Scientists at Wake Forest University Baptist Medical Center are about to embark on a human trial to test whether a new
cancer treatment will be as effective at eradicating cancer in humans as it has proven to be in mice.
will involve transfusing specific white blood cells, called granulocytes, from select donors, into patients with advanced
forms of cancer. A similar treatment using white blood cells from cancer-resistant mice has previously been highly successful,
curing 100 percent of lab mice afflicted with advanced malignancies.
Zheng Cui, Ph.D., lead researcher and associate
professor of pathology, announced the study June 28 at the Understanding Aging conference in Los Angeles.
given the go-ahead by the U.S. Food and Drug Administration, will involve treating human cancer patients with white blood
cells from healthy young people whose immune systems produce cells with high levels of cancer-fighting activity.
basis of the study is the scientists' discovery, published five years ago, of a cancer-resistant mouse and their subsequent
finding that white blood cells from that mouse and its offspring cured advanced cancers in ordinary laboratory mice. They
have since identified similar cancer-killing activity in the white blood cells of some healthy humans.
"In mice, we've
been able to eradicate even highly aggressive forms of malignancy with extremely large tumors," Cui said. "Hopefully, we will
see the same results in humans. Our laboratory studies indicate that this cancer-fighting ability is even stronger in healthy
The team has tested human cancer-fighting cells from healthy donors against human cervical, prostate and
breast cancer cells in the laboratory - with surprisingly good results. The scientists say the anti-tumor response primarily
involves granulocytes of the innate immune system, a system known for fighting off infections.
Granulocytes are the
most abundant type of white blood cells and can account for as much as 60 percent of total circulating white blood cells in
healthy humans. Donors can give granulocytes specifically without losing other components of blood through a process called
apheresis that separates granulocytes and returns other blood components back to donors.
In a small study of human
volunteers, the scientists found that cancer-killing activity in the granulocytes was highest in people under age 50. They
also found that this activity can be lowered by factors such as winter or emotional stress. They said the key to the success
for the new therapy is to transfuse sufficient granulocytes from healthy donors while their cancer-killing activities are
at their peak level.
For the upcoming study, the researchers are currently recruiting 500 local potential donors who
are 50 years old or younger and in good health to have their blood tested. Of those, 100 volunteers with high cancer-killing
activity will be asked to donate white blood cells for the study. Cell recipients will include 22 cancer patients who have
solid tumors that either didn't respond originally, or no longer respond, to conventional therapies. The study will cost $100,000
per patient receiving therapy, and for many patients (those living in 22 states, including North Carolina) the costs may be
covered by their insurance company. There is no cost to donate blood. Click here for general information about insurance coverage of clinical trials.
For more information about qualifications for
donors and participants, go to http://www.wfubmc.edu/LIFT (Web site will be available the evening of 6/27.) Cancer-killing ability in these cells is highest during the summer, so
researchers are hoping to find volunteers who can afford the therapy quickly.
"If the study is effective, it would
be another arrow in the quiver of treatments aimed at cancer," said Mark Willingham, M.D., a co-researcher and professor of
pathology. "It is based on 10 years of work since the cancer-resistant mouse was first discovered."
are selected as donors - based on the observed potential cancer-fighting activity of their white cells - will complete the
apheresis, a two- to three-hour process similar to platelet donation, to collect their granulocytes. The cancer patients will
then receive the granulocytes through a transfusion - a safe process that has been used for more than 30 years. Normally,
the treatment is used for patients who have antibiotic-resistant infectious diseases. The treatment will be given for three
to four consecutive days on an outpatient basis. Up to three donors may be necessary to collect enough blood product for one
"The difference between our study and the traditional white cell therapy is that we're selecting
the healthy donors based on the cancer-killing ability of their white blood cells," said Cui. The scientists are calling the
therapy Leukocyte InFusion Therapy (LIFT).
The goal of the phase II study is to determine whether patients can tolerate
a sufficient amount of transfused granulocytes for the treatment. Participants will be monitored on a regular basis, and after
three months scientists will evaluate whether the treatment results in clear clinical benefits for the patients. If this phase
of the study is successful, scientists will expand the study to determine if the treatment is best suited to certain types
---------------------------- Article adapted by Medical News Today from original press release. ----------------------------
Yikong Keung, M.D., a medical oncologist, is the chief clinical investigator of the study. Gregory Pomper, M.D., assistant
professor of pathology and the director of the Wake Forest Baptist blood bank, will oversee the blood banking portion of the
Wake Forest University Baptist Medical Center (http://www.wfubmc.edu/) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University
Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad
Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of
"America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by
America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third
in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Study finds adult source works in rats Results hopeful
for paralysis research
Mar. 29, 2006. 03:04 PM
have used stem cells to repair spinal cord damage in laboratory rats, restoring significant mobility in the animals and bringing
the search for a human therapy another step closer. A team led by Toronto neuroscientist Dr. Michael Fehlings extracted
stem cells from adult mice, which were transplanted into rats whose spines had been crushed. The stem cells developed into
one type of cell destroyed by the injury — the kind that produces myelin, the insulating layer that cocoons the bundle
of nerve fibres that make up the cord. Injuries that crush or compress the spinal cord destroy its
ability to regenerate myelin-forming cells, leading to paralysis. Without the myelin sheath, "nerve fibres don't conduct the
signals, they kind of short out and you don't get signals crossing," said Fehlings, medical director of the Krembil Neuroscience
Centre at Toronto Western Hospital. Dr. Oswald Steward, director of the Reeve-Irvine Research Centre
for spinal cord injury at the University of California, said the concept of using stem cells for spinal cord cell regeneration
has been applied by other scientists. But Fehlings' work "breaks new ground in a couple of ways": by showing that adult stem
cells work as well as the more ethically controversial fetal or embryonic stem cells and that the drug minocycline improved
their survival, Steward said. Fehlings said, however, that his transplanted cells, called
neural precursor cells, are not as versatile as embryonic stem cells because they can give rise only to cells of the nervous
system. In Fehlings' experiments, rats whose crushed spinal cords were
injected with adult stem cells and given a cocktail of drugs — growth hormone, cyclosporine to prevent rejection and
the anti-inflammatory minocycline — were found to walk with better co-ordination and weight-bearing ability. As well, researchers were able to get those results even when
the stem cells were injected two weeks after the injury. Current therapies that attempt to save spinal cord tissue from trauma-induced
destruction must be given within hours of injury. "Our strategy wasn't to get perfect regeneration or to try
to regrow the whole spinal cord," said Fehlings. "Our approach was really to try to replace one missing cell type. The success appears to be due to minocycline, which reduced
inflammation of the spinal cord and limited cell damage, said Fehlings, adding it also seemed to boost survival of stem cells.
Someday, stem cells might be taken from the brains of patients
with spinal cord injuries for their own treatment, Fehlings said. His study appears in today's edition of The Journal of
probe anti-ageing gene
By Roland Pease
BBC Science Correspondent08-26-05
Klotho seems to delay the effects
of old age in mice
Scientists in the United States have discovered a gene that can keep mice alive for 30% longer than normal. They say the gene has a key role to play
in many of the processes related to ageing.
Because humans have a very similar
version of the gene, the hope is that it will show a way to improve our declining years.
The gene studied in the new research
is called Klotho, named after a minor Greek goddess who spins life's thread.
The gene certainly seems to do that.
Mice - and people - with defective forms of the gene appear to age prematurely.
Now researchers have shown that by
boosting the activity of the gene, they can extend the natural lives of male mice from two to three years.
The effect is not quite so strong in
"It could be one of the significant
steps for developing anti-ageing therapy," Dr Makoto Kuro-o, assistant professor of pathology at the University of Texas'
Southwestern Medical Center and senior author of the study, told Science magazine.
Klotho seems to delay many of the effects
of old age, like the weakening of bones, clogging of the arteries and loss of muscle fitness.
This is important for those researching
the causes of ageing, whose intention is not so much to prolong life as to improve the quality of our final years.
But there may be downsides with Klotho.
The long-lived mice in the new experiments tend to be less fertile.
And the gene may also predispose people
The trick for researchers will be to
find ways of getting the life-enhancing results of Klotho while avoiding the drawbacks.
crack 40-year-old DNA puzzle and point to ‘hot soup’ at
the origin of life
A new theory that explains
why the language of our genes is more complex than it needs to be also suggests that the primordial soup where life began
on earth was hot and not cold, as many scientists believe.
In a paper published in the Journal of Molecular Evolution
this week, researchers from the University of Bath describe a new theory which they believe could solve a puzzle that has
baffled scientists since they first deciphered the language of DNA almost 40 years ago.
1968, Marshall Nirenberg, Har Gobind Khorana and Robert Holley received a Nobel Prize for working out how proteins are produced
from the genetic code. They discovered that three letter ‘words’ - known as codons - are read from the DNA code and then translated into one of 20 amino acids. These amino
acids are then strung together in the order dictated by the DNA code and folded into complex shapes to form a specific protein.
As the DNA ‘alphabet’ contains four letters - called bases - there
are as many as 64 three-letter words available in the DNA dictionary. This is because it is mathematically possible to produce 64 three-letter words from
any combination of four letters.
