January 1, 1970 (Vol. , No. )

Detlef Niese, M.D., Ph.D. Novartis

In this first chapter of a five-part series, learn about new scientific developments and recent treatment successes.


Imagine your life partner or your child being severely ill. What would it be worth to you if a doctor could exactly predict to which medicine your beloved would respond? And what doses should be enough to kill the fiend with the least side effects?

This idealistic situation is not science fiction. But we still have a lot of work to do to reach this stage. We need tools to identify patient’s profiles. Therefore we have to understand diseases better than we do now and we have to identify biomarkers: indicators on a molecular level that provide information on the physical state of a person. Biomarkers can be used diagnostically and predictively. Personalised medicine is about predicting response to therapy. Therefore we need to perform research on biomarkers and turn them into diagnostic and predictive tests.

So… why don’t we? How can anyone be opposed to such an innovation?

These were the two questions the EuropaBio Personalised Medicine Taskforce tried to answer. We organised workshops and attended conferences in which many stakeholders participated.

We experienced that stakeholders have a lot of difficulties in embracing personalised medicine in practical terms. Adjustments to their way of working are often needed. Health organisations, companies and government institutions alike, will need to rethink, recalibrate and change their standard operating procedures to allow personalised medicine approaches to be adopted by the European healthcare system.

This white paper aims to give insights in the developments and challenges regarding personalised medicines. It provides guidelines for streamlining personalised medicine developments and routes to patients.

This series aims to give insights into the developments and challenges surrounding personalized medicine, and provides guidelines for streamlining a route to patients. [© uwimages – Fotolia.com]

Why We Are So Excited

In this chapter we describe why scientific developments and recent treatment successes have made many of us so excited about personalised medicine. These successes show the effects of replacing traditional intuitive and empirical medicine by precision medicine.

Same Symptoms: Same Disease

Patients diagnosed with the same disease may react very differently to the same treatment. This observation led the Canadian physiologist Sir William Osler (1849–1919) to the statement: “If it would not be about the variability among individuals medicine could well be a science and not an art”. We are brought up with the idea that patients who have the same symptoms and whose course of disease follows similar patterns are likely to suffer from the same disease.

Scientific disciplines such as anatomy, developmental anatomy, physiology and biochemistry, helped us to get a better understanding of how a normal organism functions. Pathophysiology, micro and macro pathology and clinical chemistry helped to describe, classify and understand diseases.

However, few of these scientific advances led to a full understanding of the causes of diseases on a molecular, cellular or genetic basis. Today’s medical text books still describe and define diseases on the basis of combinations of objective and subjective symptoms, macroscopic, microscopic, pathophysiological or biochemical findings, and the presence or absence of specific pathogenic organisms or substances. Most diseases are also classified according to the affected organ or organ system.

In consequence, patients diagnosed with the same disease are considered to suffer from the same underlying pathology. They are also expected to respond to the same treatments, although clinical experience tells us that this is only true in a limited number of situations. What is causing the symptoms on a molecular level, remains often unclear.

Effective Therapies Were Educated Guesses

We have to admit that our current knowledge of disease mechanisms unfortunately has not always resulted in the development of highly effective medicines yet. The effective therapies we have, were developed intuitively or empirically, or were even discovered by chance. Examples include antibiotics, alkaloids, calcium channel blockers, immunosuppressants and cytotoxic agents.

There are many examples of medicines, which were developed on the basis of wrong assumptions, and some examples of medicines, which proved to be effective in an unexpected condition. But there are also few examples of medicines, like oral contraceptives or modern targeted medicines in oncology and rheumatology, of which the development is based on an exact understanding of the relevant mechanisms.

Different Symptoms: Same Underlying Disease

In reality patients diagnosed with the same disease based on the same diagnostic criteria show very different courses of the disease, and respond very differently to the same treatment. In clinical practice, doctors have no other choice than to optimize the treatment by trial and error.

We now know that these patients are probably suffering from different diseases. In other words: the diseases have a different underlying pathology. While the scientific progress in basic scientific disciplines such as anatomy, physiology and biochemistry has been substantial over the last centuries, we still have a very limited understanding of the molecular processes in diseases. We know even less about the factors, which may determine whether a person has an increased risk of developing a particular disease. Is “type-2 diabetes” a single homogeneous disease, for instance?

