Issue 83  December 7th 2018

Why are scientists so upset about the first Crispr babies?

A Chinese scientist recently claimed he had produced the world’s first gene-edited babies, setting off a global firestorm. If true — the scientist has not yet published data that would confirm it — his actions would be a sensational breach of international scientific conventions. Although gene editing holds promise to potentially correct dangerous disease-causing mutations and treat some medical conditions, there are many safety and ethical concerns about editing human embryos.

What happened? The scientist, He Jiankui, said he used Crispr, a gene-editing technique, to alter a gene in human embryos — and then implanted the embryos in the womb of a woman, who gave birth to twin girls in November.

Which gene did he edit and why? The gene is called CCR₅. It creates a protein that makes it possible for H.I.V., the virus that causes AIDS, to infect people’s cells. Dr. He said that with the help of an H.I.V./AIDS advocacy organization in China, he recruited couples in which the man had H.I.V. and the woman did not. He used the Crispr-Cas9 editing technique to try to disable the CCR₅ gene in their embryos, with a goal, he said, of creating babies who would be resistant to H.I.V. infection.

Why are scientists up in arms? Changing the genes in an embryo means changing genes in every cell. If the method succeeds, the baby will have alterations that will be inherited by all of the child’s progeny. And that, scientists agree, is a serious undertaking that must be done with great deliberation and only to treat a serious disease for which there are no other options — if it is to be done at all.

Discovery brings saliva test for Alzheimer’s disease one step closer

The discovery of three biomarkers that detect mild cognitive impairment and Alzheimer’s has the potential to lead to the development of a saliva test to diagnose the chronic neurodegenerative disease.

University of Alberta scientists Liang Li and Roger Dixon examined saliva samples from three sets of patients: those with Alzheimer’s, those with mild cognitive impairment and those with normal cognition. Using a powerful mass spectrometer, the pair examined more than 6,000 metabolites—compounds that are part of our body’s metabolic processes—to identify any changes or signatures between groups.

“We found three metabolites that can be used to differentiate between these three groups,” said Li, adding that while the results show promise, the sample size was small. “If we can use a larger set of samples, we can validate our findings and develop a saliva test of Alzheimer’s disease,” he explained.

A saliva test would prove useful in clinical settings for its ease and non-invasive nature. It also has the potential to detect neurodegenerative diseases sooner, allowing for early intervention.

“So far, no disease-altering interventions for Alzheimer's disease have been successful,” said Dixon. “Researchers are aiming to discover the earliest signals of the disease so that prevention protocols can be implemented.” The biomarkers could also be used to conduct efficacy testing for treatments.

What defines a stem cell? Scientists rethink the answer

For the past three years, researchers at the Hubrecht Institute in the Netherlands have been painstakingly cataloging and mapping all the proliferating cells found in mouse hearts, looking for cardiac stem cells. The elusive cells should theoretically be able to repair damaged heart muscle, so the stakes in finding them have been high. Indeed, that search, involving many labs over decades, has been marked by heated debate and, recently, a call for the retraction of more than 30 papers for falsified data.

This week, however, Proceedings of the National Academy of Sciences is scheduled to announce the results of the Hubrecht team’s work: no evidence of cardiac stem cells at all.

That conclusion, which confirms a long-standing suspicion among some in the field, cuts to the heart of a deeper question — about what it means to be a stem cell. As more sophisticated technology has revealed just how plastic and heterogeneous cell populations can be, some researchers have transitioned from viewing “stemness” as the defining trait of a cell category to viewing it as a function many types of cells can perform or contribute to.

In fact, researchers have found that… “true” stem cells vary in potency and behavior. “We’re learning there’s much more heterogeneity in what we thought were pretty homogeneous populations,” Hoggatt said. Read the article to find out why this is the case!

Researchers grow functional network of blood vessels at centimeter scale for the first time

[A] research group at the University of Delaware has pioneered methods to grow a self-assembling, functional network of blood vessels at a size relevant for human use. Jason Gleghorn and his colleagues are the first to make this system work at this scale, and their results were recently published in the journal Biomaterials.

The team embedded human blood vessel cells into a gel made of collagen, a protein found in connective tissue such as skin and joints. The goal was to determine the physical conditions necessary to make the cells grow, multiply and connect with each other so that a network of blood vessels assembled itself.

