The search for the elusive Parkinson's Family cures include not only
"Classic Parkinson's", but the Parkinson's Plus syndromes and Essential
Tremor disabilities as well.
 
Where would we be at this stage, if the National Institutes of Health hadn't
funded in part, Dr. Joseph Jankovich's studies on the etiology of
Parkinson's families of disabilities or for that matter, the work of Dr.
Jonahs Salk?
 
Dry research in the clinic or the laboratory, when economic benefit to the
profit makers is still unclear, is necessary for break-throughs.
 
It has been a relatively short period of time since the discovery that
levodopa therapy would alleviate the symptoms of the "Classic Parkinson's"
patient, verifying the diagnosis, short of an autopsy.
 
Jankovich's latest work suggests that 30% of person's diagnosed with a
familial essential tremor will eventually develop Parkinson's. Previous
works had estimated only about 10% probability.
 
Prior to 1968, when the link between levodopa treatment and "Classic
Parkinson's" was discovered, those who had been subjectively diagnosed as
having familial essential tremor by the family doctor or the neurologist,
were misdiagnosed, 30% of the time.
 
Today, neurologists and family doctors are still making the same mistake,
basing their diagnosis on family recollection of tremor in their ancestors,
and the patient's lack of resources to get the expensive MRIs or CAT scans
to rule out brain stem anomalies.
 
Now days, it takes several thousands of dollars and a year or more to
finally arrive at the Parkinson's diagnosis, taking one step at a time
in the treatment algorithm. We all receive the death sentence from birth.
Levodopa therapy gives the "Classic Parkinson's" patient a parole for a
period of time. The mis-diagnosis of familial essential tremor gives no such
parole since the present day drugs used to treat ET are ineffective in 60%
of the patients. Essential tremor is degenerative also. Logic would indicate
earlier levodopa trials in patients diagnosed with familial essential tremor
who lack resources for further diagnostic testing.
 
In the United States, 30% of the population has no access to neurological
medical care. It is only possible to receive care for "life threatening"
conditions. This lack of access keeps the number of diagnosed Parkinson's
patients artificially low, thusly, keeping Parkinson's as one of the
"step-children" at pie serving time.
 
The following was in the paper over the weekend.
 
---------------------------------------------------------------------------
NIH budget Cuts.
 
 The National Institutes of Health, which have enjoyed strong bipartisan
support, now face significant budget cuts for the first time.
 
 The health institutes calculate that their budget, $11.3 billion this year,
could be cut 10 percent to 25 percent under the Senate's fiscal plan. The
agency is telling Congress that such cuts would severely slow research on
Alzheimer's, cancer, cystic fibrosis and other diseases.
 
---------------------------------------------------------------------------
 
 These cuts could mean shortening Dr. Carol Tanner's Twins Study or the
elimination of Dr. Shirley Beyer's developmental neurobiology studies if
their grants are reduced.
 
 Dr. Beyer's project is to use the weaver mutant mouse as an animal model
of human Parkinson's disease. The same neurons that die in Parkinsonian
patients also die in these animals. She is trying to find out more about
the neurons that die by analyzing their developmental history. Perhaps some
of these findings may provide a dating transduction in a variety of cell
types.
 
--------------------------------------------------------------------------
The following is an article on the discovery of a genetically altered mouse
that help in the finding of a cure to Alzheimer's disease. It looks
surprisingly similar to Dr. Beyer's work.
 
--------------------------------------------------------------------------
Scientists create mouse with Alzheimer's
 
