Clinical laboratories and pathology groups can benefit from knowing how genetic testing is being used for other than medical testing purposes
It is useful for pathologists and clinical laboratory managers to be aware of the different ways genetic testing and DNA sequencing is being conducted. That’s because a genetic test for one purpose—such as identifying an individual’s relatives and connection to a region or a cultural group—might generate data that could become part of that person’s medical care.
Thus, an ongoing genetic study in South Africa highlighting the issue of so-called “helicopter research” will be informative for Dark Daily’s readers.
Also known as “neo-colonial science,” helicopter research describes when scientists from wealthy countries perform research in lower-income countries in ways that may be deemed exploitative or disrespectful to local populations.
“Scientists conduct helicopter research when they collect data from developing countries and marginalized communities with little to no involvement from local researchers and community members,” wrote researchers Dana Al-Hindi, and Brenna Henn PhD, in an article for The Conversation. “Helicopter research also occurs when researchers take data out of the country they collected it from without either providing benefit to or sharing the results with the community.”
In an article for The Conversation, UC Davis researchers Brenna Henn, PhD (left), and Dana Al-Hindi (right), wrote, “While we have learned a great deal from these communities, we have been unable to fulfill a common request: providing them their individual genetic ancestry result. In our attempts to overcome the logistical challenges of providing this information, we’ve grappled with the common question of how to ensure an equitable balance of benefits between researchers and the community they study. What we’ve found is that there is no easy answer.” Clinical laboratories will want to remember the term “Helicopter Research” in relation to these types of studies. (Photos copyright: UC Davis/The Conversation.)
The South Africa study, conducted over the past 12 years, aims to use genetic data “to help unravel the history and prehistory of southern Africans and their relationship to populations around the world,” the authors wrote in The Conversation.
The researchers have been using the genetic data to trace the ancestry of indigenous Khoekhoe and San peoples in South Africa as well as other populations that self-identify as “Colored.”
“Early European colonizers initially used this term to refer to indigenous Khoekhoe and San groups long before it was codified by the apartheid government in 1948,” the researchers wrote. “It persists today as an ethnic category, broadly encompassing Khoe-San groups, various East African, Indian, and Southeast Asian populations brought by the slave trade, and people of mixed ancestry.”
Challenges Sharing Genetic Data with Study Participants
Participants in the study have asked to see their personal genetic ancestry results, but the researchers noted several challenges, including local restrictions and the difficulty of presenting complex data in “an accessible and digestible form.” So, the researchers partnered with consumer-focused genetic testing company 23andMe (NASDAQ:ME).
23andMe provided additional funding for the research, assisted the researchers in community outreach, and “expanded our ability to ‘capacity-build’—that is, to make sure that the knowledge and skills we gain are shared with local institutions,” Henn and Al-Hindi wrote in The Conversation. They added that they are still dealing with questions about whether their efforts to provide equitable benefits are sufficient.
“Our research team, local collaborators, and 23andMe are all concerned about how to best address the risk of helicopter research, coercion, and any unknown risks that may arise from disclosing personal ancestry results,” they wrote.
Cape Town Statement on Fostering Research Integrity
The issue of helicopter research was a major focus at the 7th World Conference on Research Integrity (WCRI), held May 29-June 1 in Cape Town, South Africa. It was the first WCRI to be held in Africa and adopted the theme “Fostering Research Integrity in an Unequal World.”
One outcome of the conference will be an effort to produce what is known as the Cape Town Statement on Fostering Research Integrity. The statement will “highlight the importance of fairness in international research partnerships,” noted Research Professional News.
The statement “compels institutions and researchers alike to act on their responsibilities to promote equity, diversity, and fairness in research partnerships,” conference speaker Retha Visagie, DCur, told the publication. She leads the Research Integrity Office at the University of South Africa.
Conference co-chair Lyn Horn, PhD, director the Office of Research Integrity at the University of Cape Town, told the publication that it could take up to a year before a draft of the statement is ready for comment.
One overarching goal will be to “demonstrate why inequity and unfair practices in research collaborations and contexts is a research integrity (RI) matter,” the authors wrote. “Second it must identify some key values or principles and action guides that will address the issue of equity and fairness in research within the context of the complete research life cycle from research agenda setting and call to proposal development, through grant application, allocation and management of funding, data production, analysis, management and sharing, to outputs, translation, and evaluation.”
