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George Church: “We have not made artificial life, and that is not our primary goal; but this is a huge milestone in that direction.”

Harvard scientists create cell protein machinery

Harvard News Office, March 2009 — Harvard scientists have cleared a key hurdle in the creation of synthetic life, assembling a cell’s critical protein-making machinery in an advance with both practical, industrial applications and that advances the basic understanding of life’s workings.

George Church, a genetics professor at Harvard Medical School and member of Harvard’s Origins of Life Initiative, reported the creation of billions of synthetic ribosomes that readily create a long, complex protein called firefly luciferase.

Church, speaking at a Harvard Alumni Association and Origins of Life Initiative event at the Science Center on Saturday afternoon (March 7), described the advance for the first time publicly as part of an afternoon symposium called “The Future of Life.”

“We have not made artificial life, and that is not our primary goal, but this is a huge milestone in that direction,” Church said in comments on the work before the event.

Ribosomes are bodies inside of each cell that take the instructions from DNA and use them to create the proteins encoded by specific genes. Proteins are critical to forming the body’s structure, including muscles, bones and tendons, and are also critical in its daily functioning, through enzymes, for example, which control metabolism.

“The reason it is a step toward artificial life is that the key component of all living systems is the ribosome, which does protein synthesis. It is the most conserved and one of the most complicated biological machines,” Church said.

Using the bacteria E. coli, Church and Research Fellow Michael Jewett extracted the bacteria’s natural ribosomes, broke them down into their constituent parts, removed the key ribosomal RNA and then synthesized the ribosomal RNA anew from molecules.

Though the advance may create excitement among researchers interested in life’s basic functioning, Church said that the work’s industrial applications were its driving force.

Industry today manufactures proteins on a large scale using natural ribosomes, which evolved over millions of years for natural, not industrial, reasons. Church said that being able to create a ribosome means also being able to tweak it so it better fits industrial needs. One possible use would be to create mirror-image proteins that would be less susceptible to breakdown by enzymes, making them longer-lived.

“You really are in control. It’s like the hood is off and you can tinker directly,” Church said.

The advance breaks a 40-year period with little progress in artificial ribosome creation, Church said. The last significant work in this area was done in 1968, when researchers assembled an artificial ribosome, but in an unusual chemical environment rather than an environment in which protein synthesis normally occurs, as Church and Jewett did.

Church and Jewett expected creating the artificial ribosome and getting it to produce proteins would be the toughest steps in making an artificial cell. They were amazed, Church said, when the task was accomplished in just a year.

The ultimate goal is to create an artificial genome of 151 genes that they believe are the minimum to create a functioning, self-replicating cell.

“It could be that the hardest steps are still ahead of us,” Church said.

Joining Church at Saturday’s event were human genome pioneer and visiting scholar Craig Venter; Jack Szostak, professor of genetics at Harvard Medical School and Massachusetts General Hospital; George Whitesides, Woodford L. and Ann A. Flowers Professor of Chemistry and Chemical Biology; and Andrew Knoll, Fisher Professor of Natural History and professor of Earth and Planetary Sciences. Harvard Provost Steven E. Hyman introduced the event. It was moderated by professor of astronomy and Origins of Life Director Dimitar Sasselov.

Szostak presented his recent research into the creation and propagation of synthetic cells, showing that membranes form from simple fat molecules spontaneously under certain conditions. In addition to the membranes, he reviewed research into possible ways that basic genetic information may have originally been stored and conveyed in simple RNA-like molecules. His work, he said, is exploring the properties of these RNA-like molecules, seeking variations that make them better early candidates to store and replicate genetic information than either DNA or RNA, which perform those functions in modern cells, but require complex molecular machinery to do so.

In his presentation, Venter described the search for genes around the world, saying that microbes have been found on earth that can withstand radiation levels far beyond that which would be lethal to humans, that can live in corrosive liquids that would eat away a human finger dipped in it, and in a wide array of other environments. The growing library of genes from creatures of all kinds – totaling 50,000 gene families – has created a database from which industry can pick and choose genes for particular applications. Using genetic engineering, synthetic genomes can be created to do such useful things as create clean-burning synthetic fuels, he said.

