Monday, January 30, 2012

Brain Stimulation and Human Cognitive Enhancement

Who wouldn't want to be smarter? And what parents don’t want academic success for their children?

Now it appears that simple electrical devices that stimulate the brain are able to enhance human cognitive performance.

An Essay in a recent issue of Current Biology describes recent advances in “non-invasive brain stimulation” (NIBS). One approach in particular—“transcranial direct current stimulation” or TDCS—is described in detail. According to the essay, TDCS is a simple tool that is “portable, painless, inexpensive, apparently safe, and with potential longterm efficacy.” It may be used to help those suffering from impaired cognitive abilities.

More to our point, however, is that TDCS shows remarkable potential for human enhancement. Simply put, this device seems to have the power to make normal children and adults smarter than they would normally be. To quote the essay, TDCS has the potential “to enhance fundamental human capacities, such as motor and sensorimotor skills, vision, decision making and problem solving, mathematical cognition, language, memory, and attention—improvements that seem to persist without apparent cognitive side effects.”

The main point of the essay is to invite broad discussion about the neuroethics of cognitive enhancement. A good deal of attention is focused on whether TDCS or similar techniques should be used on children. The authors argue that having smarter children will benefit everyone. Their conclusion: “If it is handled judiciously, TDCS could prove to be an inexpensive and widely-deployed technology with substantial benefits to individuals and society.”

Anyone following the debate about human enhancement will see this as further evidence that in terms of the technology, “the future is here.”

Sure, there’s a lot to think about here before we rush out and strap TDCS devices on our heads. Anyone worried that mobile phones pose a health risk will probably not think this is such a good idea.

But many of us human beings value our cognitive abilities above everything else. If TDCS is a safe way to become smarter, then why not?

According to the Christian tradition, human beings are created in the image of God. One way we resemble God is through the power of intellect, which we share with the animals but which we alone exhibit to such a lofty degree that we can be compared to God. According to Gregory of Nyssa, one of the great theologians of the fourth century, “The Deity beholds and hears all things, and searches all things out." No surprise there. But then Gregory adds: "You too have the power of apprehension of things by means of sight and hearing, and the understanding that inquires into things and searches them out.”

How expected that by inquiring into all things and searching them out, we now seem to be learning how to enhance the very power of thought and discovery.

If we enhance our intelligence will we become more like God? Not quite. Intelligence may be one way we can and should resemble God, but it's not the only way. In fact, intelligence by itself can be worrisome.

Much to his credit, Julian Savulescu (a co-author in the TDCS essay) is one of very few who has urged us to pay attention to the question of “moral enhancement.” Quite simply, smarter people who are not also morally better people may turn out to be very dangerous people. So after reading the essay on how to enhance cognition, let me suggest you look at a 2008 paper by Ingmar Persson and Julian Savulescu, entitled "THE PERILS OF COGNITIVE ENHANCEMENT AND THE URGENT IMPERATIVE TO ENHANCE THE MORAL CHARACTER OF HUMANITY."

Wednesday, January 11, 2012

Are We Alone?

Our sun is a star, one of hundreds of billions of stars.

In the past 16 years, scientists have founds more than 700 planets orbiting a few of the stars beyond our sun. These distant planets are often called exoplanets, short for extra-solar planet.

Just how many exoplanets are there in our Milky Way galaxy? Were researches just extremely lucky, looking where exoplanets exist? Or do they exist nearly everywhere?

Research published in the January 11, 2012 issue of Nature supports the idea that planets are as common as stars. Each of the 100 billion stars in our galaxy has on average at least one planet.

If life exists out there, it most likely exists on planets that are roughly like our earth. Not too big and neither too far from its sun (perpetual winter) or too close (blazing heat). Of all the planets, how many are roughly on the scale of earth? Half of them at least, maybe more.

Caption: This artist's cartoon view gives an impression of how common planets are around the stars in the Milky Way. The planets, their orbits and their host stars are all vastly magnified compared to their real separations. A six-year search that surveyed millions of stars using the microlensing technique concluded that planets around stars are the rule rather than the exception. The average number of planets per star is greater than one. Credit: ESO/M. Kornmesser

Arnaud Cassan of the Institut dʼAstrophysique de Paris and lead author of the paper explains: “We have searched for evidence for exoplanets in six years of microlensing observations. Remarkably, these data show that planets are more common than stars in our galaxy. We also found that lighter planets, such as super-Earths or cool Neptunes, must be more common than heavier ones,” Cassan said in a press release issued by the European Southern Observatory (ESO).