Sally Lehrman OF THE EXAMINER STAFF
 
Thursday, Feb. 9, 1995
 
 Bay Area scientists have created a mouse that exhibits the same brain
abnormalities as humans with Alzheimer's, offering an important new tool
for understanding the disease and developing a treatment. "This mouse is a
real breakthrough . . . providing the first real hope we can progress
toward meaningful drugs," said John Groom, president and chief executive
of Athena Neurosciences, the South San Francisco company that led the
collaborative project.
 Alzheimer's is one of the top killers of Americans, with at least
100,000 people dying of the disease each year. The condition is marked by
a progressive loss of memory, dementia, and eventually death. Researchers
have found it difficult to pinpoint the cause of Alzheimer's, how the brain
changes as it loses memory, and how to go about fixing it. The lack of an
animal that developed anything like the disease has made it especially hard
to study. Mice with rodent versions of cystic fibrosis, obesity and other
conditions have become valuable tools for scientists to learn about these
diseases and the ways drugs can interfere. Scientists have tried for many
years to engineer an Alzheimer's mouse through genetic manipulation, but
never have been able to achieve changes in the brain that mimic the disease.
 In the Thursday issue of Nature magazine, Athena, its partner Eli Lilly
and Co. and their collaborators describe a mouse that develops remarkably
similar characteristics to humans with Alzheimer's. The animal develops
plaque in its brain, abnormal nerve fibers that surround the plaque like a
web, inflammatory cells and deterioration of the connections between its
nerve cells. The problems arise in two key areas of the brain related to
spatial memory and associative learning. Later this year, the Athena
scientists intend to test the animals in a complicated maze and see whether
they have memory difficulties just like humans. "I would be shocked if
these animals weren't impaired," said Dr. Ivan Lieberburg, an author of
the Nature report. Lieberburg said the mouse, which developed the
brain changes after a single gene change, helps prove the theory that
amyloid plaque formation is the cause of Alzheimer's. Now scientists can
study its precise effects.
 
-------------------------------------------------------------------------
 
The following is a recent newspaper story that puts together the genetic
science as we know it today with the plight of two boys.
 
