Country doctor James DeLine talks about his work with the Amish

In 33 years at the La Farge clinic, Dr. James DeLine has gained the trust of many Amish. He understands their beliefs and their financial limitations, and he leaves the medical decisions to the families.

Mark Hoffman, Milwaukee Journal Sentinel

MILWAUKEE, Wis.It is 5 degrees below zeroand a light powdering ofsnow swirls across the roads of Vernon County.Afew horses and buggies clop through the chillmorningair, but Perry Hochstetler leaves his buggy at the family farmand has a driver take him to his doctors appointment.

TheHochstetlersare Amish. With no health insuranceanda modest income, they cannot afford most doctors.

They can afford James DeLine, once the lone doctor in the western Wisconsin village of LaFarge. Population 750.

When he became the village doctor in 1983, DeLine had no experience treating the Amish and no idea the crucial role they would play in his work. Today, about 20% of the doctors patients are Amish or Old Order Mennonite, part of a Christian population called Plain People. They are known for their separation from the modern world and adherence to a simple lifestyle and unadorned dress.

Something of a throwback himself,DeLine, 65, is a short,bespectacledman with a walrus mustache, a doctor who carries a brown medical bag to house calls. For years, he carried his equipment in a fishing tackle box.

He knows the families on every local farm and their medical histories. He knows whos beenborn,andcalls on the mothers and infants to make sure they are healthy. He knows whos dying, and looks in on them in their final days, sitting by their bedside, talking in a gentle voice, making sure they have what they need for pain.

Amish farms are clustered together along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

As a young doctor,DeLine never imagined he would find himselfsomedaywith one foot planted solidly in medicines past, the other in its future.

The doctor who makes housecallsalso collaborates with English and American geneticists studying some of the rarest diseases on Earth. Some occur at much higher levels among the Amish, Mennonites and other closed communities that dont allow marriage to outsiders. This prohibition increases the likelihood that when a rare, disease-causing mutation appears in the community, it will take root and pass from generation to generation.

It has taken DeLine and his staff years to gain the trust of Plain People, some of whom are wary of medicine and technology.Often,theyfear that going to a hospital or clinic will mean surrendering the decision-making to doctors who neither respect their beliefsnor understand their financial limitations.

DeLine, not a religious man himself, accommodates the beliefs of patients and parents; he has always viewed them as the ultimate decision-makers.

At first glance, Hochstetler seems an unlikely candidate for a rare disease or a health problem of any kind. Work at the local sawmill and his family farm has given the 26-year-old father of two a lean muscular frame. Beneath the skin lies another story.

He has the vasculature of an 80-year-old smoker,DeLinesays.

He inherited the genetic mutation that causes an illness most people have never heard of: sitosterolemia. Only 100 cases have been described in the medical literature, but DeLine has 13 patients with the condition, including four of Hochstetlers 10 siblings and their father.

The disease prevents the body from getting rid of lipids from vegetable oils and nuts, causing them to build up and clog the arteries.

Since diagnosing the disease,DeLinehas treated Hochstetler with a cholesterol-lowering drug called Zetia.

Without diagnosis and treatment,Hochstetlercould by now havesuffereda heart attack, a trauma that Zetia should delay, thoughfor how long isuncertain. There is no cure for sitosterolemia.

Im not afraid, he says. If I die young, I guess Im going to die young. I cant do much about it. I cant say I ever get low and have the blues about it.

Saving grace: The story of an Amish community and the fight for their children's lives

A blizzard almost kept the doctor and village from their appointment.

It was February 1983. DeLine drovehis familyover hilly country roads, staring out the windshield into flurries and fearingtheir carmight not makeit to LaFarge.

DeLinehad just completed his residency at the Wausau Hospital Center. Now, a10-membercommitteeof localswas recruiting him to fill LaFargesvacancy for a doctor. Thevillage had beenwithout one for a couple ofyears.

The doctor liked the friendly villagers, a welcome change from the suit-and-tie types hed interviewed with in other places.

He was 28 years oldwith a bad car, a growing family and $30,000 in unpaid student loans. The average salary for a family doctor in America was then around $80,000, enough to settle down and beginpaying offhis debt.

But the people of LaFargewantedDeLine needed him. Their offer: $20,000.

That would have to coverDeLinesannual salary, the salary of an assistant to answer the phones and handle billing, plus all the clinic equipment andexpenses. .

DeLine took the offer.

The photo of country doctor Ernest Guy Ceriani, made famous in a groundbreaking Life Magazine photo essay by W. Eugene Smith, hangs on James DeLine's refrigerator door at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

DeLinegrew up in New Lenox, Illinois, a farming community outside Joliet.

The village of 1,750 was mostly cornfields. DeLine remembers it asthe kind of place where children grew up building forts during the day and watching bonfires at night. DeLine had twin sisters five years younger than him. Their father owned a restaurant.

From an early age, though, itjust seemed like Id be going to medical school. It was meant to be.

DeLineremembers nights when he could hear his mother struggling to breathe. He could hear his father, too, trying to persuade her to go to the hospital.

She had rheumatic heart disease and took blood thinners starting in her 30s. She sometimes joked about needing a valve job.

DeLinewas 17 when his mother went in for the procedure.

He saw her once after surgerybut I didnt like how she looked.About the third day, his mother suffered cardiac arrest. She was resuscitated but had sustained a severe brain injury. Days later, the family shut off life support. She was 42.

One week after her death, JamesDeLineset out to become a doctor,leavinghome for the University of Illinois in Urbana-Champaign.

Physician James DeLine eases into his work day starting at 5 a.m. at his home in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

University life was hard.DeLineremained so miredin grief that when he ate, he suffered terrible abdominal pain and had to lie on his stomach for relief.

Still, he took on a demanding schedule.Driven students tended to enter the more advanced honors program in either chemistry orbiology. DeLine, a physiology major, enrolled in both.

He paid for college through restaurant jobs and financial aid.

He went on to medical school, first in Champaign, then at the University of Illinois campus in Chicago. He lived in the citys Little Italysection on the nearwestside. There he met his future wife, Ann Doherty, who worked in a print shop.

DeLinegraduated from medical school on June 7, 1980. The next day, he and Ann married.

A week later, he started his residency in Wausau.

