BREAKING NEWS ITEMS [2008]

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Hour Glass

Our News Section could just as well been called a blog (short for web log), but this now-popular phrase didn't exist until very recently in the last year. Our blog is a chronological listing of news items with source references for each one interspersed with editorial remarks as we see fit to give us some perspective on where the field of gerontology is moving, even by scientists who would never refer to themselves as gerontologists.


Click for News from earlier years: 1998; 1999; 2000; 2001; 2002; 2003, 2004, 2005, 2006, 2007.


Click for a listing of Wire Services reports with virtually all the current worldwide news on the topic of human cloning [now hosted under The Reproductive Cloning Network News Page]. Click for another interesting site at The New Scientist Magazine.
For stem-cell policy news check the home page of the Genetics Policy Institute
4000 Ponce de Leon Blvd., Suite 47
Coral Gables, FL 33146; USA
Voice: 305-777-0268
FAX: 305-667-5123
URL: www.genpol.org
They have an outstanding Science Advisory Board and are particularly strong in reporting news from the United Nations.


May 18, 2005; Click for a newly-revised Better Humans website which covers many of the news items that we cover below, although they tend to be broader in their interest profile and therefore not as deeply in the specific topic of anti-aging interventions.


July 6, 2005; Click for a humorous website entitled, The Journal of Failed Experiments in Biogerontology that was described by its author, Frank Rummel, as "perhaps a little too much over the top." Click for his personal blog.


Click for The California Stem Cell Report, a blog dedicated to the coverage of the California Institute for Regenerative Medicine (CIRM). Archives of the Group's report go back to January 2005. This website may be the best way to keep yourself informed other than for CIRM itself. FYI, CIRM has recently moved its office to
Ms. Nicole Pagono
California Institute for Regenerative Medicine (CIRM)
210 King Street
San Francisco, CA 94107
Voice: 415-396-9100
FAX: 415-396-9141

Some educational websites of interest for the stem-cell area are as follows:

1. Student Society for Stem-Cell Research and Education
2. International Society for Stem Cell Research (isscr.org/public/ISSCR_Pub_Ed_Brochure.pdf)
3. National Institutes of Health (nih.gov/news/backgrounders/sstemcellbackgrounder.htm)
4. The University of Wisconsin (news.wisc.edu/packages/stemcells/)
5. clearlyexplained.com/nature/life/cells/stemcells.html
6. The American Society for Cell Biology (org/publicpolicy/issues.html#stem)
7. The Free Encyclopedia (en.wikipedia.org/wiki/Stem_cell#Stem_Cell_types)
8. The Alliance for Stem Cell Research
9. The International Stem Cell Forum based in England
10. Stem Cell Battles Politically- Oriented Website, edited by Donald C. Reed
11. Stem Cell Research News Edited by Data Trends Publications; P.O. Box 4460; Leesburg, VA 20177-8541; Voice: 703-779-0574; FAX: 703-779-2267; This is clearly a highly professional organization that makes imitators like us look like amateurs.
12. The Coalition for the Advancement of Medical Research (CAMR) (2021 K Street, N.W., Suite 305; Washington, D.C. 20006; Voice: 202-293-2856) is an umbrella organization with all the scientific and charitable disease- focused organizations that track stem-cell research-funding political issues. It includes as one of its members, The Alliance for Aging Research (AAR) of Washington, D.C., which includes SAGE Crossroads as a subunit.
13. StemCellInformation.com in association with Case Western Reserve University; Mr. Stephen Meyer tirelessly assembles hundreds of messages from news sources throughout the world on the topic of stem cells in a "YahooGroups" format. As of June 10th, he was up to Digest No. 455. If you subscribe on a daily basis, you can probably get more information than you can handle, unless you happen to be a journalist working in this area full time. Nevertheless, Internet website "hit" statistics compiled by the National Cancer Institute reveals that this website is now listed as No.161 of all websites monitored for scientific information related to medicine and health care, which is really quite remarkable.
14. Judie Brown maintains a blog for the American Life League (ALL) which is the epitome of nonsense about stem cell research. A related website called STOPP is devoted to the defeat of The Planned Parenthood Association. Gasp! Their banner states "Behold the Lord, Jesus Christ, who tries so hard to get our attention." So, I guess you can figure out their religious orientation.

Click for data on the maximum lifespan of a variety of zoological species at the Human Aging Genomic Resources website (AnAge Database) maintained by João Pedro de Magalhães now with George Church's Lab at the Harvard School of Medicine.


To Our Regular News Section Readers: If you become aware of a news item that you feel should be posted here, please contact us by E-mail ASAP.




"CIRM Appoints New Chief Scientific Officer"

Marie E. Csete, M.D., Ph.D.

