Right on target
US President Barack Obama recently pledged $215m for his precision medicine initiative. Danielle Barron discusses the future of precision medicine with InnVentis founder and CEO Thomas Wilckens, and examines the impact this will have on the current R&D environment.
“The right treatments at the right time, every time, to the right person.”
This sounds like the Holy Grail when it comes to delivering solutions to the myriad health problems of the modern world. Yet the above quote wasn’t uttered by a benevolent character in a futuristic science fiction film about the survival of the human race – it was US President Barack Obama who said it in January of this year as part of his State of the Union address.
Obama is proposing to spend $215 million on a precision medicine initiative, centered on a national study involving the health records and DNA of one million volunteers. His landmark announcement made waves throughout the political, medical and scientific communities, as the goal to deliver the most beneficial treatment to the right patient based on their genetic information became national policy.
The blunderbuss approach of many contemporary medical treatments means that a positive outcome is dependent on the individual and the shortcomings of population-based medicine have been well-documented. Drilling down what makes a person a successful candidate for a particular treatment is the new goal, and this effort began as soon as the miles of genetic code from the Human Genome Project began to be examined and elucidated.
Precision medicine, the term for which was coined by Harvard Business School Professor Clayton Christensen in 2008, promises to target therapy to those who will benefit most from it, based on knowledge of their genetic profile. Yet many critics say the Human Genome Project has essentially failed to deliver on its initial promises of new cures and better outcomes.
Too much, too fast
Thomas Wilckens, founder and CEO of InnVentis, a new company enabling precision medicine, rejects the assertion that the mapping of the human genome hasn’t been the gateway to disease cures that was originally envisioned. It is Wilckens’ belief that people expected too much, too fast.
“I would like to challenge that contention. A lot of people would say Craig Venter [one of the first to sequence the human genome] didn’t really deliver on promise but these people completely disregard that he has opened up a whole new era in biotech and a whole industry has basically been built on his pioneering work. I think he delivered more than one could ever have anticipated. However, what people disregard is that this is always a learning curve and apparently the expectations were too high, for too fast a return. When it comes to genomics now we do see the returns – they just weren’t within five years, they happened in 10 years.”
According to Wilckens, the convergence of spectator analysis, machine learning and artificial intelligence with multi-omics technologies has finally occurred, with the potential to enable an acute understanding of disease phenotypes.
Wilckens is now anticipating a “significant disruption” in the manner in which research and development is pursued and carried out. Yet he feels the integration of novel technologies with the historical academic input is lagging behind and will be a key barrier to the embedding of a precision medicine approach in the wider healthcare and medical research sphere.
“The only concern that I have is that I think the processes become so complex in a way that some R&D processes that are set up to deliver new approaches to prevent disease and eventually interfere with them in a more specific way are not suitable for an academic scenario. The reason for that is very simple; the technological conversions place new challenges on how we actually design and build discovery engines for example,” he explains, adding that this is beyond the capabilities of the average post-doctoral researcher.
“The leaders in these academic institutions are sometimes overwhelmed with bureaucracy and politics as well as everyday clinical obligations if we talk about MDs, so I think this needs to be guided by people with a long-standing experience in building the kind of platform technologies that eventually deliver new insights.” Wilckens adds that the current academic scenario can mean that data can be lost, for example when a researcher leaves to work in a different institution, i.e. the protocol for a given analytics technology might change. He sees this as an inherent risk to precision medicine.
“One of the main challenges is the divide between the world of the number crunchers and the world of academia.”
As the delivery of medicine becomes ever more precise as diseases are classified by their genetic and phenotypic (multi-omics) subtypes, smaller patient cohorts will eventually benefit from each treatment. This paradigm shift from the blockbuster drug days of yore will be hard to effect. Another problem is interpretability – understanding complex datasets will require an embedding of molecular, multi-omics derived diagnostics within everyday clinical care.
Other immediate challenges to precision medicine include funding, the acquisition of enough data to make meaningful diagnoses and to create accurate sets of subpopulations, and data analysis. Ensuring confidentiality of sensitive information is also a major concern.
We have this inherent bias but now with precision medicine there is a unique opportunity to approach conditions like rheumatoid arthritis without bias and without some kind of a hypothesis, and instead just look at the molecular basis of conditions that eventually somehow lead to a common syndrome".
”Writing in the New York Times, Mayo Clinic physician-researcher Michael Joyner called it a “moon-shot” medical research project, saying: "Unfortunately, precision medicine is unlikely to make most of us healthier." Wilckens refutes this, saying precision medicine is no match for human nature.
“The biggest obstacle to human health is the human being and their behavior. If we don’t change human behavior then we will not be able to get some of the major non-communicable diseases under control. Having said that, and it’s very cynical, knowing that we won’t change our behavior is exactly part of the opportunity for pharmaceuticals and nutraceutical companies to come up with interventions that allow us to live “sinful”, or at least somewhat sinful, lives. That is human nature. Deciphering the complexity of disease development, with disease often being bad luck is the other, even bigger opportunity for precision medicine.”
In order to create the most effective interventions, the pharmaceutical industry must change its fundamental view of common conditions. According to Wilckens, there is an “inherent bias”, which must be disputed as part of a precision medicine approach to treatment.