He would work a 24-hour shift, take 24 hours off, then head back for another 24 hours at the hospital. By the time Id stagger home for some rest, he says, I was sleep-deprived, hungry, with a headache.

The schedule bothered his wife. She missed him.In his next job, she would see even less of him.

Physician James DeLine checks on Dean Pease at Vernon Memorial Healthcare in Viroqua. Pease was admitted to the hospital for breathing difficulties.Mark Hoffman / Milwaukee Journal Sentinel

In LaFarge,DeLineworked harder than he had in his residency.

He was on call 24 hours a day, seven days a week. To make ends meet, both for his family and the clinic,DeLineworked five shifts a month in the emergency room at Vernon Memorial Hospital in Viroqua.

Some days he would work 9 a.m. to 5 p.m. at the clinic, then drive to the hospital and work 6 p.m. to 8 a.m. in the emergency room. He would return to the familys home just in time to shower and get to the clinic by 9.

There were times when he was tired, but it didnt slow him down, Marcia Bader, his now-retired office managersays. It was that deep-seated caring that kept him going.

After a morning of driving around visiting patients, physician James DeLine, right, updates the staff at his clinic.Mark Hoffman / Milwaukee Journal Sentinel

It was his wife,AnnDeLine, too.

The woman who had dreamed of being a mother did everything for the couples four children, all born within a five-year span. She washed cloth diapers and hung them out to dry. Shecooked, cleaned, took the children for walks, helped with school and play, and accepted with grace all the times when her husband was called away from holidays and birthday parties.

"The calendar of holidays does not apply," she says. "He helps people when they need him like the volunteer fireman races off when the alarm sounds; like the farmer plants and harvests when the ground and weather are ready."

"Life is lived by needs, not calendars and time slots."

This drawing is a gift from an Amish patient. James DeLine keeps it on his desk at home.Mark Hoffman / Milwaukee Journal Sentinel

Villagers embraced their doctor. Patients said they were accustomed to physicians who talked at them most of the time;DeLinelistened.

The clinic struggled financially in the early years. Not everybody paid their bills, Bader recalls. But the doctor wasnt going to send them to collection firms, and he wasnt going to stop caring for them.

The doctor and his wife became fixtures ofcommunitylife. They went to their childrens cross country meets and other school events. They attended the annual Kickapoo Valley Reserve Winter Festival.

But it was his presence in the homes of area residents that endeared him to them.

My father was diagnosed with colon cancer in 1994. The thing that always struck me was that Dr.DeLinestopped in to see my mom and dad one night after a basketball game, recalls Bonnie Howell-Sherman, editor and publisher of the weekly Epitaph-News in nearby Viola.

That was just unheard of. My mom is going through dementia now and out of all of the people shes met since shes been here, hes the one she remembers.

The villagers didnt just likeDeLine. They depended on him.

They worried about him, too.

Theres been two things about Dr.DeLinethat the whole community has been concerned about, Steinmetz said. One was, how do we keep him? The other was that hestayhealthy.

From time to time, rumors spread that the doctor was sick, even dying.

In 2007,DeLinehad noticed a problem. He would urinate, only to discover a short time later that he needed to go again.

It was prostate cancer.

Courtesy of the Viola Epitaph-News

Feeling, as he put it, reflective, maybe anxious too,DeLineapproached the Epitaph-News editor. He asked to write a series of columns for the newspaper describing his illness and treatment. He would counter the rumors with transparency. He called the column, From the Other Side.

I decided early on that I was comfortable sharing my experience with our community, he wrote in the first column. After all many of you have shared your concerns, fears and symptoms with me for nearly 25 years. Each of us knows that our turn must come for illness and eventually death.

He discussed his fears about surgery to remove his prostate Would I be able to jog again?He evensharedthe frustration of phoning to make a doctors appointment and going through endless computer prompts before reaching a live human voice.

His columns took readers through his surgery, recovery andreturn home.

The way the whole village shared the doctors illness and treatment, thats part of small-town life, explains Howell-Sherman, the newspaper editor.

Its been 12 years sinceDeLinessurgery. The cancer hasnot returned.

An Amish teen pulls farm machinery down a road in La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Of all the relationships the doctor built in LaFarge, the most challenging involved his Amish patients.

DeLine found his medical work was affected by a deeply held principle among the Amish, expressed in the German wordgelassenheit, which means yielding oneself to a higher authority. Among the Amish, the word encompasses a calmness and patience, as well as a belief that individualism must take a back seatto the good of the community and the will of God.

A sign warns motorists they may encounter horse-drawn vehicles on Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

While some Amish visit hospitals and accept modern medical techniques, others prefer natural methods and traditional treatments: herbs, vitamins, supplements and home remedies. In the LaFargearea, it is not unusual for an Amish family to turn to these methods beforedecidingto see DeLine.

Such was the case with Abie and Edna Yoder when their 8-year-old daughter, Barbara, first grew sick in spring 2015.

The girl had little appetite and suffered from a terrible stomachache and bloody diarrhea. Barbara weighed 38 pounds 19 pounds below average for an 8-year-old.

The Yoders took her to a so-called non-traditional doctor used by some of the Amish; these tend to be herbalists, specialists in natural medicine and others, all of whom lack medical degrees.He viewed her blood under a microscope and told the family she might have colon cancer.

The parents worried terribly about their daughters survival, but worried too about putting her in the hands of a traditional doctor. The scenario that haunted them had happened to a 3-year-old Amish boy with leukemia. The boy was given chemotherapy, they say, despite the excruciating pain andultimate failureof the treatment.

He begged to be released to go to Jesus, Edna Yoder recalls.

The Yoders approached a midwife, whosent her husband to speak with DeLine. The husband explained to the doctor the circumstances and the familys hesitation. Then the Yoders brought their daughter.

"Dr.DeLinemade it really clear that he would respect our wishes,Edna Yoder recalls.

Their daughter was admitted to American Family Childrens Hospital in Madison.DeLineconsulted with a pediatric cardiologist hed worked with at UW, Amy Peterson.

Dr.DeLinehad noticed that she had interesting looking bumps on her arms and on her legs, Peterson recalls. They were deposits of cholesterol. Dr.DeLineand I started thinking along very similar lines very quickly.