May 3, 2008; Click for an interview with Prof. Marie E. Csete, M.D., Ph.D., the new Chief Scientific Officer (CSO) of the California Institute of Regenerative Medicine (CIRM). In addition to affiliations with Emory University in Atlanta, UCSF, Columbia, Princeton, and CalTech (her Ph.D.), she is an anesthesiologist in her spare time! Her research specialty is stem-cells and aging.


"US Mortality and Life Expectancy for the Year 2005"

April 12, 2008; The CDC in Atlanta has now posted preliminary statistical data on US longevity for 2005, broken down by gender and age [1],
CDC Table 6 for 2005

So, for example, a US female centenarian in 2005 has 2.6 years of life remaining, on average, while a male has only 2.3 years remaining. This Table is consistent with a positive-slope linear log-mortality curve built, as a side effect, right into our Homo sapiens species' genome, providing that the genome has a chance to express its full potential.

Ref. 1. Table 6 with additional breakdowns by race (White, Black).

Note: This data supercedes the data in this News Section for April 23, 2006 and September 5, 2003.


"Gertrude Baines Celebrates 114 in Los Angeles"

Gertrude Baines 114th Birthday Party Stephen Coles with LA Mayor's Certificate Gertrude Baines 114th Birthday Party Gertrude Baines 114th Birthday Party Gertrude Baines 114th Birthday Party with Robert Young Gertrude Baines 114th Birthday Party Gertrude Baines 114th Birthday Party Gertrude Baines 114th Birthday Party: Robert Young, Stephen Coles, and Col. Robert
Johnson
Photos by Natalie S. Coles

Sunday, April 6, 2008; The eight photos above were taken on the occasion of Mrs. Gertrude Baines 114th Birthday Celebration surrounded by her numerous friends and supporters at the Western Convalescent Hospital near downtown Los Angeles. The Certificate presented by the LA-GRG was signed by our Los Angeles Mayor Antonio R. Villaraigosa. Robert Young of Atlanta, GA presented Mrs. Baines with her own copy of the Guinness Book of World Records that lists her name in the top ten. Mrs. Baines is currently the oldest person in Los Angeles, the oldest person in the State of California, the second oldest American, and the third-oldest person in the world.

Refs.:

1. Maria L. La Ganga, "She Makes 114 Look So Easy: Healthy and Content, Gertrude Baines, The World's Third-Oldest Person, Celebrates her Birthday at a Los Angeles Nursing Home," Los Angeles Times, pp. B1,8 (April 7, 2008).

2. Cindy Hu, Chinese Daily News (April 6, 2008).

3. NBC-TV News.

4. Chris Eales, "California's Oldest Person now 114: American Woman Gertrude Baines Celebrates Her 114th birthday," Suite101.com (April 6, 2008).


"UC San Francisco Course on Interstitial Lung Disease"

UCSF One-Day Course on Interstitial Lung Disease

Saturday, April 5, 2008; At this one-day CME-Credit Course taught by faculty from the UCSF campus on the topic of Interstitial Lung Disease, TGF-Beta has again been implicated in the aging process. This time TGF beta stimulates fibroblasts to synthesize excess collagen in the lungs leading to Interstitial Fibrosis and Pneumonia (Note: UIP [or Usual Interstitial Pneumonia] is an old term used by pathologists and is no longer in favor). Note that this form of pneumonia was implicated in the deaths of two of the five Supercentenarians the GRG autopsied in the last five years. We have now learned that this form of Interstitial Lung Disease does not respond to steroid or NSAID treatment and is therefore not a conventional inflammatory process. It appears that the fibroblasts secreting excess collagen migrate to the lungs from other locations in the body (secondary to injury?) and do not normally reside in the lungs. In a clinical trial, Interferon Gamma that normally inhibits TGF-beta doesn't provide any clinical relief for patients with this condition.


"CHI Stem Cell Congress in San Francisco"

Alan Trounson, Ph.D. Alan Trounson, Ph.D. Alan Trounson and Stephen Coles

March 26, 2008; Dr. Alan Trounson, Ph.D., newly appointed President of the California Institute for Regenerative Medicine (CIRM), presented at the Cambridge Health Care Institute (CHI) Stem Cell Congress at the Moscone Center in San Francisco.

Irina Conboy, Ph.D.

March 28, 2008; Dr. Irina Conboy, Ph.D., of UC Berkeley presented at the Stem Cell Congress at the last session on Friday afternoon on the topic "Understanding and Reversing Stem Cell Aging: Pathways to the Fountain of Youth." TGF-beta appears to be implicated in shutting down telomere activity in older Satellite Cells by [20 - 25] percent. For reference, Satellite Cells are the precursors to new multinucleated skeletal myocytes, the cells that normally hypertrophy with strenuous exercise. But this observation is not related to the length of the telomeres themselves, as different strains of mice start off with very different telomere lengths.


