Controlling the genetic genie

By Catherine
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Written by Catherine Bolgar

Advances in genetic sequencing techniques and discoveries about our DNA are helping to identify inherited diseases, and someday may lead to treatments or personalized medicine. But can regulation keep up with the science, securing the health benefits, while protecting those whose test results bring bad news?

Genetic tests promise great insights. They may diagnose disease or find the mutated gene responsible. They can detect whether a genetic disorder could be passed on to children, and which disorders in newborns might need early treatment. And tests can identify biological relationships, as well as victims of crime or catastrophe.

There are about 4,000 to 5,000 diseases that can be tracked back to a mutation in a known gene,” says Alastair Kent, director of Genetic Alliance U.K., in London. “There are probably more but the gene hasn’t yet been identified. They are rare, and most are incredibly rare.”

About 80% of inherited diseases become apparent soon after birth or in early childhood, he says, and most are fatal by age five. There are about 400 rare genetic conditions for which treatments can improve and prolong life, and some recent therapies may cure some people, Mr. Kent says, but “it’s too soon to tell.”

The most prevalent diseases caused by a single gene are Down syndrome, blood-related disorders such as thalassemia, sickle-cell anemia and hemophilia, followed by cystic fibrosis, Tay-Sachs disease, Fragile X syndrome and Huntington’s disease.

Cystic fibrosis treatments have improved life spans, but Huntington’s, a degenerative brain disorder, has no cure—and anyone with the genetic mutation is certain to get the disease. Understandably, people want to test for a late-onset genetic disease usually because a family member already has it. Knowing whether they too are carriers could influence important life decisions, such as whether to have children or retire.

However, you can’t just say, “do my genome,” Mr. Kent notes.

Having a defective gene, such as APOE-e4 for Alzheimer’s, or BRCA1 for breast cancer, doesn’t always lead to the disease. Women with BRCA1, for example, sometimes choose to have a mastectomy to reduce the risk.

Given the difficulties associated with such decisions, most countries try to protect genetic privacy. The European Union requires patient consent for disclosure of genetic information and bans discrimination based on genetic features. In the U.K., insurers have agreed not to ask for predictive genetic test results except for policies above £500,000 ($757,000). In the U.S., the Genetic Information Non-Discrimination Act prohibits discrimination by employers or insurers on genetic grounds.

Companies that conduct genetic tests directly for consumers also guard client privacy. 23andMe, a personal genetics company (named after our 23 pairs of chromosomes) based in Mountain View, Calif., has more than a million genotyped customers. Their data is stripped of personal identifiers such as name, address or email, and aggregated with other data, according to Emily Drabant Conley, vice president of business development.

Though the volume of genetic data is expanding, testing can accomplish only so much. “We don’t have the knowledge to interpret the information that comes out of sequencing except in a relatively small proportion of cases,” Mr. Kent notes.

While some genetic mutations will always result in the related disease, in many cases, it’s not possible to give an exact risk of developing a disorder or to predict its severity. Genetic alterations are not always informative—after all, we all have DNA variations.

“Certain conditions and diseases are genetically determined. There are a number of Mendelian diseases that are almost completely determined by your genes—for example, conditions like Tay-Sachs, cystic fibrosis, and sickle cell anemia. In other cases, genetic factors may increase or decrease a person’s risk for a particular condition, but environmental and lifestyle factors also play a role,” Ms. Drabant Conley says.

In 2009, an Italian court reduced the prison sentence of a convicted murderer after discovering that he carried genetic variants associated with a predisposition to aggressiveness.

“But if you look at people who carry that mutation, some have a fairly aggressive personality but others are successful entrepreneurs,” says Mr. Kent. “You have to be extremely careful in associating complex behavioral characteristics with underlying genetic structures.”

Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion on LinkedIn.

Photos courtesy of iStock

Will dental visits soon be easier?

By Catherine
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Written by Catherine Bolgar

New devices and materials promise to make dentist visits more pleasant, and help maintain our teeth between checkups. Here’s how.