Genetic testing confirmed their hunch. The girl had extremely rare sitosterolemia, the same illness that would later be diagnosed in Perry Hochstetler.

Treatment lowered the girls sitosterol levels and helped her gain weight.

DeLineand Peterson have since foundamong the local Amisha dozen othercases the second largest cluster of the disease in the world.

An Amish farmer makes his way to work on a fence along Highway D between Cashton and La Farge.Mark Hoffman / Milwaukee Journal Sentinel

Almost 200 diseases are found in much higher proportions among Plain People. Scientists have developed a special Amish genetics test that screens the blood for more than 120 of them.

DeLine has seen patients with more than 30of the diseases on the testand has at least two patients with diseases neverdescribed in medicine.

Across the globe, there have beenonly20 to 30 cases of a disease called BRAT1; DeLine has seen six. Babies with the illness are born rigid and are prone to frequent seizures.

When the baby is born you cant straighten the baby, DeLine says. The eyes are jerking, face twitching. Some moms say they have felt things that suggest the babies have been seizing in the womb.

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In a Wisconsin village, the doctor makes house calls and sees the rarest diseases on Earth - USA TODAY

As the quest to understand the complexities of Alzheimers continues, researchers have now identified genetic mutations related to autism that may play a role in the neurodegenerative disease as well.

The study, out of Tel Aviv University, pinpointed thousands of genetic mutations in aging human brains that overlapped with mutations involved in autism and intellectual disability. They also found that many of these mutations occurred in the cell skeleton/transport system, a network of proteins that help organize cells.

We were surprised to find a significant overlap in Alzheimers genes undergoing mutations with genes that impact autism, intellectual disability and mechanisms associated with the cell skeleton/transport system health, Illana Gozes, lead author of the study, said in a news release. Importantly, the cell skeleton/transport system includes the protein Tau, one of the major proteins affected in Alzheimers disease, which form the toxic neurofibrillary tangles

Two decades ago, Gozes and the team at the laboratory discovered a protein known as ADNP. ADNP is mainly known for its connection to ADNP syndrome, a neurodevelopmental disorder that includes intellectual disability and autism spectrum disorder. But the team of researchers identified that ADNP also experiences mutations in the brains of people with Alzheimers.

Gozes built on that in the latest study, which aimed to create a paradigm shift in how people understand Alzheimers. That viewpoint focuses on how genetic alterations that are not inherited, known as mosaic somatic mutations, lead to brain pathology and disease.

The researchers hope the research will help lead to new therapeutic channels down the road.

We found in cell cultures that the ADNP-derived snippet, the drug candidate NAP, inhibited mutated-ADNP toxicity and enhanced the healthy function of Tau, Gozes said. We hope that new diagnostics and treatment modes will be developed based on our discoveries.

Genetics continues to be a large area of research around Alzheimers and dementia. Recently, researchers discovered that a genetic mutation known as APOE3ch delayed a womans high risk of developing Alzheimers by three decades.

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Alzheimer's and Autism: Researchers Pinpoint Genetic Mutations Overlapping in Both Diseases - Being Patient

Spitting intotheplastic test tube, I felt nervous. I was offering up a piece of myself for decoding, and while this timethere was no silver-haired sage, it reminded me of a visit to a fortune teller when I was 21.

Then, I offeredthepalm of my hand in a bid to divine what fate had planned for me. Now, it wasDNA, with my saliva destined for a laboratory in southwest China, totheheadquarters ofChengdu 23Mofang Biotechnology Co., a startup thats seeking to tap a boom in consumer genetics intheworlds most populous nation.

Rising awareness of genetically-linked diseases like Alzheimers and a natural human curiosity for insight intothefuture is fueling a global market for direct-to-consumerDNAtesting thats predicted totripleoverthenext six years. In China, wherethegovernment has embraced genetics as part of its push to become a scientific superpower,theindustry is expected to see US$405 million in sales by 2022, according to Beijing research firm EO Intelligence, an eight-fold increase from 2018. Some 4 million people will send away test tubes of spit in China this year, and I had just become one ofthem.

Not only was I entering a world where lack of regulation has spawned an entire industry devoted to identifyingthefuture talents of newborn babiesthroughtheir genes, I was handing over my genetic code to a country wherethegovernment has been accused of usingDNAtesting to profile minority groups a concern that hit home whentheresults showed I was a member of one.

I wanted to see whethertheburgeoning industry delivered on its claims in China, where scientists have gained international attention and criticism for pushingtheboundaries of genetics. And as a child of Vietnamese immigrants totheUS, Ive long been curious about my ancestry and genetic makeup.

To get an idea of how this phenomenon is playing out intheworlds two biggest consumer markets, I comparedtheDNAtesting experience of 23Mofang withthefirm CEO Zhou Kun says it was inspired by:23andMe Inc., one ofthebest known consumer genetics outfits intheUS.

PushingtheEnvelope

Thedifferences betweenthetwo companies are stark.

23andMe was co-founded byAnne Wojcicki, a Wall Street biotech analyst once married toGoogleco-founderSergey Brin.TheMountain View, California-based firm has more than 10 million customers and has collected 1 billion genetic data points, according to itswebsite. Brin and Google were early investors.

By contrast, 23Mofang is run out oftheChinese city of Chengdu, and Zhou, 36, is a computer science graduate who createdthecompany after becoming convinced Chinas next boom would be inthelife sciences sector. 23Mofang expects to have 700,000 customers bytheend of this year, a number he projects will at least double in 2020.

Thedivergence betweenthetwo countries andtheir regulation oftheindustry is just as palpable. Chinas race to dominate genetics has seen it push ethical envelopes, with scientistHe Jiankuisparking a global outcry last year by claiming to have editedthegenes of twin baby girls.Theexperiment, which He said madethem immune to HIV, put a spotlight on Chinas laissez-faire approach to regulating genetic science andthebusinesses that have sprung up around it.

When my reports came back, 23Mofangs analysis was much more ambitious than its American peer. Its results gauged how long I will live, diagnosed a high propensity for saggy skin (recommending I use products including Olay and Estee Lauder creams) and gave me an optimist not prone to mood swings a higher-than-average risk of developing bipolar disorder. 23andMe doesnt assess mental illness, which Gil McVean, a geneticist at Oxford University, says is highly influenced by both environmental and genetic factors.

