Tuesday, 13 May 2008

Genetically Modified Human Embryo Stirs Controversy

Scientists create first GM human embryo 
Tuesday, 13 May 2008 

Researchers at Cornell University in New York have made a breakthrough in genetics by creating the first genetically modified (GM) human embryo. The GM embryo was produced to study how early cells in the embryo develop, but the scientists destroyed it just after five days. Led by Nikica Zaninovic, researchers at Cornell University used a virus to add a gene, a green fluorescent protein, to an embryo left over from assisted reproduction. It is believed to be the first documented genetic modification of a human embryo. 

Zaninovic's achievement was announced at the American Society for Reproductive Medicine annual meeting in 2007, but was only publicized recently when the United Kingdom's reproductive technology regulators reviewed the research. One of the authors of the study said to AP that the work was focused on stem cells. He noted that the researchers used an abnormal embryo that could never have developed into a baby anyway. 

"None of us wants to make designer babies," said Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York-Presbyterian/Weill Cornell Medical Center. Dr. Rosenwaks said the research had been approved by a review board at his medical center and been privately financed, so it did not violate federal restrictions on research involving human embryos. 

 Doctors already put foreign genes into people as part of gene therapy to treat diseases. But those genetic changes generally cannot be passed on to future generations because they are made to only certain types of cells in the body, like blood cells or muscle cells. Genetic changes made to an embryo would theoretically be heritable if the embryo became a baby. So far, this has been a no-go area for scientists and medical professionals. 

 The breakthrough has brought with it major concerns. The British regulator, the Human Fertilisation and Embryology Authority (HFEA), has even cautioned that such controversial experiments may lead to "large ethical and public interest issues". However, the HFEA has said that it is preparing for scientists to apply for licences to create GM embryos. 

A paper, published by the authority, states: “The bill has taken away all inhibitions on genetically altering human embryos for research. The Science and Clinical Advances Group [of the HFEA] thought there were large ethical and public interest issues and that these should be referred for debate.” 

 The House of Commons in Britain is about to consider legislation permitting this and other controversial reproductive technologies, such as the creation of chimeras – human-animal hybrid embryos. The first voting on this Bill took place yesterday in the British Parliament. There the MPs voted to allow, with a great majority, the plan to update the human embryology laws to continue to their next Parliamentary stage. The research raises a number of difficult ethical questions. 

Though adding a fluorescent protein was merely a proof-of-principle step, modified embryos could be used to research human diseases. Scientists say embryos wouldn't be allowed to develop for more than a few weeks, much less implanted in a woman and brought to term. If the embryos were allowed to develop, genetic modifications – which would be permanent and passed to future generations – might prevent disease. 

Modifications might also be used for other reasons – physical appearance, intellectual prowess and personality changes – though the necessary science remains hypothetical at this point. Developing such techniques would necessarily involve at this stage trial-and-error and risk-taking with human life.

Let's have that debate:
What do you think CellNEWS readers? 

  • Should genetically modified human embryos be used in research, or reproduction? Both? Neither? 
  • What would be the advantages or disadvantages? 
  • Would it OK to produce ‘designer babies’ in the future, when the technique is perfected? 

Reference: 
N. Zaninovic, J. Hao, J. Pareja, D. James, S. Rafii, Z. Rosenwaks. 
ASRM 2007 Annual Meeting, Poster session. 

Other Online Resources: 
HFEA 
......... 

ZenMaster

For more on stem cells and cloning, go to CellNEWS 
at http://cellnews-blog.blogspot.com/

Monday, 12 May 2008

Embryonic Stem Cells Are Genetically ‘Open’