"Sir Arthur Clarke [1917 -- 2008]"

Sir Arthur C. Clarke [1917 - 2008]

March 18, 2008; One of Sir Arthur's most famous quotes was that "Any sufficiently advanced technology is indistinguishable from magic."

Refs.:

1. Dennis McLellan, "Arthur C. Clarke [1917 - 2008]: Scientific Visionary Wrote 2001: A Space Odyssey'," The Los Angeles Times, pp. A1,12 (March 19, 2008).

2. Ed Park, "An Appreciation: Clarke's Universal Sci-Fi Magic," The Los Angeles Times, pp. E1,10 (March 20, 2008).

3. "Died: Arthur C. Clarke, 90, Visionary Writer of More Than 100 Science-Fiction and Nonfiction Books, in Sri Lanka," The Wall Street Journal, p. A1 (March 19, 2008).

4. John J. Miller, "Arthur C. Clarke: The Master of Science and Mysticism," The Wall Street Journal, p. D7 (March 20, 2008).

5. "Sci-Fi Guru Clarke To Have Secular Funeral," CNN (March 19, 2008.

6. Sir Arthur Clarke's Final Video.


"UCLA Seminar on Systems Biology"

Prof. James Heath, Ph.D.

March 13, 2008; Prof. James Heath, Ph.D., Elizabeth W. Gillon Professor and Professor of Chemistry and Biochemistry at CalTech and Professor of Molecular and Medical Pharmacology, UCLA, Director of the National Cancer Institutes' Nano Systems Biology (NSB) Cancer Center gave a Noon Research Seminar for the UCLA Jonsson Comprehensive Cancer Center on the topic of "Systems Biology Driven In Vitro Diagnostics and Measurement Technologies for Cancer."

Good News: In a hallway conversation after the talk, Prof. Heath stated that his nanotechnology research on CMOS indicates that Moore's Law could easily continue for another 15 to 16 years with the ideas that he has already published in Science and Nature with his UCLA students.


"The Inventor of LISP Lectures in San Diego"

Prof. John McCarthy, Ph.D.
Steve Coles with Prof. McCarthy

Wednesday, March 5, 2008; Prof. Emeritus John McCarthy of Stanford University, inventor of the term "Artificial Intelligence" at the Dartmouth Conference in the Summer of 1956 and subsequently the programming language LISP delivered a key-note address to 800 attendees this morning at the O'Reilly E-Tech (Emerging Technologies) Conference at the Marriott Hotel in San Diego, CA on the topic of "The Logical Formalization of Common Sense Reasoning." I first met Prof. McCarthy at MIT in November 1961. His office mate at 545 Technology Square in Cambridge, MA at that time was Prof. Marvin Minsky.

He moved to Stanford the next year while I moved from CMU to Stanford in 1967. Over the years, our paths crossed in Dubrovnik, Yugoslavia, Tiblisi, USSR, and Edinburgh, Scotland.

The orange colored paper-back book I am holding up in the photo is a copy of Automata Studies (Princeton University Press, New Jersey; 1956) that McCarthy co-edited with Claude E. Shannon. During our luncheon in San Diego we discussed a range of topics from nuclear weapons treaties, famous mathematicians in history, to HAL-9000 from the Stanley Kubrik/Arthur Clarke film 2001: A Space Odyssey.

- - Steve Coles

Ref.:

Patrick J. Hayes and Leora Morgenstern, "On John McCarthy's 80th Birthday, in Honor of His Contributions, AI Magazine, Vol. 28, No. 4, pp. 93-102 (Winter 2007).


"Functional Regeneration in the Peripheral Nervous System"

Prof. Jerry Silver, Ph.D.

February 21, 2008; UCLA Prof. Michael V. Sofroniew, M.D., Ph.D. introduced Dr. Jerry Silver, Ph.D. of Case Western Reserve University in Cleveland, OH who presented a talk on "Functional Regeneration Beyond the Glial Scar" to 35 Faculty, PostDocs, and Graduate Students of the UCLA Department of Neurobiology at 3:00 PM in the Neurobiology Research Building (NBS) Auditorium. Silver is a superb experimentalist and his work with rat spinal cord was truly groundbreaking. (His slides [in Keynote on a Mac, not Microsoft PowerPoint] with videos consumed 5.7 GB of memory and took 30 minutes to download onto my 16 GB PC Mobile Drive.) LA-GRG Members Steven Kaye and Bobby Brooke were in attendance.


