with. Cardiologists, oncologists and immunologists, for example, have very successful diagnostic methods. Unfortunately, the situation with neuropsychiatric diseases is completely different, because when it is possible to detect something, it is often too late. This is a very big problem: how to diagnose the disease at the initial stage, when it is still possible to stop the neurodegenerative process?
Raul Gainetdinov,
M.D., Ph.D., Professor at the Skolkovo Institute of Science and Technology (Skoltech), leading researcher at the Italian Institute of Technology (Genoa, Italy), Associate Professor at Duke University (USA), Director of the Institute of Translational Biomedicine at St. Petersburg State University.
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"Methods of early diagnosis of brain diseases are much more difficult to develop
compared to other diseases, because no one really knows how the brain works"If we talk, for example, about the treatment of cancer, then the most effective means of combating it is surgery.
Therefore, the earlier the tumor is diagnosed, the faster the cancer can be cured.
At the moment, an effective method of finding tumors is computed tomography. If physicists can develop more efficient tomographs – with higher resolution and the ability to detect tumor cells – then this will be the most promising method of detecting a tumor at an early stage.
Of course, the development of methods of early diagnosis often leads to new methods of disease therapy. But if early diagnosis of diabetes or cardiovascular diseases really makes it possible to develop prevention of these diseases, then everything is more difficult with the brain. It is much more difficult to develop treatments for brain diseases, because no one really knows how the brain works.
Take the common Alzheimer's and Parkinson's diseases. They are considered diseases of the elderly, but in fact they get sick at the age of 20 to 40 years. Now they are diagnosed only when the destruction of the brain has reached such an extent that symptoms appear.
Let's say you are 25 years old. Imagine that there is a diagnostic method that allows you to say with 100 percent probability that if you live to, say, 70 years, then you will develop Alzheimer's. But what is the point of such diagnostic methods if there is still no cure for this disease?
In general, there are two promising areas: improving devices based on physical principles – the same tomographs, as well as improving methods of chemical diagnostics based on the presence of biological molecules in the blood – markers of early stages of the disease.
Philip Haitovich,
PhD in Biology, Head of the Comparative Biology Group at the Institute of Computational Biology in Shanghai, Professor at the Skolkovo Institute of Science and Technology (SkolTech).
Portal "Eternal youth" http://vechnayamolodost.ru15.05.2015