Embryonic Stem Cells Are Genetically ‘Open’ Monday, 12 May 2008 While it has long been known that embryonic stem cells have the ability to develop into any kind of tissue-specific cells, the exact mechanism as to how this occurs has heretofore not been demonstrated. Now, researchers at the Hebrew University of Jerusalem, NCI at NIH in Bethesda, Maryland, and Canada, have succeeded in graphically revealing this process, resolving a long-standing question as to whether the stem cells achieve their development through selective activation or selective repression of genes. The collaborative research group, which included Dr. Eran Meshorer of the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University of Jerusalem, has revealed that the embryonic stem (ES) cells express large proportions of their genome “promiscuously.” This permissive expression includes lineage-specific and tissue-specific genes, non-coding regions of the genome that are normally “silent,” and repetitive sequences in the genome, which comprise the majority of the mammalian genome but are also normally not expressed. When ES cells differentiate into specific cell tissue-types, they undergo global genetic silencing. But until this occurs, the ES cells maintain an open and active genome. This might very well be the secret of their success, since by maintaining this flexibility they maintain their capacity to become any cell type. Once silencing, or genetic repression, occurs, this ability is gone. Thus, one can say that the ES cells stand at the ready until the “last minute” — prepared to engage in selective activation into specific cells — holding “in abeyance” their ability to become any kind of cells at the point and time required. To reveal the process as to how this occurs, the researchers created the first full-mouse genomic platform of DNA microarrays. Microarrays are glass-based chips that allow simultaneous detection of thousands of genes. The microarrays used in the study were not confined to specific genes only but spanned the entire genome. Hundreds of such microarrays were required in the study to cover the entire genome in different time points during stem cell differentiation. It was by observation of these sequences that the researchers were able to establish exactly how and at what point the stem cells developed into specific tissue cells and when the silencing occurs. The project carried out by the researchers appears in the latest issue of the journal Cell Stem Cell. The collaborators in addition to Dr. Meshorer who participated in the project include Tom Misteli, Ron McKay, Stuart Le Grice, Sol Efroni and Kenneth Buetow of the US National Institutes of Health, Thomas Gingeras of Affymetrix Inc. of Santa Clara, Calif., and David Bazett-Jones of The Hospital for Sick Children, Toronto. References: Global Transcription in Pluripotent Embryonic Stem Cells Sol Efroni, Radharani Duttagupta, Jill Cheng, Hesam Dehghani, Daniel J. Hoeppner, Chandravanu Dash, David P. Bazett-Jones, Stuart Le Grice, Ronald D.G. McKay, Kenneth H. Buetow, Thomas R. Gingeras, Tom Misteli, and Eran Meshorer Cell Stem Cell, Vol 2, 437-447, 08 May 2008 Chromatin in pluripotent embryonic stem cells and differentiation Eran Meshorer & Tom Misteli Nature Reviews Molecular Cell Biology 7, 540-546 (July 2006) doi:10.1038/nrm1938 ......... ZenMaster


