Archive for August, 2008

reprogrammed 0000106 Louis J. Sheehan

August 30, 2008

Louis J. Sheehan

Stem cells’ powers of self-renewal, immortality and potential for medicine inspire those who study them. But progress toward understanding them has been slow it took 20 years just to figure out how to grow embryonic stem cells in the laboratory. More recently, though, molecular techniques have enabled swift movement on two fronts.  http://louiskjksheehan.blogspot.com Researchers are starting to see how stem cells can replenish their numbers while giving rise to specialized cells. Others are learning how to turn adult skin cells into cells more like their embryonic ancestors. These advances offer hope that scientists will soon harness the capabilities of stem cells, at last fulfilling the cells’ promise.

Illustrations by Bryan Christie

Back to the Womb

Reverting adult cells to an embryonic state without creating embryos is a tricky business

The diagnosis is not good; the patient will need surgery. So the doctor plucks a hair from the patient’s head and tells her to come back in a few weeks. When the patient returns, the surgeon patches up the faulty organ by implanting healthy cells generated in the lab from the patient’s hair follicle. After a few months, the new cells have integrated into the organ and the woman’s symptoms recede. A year later, she’s healthy and living a normal life.

This is the scenario that stem cell researchers hope will be commonplace 10 or 15 years from now. A patient’s own cells perhaps taken from hair follicles, blood or skin would be transformed into cells of the heart, brain or other organs. Doctors would then transplant these converted cells into the afflicted organ to treat the illness, whether it’s multiple sclerosis, Parkinson’s disease, heart failure or diabetes.

That dream came closer to reality last November. Two teams of scientists announced that they had wound back the clock on adult human skin cells, regressing those cells to an embryonic state. Just like embryonic stem cells, these reprogrammed cells seemed capable of becoming any of the 200-plus cell types in the human body, an ability called pluripotency (SN: 11/24/07, p. 323).

“The fact that you can do something to adult cells to reprogram them was absolutely novel,” says Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, Calif. “It goes against everything that everyone had ever thought about the abilities of adult cells.”

Before, the only way to obtain pluripotent human cells had been to extract stem cells from 5-day-old embryos, which made the technique controversial. Reprogramming adult cells doesn’t involve making or destroying embryos, so the new cells called induced pluripotent stem cells, or iPS cells seemed to offer all the medical promise of embryonic stem cells without the political quagmire.

But nobody really knows how similar these new cells are to embryonic stem cells at the genetic level. Subtle differences in patterns of gene activity could undermine some of the new cells’ potential to treat diseases, or even cause the cells to behave abnormally if implanted. Before doctors can safely use reprogrammed cells in people, scientists need to know whether these new cells are truly genetic “twins” of real embryonic stem cells.

Cancer also poses a potential risk. To reprogram adult cells, scientists expose cells to four genetically engineered viruses. Each virus inserts a gene into the cells’ DNA at random locations. Such willy-nilly insertions sometimes disrupt the cells’ genes, including critical ones such as tumor suppressor genes. This viral disruption can cause cells to grow out of control and form a tumor another problem that must be solved before physicians can consider treating patients with reprogrammed cells.

Recent research is beginning to overcome these hurdles. Scientists are removing viruses one by one from their cell-conversion recipes. And new genetic studies suggest that these recipes do indeed fully reprogram adult cells fulfilling a possibility first suggested by the birth of Dolly.

Hitting the reset button

If a sheep could win a Nobel Prize, the prize for paving the way for reprogrammed stem cells would go to Dolly, the first cloned animal.

Lost in the media frenzy that followed Dolly’s birth in 1996 was a point more subtle than talk of clone armies and replacement pets. In Dolly, scientists saw proof that the DNA in a mature body cell could be “reset” to an embryonic state and then grow into every kind of cell in a newborn clone’s body, from heart muscle cells to nerve cells and bladder cells.

access

DNA METHYLATIONENLARGE | One way cells shut down unneeded genes is by attaching small molecules called methyl groups to the DNA, a process called methylation. Turning back the clock to return an adult cell to an embryonic state is largely a matter of removing this methylation.J. Korenblat

During cloning, inserting the nucleus of an adult cell and its DNA cargo into an emptied egg cell resets the adult DNA. Somehow, egg cells know how to perform this reprogramming feat.

By figuring out which proteins create and maintain this embryonic state, scientists thought they might be able to use those proteins to reset whole adult cells, not just the DNA.

Looking at the genes active in embryonic stem cells, Shinya Yamanaka and Kazutoshi Takahashi from Kyoto University in Japan found a set of four genes that, when inserted into the cells via viruses, did the trick in mouse cells in 2006 and, later, human cells: Oct3/4, SOX2, c-Myc and KLF4.

Almost immediately, stem cell researchers around the world flocked to the newly discovered recipe and began experimenting with reprogrammed cells. But work on the more controversial embryonic stem cells wasn’t abandoned. Unaltered, true embryonic cells still serve as a gold standard of “stemness” for sizing up the new cells.

“You never could have made a [reprogrammed] cell without an embryonic stem cell to compare to, to tell you what a pluripotent cell was,” says cardiologist Robb MacLellan of the UCLA David Geffen School of Medicine. Reprogrammed cells are “still very preliminary, and they will need a lot of work before you can say that they would be better or equivalent to embryonic stem cells.”

Scientists also assess the reprogrammed cells’ stemness by using them to treat disease in animals. If iPS cells are truly the same as embryonic stem cells, they should behave the same once converted to heart or nerve cells and implanted in the body.

For sickle cell anemia, at least, some evidence suggests that reprogrammed cells can do the job. Rudolf Jaenisch and his colleagues at the Massachusetts Institute of Technology corrected the faulty gene that causes sickle cell anemia in reprogrammed mouse skin cells. After coaxing the cells to develop into mature bone marrow cells, the scientists injected the cells back into the mice. Once the new cells took residence in the mice’s bone marrow, those cells began producing normal blood cells and the mice’s conditions improved, Jaenisch’s team reported last December in Science.

Reprogrammed cells can also become nerve cells and treat mice with a condition analogous to Parkinson’s disease, Jaenisch’s team showed in research published in the April 15 Proceedings of the National Academy of Sciences. In the experiments, reprogrammed cells once again appeared to behave just as embryonic stem cells would.

Another encouraging sign came from comparing which genes are switched off in reprogrammed cells and in embryonic stem cells. As an embryo develops in the womb, cells descended from embryonic stem cells gradually become more and more specialized into, say, liver or bone cells. Specialization primarily consists of shutting down unneeded genes turning off liver genes in bone cells and vice versa.

One way cells shut down unneeded genes is by attaching small molecules called methyl groups to the DNA, a process called methylation. Turning back the clock to return an adult cell to an embryonic state is largely a matter of removing this methylation. In most studies, methylation patterns of reprogrammed cells have closely mirrored those of embryonic stem, or ES, cells, leading some scientists to view the two as functionally identical.

“They’re essentially the same cells,” says Michael West, a stem cell researcher and chief executive of BioTime, a biotechnology company based in Alameda, Calif. “They’re called iPS cells, but they are ES cells as far as I’m concerned.”

Not all scientists agree. “I would say they’re not entirely the same, but they’re pretty close,” says Sheng Ding, a stem cell researcher at the Scripps Research Institute. “There’s still sort of imperfect gene activation.”

A study appearing online August 24 in Nature could finally settle the matter. Loring of Scripps and her colleagues profiled the activity of thousands of genes and proteins in reprogrammed cells, embryonic stem cells, neural stem cells and other stem cells. Comparing these activity profiles revealed a set of 19 proteins that clearly delineate between cells that are pluripotent and others, such as neural stem cells, which are not.

“We can always tell you if a cell falls into that category or not. It’s very clear,” Loring says. When her team screened reprogrammed cells based on these key proteins, those cells fell cleanly into the same group as embryonic stem cells.

“People who have looked at [reprogrammed] cells before have gotten the impression that they are different, but this shows that they’re the same,” she says. “If they hadn’t been labeled, I wouldn’t have been able to tell them apart from [embryonic stem] cells.”

The results suggest that, on a genetic level, converted adult cells are so much like true stem cells that they’re interchangeable. Except, that is, for those pesky viruses.

Breaking a few eggs

Progress on exorcising viruses from reprogramming recipes has been swift.

In January, research groups led by Yamanaka and Jaenisch separately succeeded in converting cells without the virus carrying c-Myc, the groups reported in Nature Biotechnology and Cell Stem Cell. Because c-Myc is known to increase the risk of cancer on its own, it was the first gene scientists aimed to eliminate.