“I think we’re limited primarily by our own imagination,” Venter said.

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Harvard Fuels Quest to Create Life From Scratch

Machine mimics ribosome activity, professor asserts

Boston Globe, March 2009, by Carolyn Y. Johnson — Harvard scientists have created a biological machine in the lab that manufactures proteins, mimicking the activity of a cellular structure, called a ribosome, that is critical for life.

If it is verified by other scientists, the work by Harvard Medical School professor George Church would be an important step in the quest to create life from scratch.

“The reason it’s a step toward artificial life is that the key component of all living systems – the one component that’s basically shared by all living systems – is the ribosome,” Church said in an interview Friday. “If you’re going to make synthetic life that’s anything like current life . . . you’ve got to have this highly conserved, highly complicated biological machine.”

Church said he is still writing a manuscript to describe the results in a scientific journal, but that the experiment has been successfully repeated several times in his lab over the past few weeks. Publication in a journal ensures that research is properly vetted by independent scientists.

He was scheduled to describe the work to a gathering of Harvard alumni yesterday afternoon, an unusual forum for discussing new scientific findings. Scientists not involved in the research said they were unable to comment on it without knowing more details.

Church did not literally start from scratch, building a ribosome atom by atom. But he and post-doctoral fellow Michael Jewett did synthesize the structure from basic molecules. His goal now is to create a ribosome that can replicate.

The research – part of the new field of synthetic biology and Harvard’s Origins of Life Initiative – has applications that run a wide gamut. Researchers could use such ribosomes to custom-make proteins in a dish, but they could also use the structures to get insights into the origins of life.

“I think it’s very exciting. I think from my perspective, this is really a very happy moment, because we now have a good feeling that our project is going to at least tell us something, some answers,” said Dimitar Sasselov, a professor of astronomy at Harvard who is interested in finding out whether a ribosome is capable of making proteins with a different symmetry than that found on Earth.

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American Academy of Dermatology Press Release March 2009

Scleroderma is an autoimmune disease that leads to thickening and severe scarring of skin as well as thickening and failure of internal organs, including the lungs, heart, kidneys and intestines. The disease — which the Scleroderma Foundation estimates affects approximately 300,000 Americans — can be fatal and there is no cure. A major and incapacitating complication of scleroderma is the development of ulcers on the patients’ fingers and toes that are very painful and difficult to heal. Now, researchers are studying the viability of administering stem cells topically to ulcerated fingers using bioengineered skin to help heal these wounds.

Speaking today at the 67th Annual Meeting of the American Academy of Dermatology (Academy), dermatologist Vincent Falanga, M.D., FAAD, professor of dermatology and biochemistry at Boston University in Boston and chairman of the department of dermatology and skin surgery at Roger Williams Medical Center in Providence, R.I., presented his study findings in which cultured stem cells and bioengineered skin were used to successfully treat skin ulcers of three scleroderma patients and discussed how bioengineered skin plays a critical role in this procedure.

“The concept of using bioengineered skin to heal difficult wounds, such as leg and foot ulcers, previously has been shown to be effective for chronic wounds but, in our experience, has not by itself been consistently useful in healing scleroderma finger ulcers,” said Dr. Falanga. “Through our research, we learned that our combined approach of using stem cells with bioengineered skin may provide value by ‘instructing’ the stem cells on how to stimulate healing in a difficult wound.”

As a source of stem cells, Dr. Falanga and his team of researchers focused on taking a small amount of bone marrow from the affected patients’ hip. This common procedure is performed to diagnose conditions affecting the blood or bone marrow, such as anemias and leukemia. From this sample, the intention was to grow a particular type of stem cells in the laboratory called mesenchymal stem cells, which are cells that can create other cell types, including those in skin and muscle, and are capable of repopulating damaged skin.

The delivery method used to apply stem cells to the wounds was a fibrin spray system that had not been used in humans prior to the research pioneered by Dr. Falanga and his team. Fibrin is a chemical by-product that occurs naturally in the body and helps clot blood. For each of the three scleroderma patients, up to three spray applications of stem cells were performed.

