The life of Kathleen Folbigg and the progress of genetic research

New South Wales to conduct a second inquiry into Kathleen Folbigg’s convictions. Central to this new investigation are new data on the protein calmodulin, specifically one of its coding genes, CALM2 – and a mutated form of the gene known as G114R, which can cause heart arrhythmias in young children.

In this timeline, Cosmos compare the Folbigg case story to advances in scientific understanding of the human genome; how genes code for functional proteins; and search into CALM2which will be submitted to the inquiry.

1952

GENETIC INFORMATION

Alfred Hershey and Martha Chase demonstrate that DNA contains genetic information, not proteins.

1957

RECEPTORY CELLS

Hodgkin and Keynes suggest that there may be receptors in cells that move calcium, based on a previous experiment – ​​in hindsight, this role can now be attributed to the protein calmodulin.

June 14, 1967

BORN KATHLEEN

Kathleen Megan Donovan – later Folbigg – was born in Sydney.

1968

NOBEL PRIZE

Marshall W. Nirenberg, Har Gobind Khorana and Robert W. Holley win the Nobel Prize in medicine for their interpretation of the genetic code and its function in protein synthesis.

January 8, 1969

MURDERED MOTHER

Folbigg’s mother murdered by his father.

1970

CALMODULIN PROTEIN HYPOTHESIS

The receptor hypothesized by Hodgkin and Keynes is attributed to the protein calmodulin. At this point, genetic sequencing did not exist and therefore protein analysis did not shed any light on genomics.

1977

DNA SEQUENCE

Frederick Danger develops a technique for sequencing DNA, which is later used to sequence the first human genome.

1983

LOCALIZATION GENES

James Gisella and his team find the location of a gene responsible for Huntington’s disease.

1987

MARRIAGE

Kathleen MariesCraig Folbigg.

February 20, 1989

THE FIRST SON DIES

Caleb Folbigg dies at the age of 19 days.

1990

LAUNCH OF THE HUMAN GENOME PROJECT

It aims to fully sequence the first human genome with a 15-year history.

February 13, 1991

THE SECOND SON DIES

Patrick Folbigg dies at the age of 8 months.

1992

GENETIC TESTS

A technique is being developed to genetically test embryos for diseases such as haemophilia while they are still in the womb.

August 30, 1993

THE THIRD SON DIES

Sarah Folbigg dies at the age of 10 months.

1997

CALMODULIN STUDY

Numerous studies refine the molecular function of the calmodulin protein gene family. Calmodulin is found to be a multifunctional calcium-binding protein to help regulate, among other things, the cell cycle and cell division. Like gene characterization, the function of a gene within the body does not illuminate the clinical relevance of the gene and protein.

1998

CALM2

The CALM2 gene is characterised, meaning the gene has been compared to others in its family to estimate small nucleotide differences. Gene characterization infers only related genes and does not show the function of the gene or the clinical consequences of mutations in it.

1999

DNA SEQUENCE

The first fully sequenced human chromosome has been released by the Human Genome Project.

March 1, 1999

THE FOURTH SON DIES

Laura Folbigg dies at the age of 18 months.

2001

FIRST DRAFT

The first draft of the human genome was released by the Human Genome Project, at a cost of $300 million.

2003

99.9% ACCURACY.

Human genome project completed with 99.99% accuracy. It reports about 20,000-25,000 human protein coding genes.

October 24, 2003

BELIEF

Folbigg sentenced to 40 years in prison for murder; the non-parole period is 30 years, later reduced on appeal to 25 years.

2007

TECHNOLOGY IMPROVES

Improvements in sequencing technology increase genome sequencing time 70-fold.

2008

1000 GENOMES

Launch of the 1000 Genomes project, with the aim of sequencing a large cohort of genomes. Next-generation sequencing dramatically reduces the cost of genome sequencing to $16 million.

2012

CALM STUDIES1

Study Shoes that mutations in CALM1, a close relative of CALM2, can lead to sudden cardiac arrest. The subject of this study was a 23-year-old woman who suffered sudden cardiac arrest at age four, but she was revived. From this point, many studies find correlations between CALM gene mutations and cardiac arrest.

2013

CALMODULIN MUTATIONS

Another study shows that calmodulin mutations are associated with more cardiac arrests in newborns.

2014

NEW MUTATIONS

The recently identified mutations in CALM2 are linked to susceptibility to congenital arrhythmia, a genetically inherited irregular heartbeat or heart rhythm.

2015

COST AND EFFICIENCY

The cost of sequencing an entire draft human genome drops to less than US$1500 and takes 4 to 12 weeks.

June 10, 2015

FIRST PETITION

NSW Governor David Hurley receives petition for Folbigg’s convictions to be reviewed. The petition raises a reasonable possibility of his innocence based on the forensic pathology findings.

2018

100K GENOMES

The 100K Genomes project completes the sequencing of 100,000 genomes for patients with rare diseases or cancer.

October 20, 2018

INVESTIGATION

NSW Inquiry into convictions opens.

March 2019

MERIT HEARINGS

Substantive inquest hearings are held and the genomes of the Folbigg children are sequenced.

May 2019

CAMODULIN REGISTER

The Calmodulin Registry reports that two US children died from the mutation present in the Folbigg girls, Sarah and Laura.

July 2019

NO REASONABLE DOUBT

The commissioner of inquiry finds no reasonable doubt of Folbigg’s beliefs. Functional validation of the Folbigg mutation was not completed until the end of the investigation.

November 2020

INFANT MORTALITY STUDY

A research group led by Stephen Kingsmore of the Rady Children’s Institute for Genomic Medicine in San Diego (USA) estimates that infant mortality due to genetic diseases is between 10 and 21%, but the therapeutic guidelines only covered 70% of diseases. They suggest that genomic sequencing of newborns may help reduce mortality.

CALM2 CONFIRMED

An article, “Infanticide vs. hereditary cardiac arrhythmias,” is released, showing that the CALM2 mutant variant, G114R was present in the two Folbigg girls. The authors also report that the two sons had mutations in the BSN gene, associated with severe epilepsy in juvenile mice and neurodegenerative disease during adulthood.

March 3, 2021

SECOND PETITION

Petition for Kathleen Folbigg’s pardon presented to NSW Governor Margaret Beazley.

May 18, 2022

SECOND CALL REQUEST

Beazley orders an investigation into Folbigg’s beliefs.


More on this story:

The Folbigg investigation starts today: here’s what science proves

Calmodulin regulates the heartbeat. The mutations in it could have been fatal to Folbigg’s daughters

Our Cosmos Briefing panel on the place of science in the law




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