But why there should be 64 words in the DNA dictionary which translate into just 20 amino acids, and why a process that
is more complex than it needs to be should have evolved in the first place, has puzzled scientists for the last 40 years.
of scientists have suggested theories to solve the puzzle, but these have been quickly discounted or failed to explain some
of the other quirks in protein synthesis.
“Why there are so many more codons than amino acids has puzzled scientists
ever since it was discovered how the genetic code works,” said Dr Jean van den Elsen from the Department of Biology
“It meant the genetic code did not have the mathematical brilliance you would expect from something
so fundamental to life on earth.”
One of quirks of the genetic code is that there are groups of codons which
all translate to the same amino acid. For example, the amino acid leucine can be translated from six different codons whilst
some amino acids, which have equally important functions and are translated in the same amount, have just one.
new theory builds on an original idea suggested by Francis Crick - one of the discoverers of the structure of DNA - that the three-letter code evolved from a simpler two-letter
code, although Crick thought the difference in number was simply an accident “frozen in time”.
The University of Bath researchers suggest that the primordial ‘doublet’ code was
read in threes - but with only either the first two ‘prefix’ or last two ‘suffix’ pairs of bases being
By combining arrangements of these doublet codes together, the scientists can replicate the table of
amino acids - explaining why some amino acids can be translated from groups of 2, 4 or 6 codons. They can also show how the
groups of water loving (hydrophilic) and water-hating (hydrophobic) amino acids emerge naturally in the table, evolving from
overlapping ‘prefix’ and ‘suffix’ codons.
“When you evolve our theory for a doublet system
into a triplet system, you get an exact match up with the number and range of amino acids we see today,” said Dr van
den Elsen, who has worked with Dr Stefan Babgy and Huan-Lin Wu on the theory.
“This simple theory explains many
unresolved features of the current genetic code. No one has ever been able to do this before, so we are very excited.”
theory also explains how the structure of the genetic code maximises error tolerance. For instance, ‘slippage’
in the translation process tends to produce another amino acid with the same characteristics, and explains why the DNA code is so good at maintaining its integrity.
is important because these kinds of mistakes can be fatal for an organism,” said Dr van den Elsen. “None of the
older theories can explain how this error tolerant structure might have arisen.”
The new theory also highlights
two amino acids that can be excluded from the doublet system and are likely to be relatively recent ‘acquisitions’
by the genetic code. As these amino acids - glutamine and asparagine - are unable to hold their shape in high temperatures,
this suggests that heat prevented them from being acquired by the code at some point in the past.
One possible reason
for this is that the Last Universal Common Ancestor (LUCA), which evolved into all life on earth, lived in a hot sulphurous
pool or thermal vent. As it moved into cooler conditions, it was able to take up these two additional amino acids and evolve
into more complex organisms. This provides further evidence for the debate on whether life emerged from a hot or cold primordial
“There are still relics of a very old simple code hidden away in our DNA and in the structures of our cells,” said Dr van den Elsen, who points
to several aminoacyl-tRNA synthetases - molecules involved in protein synthesis - which only look at pairs of bases in triplet
codons, as well as other physical evidence in support of the theory.
“As the code evolved it has been possible
for it to adapt and take on new amino acids. Whether we could eventually reach a full complement of 64 amino acids I don’t
know, a compromise between amino acid vocabulary and its error minimising efficiency may have fixed the genetic code in its
July 02, 2005
find offers a glimmer of hope to Parkinson's sufferers By Sam Lister, Health Correspondent
are hailing a potential breakthrough in the treatment of Parkinson’s disease and other neurological conditions following
research into an experimental drug that prompts the regrowth of lost nerve fibres.
of the brain of a Parkinson’s sufferer has shown that the treatment, a tissue- protecting protein known as GDNF, triggered
repair of damaged nerve fibres and improved body movement in patients. Scientists believe that the drug could now be applied
to other nerve growth factors used in Alzheimer’s disease and Motor Neuron disease. More than 120,000 people in the
UK suffer from Alzheimer’s, which effects movement, and although treatments are available, no cure has yet been
analysed patient, a man aged 62, was one of five people in a pilot study carried out by Steven Gill, at FrenchayHospital, Bristol. In the study, GDNF — glial cell line-derived
neurotrophic factor — was pumped through a catheter into a damaged part of the brain.
months, patients were noticing dramatic improvements in their ability to move, which continued over almost four years of treatment.
Even after ceasing medication, the patients’ progress has been maintained.
the death of the man from an unrelated heart attack in December, scientists at Bristol University studied the side of his
brain injected with GDNF and compared it with the untreated area. In Parkinson’s disease nerves containing the chemical
messenger dopamine are lost from a region of the brain known as the putamen, leading to tremors and other motor abnormalities
characteristic of the disease.
the GDNF brain, Seth Love, a professor at Frenchay Hospital’s Institute of Clinical Neurosciences, found that dopamine-containing
nerve fibres had sprouted back in the putamen. Mr Gill, a neurosurgeon, said that the evidence, which is published this month
in the journal Nature Medicine, was compelling.
“This is the first time that there has been evidence of resuscitation of dying neurons and rewiring of the brain to
is not available to patients with Parkinson’s after its manufacturer, Amgen, ceased production over concerns about its
toxicity and a mediocre improvement rate in users.
the Bristol team developed a much more refined and direct means of injecting the drug into the brain tissue, which has been credited
with the dramatically improved outcomes. To date, the most commonly used Parkinson’s drug has been L-Dopa, which only
controls the symptoms for most patients.
Korea Advances One Step Closer
to Stem Cell Therapy
By Kim Tae-gyu Staff Reporter
Korean scientists have taken another gigantic step in their plan for gene
therapy by advancing technologies of growing stem cells into specific cells.
The team, headed by Seoul National University professor Moon Shin-yong,
said yesterday that it developed human embryonic stem cells into insulin-secreting cells, one step before making beta cells
of the pancreas.
``Scientists have typically depended on gene manipulation to harvest specific
cells from stem cell batches. But we adopted a new way of using protein to make progress,’’ the 57-year-old Moon
Moon’s team injected protein into embryonic stem cells and saw them
differentiate into insulin-secreting cells, which can develop into the pancreas’ beta cells.
``If we can make beta cells of the pancreas, they can be used to deal with
diabetes. We found that proteins might open the door to the differentiation of stem cells,’’ Moon’s top
lieutenant Kwon Young-do said.
The differentiation technology is currently the most sought-after segment
by international embryologists, including world-famous cloning scientist Hwang Woo-suk.
Hwang, who cloned a human embryo for the first time in history in 2003,
said the next goal for the world would be to solve the differentiation riddles.
In fact, Moon is a close friend of Hwang and he is also a coauthor of the
embryonic stem cell research papers, printed on the Science last year and this year, led by Hwang.
Geneticists hope versatile stem cells might someday produce tissue to repair
spinal-cord injuries, diabetes or yield therapies for degenerative diseases such as Parkinson’s and Alzheimer’s.
The medical breakthrough of Moon’s team will be featured in the next
edition of international journal Molecular Therapy.
NEWYORK, June 27, 2005 -- According to research published today, investigators from MemorialSloan-KetteringCancerCenter (MSKCC) have used new techniques in the laboratory that
allowed them for the first time to derive unlimited numbers of purified mesenchymal precursor cells from human embryonic stem
cells (HESCs). Mesenchymal precursor cells are capable of giving rise to fat, cartilage, bone, and skeletal muscle cells,
and may potentially be used for regenerative stem cell therapy in bone, cartilage, or muscle replacement.
study, demonstrating the specialized techniques for isolating mesenchymal precursors and generating, purifying, and differentiating
those cells in culture, is published online and freely available in the journal PLoS Medicine (Public Library of Science).
took two lines of completely undifferentiated HESCs and by culturing them in the presence of mouse cells, stimulated them
to turn into mesenchymal cells. They then treated these cells with compounds to make them change into specialized bone, cartilage,
fat, and muscle cells. According to the study, researchers were able to confirm that these cells were all human cells and
that there was no evidence that the cells became cancerous.
precursors derived from HESCs are different from adult mesenchymal cells because they can efficiently differentiate into skeletal
muscle (adult mesenchymal cells do not) in addition to fat, cartilage, and bone. Limited numbers of mesenchymal stem cells
have been isolated from adult bone marrow and connective tissues, but harvesting these cells from any of these sources requires
invasive procedures and the availability of a suitable donor. The capacity of these cells for long-term proliferation is also
poor. In contrast, HESCs could provide an unlimited number of specialized cells.
to Lorenz Studer, MD, PhD, Head of the Stem Cell and Tumor Biology Laboratory at MSKCC and senior author of the PLoS Medicine
study, the high purity, unlimited availability, and multi-potentiality of mesenchymal precursors derived from HESCs will provide
the basis for preclinical mouse studies to assess the safety of these cells. The investigators have already taken the next
step in this research and are testing the therapeutic potential of embryonic stem cell-derived muscle cells in animal models
of muscle disorders.
University of California, Davis - MedicalCenter
UC Davis researchers discover receptor pathway for C-reactive protein and its effects
the first time, scientists have discovered how C-reactive protein, or CRP, is able to access endothelial cells. The UC Davis
researchers’ findings will be published in the July issue of Arteriosclerosis, Thrombosis, and Vascular Biology, one
of the American Heart Association’s leading journals.
