New Paradigms and the Future of Medicine

What is the future of medicine and how will we get there? On Monday morning, as part of New Horizons of Science at Yale, Director of Institutes of Systems Biology Lee Hood discussed the advent of 21st-century medicine: p4 medicine.

What are paradigm changes in biology leading to p4, or proactive medicine? There are several changes needed and all overlap and interconnect, but the main drivers in the process are:

– bringing engineering to biology through high throughput biology
– the human genome project
– cross-disciplinary biology
– systems biology

“What’s fascinating is that these four paradigm changes are creating a new foundation in medicine,” says Dr. Hood. “And they were each met with skepticism.”

What does p4 medicine represent? predictive, preventive, personalized, participatory (p4). In other words, it’s the taking of genomics and systems biology to finally unravel the complexity of pathology and seeking out preventive and personalized strategies of healthcare.

When Hood was at Caltech, he realized that he would be working on new bioinformatics technologies. At the time, they had known about DNA, RNA, proteins — but with technology, he realized, they could transform how to understand biology.

His team created five instruments that changed biology. The instruments were automated (in collecting data), integrated information, and served to produce new ways of understanding biology.

The first instrument he produced was a protein sequencer, two hundred times more sensitive than other instruments. With it, they found the first “cancer gene,” a platelet-derived growth factor. It sequenced prions related to Mad Cow Disease. It sequenced the first billion-dollar biotechnology product, epo. Also, it discovered the first blood development factor.

Why not commercialize the instruments? Hood pitched this to the University, but was told, “It’s not the role of Academia”. So, he went out to sell it himself. There have now been 14 companies founded by Hood Labs.

He discussed the human genome projecg and how, in Spring 1985, his bioinformatics technologies helped shape the feasibility of the challenge in the face of opponents who were “vehemently against” the project — because it would take a way from “legitimate science” (including the National Institutes of Health).

Why has the genome project transformed biology? It provides complete parts of gene lists, transforms biology by providing access to genomics of species, and increases understanding of evolution, understanding of nutrition, and understanding of medicine.

Another instrument, the DNA sequencer, helped bring forth a cross-disciplinary approach of meeting current medical challenges — merging chemistry, biology, mathematics, molecular biotechnology. The first cross-disciplinary department, at University of Washington, pioneered the new field of proteomics.

The problem with biology and systems biology is that it’s “way too complex,” but moving into the 21st century, scientists now have the computational and mathematical tools to turn biology into an informational science. Then, taking a systems approach, p4 medicine can attack vexing challenges of healthcare.

“If you think of yourself as a living creature, there are two types of information” that make you — digital information about your genome, and environmental imprints — the genotype and phenotype.

“It’s a combination of these two types of information that leads to most diseases,” Hood says. We need to think about the relationships between the two sets of information to effectively solve disease.

How you think about systems biology is critical: you need to be able to integrate data types, delineate biological networks, acquire global data, and formulate models for “discovery science.”

The agenda: Use biology to drive technology and computation needed to create a cross-disciplinary approach to biology.

The Institutes for Systems Biology has just had its 10th anniversary. Back in 2000 when Hood first started the institute there was a lot of skepticism, but now there are 70 more institutes worldwide.

In short, the impact made by systems biology and a computational and systems approach to disease is grand — it’s the approach of seeing etiology of disease as altered biological networks.

He shows how his technologies compute the dynamics of a brain network in prion disease in mice. They found four networks involved in the disease. There about 300 genes in a mouse, two thirds mapped into the networks.

Going on, Hood explains that blood is a window into health and disease with systems diagnosis to identify key network nodal points for early detection, prevention, treatment. In the future, we should have complete genome sequencing of families, the human proteome project, the second human genome project.

Family genome sequencing has itself demonstrated that scientists can use principles of Mendellian genetics to identify 70 percent of sequencing errors, discover variants, and more rapidly find genetic encoding that leads to disease.

What about the future? “One of the most revolutionary biology fields is single-cell analysis,” Hood says. This is along with stem cells and computational, systems, integrative biology.

Concluding, he says, there needs to be a transition in healthcare to p4 medicine, so ISB has set up partnerships for “inventing the future.” They will be creating 21st century biomedicine involving systems analysis of biology and medicine, technology development, and preventive strategies.

“P4 medicine is about 1) wellness and 2) demystifying disease,” Hood says, noting that the ultimate solution is prevention by using systems biology and bioinformatics technologies.

In the Q&A part after this talk, it was asked “when will we reach the p4 zone?” and Hood replied that there are several examples of companies that are reaching this point (and he names 23andme as a pioneer).

Some day, with Hood’s leadership and technologies, our own complex biologies will be hacked, reduced to information, for the development of healthcare strategies built around personalized medicine.

If interested in following p4 medicine as it grows in acceptance, check out ISB’s newsroom

Location:Temple St,New Haven,United States

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