Thefortune teller who pored over my palm told me I would live to be a very old woman. 23Mofang initially said I had a better-than-average chance of living to 95, before revisingtheresults to say 58% of clients hadthesame results as I did, making me not that special, and perhaps not that long-living.

When I ranthefinding pastEric Topol, a geneticist who foundedtheScripps Research Translational Institute in La Jolla, California, he laughed. Ninety-five years old?Theres no way to put a number on longevity, he said. Its a gimmick. Its so ridiculous.

Zhou saidtheaccuracy ofthelongevity analysis, based on a 2014 genetics paper, is not too bad, thoughthecompany plans to updatetheanalysis with research thats being undertaken on Chinese elderly.

But when it comes to disease,theresults of both companies showed howthescience of genetics, particularly attheconsumer level, is still a moving target.

Its All AbouttheData

After claiming I had a 48% greater risk thanthegeneral population of developing type 2 diabetes, both 23Mofang and 23andMethen revisedtheresults.

First, 23andMe cuttherisk figure from its analysis, posted in an online portal I accessed with a password.Theoverview analysis that I have an increased likelihood of developingthedisease never changed. But a few months later,thefigure was back, with a slightly different explanation: Based on data from 23andMe research participants, people of European descent with genetics like yourshave an estimated 48% chance of developing type 2 diabetes at some point between your current age and 80.

Shirley Wu, 23andMes director of health product, saidthecompany occasionally updates its analysis. My risk figure might have changed if I indicated my ethnicity and age, she said. I hadnt given any biographical details or filled out any surveys on 23andMes site.

Your risk estimates will likely change over time as science gets better and as we have more data, Wu said. We are layering in different non-genetic risk factors, and that potentially updates our estimates.

Algorithms and data underpintheanalysis of both companies, asthey do for other genetic testing firms, so it apparently isnt unusual forDNAanalysis to shift as more research and data into diseases becomeavailable. Still, I was confused.

I reached out to Topol, who said that 23andMes diabetes finding likely didnt apply to me sincethevast majority of people studied forthedisease are of European descent. Wu saidthe American company does have a predominantly European database but has increased efforts to gather data for other ethnicities as well.

23Mofang, meanwhile, also revised my diabetes risk to 26%. My genes hadnt changed, so why hadtheresults? CEO Zhou saidthecompany is constantly updating its research and datasets, and that may changetheanalysis. As time goes by,there will be fewer corrections and greater accuracy, he said.

For now, theres a possibility you can later get a result thats opposite oftheinitial analysis, said Zhou.

Additionally,theaccuracy of genetic analysis varies hugelydepending onthetraits and conditions tested because some are less genetically linkedthan others.

Zhou isnt deterred by criticism. He said 23Mofang employs big data and artificial intelligence to findthecorrelations to diseases without relying on scientists to figure it out.

While its impossible to get things 100% right,thecompanys accuracy will get better with more data, he said.

Ancestry Mystery

You might assume thatthetwo companies would offer similar analysis of my ancestry, which Ive long thought to be three-fourths Vietnamese and one-fourth Chinese (my paternal grandfather migrated from China as a young man). Born in Vietnam and raised intheUS, I now live in Hong Kong, a special administrative region of China.

23andMes analysis mirrored what I knew, but my ancestry according to 23Mofang? 63% Han Chinese, 22% Dai an ethnic group in southwestern China and 3% Uyghur. (It didnt pick up my Vietnam ancestry becausetheanalysis only compares my genetics to those of other Chinese, according tothecompany.)

That led me tothebig question in this grand experiment: How safe is my data afterthesetests?

Human Rights Watch said in 2017 that Chinese authorities collectedDNAsamples from millions of people in Xinjiang,thepredominately Muslim region thats home totheUyghur ethnic group. Chinas use of mass detention and surveillance intheregion has drawn international condemnation. What if Beijing compelled companies to relinquishdata on all clients with Uyghur ancestry? Couldthedetails of my Uyghur heritage fall into government hands and put me at risk of discrimination or extra scrutiny on visits to China?

23Mofangs response tothese questions didnt give me much solace. Regulations enacted in July gavethegovernment access to data held by genetics companies for national security, public health and social interest reasons.Thecompany respectsthelaw, said Zhou. Ifthelaw permitsthegovernments access tothedata, we will give it, he said.

Theauthorities havent made any requests for customer data yet, Zhou pointed out. Chinas State Council, which issuedtheregulations, andtheMinistry of Science & Technology didnt respond to requests for comment.

Over intheUS, 23andMe said it never shares customer data with law enforcement unlesstheres a legally valid requestsuch as a search warrant or written court order.Thecompany said its had seven government requests for data on 10 individual accounts since 2015 and has not turned over any individual customer data. It uses all legal measures to challenge such requests to protect customers privacy, said spokeswoman Christine Pai.

No Protection

New York Universitybioethics professorArt Caplansays privacy protections on genetic information are poor in most countries, including in the USand China.

I dont think anyone can say theyre going to protect you, he said. In China, its even easier for the government. The government retains the right to look.

23andMe appeals to potential customers with the lure of being able to make more informed decisions about your health, but after taking tests on both sides of the Pacific and realizing how malleable the data can be, as well as the myriad factors that determine diseases and conditions, I am left more skeptical than enlightened.

I gave away something more valuable than a vial of spit the keys to my identity. It could become a powerful tool in understanding disease and developing new medicines, but in the end its entrepreneurs like Zhou who will ultimately decide what to do with my genetic data. He plans to eventually look for commercial uses, like working with pharmaceutical companies to develop medicines for specific diseases.

We want to leverage the big database we are putting together on Chinese people, Zhou said. But first, we need to figure out how to do it ethically.

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How do consumer DNA tests from the US and China stack up? - Abacus

The question of whether it is genes or environment that largely shapes human behaviour has been debated for centuries. During the second half of the 20th century, there were two camps of scientists each believing that nature or nurture, respectively, was exclusively at play.

This view is becoming increasingly rare, as research is demonstrating that genes and environment are actually interconnected and can amplify one another. During an event at Berlin Science Week on November 7, organised by the Royal Society, we discussed how the debate is changing as a result of recent findings.

