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China What are they researching? Odd Fellows Cemetery                                                                               History Of Gustine Lake   Leverington Cemetery   Saint Marie-Bernarde Soubirous 1847 to 1875   Mechanics Cemetery

1918 Flu Epidemic A.K.A. Spanish Flu in Philadelphia

Top city officials knew it was a matter of time, before the Flu arrived in Philadelphia. It  was already in Boston. However, city officials dropped the ball when they failed to list the flu as a reportable disease.

The flu arrived in September of 1918 at a time when most medical personnel where overseas fighting in WWI. 75% of Philadelphia Hospital's doctors were in the war. Then came a sense of profound overconfidence or stupidity when on September 28, 1918, 200,000 people gathered together to fund the war effort. Two days later, 635 people came down with the flu.

Churches, schools, theaters and all public meeting places were ordered closed. By the middle of October, hospitals were full, so church parish houses and state armories became make-shift hospitals and 4500 people were reported dead, while approximately 200,000 more people were sick.

Some undertakers took advantage of the family's dead loved ones by doubling their prices to bury their dead. Piles of corpes began to rot. The city begged the federal government to send embalmers.

By November of 1918, 13,000 Philadelphia citizens were dead as a result of the flu.

Potters Fields in Philadelphia

When the city's Fairmount Section was undergoing renovations, bones were discovered on the block of 800 and N. 20th Street.

Potters Field was once located nearby at N. 19th Street and Fairmount Ave.

The burial ground at the 800 block of N. 20th Street is believed to date back to 1793 when the city experienced a Yellow Fever outbreak and the estate known as Bush Hill served as its hospital located on the same grounds. Later, the hospital would be renamed the City's Hospital for Contagious Diseases until the year 1855.

Potters Fields were located in various parts of the city for the poor, the unknown and the unclaimed.
Several locations once called Potters Fields in Philadelphia are as followed;

• NorthEast opened in 1956
• Luzerene & Whitaker (now a police parking lot)
• Washington Square

And several other locations.

The last Potters Field was the one located in the Far NorthEast.

When the Potters Field was located at Luzerene and Whitaker in 1914, it served as the final resting place for those who died in the 1918 Flu Epidemic and the Great Depression in the 1930's. At this time, it was connected with a City Hospital.

Today, "Potters Field" is not a burial ground, but a room located in the City Morgue where there is 2400 sets of ashes identified but left unclaimed.

Gustine Lake July 1954

Maria Cannon

Maria Cannon was born December 23, 1901 and died of Endocarditis at age 13 years old on July 3, 1914. She was the child of George and Mary Gallagher Cannon. Address at time of death was 207 East Street. John McCarron was listed as undertaker. Maria was interred on July 7,1914 in St John the Baptist Cemetery.

James Cannon

James was born to George and Mary Gallagher Cannon on August 9, 1909 and died of diphtheria on January 19, 1915. Address at time of death was 207 East Street. James was interred in St. John the Baptist cemetery on January 20,1915. Immediate burial was a result of the contagious nature of his disease. John McCarron was listed as undertaker.

Baby Gerald J. Silverthorn

Gerald J. Silverthorn was born on May 10, 1911 and died on September 23, 1911 and was interred at Leverington Cemetery on September 26, 1911. He was the son of James and Grace Gallagher Silverthorn. John McCarron was the undertaker.

Baby James Silverthorn

James was born premature at 71/2 months gestation and lives seven hours and 10 minutes on May 6,1906 and died at 1030pm. He was the son of James and Grace Gallagher Silverthorn. He was interred in Leverington Cemetery. Address listed was 3908 Terrace Street. Isaiah J. Ryan was the undertaker.

My Great Great Grandfather Patrick Gallagher

Born December 24, 1867 and died of Apoloxy on June 29, 1913. Parents listed were Patrick Gallagher and Grace Harkins. Husband of Hannah Gallagher, father of Grace Silverthorn, Mary Cannon, William Gallagher and Sarah (Sally) Keller. Patrick was a mill hand in a textile factory and lived at 127 Seville Street at time of death. Patrick was interred on July 2, 1913 at Westminster Cemetery. Coroner was William R. Ford.

