Nobel Laureate Professor Aaron Ciechanover : personalized medicine is already here, and it is Complex

 “Unlike humans, laboratory mice do not get depressed, don’t laugh at jokes and don’t choose the food they eat. Because of these profound differences, the transition from experimentation on rodents to treatment of humans is a complex one, which creates a bottle-neck in the development of new drugs and advanced therapies.”

Professor Aaron Ciechanover, a faculty member of the Ruth and Bruce Faculty of Medicine and Nobel Laureate in Chemistry (2004), is convinced that personalized medicine will be the next major revolution in the medical world – and will change the way medicine treats diseases. “Medicine today knows how to cure mice from cancer, but the same treatment doesn’t always work well on humans, since each person responds differently to a given drug. For example, we give the same treatment to all breast cancer patients, and are surprised when some of them are cured while others die. The reasons for these differences are because we are not well equipped with the right eyeglasses, and therefore, we fall into making false generalizations.”

Give an example.

If we are treating two breast cancer patients – one 30 years old from Ashkenazi  origins of a certain blood type, and the other 60 years old from Middle Eastern descent with a different blood type – we must understand that each patient is actually  afflicted with a different disease. Personalized medicine will equip us with more sophisticated eyeglasses, ones with a higher resolution of genetic variables and data relating to nutrition, origins and blood type, which will enable us to give each patient the right treatment.

Is it a real revolution?

Absolutely. Personalized medicine is the third revolution, after the revolution of pharmaceutical and biomedical research breakthroughs. The first revolution – the birth of the modern science of pharmacology – began by random drug discovery. For example, aspirin, developed for the purpose of providing pain relief and reducing fever, later became known for affectively preventing blood clotting and therefore protects people after heart attack. Moreover, because it inhibits inflammatory processes, it also prevents certain types of cancer. This is a drug that has become part of many people’s daily lives and in fact, is a “best-seller” (“the blockbuster”) of the drug world. As a drug, it was “discovered” anew by Felix Hoffmann, who knew of its pain relieving properties, produced it, and successfully treated his father’s rheumatoid arthritis.

Another significant revolutionary drug is none other than penicillin, the “father” of antibiotics. Penicillin was discovered by chance, by Sir Alexander Fleming when he returned from a vacation and found a fungus in a Petri dish left open on the table. This discovery changed the face of World War II in terms of mortality from war wounds, and today the use of antibiotics has become an integral part of our lives.

And the second revolution?

This is the revolution of chemistry which brought the world new tools for diagnosis and treatment. Many of the drugs and diagnostic tools were developed using mass  scanning of many chemical compounds in search of specific inhibitors to pathologic factors (enzymes, for example) that underlie the pathogenesis of diseases(for example, this is how statins that lower cholesterol were discovered), while others  were developed through more directed efforts such as analysis of protein structure and fitting modulators to the structure, development of antibodies, , etc.

So what tidings does the third revolution bring?

Personalized medicine will bridge engineering development and biology, which is trailing behind it, and is significant because it will change the face of medicine as we know it.

In what way?

Firstly, personalized medicine will zero-in on the disease of the patient. Instead of treating the disease, as is done today, we’ll treat the patient. Prior to giving treatment, a comprehensive characterization will be done on a patient, including genetic analysis and mapping of all relevant variables, such as proteins and metabolic outcomes. All this is possible on the account of the breakthroughs in the area of the genome.

Please Explain.

The first human genome was revealed in April 2000, after seven years of decoding work and an investment of close to a billion dollars. Since then only twelve years have passed, and soon we will be able to sequence a person’s genome in a few hours and at cost of hundreds of dollars only – much like the cost and time currently required today for MRI testing. This will almost become much like a routine check-up at a medical clinic or in the emergency room.

This sequencing, along with additional data pertaining to proteins, etc., will give us a very precise profile of a patient’s condition. This will be a quantum leap in diagnostic quality, which will lead to a significant efficacy improvement on a given course of treatment on a patient.

Are there other implications for “personalized medicine?”