Take literacy. Making language visible is one of the most extraordinary achievements of human beings. Reading and writing is fundamental to our ability to thrive in the modern world, yet some individuals find it difficult to learn. This difficulty can arise for many reasons, including dyslexia, a neuro-developmental disorder. But it turns out neither genes nor environment are fully responsible for differences in reading ability.

Genetics and the neuroscience of reading

Reading is a cultural invention and not a skill or function that was ever subject to natural selection. Written alphabets originated around the Mediterranean about 3,000 years ago, but literacy only became widespread from the 20th century. Our use of the alphabet, however, is grounded in nature. Literacy hijacks evolved brain circuitry to link visible language to audible language by letter-sound mapping.

Brain scans show that this reading network is apparent in pretty much the same place in the brain in everybody. It forms when we learn to read and strengthens connections between our brains language and speech regions, as well as a region that has become known as the visual word form area.

The design for building the underlying circuitry is somehow encoded in our genomes. That is, the human genome encodes a set of developmental rules that, when played out, will give rise to the network.

However, there is always variation in the genome and this leads to variation in the way these circuits develop and function. This means there are individual differences in ability. Indeed, variation in reading ability is substantially heritable across the general population, and developmental dyslexia is also largely genetic in origin.

This is not to say that there are genes for reading. Instead, there are genetic variations that affect how the brain develops in ways that influence how it functions. For unknown reasons, some such variants negatively affect the circuits required for speaking and reading.

Environment matters too

But genes are not the whole story. Lets not forget that experience and active instruction are needed for the changes in brain connectivity that enable reading to occur in the first place though we dont yet know to what extent.

Research has shown that most often problems with literacy are likely underpinned by a difficulty in phonology the ability to segment and manipulate the sounds of speech. It turns out that people with dyslexia also tend to struggle with learning how to speak when infants. Experiments have shown that they are slower than other people to name objects. This also applies to written symbols and relating them to speech sounds.

And here nurture comes in again. Difficulties in learning to read and write are particularly visible in languages with complex grammar and spelling rules, such as English. But they are far less obvious in languages with more straightforward spelling systems, such as Italian. Tests of phonology and object naming, however, can detect dyslexia in Italian speakers too.

So the difference that is found in dyslexic brains is likely the same everywhere, but will nevertheless play out very differently in different writing systems.

Amplification and cycles

Nature and nurture are traditionally set in opposition to each other. But in truth, the effects of environment and experience often tend to amplify our innate predispositions. The reason is that those innate predispositions affect how we subjectively experience and respond to various events, and also how we choose our experiences and environments. For example, if you are naturally good at something you are more likely to want to practice it.

This dynamic is especially evident for reading. Children with greater reading ability are more likely to want to read. This will of course further increase their reading skills, making the experience more rewarding. For children with lower natural reading ability, the opposite tends to happen they will choose to read less, and will fall farther behind their peers over time.

These cycles also offer a window of intervention. As we have seen in the case of Italian readers, nurture can mitigate the effects of an adverse genetic predisposition. Similarly, a good teacher who knows how to make practice rewarding can help poor readers by allowing short cuts and mnemonics for spelling. In this way, dyslexic readers can become good readers and enjoy it. Reward and practice enhance each other, leading to more motivation and more practice in a positive feedback loop.

So instead of thinking of nature and nurture as adversaries in a zero sum game, we should think of them as feedback loops where a positive influence of one factor increases the positive influence of the other producing not a sum but an enhancement. Of course, the same applies to negative feedback, and so we have both virtuous and vicious circles.

Because inheritance (genetic as well as cultural) matters, this effect is also visible on a larger scale spanning several generations. In the past, parents who sent their children to school created an advantageous environment for them and their grandchildren. But in turn, the parents benefited from the existence of a culture that invested in schools. Of course, such investments are not always spread evenly and may flow more towards those already in an advantageous position. Such a circle is sometimes referred to as the Matthew effect good things come to those who already have them.

The interactive loops between nature and nurture extend beyond the lives of individuals, playing out across communities and over generations. Recognising these dynamics gives us some power to break these feedback loops, both in our own lives and more widely in society and culture.

This article by Kevin Mitchell and Uta Frith first appeared in 2019 in The Conversation via Creative Commons License.

Image: Donar Reiskoffer/Wikimedia Commons/Creative Commons 3.0.

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Is Nature vs. Nurture an Outdated Concept? - The National Interest Online

A DNA test can reveal surprising facts about us certain genes make us more inclined to have dry earwax, for example, and others make us more likely to sneeze when we see a bright light. Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA.

Innocuous facts like these were what DNA kits were used for finding out when they first became commercially available. However, as the tests have become more sophisticated, the companies behind them have shifted their marketing focus. Users of at-home DNA tests have been known to uncover deep-rooted facts about themselves, from discovering long-lost relatives to learning of their ancestors origins and their susceptibility to genetic diseases.

Finding out that you have a pre-existing health condition might not seem like the best idea for a Christmas present, but that hasnt stopped the test kits from enjoying a surge in popularity. MIT Technology Review estimates that by the start of 2019, more than 26 million people had taken an at-home ancestry test. The market is expected to be worth $45bn by 2024.

Nevertheless, despite the emerging industrys rampant growth, there have been mounting concerns that its practices could infringe on consumers rights. Whenever people fork out $100 to $200 for a DNA test, the hidden cost of that transaction is their personal data which, from then on, is held in the databases of a private company. Once these companies obtain genetic information, its very difficult for users to get it back.

By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair

Ignorance is blissLong before people were able to take DNA tests from the comfort of their own home, psychologists worried about their possible impact on peoples mental health. Ever since the Human Genome Project was started in 1990, many scholars have maintained that DNA tests should be used with caution, on the grounds that understanding ones own health risks could lead to anxiety or depression.

Conversely, a study by the Hastings Centre found that discovering an increased risk of developing Alzheimers disease did not make people more depressed or anxious. And in the event that people discover a particularly urgent health risk like a mutation of the BRCA1 or BRCA2 genes, which puts individuals at a high risk of developing cancer at a young age any adverse psychological effects are presumably worth it to obtain this life-saving information.

However, at-home DNA tests could still pose a risk to mental health, in part because they remove medical professionals from the equation. Adrian Mark Thorogood, Academic Associate at the Centre of Genomics and Policy, warned that this is far from best practice for receiving a DNA test result. Results should be communicated through a medical professional who can interpret the result in the individuals specific context, and offer a clear description of the tests limits, he told The New Economy.