Baby Patrick Gallagher Son of William and Mary Keller Gallagher

Cause of death listed as gastroenteritis. Patrick was born January 5, 1910 and lived six hours. Coroner John W. Ford listed the infant's cause of death on January 6,1910 and the baby was interred on January 7,1910 at Westminster Cemetery. Undertaker was listed as Michael Walsh located at 116 Rector Street. Address at time of death was 143 Seville Street.

Mechanics Cemetery

"As the area became overpopulated and congested it was no longer suited to the needs of a peaceful eternal resting place, and in November 1950 the Cemetery Association voted to sell the property to the Philadelphia Housing Authority."

"The bodies were removed and reinterred at Philadelphia Memorial Park in Frazer, Chester County, which was founded in 1929 as a non-sectarian burial ground. Along with the remains of people from United American Mechanics Cemetery, three other Philadelphia area cemeteries have also moved to Philadelphia Memorial Park; German Lutheran Cemetery, Union Burial Ground and Belevue Cemetery.

Philadelphia Memorial Park became steward of the burial records when the graves were transferred, and the collections include account books, burial listings, correspondence, deeds, lot records, minutes, and receipts. The collection also includes information for Philadelphia Memorial Park. Belvue Cemetery and United American Mechanics Cemetery are the best represented burial grounds of the associated records now housed at the Chester County Historical Society."

The above information I discovered online and copied and posted it here. What is interesting to me is there was a vote to move the cemetery and that the article does not state that the cemetery fell in disarray along with Odd Fellows that was located nearby and that both cemeteries were sold to the Philadelphia Housing Authority. When Mechanics was opened between 1848 and 1849, the location at 22nd and Diamond Street was considered a rural area. After the Civil War, industry and housing took over and when the city wanted to build Housing Projects, it was cheap and easy to take over old cemeteries. Headstones were disposed of and bodies removed to mass graves in other cemeteries and then it was discovered that all bodies were not removed but built upon. If a lot holder had the money to move their loved ones, then they could do so. Most people did not have the money to move, therefore, their loved ones were removed by the city and placed elsewhere in mass graves. It was a sad time in history and when one researches it now, one discovers all the corruption that went with the removal of old cemeteries that were "in the way" in the late 1940's and 1950's. 

Good Samaritan Hospital

Opened in 1892 to treat folks who could not afford health care. It is now known as Temple Hospital.

Up Next

Now that I have locations of places and people associated with the death certificates and burial records, I want to research the following locations and people. I wonder what I will come up with so stay tuned.

1. Mechanics Cemetery
2. Potters Field
3. Samaritan Hospital
4. Merion Memorial Park Cemetery
5. Holy Cross (St. Mary's Cemetery off of Spruce Street)
6. Dr. Joseph Lehman
7. John Dever Funeral Home
8. Dr. Albert Beck
9. Charles McIvaine Funeral Home

Catherine McCaffery Death Certificate

Catherine McCaffery was the daughter of Collum McCaffery who died at age 20 years old of Tuberculosis. Dr. Joseph Lehman signed the death certificate on September 16, 1914 and Catherine was interred in St. Patrick's Cemetery in Norristown. Catherine was the sister of my Uncle Coll who married Anna Marie Gallagher. Catherine was listed as a mill worker and witness who signed death certificate was Mrs. Pester. Address at time of death was 118 Dawson Street. (19127) Dr. Joseph Lehman's address was listed as 4257 main Street and the undertaker was John Dever at 100 Rector Street. 

Baby Anna Malervy

Stillborn daughter of Daniel and Catherine Boland Malervy on February 21, 1914. Anna was interred on February 27, 1914 either at Westminster Cemetery (which appears crossed out) to Holy Cross (which is called St Mary's Cemetery) off of Spruce Street. Address at time of birth/death was 110 Canarroe Street and the funeral director was Charles McIvaine located at 4208 Ridge Ave,

Baby Edwin Schroeder

Son of Charles and Mary Mervine Schroeder born 4/10/1914 and died 9/30/1914 at Samaritan Hospital at age 5 months and 20 days old of acute gastroenteritis. At the time of death, the family resided at 3920 Gordon Street and the attending doctor was Albert Beck. Edwin was interred in Mechanics Cemetery on October 3, 1914.