--------------------------------------------------------------------------
 
Boys' Illness Leads Medical Sleuth on Genetic Hunt
 
 Charles Petit, Chronicle Science Writer
 
   Nearly 20 years ago, two young boys with elfin faces and a
baffling set of ailments were brought by their parents to a Denver
hospital. Puzzled physicians asked a young researcher, Dr. Edward
McCabe, to take a look.
  The boys were mentally retarded and small, and they had weak
muscles. A few years earlier, county welfare officials had taken the
older boy away, suspecting child abuse because the tot suffered so
many broken bones. The parents got him back when the foster family
found his bones kept breaking. Then the couple had a second boy with
the same problems.
  McCabe, then being trained in children's metabolic disorders,
embarked on an odyssey of medical detective work and intimate
involvement with the family.
  That fixation helped lead to an announcement last week by a team
of Italian, American, German and British researchers of the final
step in the atom-by-atom identification of the genetic errors found
in the two youngsters.
  The scientific report in the journal Nature describes the gene for
a disease called adrenal hypoplasia congenita, one of at least three
closely related genetic disorders those Colorado boys had.
  This constellation of diseases is so rare that the full description
of the genes responsible will not, by itself, much alter the lives of
many people.
  But the long voyage of discovery illustrates the strides made by
genetic science in just two decades. Broadly, the results are part of
the global effort called the Human Genome Project, which is aimed at
unraveling the mysterious tapestry of human heredity. In the wings is
not only the ability to detect and diagnose hundreds and perhaps
thousands of inherited diseases, but also the knowledge to prevent
them or, through gene therapy, perhaps eventually cure many of them.
  In an interview last week, McCabe, now chief of pediatrics at the
University of California at Los Angeles School of Medicine, described
the chance encounter with the family in Colorado and what followed.
  ``I was just called in to work up the case,'' he said. ``They were
honest, sort of unsophisticated country people who lived up north of
Denver. They were good parents, but the kids were sick.''
  Medical tests showed that both boys had oddly high levels of
glycerol in their blood. Glycerol, commonly used in hand lotions,
should only exist in traces in human tissue. After eliminating such
possible sources as glycerol suppositories, McCabe concluded that a
derangement in the boys' metabolism of fat was at work.
  With two brothers and reports from the family of an uncle who had
died suddenly as a child in Nebraska with similar problems, a genetic
defect was clearly the culprit. ``But back then, we had practically
no way to find the gene responsible and wouldn't know what to do
about it even if we had.''
  Further study showed that the boys actually had three diseases.
The first, previously unrecognized, was dubbed glycerol kinase
deficiency. The second, the cause of the muscle weakness, closely
resembled the well-known disease, Duchenne muscular dystrophy.
  The third was discovered a short time later, after the older boy
suddenly died within a day of a minor operation on his eyes. ``The
parents insisted on an autopsy,'' McCabe said. ``They remembered the
child abuse charges and did not want anybody thinking they had hurt
their son.''
  The autopsy revealed the boy's adrenal glands, atop his kidneys,
to be small and malformed. The glands provide many of the hormones,
such as natural steroids, that provide the body with the ability to
cope with shock. McCabe ordered the surviving brother protected from
major stress, and he was put on a regular dose of steroids to
compensate for his medical problems.
  Scientifically, the coincidence of the three diseases in two
brothers indicated that the boys had somehow inherited a defect that
damaged three neighboring genes.
  McCabe kept working on the ailment at Baylor College of Medicine
in Texas. By the mid-1980s, it was clear that the three genes were on
the X-chromosome, a long string of genes whose roles include
determination of sex characteristics.
He found himself heading a group at Baylor competing with groups in
Great Britain to clone, or copy and fully map, the gene for glycerol
kinase deficiency, and wound up in a three-way tie.
  Two of the teams, including McCabe's, then set their sights on the
third of the linked defective genes, the one that stunts adrenal
glands.
  That scientific rivalry turned to fruitful cooperation, thanks to
the intervention of Giovanna Camerino, a genetics researcher at the
University of Sassari in Italy. She called McCabe and his chief
competitor, Anthony Monaco of John Radcliffe Hospital in Oxford, to
suggest that they cooperate with her group and with a fourth team led
by Thomas Meitinger in Munich, Germany, to define the molecular
sequence of the remaining gene for the adrenal disorder.
  During the past two years, linked largely by fax and electronic
computer mail, the four teams laboriously put together the full
sequence of molecules.
  Now, 18 years after meeting the two sick little boys, McCabe knows
in detail what was wrong with them. The damaged genes that cause
Duchenne muscular dystrophy, glycerol kinase deficiency and adrenal
hypoplasia lie next to one another on what geneticists label the
short arm of the X-chromosome. Something had knocked out the middle gene
in the two boys and damaged the two flanking genes. Their mother had a
50-50 chance of passing the disease to any son, and a 50-50 chance of
passing the defective genes to any daughters who, while well, could pass
it on to their sons.
  The research has produced tests to detect the defects in
developing fetuses, allowing girls and women in affected families to
be told whether they carry the gene. Knowledge of the genes'
structures should lead to better therapies that could block some of
the signs of the disease. The third gene discovered, for adrenal
hypoplasia, also may be involved in a host of other critical
functions, including proper brain development.
  So far, McCabe has diagnosed about 50 boys with the same group of
ailments. While retarded and vulnerable to many diseases, they are
affectionate and active.
  He also has kept in close touch with the family in Colorado and
the surviving son. While extremely retarded, he is a cheerful young
man and has finished special education classes.
  ``We talk in medicine about taking information from the bench
(laboratory) to bedside and back,'' McCabe said. ``In this case, we
have done it.''
 
--------------------------------------------------------------------------
 
 In light of recent lobbying on behalf of increased funding for Parkinson's
research, the following story seems to indicate that NIH is positioning
itself into the profit stream which may indicate a shift away from research
on less profitable diseases.
 
---------------------------------------------------------------------------
 
Broad Gene Therapy Patent
 
Washington
 
 The government has won a broad patent on the first way to perform
human gene therapy, a method that covers 60 percent of the genetic
experiments approved in the United States.
 The patent, awarded yesterday to the National Institutes of
Health, covers any method of genetically altering human cells outside
the body and then inserting those cells back into a patient to fight
disease. That process is called ex vivo gene therapy.
 The NIH has licensed the patent exclusively to Genetic Therapy
Inc., a Maryland research company that collaborates with NIH. GTI
will use the patent rights to develop, and license other companies to
develop, products necessary to move gene therapy from the laboratory
to doctors' offices.
 ``I'm thrilled,'' said gene therapy pioneer Dr. W. French
Anderson, the patent's main inventor. ``It comes at a very timely
point -- investments in biotech and gene therapy are at rock bottom.
This is a shot in the arm to get some money back out of sporting
goods and fast-food establishments and back into biotech.''
 Numerous genes themselves have been patented by their discoverers,
and the University of Michigan has patented a specific treatment for
cystic fibrosis where genetic changes are wrought inside the lungs, a
process called in vivo gene therapy, Anderson explained.
 But yesterday's patent is the broadest yet, classified as a
``pioneering'' patent because the experiment on which it was based
proved for the first time that gene therapy could work. It covers any
future gene therapy done outside the body.
 