“For the first time in humans, the investigators used a fibrin spray system — which takes advantage of the immediate polymerization, or ‘gluing,’ of stem cells in fibrinogen when mixed with thrombin,” said Dr. Falanga. “Both fibrinogen and thrombin are naturally occurring substances in blood which, when mixed to form fibrin, are normally involved in the formation of a clot. In this case, the two substances, highly diluted, were used to deliver the cultured mesenchymal stem cells to the wounds of scleroderma patients in a fine transparent spray.”

After delivering the stem cells to the affected finger, the wound was covered and treated with the additional stimulus provided by bioengineered skin — a bi-layered, substitute skin that consists of living human keratinocytes (cells that make the upper skin layer) and fibroblasts (cells that make collagen) — derived from neonatal foreskin following a circumcision and preserved for medical research.

From this initial study, Dr. Falanga and his team were very encouraged by their early results. “Our combined approach resulted in dramatic healing of these extremely difficult-to-heal wounds, with new skin growth that blended in nicely with the surrounding skin,” said Dr. Falanga. “On follow-up examination, one patient who had painful and incurable finger ulcers for many years remained healed and free of pain from this procedure. Importantly, the concept of ‘instructing’ stem cells with other interventions or biological agents is significant and could be applicable to other situations where the use of stem cells is being pursued.”

Headquartered in Schaumburg, Ill., the American Academy of Dermatology (Academy), founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. With a membership of more than 15,000 physicians worldwide, the Academy is committed to: advancing the diagnosis and medical, surgical and cosmetic treatment of the skin, hair and nails; advocating high standards in clinical practice, education, and research in dermatology; and supporting and enhancing patient care for a lifetime of healthier skin, hair and nails. For more information, contact the Academy at 1-888-462-DERM (3376) or www.aad.org.

March 2009

Scientists at the Stanford University School of Medicine have identified a protein complex important in controlling whether embryonic stem cells retain their ability to become any cell in the body – a quality called pluripotency – or instead embark on a pathway of maturation and specialization. The finding is an important advance in the quest by scientists to harness the unique abilities of embryonic stem cells to treat disease and generate replacement tissue for the body.

Like a musician tuning an instrument, the complex associates with and adjusts the expression levels of other proteins important in pluripotency, perhaps by affecting how the DNA is packaged within the cells in strands called chromatin. They found that this complex associates closely with other major regulators of pluripotency, including four genes known to be able to coax adult cells to display many qualities of embryonic stem cells.

“We’ve identified a specific mechanism to maintain pluripotency that involves large-scale, genome-wide chromatin remodeling,” said Gerald Crabtree, MD. “The results are rather spectacular. They show clearly that the complex binds to and works in near-perfect concert with these four famous pluripotent factors. They are part of the same developmental program.”

Crabtree is a professor of pathology and of developmental biology at the medical school, as well as a Howard Hughes Medical Investigator and a member of Stanford’s Cancer Center. He is the senior author of two articles describing the work, which will be published online March 2 in the Proceedings of the National Academy of Sciences. The first author of both papers, Lena Ho, is a graduate student in Crabtree’s lab.

Ho began her investigation into the function of the complex, called BAF, after other researchers had found that it was important in regulating how a cell’s genetic material is wrapped around DNA packaging proteins called histones. One way of controlling how and when a gene is made into a protein involves increasing or restricting its accessibility to other proteins called transcription factors, and BAF is one of many so-called chromatin remodeling complexes that regulate this process in mammals. However, Ho found that the protein components of BAF vary according to the cell type in which they are found.

“We realized, ‘Gee, there’s something different between how this complex works in skin cells like fibroblasts and embryonic stem cells,'” said Crabtree. They began to look more closely at how BAF functions in embryonic stem cells.

The work also builds upon previous findings of Shinya Yamanaka, MD, PhD, of the University of California-San Francisco. The world of stem cell research was galvanized in 2007 with the discovery by Yamanaka of the four genes that can affect adult cells in such a way that they display many qualities of embryonic stem cells. That opened the door to the possibility of realizing the promise of embryonic stem cells without requiring the destruction of embryos. The technique of using these genes to create what are known as induced pluripotent stem, or iPS, cells is an active area of stem cell research.