The United American Mechanics and Daughters of America Cemetery was founded in 1848-1849 and situated on approximately 8.50 acres, consisting of 3,250 lots, and originally located at Islington Lane and 22^nd Street in North Philadelphia (about 22^nd & Diamond Sts.) The cemetery sold lots to Order of American Mechanic members, their family and friends. Bodies were removed to Frazer Pa. in 1951.

Mechanics in 1950

Baby Lucus Wisloski's Death and Burial Records

Baby Lucus, child of Lucus and Eva Wisloski was born at seven months gestation and died three days after his birth in 1903 and was interred in Merion Cemetery located at Bryn Mawr and Rockhill Rds in Bala Cynwyd, Pa. 19004. My Grandfather John (Wisloski) Weleski was born to Lucus and Eva one year later in 1904. Click image to enlarge.

Baby John Keller's Death Record

Name:	John Keller
Event:	Death
Event Date:	11 Aug 1870
Event Place:	Philadelphia, Philadelphia, Pennsylvania
Gender:	Male
Race:	White
Age:	0
Estimated Birth Year:	1870
Birth Date:
Birthplace:	U.S.
Marital Status:	Single
Spouse:
Father:	Gottleib Keller
Father's Birthplace:
Mother:	Mary E Keller
Mother's Birthplace:
Occupation:
Street Address:	4422 Harrison, ward 21
Residence:
Cemetery:	Ger. Luthern "E"
Burial Place:
Burial Date:	14 Aug 1870
Additional Relatives:
Film Number:	1003697
Digital Folder Number:	004000958
Image Number:	00283
Reference Number:	v 2 p 279

My Great Great Grandmother Elisabeth Voigt Keller's Death Record

Cause of death "Heart disease". If you click on image, you can view the doctor and funeral home along with where she lived at time of death, age at time of death and cemetery.

Margaret Voigt

Name:	Margaret Voigt
Event:	Death
Event Date:	16 Apr 1910
Event Place:	Philadelphia, Philadelphia, Pennsylvania
Gender:	Female
Race:	White
Age:	90
Estimated Birth Year:	1820
Birth Date:	04 Sep 1819
Birthplace:	Pa.
Marital Status:	Widowed
Spouse:
Father:	Henry Voigt
Father's Birthplace:	Pa.
Mother:	Mary Bouman
Mother's Birthplace:	Pa.
Occupation:	None given
Street Address:	1539 Norris St., 32 Ward
Residence:	Philadelphia, Philadelphia, Pennsylvania
Cemetery:	E. Laurel Hill Cem.
Burial Place:	Philadelphia, Pa.
Burial Date:	19 Apr 1910
Additional Relatives:
Film Number:	1405136
Digital Folder Number:	004009128
Image Number:	00032
Reference Number:	cn 10527

Sarah Ann Mervine's Death Record

Second wife of Alexander Mervine who died of Consumption (Tuberculosis) at age 44 yrs old in 1874.

Thanks to my cousin Maureen.

Cecelia Mervine's Death Record.

Thanks to my cousin Maureen.

Children of Alexander and Sarah Mervine

Alexander Mervine was my great great grandfather who fought in both the Mexican and Civil Wars and in the course of his long life time married three times which his last wife Mary Ann Hughes was my great great grandmother.

Alexander's longest marriage was to his second wife Sarah. What caught my interest is the deaths of three of their daughters at very young ages and the fact that all three daughters are interred in different cemeteries. As of this date, I do not know where Sarah Mervine is interred. However, I know my great great grandfather Alexander Mervine was interred in Odd Fellows. See http://ajourneyintothepast.blogspot.com/2007/05/odd-fellows-cemetery.html
As a matter of fact, his brothers were also interred in this cemetery with the exception of one brother/son.

The death records of Alexander and Sarah Mervine's three daughters are recorded under Mervine Link. However, I want to summarize their daughters records.

1. Cecelia Mervine was born in June 1858, died at the age of three weeks old on July 17, 1858 and was interred in St. George's M.E. Church Cemetery on July 17, 1858.
2. Kate P Mervine was born in 1862, died September 23, 1863 at the age of 16 months old and interred September 25, 1863 at Mount Vernon Cemetery.
3. Sarah A Mervine was born 1867, died at the age of 7 months old on July 3, 1867 and interred at Glenwood Cemetery on July 4, 1867.