CRP is a known risk marker for heart disease and, in
a study published earlier this year, UC Davis researchers Ishwarlal Jialal and Sridevi Devaraj found that endothelial cells
also produce CRP, which is increased 100-fold when cytokines are secreted by human macrophages, a key finding that helps to
explain how plaque formation is initiated.
Devaraj and Jialal have now discovered how CRP affects endothelial cells,
cells that line the cerebral and coronary arteries, and promotes plaque rupture, leading to heart attacks and strokes. CRP
appears to bind to a family of immunoglobulin-processing receptors known as Fc-gamma receptors.
"In this study we convincingly
show that CRP binds to two members of the Fc-gamma receptor family, CD64 and CD32, and that by blocking these receptors with
specific antibodies, we can reverse the detrimental effects of CRP on endothelial cells," said Jialal, the Robert E. Stowell
Chair of Experimental Pathology and director of the Laboratory of Atherosclerosis and Metabolic Research at UC Davis Medical
"This is the first time that anyone has shown how CRP is able to get into the human aortic endothelial cells.
Fc-gamma receptors CD32 and CD64 are the culprits," said Sridevi Devaraj, associate professor of pathology at UC Davis School
of Medicine and MedicalCenter.
at UC Davis and other institutions has shown that CRP induces endothelial cell dysfunction, thus promoting plaque rupture.
CRP causes endothelial cells to produce less nitric oxide and to increase the number of cell adhesion molecules. This, in
turn, allows damaging leukocytes to enter the vessels. Devaraj and Jialal also showed, in a previous study, that CRP induces
endothelial cells to produce plasminogen activator inhibitor, or PAI-1, which promotes clot formation. In addition, recent
studies suggest that plaque tissue also produces CRP.
"In future studies, we will examine the precise pathways by which
these receptors are able to mediate CRP effects so that more specific therapies can be developed to target inflammation,"
Coronary heart disease is the nation’s single leading cause of death. According to the American
Heart Association, approximately 1.2 million Americans will have a coronary attack this year. Almost a half million of these
people will die. About 7.1 million Americans have survived a heart attack. And another 6.4 million Americans have experienced
chest pain or discomfort due to reduced blood supply to the heart.
Reducing the concentration of CRP with drugs, such
as statins, has been shown to reduce cardiovascular events. Treating other risk factors such as smoking, obesity, high blood
pressure with angiotensin receptor blockers and diabetes with thiazolidinediones and metformin are also shown to reduce the
levels of CRP.
Patients with advanced heart failure significantly improved after receiving stem cell therapy,
according to results of a clinical trial presented at the annual meeting of the International Society for Minimally Invasive
Cardiothoracic Surgery (ISMICS) in New York.
The study showed, 30 days after receiving the injection of stem cells into their hearts,
patients improved an average of 41 percent in their hearts´ pumping efficiency. The distance they could walk nonstop increased
by 72 percent in a standard test widely used to assess heart patients.
After 90 days, the heart-pumping improvement was sustained and patients further increased
the distance they could walk in the standard test.
The study is the first to use human fetal-derived stem cell therapy in patients with heart failure.
Drs. Federico Benetti, Luis Geffner, Yuliy Baltaytis and Teodoro Maldonado at LuisVernazaHospital
in Guayaquil, Ecuador, performed the surgical procedure.
Advanced heart failure is an incurable and usually fatal condition. Other than heart transplanting,
current medical treatments cannot reverse the course of the disease, and only slow its progression or help control its symptoms.
New study explains process
leading to many proteins from one gene
15 Apr 2005
New findings from researchers
at UT Southwestern Medical Center help explain how the 20,000 to 25,000 genes in the human genome can make the hundreds of
thousands of different proteins in our bodies.
Genes are segments of DNA that carry
instructions for making proteins, which in turn carry out all of life's functions. Through a natural process called "alternative
splicing," information contained in genes is modified so that one gene is capable of making several different
"Alternative splicing is a key mechanism for achieving a diverse range of proteins, which contributes to the complexity of
higher organisms," said Dr. Harold "Skip" Garner, professor of biochemistry and internal medicine at UT Southwestern and senior
author of a new study aimed at understanding how and why alternative splicing occurs in humans.
The study is available
online and will be published in the April 15 issue of the journal Bioinformatics.
Errors in alternative splicing can
result in truncated or unstable proteins, some of which are responsible for human diseases such as prostate cancer and schizophrenia, Dr. Garner said. But errors also can result in proteins with new functions
that help drive evolutionary changes.
"Alternative splicing appears to occur in 30 percent to 60 percent of human
genes, so understanding the regulatory mechanisms guiding the process is fundamentally important to almost all biological
issues," said Dr. Garner.
Alternative splicing can be likened to alternative versions of a favorite cookie recipe.
If the original recipe (the gene) calls for raisins, walnuts and chocolate chips, and you copy the recipe but leave out the
raisins, you'll still get a cookie (protein) from your version, just a different cookie. Omit a necessary ingredient, such
as flour, and you'll have a mess (nonfunctioning or malfunctioning protein).
Similarly, the information in genes is
not directly converted into proteins, but first is copied by special enzymes into RNA, or more specifically, pre-messenger
While the entire gene is copied into pre-mRNA, not all of that information will be used to make a protein. RNA
segments called exons carry the protein-making information, while the segments between exons, called introns, are snipped
out of pre-mRNA by special proteins. Exons also may be snipped out. Once snipping is complete, the remaining exons are spliced
back together to form a fully functional, mature mRNA molecule, which goes on to create a protein.
the UT Southwestern researchers scanned the human genome and found that the presence of certain DNA
sequences called "tandem repeats" that lie between exons are highly correlated with the process of alternative splicing. They
found a large number of tandem repeats on either side of exons destined to be spliced out of the pre-mRNA. The tandem repeat
sequences also were complementary and could bind to each other.
"The complementary tandem repeat sequences on either
side of an exon allow the DNA to loop back on itself, bind together, pinch off the loop
containing a particular exon and then splice it out," Dr. Garner explained.
The chemical units that make up an organism's
DNA are abbreviated with the letters A, C, T and G. Strings of these letters form genes
and spell out genetic instructions. Tandem repeats have DNA sequences with the same series
of letters repeated many times, such as CACACACACACA.
Tandem repeats are "hot spots" where errors can easily be made
during the copying process; for example, an extra CA could be added or deleted from the correct sequence. These errors could
then result in a gene improperly splicing out an exon, thus making the wrong protein, Dr. Garner said. His research group
has previously shown that these sequences are highly variable in cancer, and he said the new findings could go a long way
toward understanding the genetic nature of how cancers start and progress.
"With this new understanding, we can now
predict all genes that can re-arrange in this way and even predict which might splice improperly, resulting in disease," he
Former UT Southwestern research associate Dr. Yun Lian was a co-author of the study.
The research was
funded by the National Cancer Institute, the National Heart, Lung and Blood Institute and the M.R. and Evelyn Hudson Foundation.
Contact: Amanda Siegfried firstname.lastname@example.org 214-648-3404 University of Texas Southwestern
Medical Center at Dallas http://www.swmed.edu
Small Study Suggests
Gene Therapy Slows Alzheimer's
POSTED: April 25, 2005
UPDATED: April 25, 2005
-- The first attempt at gene therapy for Alzheimer's disease patients may show promising results, according to a small study
published Sunday in the journal Nature Medicine.
The study suggests gene
therapy may significantly slow worsening of the disease in a few people who have tested it so far.
Far more research is needed
to see if the experimental treatment, which requires a form of brain surgery, really helps.
But if the approach pans
out, researchers said delivering protective substances into a diseased brain may hold the potential to rescue some dying brain
The study shows that in one
patient, the brain tissue showed new growth -- which was a first.
Alzheimer's disease is the
most common cause of dementia in older people. It's a medical condition that disrupts the way the brain works.
Alzheimer's disease affects
the parts of the brain that control thought, memory and language. Although the risk of getting the disease increases with
age, it is not a normal part of aging. The cause of the disease is unknown and there is no cure.
It is estimated that currently
4 million people in the United States may have Alzheimer's
disease. The disease usually begins after age 65; the risk of Alzheimer's disease goes up with age.
While younger people
may have the disease, it is much less common. About 3 percent of men and women ages 65-74 have Alzheimer's disease and nearly
half of those over age 85 could have the disease.
Pancreatic cell transplant
could lead to diabetes cure
By Anita Manning, USA
The first successful transplant
of insulin-producing cells from a live donor — a mother to her daughter — is being reported today by Japanese
scientists, raising hopes for a cure for severe diabetes.
Diabetes experts caution that
the procedure has been performed only once and in a patient whose diabetes was not typical. But the accomplishment is "dramatic,"
says Robert Goldstein, chief scientific officer of the Juvenile Diabetes Research Foundation.
Both the patient, a 27-year-old
woman, and her mother, 56, are healthy and have normal blood sugar levels, lead author Shinichi Matsumoto and colleagues say.
Their article was posted online Monday ahead of publication in the British medical journal The Lancet. The patient is considered
cured for now, but whether the disease will return is uncertain.