 
DAY:  WEDNESDAY
DATE: 3/22/95
-------------------------------------------------------------------------
 
Perhaps this story on BioTech will further enlighten.
 
--------------------------------------------------------------------------
 
Biotech: Teaming up to survive and thrive
 
Ralph T. King Jr.
Monday, April 24, 1995
 
 TO WALL STREET, most of the biotechnology industry is abatch of long-shot,
underfinanced wannabe drug makers --and it is no place to put your hard-
earned money. Yet big pharmaceutical companies are lining up to pour money
into the biotechs. Do they know something the Street doesn't?
 Drug companies, of course, have long kept a close eye on what the biotechs
are doing, investing in a few that seemed particularly promising. But lately
their interest has turned red hot. Deals between pharmaceutical giants and
biotech firms more than doubled in value last year and numbered nearly 200.
 Drug companies, especially European ones, are combing for prospects and
promoting their partnership appeal with an ardor that astounds biotech
executives, who are used to having to fight for every dollar of funding.
 Chiron Corp. of Emeryville (Top 100 No. 74) was swept off its feet in
November when Switzerland's Ciba-Geigy AG bought a half interest for $2.1
billion, a 96 percent premium over the stock price. In January, Affymax NV
of Palo Alto found four eager bidders for its novel yet unproven drug-
discovery technology. The company, for which earnings are still a fond
dream, sold itself to Glaxo PLC for more than half a billion dollars.
 
Research revolution
 
 What is happening is that the drug industry is rushing to join the DNA
generation. Gene-based analysis and computerization are transforming
biological research. Some time-honored techniques for creating drugs are
rapidly becoming obsolete, and an array of new methods indispensable.
Among them are automated methods to make and screen millions of drug
candidates in the time it takes a chemist using old-school methods to
process a handful. These are the kind of skills a drug company can gain
access to fast by sinking a chunk of money into a struggling biotech.
 Meanwhile, the world is awash in high-tech biotech shops with great ideas
but questionable ability to bring them to fruition. Buying such little
companies outright risks dousing their entrepreneurial fire. But forming
an alliance, usually involving fees based on progress toward goals, enables
the pharmaceutical giants to convert some fixed research costs to variable
ones and diversify risk.
 The result is that the drug and biotech industries, competitors a few
years ago, increasingly look like natural partners. "This is a strategic
redefinition of the pharmaceutical industry," says Stelios Papadopoulos, a
managing director at Paine Webber Inc. "They're walking away from early-
stage, in-house research and relying heavily on small biotech companies."
 Jean-Pierre Garnet, chairman of Smith Kline Beecham PLC's drug division,
says, "Nobody wants to be left behind." Nobody except Wall Street. The bear
market in biotech stocks drags on.
 