"We used to think that the Earth might be unique in our galaxy. But now it seems that there are literally billions of planets with masses similar to Earth orbiting stars in the Milky Way," according to Daniel Kubas, co-lead author of the paper.

If there are tens of billions of life-friendly planets just in our own galaxy, how likely is it that life exists out there somewhere? And if life exists, has intelligence evolved?

These are ancient religious and philosophical questions. The latest science certainly tilts the debate in favor of life. Sure, it’s possible that earth beat the odds: of the tens of billions of life-friendly planets, only ours has life.

Right now, there’s no evidence either way. All that science can tell us is that the planets are there, ready for the spark of life to get started.

So we are left to gaze at the night sky and to wonder as never before. For each star, there’s a planet. Is anyone out there looking back?

In Christian theology, one of the earliest statements about the Holy Spirit is that the Spirit is the “giver of life.” Hildegard of Bingen (Symponia) put it this way: “God our life is the life of all.” Or consider John Calvin, who says the Spirit is "everywhere diffused, sustains all things, causes them to grow, and quickens them in heaven and on earth."

To believe in God is to believe in the life-giving presence of God, not just here but everywhere. Thanks to this research, it turns out that the Spirit has many more planets on which to give life.

The article, "One or more bound planets per Milky Way star from microlensing observations", by A. Cassan et al., appears in the 12 January issue of the journal Nature.

Tuesday, January 10, 2012

Stem Cells and Type I Diabetes

Is this just too good to be true? That’s my first reaction when I read the press release with this headline: “Stem cell therapy reverses diabetes.”

The full report was published on January 9 by an open source medical journal, BioMed Central. If the procedure it describes can be replicated, it is promising indeed. Researchers claim to have a device that “educates” the patient’s own stem cells.

The device is called a “Stem Cell Educator.” Apparently when the patient’s blood passes through the device, stem cells naturally occurring in the patient’s blood are “educated” or re-set to a more normal, functional level. The device separates the patients blood, selecting lymphocytes for special treatment by exposing them to stem cells that were originally derived from donor human umbilical cords.

No cells are exchanged or added to the patient’s blood. Instead, the patient’s own cells are reset by exposure to specific factors given off by the donor stem cells that are kept in a living culture inside the device. After two or three hours of “education,” the patient’s lymphocytes seem to perform a lot better.

The result? Researchers claim in their report that “a single treatment produces lasting improvement in metabolic control. In initial results indicate Stem Cell Educator therapy reverses autoimmunity and promotes regeneration of isletβcells.” The need for insulin was reduced and the benefits lasted at least as long as 40 weeks after the treatment.

The study also makes this claim:

Successful immune modulation by CB-SCs and the resulting clinical improvement in patient status may have important implications for other autoimmune and inflammation-related diseases without the safety and ethical concerns associated with conventional stem cell-based approaches.

Whether these findings are replicated is a key question at this point. The claims are pretty extraordinary, but the general strategy of "re-educating" rather than replacing cells seems to be showing a lot of promise. For an example, see my earlier post, "Is Aging a Disease of Stem Cells?"

The study was led Yong Zhao of the University of Illinois at Chicago, who directed an international team and prepared the report, entitled “Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells.” The full text is published by the online journal BioMed Central and is freely available to the public.

Monday, January 9, 2012

Genes, Hybrids, and Giant Tortoises

Charles Darwin visited the Galápagos Islands in 1835. As he moved from island to island, he saw the subtle differences between finches, tortoises, and other animals. These observations led to the discovery of the theory of evolution as an expanding “tree of life,” first sketched by Darwin in his notebook entry dated just two years later in 1837.

The great tortoises of the Galápagos could not fail to impress. The greatest of all, the tortoise Chelonoidis elephantopus, can live to be a hundred years old and grow to six feet and almost 900 pounds.

Until now, it was believed that whalers hunted the great C. elephantopus to extinction shortly after Darwin’s visit. Now, however, new research suggests that a few of the great tortoises may still be alive.

Caption: G. Becky tortoises are native to Isabela Island in the Galapagos chain and have more domed shape shell. Credit: Courtesy Yale University.