The procedure was effective
using less than half the mother's pancreas. Transplantation of insulin-producing cells, or islet cells, taken from cadavers
may require up to three pancreases, though new techniques have been effective using just one.
"This is a significant advance,"
says Alan Cherrington of VanderbiltUniversity,
president of the American Diabetes Association. "What it says is that if you can get really healthy undamaged islets, it doesn't
take as many of them to cure diabetes as it would if they're subject to some trauma."
If the study's results are
duplicated, donations taken from living people could help ease the shortage of such cells, the researchers write. Whether
the cells remain viable is unknown, Cherrington says.
Nor is it clear whether the
procedure would be as effective in people, like most of those with type 1 diabetes, whose own immune cells have destroyed
their insulin-producing pancreatic cells. The Japanese patient's diabetes was caused by chronic pancreatitis, an inflammation,
so the risk of an autoimmune attack on the transplanted cells was reduced, the researchers say, and that might have improved
Diabetes experts also cautioned
that the removal of half a pancreas could place the donor at risk of developing diabetes. Only those who have no evidence
of prediabetes, obesity or other risk factors could be considered donors, Goldstein says. "It's not like taking out an appendix,"
Attempts in the late 1970s
to transplant pancreatic cells from living donors failed, partly because the anti-rejection drugs available were "primitive,"
says James Shapiro of the University of Alberta,
a co-author of the article. He pioneered the first successful islet cell transplantation using cells from cadavers five years
"It remains to be seen
whether transplant from living donors has same effect," Shapiro says. But "this is the first successful case, and I'm particularly
encouraged by the outcome."
Israeli researcher identifies
three genes that lead to longevity By ISRAEL21c staff March 15, 2005
gene CETP regulates lipoproteins (shown here) - substances that shuttle cholesterol and triglycerides through the bloodstream.
Only one in 10,000 people will celebrate
a century of life, but research by an Israeli-born scientist may increase those odds in the near future.
Dr. Nir Barzilai,
director of the Institute for Aging Research at Albert Einstein College of Medicine in the Bronx, has led a study that has
identified three genes that can lead to a long, healthy life.
Barzilai's team studied 300 Ashkenazi Jews between 95 and 108 years old and their children, many of whom
have already lived beyond the average lifespan - 77.6 years.
"People with exceptionally long lives offer us a short-cut
in understanding diseases and what prevents them," Barzilai told Newsday.
Barzilai's team were looking for
genes that are more common in these families. A specific form of any one of the three genes recently identified showed up
in 30 percent of these families, compared to 5 percent of people from families without a history of longevity.
of the genes, called CETP, is present in 8 percent of 65-year-olds and the incidence jumps to 25 percent in those who make
it to 105. CETP regulates lipoproteins, substances that shuttle cholesterol and triglycerides through the bloodstream. It
also plays a role in increasing the good form of cholesterol, HDL. Those who inherit this rare form of CETP have larger lipoprotein
particles in their blood.
The scientists are now trying to understand why these larger particles would be more protective
than smaller ones. They are also endowed with good cognitive function. By contrast, half of people over 85 suffer from Alzheimer's
disease or another form of dementia.
Barzilai said that he and his colleagues have confirmed that the CETP gene mutation
occurs more often in another population of elderly people without Alzheimer's compared with those with the mind-robbing disease.
He reported these findings earlier this week at a scientific meeting on dementia, sponsored by Albert Einstein College.
longevity gene identified is apoC-III, also involved in lipid metabolism. The third gene is APM1, which is involved in the
regulation of insulin and the inflammatory process. It's not clear how this rarer form of APM1 leads to longer life. But they
did find that the levels of adiponectin, a hormone made by the gene, are higher in the centenarians and their children, and
even higher in those with superb cognitive function.
These discoveries suggest that scientists could one day develop
medicines that manipulate proteins made by longevity genes.
That day may not be far off. Barzilai said that Pfizer
has created and is testing a cholesterol-lowering drug that seems to do the same thing CETP does.
long argued that environment plays a more important role than genes in determining lifespan. "I have people who have smoked
for 75 years, others who eat lots of meat and little vegetables and others who have never exercised," Barzilai said. Thirty
percent of the centenarians in his study are overweight or obese. "The genes seem to protect them from environmental risks,"
Indeed, some of the centenarians look and act physically and mentally 30 years younger than others, he added.
He's not sure why.
The doctor believes that the good form of cholesterol, HDL, is key to a long, dementia-free life.
"Give me a 100 year old and let me measure her HDL and I can tell you how good her cognitive function is," he said.
was the chief medic of the Israeli army before enrolling at the Technion Israel Institute of Technology in 1985. As a medical
student he provided medical assistance at third world locations, such as at a refugee camp in Cambodia (1979-80) and at a
clinic of the Kwazulu homeland in Africa (1983), and conducted biomedical research at Baylor College, NIH, and The Royal Free
Hospital in London.
His residency was in Medicine and Geriatrics at Hadassah Hospital (Hebrew University) and at Yale
University. His residency was in Medicine and Geriatrics at Hadassah Hospital (Hebrew University) and at Yale University.
Barzilai then trained in Endocrinology and Molecular Biology at Cornell University Medical College and at The Albert Einstein
College of Medicine. Barzilai is the Director of the Institute for Aging Research at the Albert Einstein College of Medicine.
He is currently an Associate Professor in the Department of Medicine, Molecular genetics and the Diabetes Research Center
and is a member of the Divisions of Endocrinology and Geriatrics. He is also the Director of the Montefiore Hospital Diabetes
Barzilai's interests focus on the basic mechanisms on the biology of aging. He was the recipient of the prestigious
Beeson Fellow for Aging Research and the Senior Ellison Foundation award. Barzilai has published nearly 100 peer-reviewed
papers, reviews and chapters in textbooks.
Genes for alcohol consumption
How much alcohol we drink could be influenced by our genes, scientists reveal in a study
published on March 17 2005.
from the Department of Experimental Psychology at the University of Bristol, in collaboration with colleagues from the University
of Oxford, found that the amount of beer, wine and other alcoholic drinks that people regularly consume, and possibly an individual's
susceptibility to addiction, may be related to differences in genetic make-up.
“Our study suggests that there's
a genetic basis to certain kinds of behaviour, including alcohol consumption.".
Dr Marcus Munafò
Lead researcher Dr Marcus Munafò, at the Department of Experimental Psychology,
said: “Our study suggests that there's a genetic basis to certain kinds of behaviour, including alcohol consumption,
which may be important in influencing whether people are at an increased risk of alcohol dependence. Understanding genetic
influences on behaviour is important if we are to understand why some people are more likely to become addicted than others.”
The scientists analysed data from almost a thousand people who gave detailed information on their drinking habits.
The research focused on a key gene that controls chemical signalling in the brain. Different versions of this gene may affect
the balance and effect of signalling molecules and in turn help to shape individual drinking habits.
not know precisely why particular genetic variants may influence behaviour, but they do have a few clues. They found that
one particular genetic variant - a version of the dopamine D2 receptor gene (DRD2) - was strongly associated with alcohol consumption.
The DRD2 gene appears to influence the ‘high' that people derive from drugs such as alcohol. People
without this variant might derive less pleasure from alcohol, and may therefore drink less.
The large-scale study,
published in The Pharmacogenomics Journal [March 2005], provides evidence that particular human genes can influence behaviour.
It is being hailed as an important advance in understanding why some of us drink more than others, and why some people might
be more vulnerable to alcohol dependence.
New breakthrough means insulin
dependence could be a thing of the past for diabetes sufferers -
A multidisciplinary team at King's CollegeHospital has successfully achieved islet cell¹ transplantation in a Type 1² diabetes
patient. This breakthrough has major implications for diabetes sufferers and has never before been achieved in the United
Kingdom. The patient, a 61 year old man, now no longer needs insulin injections, following
three transplants of islet cells isolated from cadaveric donor pancreases.
Historically, islet transplants have only
been partially successful, in that they have reduced the amount of insulin required, but the need for regular injections still
remained. The first reports of insulin independence came recently from a programme in Canada.
The King's programme is the first to report a comparable result for the UK.
This patient has proved that it is possible for islet transplants to lead to freedom from administered insulin and diabetes treatment associated problems.
The patient suffered from Type 1 diabetes
for over 30 years, experiencing increasing problems with his diabetes therapy. Prior to the islet transplant he endured severe,
potentially life threatening hypoglycaemic³ attacks, which profoundly affected his quality of life. Following the islet transplant
he is now producing his own insulin and is completely free from hypoglycaemia.
The King's team, a collaboration between
the Department of Diabetes and the Liver Unit's transplantation team, has to date transplanted three
Type 1 diabetes patients with pancreatic islet cells. The first two patients achieved partial
success, achieving relief of hypoglycaemia problems, but still requiring small doses of insulin.
Islet cells are obtained
from donor pancreases and are transplanted by injection, into the liver of the recipient. Once in the liver, the cells develop
their own blood supply and begin producing insulin. This procedure is minimally invasive and only takes around 45 minutes
There are around 250,000 people in the UK
currently suffering from Type 1 diabetes. The patients live with the constant need to be aware of their blood glucose
levels and the threat of long term complications such as blindness, renal failure, amputation and cardiovascular disease.