The conversion of mouse skin cells took longer without c-Myc 21 days instead of six but the cells otherwise appeared to be reprogrammed. During previous experiments, mice grown from embryos containing reprogrammed cells developed tumors because of c-Myc, but in these two experiments, the hybrid mice were tumor free. Yamanaka’s group also showed that the c-Myc–free technique can reset human skin cells. http://louiskjksheehan.blogspot.com

In later experiments by another group, the c-Myc–free technique enhanced with valproic acid converted more than 100 times as many cells after a week as the technique alone did. This improvement offset much of the efficiency lost by removing c-Myc, a team led by Douglas Melton of the Harvard Stem Cell Institute in Cambridge, Mass., reported in the July Nature Biotechnology.

Using simple chemicals like valproic acid to replace the virus-carried genes could be much safer than dealing with viruses, since the pharmaceutical industry has decades of experience developing and testing small-molecule drugs. These drugs can activate the cell’s same native molecular machinery as inserted genes would, thus reprogramming the cells in similar ways.

Replacing the three other virus-gene packages in the reprogramming recipe with chemicals like valproic acid (a compound commonly used in antiseizure medications) is one approach scientists are pursuing to make the conversion process more palatable to the FDA, which would have to approve any medical use of reprogrammed cells. “The FDA brings a whole extra level of scrutiny when there’s this genetic modification of cells” by viral insertion of genes, West says.

In unpublished research, Ding’s group recently replaced two more of the virus-delivered genes with simple chemicals. “Before it was four genes, now we’re down to one, and it’s only been about two years” since reprogrammed mouse cells were first created, Ding says. “We were surprised that it wasn’t really difficult at all.”

Scientists are exploring other ways to solve the virus issue as well, Loring notes. One approach could be to use a different kind of virus. Some viruses deliver genes into a cell without integrating those genes into the cell’s DNA. The genes remain free-floating in the cell body, where they can be translated into proteins. Eventually, the cell’s enzymes degrade the genes, removing the potential danger created by random insertions of foreign genes into the cell’s DNA.

Scientists could also inject the reprogramming proteins directly into the cells, rather than adding the genes that encode those proteins. But the problem with direct protein injection as well as the nonintegrating viruses is timing.

“We don’t know really how long these inducing factors have to be around in order to reprogram the cells,” Loring explains. Without some intervention by scientists, injected proteins would be degraded by the cell in a matter of hours. “If you don’t do it for long enough, you might as well not have done it.”

Loring is exploring yet another idea: microRNAs, short RNA molecules that silence specific genes. Each cell in a person’s body contains a complete set of his or her genetic code, including the four genes in the original reprogramming recipe. So adult cells already have these genes they’re just switched off. Loring hopes to reactivate the cell’s own reprogramming genes by using microRNAs to silence the proteins that keep those genes turned off.

Her lab recently identified specific microRNAs that could perform this task. While the experiments are ongoing, Loring says that these microRNAs could be delivered into cells without viruses.

Techniques for each of these approaches are developing rapidly, and many scientists expect that, one way or another, the virus issue will soon be resolved. “It’s happening pretty fast,” Ding says. “One, two years this will be done.”

The hard part

Of course, that’s not to say that stem cell therapies will be readily available in only one or two years.

Even after scientists can make virus-free, embryonic-like reprogrammed cells, perfecting the techniques for using these cells in patients will take years.

“You cannot use [converted] cells on their own for anything,” Ding notes. “You still have to differentiate the cells into something for it to be useful.”

Because reprogrammed cells can become any type of cell in the body, such cells transplanted directly into mice (and presumably people) can develop into teratomas ghastly tumors consisting of jumbles of hair, teeth, heart and other tissue types, all growing unchecked.

Before transplantation, scientists must first grow the reprogrammed cells in lab dishes under carefully controlled conditions to steer the cells into becoming heart cells, pancreas cells or whatever is needed for the therapy.

These steering techniques involve complex mixtures of signaling molecules. Scientists already know how to direct human stem cells into becoming cells of the heart, brain, pancreas and others, but in experiments on animals, cells made with these techniques don’t cope well after transplantation. Typically, the newly minted cells don’t integrate well into the organs, and most of the transplanted cells die.

“The actual survival of the cells is so poor,” MacLellan says. “This is going to be a huge issue before it will be clinically applicable.” These techniques will have to be refined further before they’ll be ready for widespread clinical use, Ding says. And that research is slow going.

Researchers estimate that it might take five or 10 years before they’ll be ready to begin clinical trials on people using cells derived from reprogrammed cells.

Scientists also want to know the full spectrum of cells in a patient’s body that can be reprogrammed. If and when therapies based on converted cells become commonplace, having to extract deep skin cells from each patient wouldn’t be particularly convenient. http://louiskjksheehan.blogspot.com

Ding suggests an easier approach: Perhaps scientists could convert cells from follicles of a patient’s hair.

Louis J. Sheehan

Advertisements

meier 0000050 Louis J. Sheehan

August 26, 2008

Louis J. Sheehan

We moderns seem to have no limits to our fascination with spies, whether in film, fiction or the occasional snatches of actual trade-craft glimpsed through cracks into their parallel universe. We’ve gorged on every kind of spook, from the ultimate rake (James Bond) to the ultimate drudge (George Smiley) — though both were arguably outdone by that long-running reality drama, “Who Outed Valerie Plame?,” which featured a glamorous spy, a zealous investigator, a vice-presidential aide named Scooter and a reporter who was the only one to spend time in jail.

So Andrew Meier, a former Moscow correspondent for Time magazine and the author of two previous books about Russia, can hardly be blamed for his enthusiasm in following the trail of a young American who was swept up in the radical swirl of the 1920s and recruited by the Soviets to spy for them in Europe and Asia, only to perish in Stalin’s camps. “As harrowing as ‘Darkness at Noon’ and as tragic as ‘Dr. Zhivago,’ ” promises the publisher’s blurb for “The Lost Spy.”

And indeed, the twists and turns of Cy Oggins’s 49-year life are astonishing. Born to Russian Jewish immigrants who changed their name from Melamdovich and settled in Willimantic, Conn., Oggins studied at Columbia, married a fiery radical named Nerma Berman and at some point in the 1920s joined the Communist Party and was sent abroad. Oggins and his wife lived first in Berlin, where he posed as a well-to-do art dealer. From there they moved to Paris, where Oggins’s work apparently included spying on a family of Romanov émigrés. Next, after a brief return to the United States, he was assigned to Shanghai and Manchuria. Finally, after some mysterious wandering, he was arrested in Moscow in 1939 and, eight years later, despite the intervention of American diplomats, killed by lethal injection. He was arrested, Meier surmises, because his boss in the Chinese spy ring had tried to defect, and he was killed because he knew too much to be released. http://louis-j-sheehan.info

“Surmises” is the key word here, because on this, as on far too many other things, Meier really doesn’t know. And therein lies the problem with “The Lost Spy.” We know where Oggins was at some junctures of his life. We meet a few of his friends (most notably Sidney Hook, the Marxist-turned-anti-Communist philosopher), examine a few grainy photographs and rummage through some Soviet and American official documents. But we never really get close to Cy Oggins. In all of Meier’s prodigious researches — and they are prodigious — he simply finds too little to flesh out the man or to tell us what he really did for, or against, the Russians. Meier struggles mightily to plug in the yawning gaps with sidebars, history and speculation. Historians are certainly within their rights in trying to supplement the historic facts with some guesses about the influences of the time and the place.   http://louis-j-sheehan.com  But in “The Lost Spy,” there are too few historic facts and far too many guesses.

Page after page, Meier tells us what Oggins might have or could have or should have known, felt, witnessed or concluded. “No document records that Cy and Nerma stood among the fighters, but it is hard to imagine them missing the chance.” “At some juncture along his journey, Cy may well have sensed a strange presence.” “It is conceivable that Cy contributed to The Voice.” In these cases, there is at least an element of retrofitting — we know how Oggins ended up, and so can presume that he was involved in such radical activities. But at some points the speculation turns to fancy, as in this addendum to a riff about why Oggins may have changed his first name from Isaiah to Cy: “It was a name that also bore the unmistakable aura of one of the heroes of the day, the legendary ex-Red Sox pitcher recently retired after 22 seasons, Cy Young.”

Meier uses the subjunctive mood to signal the reader that he is often just guessing. But, alas, he doesn’t use it often enough. There are stretches of the story in which it’s not clear whether Meier is reporting, speculating or inventing. Oggins’s arrest, for example, is recounted in graphic detail: “By the time the doors of the voronka opened, Cy was in darkness. Two men hoisted him by either arm and took him in, stopping only at the receiving room. Cy stood as a clerk wrote down his name and the date and place of birth.” How does Meier know? He would know how such arrests usually took place, since there is ample literature on this. But where did he learn that “as he sat in his cell, Cy could not help but return to the past”? The text offers no clue, and neither do the notes.