New Understanding of Diseases

Over the last decades molecular research on sick and healthy cells gave new insights in cellular signalling pathways: mechanisms involving proteins and nuclear receptors, which are essential for the normal functioning of cells but under specific circumstances may lead to diseases. These discoveries have helped us to understand and classify diseases in a new way.

We have learned a lot from rare monogenetic disorders, which allow us to study the impact of specific genetic mutations on the clinical signs and symptoms of the disease.

This research allows us to gain insight in the underlying genetic alterations and the consequences of the presence and functioning of critical proteins. The answer to the question ‘what causes diseases’ is revealing itself little by little since we are able to decipher the genetic code of a person. There is growing evidence that specific genetic mutations involving specific signalling pathways play a significant role in disease development. The scientific discipline of epigenetics stresses the influence of life style and nutrition. Understanding the role of regulating RNA will lead to new ways of therapeutic treatments.

Phenotypically similar conditions classified as the same disease may originate from different genetic polymorphisms or mutations. Similarly, diseases affecting specific organs such as various types of cancers, or certain systemic inflammatory diseases may be triggered by a single common molecular mechanism.

Biochemical, genetic, genomic and other markers identifying such mechanisms can serve as biomarkers for specific disease mechanisms and diseases. Such biomarkers can be developed into diagnostics that are able to identify the specific mechanism involved in the disease affecting a specific patient. With our growing knowledge of such mechanisms we will be able to classify diseases based on the underlying mechanisms and pathways rather than on pathophysiology, pathology and phenomenology alone.

This new disease classification will finally support the development of medicines directly targeting specific disease mechanisms present in a patient.

Recent Breakthroughs in Biomarker Research

Traditionally, oncology is the front runner in the field of personalised medicine. However, in the last decades there have been breakthroughs in other areas such as infectious diseases and haemostasis. Recently, a number of biomarker candidates have been discovered that link mode of action with disease pathophysiology within chronic inflammatory conditions including rheumatoid arthritis and asthma.

The clinical response rates to approved biologics for rheumatoid arthritis leave considerable space for improvement and predictability of the available treatments. Hence, there is currently a tremendous interest in identifying patient subsets that are more likely to benefit from a specific treatment.

Although the preliminary results of the targeted approach to treatment look promising, there are also some difficulties to be mentioned. Firstly, the identification of a disease mechanism does not necessarily mean that it can be addressed. Secondly, most cellular pathways are critical for healthy cells as well as diseased cells. Thirdly, cellular pathways consist of a sequence of reactions. If a specific molecular target is blocked or altered in this chain of events, bypass mechanisms may occur. These challenges require for their resolution further research.

Personalised Medicine is Science Driven

Personalised medicine requires a fundamental change in our comprehension of diseases. Many traditional diagnoses may have to be revised. In the future we should be able to identify underlying molecular disease mechanisms more precisely, and in consequence make more effective treatment decisions. However, despite all this progress we may not succeed in identifying the underlying mechanisms for all diseases and biomarkers alone may not be sufficient to diagnose all diseases. It is inevitable that disease classifications and diagnoses will continue to require combinations of molecular and phenotypic classifications.

The right diagnosis will lead to the right treatment. Personalised medicine offers a more scientific approach to diagnosing and classifying diseases, and in consequence will lead to more effective treatment decisions for individual patients.

Click here for the next chapter in this series, where you’ll learn how the search for predictive biomarkers is likely to change drug development research.

Detlef Niese, M.D., Ph.D., is head of development, external affairs at Novartis. The author of the introduction is Tim Kievits, managing director of PamGene and chair of the EuropaBio Task Force on Personalised Medicine.

EuropaBio represents 56 corporate members and 14 associate members and BIO regions, and 19 national biotechnology associations who in turn represent some 1800 small and medium sized biotech companies in Europe. Members of EuropaBio are involved in research, development, testing, manufacturing and commercialisation of biotechnology products and processes. Our corporate members have a wide range of activities: human and animal health care, diagnostics, bio-informatics, chemicals, crop protection, agriculture, food and environmental products and services.

This article first appeared as chapter 1 of a white paper published by the EuropaBio Personalised Medicine Taskforce entitled “Personalised Medicine: Status Quo and Challenges”.

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