When I look at the records of all the children which died in families in the 19th Century, I often wonder how the parents could endure such grief over and over again. I also wonder the reason behind interring them in different cemeteries. Did they live in the location of that cemetery? Was it the expense of burial?

Another interesting fact, I discovered by looking at burial records across several different families is "how" they are interred. Some are buried in a blanket at the cost of two dollars. Some had caskets placed in metal or cement vaults, others just had their caskets placed in the ground.

Sadly, most of the remains of my Mervine Family are lost due to Odd Fellows being removed and replaced by a housing project. Some records indicated they were reinterred in Mount Peace and/or Lawnview Cemetery. Alexander was one of the lucky ones who was reinterred at Lawnview in a mass grave and his original headstone that was removed from his grave in Odd Fellows was lost in the process. Most of the Mervines are not recorded as to where they were reinterred. However, folklore states many stones were removed from Odd Fellows, but the bodies remained and the housing project was built over the graves.

Samuel and Andrew Wisloski (My uncles)

Name:	Samuel Wisloski
Birth Date:	abt 1891
Event Type:	Burial
Burial Date:	16 Mar 1938
Burial Place:	Marion, Montgomery, Pennsylvania
Organization Name:	Westminster Cemetery Company

Also interred in same grave is his brother Andrew who was born in 1887 and died the same day.

• Lot Holder Eva Wisloski
• No vault
• Fitzpatrick Funeral Home
• St. John the Baptist Church

Eva Wisloski (My great grandmother)

Name:	Eva Wisloski
Birth Date:	abt 1874
Event Type:	Burial
Burial Date:	15 Jul 1932
Burial Place:	Marion, Montgomery, Pennsylvania
Organization Name:	Westminster Cemetery Company

• Age at death from Cancer 58
• Lot holder Eva Wisloski
• Metal Vault
• McIvaine Funeral Home
• St John the Baptist Church

Voigt Burial Records

Section 8
Lot 45
Bethany German Lutheran Cemetery

• Louise Voigt
• Amalie Merer
• Mina Voigt
• John Mayer
• Marie Louise Mayer
• Albert George Enser
• Wilhelmina Reinhart

Voigt Burial Records

Included in this grave with Friedrich Voigt are the following burials;

• Clare Spiehman
• Barbara Riess
• Andrea Wacht
• Anna Voigt 1820-1862
• Anna Viogt 1847-1854
• Ernest Viogt 1851-1853
• George Viogt 1853-1876
• Rachael Stromberger 1856-1881
• Andrew Viogt 1853-1876
• Margaret Voigt 1828-1892
• Caroline Schill

Burial Site is Bethany German Lutheran Cemetery located at Martin & Pechin.

• Section 8
• Lot 86

Name:	Friedrich Voigt
Event Type:	Burial
Burial Place:	Philadelphia, Philadelphia, Pennsylvania
Organization Name:	German Lutheran Cemetery

Gottlieb John Keller (My Great Great Grandfather)

Name:	Gottlieb Keller
Birth Date:	abt 1842
Birth Place:	Germany
Death Date:	27 Oct 1897
Death Place:	Philadelphia, Philadelphia, Pennsylvania
Age at Death:	55
Burial Date:	31 Oct 1897
Burial Place:	Roxborough
Gender:	Male
Race:	White
Cemetery:	German Lutheran
Marital Status:	Married
FHL Film Number:	1870492

Voigt Death Record

Name:	Edna Voigt
Birth Date:	abt 1898
Birth Place:	PA
Death Date:	17 Nov 1898
Death Place:	Philadelphia, Philadelphia, Pennsylvania
Age at Death:	1 month 7 days
Burial Date:	19 Nov 1898
Burial Place:	Phoenicville Pennsylvania
Gender:	Female
Race:	White
Street Address:	4362 Cresson St MYH Ward 21
Residence:	Philadelphia, Pennsylvania
Cemetery:	Morris
Father:	William C Voigt
Mother:	Luzetta Voigt
FHL Film Number:	1769735

Marriage Record of Charles and Mary Mervine Schroeder

	Charles Schroeder
	Male
:	Mervine
:	Female
:	Philadelphia, Pennsylvania, United States
	1904
:	181245
:	4141922

William and Anna McCaffery Gallagher 1940

Click on photo to enlarge.
Vital Statistics;

• William worked as a Crane Operator at Midvale Steel making 720 dollars per month.
• Address in 1940 was 4137 Terrance Street Phila Pa 19127
• Married to Anna Marie McCaffery
• Children in home were William III, John, Collum and Mary.