Without a professionals assistance, users could be left alone to battle with a troubling revelation about their health. There is also a danger that without guidance, some people could misinterpret their test result, placing undue stress on their mental health.

There is another unpleasant discovery that people can make through a DNA test one they may be even less prepared for. By taking DNA tests at home, many have unwittingly stumbled upon long-kept family secrets. Some have seen their parents go through a bitter divorce after their test revealed they were actually conceived through an affair. Others have discovered they were conceived by rape and that their mother decided to never tell them. What began as a seemingly harmless urge to find out more about their heritage ends in psychological trauma and family breakdown.

Brianne Kirkpatrick, a genetics counsellor, is part of a growing sector of therapy specifically tailored towards helping people come to terms with receiving unexpected DNA results. One cant help but wonder whether her patients end up wishing theyd never taken the test at all.

I dont recall anyone saying they wish they could go back and not learn the truth, Kirkpatrick said. But I have had a number of people say to me they wish they had found out their shocking information from a person, rather than a computer.

While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications

The fact that virtually anyone can now find out their real parentage through a simple DNA test has wide-reaching repercussions for the accountability of paternity. Historically, men have always had a much greater ability to conceal their status as a parent, as they dont have to bear the child. The world of direct-to-consumer DNA testing blows this capacity for anonymity out of the water.

This is particularly problematic when it comes to sperm donation. Anonymity is a key selling point for many potential donors, but now all their future biological offspring has to do is swab the inside of their cheek to completely compromise that anonymity. Research suggests that we could see a drop in donor rates as a result. A 2016 study in the Journal of Law and the Biosciences found that 29 percent of potential donors would actually refuse to donate if their name was put on a registry.

The wave of parental discoveries made through direct-to-consumer DNA tests raises questions about where the responsibility of the seller sits in all this. Most health professionals recommend that individuals seek out genetics counselling once they receive DNA results. Some, like Invitae, offer counselling services but arent direct-to-consumer companies. Many of those that are including 23andMe do not offer such a service. It could be argued that this shows a certain disregard for the consequences of using their product. Unfortunately, irresponsible decisions like this have tended to characterise the industrys path to success.

Genetic Wild WestIn September 2019, 17 former employees from the Boston-based genetic testing company Orig3n accused the firm of giving consumers inaccurate results. Allegedly, if a customer took the same test twice, their results could be extremely different each time. A former lab technician produced a leaked report to Bloomberg Businessweek that revealed 407 errors like this hadoccurred over a period of three months.

Part of Orig3ns USP was that it offered advice supposedly calculated based on a consumers genetic profile. Former employees have cast doubt over the companys modus operandi by claiming that the advice they gave was in fact routinely lifted from the internet. The advice given ranged from the technically correct but uninspired to the broadly unhelpful such as telling people to eat more kale and the utterly bogus, like advising clients to eat more sugar to eliminate stretch marks.

Although Orig3n is a relatively small player in the sector, news of this scam nonetheless illustrates how little protection consumers have in this nascent market. Analysts say we are currently witnessing a Wild West period in the consumer genetics space thanks to a lack of regulation, raising concerns over whether we can trust these companies with our genetic data. While we might think wed prefer to suffer a DNA leak than a leak of our credit card details, genetic data has its own unique set of complications.

In the United States, if my social security number is stolen, that is difficult, but not impossible, to get frozen, changed, etc, said Natalie Ram, an associate professor at the University of Maryland Francis King Carey School of Law and a specialist in bioethics and criminal justice. But theres literally no way to change your genetic code.

Genetics platforms like 23andMe, AncestryDNA and FamilyTreeDNA are now sitting on a goldmine of very personal data. In 2013, a 23andMe board member told Fast Company that it wanted to become the Google of personalised healthcare. If this statement makes anything clear, its that the company wasnt planning on making its millions simply by selling DNA test kits: its mission was always to amass significant amounts of data on its users, which it could then monetise.

There is a wide range of reasons why companies might want to buy genetic data. Perhaps the most benign is medical research, which genetics platforms allow users to opt in or out of. But other companies might use your genetic data to better sell you products or, conversely, deny them to you for instance, one sector that would see a clear monetary value in obtaining genetic data is insurance. In the US, the Genetic Information Nondiscrimination Act of 2008 prevents employers and health insurers from using a persons genetic information when making decisions about hiring, firing or raising rates. However, this does not include life insurance or short or long-term disability insurance.

At first glance, it seems as if theres a simple solution: if users are concerned about these risks, they should just choose for their data to be kept anonymous. However, choosing this option is not as foolproof as it once was. As long ago as 2009, researchers demonstrated that they could correctly identify between 40 and 60 percent of all participants in supposedly anonymous DNA databases by comparing large sets of that data with public datasets from censuses or voter lists. Since that experiment, DNA databases have grown massively.

With access to four to five million DNA profiles, upwards of 90 percent of Americans of European descent will be identifiable, said Ram. Its verging on a comprehensive DNA database that no US state or jurisdiction has suggested would be appropriate.

Shaping the lawWith comforting statements like your privacy is very important to us (ancestry.co.uk) and we wont share your DNA (familytreedna.com) emblazoned on their websites, some genetics platforms seem to be making privacy their number one priority. In the US, 23andMe and Ancestry are part of the Coalition for Genetic Data Protection, which lobbies for privacy protection in the DNA space. However, while the coalition advocates genetic data privacy in a specific context, it argues for a one-size-fits-all policy concerning all data. By comparison, the EUs General Data Protection Regulation regards genetic information as personal data, which makes DNA unique from other kinds of data.

There is a fundamental legal problem with boxing genetic data in with all other varieties, including the data that social media websites collect about us. In most cases, what a person does on the internet implicates them alone genetic data is different. We share our DNA with members of our family, which means that sharing it without their consent can be problematic.

Even if I can consent to using my DNA to identify me, that should not extend to my ability to consent to using my DNA to identify my relatives, said Ram. The reason I think thats a really critical distinction is because genetic relatedness is almost always involuntarily foisted upon us. So we dont choose our parents, we dont choose how many siblings we have. Its a product of biology, not a product of choice.

