DNA sequencing firm partners with big HIT players

Illumina, a key vendor of DNA sequencing firm to enable clinicians and researchers to read and comprehend genetic variations, is partnering with IBM and Philips in separate genomic research projects.

IBM will integrate its Watson for Genomics decision support product, deployed on technology from Quest Diagnostics, with solid tumor profiling panel of Illumina that can depict a set of variants across 170 different kinds of genes to assist in development of personalized treatment options for cancer sufferers.

This will speed a procedure that generally now takes about a week to complete. The challenge in genomic testing is the expertise needed to give interpretation services, claims Rob Merkel, vice president of oncology and genomics at IBM Watson Health, and Watson can do the process in about 5 minutes.

“Illumina, the DNA sequencing firm, will integrate our interpretations into its latest 170-gene panel,” Merkel states. “When you sequence a tumor against healthy tissue, you can observe variations between healthy tissue and the tumor by comparing the DNA side by side.”

To do this, Watson compares the DNA to develop molecular profile analyses to recognize aberrations causing the tumor, establish biological pathways of the tumor and conduct drug analyses, all to verify what medicines and/or clinical trials are best suitable for the sufferer.

In its agreement with Philips, Illumina will integrate its DNA sequencing with Philips’ cloud-based genomics platform to support the acquisition, analysis and interpretation of genomics information during cancer research.

Both agencies are seeking U.S. healthcare systems to work with them in establishing oncology precision medicine programs. Participating researchers will have approach to advanced analytics, thorough learning technologies and a range of reference materials.

The aim is to seek new ways to quickly and precisely interpret genomic findings in the context of a sufferer’s condition, in accordance to Philips.

“While cancer sufferers can have hundreds of gene variants in their tumors, merely a small number might really drive the individual’s specific cancer or might have actionable therapeutic implications for a specific patient. The sufferer’s history, related lab tests and cancer type are required for a meaningful interpretation of the genomic data,” a Philips spokesman points out.

 

‘Medicalized’ smartphones to put health information in hands of sufferers

The world is on the verge of a 4^th industrial revolution, featured by artificial intelligence, robots, big data, and thorough learning and analytics, but medicine is yet stuck at the start of the 3^rd industrial revolution, which has already brought digital abilities to billions of persons globally.

That is the contention of Eric Topol, MD, director of the Scripps Translational Science Institute and chief academic officer of Scripps Health in La Jolla, Calif., who claims that the digital revolution has been appearing since the middle of the previous century. Even so, the healthcare industry sustains to just minimally leverage IT.

Although, Topol, a practicing cardiologist at the Scripps Health observes mobile tools as the technological enabler for the “democratization” of medicine by offering sufferers control of their own health information, which has historically, been the key domain of all doctors.

Clients are “moving from passengers to co-pilots,” challenging the conventional “doctor knows best” mindset among physicians, in accordance to Topol. Initially, medicine has been reluctant to make such alterations.

Nevertheless, with more than 80% of U.S. adults owning smartphones, he considers healthcare is on the cusp of a significant shift in who controls information. That transformation of control will effectively move power from physicians to sufferers, who will play a dramatically more key role in their own care. In the future, clients armed with mobile phones will accumulate information from wearable sensors to stop or better treat health situations, Topol stated, with these tools facilitating the role of a digital medical assistant.

On-demand the medicine is the core element of the future, and face-to-face office visits are going to become the minority of physician-sufferer communication moving forward, Topol assumed. In fact, he discussed that the sufferer’s bedroom will become the hub of remote monitoring, giving continuous detecting of vital symptoms from the home, as well as virtual consultations through telehealth-enabled smartphones. “The telemedicine revolution has ultimately arrived, and it is moving towards prime time.”

In accordance to Topol, a professor of genomics, mobile health technology won’t just markedly cut healthcare prices but will put personalized medicine in the hands of sufferers by contextualizing the information they produce in their real world, not merely the office of doctor.

“In a small droplet of blood, there is much information,” Topol analyzed, which can be tested at home by clients. “It is not merely blood. It could be also the sweat, urine, and breath.” There is going to be pocketing DNA sequencers the size of a flash drive that persons will utilize immensely, he assumed. “They already exist now-a-days.”

Additionally, clients today can order a mobile tool through Amazon for $69 and conduct a cardiogram anytime they need “when they feel that is something’s not correct, when they are dizzy or when they feel their heart is racing,” he stated. An algorithm embedded in the smartphone software updates sufferers on their heart rhythm, which can “preempt having to go to an emergency room when most of the period (the condition of person) is normal.”

By wearing a small sensor on the arm or abdomen connected to a smartphone, diabetic sufferers can get glucose readings every 5 minutes, in accordance to Topol. Further, he claimed that an experimental contact lens being established by Google can painlessly measure glucose levels in tears, replacing the finger sticks that millions of persons with diabetes utilize to draw blood.

For persons with Parkinson’s disease, Topol disclosed that there is a free app that, at any moment in period, quantifies an individual’s tremor, voice, and gait to assist to evaluate whether they should take their medication and in what dose.