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Thursday, 8 May 2008

CIRM Award Funds to Build California Stem Cell Labs

Next big investment in stem cell research in California Wednesday, 07 May 2008 CIRM, Donors and 12 California Institutions Commit $1.1 Billion to Stem Cell Research in California. The governing board of the California Institute for Regenerative Medicine (CIRM), the state’s stem cell agency, voted today to distribute $271 million to 12 institutions to build stem cell research facilities throughout California. The institutions committed an additional $560 million from charitable donations and their internal reserves, bringing the total state-wide investment in new research space to $831 million. This leverage of the state’s stem cell funds was further increased by additional institutional commitments for faculty recruitment packages and other related capital costs. In total, the state funding will have leveraged $1.1 billion in new resources to accelerate the pace toward therapies for patients with chronic and debilitating disease and injury. Investment in research infrastructure to extend California’s state-of-the-art research capacity is a critical part of the agency’s scientific strategic plan to sustain and build California’s global leadership in stem cell research and to accelerate the field as a whole. All the institutions have agreed to expedited construction schedules that will deliver nearly 800,000 square feet of facilities with researchers in the labs within two years. This accelerated schedule should create thousands of construction jobs at a time when the state economy needs them. “This Prop. 71 stem cell research facilities program is one of the largest building programs ever dedicated for a new field of medical science and it will deliver an impact that will be felt world-wide,” commented Robert N. Klein, chairman of the governing board of the state stem cell agency. “As a patient advocate, I am inspired by the amount of leverage California research institutions have contributed from their charitable donors and from their reserves. Their incredible commitment underscores the promise that stem cell research holds for patients suffering from chronic disease and injury.” In a statement issued today, Governor Schwarzenegger said: “This will go a long way toward medical research that could save lives and improve them for people with chronic diseases. But also, this kind of public-private investment in a growing jobs sector is exactly the kind of good news our economy needs right now.” The Major Facilities Grant program was launched in August 2007 as a two-part application process. In the fall, the agency’s Scientific and Medical Research Grants Working Group evaluated the scientific merit of 17 proposals submitted in response to the request for application. On January 16, 2008 the ICOC approved Part 1 of the applications, inviting 12 institutions to advance to the second and final part of the application process. Part 2 of the application focuses on the technical aspects of an applicant’s building program and how the scientific program aligns with the CIRM’s objectives, and why the program represents a good value for California taxpayers’ investment. The review was conducted by the 10-member Scientific and Medical Research Facilities Working Group (Facilities Working Group) made up of real estate experts, patient advocates and the chairman of the ICOC. This meeting was open to the public. “These facilities will house basic and clinical researchers working collaboratively, with stem-cell-specific core labs literally ‘down the hall’ – an arrangement that is instrumental to our ability to accelerate the pace of research toward clinical application” said Dr. Alan Trounson, president of CIRM. “Because of this, we believe these facilities will be an instrumental part of advancing one of CIRM’s primary objectives of helping to speed the delivery of stem-cell based therapies and cures into the clinic and to patients.” CIRM had originally pledged to award $262 million in this round of grants, which would have taken the facilities grants by CIRM to the maximum allowed for “bricks and mortar” under Proposition 71. Today’s total of $271 million results from asking the institutions to breakout costs for scientific equipment, which CIRM routinely funds from the research portion of its bond allocation. This allowed CIRM to supplement its facilities total with $9 million from the research pool. “I was very pleased that the review process allowed us to make complete, thorough and fair evaluations of the applications,” said David Lichtenger, Chair of the CIRM Facilities Working Group (FWG), and President and CEO of Integrated Facilities Solutions (IFS) in Palo Alto. “I was also very encouraged to see that many of the applicants are at the forefront in designing innovative research space that efficiently used open and common areas to foster collaboration and flexibility in use.” “I am thrilled that there appears to be sufficient funds that all 12 proposals can move forward to completion because these facilities should dramatically accelerate the pace of getting new therapies to patients,” said David Serrano Sewell, vice chair of the CIRM FWG and Deputy City Attorney in the San Francisco City Attorney’s Office. The 12 institutions had originally requested $336 million in funding from CIRM. At its April 4 - 5 meeting the FWG scored each proposal on set criteria and then reduced each institution’s request by the percentage their score was below 100. For example, if a proposal received a 92, the institution’s request was reduced by eight percent. That reduced the funding gap from $74 million to $27 million. Moving $9 million of the requests into equipment costs reduced the gap to $18 million. This remaining gap was mitigated by offering institutions the chance to receive their award this summer at a discounted rate, rather than two years from now at completion of the projects as was initially contemplated. Eight institutions decided it was financially advantageous for them to take the award now with a nine percent reduction. This closed the gap and the remaining, relatively new and emerging institutions, could get the full funding recommended by the FWG. “California is at the epicenter of stem cell research,” said Eli Broad, founder of The Eli and Edythe Broad Foundation, which has committed more than $50 million to stem cell research at the Broad Institute for Integrative Biology and Stem Cell Research at USC and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “By creating new research centers and attracting the very best scientists from around the world, we will enable the rapid progress of one of the most promising areas of scientific and medical research today. The partnership between public institutions, the state, private foundations and donors demonstrates the unprecedented commitment California is making to stem cell research. The Broad Foundation is pleased to be the largest private donor to stem cell research in California.” "The important thing to me is that stem cells might not only extend life, but also improve the quality of life, as so many people suffer in their later years. But I think stem cells will have applications across the entire life span" stated Lorry Lokey, a donor to Stanford University’s project. Edward Thorp, a donor to the University of California, Irvine project states: "Vivian and I believe that private donations like ours in support of stem cell research at UCI will have a benefit both to our community and to our country that is immeasurably greater than the amount of the gift. Stem cell research promises to transform the treatment of disease and to give us longer, healthier lives. We expect donor support will allow continuing breakthroughs by UCI's stellar research team and that this will be leveraged by attracting many times as much in continuing state support." Ray Dolby, a donor to the University of California San Francisco project stated: “Dagmar and I are very happy to see the ongoing progress of CIRM activities and wish the project continued success." Li Ka-shing, a Hong Kong philanthropist and entrepreneur and donor to the University of California, Berkeley project stated: “When I made a gift to support the establishment of the Li Ka Shing Center for Biomedical and Health Sciences at Berkeley, I was inspired by the passage of Prop. 71 and the promise of significant advances in stem cell research. I am pleased to partner with UC Berkeley and with CIRM to support focused efforts targeting the root causes of some of today's most devastating diseases and translate discoveries into new therapies.”