Researchers have found what they believe are direct offspring of purebred C. elephantopus tortoises. By testing the genes of living tortoises, researchers concluded that they were studying hybrids. One parent was from a related species, C. becki. But the other parent was clearly C. elephantopus. And since the living tortoises were still quite young, researchers were drawn to the obvious conclusion that the C. elephantopus parent lived until a few decades ago and may still be roaming the slopes of Isabela Island.

So now it’s a race against time to find surviving purebred C. elephantopus tortoises in hopes that enough of them still exist so the species—truly one of the great animal species—can be brought back from what seemed like extinction. According to the report, “purebred tortoises of the recently ‘extinct’ C. elephantopus from Floreana Island are very likely still alive today.”

Caption: This tortoise is a hybrid of G. Becky and C. elephantopus, a species native to Floreana Island some 200 miles away and thought to be extinct. Genetic analysis of tortoise population on Isabela Island suggests purebred individuals of C. elephantopus must still be alive on Isabela. Credit: Courtesy of Yale University

One interesting parallel. Using a similar approach, researchers have recently concluded that human beings are also hybrids. For example, many of us contain genes from our Neandertal ancestors. The big difference, of course, is that our interbreeding occurred tens of thousands of years ago. In either case, hybridization or interbreeding occurs when the twigs at the end of Darwin's tree of life come together. As evolutionary biologists are discovering, speciation (or branching) is critical to evolution, but so is interbreeding or hybridization.

According to the report, “To our knowledge, this is the first rediscovery of a species by way of tracking the genetic footprints left in the genomes of its hybrid offspring.” The report, "Genetic rediscovery of an ‘extinct’ Galápagos giant tortoise species," appears in the January 9, 2012 issue of Current Biology.

Friday, January 6, 2012

Hope for Aging Brains

When electrical wires lose their insulation, they have to be replaced. When the nerves and brain cells in our bodies lose theirs, they regenerate it naturally.

Up to a point, that is. As the decades pass, our bodies lose the ability to regenerate themselves. The results are obvious: wrinkled skin, weak muscles, and forgetful brains.

All the more tragic for those among us with diseases that attack the very processes of regeneration. Multiple sclerosis (MS), for example, keeps the body from restoring the insulating layers that protect nerve fibers. The insulation—“myelin”—breaks down naturally. In most human brains, “remyelination” is a constant process, rebuilding the myelin that protects the brain cells and allows them to do their work. For people with MS, remyelination is under attack.

Working with mice, researchers seem to have found a way to reinstate the remyelination process. In a report in the January 6 issue of Cell Stem Cell, researchers at Harvard and Cambridge Universities show that the capacity for remyelination can be restored in aging mice.

The cells that are responsible for remyelination are still present in the aging mouse. It’s just that they have been switched off. By exposing these cells to switching signals present in a much younger mouse, researchers were able to reverse the effects of aging on the cells that do the work of remyelination.

How did they do this? They literally joined the old and the young mouse together surgically. This allows their blood to circulate together. In the young blood, apparently, were various chemical signals that reset the switches in the cells of the brains of the aging mice. The result: spontaneous remyelination.

According to Robin Franklin, one of the researchers, the study shows that “age-associated decline in remyelination is reversible. We found that remyelination in old adult mice can be made to work as efficiently as it does in young adult mice.” Franklin, who is Director of the MS Society's Cambridge Centre for Myelin Repair at the University of Cambridge, made her comments in a press release issued by her university.

What’s perhaps most interesting about this report is that it is a kind of stem cell research that doesn’t implant stem cells. It works on the principle that stem cells already exist in the patient’s body but that they’ve been silenced by age or disease. They need to be switched back on or rejuvenated. According to Franklin, “remyelination therapies do not need to be based on stem cell transplantation since the stem cells already present in the brain and spinal cord can be made to regenerate myelin - regardless of the patient's age."

As interesting as this is, it is important to stress that this is a “proof of concept” study. The techniques here are simply not applicable to human beings. They are encouraging because they suggest that perhaps some day, researchers will discover just what it is in the young body that keeps it young. What are the specific factors that keep the body’s own stem cells switched on? And if it circulates in the blood as this study shows, perhaps these factors could simply be injected.

Of course, if researchers discover how to do this, it’s not just people with diseases like MS who will be interested. One of the interesting social features about this work is that it is funded in part by the UK MS Society and the American MS Society. In other words, the funding is motivated by the search for a cure for a very specific disease. But the mice is the study were aging, not ill. That suggests to me, at least, that the larger portion of the “beneficiaries” of this work will be aging humans, not those with MS. If so, then this study is one more step in the quest of human enhancement, suggesting that it may be possible to reverse aging in the one part of the body where it is most feared—the human brain.

