Personalized Medicine Changes the View on Disease – and Ourselves

When anyone of us is confronted with a cancer diagnosis, we want the best possible care. Nowadays, doctors often test the tumor’s genome, its receptors and its sensitivity to antibody treatment. Forty years ago, there were only ‘one size fits all’ cancer treatments – some patients survived, many died. Today doctors can not only treat the tumor, but can also predict which drug will be most likely to prevent the cancer from coming back; for this, the patient’s genome needs to be analyzed. This is what personalized medicine is all about: treating each patient with a drug that fits this patient’s genotype as well as possible. Nobel laureate Aaron Ciechanover called it the third revolution of drug research, after the serendipitous finding of medicines like penicillin and the methodical search for target substances since the 1970s.
Aaron Ciechanover, Nobel Prize in Chemistry 2004, calls personalized medicine the 'third revolution' in drug research, #lnlm14. Photo:

Aaron Ciechanover, Nobel Prize in Chemistry 2004, characterizes 21st century medicine with four P’s: it’s personalized, predictive, preventive – and it should be participatory. #lnlm14, Photo: Ch. Flemming, Lindau Nobel Laureate Meetings

But analyzing complete genomes, a procedure that gets cheaper every month, has side effects. Last year, actress Angelina Jolie shocked the world by revealing her double preventive mastectomy. Genetic tests had revealed a mutation in her gene BCRA1, meaning a 87 percent likelihood for her to develop breast cancer, and a 50 percent chance for ovarian cancer – her mother had died of this disease aged 56. Now, after the operation, her breast cancer probability has dropped below five percent. This mutation is quite rare and well studied; BRCA mutations account for fewer than five percent of all breast cancer cases. But families with a mutation like this have usually suffered in the past, having seen numerous women die at a young age. Ms. Jolie says herself, ‘Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.’
Ms Angelina Jolie at the launch of the UK initiative on preventing sexual violence in conflict, 29 May 2012. Photo: Foreign and Commonwealth Office 2012, Creative Commons

Angelina Jolie is not only an Oscar-winning actress and director, she is also a UN special envoy: here, she talks at the launch of the UK initiative on preventing sexual violence in conflict in May 2012. One year later, she made her double preventive mastectomy public. Photo: Foreign and Commonwealth Office 2012, Creative Commons

When talking about preventive genetic testing, the one concern most often voiced is: What about the right not to know? Some people want to know all their risk factors and act accordingly, like Ms. Jolie. Others are happier not knowing, taking on each challenge as it comes. But if many family members have been diagnosed with a potentially dangerous mutation – each close relative will know. How will people cope with this unwanted information? And will insurers or government agencies get their hands on these data sooner or later? For the US, the Genetic Information Nondiscrimination Act (GINA) is supposed to protect citizens’ data, and the Supreme Court has ruled last year that natural genes cannot be patented. But since scientific progress moves forward, concerns for genetic privacy prevail – new tests or therapies often require new regulations. Aaron Ciechanover summarizes, ‘It seems that diagnostic technologies are always preceding our ability to handle them.’
Aaron Ciechanover stresses the importance of genetic information protection, because 'personalized medicine penetrates into the most sensitive layer of our existence.' #lnlm14, Photo: Ch. Flemming

Aaron Ciechanover stresses the importance of genetic privacy, because ‘personalized medicine penetrates into the most sensitive layer of our existence.’ #lnlm14, Photo: Ch. Flemming/Lindau Nobel Laureate Meetings