"Stem Cell World Congress in Palm Springs"

Prof. Thomas Skutella of Germany Raphael Gorodetsky and Stephen Minger Bernie Siegel of Florida
Steve Coles, Bernie Siegel, and Christine Mummery

February 11-12, 2008; The Second Annual Stem Cell World Congress was held at the Wyndham Hotel in Palm Springs, CA (the first conference was in La Jolla, CA) for approximately 80 attendees. The first speaker was Prof. Thomas Skutella of Tuebingen University in Germany talking about Male Germ-Line Stem Cells (Spematogonia). Bernard Siegel, Esq. Executive Director of the Genetics Policy Institute of Wellington, FL gave the Keynote Address at the end of the first day. Prof. Guoping Fan of UCLA gave the last talk on methylation patterns in pluripotent stem cells. It was truly an international event with the great majority of the talks coming from European researchers.


"HGPS Can Serve As a Model for Natural Aging"

HGPS 8 yo boys
Two 8-yo boys afflicted with Hutchinson-Gilford Progeria Syndrome (HGPS). Contrary to the notion that HGPS is only a 'cartoon of aging', it may well "serve as a model for the normal aging process in all humans."

February 7, 2008; FOCUS ON RESEARCH:
1. Bruce Korf, M.D., Ph.D., Birmingham, AL
"Hutchinson Gilford Progeria Syndrome, Aging, and the Nuclear Lamina,"
NEJM, Vol. 358, No. 6, pp. 552-5 (February 7, 2008).
"We are living in a time that will probably be remembered as a golden age of discovery in human genetics. Most of the recent excitement has focused on the identification of genes that contribute to the risk of common diseases, so it is easy to forget how much can be learned from the study of rare "single-gene" disorders..."

2. "Phenotype and Course of Hutchinson-Gilford Progeria Syndrome,"
Melissa A. Merideth, M.D., M.P.H., Leslie B. Gordon, M.D., Ph.D., Sarah Clauss, M.D., Vandana Sachdev, M.D., Ann C.M. Smith, M.A., Monique B. Perry, M.D., Carmen C. Brewer, Ph.D., Christopher Zalewski, M.A., H. Jeffrey Kim, M.D., Beth Solomon, M.S., Brian P. Brooks, M.D., Ph.D., Lynn H. Gerber, M.D., Maria L. Turner, M.D., Demetrio L. Domingo, D.D.S., Thomas C. Hart, D.D.S., Jennifer Graf, M.S., James C. Reynolds, M.D., Andrea Gropman, M.D., Jack A. Yanovski, M.D., Ph.D., Marie Gerhard-Herman, M.D. Francis S. Collins, M.D., Ph.D., Elizabeth G. Nabel, M.D., Richard O. Cannon, III, M.D., William A. Gahl, M.D., Ph.D., and Wendy J. Introne, M.D.
NEJM, Vol. 358, No. 6, pp. 592-604 (February 7, 2008).

Abstract:



Background: Hutchinson Gilford Progeria Syndrome is a rare, sporadic, autosomal- dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. The genetic basis of most cases of this syndrome is a change from Glycine GGC to Glycine GGT in codon 608 of the Lamin A (LMNA) gene, which activates a cryptic-splice donor site to produce abnormal Lamin A; this disrupts the nuclear membrane and alters transcription.

Methods: We enrolled 15 children between [1 - 17] years of age, representing nearly half of the world's known patients with HGPS, in a comprehensive clinical protocol between [February 2005 - May 2006].

Results: Clinical investigations confirmed sclerotic skin, joint contractures, bone abnormalities, alopecia, and growth impairment in all 15 patients; cardiovascular and central nervous system sequelae were also documented. Previously unrecognized findings included prolonged prothrombin times, elevated platelet counts and serum phosphorus levels, measured reductions in joint range of motion, low-frequency conductive hearing loss, and functional oral deficits. Growth impairment was not related to inadequate nutrition, insulin unresponsiveness, or growth-hormone deficiency. Growth-hormone treatment in a few patients increased height growth by 10 percent and weight growth by 50 percent. Cardiovascular studies revealed diminishing vascular function with age, including elevated blood pressure, reduced vascular compliance, decreased ankle brachial indexes, and adventitial thickening.

Conclusions: Establishing the detailed phenotype of HGPS is important because advances in understanding this syndrome may offer insight into normal aging. Abnormal Lamin A (Progerin) appears to accumulate with aging in normal cells.


"Understanding Stem-Cell Self-Renewal and Quiescence"

Stephen D. Nimer, M.D.

February 6, 2008; Prof. Stephen D. Nimer, M.D., Head of the Division of Hematologic Oncology at Memorial Sloan-Kettering Cancer Center of New York City gave the weekly Noon Hematology Case Conference at UCLA on the topic of Chronic Leukemias. He noted that the Extra Cellular Matrix in the bone marrow provides a relatively quiescent niche that is protected from exposure to free radicals. Whenever a stem cell is stimulated to divide, if it divides horizontally with both daughter cells touching the stroma, they will both become stem cells. However, if the division takes place vertically, the cell not touching the stroma will break off and differentiate into a progenitor cell fated to migrate into the blood stream. Non-quiescent stem cells will naturally differentiate along a pre-determined direction unless a particular genomic network is expressed that retains both daughter cells in a multipotent state.