Devices: Dentists may soon be able to eliminate tooth cavities quickly and painlessly without any drilling or filling. Tooth-destroying plaque, which feeds on dissolved food, comprises a complex mixture of bacteria that release acids into teeth, slowly dissolving dental minerals. But researchers at Reminova Ltd., a King’s College London corporate spinoff, have developed a device that re-inserts the calcium and phosphate minerals.

“We can stop the process and we can reverse it,” says Christopher Longbottom, fellow at King’s College London and Reminova co-founder. It’s not straightforward, but he says, we “can speed up the process of remineralization.”

Two or three agents clean out the proteins and lipids that have seeped through the plaque and replaced the minerals, then a tiny, imperceptible current drives the good minerals back into the tooth. The process takes about one hour, which Reminova hopes to reduce to between 20 and 30 minutes.

An alternative method is for a graphene sensor 50 microns thick (i.e., half the width of a human hair) with gold electrodes acting as an antenna, to be printed onto water-soluble silk and “tattooed” onto the tooth. As Manu Sebastian Mannoor, assistant professor at the Stevens Institute of Technology in Hoboken, N.J., explains, the graphene, which conducts the bacteria’s electrical charge, is coated with peptides that bind to bacteria such as streptococcus mutans, listeria or salmonella.

A dentist could read the sensor like a radio frequency identification (RFID) tag to ascertain the extent of any decay or disease. The latter might include Heliobacter pylori, which is associated with stomach ulcers and cancer when found in saliva. Sensors could also be attached to bacteria-hosting objects such as hospital door handles or intravenous bags, warning of exposure to the likes of staphlylococcus.

Materials: For over 150 years, dentists have filled tooth cavities with mercury-based silver amalgam. More recently, researchers have sought alternatives, encouraged not least by the 2013 United Nations Minamata Convention on Mercury, which aims to reduce its harmful health and environmental effects.

One such possibility, for use as fillings and crowns, is glass ionomer cements. These enjoy numerous advantages: they don’t need an intermediary adhesive to bond to the tooth; like a tooth they expand and contract as temperatures change; they’re biocompatible; and they release fluoride. However, “the strength of these materials has not yet reached an optimal level,” says Ana Raquel Benetti, dentist and researcher at the Department of Odontology at the University of Copenhagen.

Dr. Benetti and Dr. Heloisa Bordallo studied the structure of conventional glass ionomer cements, with the aim of improving their durability. “Our work shows liquid mobility within the cements,” Dr. Benetti explains.

By improving the binding of the liquid to the cement structure, the material might become stronger.”

In other advances, scientists at the University of Rochester and University of Pennsylvania have found a way to use nanoparticles to deliver the antibacterial agent farnesol to plaque. Meanwhile, researchers at Anhui Medical University in Hefei, China, and the University of Hong Kong drew inspiration from the way mussels attach themselves to surfaces, and used a similar polydopamine to coat teeth, which helps remineralize their dentin, or interior.

And scientists at the Ninth People’s Hospital, Shanghai Key Laboratory, Shanghai Research Institute of Stomatology and Shanghai Jiao Ton University in China found that graphene oxide can fight bacteria in the mouth. Unlike treatments for tooth and gum-disease that rely on antibiotics (despite increasingly drug-resistant bacteria), graphene oxide destroys the bacteria’s cell walls and membranes, inhibiting their growth. One day, we might all protect our teeth with nanosheets.

 

Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

Photos courtesy of iStock

Calling in Sick

By Catherine
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Written by Catherine Bolgar


One day, your phone might detect that you have cancer and alert your doctor. It’s among the new diagnostics being developed to spot health problems faster.

Cancer cells, bacteria and certain non-infectious diseases give off volatile organic compounds which the blood eventually transports to our lungs to be expelled into the atmosphere, explains Hossam Haick, professor at Haifa’s Israel Institute of Technology. He is part of a team developing a handheld device with gold nanoparticle sensors that can detect volatile organic compounds in breath samples.

