The potential of stem cell therapy is huge--these potent cells have the ability to develop into just about any tissue type that exists, and many dream of using them for healing spinal cord injuries, reversing Alzheimer's, and curing Parkinson's. But while the idea is lovely in theory, stem cells are remarkably fickle and susceptible to chemical and physical cues that researchers are only just beginning to understand.

For instance, scientists have been trying to find a way to use embryonic stem cells to help mend injured hearts in the aftermath of a heart attack. The stiff, scarred muscle that results from oxygen deprivation can greatly decrease a heart's ability to pump blood to the rest of the body, and the regenerative power of stem cells have long seemed a good solution. But early trials, in which experimenters simply injected the cells straight into the injured heart tissue, showed unexpected results: Rather than differentiating into healthy, beating cardiac cells, they instead took their cue from the hardened scar tissue and began developing into something more akin to bone.

Recent studies have suggested that part of the reason for this is that embryonic stem cells are incredibly susceptible to physical cues from their surroundings. A few years ago, bioengineer Adam Engler showed that when the exact same stem cells are placed on soft, medium, or hard substrates, they differentiate into brain-, muscle-, and bone-like cells, respectively. Even something as simple as the stiffness of their surroundings impacted the cells' development.

Now Engler, a stem cell biologist at the University of California at San Diego, and graduate student Jennifer Young, have taken this research a step further. In a study they presented yesterday at the American Society for Cell Biology (ASCB) meeting in San Diego, Young and Engler studied embryonic chicken hearts with atomic force microscopy to determine how their stiffness changed during the two-and-a-half weeks post-fertilization. They created a matrix that closely replicated the stiffening rate, then placed embryonic chicken cardiac cells on it to see how they developed. Compared to cardiac cells grown on static gels, which remained developmentally stuck, those growing on the dynamic matrix showed remarkably similar markers to cells that developed inside the embryo itself.

"The hope, from a therapeutic standpoint, is that you could take the material with your stem cells and inject them together," Engler says. "We would encapsulate the cells, inject them with the dynamic gel, and hope the gel would form in the [injured cardiac] tissues and provide the appropriate mechanical cues."

Granted, the experiments are still in very early stages, and Engler and Young haven't yet tried their matrix with human embryonic stem cells; that's their next step. But just the knowledge that it might be possible to force embryonic stem cell differentiation with mechanical cues is a substantial advance. Of course, whether an injured heart would be able to incorporate this new tissue is another question altogether.

These videos show beating heart cells growing on a scaffold. In the first video, beating of chicken embryonic heart cells on stiff matrices, which exhibit scar-like rigidity, is impaired and the frequency great reduced.

Beating frequency is better maintained on matrices that closely mimic in vivo elasticity, such as shown in the below video.

Credit: Young and Engler, UCSD

Norman Borlaug. Credit: United States Department of Agriculture.

Norman Borlaug, the world's greatest farmer, and a distinguished agronomist, died at the weekend, aged 95. His was a long and productive life of heroic proportions. The honours humanity heaped on "Norm" included the Nobel Peace Prize, Congressional Gold Medal and the Presidential Medal of Freedom: a hat-trick shared only with Martin Luther King, Nelson Mandela, Mother Teresa and Elie Wiesel.

Yet only a day earlier, UPI reported a story that Norm, famously unassuming, would undoubtedly have been happy to see get more attention than his widely reported death--the fact that Ug99, a variant of the stem rust that is the principal blight of wheat, mankind's major food-source (and the core of Borlaug's lifework), continues its insidious march into South Asia. It now threatens the food supplies of at least 26 countries. For Borlaug, it was always all about the food--and food's dark shadows, hunger and famine, which had haunted and driven him since his youth amid the dust-bowls of The Great Depression.

As George Santayana famously remarked in The Life of Reason, "Those who cannot remember the past are condemned to repeat it". Borlaug lived long enough to both remember the Depression--and warn against its repetition. At a conference of world experts gathered to highlight the dangers of Ug99, Borlaug--then in his nineties--was the only person present to have personally experienced what a stem rust epidemic meant. For while there is an impressive nomenclature to capture the elements--basidiospores, dikaryotic urediniospores, stomata - the truth is grimly physical: despairing farmers in fields of rotting plants, a long way from happy breakfast cereal images. With Borlaug's death, we have lost a link to a past that truly has the capacity to become a nightmarish future. And the reasons for that, while complex, lie in the bitterly contested politics of technological innovation.

For before he'd even been buried, the usual suspects were out and about, spouting an environmentalist critique of Borlaug's extraordinary achievement: more or less feeding the world for the last half century. For example, Graham Harvey, who advises on the farming strand on the world's longest-running radio soap, The Archers, felt fit to write in The Times of the "worrying consequences" and "widespread environmental damage" of Borlaug's Green Revolution, which is widely reckoned to have fed billions of people, as well as saving many millions of hectares of wilderness from agricultural use. There are, of course, issues (when are there not?) and Norm never shied from them. But as he repeatedly noted, such hand-wringing does very little for the millions of children "who cry themselves to sleep with hunger each night."