Another conference speaker, Francis Kombe PhD, told attendees the statement will offer guidance specifically to institutions such as universities, journals, and funding organizations, the journal Science reported. That stands in contrast to earlier statements on helicopter research, which were geared more toward individuals and small groups.
How any of this will impact clinical laboratories and pathology groups remains unclear. Nevertheless, it is worthwhile knowing how gene sequencing is being used by researchers for purposes other than to guide diagnoses and treatment of patients.
Of interest to clinical pathologists is the finding that sequencing the genomes of Humans and Neanderthals revealed a link between severity of COVID-19 infections and Neanderthal DNA
Genetic scientists from the University of California Santa Cruz have learned that just 7%—or less—of our DNA is unique to the human species, with the remainder of our genomes coming from other archaic species, such as Neanderthal and Denisovan.
Why should this matter to pathologists and clinical laboratories? Because a broader knowledge of how DNA evolves may help researchers and healthcare providers better understand how a modern family’s DNA can change over generations. In turn, these insights may lead to precision medicine tools for personalized diagnosis and treatment.
“We find that a low fraction, 1.5 to 7%, of the human genome is uniquely human, with the remainder comprising lineages shared with archaic hominins from either ILS [incomplete lineage sorting] or [genetic] admixture,” wrote the paper’s authors.
To complete their study, the researchers used DNA extracted from fossils of Neanderthals and Denisovans, as well as genetic information from 279 people from various locations around the world.
One goal was to determine what part of a modern human’s genome is truly unique. Though only a small percentage of our entire genome, those portions are important.
“We can tell those regions of the genome are highly enriched for genes that have to do with neural development and brain function,” Richard Green, PhD, Associate Professor of Biomolecular Engineering at the University of California Santa Cruz and co-author of the paper, told the Associated Press (AP).
In addition to highlighting what makes modern humans unique as a species, the study also suggests, “That we’re actually a very young species. Not that long ago, we shared the planet with other human lineages,” said Joshua Akey, PhD, Professor of Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics at Princeton University. Akey co-authored the Science Advances research paper.
Human/Neanderthal Genetic Overlap
The genetic research being conducted at the University of California Santa Cruz is just the most recent in a flurry of studies over the past decade investigating the Neanderthal genome. Most of these studies point to the vast similarities between humans and Neanderthals, but also to how similar humans are to each other.
“Humans have more than three billion letter pairs of DNA in their genome: It turns out less than 2% of that spells out around 20,000 specific genes, or sets of instructions that code for the proteins that make our tissues,” wrote zooarcheologist Anna Goldfield, PhD (above), Adjunct Instructor Cosumnes River College in Sacramento, Calif., and at the University of California, Davis, in Sapiens. “All humans share the same basic set of genes (we all have a gene for earwax consistency, for example), but there are subtle variations in the DNA spelling of those genes from individual to individual that result in slightly different proteins (sticky earwax versus dry earwax) … Overall, any given human being is about 99.9% similar, genetically, to any other human being,” she added. It is those variations that could lead to precision medicine treatments, personalized drug therapies, and clinical laboratory tests that inform physicians about relevant genetic variations. (Photo copyright: Boston University.)
Practically Everyone Has Neanderthal DNA
Understanding that humans and Neanderthals are 93-98.5% similar genetically may—or may not—come as a surprise. In delving into those similarities and differences researchers are making interesting and potentially important discoveries.
For example, researchers have studied a gene that occurs in both modern humans and Neanderthal fossils that has to do with how the body responds to carcinogenic hydrocarbons, such as smoke from burning wood. Neanderthals were far more sensitive to the carcinogens, but also had more genetic variants, such as single-nucleotide polymorphisms, that could neutralize their effects.
Most modern humans carry some Neanderthal DNA. For some time, scientists thought that Africans likely did not carry Neanderthal DNA, since ancient people tended to migrate out of Africa and met Neanderthals in Europe. More recent research, however, shows that migration patterns were more complex than previously thought, and that the ancient people migrated back to Africa bringing Neanderthal DNA with them.
“Our results show this history was much more interesting and there were many waves of dispersal out of Africa, some of which led to admixture between modern humans and Neanderthals that we see in the genomes of all living individuals today,” Akey told CNN.
Neanderthal DNA and COVID-19
Researchers have found that having Neanderthal DNA may affect the health of modern people who carry it. Perception of pain, immune system function, and even hair color and sleeping patterns have been associated with having Neanderthal DNA.