(Press the picture for larger version)

The table above details the amount of funding (in US$) each applicant will receive from CIRM, the donor and institutional funds, the total building cost, the additional funds committed for faculty recruitment and other project costs, and total project costs.
Major Facilities Grants The objectives of the CIRM Major Facilities Grant Program are:
  • Funding new facilities – and encouraging investments by others in new facilities – that are free of any federal funding so as to allow research and development of therapies based on human embryonic stem cell (hESC) and other stem cell approaches to proceed in California without restrictions imposed by the federal government.
  • Developing stem cell research centers that will expand research capacity and capabilities in California while bringing stem cell-related researchers together in a collaborative setting.
  • Funding new facilities and improvements where research institutions have determined that existing facilities are inadequate or are lacking altogether and thus pose a challenge to the development of therapies and cures for diseases being addressed at these institutions.

The applications seek funding to establish one of three types of CIRM facilities:

  • CIRM Institutes to carry out stem cell research in three categories: basic and discovery stem cell research, preclinical (translational) research, and preclinical development and clinical research. CIRM funding for these projects will be up to $50 million.
  • CIRM Centers of Excellence to conduct stem cell research in any two of the three categories listed above. CIRM funding for these project will be up to $25 million.
  • CIRM Special Program to conduct specialized stem cell projects in one of the categories listed above. CIRM funding for these project will be up to $10 million.

CIRM Grants Awarded Since the Start: Since April 2006 when the CIRM awarded its first scientific grants under the California Stem Cell Research and Cures Initiative, the Institute has funded 168 grants totalling more than $530 million for investigator-initiated research grants and training to 22 California non-profit and academic institutions.

  • The first grants directed $37.5 million for training 169 pre-doctoral, post-doctoral, and clinical fellows at 16 non-profit and academic research institutions.
  • In 2007 the ICOC approved 73 Leon J. Thal SEED Grants totalling more than $46 million to bring new ideas and new investigators into the field of human embryonic stem cell (hESC) research;
  • 28 Comprehensive Research Grants totalling nearly $72 million to support mature, ongoing studies on hESCs by scientists with a record of accomplishment in the field;
  • 17 Shared Research Laboratory Grants totalling more than $50 million;
  • 22 New Faculty Awards of more than $54 million to encourage the next generation of clinical and scientific leaders in stem cell research;
  • and today’s Major Facilities grants to 12 institutions totalling $271 million.

About CIRM: CIRM was established in 2004 with the passage of Proposition 71, the California Stem Cell Research and Cures Act. The state-wide ballot measure, which provided $3 billion in funding for stem cell research at California universities and research institutions, was overwhelmingly approved by voters, and called for the establishment of an entity to make grants and provide loans for stem cell research, research facilities, and other vital research opportunities. To date, the CIRM governing board has approved 168 research and facility grants totalling more than $530 million, making CIRM the largest source of funding for human embryonic stem cell research in the world. .........

ZenMaster
For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html