In a delightfully dry denunciation of those vaguely in favor of a global "organic" solution, on Penn and Teller's Bullshit! series, Norm noted that "Producing food for 6.2 billion people ... is not simple." He added, "[Organic approaches] can only feed four billion--I don't see two billion volunteers to disappear." Indeed, a useful distinction could be made between the green--those concerned with a more or less hypothetical future, but nonetheless adept at whipping up public and media concern (and seeming oceans of public funding courtesy of a cadre of mountebank politicians) and those working at the sharp end, like Norm, who we might call brown. In other words, those working in a world involving the suffering of mainly brown-skinned people who, to paraphrase Neville Chamberlain, live in far-away countries, and of whom we know little.

Norm exuded an old-school charm in person, but had little truck for those with no experience of the "back-breaking" hardship of actually growing food. Even in his tenth decade, his passion was for the poor. He politely, but witheringly, disdained the indulgences of the comfortable cadre of environmentalists in the West who knew not of what they speak. (He also had sharp and pithy words about the synthetic pesticide DDT, not least in terms of the near-genocidal impact of banning it on countless millions of African malaria sufferers). He was a big hitter in a debate all too often mired in emotionalism.

Ronnie Coffman of the Borlaug Global Rust Initiative (BGRI) notes that "we have a lot of complaints about the green revolution, but those who complain have little awareness of the alternatives ... because stem rust is a global disease, it's not a national disease. We have to hang together on this thing or we will all hang separately, because you cannot defend yourself alone." Three weeks ago Coffman met a frail Borlaug, and this humble American hero gave a last, stark warning: "Don't relax. Rust never sleeps."

We honour him best by helping create the political will, and sustainable funds, to prevent the kind of global famine that was the stuff of his nightmares. Norm deserves a quiet night.

John Pollock reviewed "The Man Who Fed the World: Nobel Peace Prize Laureate Norman Borlaug and His Battle to End World Hunger" in the January/February 2008 issue of Technology Review. He is a consultant and author based in London.

Submitted in response to Technology Review's interview with Leonard Hayflick. See "Can Aging Be Solved?"

Entropy is not the most fruitful perspective from which to view aging. There are varying error rates in biological information processes depending on the cell type, and this is part of biology's paradigm. We have means already of determining error-free DNA sequences even though specific cells will contain DNA errors, and we will be in a position to correct those errors that matter.

The most important perspective in my view is that health, medicine, and biology is now an information technology, whereas it used to be hit or miss. We not only have the (outdated) software that biology runs on (our genome), but we have the means of changing that software (our genes) in a mature individual with such technologies as RNA interference and new forms of gene therapy that do not trigger the immune system. (I am a collaborator with a company that performs gene therapy outside the body, replicates the modified cell a million-fold, and reintroduces the cells to the body, a process that has cured a fatal disease--pulmonary hypertension--and is undergoing human trials.)

We can design interventions on computers and test them out on increasingly sophisticated biological simulators. One of my primary themes is that information technology grows exponentially, in sharp contrast to the linear growth of hit or miss approaches that have characterized medicine up until recently. As such, these technologies will be a million times more powerful in 20 years (by doubling in power and price performance each year). The genome project, incidentally, followed exactly this trajectory.

Hayflick cites the automobile as an example to support his thesis that you cannot stop aging. Yes, automobiles will wear out if you don't maintain them adequately. However, we do have the knowledge to perfectly maintain automobiles and completely prevent aging. There are century-old automobiles around in vintage (perfect) condition that are still driven around. That is because the maintenance was sufficiently aggressive for those cars. Most people don't think it's worth the trouble with regard to an automobile, but it will be worth the trouble for our bodies. With regard to automobiles, we have all of the knowledge and tools needed to completely stop aging. We do not yet have all of the knowledge and tools to do this with the human body, but that knowledge is growing exponentially.

As for the implications of radical life extension, Hayflick assumes that nothing else would change. But the same technologies that will bring radical life extension will also bring radical expansion of resources (nanoengineered solar panels, water and food technologies) and radical life expansion (merging with the intelligent machines that we are creating, virtual reality from within the nervous system, etc.). We have already democratized the tools of creativity so that kids in their dorm room can create a full-length high-definition motion picture or write software that results in disruptive change (e.g., Google). Hayflick has not considered the implications of these recent developments. We don't have to do any of these things perfectly (and there is no such thing as perfection in the real world)--just well enough to stay ahead of the curve.

Our intuition is linear, so many scientists, such as Hayflick, think in linear terms and expect that the slow pace of the past will characterize the future. But the reality of progress in information technology is exponential, not linear. My cell phone is a billion times more powerful per dollar than the computer we all shared when I was an undergrad at MIT. And we will do it again in 25 years. What used to take up a building now fits in my pocket, and what now fits in my pocket will fit inside a blood cell in 25 years.

With regard to Hayflick's own limit, he acts as if that limit is impossible to engineer. Just in recent years we have discovered that just one enzyme controls the telomeres and that cancer cells use telomerase to become immortal. Now, I realize that it is not a simple matter to just apply telomerase to overcome this particular aging limit, as we have to figure out how to administer it, and we don't want to encourage cancer, but these are all solvable engineering problems.