The legal issues surrounding genetic relatedness were put to the test in 2018 when police discovered the true identity of the Golden State Killer, who terrorised California in the 1970s and 1980s in a homicidal spree. Law enforcement officials were able to convict him only because they had succeeded in connecting the DNA of the suspect with that of a family relative on GEDmatch, a genetic database in the public domain. Across the US and around the world, people celebrated the arrest of a notorious criminal. The only problem was that the means of capturing him was not necessarily legal.

Prior to the case, GEDmatchs site policy made no explicit reference to the potential use of consumers data by law enforcement. However, the company defended itself by saying that users should have assumed it could be put to that use.

While the database was created for genealogical research, it is important that GEDmatch participants understand the possible uses of their DNA, including identification of relatives that have committed crimes or were victims of crimes, said GEDmatch operator Curtis Rogers in a statement.

Some genes even result in people being more attractive targets for mosquitoes, so if youve ever felt personally singled out by the insect during the summer months, its not a cruel conspiracy its your DNA

However, privacy advocates like Ram argue that users consent for law enforcement to look at their data should not have been assumed. At least from a constitutional perspective in the United States, individuals ought to be recognised to have whats called an expectation of privacy in their genetic data, even if they use one of these services, she told The New Economy.

After the case, genetics platforms updated their policies to clarify their position on law enforcements use of peoples data. Interestingly, they took very different stances. While 23andMe and Ancestry said they would not allow law enforcement to search through their genetic genealogy databases, FamilyTreeDNA updated its policy to say it would give up data to officials, but only in the investigation of violent crimes. Users didnt know it at the time, but FamilyTreeDNAs policy update was already too little too late: in January 2019, it was revealed that the company had been secretly working with the FBI for nearly a year to solve serious crimes, without informing its users.

The Golden State Killer case exposed how little protection consumers really had in the direct-to-consumer genetics market. It showed that genetics platforms were capable of suddenly changing or contradicting their own policies and even, in the case of FamilyTreeDNA, betraying the trust of consumers.

Some might argue that this infringement on genetic privacy is simply the price we must pay to catch dangerous criminals. Of course, without the use of a genealogy database, the Golden State Killer may never have been caught. But the fact that genetic data can be harnessed to solve very serious crimes should not justify law enforcements unbridled access to such databases. Abuses of power do happen and, in the context of direct-to-consumer DNA tests, they already have: in 2018, for example, Canadian immigration officials compelled a man to take a DNA test and upload his results to FamilyTreeDNAs website. They then used the website to find and contact some of his relatives in the UK to gather more evidence in order to deport him.

Todays consumers are continually adjusting to shrinking levels of privacy. From the introduction of video surveillance and the mapping of residential areas on Google Earth to the revelation that Facebook harvests vast amounts of user data, we have seen the public react in the same way again and again: there is an initial public outcry, and then consumers simply adjust to the new level of diminished privacy. Our response to the rise of genetics platforms risks the issue being consigned to the same fate.

It is up to regulators to protect individuals right to privacy. While our genetic data may be something of a genie out of the bottle, that should not give the companies that collect it free rein over who sees it and what they choose to do with it.

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Collection of genetic data leads to privacy concerns - The New Economy

The international group of scientists knew they were setting out to investigate an explosive subject: the hereditary basis of human same-sex behavior. Even so, the members of the prestigious Broad Institute in Cambridge, Massachusetts, may not have anticipated the magnitude of the public furor that erupted when they published their study, which identified several markers in certain genetic loci in the human genome related to same-sex sexual experience. The storm of reactions ranged from those who welcomed something seen as heralding significant progress in the field, to others who maintained that it would have been better if the scientists hadnt published anything.

The research results were published in full in the journal Science, at the end of August. This was the most extensive study of its kind ever conducted (there were about a half a million subjects), in which use was made of the GWAS (genome-wide association studies) method to analyze genetic big data. The researchers discovered five genetic markers (frequent, minor changes in the DNA segments of certain chromosomes) that appeared repeatedly among individuals who reported having had same-sex sexual experiences. Slight and frequent genetic variations were identified in both women and men, two others in men only and one more only in women.

No less important in the study, entitled Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior, is the scientists claim that a large number of genetic markers, perhaps even thousands, might operate simultaneously together although each in and of itself is of minuscule weight and influence ones same-sex orientation. Moreover, their study led the researchers to the conclusion that human genetics can explain up to 32 percent of same-sex sexual behavior.

What is at issue here, however, is not what the study contains but what it does not contain. As Melinda Mills, a sociology professor at Oxford, writes in the same issue of Science, there is no way that the researchers findings can be used as a tool to accurately predict same-sex behavior. Specifically, the fact that genetics can explain up to 32 percent of the fact that someone is gay or lesbian, does not mean that sexual identity is determined primarily by environmental factors not to mention social ones. This story is far more complex and has not yet been fully deciphered. Mills views are shared by Andrea Ganna, one of the chief authors of the new study.

What we basically do is statistical associations between having and not having these genetic markers and having or not having same-sex behavior, Ganna told Haaretz in a phone interview. Because we had this uniquely large study, he continued, which allowed us to have robust conclusions, and because we had the technology to measure the genetic markers of so many individuals, the time was right to confirm something that we expected: There is no one specific gay gene. Instead there are a lot of relatively common genetic markers, genetic mutations, that have a small effect on same-sex behavior.

At the same time, adds Ganna, a geneticist at Harvard Medical School and at Finlands Institute of Molecular Medicine, Not everyone is interpreting the fact that theres no single gay gene in the right way.

Gannas concern is shared by scientists around the world. Theyre worried that the researchers findings will fuel prejudice and discrimination against the LGBTQ community, and even spark calls for genetic engineering and genetic diagnosis among its members. So serious are these apprehensions that some have wondered whether the study would not do more harm than good.

As a queer person and a geneticist, I struggle to understand the motivations behind a genome-wide association study for non-heterosexual behavior, Joseph Vitti, a postdoctoral researcher at the Broad Institute, wrote on its blog, adding, I have yet to see a compelling argument that the potential benefits of this study outweigh its potential harms [T]he results presented not only oversimplify the question of biological causality, but also threaten direct damage by perpetuating the stereotype of LGBTQIA+ people as imprudent, while also likening same-sex attraction to a medical or psychological disorder.

