The Lifetime Initiative released a roadmap to revolutionize health care in Europe by implementing cell-based interceptive medicine in a perspective article published Sept. 7 in Nature. The group aims to change the point at which medical care intervenes from symptom onset to when cells first diverge from a healthy path by developing an integrated, pan-European platform that leverages single cell multi-omics and imaging, artificial intelligence/machine learning, and patient-derived experimental and computational disease models – all within the next decade and for the tidy sum of €1 billion (US$1.3 billion).

The Lifetime Initiative arose from the combined efforts of more than 100 European institutions and medical centers as well as 80 private companies, European scientific societies, and research funding organizations to more effectively prevent and treat disease, improve quality of life, stimulate the European economy and secure leadership in cell-based interceptive medicine.

“What we are trying to do is detect disease much earlier than ever and use technology to discover how to bring cells from disease path back to health,” Nikolaus Rajewsky, scientific director of the Berlin Institute for Medical System Biology at the Max Delbrueck Center for Molecular Medicine and coordinator of the Lifetime Initiative, told BioWorld.

Transformative technology

Achieving these lofty goals depends on at least four technological advances. The first is a huge task, developing AI or machine learning technology that can integrate spatial multi-omics, imaging, and other data from existing databases distributed across multiple countries.

“I don’t doubt this will be accomplished,” Rajewsky said. “The current state of machine learning is to detect complex patterns in the data, however, we are also developing approaches where machine learning can identify good causal models to explain data, predict causes and consequences of disease. This will be an incredibly powerful tool to develop new therapies and intercept the disease course.”

Secondly, the project requires integrating analysis of genomes, proteomes, lipidomes, transcriptomes, epigenomes, metabolomes and more into a comprehensive view that will reveal the diversity of cell subtypes and states and their surrounding environment to reveal critical information on the changes in cell composition associated with diseases. That, Rajewsky said, will provide “information on how cells make decisions, why they are becoming sick, and how to target them to bring them back to health.”

Advances in CRISPR-Cas9 that make gene editing easier and safer to prevent or treat disease are also needed. Currently, the editing process can produce unintended effects as a result of off-target DNA changes. The size of the CRISPR-Cas9 molecular complex can also make delivery of the tool challenging.

Personalized organoids will also be central to the endeavor. “If we can grow in a lab an organoid from an individual that mimics the colon of the person, we can try compounds on that organoid without experimenting on the person,” Rajewsky explained. That allows maximum customization of therapies and testing of response without exposing the patient to potentially toxic side effects.

Disease priorities

The Lifetime Initiative focuses on five major disease classes: cancer, neurological, infectious, chronic inflammatory, and cardiovascular diseases. “We have developed a mechanism to select diseases particularly suited to our approach. Some diseases are very difficult to approach with this method, others are more amenable. We have created a clinical launchpad where experts from various disciplines come together to determine which ones to start,” Rajewsky noted. “We also looked at how many patients are affected and how big would be the difference to existing approaches.”

Of the five disease classes selected, cancer and infectious diseases may be the closest to being able to implement cell-based interceptive medicine today. That bodes well for using the technology the initiative is developing to better understand COVID-19 as well over the next few years. Lifetime has assembled a core task force to identify appropriate short-term and long-term measures to study the disease and created a registry with the Human Cell Atlas to track resources, knowledge and new developments in the ongoing battle against SARS-CoV-2.

Creating a platform to better understand COVID-19 increases the already significant value of the undertaking. "By implementing interceptive, cell-based medicine we will be able to considerably improve treatment across many diseases,” said Lifetime Initiative Co-coordinator Geneviève Almouzni, director of research at CNRS, honorary director of the research center from Institut Curie in Paris. “Patients all over the world will be able to lead longer, healthier lives. The economic impact could be tremendous with billions of Euros saved from productivity gains simply for cancer, and significantly shortened ICU stays for COVID-19. We hope EU leaders will realize we have to invest in the necessary research now."

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