"Vigorous Exercise Slows the Erosion of Telomeres"

January 28, 2008;
"The Association Between Physical Activity in Leisure Time and Leukocyte Telomere Length,"
Lynn F. Cherkas, Ph.D., Janice L. Hunkin, B.Sc., Bernet S. Kato, Ph.D., J. Brent Richards, M.D., Jeffrey P. Gardner, Ph.D., Gabriela L. Surdulescu, M.Sc., Masayuki Kimura, M.D., Ph.D., Xiaobin Lu, M.D., Tim D. Spector, M.D., FRCP, and Abraham Aviv, M.D.,
Archives of Internal Medicine, Vol. 168, No. 2. pp.154-8 (2008).

Abstract:

Background: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers.

Methods: We studied 2,401 white twin volunteers, comprising 2,152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders.

Results: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P < .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P = .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P = .03).

Conclusions: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.

Author Affiliations: Twin Research and Genetic Epidemiology Unit, King's College London, St. Thomas' Hospital Campus, London, UK (Drs. Cherkas, Kato, Richards, and Spector and Mss Hunkin and Surdulescu); and The Center of Human Development and Aging, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ; USA (Drs. Gardner, Kimura, Lu, and Aviv).

________________________

Refs:

1. Rob Stein, "Exercise Could Slow Aging Of Body, Study Suggests," The Washington Post, p. A1 (January 29, 2008).

2. "People Who Exercise Are up to Nine Years Biologically Younger Than Those Who Don't, a UK Study Found," The Wall Street Journal, p. A1 (January 29, 2008).

3. Andrew T. Ludlow, Jo B. Zimmerman, Joseph W. Hearn, Sarah Witkowski, Bradley D. Hatfield, and Stephen M. Roth, "Relationship Between Exercise Energy Expenditure and Telomere Length and Telomerase Activity," The FASEB Journal (2007).

4. "Live Long and Perspire: Exercise May Slow Aging at Chromosomal Level," Science News, Vol. 173, No. 5, p. 69 (February 2, 2008).


"President Bush's Inconsistent Logic on Stem Cells in the State of the Union Address"

State of the
Union

January 28, 2008; Below is a selected quote from President George W. Bush's remarks in his last State-of-the-Union Speech delivered to the US Congress tonight regarding the topic of stem cells [1]...

"On matters of life and science, we must trust in the innovative spirit of medical researchers and empower them to discover new treatments while respecting moral boundaries. In November, we witnessed a landmark achievement when scientists discovered a way to reprogram adult skin cells to act like embryonic stem cells. This breakthrough has the potential to move us beyond the divisive debates of the past by extending the frontiers of medicine without the destruction of human life." [Applause.]

"So we're expanding funding for this type of ethical medical research. And as we explore promising avenues of research, we must also ensure that all life is treated with the dignity it deserves. And so I call on Congress to pass legislation that bans unethical practices such as the buying, selling, patenting, or cloning of human life." [Applause.]

GRG Editorial...

iPS cells are good. But destroying preimplantation SCNT-derived blastocysts is bad. But what if iPS and hESC's are in the same indistinguishable equivalence class of totipotent/pluripotent cells? (Sort of like the problem that the FDA faced in trying to distinguish between milk from a cloned cow and a cow born in the traditional manner, i.e., no difference.) So how can one be bad and the other be good? They're either both bad or both good, no?

Here are three views [2] as to why iPS cells may not be what President Bush advertised in his State-of-the-Union Address last week...

Geron Corp. is sticking with human Embryonic Stem Cells (hESC's) rather than iPS (induced Pluripotent Stem Cells). "Even if iPS cells can be grown without the aid of a potentially cancer- causing virus, these cells can't possibly be used for therapies. Starting with a skin cell that might have been altered by aging or with toxins instead of a pure 'crystal-clear' human embryo would add unpredictable risks."
--- Tom Okarma, M.D., Ph.D., CEO, Geron Corp. Menlo Park, CA

"Even if iPS cells eventually prove safe for use in humans, the notion of generating individually- tailored cell populations for every patient will still be 'a pipe dream'. Patient-specific therapy is totally impractical. You would need millions of cell lines. Furthermore, there is no time to generate [autologous] cells if they are needed rapidly, as after a heart attack or a spinal cord injury."
--- Robert Lanza, M.D., Chief Scientific Officer, Advanced Cell Technology, Worcester, MA

"The idea that you would use iPS cells for individual treatments is preposterous. It takes six months of really hard work to make a cell line."
--- Stephen Minger, Ph.D., King's College London, UK.