And what about patients who cannot understand probability calculations? Will a positive test make them severely depressed, or even seek extreme measures that are not adequate in their case? Or will a negative result make them careless, missing medical checkups or having an unhealthy lifestyle? Not only patients face new challenges – some doctors have difficulties presenting this kind of information comprehensively and sensitively. Furthermore, conscientious doctors need to research each single case: Does this drug fit my patient’s genotype? Is it even approved for it? (Yes, FDA approvals might be limited to certain genotypes these days.) But even if the drug label specifies a genotype, it often doesn’t name the appropriate dosage. When correct genetic tests can result in major problems for everybody involved – what about inaccurate tests? At the moment, several political debates concentrate on the regulation of genetic tests, since they are considered medicine devices, not drugs, and don’t even need to be subjected to clinical trials. The debate in the US and the EU is ongoing. Despite all challenges, healthcare is moving inexorably in the direction of personalized medicine – and questions like the ones asked here will become ubiquitous. Ciechanover describes the present-day situation as a ‘twilight zone’, ‘We know what we have, but we don’t know what to do about it.’ But if we still want the best possible care, we have to start looking for answers. Nobel laureate Aaron Ciechanover on the history of drug development and his views about 21st century medicine in Lindau:
Susanne Dambeck

About Susanne Dambeck

Susanne Dambeck is a science writer in English and German, and author of several nonfiction childrens' books. A political scientist by training, she has worked in politics, television and as a biographer. Apart from scientific findings, she is interested in people and in storytelling in different languages.

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3 comments on “Personalized Medicine Changes the View on Disease – and Ourselves

  • This is one fine lecture.

    About 22 minutes into his presentation, Dr. Ciechanover presents a slide that lists seven technical issues.

    To this we need to add an eighth technical issue – clinical trial design.

    Prevailing randomized controlled trial (RCT) designs date back to 1948 – streptomycin for TB.

    These RCT designs were a breakthrough for their time. However, such designs evaluate treatments and their effects largely one by one and use group averages in a way that washes out the effects of individuality. Such designs often fail because they do not investigate patients and other people as the unique individual complex adaptive systems that they really are.

    This technical issue now has a specific scientific and technical solution. This solution is to apply a computational algorithm, embodied in software. It applies best when to time series data for two or more variables about one individual. These variables can be either (i) internal to or characteristic of the individual or (ii) part of the individual’s environment. Treatments are environmental variables delivered with therapeutic intent.

    DataSpeaks software provides inherently standardized scores that quantify the amount and the positive or negative direction of evidence for interactions over time. These scores describe and help predict how the individual works over time.

    For diagnosis, DataSpeaks often can provide more objective, specific, mechanistic, and actionable diagnoses of many chronic functional disorders.

    Benefit and harm scores are a variation of interaction over time scores that apply when evaluators know the toward and untoward directionalities of response variables. As examples, higher levels of good cholesterol and human functioning are beneficial while higher levels of disturbing signs and symptoms are harmful.

    DataSpeaks can enable benefit and harm scores that are reliable, valid, detailed, and comprehensive of multiple treatment effects for each individual patient. The current version of DataSpeaks software can do this for up to 8 analysis parameters simultaneously – dose, response variable level, and up to six optional analysis parameters to investigate temporal dynamics. To help assure that these scores are valid, it is best to randomized doses over time for each individual.

    DataSpeaks provides scores that are well suited for statistical analyses when there are two or more individuals.

    Accordingly, many group RCTs can be conducted as coordinated sets of advanced design single patient or N of 1 RCTs. Doing so would help integrate clinical research and practice in ways that help obviate the translation problem. This also would speed drug development. We can provide better outcomes at lower cost.

    Clinical trials conducted to evaluate safety and efficacy would begin by measuring benefit and harm starting at the level of each individual. Conventional RCT designs do not actually measure benefit and harm.

    The resulting scores can help identify what genetic differences mean. DataSpeaks can help advance P4 Medicine.

    DataSpeaks can help enable the vision so adequately presented by Dr. Ciechanover.

  • Eli Baine says:

    Thank you so much for sharing this information. With all of the advances in technology and medicine it is natural that our medicine is becoming more personalized. Every case is different and doctors need to be flexible and expand their possibilities for treatment. I am glad to see that private care centers are growing so as to alleviate the number of patients in hospitals where they would receive less personalized care.
    Eli |

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