Wall Street remains wary
 
 Many stock investors, burned by failed promises and capital losses, refuse
to get sucked in. In a stock group that has seen steep spikes two or three
times during the past decade, some analysts claim to see a familiar pattern
of hype as investment bankers promote mergers in the group.But in a way,
Wall Street and the drug industry may both be right. Some analysts suggest
that issuing public equity may be a poor way to finance ventures as
speculative as biotech companies; of the 240 that are public, at least half
have only enough cash to continue for 18 months, according to Recombinant
Capital, a San Francisco consulting firm. These classic biotech shops that
bet everything on a few molecules make drug giants wary, too. It is the
biotechs with broadly enabling technology, rather than a few intriguing
compounds, that are the hot tickets. And some don't even chafe at the idea
of losing their independence.
 Alejandro Zaffaroni, founder of Affymax, says, "My goal from the very
beginning was to transform our company into a lead discovery center for
big pharma." Affymax is an example of a biotech offering an "arrow"
technology -- often contrasted with those that have "target" technologies.
An arrow technology might offer ways to guide drugs to a given site within
the body, or ways to concoct and test a vast number of drug recipes. What
Glaxo got by buying Affymax was access to a disposable microchip, crammed
with a million fragments of DNA, that acts like a computerized test tube.
When partial DNA extracted from blood is squirted on the chip, it attaches
to the one spot in a million that is its chemical complement; there it emits
a light, which is scanned by laser and processed by computer. The chip can
reveal in minutes how an experimental drug might interact with, say, the
gene that causes cystic fibrosis, or tell whether a patient is a carrier
of that gene. The so-called target companies go after body sites involved
in disease, providing methods to pinpoint molecular locations at which a
drug could intervene.
 Human Genome Sciences compiles inventories of new sites and clues to their
functions.
 Onyx Pharmaceuticals Inc. of Richmond, having found targets along cancer's
metabolic pathway, penned a $75 million collaboration with Bayer AG in May
1994. The deal is similar to most such pharmaceutical-biotech alliances,
in which the biotech partner contributes a proprietary technology or drug
candidate in exchange for upfront or equity payments and research funding,
plus milestone payments based on key results in the clinic. Royalties or
profit sharing loom on the back end.
 Drug company interest runs deep The depth of drug-company interest in
technology purveyors is evident at biotech gatherings, which invariably
swarm with pharmaceutical executives or representatives.
 In January, Hambrecht & Quist's annual health care conference in San
Francisco drew 165 of them, up 30 percent from the year before. Bayer is a
good example. The German aspirin maker's research chief flew in to meet
with a group of start-up company scientists in February at a Lake Tahoe
retreat attended by seven of his counterparts at other drug firms. Bayer
has its biotechnology center in Berkeley, where it is building a $100
million manufacturing plant and has 20 specialists devoted to scouting out
potential partners. Last year it signed up two, and this year it expects
to recruit up to half a dozen others. Its $70 million deal with Arris
Pharmaceutical Corp. of South San Francisco involves a technique for
attacking inflammation such asasthma, allowing Bayer to drop similar work
internally. Five drug giants besides Bayer, all European, have taken
front-row seats in the San Francisco area, the largest concentration of
biotech firms. One advantage European firms have is that many are closely
held and don't face the kind of short-term earnings pressure American rivals
do. The chance to cherry-pick promising but cash-poor biotech firms lures
even some biotech companies -- the big ones. Genentech Inc. (Top 100 No. 57)
is pouring money into Scios Nova Inc. of Mountain View for a shot at half
the profits from a kidney-failure treatment, and AmgenInc. snapped up a
bunch of drug leads by buying Synergen Inc.
 Any big drug company can offer some of the things most biotechs lack, such
as the ability to shepherd drugs through clinical trials, devise large-scale
production processes and market worldwide.
 
The ultimate bait
 
 Of course, money is the ultimate bait. Drug companies spend about $4
billion a year on basic research, 20 percent of it for external projects
in either the biotech sector or academia. That portion will double in five
years, predicts Viren Mehta, an analyst with Mehta & Isalyin New York. With
all this drug-company money flowing into the biotechs -- and occasionally
a takeover popping at a fat premium -- why shouldn't stock investors go
along for the ride? Unfortunately, the drug firms' interest hasn't really
made it easier to decide what a speculative, development-stage biotech
should sell for.
 Denise Gilbert, Affymax's chief financial officer, says she tried in vain
to value technology-based companies during her previous career as a biotech
analyst. The $539 million price Glaxo paid was based not on any earnings
projection but on the estimated cost of duplicating Affymax's skills.
 
--------------------------------------------------------------------------
 
All of this preoccupation with profits, pre-empting your competitors by
patenting genes has caused opposition. Parkinsonians, look at both sides and
the grey areas of their arguments. Is the controversy, GREED vs Right? What
ever side has the most money vs the loudest voice will prevail and in the
end, our medications will either increase or decrease in number and either
way, they will cost more.
 
Here is the other viewpoint, from the paper again.
 