Refs.:

1. State of the Union Address (9:00 PM EDT; January 28, 2008).

2. Constance Holden and Gretchen Vogel, "A Seismic Shift for Stem Cell Research: The Development of Pluripotent Cells form Individual Skin Cells Has Opened Up a New World of Research, But Scientists Say They Still Need To Work with Embryonic Stem Cells," Science, Vol. 319, No. 5863, pp. 560-3 (February 1, 2008).


"Stemagen Reports Human Therapeutic Cloning in San Diego"

Stemagen Corp.

"Major Advancement Towards Creating Patient-Specific and Disease-Specific Stem Cells For Therapeutic Use"

January 17, 2008; La Jolla, CA - - Stemagen, a privately held embryonic stem-cell research company, announced today it has become the first in the world to create, and meticulously document, a cloned human embryo using Somatic Cell Nuclear Transfer (SCNT). Stemagen CEO, Samuel H. Wood, M.D., Ph.D., a co-author of the publication and a donor of the cells from which the embryos were cloned, terms this achievement "a critical milestone in the development of patient-specific embryonic stem cells for human therapeutic use, potentially including developing treatments for Parkinson's, Alzheimer's and other degenerative diseases." Stemagen's research is exhaustively detailed in a paper published in today's issue of the highly regarded peer-reviewed scientific journal Stem Cells.

"This is not merely a technical improvement on previous research in this area," said Andrew French, Ph.D., lead author on the paper, "Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer (SCNT) with Adult Fibroblasts." "No other scientific group has documented the cloning of an adult human cell, much less been able to grow it to the blastocyst stage, the stage at which it is the adult donor cell that is driving embryonic development, the stage that yields the cells (the inner cell mass) from which embryonic stem cell lines are made," said French, who is Stemagen's Chief Scientific Officer. [Embryonic stem cells hold great promise for developing treatments for many degenerative diseases like Alzheimer's, Parkinson's, and Muscular Dystrophy.]

Five blastocysts were developed from 25 donated mature oocytes. Three were confirmed to be clones based on DNA fingerprinting demonstrating the presence of the skin cell donor DNA in the blastocyst, while one was further confirmed to be a clone by an additional mitochondrial DNA (mtDNA) analysis which revealed the presence of oocyte donor mtDNA without any oocyte donor nuclear DNA. For technical reasons, the genetic material in the remaining two blastocysts did not amplify to the extent required for analysis, and so while it is likely they were clones, the evidence required to claim that with certainty was not present. Thus, in this study, cloned blastocysts were successfully created from approximately 10 percent of all mature donated oocytes, an unexpectedly high rate given past research in this field.

The oocytes used in this study were donated by egg donors and intended parents undergoing egg donation cycles for reproductive purposes at the Reproductive Sciences Center in La Jolla, a leading fertility center specializing in egg donation and other advanced assisted reproductive technologies. Stemagen and the Reproductive Sciences Center worked closely, over an extended period of time, with a leading independent Institutional Review Board (IRB) to develop procedures ensuring that all parties received comprehensive informed consent and that procedures were in place to protect their confidentiality in the process. All research procedures, including the culturing of the skin cells (fibroblasts) were performed under clinical laboratory conditions in close cooperation with the Assisted Reproductive Technologies (ART) Laboratory of the Reproductive Sciences Center, directed by Catharine Adams, Ph.D. French notes, "An important reason for the success of our SCNT procedures depended on the close coordination between our laboratory personnel and fertility center laboratory staff. Timing is a critical element in maximizing the probability of success in this type of procedure."

Wood points out that this research was exhaustively scrutinized by some of the world's most respected scientists and underwent an exceptionally rigorous process of verification, "This achievement was so critical to our field, we felt we should spare no effort in the process of establishing the validity of our work." DNA fingerprinting is the scientifically accepted method for determining if an embryo is a true clone. According to French, "All samples were subjected to this type of analysis to determine their true genetic makeup."

For that, the company turned to Genesis Genetics, a recognized worldwide leader in the field of reproductive embryonic analysis. Company founder and CEO, Mark Hughes, M.D., Ph.D., said "We were proud to collaborate with Stemagen in this important accomplishment. As the leading provider of genetic diagnosis of human embryos, it was important for an independent company like Genesis Genetics to be involved in the verification of this achievement."

Stemagen, Inc., is dedicated to the production of patient-specific embryonic stem cells for therapeutic use through SCNT and "uniparental" embryonic stem-cell technology.

_________________________

TECHNOLOGY DEVELOPMENT:
"Development of Human cloned Blastocysts Following Somatic Cell Nuclear Transfer (SCNT) with Adult Fibroblasts,"

Andrew J. French [1*], Catharine A. Adams [2], Linda S. Anderson [2], John R. Kitchen [3], Marcus R. Hughes [3], and Samuel H. Wood [4]
Stem Cells (on-line January 17, 2008).