It’s not yet known exactly how embryonic-stem-cell BAF, or esBAF, works, though the researchers suspect it may have something to do with its ability to remodel chromatin around other genes involved in pluripotency. However, they did discover that esBAF, can both activate and inactivate the expression of these genes. It’s possible that this refining, or focusing, role is needed to keep embryonic stem cells walking the line between self-renewal and differentiation.

The researchers are now investigating whether they can manipulate the subunits of the BAF complex in such a way to make fibroblasts pluripotent. They’re also curious as to whether small molecules or chemicals modulate the complex’s function. If so, it may be one step toward more efficient regenerative medicine, according to Crabtree.

Notes:

Additional Stanford collaborators on the research include Jehnna Ronan; Jiang Wu, PhD; Brett Staahl; Lei Chen, MD; Ann Kuo; and Julie Lessard, PhD. The work was done in collaboration with the group of Keji Zhao, PhD, at the National Institutes of Health in Washington, D,C. The work was funded by the Howard Hughes Medical Institute; the NIH; the National Heart, Lung, and Blood Institute; and the Agency of Science, Technology and Research of Singapore.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.

Source: Krista Conger
Stanford University Medical Center

Article URL: http://www.medicalnewstoday.com/articles/140917.php

Main News Category: Stem Cell Research

Also Appears In: Genetics,

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A continuous recording of the blood circulation of the hand of a healthy test person; the graph (above) shows the average blood circulation, and b through d show the entire situation for the period of time on the graph: the heart beat can be observed. (Credit: Image courtesy of University of Twente, The Netherlands)

University of Twente, The Netherlands, March 22, 2009 — Burns or other disorders that disrupt the blood flow in tissues will soon be easier to assess thanks to a camera that is capable of imaging blood circulation in real time.

Compared to an earlier version, the new optical perfusion camera (TOPCam) from Twente, the Netherlands, is a significant improvement with regard to speed, so that even small variations in blood circulation are immediately visible. The camera is now ready for clinical application. Researchers of the Institute for Biomedical Technology (BMTI) of the University of Twente are publishing an article on the camera in the March number of Optics Express.

After earlier successful tests at the Martini Hospital in Groningen, the Netherlands, the researchers have made a number of significant improvements to the camera. The speed of the earlier version was commended by doctors and nurses, but real-time images of variations in the blood circulation were not yet possible. They are now, though, according to researcher Wiendelt Steenbergen: “We can now see rapid variations in blood circulation, too, for example when the circulation gets going again after occlusion of an arm or after a transplant.” The measured reaction gives an immediate impression of the condition of the vascular bed.

The researchers were able to reach these high speeds by using a broad laser beam to simultaneously illuminate the entire area of skin in question. Images are made of the tissue with a high-speed camera. Laser light that is scattered by moving red blood cells gives variation in the clarity of the pixels as a result of the Doppler Effect. Up till now it had been a problem transferring all the data to the computer quickly enough, but real time images are now enabled by making better use of the camera memory.

Now that the newest modifications have been made, the camera is ready for clinical application, Steenbergen says. The TOPCam is also suitable for other applications such as the assessment of blood circulation in diabetics. This research, which was carried out by the BMTI, was financed by the Technology Foundation (STW).

Journal reference:

1. Matthijs Draijer, Erwin Hondebrink, Ton van Leeuwen, and Wiendelt Steenbergen. Twente Optical Perfusion Camera: system overview and performance for video rate laser Doppler perfusion imaging. Optics Express, 2009; 17 (5): 3211-3225 DOI: 10.1364/OE.17.003211

ScienceDaily.com, March 21, 2009 — Scientists know that alcohol affects the brain, but the specifics remain unclear. One possibility is that alcohol may increase or decrease the release and the synthesis of endogenous opioid peptides – endorphins, enkephalins and dynorphins – in distinct brain regions important for drug addiction.

For the first time, a rodent study has confirmed that low to moderate levels of alcohol alter beta-endorphin release in the midbrain/Ventral Tegmental Area (VTA) region, producing the pleasant effects that likely reinforce alcohol consumption.