---------------------------------------------------------------------------
 
80 Church Groups Ask Ban on Gene Patents /They decry `marketing human life'
 
 Louis Freedberg, Chronicle Washington Bureau
  Washington
 
 Opening a far-reaching debate that pits science against religion,
leaders from every major religious denomination in the United States
called yesterday for imposing an immediate moratorium on patents for
human genes and genetically engineered animals.
``Marketing human life is a form of genetic slavery,'' said Richard
Land, executive director of the Christian Life Commission of the
Southern Baptist Convention. ``Instead of whole persons being marched
in shackles to the market block, human cell-
lines and gene sequences are labeled, patented and sold to the
highest bidders.''
 Land, along with representatives of 80 denominations that are
often at odds with each other on such controversial issues as school
prayer and abortion, called on Congress to hold hearings on the
matter and to revise the law that leaves it up to the U.S. Office of
Patents and Technology to license gene-related products.
 Representatives of the biotechnology industry, however, said a
moratorium would halt the development of life-saving drugs. Without
the incentive of patent rights, they said, companies would be
reluctant to invest the tens of millions of dollars needed to bring
drugs to the marketplace, often to benefit patients with such
life-threatening diseases as AIDS, cancer and diabetes.
 ``This would be absolutely terrible for our industry,'' said Kirk
Robb, president of Genentech in South San Francisco. ``Some small
companies would go out of business. Others would drastically reduce
what they are doing.''
 Genentech, one of the two largest biotechnology companies in the
nation, has developed gene-related products like human insulin;
Factor 8, used for treating children with hemophilia; and TPA, known
as a ``clot buster'' to stop heart attacks. Genentech now has close
to 1,000 patents, not all of which are gene related.
 Industry representatives say the religious leaders misunderstand
what gene patenting is all about. They insist that owning a patent,
which grants exclusive rights to market a genetic invention for 17
years, does not mean that a company owns the gene.
 ``A patent on a gene does not confer ownership of that gene to the
patent holder,'' said Carl Feldbaum, president of the Biotechnology
Industry Organization. ``It only provides temporary legal protections
against attempts by other parties to commercialize the patent
holder's discovery or invention.''
 He said that virtually all biotechnology firms are small, have no
products on the market and need to raise funds from investors to
conduct research that leads to new drugs. Without the incentive of
patent protection, raising the necessary venture capital would be
nearly impossible.
 Jeremy Rifkin, president of the Foundation on Economic Trends in
Washington, the main organizer of the statement signed by religious
leaders, declared that argument to be ``nonsense.'' ``There are
thousands of successful product on the market, including drugs,
medical procedures and farm products which are not protected by
patents,'' he said.
 After the Supreme Court ruled in 1980 that Exxon Corp. was
entitled to patent a genetic product used to treat oil spills, the
U.S. Patent and Trademark Office has routinely awarded patents on
human genes.
 Yesterday, the office issued a statement saying that it simply
follows the law in issuing patents, citing the high court ruling that
patent laws provide protection for ``literally anything under the sun
known to mankind'' involving human intervention.
 ``The Patent and Trademark Office does not have the authority to
deny a patent on any subject matter that the patent laws and the
federal courts deem to be patentable,'' the statement read.
 Those statements avoided what to many is at the root of a
discussion about the nature of life.
``This issue is going to dwarf the pro-life debate within a few
years,'' said Land. ``I think we are on the threshold of mind-bending
debates about the nature of human life and animal life. We see
altering new life forms as a revolt against God's sovereignty and the
attempt by humankind to usurp God and be God.''
 But Susanne Huttner, director of the University of California's
Research and Education Program, said that a person or an animal is
made up of billions of cells organized into complex tissues and
organs. ``An individual gene and the protein it encodes are important
but insufficient for `life' judged as a complex organism,'' she said.
 Outside the room where the religious leaders held their press
conference, a healthy-looking Paul Lieberman, 59, of Stratford,
Conn., dissented strongly with one of his own leaders, Rabbi David
Saperstein, director of the Reform Action Center of Reform Judaism.
 Lieberman said that four years ago he began taking the
gene-related drug Cladrabine when he was diagnosed as having a
specialized case of ``hairy cell'' leukemia. He said the drug worked.
 ``As a liberal Jew, I always felt that healing people was more
important than ethics,'' said Lieberman, who was in Washington at the
request of Orthobiotech, the drug's manufacturer. ``If we follow the
Talmud, to save one life is to save the world.''
 