Such attempts to graft a persona onto Oggins are unfortunate, and sometimes grating, because Meier’s sketches of the background to his narrative — the radical scene in New York in the 1920s, the Soviet intrigues in Berlin, Paris and Shanghai, the murderous cynicism of Stalinism — are well researched and often quite fascinating in themselves. We meet a Russian Romanov living in faded splendor in Paris, we find J. Edgar Hoover building up his army of informants and agents, we are offered vignettes of malicious Soviet projects in Europe, ranging from counterfeiting to assassination. But here again, we are never sure whether Oggins had anything to do with these events. Meier describes in some detail, for example, an elaborate counterfeiting operation by the Soviets that “may have” been run out of the house in Berlin where Oggins lived. “Were Cy and Nerma involved? The spy memoirs, court records and once-secret archives in Berlin and Moscow yield no trace.” http://louis-j-sheehan.com

Perhaps that is the true story here, how little trace remains of an immigrant’s son who got caught up in the radicalism of the ’20s and ended up devoured by the very “new world” he dreamed of. Meier’s problem may be that he tried too hard to turn this into a “Darkness at Noon” or a “Dr. Zhivago” — which, unlike the story of poor Cy Oggins, are fiction. http://ljsheehan.livejournal.com

traumas

August 23, 2008

Louis J. Sheehan.  There’s good news and, not surprisingly, bad news for children and teenagers grappling with the psychological aftermath of trauma. On the up side, research shows that certain interventions ease post-traumatic stress disorder and other trauma-related problems in young people. On the down side, most mental-health practitioners use trauma treatments for kids and teens that lack scientific support.  http://Louis2J2Sheehan2Esquire.US

These conclusions come from an extensive research review conducted by the Task Force on Community Preventive Services, an independent group of 12 investigators partly funded by the federal government. Its findings appear in the September American Journal of Preventive Medicine.

To make matters worse, pediatricians and school officials rarely screen children for past exposure to traumatic events and resulting psychological symptoms, the task force notes. Efforts are underway to develop web-based guides for parents and teachers to identify and help kids experiencing trauma-related problems.

Although the review focuses on Western countries, research has also just started to explore the use of trained non-professionals to treat traumatized children in developing nations, where mental health workers are scarce.

Kids with trauma-related psychological problems tend to do poorly in school if they remain untreated or are inadequately treated, remarks psychologist and social worker Marleen Wong of the University of Southern California in Los Angeles.

An estimated one in eight children have experienced physical or sexual abuse, neglect, bullying and other types of maltreatment. More than one in three have witnessed violence or experienced it indirectly, such losing a parent to murder but not witnessing the crime. Children experiencing such traumas can develop PTSD or other mental disorders.

“In mental health as in education, trauma leaves children behind,” Wong says. Minority children’s regular exposure to violence in poor communities contributes to the academic achievement gap between black and white students, in her view. http://Louis2J2Sheehan2Esquire.US

Evidence indicates that individual and group cognitive-behavioral therapy reduces symptoms of PTSD, depression, anxiety and related behavior problems in traumatized children and adolescents, the task force reports. Cognitive-behavioral techniques include discussing or writing about traumatic experiences, learning relaxation techniques and replacing paralyzing fears with more realistic assessments. Weekly sessions can extend over one to three months.

The review finds insufficient evidence to recommend any of five other treatment approaches — play therapy, art therapy, drug therapy, psychodynamic therapy or psychological debriefing.

Play therapy and art therapy encourage youngsters to express and control traumatic experiences through these activities. Drug therapy typically prescribes antidepressant or anti-anxiety medication to young trauma victims who have PTSD. Psychodynamic therapy focuses on understanding and changing unconscious reactions to traumatic events. Debriefing consists of group discussions and education conducted one to three days after a traumatic event.

More than three-quarters of U.S. mental health professionals who treat children and teens with PTSD have reported using treatments that have not been scientifically reviewed or for which effectiveness could not be determined by the task force.

“That’s disappointing, but it’s encouraging that a substantial body of evidence supports both individual and group cognitive-behavioral therapy,” says task force director and epidemiologist Robert Hahn of the Centers for Disease Control and Prevention in Atlanta.

Several studies of eye-movement desensitization reprogramming, a controversial trauma treatment, were included in the task force’s review of cognitive-behavioral therapy. In EMDR, patients visually track a therapist’s back-and-forth hand movements. Treatment also includes confronting traumas and revising trauma-induced fears. It is these cognitive-behavioral components of EMDR, not the eye movements, that offer emotional relief to young trauma victims, Hahn says.

Although the new review provides “important confirmation” that cognitive-behavioral therapy quells PTSD and other problems in young trauma victims, it will be difficult to train enough practitioners to provide such treatment to large numbers of natural disaster and war survivors in developing countries, remarks psychologist Mark van Ommeren of the World Health Organization in Geneva.

Researchers should also examine social interventions, van Ommeren says. Disrupted social networks in the wake of disasters powerfully provoke psychological problems in children, he notes.

Social interventions include providing family reunification services, restarting formal or informal schooling, creating group activities for isolated children and recruiting teens for relief efforts. Such interventions show promise as ways to assist former child soldiers in Africa (SN: 6/7/08, p. 5).

Social strategies are much harder to study than clinical ones are. The task force evaluated all clinical treatment studies of children and teens exposed to various traumas published up to March 2007. Hahn’s team reviewed only studies that included non-treated comparison groups and met other qualifying criteria.

The final review consisted of 11 studies of individual cognitive-behavioral therapy, 10 studies of group cognitive-behavioral therapy, four studies of play therapy, one study of art therapy, two studies of psychodynamic therapy, two studies of drug therapy and one study of psychological debriefing. Louis J. Sheehan.

grades 0000007 Louis J. Sheehan

August 21, 2008

New Grading Policies
Roil Dallas Parents, Teachers

Scores, Deadlines
Are Eased in Plan
To Limit Dropouts
By JEFFREY BALL
August 20, 2008; Page A2

DALLAS — As students prepare to return to school here Monday, teachers and parents criticized the relaxation of the district’s grading policies in a state that helped trigger national testing requirements.

[falling behind]

The Dallas Independent School District’s new policies give students who do poorly more chances to improve their grades. Among the changes: High-school students who fail major tests can retake them within five school days, and only the higher scores count.

School officials say the changes are designed to reduce one of the highest dropout rates in the state. According to the Texas Education Agency, 25.8% of students in the Dallas district who enrolled as ninth-graders in 2003 dropped out before their class’s scheduled 2007 graduation.

But the policies have sparked criticism since the Dallas Morning News reported them last week, with angry parents and teachers contending that the district is watering down educational standards for its more than 160,000 students.

“These kids have already gone too far in not being held accountable,” says Tracy Dotie-Hill, who has one daughter in Dallas’s W.E. Greiner Middle School and another who just graduated from the district’s Skyline High School. “When you go into the work force, if you don’t meet the standards or deadlines, you have to reap the consequences.”

Teachers say the policy undermines their authority. “It’s micromanaging and not trusting the fact that we are professionals,” says Diane Birdwell, who teaches 10th-grade world history in a Dallas high school and is executive vice president of the Dallas chapter of the National Education Association, a teachers’ union.

Dallas school administrators say they aren’t lowering standards — they are giving students additional chances to meet existing requirements.

“Chief among the reasons children drop out of school is because they are failing their course work,” says Denise Collier, the Dallas district’s chief academic officer. “We don’t want to give them a pass, but at the same time we don’t want to pass them over.”

The Dallas policies appear to fly in the face of a national trend toward tougher grading standards, according to Dan Goldhaber, a research professor at the University of Washington’s Center on Reinventing Public Education.

More than a decade ago, loose standards by local districts led several states — including Texas — to exercise tougher control over their public schools. Later, the federal government raised its oversight, implementing the 2001 No Child Left Behind Act. That law has itself come under some criticism for emphasizing standardized-test scores.

“This is the reason we’ve gotten to this place,” Mr. Goldhaber says, referring to the new Dallas grading policies. “It really does look like the lowering of standards.”

The new Dallas policies stipulate that students must be given at least one chance to make up work they don’t turn in on time, with any penalty to be determined by the school, and that high-school students enrolled in regular courses can be assigned no more than ten hours of homework a week.

In addition, no student can receive a final score lower than 50 out of 100 on a report card — a policy the district says has existed in the past.