Scientists have even found a potential link between severe COVID-19 infection and Neanderthal DNA, CNN reported.
The researchers added, “It turns out that this gene variant was inherited by modern humans from the Neanderthals when they interbred some 60,000 years ago. Today, the people who inherited this gene variant are three times more likely to need artificial ventilation if they are infected by the novel coronavirus SARS-CoV-2.”
Of course, these links and associations are preliminary science. John Capra, PhD, Research Associate Professor of Biological Sciences and Associate Professor of Biomedical Informatics at the University of California, San Francisco says, “We can’t blame Neanderthals for COVID. That’s a damaging response, and that’s why I want to emphasize so much [that] the social and environmental factors are the real things that people should be worrying about,” he told CNN.
“That said,” he continued, “as a geneticist, I think it is important to know the evolutionary history of the genetic variants we find that do have effects on traits. The effects of Neanderthal DNA traits are detectable, but they’re modest.”
Nevertheless, genetic scientists agree that understanding the genetic roots of disorders could lead to breakthroughs that result in new types of clinical laboratory tests designed to guide precision medicine treatments.
Studies show consumer genealogy databases are much broader than is generally known. If your cousins are in such a database, it’s likely you are too
Recent news stories highlighted crime investigators who used the DNA data in consumer genetic genealogy databases to solve cold cases. Though not widely known, such uses of direct-to-consumer DNA databases is becoming more commonplace, which might eventually lead to requests for clinical laboratories to assist in criminal investigations involving DNA data.
Case in point: investigators found the Golden State Killer, a serial killer/rapist/burglar who terrorized multiple California counties over a dozen years in the 1970s to 1980s, after uploading a DNA sample from the crime scene to GEDmatch, an open-data genomics database that features tools for genealogy research. They made the arrest after discovering a distant relative’s DNA in the genealogy database and matching it to the suspect, CBS News revealed in a 60 Minutes Overtime online report.
These and other investigators are using a technique called familial DNA testing (AKA, DNA Profiling), which enables them to use genetic material from relatives to solve crimes.
Clinical laboratories oversee DNA databases. Could DNA databases—developed and managed over years by medical laboratories for patient care—be subpoenaed by law enforcement investigating crimes?
The question raises many issues for society and for labs, including privacy responsibilities and appropriate use of genetic information. On the other hand, the genetic genie is already out of the bottle.
Leveraging Familia DNA to Solve Crimes a New Trend
“The solving of the Golden State Killer case opened this method up as a possibility, and other crime labs are taking advantage of it. Clearly, a trend has started,” Ruth Dickover, PhD, Director of Forensic Science, University of California, Davis, told the Los Angeles Times.
Indeed, the use of familial DNA testing is moving forward. The Verge reported 19 cold case samples have been identified in recent familial DNA testing and public database searches. It also said two new published studies may propel the technique further.
One study, published in the journal Science, suggests nearly every American of European ancestry may soon be identified through familial DNA testing.
The other study, published in Cell, shows that a person’s relatives can be detected when forensic DNA data are compared with consumer genetic databases.
Noah Rosenberg, PhD (above left), Professor of Population Genetics and Society Biology at Stanford University, is shown above working with Jaehee Kim, PhD (right), a Postdoctoral Research Fellow in Biology, on math that could be used to track down relatives in genealogy databases based on forensic DNA. “This could be a way of expanding the reach of forensic genetics, potentially for solving even more cold cases. But at the same time, it could be exposing participants in those databases to forensic searches they might not have anticipated,” he told Wired. (Photo copyright: Stanford University/L.A. Cicero.)
15 Million People Already in Genealogy Databases
Researchers at Columbia University in New York and Hebrew University of Jerusalem told Science they were motivated by the recent trend of investigations leveraging third-party consumer genomics services to find criminals. But they perceived a gap.
“The big limitation is coverage. And even if you find an individual it requires complex analysis from that point,” Yaniv Erlich, PhD, Associate Professor at Columbia and Chief Science Officer at MyHeritage, told The Verge. MyHeritage is an online genealogy platform.
Others offering consumer genetic testing and family history exploration include 23andMe and Ancestry. As of April 2018, more than 15 million people have participated in direct-to-consumer genetic testing, the researchers noted.