 
DAY:  FRIDAY
DATE: 5/19/95
--------------------------------------------------------------------------
 
In closing, there have been two stories worth adding to this long collage.
One involves finding a gene that turns on other cells, which may be useful
in regenerating neurons. The other is the discovery of the gene which
determines the sex of child.
 
--------------------------------------------------------------------------
Gene found that keys nervous system growth
 
Warren King
Tuesday, May 16, 1995
 
SEATTLE -- Scientists have discovered a gene that is key to
the development of the nervous system, a finding that
eventually could lead to treatments for diseases such as
Alzheimer's and Parkinson's.
 The gene, named "NeuroD," helps switch on other genes to
form some of the cells most basic to life.
 If it is as important as researchers suspect, it could
someday be used to replace nerve cells damaged by
devastating neurological diseases.
 "Many pieces have yet to be put together to understand
the pathway (of development)," said Lauren Snider, a
member of a research team at Fred Hutchinson Cancer
Research Center in Seattle. "We have to know more of that
story."
 Snider said the research, conducted mostly on frog
embryos, found that the NeuroD gene was involved in the
very earliest stages of life, when cells are
differentiating to form the basic body systems. Genes
provide a sort of blueprint for the making of these basic
proteins and cells.
 
 05/16/95 17:50 PST
-------------------------------------------------------------------------
Scientists Find How Boys Will Be Boys /
A genetic switch governs gender of an embryo
 
Washington
 
 Researchers have isolated a genetic switch that separates the boys
from the girls. It turns off the female in the human embryo and
starts biological changes that eventually put hair on the chest.
 Dr. Michael Weiss of the University of Chicago said the new study
advances the understanding of the complex cascade that determines
whether people are male or female and sheds new light on how this
process can sometimes go awry.
 In their research, to be published today in the journal
Science, Weiss and his team used sophisticated imaging techniques to
explore on an atomic level the biological pathway to manhood. Their
research report traces the development of maleness, from the turning
on of the SRY gene, which is on the Y chromosome, to the work of
another gene, called MIS, that removes the female parts of the
original embryo.
 Weiss said science has long known that everybody at conception is
female, but the precise biological mechanism that changes an embryo
to male is still incompletely understood. Solving the puzzle on the
molecular level may answer questions about other basic cellular
changes, such as the development of cancer.
 ``If we can understand the general switches involved in sex
determination, then we could possibly relate that to other basic
processes, such as how organs differentiate or how cancer arises,''
he said.
 For the first weeks after conception, all mammal embryos start
forming the basic female structures -- uterus, fallopian tubes and
vagina.
 ``The embryo destined to become a boy begins as a female,'' Weiss
said in an interview. ``It lays down first female structures and not
male structures at a phase when the embryo looks like a recognizable
mammal, with toes, fingers and eyes and a heart. This is 35 to 40
days into human gestation.''
 After that, he said, a gene called SRY switches on to start the
embryo on its way toward manhood. The new study shows that SRY also
triggers the work of another gene, called MIS, that dissolves the
female parts of the original embryo.
 ``SRY is the master switch,'' said Weiss. ``For the first time we
have shown that SRY can activate a male specific pattern of gene
expression leading to activation of MIS, which is the key signaling
molecule for half of the male pathway.''
 Sex determination in mammals originates with the chromosome of the
sperm that fertilizes the egg. Male sperm can carry one of two
chromosomes, X or Y. The Y chromosome is the male element that
carries the SRY gene. The female egg has an X chromosome.
 If the egg is fertilized with the father's X chromosome, then the
embryo continues its development as a female. But if the egg is
fertilized with Y, then the SRY gene sets off a series of changes
that eventually creates a male.
 ``The XY embryo (containing the X chromosome from the mother's egg
and the Y chromosome from the father's sperm) has two critical tasks
to accomplish,'' said Weiss. ``The first is to build male organs. The
second is to cause the female structures to go away.''
 
 
John Cottingham         NEW ADDRESS:          [log in to unmask]