Controversial DNA Forensic Technique Catches California Serial Killer

Robert Enneser by Robert Ennesser

On July 7, 2010, Lonnie David Franklin, Jr., was arrested and accused of murdering eleven people between 1985 and 2007.  Franklin had been dubbed the "Grim Sleeper" because he is believed to have taken a 14 year hiatus from killing between 1988 and 2002.  What led to his arrest after 25 years of eluding police? A controversial technique known as a "familial DNA search," in which DNA evidence from Franklin’s victims or crime scenes was closely matched to DNA obtained from his son.  Franklin’s son was convicted of a felony, and DNA collection is a normal procedure after a felony conviction.  Despite the success of the police in catching a serial killer, there is debate as to whether it is fair to use family members’ DNA to track down criminals.

On the national level, DNA information is stored by the FBI in the Combined DNA Index System (CODIS), which contains more than 8 million genetic profiles.  It has assisted in more than 116,000 investigations, including nearly 11,000 in Illinois.  Each CODIS profile contains information from 13 genetic markers composed of short tandem repeats (STRs) – repeated patterns of DNA scattered throughout the genome. Initially, CODIS included only violent felons but subsequently expanded to include all felons and later all felon arrestees.   Individual states have their own databases with differing inclusion requirements.  Some states do not expunge DNA profiles of arrestees later found innocent, other that do often require long, complicated procedures.  The FBI does not use familial DNA searches, but states are free to use the searches if they choose.  As a result, in California and Colorado, DNA of people never convicted of a crime and not under individual suspicion can be compared against DNA found at a crime scene. 

Continue reading

GMO Regulatory Practices: Food for Thought

Robert Enneser by Robert Ennesser

Genetically Modified Organisms, or GMOs, are often considered to be a fruit of our achievement in genetic engineering.  Inventors made waves in 2004 with the first GMO pet, Glofish®, fluorescent zebra fish-like pets that literally glow.  The proponents of GMO crops assert that they will help feed people around the globe by producing crops in more areas and larger quantities.  But there are also potential downsides of GMOs.  First, genetically-engineered crops can contaminate conventional crops, such as through seeds spread by wind.  Second, many crops are engineered to be resistant to the common herbicide glyphosate, but there is evidence of an increasing prevalence of weeds resistant to glyphosate.

There is a regulatory agency in place to address concerns raised by GMO crops.  Under the Plant Protection Act (PPA), the Animal and Plant Health Inspection Service (APHIS) of the United States Department of Agriculture (USDA) regulates the introduction of genetically engineered plants (which it terms “plant pests”) within the United States.  A manufacturer may petition APHIS if it believes its genetically engineered plant is not a “plant pest” and should be available to be freely sold and planted (deregulated).  The deregulation process requires APHIS to analyze the potential impact of the GMO on the environment pursuant to the National Environmental Policy Act of 1969 (NEPA).  Generally, APHIS files a brief environmental assessment (EA), but if it determines that the seeds could significantly affect the environment, APHIS must complete a detailed environmental impact statement (EIS).

Continue reading

BRCA in the Outback: The Australian Gene Patent Challenge

DamonGuptaby Damon Gupta

The U.S. case challenging the validity of gene patents is moving to the next step in the U.S. legal system.  Myriad Genetics has filed a notice of their intent to appeal the Southern District of New York’s decision invalidating patent claims on the BRCA1 and BRCA2 gene sequences and methods of determining the existence of mutations associated with breast cancer, of which Myriad is the exclusive licensee.  The Court of Appeals for the Federal Circuit will be next in line to hear the case and determine whether to affirm or deny the lower court’s decision.

The validity of gene patents is also being challenged in Australia, and Myriad is a party to the lawsuit.  June 8, 2010, Rebecca Gilsenan, an attorney with the Maurice Blackburn law firm, filed a lawsuit pro-bono on behalf of applicants (plaintiffs), Cancer Voices Australian, an advocacy group for all cancer patients in Australia, and Yvonne D’Arcy, a Brisbane woman diagnosed with breast cancer who could not afford BRCA1 testing by the exclusive licensee of the challenged Australian gene patent.

Continue reading

The FDA Crashes the Spit Party: Direct-to-Consumer Genetic Testing is Under Investigation

Jake Meyer by Jake Meyer

Direct-to-consumer (DTC) genetic tests are genetic tests that are marketed directly to the public, instead of through a physician.  DNA is collected for DTC genetic tests through either saliva kits or cheek swab kits that can be used in the comfort of a person's home and then mailed to the company for analysis.  Customers of the DTC genetic testing company deCODEme use a "buccal DNA collector" to collect DNA for analysis, by gently scraping the inside of his or her cheek.  The DTC genetic testing company, 23andMe sells a kit that includes a saliva collection device, called a Spit Kit.  In fact, 23andMe made headlines by hosting a "spit party" in New York during the New York Fashion Week.  DTC genetic tests offer a wide variety of tests, providing people with information regarding their ancestry; their chances of developing a disease, condition, or trait; their nutritional profile; and their responses to particular drugs.  However, providing this type of genetic information does not come without risks, particularly when the genetic information is not put into context or interpreted by a physician.  There has been little regulation of DTC genetic testing, but now the Food and Drug Administration (FDA) is taking notice.