Each disease has a unique breath print, he says. The team’s sensors can detect 23 diseases, including cancers of the lung, breast, ovaries, head and neck, lung, stomach, kidney and prostate, as well as pulmonary hypertension, tuberculosis, and even Parkinson’s disease and Alzheimer’s disease.

Cancer “exists in humans for five to 15 years before we start to see its effects,” Dr. Haick says.

If we want to detect cancer early, we have to do it when people feel good. That’s why we want to detect it by exhaling. It’s painless, so people will be willing to do it.”

Dr. Haick started with lung cancer in 2007. “If you detect lung cancer early, the survival rate is 70%,” he says. “If the cancer is at advanced stages, the survival rate is 9%-15%.”

Today, X-rays and computerized tomography scans detect tumors, but only a biopsy (i.e surgery) can determine if they are malignant—and 96% are not, Dr. Haick says. The sensors can distinguish between benign and malignant cancer, thus reducing the need for biopsies.
Dr. Haick hopes to produce a handheld device for around $800, affordable for clinical doctors. He’s also working with a European consortium to integrate the device into smart phones. “When we speak on the phone we exhale a lot of breath, and we can use that to monitor disease,” Dr. Haick says. The phone would alert the owner’s doctor, who would decide how to manage the results.

Similarly, a team at the Mayo Clinic in Rochester, Minn., is working on a noninvasive screening for several cancers simultaneously, by detecting DNA markers in a blood or stool sample.

While cancer lurks for years, infections can become serious in hours. On TV dramas, doctors examine samples under microscopes and find the solution in minutes. In reality, samples are sent to a lab where they are cultured—which can involve growing bacteria or viruses for six to 24 hours—or undergo polymerase chain reaction (PCR), a complex process that takes about six hours.

Emergency room patients with an infection can’t wait that long, so doctors immediately administer a range of antibiotics. But overuse of antibiotics has led to resistance, and in any case the drugs don’t work on viruses.

Jeong-Yeol Yoon, professor of agricultural and biosystems engineering and biomedical engineering at the University of Arizona in Tucson, has found “a whole new way of doing PCR” utilizing interfacial effects, that’s cheaper, easier and much faster—the whole process takes less than 10 minutes.

Normally, PCR identifies the pathogen by looking at the DNA in the sample. The DNA is first extracted and purified, which can take three or four hours. The amount of DNA is tiny, so it’s amplified by an enzyme and heated and cooled repeatedly. Each cycle doubles the DNA, so “if you repeat the cycle 30 times you’ll have about a million copies, theoretically,” Dr. Yoon explains.

Dr. Yoon’s team instead uses an approach called droplet-on-thermocouple silhouette real-time polymerase chain reaction (DOTS qPCR). The method can identify infection after just three to eight cycles. And the process uses water droplets, which separate contaminants, eliminating the time-consuming step of purifying the sample. The entire process, from sample to answer, can take just five to 10 minutes.

Regular PCR requires expensive equipment and trained lab personnel. But Dr. Yoon hopes to make a fully automated DOTS qPCR device for under $1,000, so it can be used in poorer countries where diseases such as Ebola, MERS, SARS and bird flu require speedy quarantines to prevent epidemics.

Genetics play a key part in other new early diagnostics methods. For example, Stanford University researchers have identified a pattern of gene activity that could lead to a quick blood test for sepsis, which kills 750,000 people annually in the U.S. alone. Meanwhile, a University of Utah team has found DNA anomalies that predict how an ovarian-cancer patient will respond to platinum-based chemotherapy. And scientists at the University of Toronto are using next-generation sequencing to match a sample against a database of thousands of bacteria and viruses, eliminating the need to test one by one.

 

Catherine Bolgar is a former managing editor of The Wall Street Journal Europe. For more from Catherine Bolgar, contributors from the Economist Intelligence Unit along with industry experts, join the Future Realities discussion.

Photos courtesy of iStock



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