1. Stemagen Corporation
La Jolla, CA; USA
2. The Reproductive Sciences Center
La Jolla, CA; USA
3. Genesis Genetics Institute, LLC
Detroit, MI; USA
4. Stemagen Corporation
La Jolla, CA; USA
The Reproductive Sciences Center
La Jolla, CA; USA

* To whom correspondence should be addressed. E-mail: afrench@stemagen.com

Submitted on April 4, 2007; Accepted on January 3, 2008

Abstract:

Nuclear Transfer Stem Cells (NTSC) holds considerable promise in the field of regenerative medicine and cell-based drug discovery. In this study, a total of 29 oocytes were obtained from three young ([20 24] yo) reproductive egg donors who had been successful in previous cycles. These oocytes, deemed by intended parents to be in excess of their reproductive needs, were donated for research without financial compensation by both the egg donor and intended parents after receiving informed consent. All intended parents successfully achieved ongoing pregnancies with the oocytes retained for reproductive purposes. Mature oocytes, obtained within 2 hours following transvaginal aspiration, were enucleated using one of two methods, extrusion or aspiration, after 45-min. incubation in Cytochalasin B. Rates of oocyte lysis or degeneration did not differ between the two methods. Somatic Cell Nuclear Transfer (SCNT) embryos were constructed using two established adult male fibroblast lines of normal karyotype. High rates of pronuclear formation (66%), early cleavage (47%) and blastocyst (23%) development were observed following incubation in standard IVF culture media. One cloned blastocyst was confirmed by DNA and mtDNA fingerprinting analyses and DNA fingerprinting of two other cloned blastocysts indicated they were also generated by SCNT. Blastocysts were also obtained from a limited number of parthenogenetically activated oocytes. This study demonstrates, for the first time, that SCNT can produce human blastocyst stage embryos using nuclei from a differentiated adult somatic cell, and provides new information on methods that may be needed for a higher level of efficiency for human therapeutic cloning.

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Key Words: egg donation, therapeutic cloning, human, embryo, somatic cell nuclear transfer, oocytes, blastocysts

Refs.:

1. Terri Somers, "Successful Embryo Cloning Documented: S.D. Firm's Work Major Step toward Creating Stem-Cell Lines," San Diego Union-Tribune (January 17, 2008).

2. AP, "Scientists Make Cloned Embryos from Skin Cells" CNN (January 17, 2008).

3. AP, "Lab Reproduces Cloned Human Embryo Research," The Los Angeles Times, p. A17 (January 18, 2008).

4. "Early-Stage Human Embryos Cloned from Adult Cells," Nature, Vol. 451, p. 386 (January 23, 2008).


"Complete Organs Grown from Stem Cells"

Rat Hearts
Researchers stripped cells from a rat heart and replaced them with fetal stem cells, getting them to grow into a beating "bioartificial" heart.

January 14, 2008; As published in Nature Medicine, researchers in at the University of Minnesota have fabricated a beating rat heart using fetal stem cells in an Extra Cellular Matrix [1].

Abstract:

About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 days by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.

GRG Editorial: This work proves that the Extra Cellular Matrix (or ECM) is critical in establishing the growth boundaries and final dimensions of an organ. The contractility of this organ was only 2 percent of a normal rat heart for its size, so it would never function as a heart transplant for a rat in need of one. But we need to emphasize that, ultimately, our goal is not to grow complete autologous organs ex vivo, using iPS cells or whatever to populate a pig's Extra Cellular Matrix, and then implant them surgically back into the body, but to establish the rejuvenation of tissues in situ using chemokines to stimulate quiescent, pristine adult stem cells in each organ, as I speculated four years ago back in 2004. But there are also problems with this approach, as Dr. Chris Heward recently pointed out. "Adult stem cells may have knowledge of how to create a new car assuming an infrastructure of an assembly-line factory in place to manufacture cars but not the sort of exotic knowledge a classic car hobbyist uses to keep an old car in running order. Nature never had a need for that sort of knowledge, and it may not exist in natural biology, in the same sense as heart transplant surgery was never invented by Nature. Surgery is a truly exotic intervention from the point of view of evolutionary biology. But Chris's objection is only speculation as well. We'll have to try it out before we know the answer. In the mean time, any little bit of progress will be helpful toward achieving our long-term goal. - - L. Stephen Coles

Refs.:

1. Harald C. Ott, Thomas S. Matthiesen, Saik-Kia Goh, Lauren D. Black, Stefan M. Kren, Theoden I. Netoff, and Doris A. Taylor, "Perfusion-Decellularized Matrix: Using Nature's Platform to Engineer a Bioartificial Heart," Nature Medicine (January 13, 2008).