Babies Born Addicted

By Catherine Olian
Rock Center
They are the youngest victims of the prescription drug epidemic, tiny babies born already addicted to the drugs their mothers were taking when they were pregnant. More than13,000 babies a year are born in America addicted to prescription painkillers like OxyContin, hydrocodone and other narcotic drugs, according to a recent study released by the Journal of the American Medical Association.
Rock Center visited three hospitals and spoke to doctors at many more. These babies may seem normal at birth, but within days they start having symptoms like severe shaking, tremors and more.
“They vomit. They have diarrhea. They'll often have fever, sweating…extreme irritability,” said Dr. Mary Newport, the director of the neonatal unit at the Spring Hill Regional Hospital north of Tampa, Fla., in an interview airing Thursday at 10pm/9c on NBC.
The newborns also have trouble sleeping, feeding and they often shriek in pain, their bodies craving the medication they’re addicted to. The number of babies born this way has increased dramatically over the past five years, Dr. Newport said. This year she expects to treat nearly 20 times the number of infants going through withdrawal than she did in 2007.
“It’s terrible,” Newport said. “We sometimes feel that we have a neonatal drug rehabilitation unit.”

---

A baby experiencing withdrawal from painkillers
Annabella was just a few weeks old and she couldn’t stop crying. The only way the nurses could treat her symptoms was to give her morphine, a narcotic similar to the drug her mother took. As shocking as it may seem to give a baby multiple doses of morphine a day, Dr.Newport said, “if we don’t treat the baby…the baby will develop seizures and the baby can die.” Death can result from violent seizures, Dr. Newport said, that cause the baby to stop breathing, cutting off oxygen to the baby’s heart and other vital organs.
Many women become addicted to painkillers after they’ve been prescribed them by their doctors. Others, like Annabella’s mother, 20-year-old Katelynn Yost, start taking painkillers recreationally, never thinking they’ll become addicts.
“I thought I was going to stay in school and go to college,” Yost said. “I didn’t think I would end up doing drugs and being addicted to them.”
When she unexpectedly got pregnant, Yost decided to get drug treatment for the sake of her child.
“I want to be there for my baby now and help her have a good life,” she said. But first, Annabella had to go through the painful stages of withdrawal. “I know it’s all my fault,” Yost said. ”I’m the one that did it to her. It really hurts.”
There are no easy answers for pregnant addicts. Even if they want to get off the drugs quickly, doctors advise them not to. Going cold turkey could cause them to miscarry. Instead, the women are switched from the painkillers they are on to methadone or buprenorphine, drugs that keep them stable and help curb their cravings. Unfortunately, these drugs can also cause severe withdrawal symptoms in newborns.

Treating pregnant women addicted to prescription meds
“You’re told either you can take the methadone and your child could be born addicted, or you detox, stop taking everything and your baby could die,” one pregnant addict told us. Either way, “I’m deathly scared.”
The sheer volume of babies born addicted is putting a strain on the healthcare system. Healthy newborns typically stay in the hospital for a few days, but these babies stay weeks and sometimes months, at an average cost of more than $50,000 per child, according to the Journal of the American Medical Association. Doctors at the Cabell Huntington Hospital in Huntington, West Virginia told us that sometimes the neonatal unit is so full of babies going through withdrawal that newborns with other problems like prematurity have to be turned away due to lack of space.
Dr. David Chaffin, a maternal fetal medicine specialist at Marshall University Medical Center participated in a multi-hospital study that had a stunning result: at least 10 percent of all babies in West Virginia are born with prescription narcotics in their systems. He calls painkiller addiction among pregnant women “a monstrous tidal wave” with no end in sight.
As for little Annabella Yost, she finished going through withdrawal. She’s off all drugs and her mother says she’s doing well. The outlook for these babies is guardedly optimistic, but until large scale, long-term studies of these kids have been completed, no one really knows if they’ll have problems later in life.
All that the doctors can say for sure is that as long as women keep abusing prescription pain pills and doctors keep overprescribing them, expect to see more and more babies suffer the consequences.
“They are the innocent victims,” Dr. Newport told us. “They had no control over it and yet they suffer tremendously for it.”