Hypoglycaemia is also an ever-present threat. Hypoglycaemia can vary from being mildly uncomfortable to life threatening.
People with Type 1 diabetes often live extremely regimented lives, requiring self blood testing four
times or more times per day, injecting insulin five times per day and constantly being aware of the food they eat, level of
exercise and levels of alcohol consumption.
Professor Stephanie Amiel, Consultant in Diabetes commented: “This
breakthough is hugely exciting. The implications for the future are enormous. Eventually, this could mean the end of insulin
dependence for all Type 1 diabetes sufferers. In its current state of technology though, islet transplantation is not perfect.
We do not have enough organ donors, therefore we cannot extract enough islets to help all Type 1 patients. More research needs
to be done to perfect the islet isolation procedures and the drugs we use to prevent rejection of the islets and recurrence
of the diabetes. At present we can therefore only offer this treatment to patients, in whom conventional treatments are failing
in a major way. However, it is our aim that ultimately all people with Type 1 diabetes would become eligible for islet transplantation
and free from insulin dependence.”
Mr Nigel Heaton, Consultant Liver Surgeon, commented: “This breakthrough
in islet transplantation is remarkable. King's is the first centre in the UK
to achieve insulin independence in Type 1 patients. The research approach at King's is totally multidisciplinary, with experts
across specialities in diabetes, liver transplantation, cell isolation and radiology all working together.
“The result of this work will have far reaching implications, not only for Type 1 diabetes patients, but also
in the wider area of cell research. We have shown that cell transplantation, with both pancreatic islet cells and previously
with hepatocyte cells, can offer patients a valuable alternative to conventional treatments.”
The islet cell
research has been funded by King's College Hospital Charitable Trust and Dixons Charitable Foundation. The clinical costs
are supported by DiabetesUK.
Brodie, Islet Project Coordinator, Diabetes UK commented:
‘We're delighted this procedure has been such a success. To have someone with Type 1 diabetes completely insulin free
is a fantastic achievement. Diabetes UK has always believed
that islet research could provide a cure for Type 1 diabetes. We continue to fund islet research in the UK
and hope many more people will be able to have this pioneering treatment.'
Notes to Editors
1. Islet cells
are found in the pancreas and produce insulin
2. Type 1 diabetes often starts in childhood and once present is irreversible. It occurs as
a result of the cells in the pancreas that produce insulin being destroyed. Usually, the destruction of the insulin making
cells is the result of an autoimmune process, in which the body fails to recognise the cells as its own and destroys them.
This destruction results in total insulin deficiency. Prior to this breakthrough the only treatment for Type 1 diabetes was insulin injections.
3. Hypoglycaemia is a condition where by
blood glucose falls to a dangerously low level during the daily course of insulin therapy. If the blood glucose falls until
it reaches a point where it is too low to support normal brain function, then confusion, abnormal behaviour, and aggression
can result. If nothing is done, eventually glucose levels fall so low and brain function is so abnormal that unconsciousness
and seizures can occur, ending in coma. Such episodes of severe hypoglycaemia are more common in people who have suffered
from diabetes in excess of 15 years and in people who are attempting very tight glucose control in order to prevent the other
long term complications of diabetes.
4. In 2003 a breakthrough in hepatocyte (liver) cell research was announced at
King's. Hepatocyte cells transplanted into the diseased livers of patients with particular conditions were found to act as
a bridge to transplantation - keeping the patient alive until a suitable donor liver could be found. Hepatocyte transplants
were also found to negate the need for a whole organ transplants in some patients by creating healthy new cells in failing
livers. There is an important link with the islet research programme in that both require the precise and controlled isolation
of cells from donated organs so that the recipient patient receives only an infusion of active cells rather than needing to
undergo the major surgery of full organ transplant. This research continues.
NEWYORK (Reuters Health) - We may not be very far away from a time
when dentists offer to help people with damaged or missing teeth grow new ones, according to new research presented on Wednesday.
A series of presentations at a dental meeting demonstrate that techniques using stem cells and gene therapy to regenerate
teeth are producing promising results, suggesting this technique may not be far off.
"I think it's looking like quite
an exciting technology for the near future," said Dr. Tony Smith, editor of the Journal of Dental Research, who was not involved
in any of the newest studies.
Smith explained that the presentations describe techniques that enable dentists to coax
existing teeth into repairing and regenerating themselves, and techniques where dentists can "start from scratch."
Clearly, techniques that
involve adding new tissue to already-existing teeth are "probably a bit closer on the horizon," perhaps within a "handful
of years," Smith predicted. Techniques that grow teeth from scratch will likely take at least another 10 years to perfect,
In some instances, researchers
are trying to reprogram cells in the mouth to behave like tooth-growing cells, convincing them they have to produce new teeth,
Other techniques being explored
involve using stem cells, which have the potential to become any type of cell or tissue. In one study being presented at the
meeting, researchers successfully extracted stem cells from the pulp of adult teeth, Smith said. The next step is to examine
whether it's possible to use these teeth to regenerate new dental tissue, he said.
Other research being unveiled
describes tests of different approaches to select stem cells from pulp, and all shows "different degrees of success," Smith
These techniques may one day
help people whose teeth have decayed from very bad cavities, who have lost teeth in an accident, or whose teeth have worn
down from acid or hard brushing, among other conditions, he predicted.
The findings are being
presented Wednesday, Thursday and Saturday during the 83rd General Session of the International Association for Dental Research
in Baltimore, Maryland.
WASHINGTON (Reuters) - Stem cells taken from human embryos were coaxed into
becoming motor neurons in an experiment that might one day help scientists repair damaged nervous systems, researchers reported
The study supports claims by stem cell researchers that they can train embryonic
stem cells to develop on demand into any type of tissue in the body.
They hope this technology will eventually transform medicine and allow cures
for a range of diseases -- in this case, nervous system injuries and diseases such as Lou Gehrig's disease.
The team at the University of Wisconsin used stem cells that are approved for research by the federal government. Their experiment was funded
by the National Institutes of Health and the Amyotrophic Lateral Sclerosis Association, which is seeking a cure for the untreatable
and paralyzing condition also known as Lou Gehrig's disease.
Su-Chun Zhang and colleagues said their trial-and-error study helped them
learn how motor neuron cells, which are key to the nervous system, develop in the first place.
Motor neurons transmit messages from the brain and spinal cord and help control
almost every movement in the body.
Patients with motor neuron diseases or spinal cord injuries lose control of
The hope is to repair or replace these damaged cells.
Writing in the journal Nature Biotechnology, Zhang and colleagues said they
delivered a carefully timed cocktail of proteins to their cells to direct their development.
"You need to teach the (cells) to change step by step, where each step has
different conditions and a strict window of time," Zhang said in a statement. "Otherwise, it just won't work."
And Zhang said the experiment showed that human stem cells do not necessarily
differentiate in the way that other animal stem cells do.
"We cannot simply translate studies from animal to humans," Zhang said.
The administration of President Bush does not support the use of human embryonic
stem cells except in limited circumstances using cells already in existence as of 2001. Federal funds may not be used to take
new stem cells from human embryos, which are destroyed in the process.
Opponents of human embryonic research say this is tantamount to murder, while
supporters say embryos from fertility clinics are slated for destruction anyway and point to the potential benefits from research.
11/18/04 -- For the first time researchers have shown that transplanted stem cells can preserve and improve vision
in eyes damaged by retinal disease. In the cover article in the November 2004 Investigative Ophthalmology and Visual Science,
scientists from Harvard’s Schepens Eye Research Institute describe results of a mouse study in which transplanted stem
cells develop into retinal cells, prevent the death of “at risk” retina cells in the recipient mice and improve
the vision of treated mice. “These findings hold great promise for potential treatments for people suffering from macular
degeneration, diabetic retinopathy and other retinal diseases,” says Michael Young, PhD, an assistant scientist at Schepens
Eye Research Institute and the lead author of the study.
retina is a tissue-thin membrane at the back of the eye responsible for sending light and images from the outside world through
the optic nerve to the brain, which interprets them. The retina contains light sensitive cells, known as rods, which make
it possible for us to see in black and white and in low light, and cones, which are responsible for color and high-acuity
vision. In diseases such as macular degeneration, it is these cells that are being destroyed.
that stem cells - cells that have the capacity to change into other kinds of cells - could potentially save vision, Young
and his team decided to test their theory in mice. They transplanted retinal stem cells from young “green” mice
into the eyes of normal-colored mice that had retinal disease. Green mice are genetically raised so that all their tissues
are fluorescent green. The green color makes it possible to detect where the transplanted cells are and how they are growing
several weeks the team evaluated the eyes of the treated mice and found that the green cells had migrated to where they were
needed in the damaged retina and had changed into what looked like normal retinal cells. The scientists also found that many
of the cone cells that were on the verge of dying before the transplant appeared to regain or retain their function. The researchers
speculated that the transplanted cells were secreting a factor or substance that saved these fragile cells. (There is growing
evidence that rod cells keep cone cells alive by secreting a special factor)
test whether the mice with transplanted stem cells could see better, the team then placed them and the control mice (without
the transplants or with non-stem cell transplants) in dark cages and flashed a series of increasingly lower level lights at
both groups over a period of time. Mice are photophobic and stop their normal activity when they detect light. The researchers
took advantage of this natural response and found that the mice with the transplanted tissue continued to respond to the light
as it reached the lowest levels. The control mice did not.