The journal report ends with this comment: “Moreover, this work demonstrates that the CNS maintains its responsiveness to age-regulated circulatory factors, such that age-dependent deficiencies in repair of these tissues can, in part, be reversed by circulating factors.”

The paper, “Rejuvenation of regeneration in the aging central nervous system,”' is published in the January 6 issue of Cell Stem Cell.

Thursday, January 5, 2012

Chimeric Monkeys? Where Do We Go From Here?

What is a “chimeric monkey”? Why would anyone want to create them? And why should anyone care?

In ancient myth, a chimera was an animal with a human head and, say, the body of a horse or a lion. That’s not what’s going on here.

In biology today, a chimera is an animal that comes from two or more embryos. This happens naturally, when twins are conceived but the two fertilized eggs fuse into one embryo, eventually producing one individual.

In research, scientists create chimeras in order to study how cells function. Mice chimeras are now commonplace in stem cell labs around the world. Researchers add stem cells to an early-stage mouse embryo (a blastocyst). If the experiment goes well, the developing mouse will have cells from two sources: the “host” embryo and the implanted cells. The implanted cells often integrate into the body and brain of the mouse pup. By this test, researchers know that the implanted cells are truly stem cells—or, more precisely, that they are pluripotent, capable of becoming any type of cell in the mouse body.

Caption: Chimero, a chimeric Rhesus monkey produced by aggregating six Rhesus blastocysts. Photo credit: OHSU.

Researchers also implant human stem cells into mice. If they multiply and are fully integrated into the body, it’s pretty clear that they are pluripotent and capable of functioning within a living biological system and not just in a dish in a lab. In that case, the mouse is an “inter-species” chimera. Two embryos, of course, but from two different species, human and mouse.

For all the ways in which mice resemble human beings, there are big differences, some of which are particularly noticeable at the earliest stages of life. So when researchers at the Oregon National Primate Research Center at Oregon Health & Science University tried to put pluripotent monkey stem cells into monkey blastocysts, they failed. At the blastocyst stage, Rhesus monkeys don’t behave like mice.

The Oregon team, led by Shoukhrat Mitalipov, kept trying other approaches, finally discovering a completely different technique. Instead of using embryonic or pluripotent stem cells and adding them to a blastocyst, they backed things up, at least in terms of embryonic development. How far back? All the way to the four-cell stage. When a Rhesus monkey egg is fertilized (in this case, in a lab dish), it divides into two cells, then four. What happens if two cells in one blastocyst were combined with two cells from another blastocyst? Success—but still only partly so.

So they tried another approach, one that seems complex and counterintuitive. Researchers “aggregated” three blastocysts—and “they” began to function as one embryo. Four blastocysts—same result. Five, even six blastocysts. They did this 29 times and produced 29 viable chimeric embryos. Or to quote the original paper: “Remarkably, all 29 aggregates developed to blastocysts…”

Just what will this mean for the field of stem cell research? At the very least, this research points to the complexity of living biological systems. It’s nice to think that researchers can extract pluripotent stem cells, keep them multiplying indefinitely, direct them to develop just the right way, and implant them into the human body to regenerate tissues. If only it were that simple. As the field advances, it is clear that what was once called “pluripotency”—the ability to become any cell type—is anything but clear or simple to define.

All the more reason, I believe, why the field needs to move forward as a whole. It’s morally and scientifically simplistic to say that the field can advance without cells from embryos.

But does the Oregon work suggest a step too far? For many, it may be morally permissible to work with cells derived from blastocysts, perhaps donated from IVF clinics and due to be discarded anyhow. But what the Oregon work seems to signal is that when it comes to primates—including human beings—the cells in the living blastocyst are significantly different from the cells derived from the blastocyst. The cells in the living blastocyst, though dynamic and changing, can be regarded as totipotent, capable of becoming any cell type including the placenta and umbilical cord. Cells derived from the blastocyst—human “embryonic” stem cells or pluripotent cells—have lost part of this potential.

Does this mean that research, in order to go forward, needs access to cells as they exist in living blastocysts? That would be a step clearly beyond federal funding guidelines (the “Dickey-Wicker Amendment”). Even with private funding, it would likely exceed what most Americans can support. In some states and many countries, it would be plainly illegal.