Addiction is a Brain Disorder as Proven by Science

Gene Experiment Confirms a Suspected Cocaine Action

 This is ground breaking exciting stuff. As a post note, I completed a research project on just this subject of genes and the addicted brain that ended up being a 50 slide powerpoint presentation. It is fascinating to discover that there are specific genes that sit on specific chromomsomes whether it be the short arm or long arm of that chromomsome that get passed on together through conception. Having a strong background in the sciences then educating in behavioral health has created a vast interest in genetics for me though it can be rather boring to others.

October (Vol. 21, No. 4)

April (Vol. 21, No. 3)

February (Vol. 21, No. 2)

 

NIDA

      

Cocaine produces the long-term brain changes that underlie addiction in part by activating certain genes. Dr. Eric Nestler and colleagues at the University of Texas Southwestern Medical Center and Harvard Medical School have shown that the drug achieves this activation at least in part through a process called chromatin remodeling.

Chromatin and DNA Helix Form Chromosomes: Nucleosomes slide apart during chromatin remodeling, increasing transcription factors' access to a gene and thereby activating it. The DNA will then make mRNA, the blueprint for protein production.

The finding opens up a new avenue for potential therapies for addiction. "Our research suggests that testing chemical compounds that reverse chromatin remodeling is a promising approach to seeking treatments for drug abuse. This is already a major strategy for cancer therapy development," says Dr. Nestler.

Genes Regulate Crucial Proteins

Cocaine activates the genes that provide the templates for building the proteins cFos, ΔFosB, BDNF, and Cdk₅, among others. Researchers have linked the resulting higher brain levels of some of these proteins with long-term consequences of chronic drug abuse. For example, accumulation of long-lasting ΔFosB correlates with cocaine craving and drug self-administration in animals, and may contribute to longlasting structural changes in cocaine abusers' brain reward systems. As researchers continue to trace out the consequences of cocaine-induced gene activation, Dr. Nestler and colleagues pursued a related inquiry: How does it happen? Their candidate explanation was chromatin remodeling, a basic mechanism cells use to alter levels of the body's vast array of proteins to suit new circumstances and challenges (see insert below).
Chromatin consists of the deoxyribonucleic acid (DNA) double helix that carries an organism's genes wrapped around complexes of histone proteins. The unit of chromatin is called the nucleosome, and chemical processes control how tightly packed nucleosomes are. Chromatin remodeling occurs when this packing becomes more or less compact. As the nucleosomes bunch up or spread out, some genes move into positions that increase—and others into positions that decrease—their ability to interact with RNA polymerase, the enzyme that executes the first step in protein building. This helps determine how much of the protein blueprinted by each gene will be made.
To test their hypothesis that cocaine activates genes by inducing chromatin remodeling, Dr. Nestler and his team compared tissue taken from the striatum of rats exposed to the drug and others given saline. Specifically, they assayed the tissue for the end products of two chemical reactions known to modify chromatin's shape: acetylation and phosphoacetylation of its primary molecular components, histone ₃ (H₃) and histone ₄ (H₄). Both of these reactions remodel chromatin in ways that increase gene expression.

The findings bore out the hypothesis. Within 30 minutes of a single injection, the chromatin associated with the cFos gene in the cocaine-exposed animals contained twice as much acetylated H₄ than that in the control animals, and phosphoacetylated H₃ also was higher. The time course of these effects jibed with previous observations that cocaine induces a rapid, transient increase in levels of the cFos protein. They were no longer present in tissues taken 3 hours after the injection, and they stopped occurring when animals were given repeated cocaine doses over an extended period. These data support scientists' conception of the cFos gene as an early responder to acute neural disruptions, with little or no direct role in situations of recurrent disruption.

As with cFos, a single cocaine injection elevated acetylated H₄ in chromatin linked to the FosB gene, but the levels returned to baseline within 3 hours. Repeated cocaine did not induce H₄ acetylation in FosB geneassociated chromatin, but did cause H₃ acetylation. The researchers say that the switch from H₄ acetylation after a single cocaine exposure to H₃ acetylation after chronic exposure may mark a turning point in developing addiction.