are the first steps toward the use of stem cells for saving existing vision and then—down the road—restoring vision
that has already been lost,” says Young, who believes that stems cells will have many roles to play in the fight against
blinding diseases. Young and his team are now investigating the same phenomenon in pigs, whose eyes are larger and more like
Schepens Eye Research Institute
ally rescues gene-blocking therapy
10 November 04
may have found a way to stabilise tiny pieces of interfering RNA – which hold great promise as a new treatment strategy
for a wide range of diseases.
using one of the most reviled substances in medicine – cholesterol - to stabilise interfering RNA for delivery, researchers
at biotech company Alnylam have been able to shut down a specific gene in animals with a simple injection.
is a pretty simple solution to the daunting problem of delivery that people thought would hold up the technology," says John
Rossi, an RNA interference researcher at the City of Hope hospital in Duarte, California,
has no connection with Alnylam. "If this works for other disease genes and viral targets, it will revolutionise the use of
is part of an ancient defence system against invading viruses. When a gene is switched on, it produces messenger RNAs that
are used to make the protein the gene encodes. But if small interfering RNAs (siRNAs) with a sequence matching part of a particular
gene get into a cell, the defence system is activated that destroys all the messenger RNAs, blocking production of the protein.
medical potential is huge. The ability to shut down genes at will offers new ways of treating everything from cancer and viral
infections to certain inherited diseases. And designing siRNAs that silence a specific gene is far easier and faster than
any of the methods used to discover conventional drugs.
tricky part is getting siRNAs into cells. Swallow them, and they are destroyed. Inject them into the blood, and they are quickly
chewed up by enzymes. And even if they did not get chewed up, few siRNAs would end up inside cells.Researchers have had some success delivering siRNAs using tricks such as injecting them under high pressure
or delivering them directly to one organ, such as the eye: an siRNA treatment for a retinal disease will be the first RNAi
therapy to get to human trials.
these methods are limited. The aim of researchers is to deliver siRNAs by a pill or injection, like conventional drugs. "We
wanted to give siRNAs drug-like properties -stability, bioavailablity - and joining them to cholesterol helped us do that,"
says Hans-Peter Vornlocher of Alnylam Europe in Kulmbach, Germany.
with some chemical changes to toughen the backbone of the siRNAs, the added cholesterol allows the siRNAs to bind to proteins
in the blood, increasing their stability 15-fold. And the fatty molecule also helps siRNAs sneak inside cells, although the
exact mechanism is not understood.
test these souped-up siRNAs, the researchers chose, somewhat confusingly, to silence a gene called apoB that controls the
level of cholesterol in blood. When mice were injected with cholesterol-linked siRNAs designed to target apoB, the blood levels
of the apoB protein dropped by nearly 70 per cent - and cholesterol levels also plunged. Non-cholesterol-linked siRNAs or
siRNAs that were not perfect matches to the apoB sequence had no effect.
the near term, siRNAs do not pose any serious competition for existing cholesterol-fighting drugs such as statins. It is not
yet clear if the siRNAs’ effects last longer than 24 hours, for example, and the large doses needed would be extremely
it appears the technique could be adapted to silence genes involved in a wide range of diseases. Although the apoB gene is
only active in the liver and intestine, the modified siRNAs were also able to penetrate many other tissues, including heart,
kidney, fat and lung.
reference: Nature (vol 432, p 173)
Unravelling of human code paves way for new treatments
JAMES REYNOLDS SCIENCE
TAILORED therapies to target a range of diseases, such as diabetes and breast cancer, may
be a step closer after the final draft of the gene-rich part of the "human book of life" was published yesterday.
sequence provides a blueprint of the genes that make life possible and is accurate to only one error in 100,000 "letters"
of code, an article in the journal Nature reveals.
Analysis of the new data shows that the human genome, which is
the entire genetic map of an organism, contains between 20,000 and 25,000 genes. Surprisingly, the number of genes is possibly
only 5,000 more than that of the nematode worm, one of the simplest organisms on the planet.
Of the genes that have
been identified, 1,183 were only recently discovered by a process known as "gene duplication".
Scientists also found
that 37 genes seem to have recently "died" by developing a mutation that made them non-functional, although it does not affect
The work, which was conducted by the International Human Genome Sequencing Consortium (IHGSC),
builds on the historic publication of the first draft of the whole human genome in 2001. The publicly funded IHGSC and the
private company Celera announced completion of the first drafts in jointly published papers three years ago.
the drafts were some way off being perfect, as both groups were missing about 10 per cent of what is known as the "euchromatin"
- the crucial gene-rich portion of the genome.
Genes are sequences of DNA that provide the coded instructions for making proteins. Other parts of the genome consist of DNA but not genes.
Jane Rogers, the head of DNA sequencing
at the Cambridge-based Sanger Institute, which conducted much of the work for the first draft in 2001, explained: "What we
find in the human genome is that the majority of it is made from a fairly unique gene-containing sequence, and this is what
is known as the euchromatic part.
"That holds the information that provides the codes for proteins and the regulation
of their production. This is important because it provides most of the instructions to make the materials that we humans consist
The sequence, published throughout the world yesterday, is estimated to cover 99 per cent of the gene-containing
part of the genome. It has just 341 gaps remaining and consists of unbroken runs of code averaging 38 million bases - the
chemical "letters" that make up DNA.
IHGSC scientists wrote in Nature: "The genome sequence reported here should serve as a firm foundation for biomedical research
in the decades to come.
"It allows systematic searches for the causes of disease - for example, to find all key heritable
factors predisposing to diabetes or ... mutations underlying breast cancer - with confidence that little can escape detection."
wrote: "That this draft is again missing a small portion of the euchromatin does not mean that the
information is unusable.
"Making this sequence available to researchers from the outset has really stimulated biological
exploration and changed the way that researchers carry it out.
"So instead of starting with needing to identify a
piece of DNA that has
an effect, they will actually go to the database first and look for the sequence and start their experiments from there.
pieces are still missing throughout the genome, and it is of the utmost importance that we now try and find those.
are now trying to define where variations occur in the human genome that we can then say are causative for disease. If we
can do that reliably, that would then allow us to look in populations of people who have specific diseases and see if we can
observe the changes that occur in the genome.
"If we do see the changes it will then tell us if it is the reason for
the disease. There is some prospect in future for the potential for gene therapy if we need to replace a gene, and there are
many more opportunities as well. For example, if we have a mutation that affects some sort of metabolising enzyme, a patient
might not respond to one type of drug very well, but they could respond to another. Having that information could direct the
prescription of drugs to be far more effective."
Professor Robin Lovell-Badge, the head of developmental genetics
at the National Institute for Medical Research in London, wrote: "This will greatly increase our understanding
of what happens in cases of genetic disease and issues about interaction between genes and environment.
"If you take
heart disease or certain types of diabetes, people who suffer from strokes and even behavioural problems, these are all likely
to be influenced by a combination of different genes. Knowing what the full set of genes are is an incredibly useful starting
point to gaining knowledge of what causes those ailments.
"We can also begin to discover why some people respond well
to certain drugs, and others do not, which is clearly influenced by genetics.
"All these things will be enormously
helped by having the full sequence, as it used to take years to find a single gene responsible for conditions such as cystic
fibrosis. Now we can just consult the database."
In an accompanying article, Dr Lincoln Stein, from the ColdSpringHarbor Laboratory in New York, said the finished gene sequence had roughly doubled
the total time and cost of the human genome project.
He wrote: "Does it contribute anything new to our understanding
of the genome? It does indeed, and to prove the point the authors of the current paper describe several large-scale analyses
of the genome that would have been difficult to perform on the draft sequence. Absolute completeness [of the sequencing project]
will be elusive, but ... obtaining the substantial majority of the information will greatly accelerate the pace of biomedical
research in thousands of laboratories."
Dr Stein concluded: "In sequencing the human genome, the researchers have
already climbed mountains and travelled a long and winding road.
"But we are only at the end of the beginning: ahead
lies another mountain range that we will need to map out and explore as we seek to understand how all the parts revealed by
the genome sequence work together to make life."
In an accompanying Nature paper, scientists led by Dr Evan Eichler,
from the University of Washington in Seattle, said
the new sequence showed up shortcomings in the technique used by Celera.
The company took a controversial shortcut
called the "whole genome shotgun method", which involved blasting apart the genome, sequencing random fragments, and using
a computer to fit them together like pieces of a jigsaw puzzle.
Dr Eichler’s team found that the technique missed
many duplicated DNA regions
and may not provide an accurate picture of the genome.
Much of our DNA is disposable, study suggests
probably humans, can survive despite having whole pages of DNA ripped out of their "book of life", scientists claimed yesterday.
Researchers deleted more than two million bases - the chemical "letters" of the DNA code - from the mouse genome. To the surprise of
the scientists, the mice shrugged off the loss and were virtually unaffected.