Certainly. And it has already been named thefour P’s medicine: Personalized,  Predictive,  Preventive and Participatory. This term was coined by the father of this revolution, Professor Leroy Hood. In addition to its being personalized, it will also be predictive – it will tell us what diseases we can expect to be diagnosed with based on our genetic profile and according to other data. It will allow us to predict the interaction between patients and drugs, and thereby prevent many side-effects. It is important to note that side-effects are the sixth leading cause of deaths in hospitals today.

Thirdly, based on the predictive element previously mentioned, sophisticated preventative medicine will develop; fourthly, this will become a form of participatory medicine, in other words, patients will play a greater role in making decisions regarding his/her ailment, based on the information provided by their medical team.

So the patient will be able to decide?

The era of “I am the doctor here, trust me, ” has come to an end for many reasons, namely due to the availability of information (like the Internet) and the spread of lawsuits against doctors. The doctors of the future will be more like consultants, who will transfer significantly more responsibility about treatment decisions to the patient and their families.

And so medicine will become more humane?

Absolutely not. This is the mistake of romantics and social scientists. On the contrary, personalized medicine may become more technical and less humane. It will be more accurate, and will provide doctors with unprecedented tools to treat the specific illness of their patient, but no, it probably won’t be more humane.

It’s not so bad if it will eliminate all diseases.

We should not mislead ourselves by such illusions. We are dealing with complex processes, that we may never know the “side-effects” in its broadest sense. And even if this medicine can prolong our lives, we must understand that there is a price tag to it.

Which is?

In the past, people died because of simple infections. In the last century the world was introduced to antibiotics, vaccines, sophisticated diagnostic tools, surgical intervention options, and better understanding of dietary risk factors, hygiene and sanitation – small revolutions and discoveries that changed the world of medicine and extended our life span drastically.

 

How drastically?

For 4, 000 years, the lifespan of humans has increased about twenty years (from 30 to 50 years of age), then, in the twentieth century alone, it grew by an additional thirty years. In other words, in one century life expectancy increased more than in the thousands of years before it.

What about the price tag?

We all want to live a good long life, and every report on prolonged life extension delights us, but it is important to understand that such developments extracts a high price. Successes we have had in eradicating diseases in the twentieth century have given rise to “new diseases” such as neurodegenerative diseases including Alzheimer’s and Parkinson’s, which strips the soul from the body, and other degenerative diseases such as cancers and vascular diseases. Consequently, the new revolution, the revolution of personalized medicine, is heavy-laden with landmines, and I’m afraid it will not bring an end to diseases.

What are the major challenges in the medical field?

The most complex challenges will be in handling multiple genetic disorders, including mental illnesses. Mental illnesses are very complex disorders, and we still don’t know much about the physical mechanisms that trigger them. Today, we are only beginning to understand the interactions between genetics and autism, but there is a long way ahead of us still.

What major problems will the third medical revolution bring?

I believe that the problems ushered in by this new revolution are mainly social, religious and bio-ethical rather than purely scientific-medical. As previously mentioned, the future of medicine will be able to better predict anticiated diseases – but what do we do with this knowledge? If we perform a mastectomy on a cancer patient, and then reveal that she is a carrier of a gene that makes her susceptible to breast and ovarian cancer, will we recommend that she undergo a double mastectomy? Do we stop here or urge her to undergo an oophorectomy (ovary removal surgery)? Will we advise her to warn her daughters that they may be carriers of the same gene? Or is the correct mortal imperative to settle the specific surgical cure and not add “non-relevant” information to the discussion of treatment. Is this really irrelevant information?

Do you mean to say that information is a landmine?

In many cases in life, it seems as if lack of knowing and uncertainty is intolerable. In medicine, this may be the opposite: certainty is insufferable, and ambiguity protects us. Not knowing our fate – the fact that we don’t know what is written about us in the “Book of Life” – this is an important part of the stability factors in our lives.  For as long as personalized medicine will advance, our destiny will or may (depending on the eye of the beholder) lose its providence, and very quickly we will discover that knowing the future is a heavy burden. In summary, we have new abilities, but we still don’t have the means by which to deal with their consequences.

Distinguished Professor Aaron Ciechanover gave a lecture on “Personalized Medicine” at a joint symposium held by the Technion’s Ruth and Bruce Rappaport Faculty of Medicine and the Department of Occupational Therapy of the University of Haifa. 

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