Experience Restructures Chromatin

Chromosomes (pictured) are very long, continuous pieces of DNA that contain genes that help determine an individual's identity. Humans have 23 chromosome pairs with an estimated 30,000 genes.The DNA sequence wraps around proteins that give the chromosome a structure; together, they form chromatin. Cocaine and other external agents and experiences can alter the configurations of these proteins. Depending on the type of chemical change, the chromatin either bunches up or stretches out, activating or silencing genes along the DNA sequence.

Chromatin reshaping seems to underlie healthy adaptations such as learning and memory as well as disease processes—including cancer, seizures, schizophrenia, and depression. In another study, for example, Dr. Nestler's team found that social stress turned on a particular gene in the brains of mice through chromatin remodeling, a long-lasting change that corresponded with a behavioral indicator of depression. Antidepressant medication reversed both the behavioral sign of depression and the elevated gene activity, underscoring a key point about the modifications: experience and chemical agents can alter gene expression through chromatin remodeling, but such changes are reversible.

"More research is needed to identify the specific molecular basis of this switch," says Dr. Nestler. "However, prior work in my laboratory and with collaborators is starting to fill in a picture of why H₃ acetylation and FosB's activation and subsequent triggering of ΔFosB after chronic cocaine might be important. We believe that this series of molecular events, and probably others, mediate the long-term behavioral and neural changes that underlie the transition from drug abuse to addiction," says Dr. Nestler. The experiments and assays also showed:

• A single cocaine injection did not affect BDNF or Cdk5 gene-associated chromatin, but chronic exposure induced H₃ acetylation of both. Once initiated, the effects were long-lasting. The quantities of modified H₃ in BDNF gene-associated chromatin in exposed animals increased from 3-fold of those of salinetreated animals at day 1 to 14-fold at day 7. Acetylated H₃ related to the Cdk5 gene were more than two-fold those of saline 1 day after the last injection, and started to return to control levels only 7 days after cocaine cessation. Such persistent and robust gene activation long after the last dose of cocaine is striking in contrast with the relatively short-lived activation observed for cFos and FosB
• .
• Elevations in the ΔFosB protein selectively activated Cdk5—the only gene examined in the study that was turned on in this way. This finding suggests that ΔFosB may influence histone modifications by recruiting the chemical agents of chromatin remodeling to some target genes.

"Understanding how cocaine turns on these genes could help addiction researchers develop potential treatments that counteract the effects of drug abuse at the molecular level. Agents that reverse chromatin remodeling are available, and we are examining whether they block cocaine's cellular effects," says Dr. Nestler.

"Taken together with other studies showing that drugs induce long-term structural changes to brain cells, Dr. Nestler's findings show that chromatin remodeling is one way that such neural modification might occur. Such alterations are not necessarily permanent, and studies are needed to determine whether abstinence or other behavioral modifications further restructure chromatin to a state similar to that seen prior to drug exposure," says Dr. Joni Rutter of NIDA's Division of Basic Neuroscience and Behavioral Research. Whether nonstimulant drugs of abuse also act through chromatin remodeling is another important area for future research, she says.

A Connection With Cocaine-Related Behavior

In other experiments, Dr. Nestler and colleagues linked chromatin remodeling to cocaine's behavioral effects by examining its role in a laboratory stand-in for human cueinduced drug seeking called conditioned place preference (CPP). By exhibiting CPP—lingering in a part of a cage where it has received a drug—an animal indicates that it is seeking more of the drug (see "Animal Experiments in Addiction Science (Archives)"). The researchers hypothesized that augmenting or preventing histone modifications during drug administration sessions would increase or decrease CPP, respectively.

Cocaine Turns on Genes by Altering Chromosomal Proteins:

The researchers found chemical modifications to histone 3 (H₃) and histone 4 (H₄)—major proteins that form the structure of chromosomes—at areas linked with four genes. Acetylation of H₃ and H₄ and phosphoacetylation of H₃ alter the proteins' chemical structure, facilitating gene activation.

Experiment: Acute CocaineRats received a single injection, either saline or cocaine (20 mg/kg).