Among large school districts in Texas, Dallas’s dropout rate is second only to San Antonio’s, and it is higher than the 22.1% rate in Houston, the state’s largest school district. Almost two-thirds of the students in Dallas’s 225 schools are Hispanic, while 29% are African American and 5% are non-Hispanic white.

Some Dallas parents say the changes are necessary. “We’re going to have to come up with some concepts [to keep] a child in school,” says Ola Allen, president of the parent-teacher association at Skyline High School.

But the move could hurt students overall, says David Figlio, a professor of education and economics at Northwestern University. “It wouldn’t surprise me at all if it helps on the margin with the dropout problem but ends up reducing the incentive for students to do well,” he says. “This is a case in which there’s no free lunch.”

Write to Jeffrey Ball at jeffrey.ball@wsj.com1

URL for this article:
http://online.wsj.com/article/SB121919578444955351.html
Hyperlinks in this Article:
(1) mailto:jeffrey.ball@wsj.com
Copyright 2008 Dow Jones & Company, Inc. All Rights Reserved
This copy is for your personal, non-commercial use only. Distribution and use of this material are governed by our Subscriber Agreement and by copyright law. For non-personal use or to order multiple copies, please contact Dow Jones Reprints at 1-800-843-0008 or visit www.djreprints.com.
Louis J. Sheehan

<!–
LoadIframes()
// –>

Victorian 0000006 Louis J. Sheehan

August 21, 2008

WHAT: The world’s first computer
WHEN: 2008
HOW: A Victorian gentleman named Charles Babbage invented “Difference Engine No. 2” in 1849, but he never managed to build it.
WHERE: Silicon Valley’s Computer History Museum in Mountain View, California, houses one of the world’s largest collections of dingy beige boxes and other computing artifacts. This five-ton metal contraption, finished this year according to Babbage’s original drawings, joins them through May 2009.

Louis J. Sheehan

Hirchhike 0000004 Louis J. Sheehan, Esquire

August 21, 2008

Incan stonework in one direction, stepped agricultural terraces in another: Your eyes lock on the mountains surrounding Machu Picchu, and at last you’ve found peace and quiet. Then you’re ready to move on. You click on Antarctica, choose a region, and zoom in. Suddenly you’re standing on an iceberg in the middle of a group of playful Adélie penguins on rocky, volcanic Franklin Island (above right).http://Louis-J-Sheehan.de

The 360° World Atlas DVD lets anyone with a computer become a virtual hitchhiker, no packing or neck-craning required. Creator Everen Brown does all the hard work for you. He jets around the globe, lugging a 40-pound bag full of 600 rolls of film past airport security, and picks a picture-worthy spot. Then he takes one of the world’s last Globuscope rotational cameras (no longer in production), holds it over his head (sometimes he lies on his stomach), and waits (sometimes for hours) for the right shot. When he sees it, snapping the picture takes only a second. The lens rotates full circle, so you get to see what’s across from the Taj Mahal’s minarets too. Once Brown develops the film, he embeds the images into an interactive atlas ($69.95, www.360atlas.com) that shows off head-turning views, panorama style.  http://Louis-J-Sheehan.de

clone 0000003 Louis J. Sheehan

August 21, 2008

Louis J. Sheehan.  Whether defying the dean of the University of Pennsylvania School of Medicine so he could publish a book on world health or challenging the titans of cosmology, Robert Lanza has never followed the script. It’s no wonder, then, that this renegade doctor would lead the charge into medicine’s most controversial turf: the creation of cloned embryos for therapy and the engineering of spare human parts.

The value of therapeutic cloning has long been clear to Lanza, who did his early work with South African heart transplant pioneer Christiaan Barnard. Starting from those early days, Lanza understood that the barrier to tissue transfer was rejection by the recipient. From an entire organ to a dose of embryonic stem cells, if the tissue’s DNA came from anyone else, the transplant would be rejected without the aid of harsh immunosuppressive drugs. “The treatment could be worse than the problem,” Lanza found. But embryonic clones, the source of an endless supply of stem cells imprinted with one’s personal DNA, could alter the equation in favor of the patient and augur a paradigm shift in medicine on par with the changes brought about by antibiotics and vaccines. http://Louis-J-sheehan.info

Lanza’s single-minded quest to usher in this new age has paid dividends in scientific insights and groundbreaking discoveries. Today a world force in the field of regenerative medicine, he’s close to delivering cellular therapies that might reseed the immune system, heal damaged hearts, even save limbs. Yet for almost 20 years government policy has kept his innovations literally on ice. He has been called a murderer for tampering with embryos, and personal threats were so common at one point that he believed he would be killed.

Enduring tough times and fighting for his beliefs suit Lanza well. He grew up poor in the Rox­bury section of Boston and, later, suburban Stoughton, where he had a difficult relationship with his mother and was distanced from his professional gambler father. Year round, Lanza says, he was rarely allowed inside his own house except to eat dinner and sleep. With nowhere else to go, he spent his youth roaming the nearby wilderness immersed in nature’s mysteries.

Though initially labeled “slow” at school, in 1969 Lanza distinguished himself by transferring genes from black chickens to white ones when he was just 14, a mere three years after scientists cracked the genetic code. That extraordinary early feat, eventually published in Nature, signaled a raw scientific talent that his mentors (who came to include Jonas Salk and B. F. Skinner) likened to Einstein’s. In a 2001 article, U.S. News & World Report called Lanza the “living embodiment” of the fictional genius in the movie Good Will Hunting, whose Massachusetts accent is as thick as Lanza’s own.

Today Lanza lives on an island in a small Massachusetts lake, keeping a veritable museum of fossils and dinosaur bones and surrounded by the nature he cherishes. DISCOVER senior editor Pamela Weintraub interviewed Lanza at his Worcester office.

You have always bucked authority, haven’t you?
In the real world, people had a different plan for me, the boy from Roxbury with a family so rough and lacking in education. There would be fights. The police would be called.

The Stoughton public school system had three classes in elementary school: A, B, and C. I was put in the C class with the kids throwing spitballs at the teachers, the ones who had been held back.

How did you cope?
There was a golf course nearby, so I earned money by collecting and returning golf balls. When I had saved $18.95, I had enough to mail-order a little squirrel monkey, sitting in the palm of a woman’s hand, that was advertised in the back of Field & Stream. I sent in my money and forgot about it, but a year later I came home from school and there’s this monkey in the middle of the kitchen, tied up inside a box with these pellets in it. “Stay away; it will attack,” my mother said, but here was this little teeny baby squirrel monkey. It was sneezing; it had a cold. I went up to it and it just curled up. And it became my best friend. It was just like a little person—little fingerprints, everything. It was actually smarter than a lot of my friends.

Back then I was on my own. I went into ponds to get snapping turtles. I would go out for miles in the middle of the winter, using footprints to track raccoons. I fell through the ice on a pond 15 miles from civilization up to my waist when it was below zero. I would go up in trees and catch little screech owls in their holes. I’d go on long excursions trying to figure out how the universe worked. Even at that early age, I was in awe and wonder of the world.

A squirrel monkey and nature sustained you. Was that enough?
Fortunately, I also had a neighbor, Barbara O’Donnell, and her husband, Eugene—wonderful people. If I brought a bug to them, they’d buy me a magnifying glass; if I found a bird egg, they’d get me a book on birds. Every now and then you run into an extraordinary human being who does things selflessly, and Barbara O’Donnell was like that. When a black family moved in next door, the neighborhood tried to stop it, but Barbara interceded. She always fought for what was right. They say that you incorporate the superego structure of your parents. Well, not my parents, but hopefully I’ve incorporated Barbara’s and Gene’s. Today my colleagues and the [Catholic] Church and the president and even the pope can attack me and it’s just like, you know what? I’ve seen a lot worse. Say what you want. I’m doing what I think is right.

It’s lucky that you were able to find such kindness and support. Yet school officials still kept you in the C class?
When I was in the fifth grade, my teacher realized that I didn’t fit in the C class and encouraged me to do a science project, so naturally I did it on animals, and my best friend, Steven, did his on rocks. He won first prize and I won second. That was my first entry. That’s when I began to feel I shouldn’t have been pegged because of my family circumstance, and that people should be able to prove themselves.

I take it that’s what you did to prove yourself.
Every year after that I did a science project, and in the eighth grade, Barbara O’Donnell, my neighbor, became my science teacher. If not for what she did for me then, I wouldn’t be here today. She arranged for me to be in the honors biology class in high school, something that was actually open only to the students at the top of the A division. It caused chaos because I leaped over all these people ahead of me. “In this one honors class, biology, they’ve got this loser….What is this the rats dragged in?” I was determined to prove them wrong. So I hatched an idea to win the whole science fair, something that only seniors had done. My plan was to alter the genetic makeup of a white animal and make it pigmented.