The deleted sequences were from regions
of the genome not known to have any essential function. Eddy Rubin, the director of the Joint Genome Institute in Walnut Creek,
California, where the work was carried out, said: "We were looking particularly for sequences that might not be essential.
Nonetheless, we were surprised, given the magnitude of the information being deleted from the genome, by the complete lack
of impact noted.
"From our results, it would seem that some non-coding sequences may, indeed, have minimal, if any,
Controversy surrounds the DNA "desert" that makes up 98 per cent of the human genome.
Genes are sequences of
DNA that provide the essential instructions for making proteins.
But large swathes of DNA exist
between the genes that appear to be barren wasteland with no purpose.
Some experts believe this "junk" DNA may not be as useless as it seems and plays a hidden role. But the new research, published
in the journal Nature, indicates that large parts of the genome really are disposable.
Gene Tweak Ends Procrastination
Lacking brain receptor, slacking monkeys become workaholics
8/12/2004 2:52 PM
Just in time for back-to-school season, researchers have turned procrastinating monkeys
into workaholics by suppressing a gene that encodes a receptor for a key brain chemical.
The receptor, for the neurotransmitter dopamine, is important for reward learning. By suppressing it, researchers at the US National Institute of Mental Health (NIMH) in Bethesda, Maryland caused monkeys to lose their sense of balance between reward and
the work required to get it.
"Like many of us, monkeys normally slack off initially in working toward a distant goal. They
work more efficiently—make fewer errors—as they get closer to being rewarded," says Barry Richmond of the NIMH Laboratory of Neuropsychology. "But without the dopamine receptor, they consistently
stayed on-task and made few errors, because they could no longer learn to use visual cues to predict how their work was going
to get them a reward."
The ability to associate work with reward is thought to go awry in many mental disorders, says
Richmond, including schizophrenia, mood disorders and obsessive-compulsive disorder (OCD).
"For example, people who are depressed often feel nothing is worth the work," says Richmond.
"People with OCD work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will
work feverishly for rewards that aren't worth the trouble to most of us."
For their study, Richmond and colleagues used a molecular technique to shut off expression of a gene encoding receptors called D2. They created a DNA antisense agent—a genetic mirror
image that shuts off production of target proteins—and injected it into an area of the brain called the rhinal cortex.
The area was targeted because it's rich in dopamine and was previously associated with reward learning. The antisense agent
turned off D2 expression for several weeks.
Reward learning impaired
Injected monkeys had been trained to release a lever when a spot on a monitor turned from red
to green. If they did it right, the spot turned blue. A gray bar on the monitor indicated their progress, and when they successfully
completed a trial they would get a juice treat.
Before the gene tweak, the monkeys would make fewer errors as they got closer to receiving a
reward. After the gene tweak, they couldn't associate visual cues with workload and therefore couldn't figure out how much
more they had to work to get a reward.
"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing
the experimental task, irrespective of how distant the reward might be," says Richmond. "This was conspicuously out-of-character
for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a
Besides helping researchers understand reward learning—and giving hope to procrastinators
everywhere—the study also points to a new technique for exploring molecular aspects of behavior.
It blocks gene known to trigger cancer,
say US scientists
SCIENTISTS at Stanford University have discovered an antibiotic capable of turning off cancer cells in mice.
It could offer hope to cancer treatment in future.
The drug worked by blocking a gene called Myc, known to trigger cancer.
The mice, whose liver cells had been altered to carry the modified Myc gene remained cancer free for as long as they took
When it was stopped they developed aggressive liver cancer, the reseachers found.
When they were put back on the diet, all of them showed rapid regression: the liver cancer was eliminated, and liver cells
seemed to behave normally.
Cancer experts said the study held promise for human cancer drugs.
The findings might also apply to cancers of the breast, bowel and prostate, the researchers hope.
All of these cancers, as well as liver cancer, begin in cells that line the body called epithelial cells - a gene that
could contribute to as many as one in seven cancer deaths, according to Cancer Research UK.
Unlike the normal version of the gene, the modified version stayed permanently switched on, meaning cells were constantly
dividing and some became cancerous.
Feeding the mice the antibiotic, doxycyline, turned the faulty Myc gene off so cancer growth was blocked.
The scientists turned the Myc gene on and off like a tap, and turned cancer on and off at the same time.
They also found that some of the apparently normal cells retained the ability to become cancerous, which could explain
why cancers often recur after chemotherapy.
Lead researcher Dr Dean Felsher said: 'The exciting thing is you can turn cancer cells into something that appears to be
But the battle against cancer hasn't been won yet.
Now a drug has to be found that would be safe for human patients, and yet have the same impact. - Wire services.
Oxford geneticists have closed in on the genetic basis for risk factors of metabolic diseases such as hypertension,
obesity and diabetes.
Studying 1,300 patients and healthy volunteers from over 400 families across Oxfordshire, the research team
located several variations in the DNA sequence of the lipid phosphate SHIP2 gene which are associated with an increased risk
for a cluster of common and increasingly frequent disorders, referred to as the 'metabolic syndrome' or 'Syndrome X'. Syndrome
X, whose genetic basis is as yet unexplained, includes obesity, hypertension, type 2 diabetes and dyslipidaemia, and is a
common risk factor for cardiovascular disease and atherosclerosis.
SHIP2 is a key cellular regulator of the biological effects of the hormone insulin which lowers the levels
of blood sugar. Reduced insulin action, also called insulin resistance, is the common feature of the pathological components
of the Syndrome X.
Dr Dominique Gauguier, Wellcome Senior Research Fellow at the Wellcome Trust Centre for Human Genetics at
Oxford University, and his team identified 50 sequence variants in SHIP2 which were used to test their possible association
with the different disease components of the Syndrome X diagnosed in the patients.
Dr Gauguier said: 'Epidemiological studies find that obesity, hypertension and type 2 diabetes are frequently
associated, but we do not understand the exact causal relationships between these diseases, though environmental factors,
for example diet and lifestyle, certainly play an important role.
'Genetic studies have generally looked at these diseases independently. Our recent findings, which are among
the first demonstrations of an association between gene sequence variants and the disease components of the Syndrome X, emphasise
the need of extensive and accurate biological information in patients for tackling the genetics of metabolic disorders.
'Another original feature of our research is that we have actually been able to translate our previous studies
in a rat model of the Syndrome X, which carries a functional mutation in SHIP2, to human genetics.
'The next step is now to attempt a replication of our results in other large groups of patients characterised
for features of the metabolic syndrome. Six research groups around the world are currently helping us do that.
'If we are correct, we may have found a tool for screening patients to see whether they are at increased risk
of developing diabetes, hypertension, obesity or cardio-vascular disease. Our findings may have great potential for the prevention
of metabolic disorders and, in predicting disease onset, may provide an opportunity for early intervention through changes
in diet and lifestyle in people carrying the sequence variants in SHIP2.'
For further information please contact the Press Office on 01865 280528.
Notes to editors:
The research will be published in: Pamela Kaisaki et al, 'Polymorphisms in type II SH2 domain
–containing Inositol 5-Phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic
syndrome', Diabetes 53, July 2004. Online publication is already available at http://diabetes.diabetesjournals.org.
The Wellcome Trust Centre for Human Genetics (WTCHG) was established in 1994 to undertake
research into the genetic basis of common diseases. The scientific objective of the Centre is to explore all aspects of the
genetic susceptibility of disease including the localisation of genes involved in common diseases, characterisation of the
variants responsible for susceptibility, the understanding of how these DNA variants may contribute to risk of disease in
the population and finally, how such genetic factors contribute biologically to a disease process. The Centre houses multi-disciplinary
research teams in human genetics, functional genomics, bioinformatics, statistical genetics and structural biology.
Boulder, CO (August 16, 1997)- The discovery of the gene that directs the activity of telomerase could be an important
discovery for researchers developing new treatments for cancer.
Telomeres are DNA sequences found at the ends of eukaryotic
chromosomes which maintain the fidelity of genetic information during replication. Under normal circumstances the telomeres
become shorter and shorter with each cycle of cell division. A sufficiently short telomere is believed to signal the cells
to stop dividing. The telomerase enzyme is a ribonucleic protein that synthesizes telomeric DNA on chromosome ends.
About three years ago, researchers announced that telomerase
appeared to be responsible for the unchecked growth of human cancer cells. Unlike normal cells, in cancer cells telomerase
appears to grant the cell immortality by maintaining telomere length so that the cell never receives a signal to stop dividing.
Now researchers at Colorado University in Boulder have identified the gene responsible for activating telomerase, 'telomerase
"Correlation of telomerase activity and cancer has been shown
previously, but there has been little evidence for a causal relationship between the two. Having the human telomerase gene
may aid in testing the relationship," said Toru Nakamura, a CU-Boulder researcher, Howard Hughes Medical Institute scientist
and lead author on the study. Nakamura.
Before the discovery of the telomerase gene, "Cancer researchers
knew telomerase only indirectly, by following the reaction it catalyzed," said team leader Thomas Cech, who shared the 1989
Nobel prize for chemistry. "Now we have the ability to make lots of pure telomerase to understand its properties and learn
how to inhibit it."