Gene	Results
	30 min.	1 hr.	90 min.	3 hr.	1 day	7 days
cFos	Acetylated H4 Phosphoacetylated H3			Normal Histones	Normal Histones
FosB	Acetylated H4
BDNF	No change
Cdk5	No change

Experiment: Chronic CocaineRats received an injection of either saline or cocaine (20 mg/kg) daily for 7 days.

Gene	Results
	30 min.	1 hr.	90 min.	3 hr.	1 day	7 days
cFos	No change
FosB	Acetylated H3		Normal Histones
BDNF	Acetylated H3					Normal Histones
Cdk5	Acetylated H3					Normal Histones

Experiment: Cocaine WithdrawalRats received an injection of either saline or cocaine (20 mg/kg) daily for 7 days and did not receive the drug again.

Gene	Results
	30 min.	1 hr.	90 min.	3 hr.	1 day	7 days
cFos	Effects too transient to examine
FosB	Effects too transient to examine
BDNF	Acetylated H3: Levels rise to 3-fold those associated with saline injection after 1 day, and to 14-fold after 7 days.
Cdk5	Acetylated H3: Levels rise to 3-fold those associated with saline injection after 1 day, and return to normal after 7 days.					Normal Histones

The investigators administered cocaine to mice daily for 4 days. Before each administration, they treated one group with a drug that enhances histone acetylation (trichostatin A, TSA) and another with a virus that expresses an enzyme that blocks this particular modification (herpes simplex virus, HSV). When placed back in the test cage on day 5, the group given TSA doubled the time spent in the drug-associated cage, on average, relative to the control group. In contrast, the group given the HSV vector lingered in the test cage for one-third of the time spent by its control group.
The findings suggest a causal link between histone acetylation in the striatum and sensitivity to cocaine's behavioral effects.

"The team had already demonstrated that chromatin remodeling plays a role in the rewarding aspects of cocaine abuse by including a group of animals that self administered the drug in the study. Their CPP experiment further strengthens the connection between histone restructuring and behavioral aspects of addiction and suggests that agents that reverse chromatin restructuring hold promise as potential therapies," says Dr. Rutter.

Epigenetics: The Promise of a New Science

This has been a subject I have been studying for the last three years and I teach at the facility in which I work. Addiction is not a moral issue nor is it a sign of weakness. It is genetics in combination with environmental factors. Today, we have a better understanding of the source of the issue and have learned that if a child is genetically set up for addiction, protective factors need to be in place. We are still working on exactly what these environmental factors should be.

NIDA

 Recently, scientists have developed a more sophisticated understanding of the ways in which genetics influences a person's health. The complement of genes a person inherits at birth is, of course, essential. But all genes are not created equal; only some genes are "expressed"—that is, actively participate in protein production. Today, a new field of scientific inquiry, called epigenetics, investigates the cellular mechanisms that control gene expression and its impacts on health and behavior.                    

Epigenetic processes allow experience to influence cellular processes. For example, epigenetic alterations that accumulate during a person's lifetime can contribute to aging, the development of cancer, obesity, and other health conditions.

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NIDA is funding studies to learn how epigenetic mechanisms figure in the neurobiology of drug abuse and addiction. In a dozen projects, researchers are elucidating the links between exposure to drugs of abuse, epigenetic processes, gene function, and neurobiological and behavioral changes in animal models of addiction. A recent study, for example, showed that cocaine triggers an epigenetic process called chromatin remodeling and that this contributes to rats' behavioral responses to the drug ("Gene Experiment Confirms a Suspected Cocaine Action"). Cocaine-induced epigenetic changes may increase the number of neural connections between the reward pathway and other brain regions that regulate emotions and memories to drive craving. We see every reason to hope that increased understanding of drugs' effects on epigenetic processes in the brain will open the door to analogous new addiction therapies.

National Institutes of Health (NIH) Director Dr. Elias Zerhouni has charged NIDA with a key role in developing a program within the NIH Roadmap Initiative on epigenomics—the analysis of epigenetic changes across a species' entire genetic blueprint. This agency-wide effort aims to provide researchers with standard tools and technologies to develop comprehensive epigenome maps that potentially will point the way to more effective responses to a wide range of health problems. To learn more about the Roadmap Epigenomics Program, visit commonfund.nih.gov/epigenomics.