The genetic code had been cracked only three years earlier, in 1966. Still you planned what amounts to genetic engineering.
My honors biology teacher told me it was impossible. That made it a challenge. I saved up nickels and dimes from the golf balls and took a bus and trolley to Harvard’s Countway Library of Medicine. I ended up finding an article on extracting nuclear protein [containing DNA] from cells using ethanol. Barbara drove me to a farm to get eggs laid by pigmented chickens and we tracked down another farm to get eggs from white Plymouth Rock chickens. I still remember trying to get the equipment. I went to the hospital and talked them into giving me syringes. Another hospital gave me penicillin so my animals wouldn’t get infected, and I found a guy who worked at one of the state labs who had a centrifuge and chemicals in his basement—that’s where I extracted the DNA. But most of the work I did at home. My mother would not allow me to have anything in the house, so I found an unfinished back room next to the furnace in the basement, and there, in a little corner, I built an incubator for the white chicken eggs. At a very early stage, I introduced the pigmented genes into the white embryos with a syringe. Which, of course, was very problematic because I had to figure out how to make the eggs so you could see where the right spot was, and most of ’em you would kill or they would die. There I was trying to alter the genetic makeup of a chicken, and my mother’s talking to a neighbor saying, “Oh, yeah, Robby is trying to hatch chicken eggs.”

+++

Robert Lanza

Did it work?
Some of the white chickens were born with patches of pigmentation. But to truly prove it, I had to make my experiments blinded and controlled. What I needed was to do these experiments more correctly, not in my basement, and now I’m thinking, “OK, I really need to talk to someone who understands this stuff. So I’m gonna go to the greatest place on the planet, Harvard Medical School, and I’m gonna talk to a Harvard doctor. Now it’s time to take this up a notch. We’re gonna get serious.”

Did you make an appointment?
Oh, no. I didn’t even know where I was going. I’m walking around asking people how to find Harvard Medical School. I had no clue. I finally find it, with all that granite and slab stairs worn from the generations of people coming and going. My endorphins are flying. I go to the front door and the guard would not let me through. I’m not giving up that easy. I went all around the building trying all the doors, but everything’s locked. So I stood by some Dumpsters trying to look inconspicuous until someone came by—this little short guy, bald, with khaki pants and a bunch of keys in his hands. I figured it was the janitor. So he opens the door and I just sort of slip in. He keeps walking, but about halfway down the corridor he turns around and says, “Can I help you, sir?”

“No. I’m looking for a Harvard doctor,” I said.

Now, what I didn’t know was that this was Steven Kuffler, chair of neurobiology. Instead I told him that I was friends with a janitor who lived down the street from my house and that I worked at the school cafeteria washing plates. I’m from the underprivileged class too, I said. He knew I thought he was the janitor. He said, “Why are you here?” I said, “Oh, it’s got to do with nuclear protein and inducing melanin synthesis in albino chickens.” I could see that I was impressing him. He has no idea what DNA is, [I am thinking]. Finally he said, “Well, I think I know someone who can help you.” I remember him bringing me up in the elevator, past all the spaghetti wire, all that neurobiology equipment and circuits—it was so awesome and impressive—right to Josh Sanes, who now runs the brain center at Harvard. He was just a grad student at the time, putting probes in caterpillars and looking at their neurons. I talked to Josh all day. Eventually they invited me back to repeat the experiments correctly. The paper was ultimately published in Nature in 1974. Every now and then the janitor would show up and I was so excited to see him. It was only later that I found out who he was.

So what happened back at the high school?
The teacher gave me a C and everyone else got an A. He didn’t like the way I wrote it, but the grade was changed after I won the state science fair. The night of the science fair, my mother tried to stop me from leaving. “You’re not going anywhere,” she said. Barbara was out front honking the horn, waiting to give me a ride. I said, “Ma, I’m going. I don’t care what you say.” This was the first time I rebelled like that. I remember her breaking down in tears. When I arrived, the whole gymnasium was overflowing out the back door. Then they went from the bottom up, fourth grand award, third grand award. And then I was first grand award, and I noticed my mother was in there—she did show up at the end. Then I got the Massachusetts Medical Society Award, and The Boston Globe gave me an award. That was my vindication that I wasn’t stupid.

You got to the Ivy League, and soon you were working with heart transplant surgeon Christiaan Barnard. How did that happen?
At the University of Pennsylvania, I was in the University Scholars Program. We could take any classes we liked as undergraduates, so I started taking medical school classes in 1975. It was a wildly exciting time for heart transplant medicine, so I wanted to go to South Africa to work with Christiaan Barnard. I wrote to Barnard, and he said, “Yeah, you can come.” It was fascinating but horrific. Some of the heart transplant patients had run out of their immunosuppressive drugs; they couldn’t breathe. They were in wheelchairs. Their bodies were rejecting the organs and they were dying with their families all around them. Anyway, I came back to Philadelphia with a whole pile of papers coauthored with Barnard.

I spent a couple of years rolling pennies and eating canned spinach and pasta while I tried to understand the universe.

Obviously you didn’t go into surgery. What came next?
By the time I graduated from medical school, heart transplant surgery had become conventional, so I moved to Los Angeles and did something I’ve never told anyone else about: I spent a couple of years rolling pennies and eating canned spinach and pasta while I tried to understand the universe, an effort I felt had reached a dead end.

Dropping everything to spend years thinking about cosmology could be called self-indulgent.
For me it was the equivalent of hiking around Europe—I was hiking through the universe, and I needed the intellectual freedom to just think. I’ll tell you, putting the puzzle together is not trivial, but after two years I had a new theory of the universe.

Your book on that work, called Biocentrism, cowritten with the astronomer Bob Berman, will be out soon. In it you propose that our current theories of the universe will never work unless they account for life and consciousness. Can you explain?
Look at this coffee cup. You say it’s right there, but the truth of the matter is you can’t see that through your brain. Your brain has a bone around it. What is happening is that what you see is reconstructed in your mind. We have these words space and time, but you can’t touch them. They’re not objects, they’re not things, they go forever. Space and time are really tools of animal sense perception, the way we organize and construct information.

You have suggested that reality is determined by the conscious observer. Most physicists view consciousness as an accident.
There was a paper published in Science this February, and what it showed was that if you do an experiment with a photon, put it in the apparatus, that what you do right now actually changes an event that already occurred in the past. Now isn’t that bizarre? That is the same universe that you and I are in. How can the physics in this experiment actually show that if you do something right now it retroactively changes an event that has already happened? You can play your little games with it, but any way you cut the pie, if you observe something it acts as a particle, and if you don’t it acts as a wave. It is not an artifact of the system. Those experiments are real. Get over it.

You’ve said physical laws are exactly balanced for life to exist.
If there were one-billionth of a difference in the mass of the Big Bang, you couldn’t have galaxies. If the gravitational constant were ever-so-slightly different, you couldn’t have stars, including the sun, and you would just have hydrogen. There are 200 parameters like this. We now have people out there talking about an intelligent design, saying “God” is the explanation. But it is really because quantum theory is right: Everything is observer-determined and the past and present are relative only to you, as the observer. It all fits, but the problem is, you then do need to accept what people will not accept: When you turn your back to the moon, it no longer exists.

Despite the cosmic uncertainty, you went on to pursue a most tangible goal.
Considering my small role in the universe, I thought I could best apply myself to trying to treat or even cure diabetes, and possibly other diseases that affect the health and lives of millions. Instead of transplanting whole organs like the heart, I decided to work with cells—from a biocentric viewpoint, the fundamental units of reality and the bedrock of our observer-determined world. The person I approached was Patrick Soon-Shiong, a UCLA professor who was trying to transplant the insulin-producing cells called islets as a treatment for diabetes. The hurdles there were similar to those we faced with heart transplants: overcoming a shortage of tissue and preventing rejection.

+++

Robert Lanza

What was the strategy?
At first I thought we could isolate islets from cadavers or animals and protect them from rejection by putting them in little capsules. We managed to get around that with our first patient, a Boeing executive with pancreatitis. He had to have his pancreas removed, and instead of throwing his gland away, we took it back to the lab and got maybe 50,000 to 100,000 of these insulin-producing cells. We injected the cells back into his portal vein and they took up home in the liver and the guy was fine. It made a lasting impression on me because what it meant was that if you could deliver a person’s own cells, you would eliminate the risk of rejection, and you could give the patient insulin-producing cells without the need for insulin injections for the rest of his life.