“My favourite example is rheumatoid arthritis. We continue to pretend that we know what arthritis is. The fact that most drugs only work for 10 to 20 or 30 per cent of patients and after some time they don’t work at all anymore suggest that we actually are talking about a syndrome. We have this inherent bias but now with precision medicine there is a unique opportunity to approach conditions like rheumatoid arthritis without bias and without some kind of a hypothesis, and instead just look at the molecular basis of conditions that eventually somehow lead to a common syndrome.”
Dogmas and errors
This will serve to remove what Wilckens says are long-perpetrated dogmas and errors in the way that common diseases are addressed. He is quick to differentiate the concept of precision medicine from the much-lauded “personalized medicine” approach, which he says was a misleading title given to the new era of more specifically targeted therapies.
“People often confuse precision medicine as being interchangeable with personalized medicine but that is rubbish. That is a very different paradigm introduced by an economist that was analyzing the needs of the healthcare system. While drugs will become more precisely targeted to the person, that doesn’t mean that every person gets their own drug – that is ridiculous. But we will be able to stratify cohorts much more precisely, particularly when we examine the different phenotypes, and diagnostics and therapeutic decision with be guided by algorithms.”
That work is starting in earnest as you read this, and companies such as Craig Venter’s Human Longevity,Google’s Calico, Foundation Medicine and soon Wilckens’ InnVentis, are leading the pack. Wilckens says the work they are doing will have a profound impact on the evolution of the pharmaceutical industry and drug development and will lead to a paradigm shift in R&D.
“I can tell you from the feedback we get from senior executives in big pharma companies about our business model that this is exactly the way precision medicine will evolve.”
If you look at the way large pharma companies are pursuing their internal research projects, there is a very rigid protocol – I actually know of a case here in Munich where a large pharma company is bringing in the people to make sure blood is being taken in a highly standardized manner. It makes a difference depending on whether you sit or if you lie down when looking at a metabolomics analysis".
As Wilckens emphasizes, reliable and valid data is needed in order to create new products and services, but is this data only as reliable as the person interpreting it? What about persuading a new generation of doctors to specialize in genetics and not disease areas?
“If you look at the way large pharma companies are pursuing their internal research projects, there is a very rigid protocol – I actually know of a case here in Munich where a large pharma company is bringing in the people to make sure blood is being taken in a highly standardized manner. It makes a difference depending on whether you sit or if you lie down when looking at a metabolomics analysis.
“Can you expect an MD to take during his or her busy daily routine to even consider that? Should post-docs and students do this? No. You have to have a different way – we have to make sure there is a very rigid integration of standard operation procedures (SOPs) in the way that we collect samples for analysis, including those in academic centers. Studies have to become not only reproducible, but also comparable, a major challenge. It is just that the system right now has an inherent bias that we too often fail in our approach to designing experiments. With regard to actionable information for MDs, we don’t necessarily need differently educated doctors – we need tools that are well designed and can actually integrate data so they are appropriately visualized and MDs and decision makers can instantly see that something is different, ideally with content to enable precise decisions.”
This doesn’t mean “death by data” for medicine, either. Wilckens acknowledges that even with artificial intelligence, the human brain is far better at recognizing outliers or relegating dubious findings from machines. He also admits that the mobile information technologies required for precision medicine must be developed in a cohesive fashion, and this represents a further challenge for the field.
“The whole life sciences and biomedical community needs its own ICT architecture for a myriad of reasons. The complexity of the data and the challenges regarding safety and security are significantly more complex and difficult than it is for an industrial financial project. That is one of the major challenges that needs to be tackled. We have all the building blocks – the technologies and analytics methods like machine learning and so forth are there.”
“Google with all their experience are probably leading the way in terms of intelligent data analysis. The way we explore data and the way we share data needs to find scalable solutions also in a way that it is integrated and ideally not different silos across in the world. It makes things a lot more complicated. Pharma, biotech, companies like Google, HP, IBM, Intel… that is a major challenge to come to standardized solutions.”
A new audience
So what does Wilckens think of Obama’s precision medicine initiative? Met with scepticism in some quarters, it has nonetheless brought the concept to a whole new audience. Wilckens says it will have a major impact on the profile of precision medicine and cautions naysayers and cynics to hold their tongue for now.
“People making criticisms should first of all look at the impact that his message has worldwide, not just in the US, in putting precision medicine on the radar of the media of funding agencies and of the wider industry. He cannot be thanked enough for putting that alongside national security in his address to the nation! It is even helping us here in Germany – people were not talking about precision medicine until very recently when they read about it in the newspapers.
“We need more support, more funding, and more awareness for the needs and challenges facing society regarding healthcare. I think that this is a tremendous step forward in a new era where we will see disruption by precision medicine and related R&D as well as new business models.”
Wilckens says that while Obama should be given due credit for creating heightened public awareness of precision medicine, however, the movement is self-propagating.The proof is already there, he says, for how algorithms will replace intuition or evidence-based decision making with data driven, and machine learning/artificial intelligence supported systems. In short, the road to precision medicine is one way traffic.
“He is helping to push things a bit more in this direction but the trend is inevitably there. We started building InnVentis as a scalable R&D platform and business model from technology convergence 2 years ago and this is in line with a trend which is simply evolving from within itself because we need new methods to harvest and analyse mass (omics) data to enable precision medicine, so it is inevitable.”
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