Concerns about DTC genetic testing were recently raised when Pathway Genetics announced that it was planning to sell saliva collection kits at Walgreens and CVS stores.  After the announcement, the FDA sent a warning letter to Pathway and the U.S. Congress began an investigation of the marketing practices of three DTC genetic testing companies (including 23andMe).  A mix-up at one of the DTC genetic testing companies brought further scrutiny.  On June 4th, 2010, 23andMe announced that up to 96 of its customers "may have received and viewed data that was not their own."  June 10, 2010, the FDA sent letters to five DTC genetic testing companies (23andMe, Navigenics, deCODEme, Illumina, and Knome) stating that the companies must either apply for approval or discuss why certain test claims don’t need the FDA’s approval.  The letters indicated that the FDA considers the DTC genetic testing offered by these companies to be a device "intended for use in the diagnosis of disease or other conditions" under 21 U.S.C. § 321(h) and therefore subject to regulation.

Continue reading

Spider Walkers: DNA Nanobots Indicate Cooperation Among Nanotechnology Researchers

Robert Enneser by Robert Ennesser

In 1676, Issac Newton wrote to rival researcher Robert Hooke, "[y]ou have added much in several ways, and . . . [i]f I have seen a little further it is by standing on the shoulders of giants."  Scientific and medical innovation occurs when the greatest numbers of researchers are able to use the best materials and methods available to develop new technologies and treatments.  Nanotechnology and genetics are two heavily patented areas with promising medical applications.  Unlike some current genetics companies that use patents to block researchers from studying their gene and developing new technologies, several recent nanotechnology studies are evidence that scholars across the country are working together and building off of each others' results. 

Two recent studies in Nature have illustrated how innovation builds from research findings of multiple groups.  Both studies make use of a technique known as "DNA origami"  DNA origami is the precise, nanoscale folding of a single strand of DNA on a synthetic scaffold.  DNA origami has been used to produce DNA in particular nanoscale structures, shapes, and patterns.  In the first study, a group of researchers led by biochemist Milan Stojanovic of Columbia University created molecular "robots" which move on top of a DNA origami pattern. Their robot "spider" is composed of a body and includes 3 legs which interact with a trail created by the researchers on the DNA origami pattern.  The body of the spider is made of a streptavidin molecule, a protein often used in biotechnology experiments which can be used to visualize nanoscale structures by attaching a molecule that fluoresces when excited by fluorescent light.  In the second study, a team of scientists led by Professor Nadrian Seeman at New York University created a DNA "assembly line" that can create 8 different arrangements of gold particles.  Seeman created a tiny robot "walker" composed of single-stranded DNA fragments with three "hands" that pick up and bind cargo and four "feet" that bind to a path on a DNA origami pattern.  Professor Seeman is regarded as the creator of DNA nanotechnology and was awarded the Kavli Prize in Nanoscience on June 4th, 2010.

Continue reading

The Creation of a Synthetic Cell Opens New Possibilities and Perhaps New Dangers

Jake Meyer by Jake Meyer

The biotechnology age has progressed at a rapid pace.  Every few years a new discovery in biotechnology leaves us wondering about new possibilities.  In 1997, Dolly the sheep was the first successfully cloned animalIn 2000, the Human Genome Project announced that it had assembled the first working draft of the human genomeAnd now in 2010 a team of researchers has created the first synthetic cell.  But sometimes lost with an eye-opening discovery is the story of Frankenstein and the question posed by Mary Shelley’s novel: How much tinkering should we do?  Or, updated for the 21st century, how should we regulate our new tinkering?

May 20, 2010, Researchers at the Craig Venter Institute created the first self-replicating synthetic bacterial cell.  A synthetic genome, 1.08 million base pairs long was designed by a computer, chemically made in a laboratory, and placed within a bacterium cell.  Through replication of the cell the original genome is lost and only the synthetic genome remains resulting in a new self-replicating cell controlled by the synthetic genome.  The discovery opens the possibility of engineering microbes that produce useful substances, such as vaccines and biofuels.  One possible use of this technology that is being explored is to construct genomes of photosynthetic bacteria to use light energy to produce hydrogen gas from water, which can be used as a fuel source. 