“Some of the functions of opioid peptides are similar to those of the opiate morphine,” explained Christina Gianoulakis, a professor in the departments of psychiatry and physiology at McGill University, and the study’s corresponding author. “Like morphine, endogenous opioid peptides can induce analgesia and a mild euphoric effect, reduce anxiety, and may lead to a general feeling of well being. Therefore, increased release of endogenous opioid peptides in response to drinking could be partially responsible for the mild euphoric and anxiolytic effects associated with low to moderate amounts of alcoholic beverages.” Gianoulakis is also with the Douglas Mental Health University Institute.

“The brain’s natural opioids have been implicated in many physiological functions such as pain and pleasure,” added Dzung Anh Le, a senior scientist at the Centre for Addiction and Mental Health, University of Toronto. “Alcohol has long been thought to release these peptides, but previously the only way to confirm this was to rely on test tube experiments using extracted tissue samples, and findings from these studies were indirect and offered extremely limited interpretation.”

Le said that researchers suspected that dopamine was a key brain chemical in one of the most heavily implicated pathways likely involved in drug and alcohol addiction, the VTA.

“One mechanism by which alcohol produces its euphoric or rewarding effects is through the stimulation of natural opioid peptides in the VTA, which consequently activates dopamine in this critical pathway,” Le said. “Until now, no one has been able to answer whether alcohol is actually capable of triggering opioid release in the VTA.”

Researchers injected male Sprague-Dawley rats with either saline or alcohol (0.8, 1.2, 1.6, 2.0, and 2.4 grams alcohol/kg of body weight). Using an in vivo microdialysis technique, study authors tracked the response of endorphins, enkephalins, and dynorphins at the level of the midbrain, including the VTA.

“We found that low to moderate but not high doses of alcohol increase the release of beta-endorphin in the VTA, one of the brain regions shown to be important for mediating the rewarding effect of alcohol,” said Gianoulakis. “This supports a role of beta-endorphin in mediating some of the rewarding effects of alcohol. However, the same doses of alcohol that increase beta-endorphin release in the VTA have no significant effect on the release of enkephalins and dynorphins, the other two families of endogenous opioid peptides we examined.”

Gianoulakis said that readers should remember that it is the low to moderate doses of alcohol that are associated with mild euphoria, decreased anxiety and a general feeling of well being. “On the other hand, high doses of alcohol are known to induce sedative and hypnotic effects, and often increase rather than decrease anxiety.”

“This research has confirmed a role of endogenous opioids in mediating alcohol addiction, and has delineated a pathway within which they may be involved,” said Le. “It also goes further to specifically isolate an opioid peptide that may be most critically involved in a specific region of the brain. Endorphins are the natural peptides that most closely mimic the pharmacological properties of morphine, and of the three opioid families, they likely produce the greatest ‘high.'”

Furthermore, Le added, methods used in this study are groundbreaking. “Dr. Gianoulakis and her team can track changes over time in living and freely moving animals,” he said. “This has a profound implication on research in this area, as the effects of alcohol can be measured from an intact ‘living’ brain, in animals that are relatively uninhibited and unstressed within their environment.”

Both Gianoulakis and Le said these findings will help future treatment options.

“VTA beta-endorphin appears to play a significant role in alcohol reinforcement, and may partially explain the effectiveness of naltrexone – an opioid receptor antagonist currently used as treatment of alcoholism – in reducing alcohol consumption by some individuals,” said Gianoulakis.

“While current alcoholism treatment blocks opioids in a nonspecific fashion, this research suggests that a more targeted approach would be more beneficial,” said Le. “Researchers now have to specifically target endorphins in the VTA to see if it really does affect alcohol abuse and craving.”

“Readers should understand that drinking only low amounts of alcohol will increase endorphin release and produce pleasant effects,” said Gianoulakis. “Thus, if after consumption of about two drinks of alcohol an individual does not experience the pleasant effects of alcohol, he or she should stop drinking. Consumption of high amounts of alcohol will not only fail to increase the release of endorphins, but may stimulate other systems in the brain that may lead to the development of anxiety and depression.”