Additionally, ear infections are a usual reason for parents to take their kids to the pediatrician. Although, he stated that mothers and fathers can utilize their smartphones to diagnose their kid’s ear infection through the cloud with an algorithm that investigates images for the availability of fluid trapped in the middle ear.

Hospital-based sleep studies, which are believed to be among the top revenue drivers for several health networks, could also be a thing of the past in Topol’s emerging app economy. He inquired: How many persons would go to a sleep lab and pay $4,000 for a sleep research when you can take a sensor in a reusable Band-Aid that charges $1 to make and gains nearly all of the similar information?

When it comes to other modern sensor technology, Topol stated that it is now possible to observe sweat and physiologic metrics with skin sensors. “For instance, exposure to the proposed pesticides and even things such as nitric oxide which could assume an asthma attack.”

 

Healthcare tailors with precision medicine

Next-Generation Sequencing (NGS) is generating tomorrow’s cures. Illumina (Solexa) sequencing, Roche 452 sequencing, Ion torrent (Proton/PGM) sequencing, and SOLiD sequencing are revolutionizing the study of genomics and molecular biology. Next-generation sequencing is enabling precision medicine for an individual sufferer by connecting potential biomarkers to access clinical results. This is digital healthcare.

The breakthrough

The 1^st DNA sequencing began in the early 1970’s, but this was slow and extremely expensive which prevented scaling for the benefit of population health. By the period of 1990’s many new methods for DNA sequencing were developed and by the year 2000, these procedures were executed commercially by DNA sequencers (a scientific instrument used to automate the DNA sequencing process). Next-generation sequencing is high-throughput DNA sequencing, which sequences millions or billions of DNA strands in parallel, reducing the need for the fragment-cloning methods utilized in Sanger genome sequencing – making better the speed critical for patient usability.

Exposure to tobacco smoke causes immediate damage, says new surgeon general's report

Report focuses on how tobacco smoke causes disease

Exposure to tobacco smoke – even occasional smoking or secondhand smoke – causes immediate damage to your body that can lead to serious illness or death, according to a report released today by U.S. Surgeon General Regina M. Benjamin.  The comprehensive scientific report - Benjamin’s first Surgeon General’s report and the 30^th tobacco-related Surgeon General’s report issued since 1964 - describes specific pathways by which tobacco smoke damages the human body and leads to disease and death.

The report, How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease, finds that cellular damage and tissue inflammation from tobacco smoke are immediate, and that repeated exposure weakens the body’s ability to heal the damage.

“The chemicals in tobacco smoke reach your lungs quickly every time you inhale causing damage immediately,” Benjamin said in releasing the report.  “Inhaling even the smallest amount of tobacco smoke can also damage your DNA, which can lead to cancer.”

"Over the last two years we have stepped up efforts to reduce tobacco use, including implementing legislation to regulate tobacco products, investing in local tobacco control efforts and expanding access to insurance coverage for tobacco cessation" said Secretary of Health and Human Services Kathleen Sebelius. "This will remain a key priority of this Administration."

The report also explains why it is so difficult to quit smoking. According to the research, cigarettes are designed for addiction. The design and contents of current tobacco products make them more attractive and addictive than ever before. Today’s cigarettes deliver nicotine more quickly and efficiently than cigarettes of many years ago.

Tobacco smoke contains a deadly mixture of more than 7,000 chemicals and compounds, of which hundreds are toxic and at least 70 cause cancer. Every exposure to these cancer-causing chemicals could damage DNA in a way that leads to cancer. Exposure to smoke also decreases the benefits of chemotherapy and other cancer treatments. Smoking causes more than 85% of lung cancers and can cause cancer almost anywhere in the body. One in three cancer deaths in the U.S. is tobacco-related.

The report describes how the delicate lining of the lungs becomes inflamed as soon as it is exposed to the chemical mixture in cigarette smoke. Over time, the smoke can cause chronic obstructive pulmonary disease including emphysema and chronic bronchitis.

Even brief exposure to secondhand smoke can cause cardiovascular disease and could trigger acute cardiac events, such as heart attack. The report describes how chemicals from tobacco smoke quickly damage blood vessels and make blood more likely to clot. The evidence in this report shows how smoking causes cardiovascular disease and increases risks for heart attack, stroke, and aortic aneurysm.

Smoking causes many other harmful effects throughout the body, including making it harder for diabetics to control their blood sugar.  Smoking makes it harder for women to get pregnant and can cause a miscarriage, preterm delivery, low birth weight, as well as damage to fetal lungs and brain tissue. Babies who are exposed to secondhand smoke are more likely to die from sudden infant death syndrome, the report finds.

“This report makes it clear – quitting at any time gives your body a chance to heal the damage caused by smoking,” the Surgeon General said. “It’s never too late to quit, but the sooner you do it, the better.”

Fortunately, there are now more effective ways to help people quit than ever before. Nicotine replacement is available over the counter and doctors can prescribe medications that improve the chances of successful quit attempts. Smokers can also call 1-800-QUIT-NOW for help.