The study aimed to find the likelihood that a person can be identified using a long-range familial search. It included these steps and findings:
Statistical analysis of 1.28 million people in the MyHeritage database;
Pairs of people with “identity-by-descent” were removed to avoid bias, such as first cousins and closer relationships;
Researchers aimed at finding a third cousin or closer relatives for each person in the database;
60% of the 1.28 million people were matched with a third cousin or closer relative.
“We project that about 60% of the searches for individuals of European-descent will result in a third cousin or closer match, which can allow their identification using demographic identifiers. Moreover, the technique could implicate nearly any US individual of European descent in the near future,” the researchers wrote.
In an interview with Wired, Erlich added, “The takeaway is it doesn’t matter if you’ve been tested or not tested. You can be identified because the databases already cover such large fractions of the US—at least for European ancestry.”
Matching Forensic and Consumer Genetic Data
Meanwhile, the study published in Cell by researchers at Stanford University, University of California, Davis, and the University of Michigan also suggests investigators could compare forensic DNA samples with consumer genetic databases to find people related to criminals.
That study found:
30% to 32% of people in a forensic database could be related to a child or parent in a consumer database;
35% to 36% could be tied to a sibling.
These studies reveal that genetic data and familial DNA testing can help law enforcement find suspects, which is a good thing for society. But people who uploaded DNA data to some direct-to-consumer databases may find themselves caught up in searches they do not know about. So may their cousins.
Dark Daily recently covered other similar studies that showed it takes just one person’s DNA to reveal genetic information on an entire family. (See, “The Problems with Ancestry DNA Analyses,” October 18, 2018.) These developments in the use of DNA databases to identify criminals should be an early warning to clinical laboratories building databases of genetic information that, at some future point, law enforcement agencies might want access to those databases as part of ongoing criminal investigations.
Without the beneficial bacteria, infants can develop gut dysbiosis, which can lead to severe chronic diseases
Another key insight into how the human microbiome performs essential functions has been discovered by a research team at the University of California, Davis (UCD). They have learned that nearly all babies born in developed nations no longer have a specific strain of bacteria called B. infantis, which digests a certain type of sugar found in breast milk.
Microbiologists, clinical laboratory scientist, and pathologists will find the UCD researcher’s discovery to be a fascinating insight into a newly-understood function of the human microbiome. Assuming that further research confirms these early findings, it also could lead to a medical laboratory assay for use during pregnancy or after delivery that would enable physicians to determine if the newborn is missing this strain of bacteria and what therapies would be appropriate.
Babies in Developed Nations Lack Beneficial B. infantis Bacteria
“The central benefits of having a microbiota dominated by B. infantis is that it crowds all the other guys out—especially pathogenic bacteria, which can cause both acute illnesses and chronic inflammation that leads to disease,” UC Davis researcher Bruce German, PhD, Professor and Chemist, Food Science and Technology, told the New York Times.
The UC Davis researchers published their study findings in mSphere, a journal of the American Society for Microbiology. In their paper they note that Bifidobacterium Infantis or B. infantis, a beneficial bacteria that aids in digestion, is missing from the microbiomes of infants in developed nations, such as the United States.
The study hypothesized that the reduction and eventual absence of B. infantis in American babies was the consequence of three factors:
An increase in cesarean births;
Use of commercial formulas instead of breast milk; and,
Heightened use of antibiotics.
According to the New York Times, “Dr. German and his colleagues learned about the missing bacterium by studying breast milk. They found that the milk contains an abundance of oligosaccharides, carbohydrates that babies are incapable of digesting. Why would they be there if babies can’t digest them? They realized that these carbohydrates weren’t feeding the baby—they were feeding B. infantis.”
Good versus Bad Gut Bacteria
Because 70-80% of our immune system resides within our gastrointestinal tract, gut bacteria play an important role in our overall health. Breast milk contains essential probiotics and anti-inflammatory compounds that help “friendly” bacteria flourish in the infant gut.
There are more than two hundred different sugars or carbohydrates found in breast milk, known as human milk oligosaccharides (HMOs). They are one of the most copious components in breast milk but are completely indigestible by humans. So, why are they there?
Because they serve a critical role as food for microbes or prebiotics. Scientists have discovered that HMOs present in breast milk are there to feed the B. infantis, not to nourish the baby.
HMOs also act as a decoy to confuse undesirable bacteria from doing damage in the gut.