2. Lawrence K. Altman, "Researchers Create New Rat Heart in Lab" The New York Times (January 13, 2008).

3. BBC News, "'Spare-Part Heart' Beats in Lab: The stripped-out shell of a heart has been made to work again -- using brand new cells planted inside it. The new heart was grown on a basic tissue scaffold" (January 13, 2008).

4. CNN-TV (January 14, 2008; 8:55 AM PST; TRT= 2:18 min).

5. "Hearts of Dead Rats Revived," The Los Angeles Times, p. A10 (January 19, 2008).

6. Patrick Barry, "Phoenix Heart: Replacing a Heart's Cell Could Ease Transplants," Science News, Vol. 173, No. 3, pp., 35-6 (January 19, 2008).


"ACT Improves Yield of PGD-Derived Stem-Cell Lines"

Pre-implantation Genetic Diagnosis of Blastomere
A photomicrograph shows a single cell being removed from an eight-cell-stage human embryo. The biopsied cell undergoes a procedure to make it act like an embryonic stem cell, while the rest of the embryo is allowed to continue normal development.

January 11, 2008; Extracting one out of eight cells from a Blastomere for genetic testing is called Pre-implantation Genetic Diagnosis or PGD. The remaining seven cells do just fine in producing a normal, healthy child providing that the parents decide, after the testing, to go forward with a pregnancy. According to the Society for Assisted Reproductive Technology (SART), about 5,000 IVF couples opt for PGD every year. Dr. Robert Lanza, M.D. Chief Scientific Officer of Advanced Cell Technology in Worcester, MA, reports that he has achieved an increase in efficiency of creating stem-cell lines by PGD from only 2 percent in August 2006 [1] to 50 percent today [2].

Even though this approach, in principle, does not destroy any embryos, bioethicists and politically conservative Christians still object on the grounds that this approach represents what they call the commodification of human embryos, a starting point for harvesting raw materials from young human beings. [4]

Refs:

1. I. Klimanskaya, Y. S. Chung, S. Becker, S. J. Lu, and Robert Lanza, "Human Embryonic Stem-Cell Lines Derived from Single Blastomeres," Nature, Vol. 444, No. 7118, pp. 481-5 (August 23, 2006).

2. Young Chung, Irina Klimanskaya, Sandy Becker, Tong Li, Marc Maserati, Shi-Jiang Lu, Tamara Zdravkovic, Dusko Ilic, Olga Genbacev, Susan Fisher, Ana Krtolica, and Robert Lanza "Human Embryonic Stem Cell Lines Generated without Embryo Destruction, Cell Stem Cell, Vol. 2, No. 1 (January 10, 2008).

3. Gautam Naik, "Scientists Create Stem-Cell Line," The Wall Street Journal, pp. A1, B4 (January 11, 2008).

4. Karen Kaplan, "Stem Cells Created, with Embryos intact," The Los Angeles Times, p. A15 (January 11, 2008).

5. "Embryos Survive Stem-Cell Harvest: Company Urges White House To Endorse Technique," MSNBC.COM . (January 10, 2008).

6. Colin Nickerson, "Firm Says It Can Get Stem Cells with No Harm to Embryos: Massachusetts Company Challenges Bush To Approve Lines," The Boston Globe (January 11, 2008).

7. "Stem Cells: Potent Alternative: Reverse-Engineered Human Stem Cells May Leapfrog the Embryonic Kind," Scientific American, Vol. 298, No. 2, pp. 16,18 (February 2008).

8. Masato Nakagawa, Michiyo Koyanagi, Koji Tanabe, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Keisuke Okita, Yuji Mochiduki, Nanako Takizawa, and Shinya Yamanaka, "Generation of Induced Pluripotent Stem Cells without Myc from Mouse and Human Fibroblasts," Nature Biotechnology, Vol. 26, No. 1, pp. vii, 101-6 (January 2008).


"Chinese Piglets Glow Green in UV Light"

Chinese Pigs Glow in UV Light Chinese Pigs Glow in UV Light
Two of eleven piglets show that they possess Green Fluorescent Pigment (GFP) under UV light in Harbin, China. "A transgenic pig gave birth to eleven piglets," China Daily said.

Wednesday, January 9, 2008; Beijing, CHINA (China Daily/Reuters) -- A cloned pig whose genes were altered to make it glow fluorescent green has passed on the trait to its young, a development that could "lead to the future breeding of pigs for human transplant organs," a Chinese University reported. "The glowing piglets' birth proves transgenic pigs are fertile and able to pass on their engineered traits to their offspring," according to Prof. Liu Zhonghua, who oversees the breeding program at Northeast Agricultural University.

Refs.:

1. MSNBC.

2. "Little Green Piglets Could Aid Humans," The Los Angeles Times, p. A15 (January 12, 2008).


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