Paper-Based Medical Technology

Michael weilert MD synthetic biology

Recently, researchers in synthetic biology have been bringing together science, engineering and computing to understand and copy biological life to help achieve new breakthroughs.  There were recently two studies published in the journal Cell, which show how advances in synthetic biology could eventually lead to cheap, reliable diagnostics for diseases such as Ebola, which could be done quickly in the field using only drops of blood or saliva on strips of paper embedded with synthetic biology circuits.

In the first of these studies, scientists from Harvard describe how they brought lab-testing ability to pocket-sized slips of paper by embedding them with synthetic gene networks.  They also spoke about how they created various diagnostics, including strain-specific Ebola virus sensors.  Until recently, progress in synthetic biology has been limited, since scientists were only able to develop synthetic mechanisms within living cells.  However, the research team was able to create a system that allowed them to design synthetic versions of biological mechanisms outside of cells.  The researchers explain how they’ve harnessed the genetic machinery of cells, and then embedded them in the fiber matrix of paper, which can then be freeze-dried for storage and transport, allowing researchers to take synthetic biology out of the lab setting and use it anywhere.

Through their work, the researchers have developed a wide range of diagnostics and biosensors, which incorporate proteins that fluoresce and change color to show that they’re working.  Once they’ve been freeze-dried, these paper-based tools can be stored for up to a year.  To be activated, all you need to do is add water.  When used in a laboratory, this technology allows researchers to save both time and costs compared to conventional methods; certain procedures that would typically take between 2 and 3 days can now be done in as little time as 90 minutes.

For their second study, the researchers created an Ebola sensor through the “toehold switch”, a flexible and highly programmable system for controlling gene expression.  While the toehold switch was originally used to work inside living cells, the team was able to change its function to their signature freeze-dried paper method.  The toehold switch can be programmed to switch on the production of a specific protein after detecting the proper sequence of genetic code.  According to the team, it’s also possible to link multiple toehold switches to each other and create a complex circuit to carry out a series of steps, such as detecting a pathogen and then delivering the appropriate therapy.


The Effectiveness of Health Apps

Michael Weilert MD Health Apps

Various health apps

These days, it seems like there’s a mobile app for just about everything.  Currently, nearly 20% of smartphone users have at least one app on their phone that allows them to track and/or manage their health, and by next year, it’s been estimated that 500 million smartphone users around the world will be using one.  They allow us to monitor nearly every factor that impacts health, including weight, blood pressure, exercise, cholesterol levels, heart rate, sleep quality and even help detect cancer.  While these seem to have some great benefits, there are a lot of people who still have mixed feelings about these apps.

Last year, the IMS Institute for Healthcare Informatics analyzed over 40,000 health care apps, and discovered that only 16,275 of these are directly linked to patient care and treatment, while others do nothing more than provide information that doesn’t improve patient health or well-being in any way.  The apps that are downloaded most frequently claim to help with dieting, weight loss and fitness, such as MyFitnessPal, which generated 40 million users last year alone.  However, the report from IMS claims that this app’s effectiveness didn’t meet its popularity.  They pointed out that very few studies show how effective calorie-counting apps are.  A study from the University of Massachusetts Medical School had similar findings.  The team found that 25% or fewer lifestyle-based strategies for weight loss, such as portion control and identifying reasons behind overeating, were only incorporated in 28 of the apps, which means that they were most likely not at all effective for weight loss.

These results reveal that many app developers aren’t even including proven behavioral strategies in their apps, and without long-term data on whether these apps work, most doctors are hesitant to recommend them as an effective solution for poor eating habits.  However, not all research condemns the effectiveness of such apps; one 2012 study from Northwestern University claimed that an app that tracked eating and physical activity helped users lose 15 pounds and keep the weight off for at least a year.  However, the team admitted that the app was only effective when used alongside other weight loss support, such as nutrition and exercise classes.

While some weight loss apps are ineffective, others could actually be detrimental to health; last year, researchers from the University of Pittsburgh Medical center questioned the accuracy of four health apps that claim to detect skin cancer.  The team discovered that even the most accurate of cancer-detecting apps missed 18 of the 60 lesions diagnosed as melanoma, having deemed them “low-risk” for cancer.  Of course, these apps state that they’re only designed for educational purposes, and shouldn’t take the place of actual medical care, but researchers are nonetheless worried about these findings.  The amazing thing is that you don’t need to be a medical professional, or even source medical input to develop a health app, which many find disconcerting.


New Drug For Leukemia

A new drug target for treating leukemia has been identified as part of the largest ever genetic analysis of tumor growth in childhood blood cancer.  T-cell acute lymphoblastic leukemia is one of the most common and aggressive childhood blood cancers.  Every year, an estimated 500 american youths with this blood cancer fail to achieve remission through standard chemotherapy.  With genetic scanning techniques, researchers at NYU Langone Medical Center identified 6,023 long, non-coding strands of RNA active in immune system T cells taken from a group of T-cell acute lymphoblastic leukemia patients.  These strands of RNA from the 15 patients were not active in the healthy T cells of three young people who didn’t have leukemia.

Publishing their findings in the journal Cell, researchers describe how they were able to block the action of one of these RNA strands, leukemia-induced non-coding activator RNA-1 or “LUNAR1”, which slowed leukemia progression.  Long-coding sequences of RNA, such as LUNAR1, are more frequently being recognized as important in regulating cell functions.  Beforehand, they were more though of as “junk DNA”, which help transcribe DNA without fully assembling proteins.  Although LUNAR1 does not produce cancerous proteins itself, it forms an important part of the signaling action of a protein related to many cancers.


Leukemia cells, as seen underneath a microscope.

The researchers discovered LUNAR1 through examining RNAs active in a biological pathway known as NOTCH1.  This pathway is active in at least half of all T-cell actue lymphoblastic leukemia patients, and the researchers discovered that LUNAR1 was the most highly expressed long, non-coding RNA associated with NOTCH1.  Among normal T cells, NOTCH1 is inactive, and LUNAR1 and another long, non-coding RNAs are not transcribed and can’t bind to an activate IGF-1R.  They found that LUNAR1 was overproduced in 90% of the leukemia patients in the study.  Drugs that block LUNAR1 could therefore form the basis of an alternative treatment to chemotherapy, which kills both healthy cells and cancer cells.

The study reveals that LUNAR1 is highly specific for T-cell acute lymphoblastic leukemia, and plays a key role in how this cancer develops.  To test this hypothesis, the scientists transplanted human leukemia T cells into mice and then successfully stalled tumor growth in a subset of the mice by chemically blocking LUNAR1.  This research suggests that future therapies for cancer should take into account the RNA make-up of individual patients, as well as mutations in their DNA.  The team now needs to develop drugs that will more effectively inhibit LUNAR1, perhaps through targeting its component nucleotides.