How did you get from islet cells to embryonic ones?
Around 1990, when I was still at UCLA, I was approached by BioHybrid­ Technologies in Shrewsbury, Massachusetts. At first I thought, “Why would I leave sunny California to go back to the rain and slush and snow?” But I went out for the interview and the president, a brilliant man named Bill Chick, asked me what would make me happy. I threw out what I thought was a preposterous figure for a salary, and when I got home there was a message saying it had been accepted. I didn’t realize at the time that it was below the market rate. At the company Christmas party I met his daughter, and she said, “So you’re the one with the tacky tie. You’re the one my father stole.”

It turned out that Chick had suffered from diabetes since childhood. Now he was dying, but he wanted to save himself by using the encapsulation method I had proposed at UCLA. It was a race against the clock—Bill had so much angioplasty and heart surgery he was being glued together. After a while we actually succeeded in dogs. We got islet cells from the pancreases of healthy dogs, encapsulated them, and transferred them to diabetic dogs, who became insulin independent. That’s when I learned about Dolly, the sheep cloned by the Roslin Institute in Edinburgh, Scotland, and I said, “Aha! That’s it.” If you can create an embryo genetically identical to the adult—that is, a clone—you can harvest immune-compatible cells to replace any tissue you might want without fear of rejection. http://Louis-J-sheehan.info

In essence the clone would supply stem cells to the parent?
Right. You can do all kinds of tricks with embryonic stem cells, but if they come from another individual, you still have the problem of rejection. You still need powerful immunosuppressive drugs that cause cancer. My idea was to clone the sick individual, not for reproduction but for therapy. The stem cells produced through this therapeutic cloning would, like other embryonic stem cells, be capable of developing into many cell types and serve as a repair system for whatever part of the body required replenishment at the time. You solve the rejection problem, and you have unlimited amounts of tissue. I tried to convince Bill to try this, but he wouldn’t budge. In the end he had strokes and didn’t know what was going on. He died in 1998 in front of my eyes.

Then I learned there was a cloning company right up the street from BioHybrid that was the top in the world, called Advanced Cell Technologies, or ACT. It was almost like fate. By then I was attached to Massachusetts. I’d bought a little island, where I lived. I had all my fossils and dinosaur bones there, and I had landscaped it. My island had swans; it had a beaver and a beaver den 10 yards from my door. I wanted to stay around.

So you went to ACT and asked for a job?
Before they would hire me, they gave me a task that was like bringing back the witch’s broom. There was a question about whether the National Institutes of Health would allow the work. Even though this was for therapy and not reproduction, it still involved cloning embryos, and the public was totally against it. Many considered it murder. So I was asked to get all the Nobel laureates in the country to sign a letter to support embryonic stem cell research, addressed to Harold Varmus, the head of the NIH. This was in the old days, when everything was by fax. Actually, I had this whole drawer of all the letters signed by 70 Nobel laureates. The effort was published in Science, and a few months later, many college presidents also signed on.

At the time, ACT was a subsidiary of a poultry genetics company, doing work in agriculture. When I joined they made the move from animal cloning to human therapy, and we knew we would get hit, big-time. I may be the only person who’s had the [Catholic] Church, the pope, and a couple of presidents condemn my work. At one point we had bodyguards here. There was a bombing up the street; then a doctor at a local in vitro fertilization clinic was targeted. I didn’t think I would be alive for more than a few years.

And you, alone on your island, were so vulnerable to attacks.
I would go for a walk, listening for sounds. I was one of the most visible people in cloning and yet I was isolated. I figured there was more than a 50 percent chance that I would be knocked off. But I wanted to go out trying. I’ve always followed my heart.

Can you describe the original groundbreaking work at ACT?
We injected human DNA from an adult cell into an egg from which the nucleus had been removed. We managed to clone early-stage embryos that grew to four or six cells in size. This was obviously far short of getting stem cells, which require a blastocyst [an embryo with a larger cluster of cells]. In fact, even to this day, a decade after the cloning of Dolly, scientists still have not cloned human embryos developed enough to generate patient-specific cells.

You’ve been exploring other ways of producing patient-specific cells. What are they?
We recently published a paper on a cell we created called a hemangioblast, which exists only transiently in the embryo but not in the adult. I think of them like unicorns, these elusive cells that we had hypothesized and sought for years. With the ability to become all of the blood cells—including your immune cells, red blood cells, all of your blood system, as well as vasculature—hemangioblasts have been biology’s holy grail. What we discovered is that we can create literally millions or billions of these from human embryonic stem cells. Now that we have them, we are harnessing, for the first time, one of nature’s early, most profoundly powerful cellular building blocks. The point is, we can use transient, intermediate cells like hemangioblasts as a toolbox to fix the adult so you don’t have to have limbs amputated, so you may not have to go blind, to prevent heart attacks. We can direct their development into different cell types by adding certain molecules to them as they divide.

If you can create an embryo genetically identical to the adult, you can replace any tissue without fear of rejection.

How does it work?
We found that when we injected these cells into a damaged, is­che­mic limb, there was almost 100 percent restoration of blood flow in a month. Before, the limb would have been amputated, but now it was restored. As to heart attack, injection of the cells cut the death rate in half.

Since these cells give rise to the immune system, what about using them to treat autoimmune diseases?
There are more than 80 autoimmune diseases. What’s interesting is that when you do a bone marrow transplant for cancer, some of those with autoimmune disease go into remission, as if the immune system has been eliminated and allowed to rebuild from scratch. Using hemangioblasts that are the progenitors of the immune system, we’re hoping we can replace the immune cells too.

+++

Are there other, intermediate embryonic cells that might, in similar fashion, give rise to the nervous system or brain?
Yes. The way to think of this is that you have a tree with branches that give rise to all of the different tissue types of the body. The hemangioblast, for instance, gives rise to one branch—to blood cells, vessels, and the immune system. But there are also neural stem cells as well as early progenitors that have this plasticity in most of the other systems of the body. Right now we’re trying to discover how to isolate and expand them.

You’re a bit limited using just cells. You started out with Christiaan Barnard transplanting hearts.
To realize the full potential of stem cells, we must learn to reconstitute them into more complex tissues and structures. So if we want to make an artery or bones or even an entire kidney or a heart, we need to learn to assemble and grow them on a biodegradable scaffold, which the body can later absorb. In one study we used the cells to make little kidneys that even produced urine. The urine had concentrated creatine or urea, meaning the kidneys were actually removing toxic materials from the blood. Entire bladders have been grown this way. Other researchers are doing bones, heart valves, and cartilage for joints.

The officer had a 16-year-old son who would go totally blind in two years without the therapy. I was almost in tears.

This seems like lifesaving technology on an unprecedented scale, yet the work has been stymied by politics. It must be frustrating to have these cells sitting around the lab, in storage, when you could be helping people.
Four years ago I was driving to work, going up a hill on a quiet little road with a speed limit of 15 miles an hour. I was in a rush and whirled into the parking lot, and there’s this police cruiser next to me. I almost hit it. “Oh, jeez, now I’m screwed,” I thought. I went into my office, started working, and a few minutes later a scientist from the next office over comes in and says, “Bob, there’s a police officer out there who wants to see you. He has handcuffs and a gun.” The whole lab is thinking he’s there to arrest me. He says, “Dr. Lanza, could I speak to you in your office?” so I brought him in. It turns out that I had just published a paper showing that we could create human retinal pigment epithelial cells capable of restoring visual function in animals. The officer had a 16-year-old son who would go totally blind in two years without the therapy. By the time he finished his story, I was almost in tears because we had these cells and they had been frozen at that point for nine months.

Why couldn’t you take them out of storage to help the boy?
We didn’t have $20,000, which is what we needed to do the preclinical studies required for working with people. At that point, our phones had been turned off. We didn’t have a fax machine. I couldn’t even afford bottled water for my pipettes. The point is, there is just no funding because basic research is generally funded by the government and the government will not fund stem cell work.

What else are you storing, still unfunded, in the vault?

We have cells that reverse paralysis in sheep that have spina bifida and can’t walk. After we injected our cells, the first animal that we treated returned to normal and was walking fine. The same model could work for paralyzed humans, but without funding, we haven’t been able to repeat the experiment in five years. People are in wheelchairs when there could be a cure.

A few years ago a woman contacted me. In the course of chemotherapy for a tumor, something must have been activated, and for some unknown reason the glial cells in her cerebellum had started to degenerate. She was a lady with all these kids. Slowly she started to lose her ability to talk. She began to use a walker. She got worse and worse, and then, not long ago, she died.