Continue reading

Rebecca Skloot’s Journey into the Life of Henrietta Lacks

Lori Andrews by Lori Andrews

In 1890 a man sold the rights to his body after death to the Royal Caroline Institute in Sweden for research purposes.  Later, he tried to return the money and cancel the contract.  In the subsequent lawsuit, the court held that he must turn his body over to the Institute and also ordered him to pay damages for diminishing the worth of his body by having two teeth removed.

Photo of Lori Andrews and Rebecca Skloot

Lori and Rebecca Skloot

Today, it would be an anathema for a person’s body to be used against his wishes or for a research subject not to be allowed to withdraw from a study.  In fact, the Uniform Anatomical Gift Act allows people to change their minds and withdraw a previous agreement to donate organs and tissue after their death and the Federal research regulations allow people to withdraw from studies without penalty or loss of benefits.  Yet the law is murky regarding research on a person’s tissue outside of his body and some modern doctors and researchers emulate the Royal Carolina Institute and stake their claims on materials from people’s bodies.

In 1951, a 31-year-old African-American woman, Henrietta Lacks, died of ovarian cancer.  Without the knowledge or consent of Lacks or her family, her tissue was taken and made into a cell line that has been extremely valuable for research and is still sold today.  In an interview in 1994, her husband said, “As far as them selling my wife’s cells without my knowledge and making a profit — I do not like that at all.  They are exploiting both of us.”
Body Bazaar Cover Image
Dorothy Nelkin and I wrote about Henrietta in our 2000 book, Body Bazaar: The Market for Human Tissue in the Biotechnology Age.  Over the past decade, journalist Rebecca Skloot probed more deeply.  In The Immortal Life of Henrietta Lacks, Skloot tells a moving story of how the unauthorized use of Henrietta’s cells (known to scientists as HeLa cells) provided the foundation for most modern medical discoveries.  I caught up with Rebecca Skloot on her whirlwind book tour when she spoke at the Northwestern Medical School.

Skloot-Book-CoverShe described how Henrietta’s cells formed the basis for much of the scientific enterprise across the world in the decades since her death.  Virtually every high school biology student, every medical student, and every vaccine maker has manipulated her cells.  While fortunes have been made on the foundation of the HeLa cells, her own children lacked access to education and basic health care.  In fact, when her children were contacted decades after her death by researchers wanting their tissue, they completely misunderstood what scientists meant by research on their mother’s cells.  They visualized their mother as still alive, in a cell, being researched upon.

But they are not the only people kept in the dark about tissue research.  How many people realize that their tissue is being used today without their knowledge and consent?  Over 282 million archived and identifiable pathological specimens from more than 176 million individuals are being stored in United States repositories.  Some specimens are anonymized or coded and not identified with specific individuals; others carry patient names or codes that allow personal identification.  Virtually everyone has his or her tissue “on file.”

Expanding markets have increased the value of this tissue, and institutions — hospitals, research laboratories, and the state and federal repositories that store tissue samples — find they possess a capital resource.  Medical centers have deals in place with biotech companies to do genetic research on their hospital patients’ tissue without the patients’ permission.

This lackadaisical approach to consent has recently been called in question.  A Native American group, the Havasupai, gave tissue to a scientist for research on diabetes.  Instead, the scientist undertook research about schizophrenia and in-breeding, which stigmatized the Havasupai, and research about geographical origins, which conflicted with the Havasupai’s religious beliefs.

When the researcher was challenged in federal court, the judge found that the Havasupai had asserted valid claims for intentional infliction of emotional distress, negligent infliction of emotional distress, civil rights violations, negligence and gross negligence.  In April 2010, the researcher’s university settled with the Havasupai, paying $700,000 to 41 members of the tribe for using their tissue without appropriate informed consent.

The attention being paid to Skloot’s excellent book and the good news of a settlement in the Havasupai case are spurring societal discussion about the use of tissue samples.  Clear laws and regulations are needed to assure that no one’s tissue is used without specific informed consent.

The specifics of Henrietta Lacks saga will soon be made into a movie, with Oprah as an executive producer.  But her story affects us all.  Hospitals, universities, research centers, and private depositories retain pathology samples and genetic data collected in the course of surgical procedures or research projects — a fact unknown to most patients.  New laws are needed to make sure we are not a nation of guinea pigs.

Guilt by Association: Familial DNA Searching Implicates Many On the Quest to Find The One

JenAckerby Jen Acker

When DNA is left behind at a crime scene, investigators usually run the sample through a DNA database.  All states collect DNA samples from convicted felons, and some even collect DNA from suspects brought into custody.  If the DNA found at the crime scene matches a sample in the database, a suspect has likely been identified.  Sometimes, an exact match may not be found, but a very close match may exist:  this is the essence of familial DNA searching.  These near-matches may spell trouble for the innocent relatives of people with criminal histories. 