[Using] a powerful confocal microscope at the Delaware Biotechnology Institute, the group found that the density, or stiffness, of the collagen gel affected how the cells suspended within it behaved, ultimately affecting the size and connectivity of the vessels. The team found that by perturbing their system in a specific way, they could affect the size and shape of the vessel networks under assembly.

Gleghorn's team also found that their lab-grown blood vessels were perfusable, suggesting that blood could flow through them without leaking out of the vessels into surrounding gel. The vessel networks can also form throughout a variety of shaped gels, meaning that this system could be useful for building blood vessel networks in tissues with complicated shapes, such as the meniscus cartilage that pads your knees or a large skin graft for burn patients.

A universal DNA nano-signature for cancer

Researchers from the University of Queensland's Australian Institute for Bioengineering and Nanotechnology (AIBN) have discovered a unique nano-scaled DNA signature that appears to be common to all cancers.

Based on this discovery, the team has developed a novel technology that enables cancer to be quickly and easily detected from any tissue type, e.g. blood or biopsy. [The study] reveals new insight about how epigenetic reprogramming in cancer regulates the physical and chemical properties of DNA and could lead to an entirely new approach to point-of-care diagnostics.

In healthy cells, these methyl groups are spread out across the genome. However, the AIBN team discovered that the genome of a cancer cell is essentially barren except for intense clusters of methyl groups at very specific locations. This unique signature -- which they dubbed the cancer "methylscape", for methylation landscape -- appeared in every type of breast cancer they examined and appeared in other forms of cancer, too, including prostate cancer, colorectal cancer and lymphoma.

They also discovered that, when placed in solution, those intense clusters of methyl groups cause cancer DNA fragments to fold up into three-dimensional nanostructures that really like to stick to gold. Taking advantage of this, the researchers designed an assay which uses gold nanoparticles that instantly change colour depending on whether or not these 3D nanostructures of cancer DNA are present.

No bleeding required: Anemia detection via smartphone

Biomedical engineers have developed a smartphone app for the non-invasive detection of anemia. Instead of a blood test, the app uses photos of someone's fingernails taken on a smartphone to accurately measure how much hemoglobin is in their blood. The results are scheduled for publication in Nature Communications.

"All other 'point-of-care' anemia detection tools require external equipment, and represent trade-offs between invasiveness, cost, and accuracy," says principal investigator Wilbur Lam, MD, Ph.D. "This is a standalone app whose accuracy is on par with currently available point-of-care tests without the need to draw blood."

The app is part of the Ph.D. work of former biomedical engineering graduate student Rob Mannino, Ph.D., who was motivated to conduct the research by his own experience living with beta-thalassemia, an inherited blood disorder caused by a mutation in the beta-globin gene.

Mannino and Lam say that their app could facilitate self-management by patients with chronic anemia, allowing them to monitor their disease and to identify the times when they need to adjust their therapies or receive transfusions, possibly reducing side effects or complications of having transfusions too early or too late. The researchers say that the app should be used for screening, not clinical diagnosis.

Diagnostic stewardship reduces C. difficile testing, saves money

Gregory R. Madden, MD, an infectious disease clinical fellow at the University of Virginia Medical Center, explained that the most common test used in hospitals to detect C. difficile — the nucleic acid amplification test — is unable to differentiate between infection and colonization in patients.

“As a result,” Madden told Infectious Disease News, “it is estimated that up to half of patients who test positive for C. difficile in the hospital may not actually require treatment, which ultimately leads to wasted health care dollars.

In a retrospective cost analysis, Madden and colleagues explored computerized clinical decision support (CCDS) -related cost savings from reduced testing and fewer hospital-onset C. difficile infection events, as well as the cost of building the tool and providing financial incentives to staff for improving C. difficile testing.

They estimated that the total laboratory cost — defined as materials and labor — was $31.36 per test. Additionally, the estimated attributable cost per hospitalized C. difficile infection case was between $3,669 and $9,197. Staff received a 0.8% financial incentive based on their salaries, according to the study. The researchers estimated a $1,000 cost associated with the technology used to create the CCDS tool, including developing the question algorithm and building and testing the software. All told, the cost analysis revealed a net annual savings of $61,524 related to the CCDS, largely due to the reductions in inpatient C. difficile infection treatment and laboratory diagnostics, Madden and colleagues said.