The study was funded by the Natural Sciences and Engineering Research Council of Canada.

Obama Administration Offers $535 Million Loan Guarantee to Solyndra, Inc.

Investment Could Lead to Thousands of New Jobs

March 20, 2009, Washington, DC – Energy Secretary Steven Chu today offered a $535 million loan guarantee for Solyndra, Inc. to support the company’s construction of a commercial-scale manufacturing plant for its proprietary cylindrical solar photovoltaic panels. The company expects to create thousands of new jobs in the U.S. while deploying its solar panels across the U.S. and around the world.

“This investment is part of President Obama’s aggressive strategy to put Americans back to work and reduce our dependence on foreign oil by developing clean, renewable sources of energy,” Secretary Chu said. “We can create millions of new, good paying jobs that can’t be outsourced. Instead of relying on imports from other countries to meet our energy needs, we’ll rely on America’s innovation, America’s resources, and America’s workers.”

Secretary Chu is moving aggressively to accelerate important Department of Energy investments that can create jobs and transform the way America uses and produces energy. This allows the Department of Energy to offer its first loan guarantee within the first two months of the Obama Administration. This loan guarantee will be supported through the President’s American Recovery and Reinvestment Act, which provides tens of billions of dollars in loan guarantee authority to build a new green energy economy.

Solyndra’s photovoltaic systems are designed to provide the lowest installed cost and the highest solar electricity output on commercial, industrial and institutional roof tops, which are a vast, underutilized resource for the distributed generation of clean electricity. Solyndra’s proprietary design transforms glass tubes into high performance photovoltaic panels which are simple and inexpensive to install. By replacing power generated from fossil fuel sources, the electricity produced from the solar panels will reduce emissions of greenhouse gases.

Based in Fremont, CA, Solyndra is currently ramping up production in its initial manufacturing facilities. Once finalized, the DOE loan guarantee will enable the company to build and operate its manufacturing processes at full commercial scale.

Solyndra estimates that:

· The construction of this complex will employ approximately 3,000 people.

· The operation of the facility will create over 1,000 jobs in the United States.

· The installation of these panels will create hundreds of additional jobs in the United States.

· The commercialization of this technology is expected to then be duplicated in multiple other manufacturing facilities.

Secretary Chu is offering the loan guarantee by signing a “conditional commitment” today, following approval this week by the Department of Energy’s Credit Review Board. Just as homebuyers who have been approved for a loan are required to meet certain conditions before closing, the conditional commitment will require Solyndra to meet an equity commitment as well as other conditions prior to closing. Today’s action signals the Department’s intent to move forward on Solyndra’s application for $535 million loan guarantee provided the company meets its obligations.

Before offering a conditional commitment, DOE takes significant steps to ensure risks are properly mitigated for each project prior to approval for closing of a loan guarantee. The Department performs due diligence on all projects, including a thorough investigation and analysis of each project’s financial, technical and legal strengths and weaknesses. In addition to the underwriting and due diligence process, each project is reviewed in consultation with independent consultants.

Secretary Chu initially set a target to have the first conditional commitments out by May – three months into his tenure – but today’s announcement significantly outpaces that aggressive timeline. Secretary Chu credited the Department’s loan team for their work accelerating the process to offer this conditional commitment in less than two months, demonstrating the power of teamwork and the speed at which the Department can operate when barriers to success are removed.

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Stephen Crowley/The New York Times
Sam Kass, an assistant White House chef, left, and Dale Haney, the White House gardener, at the site of the new vegetable garden on the South Lawn.

The New York Times, March 20, 2009, by Marian Burros — Michelle Obama will begin digging up a patch of the South Lawn on Friday to plant a vegetable garden, the first at the White House since Eleanor Roosevelt’s victory garden in World War II. There will be no beets — the president does not like them — but arugula will make the cut.

While the organic garden will provide food for the first family’s meals and formal dinners, its most important role, Mrs. Obama said, will be to educate children about healthful, locally grown fruit and vegetables at a time when obesity and diabetes have become a national concern.