You could have helped her?
Yes, we have cells that probably could have helped her with a single injection. One of her sons kept coming and asking, “Is there anything you can do?” But we didn’t have the resources to go through the process at the FDA. It’s heart wrenching to see this happening, knowing that this work is being held up.

Amid all this, are you still trying to achieve your first dream, harvesting embryonic stem cells from human clones?
We’re continuing this work, but with less urgency since the discovery of induced pluripotent stem cells, or iPS cells—adult cells that have been reprogrammed back to an embryonic state. We’re working on new ways to reprogram skin cells that would allow us to safely create a bank of stem cell lines that would closely match the population as a whole. It turns out that only 100 cell lines could give you a complete haplotype, or immune, match for 50 percent of the U.S. population. These reprogrammed cells are not as controversial since you don’t use cloning or embryos.

What do these technologies portend for human longevity?
It turns out that the human life span plateaus as it approaches a roof of about 120. By eliminating infectious diseases, some chronic diseases, and cancer, we can get the life span past 100. I think with tissue engineering we can patch you together like a bicycle tire, replacing a kidney with a kidney and a heart with a heart, to about 120 years. That was always my thinking: That was the limit. But with these hemangioblasts, I now have questioned my own rules. These cells can go in and fix the damaged tissue inside, almost like nanoparticles. We may be able to do the same thing with similar cell lines for neurons, where we can repair the damage in the brain itself. So if it continues the way it’s going, we may break that ceiling, like breaking the sound barrier. I’d be very hesitant to put a lid as to where longevity is going to go.

You’re launching the future of medicine, but it is still on hold.
Rather than curing disease, we’re trying to get around theological problems. It’s not what I signed up for in medical school. I can’t tell you how many times I’ve thrown my hands up and said, “Enough, I can’t take it anymore,” but then I’m back the next day. We’re crippled, but they can’t stop us forever. We’ve now got enough irons in the fire and hopefully ways to bypass many of these objections. But it’s just a shame that the research has been held up so long. We’re living through a paradigm shift. People are going to look back at us and say, “They used to cut people’s legs off.” Then they’ll just give an injection and the blood flow will be restored and the limb saved. If I were a patient and I knew I was going to have my leg cut off and something could be done, I would be demanding it. But most people, even most scientists, don’t realize what we’re capable of. I realize it because I’m doing the work and I can see what’s possible before my eyes.

task 0000002 Louis J. Sheehan

August 21, 2008

In a neat example of Internet-enabled “crowdsourcing,” the method of distributing a large task to many contributors, researchers are using an anti-spam program to get people to decipher damaged or faded texts, one word at a time. Chances are that if you’ve solved one of those distorted-word tests to secure an account with Facebook, Craigslist, or Ticketmaster, you’ve helped The New York Times inch a little closer to digitizing its entire print newspaper archive from 1851 to 1980 [CNET]. Louis J. Sheehan.

The program, known as reCAPTCHA, is widely used to ensure that humans, rather than spam bots, are commenting on blogs (including some of DISCOVER’s) and signing up for free email accounts. “More web sites are adopting reCAPTCHAs each day, so the rate of transcription keeps growing,” said [lead researcher Luis] von Ahn. “More than 4 million words are being transcribed every day. It would take more than 1,500 people working 40 hours a week at a rate of 60 words a minute to match our weekly output” [Telegraph]. The service is available for free to any site.

Ahn’s lab uses two different optical character recognition (OCR) software programs to scan an old book or newspaper article and convert it into a digital, searchable file. But when the programs disagree on the reading of a word, that word is added to the reCAPTCHA database, and used as part of an anti-spam puzzle. According to a report published in the journal Science [subscription required], humans decipher such words with 99 percent accuracy.

In 2000, von Ahn helped invent the first “CAPTCHA,” which stands for “Completely Automated Public Turing test to tell Computers and Humans Apart,” with a nod to the early computer scientist Alan Turing. The new reCAPTCHA cleverly slips a useful task into what has already become a mundane Internet activity. Says Ahn: “We are demonstrating that we can take human effort — human processing power — that would otherwise be wasted and redirect it to accomplish tasks that computers cannot yet solve” [Wired News].

Last year DISCOVER saw how humans could act as artificial artificial intelligence at the Amazon Mechanical Turk, another fine example of crowdsourcing.

Image: Science/AAAS

August 14th, 2008 Tags: , ,
by Eliza Strickland in Technology | 19 comments | RSS feed | Trackback >

19 Responses to “Computers Exploit Human Brainpower to Decipher Faded Texts”

  1. Jeremiah Says:
    August 15th, 2008 at 7:36 am Um… shouldn’t that be “This aged portion of society was”? Haha.
  2. john powell Says:
    August 16th, 2008 at 11:33 am A Mental Blockage

    In the current is often found
    Unknown particles of sky and ground.
    Oft they appear as phantasms or as dreams
    Or oft illusions of what is or only seems.

    Nonetheless they do appear as real or imagined fear
    Or as unknowns, unnaturals, torments to eye and ear.
    Look what the fresh new breeze doth bring–
    With its mysterious voice, it doth sing.

    Soft on the air with voice or visual treat,
    It lays its bearing or bounty at your feet.
    Now it is yours, this new thought;
    By this new wind, it is brought.

    Up from the abyss or down from heaven,
    In a current, air now is given.
    It’s oft a creature of what we ingest
    That gives unto us this worst or best.

    Oh, the hazards of seeing or hearing
    That soon become our reasons for fearing!
    The things accepted without investigation
    Causes the brain its mental constipation.

    120205

  3. Sir Mildred Pierce Says:
    August 17th, 2008 at 5:06 pm “Um? shouldn?t that be ?This aged portion of society was?? Haha.”

    Common mistake. “society” is a plurality, and as such is treated as such in the grammar. Another good example is one might say “Queen is Freddy Mercury, Brian May…” but the proper way to say it would be “Queen are Freddy Mercury, Brian May…” etc.. the brain thinks otherwise because the previous word doesn’t end in “s”, but nevertheless it’s a plurality and thus, treated as such.

  4. Sir Mildred Pierce Says:
    August 17th, 2008 at 5:10 pm Or rather “This aged portion of society” as a whole is a plurality, not just “society”…

    I would like to see the famous “Roswell Memo given the treatment, as it seems previously only those biased to the answer that the memo really does talk about aliens and discs are teh only ones interpreting it.

  5. Duck Says:
    August 17th, 2008 at 5:13 pm Hm, how then does the system verify if the typed-in word is correct? Wouldn’t someone have to physically write out the correct answer so the CAPTCHA would know later on if someone entered the correct word, or something else. I could just write ‘poop’ and it wouldn’t catch it.
  6. Ash Says:
    August 17th, 2008 at 5:19 pm I’m all for typing inane responses to articles if it means the furthering of literacy.
    Imagine if Youtube incorporated it.
  7. @MildredPierce Says:
    August 17th, 2008 at 5:22 pm Actually, that depends on whether your speaking British English or American English. In British English, collective nouns are treated as plural, “The class were…”, “The team were…”, “U2 are…”, but in American English they are treated as singular nouns.

    Furthermore, in the example above it should be “was” no matter what side of the Atlantic you’re on. The “was” refers to “this [aged] portion”, which is clearly singular because of the “this”. If the quote were “The aged portion of society…” then it would depend on B.E. vs. A.E.

    I’m guessing the quote is an archaic formulation.

  8. @Duck Says:
    August 17th, 2008 at 5:24 pm The system gives the same words to multiple people. If they agree on what the word should be, then the word is accepted as correct. If some of the writers disagree, then the word is given to more people.
  9. Grimmygrim Says:
    August 17th, 2008 at 6:01 pm Portion is singular so “was” would be correct. Using “was” or “were” would depend on the context (are they talking about the portion or the society). I’m leaning towards “was”.
  10. ayeroxor Says:
    August 17th, 2008 at 6:07 pm “Um… shouldn’t that be “This aged portion of society was”? Haha.”

    It can be either. Haha.

  11. Jmar Says:
    August 17th, 2008 at 6:12 pm I do not understand how this would work for “new words”, yet to be deciphered. Above someone suggested it sent the word to multiple people… does the first person have to wait until enough people verify? Haha. All my experence with this CAPTCHA has been instant either correct or incorrect, from my understanding it’s asking me to verify, not decipher. Am I just not getting a “new word” or what?
  12. rprebel Says:
    August 17th, 2008 at 7:17 pm It sounds like CAPTCHAs, for the commenter, aren’t new words at all. When I type ’suffolk’ and ‘chiffon’ into the little box below this bigger box, I’m not helping to decipher anything. I’m placing a vote in an election that’s already been decided. They’re also annoying, but spam is moreso.
  13. Ron Delta Says:
    August 17th, 2008 at 8:41 pm Wow dude, thsoe folks are pretty amazing arent they. Very smart bunch.