“Bad” bacteria are inclined to latch onto sugar molecules in intestinal cells. Because HMOs are very similar to those sugar molecules, the undesirable bacteria will instead latch onto the HMOs in a baby’s gut and leave vulnerable intestinal cells alone.
The primary benefits of B. infantis include:
Production of short-chain fatty acids. When infantis digests HMOs, some short-chain fatty acids are released, which provide energy and help control yeast and fungus growth.
Support for gut integrity. infantis signals gut cells in infants to generate proteins that fill gaps between intestinal cells. These gaps can be dangerous as they may allow toxins and bad bacteria to get into the bloodstream.
Keeping undesirable bacteria at bay. infantis consumes HMOs and usurps space in the gut so potentially dangerous bacteria cannot take up residence or cause problems.
Release of sialic acid. As it devours HMOs, infantis churns and releases sialic acid, a crucial nutrient for the brain development of infants.
Production of folate. infantis also produces folate, which is necessary for infant development and growth and the creation of red blood cells.
“The need for clinicians to have a quick and reliable method to determine Bifidobacterium levels in [a] baby’s gut, and an effective way to replace the right Bifidobacterium to correct dysbiosis when detected, are the critical next steps for infant health,” noted Jennifer Smilowitz, PhD (above), Associate Director of Human Studies Research Program for the Foods for Health Institute at UC Davis, and one of the study authors, in a news release. (Photo copyright: UC Davis.)
Alarming Changes to Infant Gut Microbiome
The UC Davis study is the latest example of new insights about the microbiome, which refers to the collected genetic material of human microbiota. This promising field of research is expected to lead to a better understanding of how human gut bacteria affects resistance to certain chronic diseases, such as cancer, and to new clinical laboratory treatments and drug therapies.
Different research initiatives involving the human microbiome continue to indicate that gut bacteria can be a source of useful biomarkers for improving the health of individuals. Dark Daily has covered the study of human microbiome and development of new cancer therapies based on that research for many years.
Microbiome research, however, sometimes uncovers negative findings as well.
Lack of B. infantis, a principle gut microbe, can contribute to gut dysbiosis, which has been linked to chronic health conditions such as:
Researchers observed that reduction in B. infantis in the infant gut also has resulted in a rise in the pH of infant fecal matter. An analysis of 14 clinical studies performed between 1926 and 2017 showed a startling increase of pH from 5.0 to 6.5 in infant stools.
“These alarming changes to the infant gut microbiome and thus, gut environment, may be due to modern medical practices like antibiotics, C-sections, and formula feeding,” Jennifer Smilowitz, PhD, Associate Director of Human Studies Research Program for the Foods for Health Institute at UC Davis, and one of the study authors, noted in a news release. “These are all potentially life-saving medical practices but have unintended consequences on the infant gut microbiome. As a result, certain pathogenic bacteria—those linked to higher risk of health issues, such as colic, eczema, allergies, diabetes, and obesity—thrive.”
The process by which the researchers in this study identified the missing bacteria illustrates how more refined ways to examine molecules in the body are providing streamlined tools to identify elements within the body and their interaction with each other.
This new insight is one more confirmation that the human microbiome will be the source of useful diagnostic biomarkers, associated with medical laboratory therapies that can improve the health of individual patients.
Because of ongoing advances in gene sequencing and the data analytics needed to interpret that information, new approaches to clinical care are becoming available to physicians and pathologists
COLD SPRING HARBOR, NEW YORK—Internationally-recognized as a leader in bringing together the brightest minds in genetics, the Banbury Center at the Cold Spring Harbor Laboratory (CSHL) produced a three-day conference here last week to explore the future state of anatomic pathology and identify opportunities in genetic medicine and image sciences that play to the strengths of the nation’s pathology laboratories.
The Cold Spring Harbor Laboratory has a long history and an enviable reputation. It was founded in 1890 to train teachers in biology. However, by 1904, the laboratory’s mission had been expanded to include research in genetics. In 1924, the research mission was further enlarged to include quantitative biology—in particular, physiology and biophysics.
It was in 1968 that Nobel laureate James Watson, then a professor at Harvard University, accepted the directorship of the Cold Spring Harbor Laboratory while also keeping his professorship at Harvard University. Watson served at some level of leadership until 2008, when he became Chancellor Emeritus. Currently CSHL laboratory houses about 200 research-related personnel. (more…)
