Why you should care

As cellular reprogramming and genome editing converge, the combination could have the same kind of impact that drove the Silicon Valley tech revolution.

Consider the transistor, the integrated circuit and the silicon chip — not one but three technologies that converged only a few years ago. Add the efforts of clever programmers, engineers, visionaries, designers and capitalists. Stir well and, voila, our everyday world and the nature of social interactions changed forever.

Artistic rendering of yellow, red, blue and green cells.

In 2006, the Yamanaka lab identified four factors that, when co-transfected and expressed in mouse adult fibroblast cells, caused those fibroblasts to revert back to a pluripotent like state.

Source Stem Cell Schoool

Now consider the life sciences, where we have yet to experience a broad-based technology-driven transformation to rival what the information technology (IT) sector has wrought. In the last century, we made great strides in improving human health and longevity, thanks to everything from indoor plumbing to mass immunizations. But the recent retreat of both federal funding and venture capital from the life sciences sector signals a societal disappointment rather than excitement over what can come next.

As cellular reprogramming and genome editing converge, the combination could have the same kind of impact that drove the Silicon Valley tech revolution.

That could soon change. As cellular reprogramming and genome editing converge, the combination could have the same kind of impact that drove the Silicon Valley tech revolution. To illustrate, let’s look at how 4 + 9 = $600 billion. The number 4 refers to the “Yamanaka factors” used to coax very ordinary human skin cells to become the most special cells of all — pluripotent stem cells from which all the various cells and tissues of our bodies are derived. Shinya Yamanaka discovered that the developmental fate of a human cell — to be a heart, brain or liver cell, for example — is not irreversible, but can be controlled by manipulating the function of only four genes.

Scientists all over the world are using cellular reprogramming technologies (not always with four genes) for a variety of important purposes, one of which is to create authentic models of human disease within the laboratory. For example neuroscientist Yadong Huang converts skin cells derived from patients with genetically determined Alzheimer’s disease (AD) into brain cells, which then proceed to undergo pathological changes that mirror what happens in the intact brain. By comparing these to brain cells derived from normal individuals, we can open new doors to discover drugs for preventing AD, a formidably challenging area of medical research in which all efforts up to now have failed.

What makes Cas9 so special is its ability to be directed to a specific site in the genome.

The number 9 stands for Cas9, a bacterial protein that forms the basis for several emerging technologies to edit or control our genes with unprecedented precision and dexterity. Comparing any two human beings or their cells brings into play, on average, differences in about a million places in their two genomes, thereby muddying the waters for those seeking to discover new drugs.

Enter Cas9, a protein that cuts DNA, not in itself a unique property. But what makes Cas9 so special is its ability to be directed to a specific site in the genome by a “guide RNA,” a property that provides genetic engineers with something like a laser beam instead of a shotgun blast with which to engineer genes.

These new tools can be exceptionally valuable to life scientists tackling the really tough stuff like Alzheimer’s disease.

Jennifer Doudna has created a Cas9-based technology called CRISPR that makes it possible to correct disease-causing mutations in cells by reprogramming to produce what are called “isogenic controls.” This means that the diseased cells have exactly the same genome as the normal cells, except for the disease-causing mutation, thereby providing a much more powerful starting point for drug discovery. Newer technologies based on Cas9 being pioneered by Stanley Qi and others allow scientists to turn specific genes on or off at will (see Ill-fitting Genes). When combined with cellular reprogramming, these cool new tools can be exceptionally valuable to life scientists tackling the really tough stuff like AD.

The number $600 billion is half of the $1.2 trillion per year that we should expect to pay for the medical care of AD patients in the U.S. by 2050 if no effective measures can be found to prevent this grim and untamed malady. That’s more than $3,000 every year from every American. New drugs effective enough to work in even half of the individuals who otherwise would become enfeebled by AD would cut that figure in half when they become available by 2020. Discovering such new medicines is by no means assured of course, but the convergence of cellular reprogramming, genome editing and other technologies in life sciences, following the conceptual lead of the IT industry, offers our best shot at progress combatting such difficult problems as AD.

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