Telomerase contains both RNA and protein components. The
RNA portion of the enzyme binds to the DNA in the telomere while the protein component lures DNA subunits into the region
and attaches them to the end of the chromosome. The newly discovered protein forms a complex with the telomerase RNA and does
the job of telomeric DNA synthesis, explained Nakamura.
Researchers at the Whitehead Institute for Biomedical Research
have been pursuing a similar line of inquiry to the Boulder team and announced related finding. The team announced its findings
(isolation and cloning of the catalytic ic subunit of human telomerase) simultaneously with the Boulder team.
"The telomerase enzyme is an ideal target for chemotherapy
because this enzyme is active in about 90 percent of human tumors, but inactive in most normal cells. Pharmaceutical
companies have screened thousands of compounds to find agents capable of blocking telomerase. Now that we know the identity
of the catalytic subunit, drug development should move much faster," said Dr. Robert A. Weinberg of the Whitehead Institute.
Researchers believe the telomerase research holds particular
promise for the development of new cancer diagnostic tools. The hope is that by developing ways to detect telomerase activity
in cells, it may be possible to diagnose cancer early, before tumors form.
Telomerase belongs to a class of enzymes known as reverse
transcriptases that use RNA as a template for creating DNA. A number of anti-AIDS drugs were designed to inhibit reverse transcriptase
in HIV, a retrovirus. The experience gained in developing anti-retroviral drugs may give cancer drug developers a head start,
since reverse transcriptases share a common amino acid sequence and are expected to have similar three-dimensional structures.
It is possible that variants of existing AIDS drugs might be able to inhibit telomerase.
"The beauty of this finding is that we already know
a great deal about the structure of reverse transcriptase inhibitors. We have a good starting point for developing anti-telomerase
drugs," said Christopher Counter, a post-doctoral fellow in the Weinberg lab.
The discovery of the gene for the protein called is
reported in the Aug. 15, 1997 issue of Science. The Whitehead Institute research will appear in the Aug. 21 issue of
Cell (embargo permission granted by Cell).
Progresses Toward Anti-Aging Pill Targeting a specific gene can prevent cell death
By Ed EdelsonHealthDay Reporter
THURSDAY, June 17
(HealthDayNews) -- In the latest report on a promising anti-aging strategy, scientists provide a detailed description of how
a simple pill could one day help brains and other essential organs work better late in life.
The pill would increase
activity of a gene that produces molecules called sirtuins, which block the programmed process by which the body rids itself
of aging cells, said Haim Y. Cohen, a senior research fellow at HarvardMedicalSchool.
A report in the
June 18 issue of Science by Cohen and his colleagues focuses on the gene for one sirtuin, SIRT1. One study showed that rats
fed a low-calorie diet produced more SIRT1 than those allowed to gorge themselves on unlimited food, the report said.
human cells grown in the laboratory showed that SIRT1 reduces the activity of a factor known as Bax that encourages the programmed
cell death process called apoptosis.
confirm previous work explaining why low-calorie diets can extend life, Cohen said. Work along these lines has been done before,
not just at Harvard but at several other institutions.
"In any organism,
you can extend lifetime by 30 to 40 percent if you cut calories by 30 percent," Cohen said. "This paper shows that you can
hold back apoptosis by increasing the amount of SIRT1 that is produced."
Studies have shown
that a low-calorie diet does not extend the life span of animals bred to lack sirtuins, Cohen said.
The hunt now is
on for molecules that can target the SIRT1 gene in specific organs, such as the brain, he said. "If you delay cell death in
the brain, you allow the organ to function longer," he said.
The Harvard group
is one of several in the forefront of anti-aging research, with sirtuins playing a central role. A year ago, the Harvard researchers
reported that resveratrol, a compound found in red wine, can extend cell life.
already are testing sirtuin-promoting drugs in animals. The commercial possibilities of the work are clear. The Harvard researchers
have ties with Biomol Research Laboratory, a Pennsylvania biotechnology company,
and scientists in other laboratories working on sirtuins have comparable relationships.
Cohen will not predict
how long it might take for a viable product to emerge from research, but he tends toward the optimistic.
"I'm not sure that
it will take a very long time in the laboratory," he said.
Stem cells, the body's master cells, are an effective treatment for patients
who have had a heart attack, researchers have found.
Sixty patients were treated either with stem cells taken from their own bone
marrow, or with the best conventional treatment.
After six months, it was found the hearts of those who received the stem cell
transplants were working better.
The University of Freiberg research is published in The Lancet.
Stem cells have the capability of turning into any other cell. In this case,
scientists believe they turn into new blood vessel or heart muscle cells.
Patients who undergo the procedure have stem cells taken from their own bone
marrow and injected directly into the heart muscle.
Because the stem cells come from the patient's own body, the transplant will
not be rejected.
In this study, the researchers found that the treatment had improved the functioning
of the heart's left ventricle by 7%.
In comparison, the patients given the best medical therapy but no transplant
saw a 0.7% improvement in their condition.
The scientists said the beneficial effects could not be explained solely by
bone marrow cells transforming into heart muscle.
Instead they believe the stem cells promoted the secretion of chemicals by
heart tissue that encouraged growth.
Dr Helmut Drexler, from Germany's University of Freiburg, who led the research,
said the team's findings supported the idea that a patient's own bone marrow cells could be used to help them recover after
a heart attack.
But he added: "Larger trials are needed to address the effect of bone marrow
cell transfer on clinical endpoints, such as the incidence of heart failure and survival."
Ian Rosenberg, a UK heart attack patient who had the pioneering treatment
in Germany, was so impressed at how it changed his life that he set up a charity to fund stem cell research in the UK.
He told BBC News Online: "It was a miracle. For over two years, I couldn't
get around and go out. I had to have my bedroom downstairs.
"Now I can run up and down all the time. It didn't happen immediately, but
I gradually felt better over around six to eight weeks."
next advances in biology may rely on networked systems research, but will have little to do with computers or telecommunications
if an influential group of researchers has its way, techniques used to analyze interconnected systems will provide a better
understanding of the most complex network of all: the human body.
the ambition of scientists in systems biology, a burgeoning field which aims to understand the workings of the nuts and
bolts of living organisms through the interactions of the thousands of pieces of DNA, RNA and proteins
that network together in each cell of our body.
to its proponents, systems biology will revolutionize medicine, transforming it from something that is mainly reactive (with
an emphasis on treating diseases) into something that is predictive and will eventually prevent diseases getting hold in the
first place. Systems biology devotees, like Alfred Gilman, winner of the 1994 Nobel Prize in medicine, believe the field represents
the most promising front in modern medical research.
have spent the past 50 years taking apart biological systems piece by piece. Now the future of biological research depends
on putting them back together," said Gilman, currently chairman of pharmacology at the University of Texas Southwestern Medical
Center at Dallas,
at the opening of a systems biology center at the university earlier this year.
biology will enable predictive and preventive medicine," said Hood. "This will move medicine from its current reactive state
to this new mode in the next 10 to 20 years."
field incorporates analysis of the expression of hundreds of different genes and proteins that give clues into the origins
of cancer and other diseases. Systems biologists aim to understand how cells work by seeing biology as a network of systems,
consisting of genes written in DNA, which send messages about the cell written in RNA, which provide the recipes for proteins, which do the work of life
in our bodies. Understanding the networks will lead to tests that will identify diseases such as cancer, diabetes and AIDS.
and his colleagues have looked at such networks in yeast, comparatively simple organisms with only 6,000 genes. Even in yeast
cells, there is a staggering amount of information, with each gene churning out hundreds of chunks of RNA and proteins. The
complexity level increases exponentially for humans, with tens of thousands of genes.
research into prostate cancer determined that the expression patterns of genes and proteins in diseased cells change as the
cancer progresses. Such findings could potentially lead to earlier detection of prostate cancer.
research requires serious computing power and some radical new technology. Hood, who invented the DNA-sequencing machine and won the Kyoto Prize in 2002, is uniquely qualified for the job.
particular, Hood is interested in emerging nanotechnologies and microfluidics devices that can collect large amounts of information
in short periods of time. Worldwide, much effort is being put into developing a tiny device -- known as a "lab on a chip" -- that with a drop of blood can analyze the expression of hundreds
of different genes and proteins. This information will be the key to diagnosing health and predicting future conditions, scientists
in systems biology require cooperation from scientists in multiple fields, pulling together the expertise of biologists, physicists,
computer scientists, chemists, engineers and mathematicians.
biology is an idea whose time has come," said Hood. "But it is not for everyone. It requires a culture and integration of
biology, technology, computation and medicine that is not possible in most institutions."
systems biology progresses in line with Hood's expectations, one consequence may be the elimination of so-called physics envy suffered by biologists, whose work has traditionally not centered on
mathematical expertise. Such progress would also move the digital revolution currently underway in biological sciences to
an entirely new level.
biologists, the words "digital revolution" don't suggest iPods or wireless broadband so much as a cascade of changes that
have occurred since the realization that the recipe for life, DNA, is a digital code. That recognition led to the sequencing of the code and is now leading to the realization that biology is an informational science.
says such a realization may lead to discoveries that are nothing less than revolutionary.
wildest dream is that from a single cell I will be able to delineate the networks of life and from that figure the logic of
life for the individual system -- be it a network of proteins, a cell, an organ or an individual organism," he said.