To help communicate the report findings as widely as possible, the Surgeon General unveiled an easy-to-read guide with practical information about how tobacco smoke causes disease, A Report of the Surgeon General: How Tobacco Smoke Causes Disease: What It Means to You.

Copies of the full report, executive summary, and the easy-to-read guide may be downloaded at www.surgeongeneral.gov/library/tobaccosmoke/index.html.

To order printed copies of these documents, go to http://www.cdc.gov/tobacco and click the Publications Catalog link under Tools & Resources.
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Contents: Human & Health Services USA

Lab-on-chip traces circulating tumor cells

Liesbet Lagae is group leader of the nano-enabled systems group in IMEC. She is involved in several European and national research projects concerning magnetic and optical materials and devices and their application in the field of biosensing. Liesbet Lagae holds a PhD from the Catholic University of Leuven. Contact: Liesbet.Lagae@imec.be

Imagine a medical laboratory performing a genetic test to detect metastasis from blood in a breast cancer patient. Shrink this laboratory down to an area of 1x1cm² and you have a lab-on-chip. The tools in the real-life lab are replaced by microsystems, the medical staff placing the blood sample in subsequent tools, is replaced by microfluidic channels. The huge advantage of such systems is that they enable a fast, easy-to-use, cost-effective test method which can be performed in a doctor’s office or even near the patient’s bed.

Unfortunately, there are no real lab-on-chip systems on the market yet. The systems that are commercially available – often wrongfully labeled ‘lab-on-chip’ – only perform one task, for exa mple moving a fluid from one place to another. True lab-on-chips are multifunctional.

Technologies for true multifunctional lab-on-chip systems are being developed by research labs worldwide. One of these labs is situated in the Belgian nanoelectronics research center IMEC. They develop for example microsystems that are able to pick up specific cells in blood samples, to perform cell lysis, to realize amplification and detection of the cell’s genetic material.

Together with a German SME, specialized in test kits for detecting circulating tumor cells (CTC) in cancer patients, IMEC tailored its generic lab-on-chip technologies towards this application. Three lab-on-chip modules were developed integrating the different analytical steps for the isolation and characterization of circulating tumor cells in a blood sample.

Figure 1: Schematic presentation of the different operations to be performed by the lab-on-chip for the isolation and characterization of rare cells.

Circulating tumor cells are tumor cells that invade the bloodstream and cause distant metastases. The levels of CTC detected in metastatic breast cancer patients before and after therapy were shown to be significant predictors of progression and overall survival. The very low levels of CTC in peripheral blood, i.e. down to less than 1 cell per ml, make their detection very challenging.

Module 1: Cell isolation and detection

In a first step, the blood sample is injected into the LOC and mixed with antibody-coated magnetic beads. These beads bind specifically with the tumor cells. Next, a magnetic force is applied, allowing the transport of both the bead-cell complexes and excessive beads. Due to their different magnetophoretic mobility, the bead-cell complexes have a different velocity and can be separated from free beads. Combining such an isolation device with an H-shaped fluidic channel allows to specifically force the beads-cell complexes into the detection channel, where they are counted by flowing them over a spin-valve magnetic sensor.

Figure 2: Cell isolation device bridged between two channels. Cell-bead complexes are moved towards a detection channel, while free beads are flown to the outlet.

Module 2: RNA extraction and amplification

Following isolation and detection, the CTC are lysed and their mRNA is extracted. The genes that are important for the identification of the tumor cells are amplified (cDNA). For this step, MRC Holland has developed kits for the multiplexed amplification of specific breast cancer genes.

The microsystem for cell lysis and mRNA amplification is based on an intelligent design of heating elements, active cooling principles and fluidic channels together with IMM, a german institute specializing in microfluidics.

Module 3: DNA detection

In the detection module, the amplified cDNA is identified. This can be done using an array of electrochemical or magnetic sensors. With the electrochemical detection (implemented by URV), one can reach a sensitivity in the range of nanomolar, while the magnetic-based detection is currently much more sensitive (picomolar). The magnetic-based detection strategy consists of binding functionalized magnetic beads to the target cDNA and counting these complexes with a magnetic sensor.

Even in the large equipment that is used today to count tumor cells in blood (e.g. Cellsearch), this extra step of DNA detection is not performed. However, it increases the test reliability and provides interesting information for doctors about the subclasses that the tumor cells belong to so that the best therapy can be selected.

Many possibilities

Today, the three modules described above are ready and are being tested with spike blood (i.e. blood with a known number of tumor cells). In a next phase, the lab-on-chip modules will be tested with blood from patients, and finally the modules will be integrated on one chip.

Future work will focus on clinical studies using the LOC approach as well as evaluating other application domains for the LOC technology, for example: detecting other sorts of cancer, tracing fetus cells in the blood of the mother (to detect mucoviscidose or other genetic diseases) or assisting in stem cell research.

This research was performed in the framework of the European MASCOT project. Project partners are: IMEC, Universitat Rovira i Virgili (URV), Fujirebio Diagnostics AB , Institut für Mikrotechnik Mainz (IMM) , AdnaGen AG, Norwegian Radium Hospital and MRC-Holland.