And yet this is exactly what lead Oregon researcher Shoukhrat Mitalipov seems to have in mind. "We need to study not just cultured embryonic stem cells but also stem cells in embryos,” Mitalipov said in a release from the journal Cell. “It's too soon to close the chapter on these cells." Is that OK as long as he sticks to non-human primates?

Mitalipov is clearly right: "We cannot model everything in the mouse." Rodents and primates are different in unexpected ways at the earliest stages. Stem cells inserted in mouse blastocysts form chimeras, but not in primate blastocysts.

Quoting Mitalipov once again: "The possibilities for science are enormous." All the more reason to think this through. As complex as the science might be, the moral and religious implications are even more complex.

I for one need time to think this through. I hope to be back here before long with some more thoughts. For now, let me recommend a statement that I helped prepare a few years ago on the question of chimeras.

The paper, "Generation of Chimeric Rhesus Monkeys," was released on January 5 and will appear in the January 20, 2012 issue of the journal, Cell.

Tuesday, January 3, 2012

Is Aging a Disease of Stem Cells?

Is aging a disease? And if it is a disease, what “causes” it? Is it simply natural for bodies to age over time, or is something wrong with them, something that could be “fixed”?

In a report in the January 3 issue of Nature Communications, researchers at the University of Pittsburgh School of Medicine report on work with mice that are bred especially to age quickly. The mice have a version of progeria, a disease in humans that causes children to age well before their time.

The research team looked at differences in stem cells or progenitor cells, which healthy bodies naturally keep in reserve as a source for new cells to replace worn-out cells. Not surprisingly, they found that the progeria mice had fewer progenitor cells than their healthy counterparts. What’s more, the few progenitor cells in the progeria mice failed to function normally. For example, they didn’t produce replacement cells as needed.

If that’s the problem, can it be “fixed”? The researchers, led by senior investigators Johnny Huard and Laura Niedernhofer, injected the rapidly-aging progeria mice with progenitor cells from the muscles of healthy mice. The result was pretty amazing.

"We wanted to see if we could rescue these rapidly aging animals, so we injected stem/progenitor cells from young, healthy mice into the abdomens of 17-day-old progeria mice," Dr. Huard said in a press release issued by the University of Pittsburgh. "Typically the progeria mice die at around 21 to 28 days of age, but the treated animals lived far longer—some even lived beyond 66 days. They also were in better general health."

How did this work? Did the injected cells start producing replacement cells? Possibly, but the main effect of the injected cells seems to have been to change the host cells in the body of the progeria mice. In other words, the injected healthy progenitor cells changed the progeria mouse’s own cells into more healthy, more normal cells.

"This leads us to think that healthy cells secrete factors to create an environment that help correct the dysfunction present in the native stem cell population and aged tissue," Dr. Niedernhofer said. "In a culture dish experiment, we put young stem cells close to, but not touching, progeria stem cells, and the unhealthy cells functionally improved." Fascinating!

What about mice that are aging normally? Would the injection of progenitor cells from younger mice, for example, also “rescue” non-progeria but aging mice?

Whether anything like this could be done safely in human beings is a big question that will require a lot more research. It may turn out that injecting progenitor cells into a human patient with premature aging might help stall the aging but might also create other problems, such as cancer. In time, it may be possible to get the benefits while managing the risks.

The Pitt research, although dealing with mice with progeria, opens profound questions about humanity, aging, enhancement, and the possibility of extending the human lifespan.

The biggest question of all is whether something like this would slow the aging process in normal or healthy human beings. In other words, is this yet another possible pathway to human enhancement? Could this be used to “treat aging as a disease”?

Is aging a disease? Dr. Niedernhofer’s comment is revealing: "Our experiments showed that mice that have progeria, a disorder of premature aging, were healthier and lived longer after an injection of stem cells from young, healthy animals," Dr. Niedernhofer said. "That tells us that stem cell dysfunction is a cause of the changes we see with aging." A dysfunction? A disease? A difference?

On the question of religion and the morality of extending the human lifespan, probably the best book on the market is Religion and the Implications of Radical Life Extension, edited by Calvin Mercer and Derek Maher. I have an essay in the book reflecting on the question from the standpoint of Christianity.

My take? Extending the human lifespan is not immoral or obviously wrong, but Christians hope for a transformation, not an extension. More of the same is too little.

The report appeared in the January 3 issue of Nature Communications. It is entitled Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model and is available free to the public.