“My hope,” the first lady said in an interview in her East Wing office, “is that through children, they will begin to educate their families and that will, in turn, begin to educate our communities.”

Twenty-three fifth graders from Bancroft Elementary School in Washington will help her dig up the soil for the 1,100-square-foot plot, in a spot visible to passers-by on E Street. (It is just below the Obama girls’ swing set.)

Students from the school, which has had a garden since 2001, will also help plant, harvest and cook the vegetables, berries and herbs. Virtually the entire Obama family, including the president, will pull weeds, “whether they like it or not,” Mrs. Obama said with a laugh. “Now Grandma, my mom, I don’t know.” Her mother, she said, will probably sit back and say: “Isn’t that lovely. You missed a spot.”

Whether there would be a White House garden had become more than a matter of landscaping. The question had taken on political and environmental symbolism, with the Obamas lobbied for months by advocates who believe that growing more food locally, and organically, can lead to more healthful eating and reduce reliance on huge industrial farms that use more oil for transportation and chemicals for fertilizer.

Then, too, promoting healthful eating has become an important part of Mrs. Obama’s own agenda.

The first lady, who said that she had never had a vegetable garden, recalled that the idea for this one came from her experiences as a working mother trying to feed her daughters, Malia and Sasha, a good diet. Eating out three times a week, ordering a pizza, having a sandwich for dinner all took their toll in added weight on the girls, whose pediatrician told Mrs. Obama that she needed to be thinking about nutrition.

“He raised a flag for us,” she said, and within months the girls had lost weight.

Dan Barber, an owner of Blue Hill at Stone Barns, an organic restaurant in Pocantico Hills, N.Y., that grows many of its own ingredients, said: “The power of Michelle Obama and the garden can create a very powerful message about eating healthy and more delicious food. I don’t think it’s a stretch to say it could translate into real change.”

While the Clintons grew some vegetables in pots on the White House roof, the Obamas’ garden will far transcend that, with 55 varieties of vegetables — from a wish list of the kitchen staff — grown from organic seedlings started at the Executive Mansion’s greenhouses.

The Obamas will feed their love of Mexican food with cilantro, tomatillos and hot peppers. Lettuces will include red romaine, green oak leaf, butterhead, red leaf and galactic. There will be spinach, chard, collards and black kale. For desserts, there will be a patch of berries. And herbs will include some more unusual varieties, like anise hyssop and Thai basil. A White House carpenter, Charlie Brandts, who is a beekeeper, will tend two hives for honey.

The total cost of seeds, mulch and so forth is $200, said Sam Kass, an assistant White House chef, who prepared healthful meals for the Obama family in Chicago and is an advocate of local food. Mr. Kass will oversee the garden.

The plots will be in raised beds fertilized with White House compost, crab meal from the Chesapeake Bay, lime and green sand. Ladybugs and praying mantises will help control harmful bugs.

Cristeta Comerford, the White House’s executive chef, said she was eager to plan menus around the garden, and Bill Yosses, the pastry chef, said he was looking forward to berry season.

The White House grounds crew and the kitchen staff will do most of the work, but other White House staff members have volunteered.

So have the fifth graders from Bancroft. “There’s nothing really cooler,” Mrs. Obama said, “than coming to the White House and harvesting some of the vegetables and being in the kitchen with Cris and Sam and Bill, and cutting and cooking and actually experiencing the joys of your work.”

For children, she said, food is all about taste, and fresh and local food tastes better.

“A real delicious heirloom tomato is one of the sweetest things that you’ll ever eat,” she said. “And my children know the difference, and that’s how I’ve been able to get them to try different things.

“I wanted to be able to bring what I learned to a broader base of people. And what better way to do it than to plant a vegetable garden in the South Lawn of the White House?”

For urban dwellers who have no backyards, the country’s one million community gardens can also play an important role, Mrs. Obama said.

But the first lady emphasized that she did not want people to feel guilty if they did not have the time for a garden: there are still many changes they can make.

“You can begin in your own cupboard,” she said, “by eliminating processed food, trying to cook a meal a little more often, trying to incorporate more fruits and vegetables.”