Individuals related by blood have similarities in genetic material.  Therefore, the stored DNA of a man who has a criminal record could be used to identify his brother who does not have a criminal record.  Similarly, DNA taken from children born out of a rape has been used to identify their father, the rapist.  In at least one high profile case, familial DNA searching was used to free an innocent man who spent 19 years behind bars.

Despite the potential for identifying suspects, familial searching is not without debate, and its legality has not been vetted in the courts.  Critics contend that familial DNA searching raises concerns regarding privacy and illegal search and seizure.  While DNA near-matches indicate that a relative of a convicted criminal is likely implicated, near-matches do not indicate precisely which relative.  The fear is that family members become guilty by DNA association even when law enforcement has no other evidence to support the connection.

Continue reading

The Effect of NIH’s Genetic Testing Registry on Direct-to-Consumer Genetic Testing

Keith Syverson by Keith Syverson

In March 2010, the National Institutes of Health (NIH) announced that it is creating a voluntary national Genetic Testing Registry to provide easy public access to information regarding the availability and utility of genetic tests. The registry, which is slated to be available in 2011, will collect information from clinical, commercial, and research testing organizations and display it in a database geared towards physicians and patients. The announcement came almost two years after the Secretary Advisory Committee on Genetics, Health, and Society (SACGHS) published recommendations suggesting that the NIH establish a web-based registry for laboratory genetic tests. Ideally the registry will include information about the analytical validity, clinical validity, and the clinical utility of genetic tests. This information is particularly important for consumers who wish to utilize direct-to-consumer (DTC) genetic testing options such as 23andMe or Navigenics. Although the database is a step in the right direction for ensuring that patients and doctors receive accurate information regarding genetic testing, the registry may not alleviate the problems associated with direct-to-consumer genetic testing.

Continue reading

S.D.N.Y. Holds That Patent Claims on Breast Cancer Genes Are Invalid

Jake Meyer by Jake Meyer

On March 29th, 2010, Judge Sweet of the United States District Court in the Southern District of New York declared that the challenged patent claims, owned by Myriad genetics, that cover the BRCA1 and BRCA2 breast cancer genes are invalid.  The full opinion is available here.  I had previously blogged about the plaintiffs in the case here, and I previously blogged about Judge Sweet’s denial of the defendant’s motion to dismiss here.  This was the first case to raise the argument that gene sequences and correlations between gene mutations and disease are unpatentable subject matter under 35 U.S.C. section 101.

There were two types of claims at issue in the case:  1) claims to “isolated” DNA containing the BRCA1 or BRCA2 sequence or certain segments of those sequences, and 2) claims to methods of comparing two BRCA1 or BRCA2 sequences to determine whether a mutation that predisposes a subject to cancer is present.  Judge Sweet found that both of these types of claims were invalid subject matter.

U.S. patent law does not allow for the patenting of products of nature.  As Judge Sweet recognizes this in his opinion there is a “judicially created ‘products of nature’ exception to patentable subject matter, i.e. ‘laws of nature, natural phenomenon, and abstract ideas.'”  Judge Sweet applied analysis from the 1980 Supreme Court case Diamond v. Chakrabarty to determine whether the product claims directed to “isolated” DNA were patentable.  The Supreme Court in Chakrabarty held that a genetically engineered bacterium was patentable because the “patentee had produced a new bacterium with markedly different characteristics from any found in nature.”  Sweet found that the requirement that an invention have “markedly different characteristics” from a product of nature to be patentable had been stated (although using different language) in earlier cases as well, such as in the Supreme Court case American Fruit Growers and in the Court of Customs and Patent Appeals case In re Merz.

Judge Sweet held that the “isolated” DNA was not “markedly different” than DNA inside the human body.  The analysis focused on the DNA’s unique role as both a physical molecule and as information.  While the “isolated” DNA was removed from the body, the information embodied by the DNA was not changed:

In light of DNA’s unique qualities as a physical embodiment of information, none of the structural and functional differences cited by Myriad between native BRCA1/2 DNA and isolated BRCA1/2 DNA claimed in the patents-in-suit render the claimed DNA “markedly different.”  This conclusion is driven by the overriding importance of DNA’s nucleotide sequence to both its natural biological function as well as the utility associated with DNA in its isolated form.  The preservation of this defining characteristic of DNA in its native and isolated forms mandates the conclusion that the challenged composition claims are directed to unpatentable products of nature.

The second types of claims to methods of comparing two BRCA1 or BRCA2 sequences to determine whether a mutation that predisposes a subject to cancer is present were found invalid because they involved a law of nature and did not satisfy the Federal Circuit’s machine-or-transformation.  When a method claim makes use of a law of nature, the claimed method must either use a specific machine or apply a transformation to be patentable.  Judge Sweet found that the method did not include a transformation and since the claims did not include the use of a specific machine the method claims were directed to an unpatentable law of nature.