    RD
    www.anondo.alturl.com

  14. Fabrizio Says:
    August 17th, 2008 at 8:47 pm Andrei Broder was the first to invent a CAPTCHA when at Altavista and not Luis von Ahn
  15. Hank Roberts Says:
    August 17th, 2008 at 9:09 pm When all else fails, read the fine manual:

    http://recaptcha.net/learnmore.html

    “how does the system know the correct answer to the puzzle? Here’s how: Each new word that cannot be read correctly by OCR is given to a user in conjunction with another word for which the answer is already known. The user is then asked to read both words. If they solve the one for which the answer is known, the system assumes their answer is correct for the new one. The system then gives the new image to a number of other people to determine, with higher confidence, whether the original answer was correct.”

    See also: http://web.sbu.edu/history/tschaeper/Hist101/101wwwfbacon.html

  16. Jerome Says:
    August 18th, 2008 at 2:09 am Yes, that’s not clear to me either… if I’m deciphering the word, how does the program know what is correct?
  17. thomas Says:
    August 18th, 2008 at 3:21 am Here’s how they do it (From the website):

    “But if a computer can’t read such a CAPTCHA, how does the system know the correct answer to the puzzle? Here’s how: Each new word that cannot be read correctly by OCR is given to a user in conjunction with another word for which the answer is already known. The user is then asked to read both words. If they solve the one for which the answer is known, the system assumes their answer is correct for the new one. The system then gives the new image to a number of other people to determine, with higher confidence, whether the original answer was correct.”

    Very cool idea.

  18. komatzu Says:
    August 18th, 2008 at 10:59 am @thomas: thanks for the answer!
    I think it should have been mentioned in the article.
  19. Fat Jolly Penguin Says:
    August 20th, 2008 at 6:39 pm ““Um… shouldn’t that be “This aged portion of society was”? Haha.”

    It can be either. Haha.”

    Actually, it should be “was.” The subject of the sentence is “portion.”

Louis J. Sheehan

Iran’s rockets 0000001 Louis J. Sheehan

August 21, 2008

Louis J. Sheehan.  On Sunday, the Iranian state television network showed impressive footage of a slender white rocket blasting off from a launch pad, leaving behind billows of smoke. Iranian officials say that the rocket, named Safir, or “ambassador,” successfully reached orbit, demonstrating the technological known-how to send up satellites. The rocket released equipment that beamed flight data back to ground control, said Reza Taghipoor, the head of Iran’s Space Agency, in a live television interview [AP].

Yet shortly after Iranian officials boasted of their fledgling space program, unnamed sources from the U.S. Defense Department began disputing those claims of a successful launch. “The Iranians did not successfully launch the rocket,” a senior U.S. defense official told CNN Monday. The two-stage rocket could have been capable of launching a satellite into space, but the U.S. intelligence assessment shows that the second stage “was erratic and out of control,” said the official, who declined to be identified because of the sensitivity of the intelligence. The rocket “did not perform as designed,” the official said [CNN].

Iran’s rocket-building capacities are of urgent interest to the United States and its allies, because the rockets used to send satellites into space could also be used to deliver nuclear weapons. In light of the ongoing dispute over Iran’s nuclear program, U.S. officials responded to this weekend’s attempted launch with dismay. White House spokesman Gordon Johndroe said: “The Iranian development and testing of rockets is troubling and raises further questions about their intentions. This action and dual use possibilities for their ballistic missile programme are inconsistent with their UN Security Council obligations” [BBC News].

Ahmadinejad has made Iran’s scientific development one of the main themes of his presidency, asserting that the country has reached a peak of progress despite sanctions and no longer needs to depend on foreign states for help. “This satellite, the rocket and the launch station are entirely Iranian-built, achieved by particularly talented scientists and technicians,” Ahmadinejad told reporters in Turkey last week, announcing that the satellite would be launched soon [AFP]. Iranian officials have said they need satellites to monitor for natural disasters and improve telecommunications.

Image: Islamic Republic News Agency

August 18th, 2008 Tags: , , ,
by Eliza Strickland in Space, Technology | 6 comments | RSS feed | Trackback >

6 Responses to “Pentagon Disputes Iran’s Boast of Sending a Rocket Into Orbit”

  1. BiBiJon Says:
    August 18th, 2008 at 5:11 pm Lets face it. If Iran claimed it had manufatured a toothpick, you would find somebody, somewhere, call it a hoax.

    Anyone interested in a reality check on Iran, please see
    http://www.bibijon.org/iranimage/

  2. Dragutin Dimitrijevic Says:
    August 18th, 2008 at 6:15 pm Very true BiBiJon. The American and Israeli propaganda campaign to demonise Iran is comically inconsistent. On the one hand we’re told that the Iranians are building their own carbon-fibre centrifuges and they’re enriching uranium, both efforts being highly complex engineering achievements. They’re a year or two away from assembling a nuclear warhead we’re led to believe. That feat is an extraordinary technical challenge over and above merely enriching uranium. Beware, the Americans and Israelis tell us, those sneaky and mean ol’ Iranians are talented. Especially at building the same scary weapons that the Americans and Israelis already have.

    On the other hand the Americans report that those Iranian stumble-bums can’t even launch a rocket into low earth orbit and properly discharge a small test payload. Haw haw. Boy are those Iranians dumb and backward.

    So which is it? Talented and cunning super-duper engineers and scientists or dumb and backward wannabes, quasi-third worlders?

  3. Matt Metcalf Says:
    August 18th, 2008 at 8:27 pm That’s a good point, except that the U.S. built (and used) nuclear weapons in 1945 and didn’t have the technical capability to reliably put something in orbit until more than 10 years later.

    Nobody is saying that the Iranians are dumb… just that they don’t have the technical know-how to reliably complete the extraordinarily complex task of launching something into orbit.

    I should point out, though, that SpaceX has had three attempts that have failed, and the Iranians have (apparently) had one. I don’t know of any rockets that have successfully reached orbit the first time they tried.

  4. BiBiJon Says:
    August 18th, 2008 at 8:51 pm Matt,

    The point is the tone of the article. Typical of most articles, a mix of ridicule, envy, insult and disparagement. Not to mention articles, and comments that diagnose Iranians as suicidal, genocidal, etc.

    If people are that interested about Iran, do a bit of research. Start with http://www.bibijon.org/iranimage/

  5. Kiumars Says:
    August 20th, 2008 at 1:59 am There seems to be an orchestrated attempt to undermine Iran’s progress and achievements, we saw this again a few weeks ago when the western media (especially those owned by Murdock) claimed that Iran had faked the photo of launching a few other missiles; where Iran actually had only issued a video and no photos!
    There is no doubt that there are technical problems that Iran faces and that is why these tests are carried out and that is what these tests are all about. USA still has major technical problems with the Shuttle and bits and pieces fall off it every time it is launched!

    Iranians can do it and will do it and I am sure they will do it as well as anyone else does it (or maybe even better).

    By the way the video of the launch is on BBC website and YouTube!

  6. BiBiJon Says:
    August 20th, 2008 at 9:09 am A high ranking official who requested not to be named for reasons that includes ‘he may be talking out of his hat’, or that ‘he may be simply lying’, has stated that Eliza Strickland’s article is an example of good journalism.

Locks 992288 Louis J. Sheehan

August 21, 2008

As the paparazzi wait for celebrities to walk by with perfect hair, researchers have found a way to create perfect hair graphically. Scientists at the University of California at San Diego used cameras and light sources in a new way to create ultra-realistic hair on animated figures.

The researchers took 2,500 images with 16 cameras, used 150 light sources, and set up three projectors to determine the exact position of each strand of hair and imputed the data into a complex model. Most animated films shown in theaters today typically only show characters with treatment done to the top layer of their hair. The secret to this new model is that it looks at hairstyles from all angles to focus in on individual stands and reproduce the strands from the scalp.

The model shows how light reflects off of 100,000 hair strands —an important feature, especially when animators need their characters to look normal when the wind blows and when the sun shines. “We want to give movie and video game makers the tools necessary to animate actors and have their hair look and behave as it would in the real world,” says U.C. San Diego computer scientist Matthias Zwicker.

The applications of this new hair model could go beyond Hollywood. In Second Life, people can choose to create avatars that look like superheroes. However, polls reveal that most adults prefer to make avatars look like themselves. Louis J. Sheehan