Moreover, a website called The American Conservative posted an article entitled Not Born This Way After All? which wondered, skeptically: If the study proves that homosexuality is related to the environment, above all, and not to heredity why isnt it right and proper, in scientific terms, to allow those who so desire to undergo treatment in order to reduce their same-sex desires, which have now been shown not to be genetic?

That, however, is a simplistic reading of the studys findings. According to Michael Bailey, a professor of psychology at Northwestern University in Illinois, who was not involved in the study but has been conducting research on sexual orientation for 30 years, Its very important to understand that environment does not simply refer to social surroundings, like what your parents teach you and what kids you know, trauma and so on theres also a biological environment that begins right after conception.

Three years ago, Bailey and several colleagues published a survey of all the studies and professional literature in the field. The best studies have shown that genes are probably important but not overwhelmingly important, he tells Haaretz. We estimated in our 2016 review that 30 percent of the variation in sexual orientation is due to genetic variations. It may be this finding that led him to conclude that it is the biological environment that is mostly important. Bailey is convinced that men are born with their sexual orientation and that it is not subsequently acquired at any stage. He notes that there are several cases, I think there are seven throughout the professional literature, in which a baby boy was changed into a girl for medical reasons and was raised as a girl. When you follow these individuals through adulthood, you find that they are attracted to women and not to men.

In Baileys view, the best example of how biological-environmental factors can influence sexual orientation is the fraternal birth order effect. The phenomenon, whose existence is well established, he says, shows that the more older brothers a man has, the more likely he is to be homosexual. In practice, every older biological brother increases the probability that the youngest brother will be gay by about 33 percent. Thus, if the probability that a man with no older brothers will be gay is 2 percent, one older brother will increase the probability to 2.6 percent, and a second, third and fourth brother to 3.5 percent, 4.6 percent and 6 percent, respectively. Whats not yet clear is the reason for this.

In my mind, Bailey suggests, the best hypothesis as to why this happens is that a mothers immune system becomes increasingly active and produces antibodies against male proteins over successive births.

Fingers and hands

Behind this hypothesis is one of the most influential figures in the field, American-Canadian clinical psychologist and sexologist Ray Milton Blanchard. He was also among those who linked the fraternal birth order effect to another phenomenon of interest to scientists: the connection between being left-handed and having a same-sex orientation. The most extensive study in this regard was conducted in 2000, incorporating 20 different studies involving 7,000 gay male and female subjects and 16,000 heterosexual ones. It was found that gay men were 34 percent more likely to be left-handed. The situation was more extreme among lesbians: They were seen to have a 91 percent greater chance than straight women of writing with their left hand.

As a result, six years later, a research team led by Blanchard argued that the fraternal birth-order effect is relevant only among right-handed men. The reason is that, in any case, left-handed men who dont have older brothers already have a greater likelihood of being gay than right-handed men with such siblings.

A persons dominant hand turns out to be significant in another sense as well. An article published two years ago (about a study in which all the subjects had taken part in a gay pride parade in Toronto) found a connection between that hand and the gay persons role in bed: that is, the proportion of left-handed gays who defined their sexual behavior as passive or versatile (i.e., sometimes passive, sometimes not) was significantly higher than among those who described themselves as actives who clearly tended to be right-handed.

In research conducted over the years on the subject of the connection between sexual orientation and other attributes of the body, the hand holds a place of honor. But while Blanchard developed his theory on the basis of the whole hand, sometimes a few fingers are also enough: two, to be exact. In his 1998 study, British biologist John Manning confirmed a relatively old hypothesis, first put forward in Germany almost 150 years ago. Its gist is that the proportion between the length of index and ring fingers is, typically, different in men and women. Manning found that this phenomenon was detectable as early as age 2, which led to the observation that its source lies in the differences in testosterone and estrogen levels that already exist in the womb hereinafter: a biological-environmental factor.

Manning did not emphasize the element of sexual orientation in the two books and over 60 articles he wrote on this subject, but in the two decades that have elapsed since his study, more than 1,400 papers have been written on the ratio between the length of the second and fourth fingers (known as 2D:4D) and the connection between it and the level of risk of contracting certain diseases, as well as personality traits, cognitive and athletic abilities and sexual orientation.

One such study, published in 2010, maintained that straight and lesbian women are differentiated by the ratio between the length of the index and ring fingers, with lesbians tending to show a more masculine ratio i.e., closer to the average difference between the length of the fingers, among men. However, no such differences were found between gay and straight men.

Last year a team of scientists led by a British psychologist measured the fingers of 18 pairs of identical female twins, one lesbian, the other straight. Overall, differences in proportion were documented only in the lesbians and only in their left hand, and were comparable to the situation among men. This fact, the team concluded, could indicate a heightened exposure to testosterone in the womb but their study was based on a very small sample and drew much criticism. The critics charged that the conclusion was based on an overly simple means of measurement: of the way only two variables impacted each other. And, they added to bolster their argument, findings of studies involving those fingers have not been replicated in scientific experiments.

The field of gay science has been on a roll in recent years, but has a far longer history. Its modern phase dates to the early 1990s, when scientists began to publish increasing numbers of studies arguing that sexual orientation has a biological component. A leading scientist in this field is British-American neurobiologist Simon LeVay, who in 1990 performed autopsies on the bodies of 41 people: 19 gay men, 16 straight men and nine women. He discovered that the brain cells known as INAH-3 among the deceased gay men were relatively small, and closer in size to those of women than to heterosexual males.

In 1991, LeVay told Haaretz in a phone conversation, I published a study that got a lot of media attention, related to my observation that there was a region inside the hypothalamus that was different in size between men and women, and also between gay and straight men My additional finding was the difference in size between gay and straight men in this region inside the hypothalamus that is involved in the regulation of sexual behavior.

Adds LeVay, My general feeling is that there are certainly strong biological influences on peoples sexual orientation, but we cant say everything is genetic.

In the spirit of the period, and in light of the AIDS epidemic at the time, LeVay tried to be as cautious as possible about his conclusions. Its important to stress what I didnt find, he said in an interview to Discover magazine, in 1994. I did not prove that homosexuality is genetic, or find a genetic cause for being gay. I didnt show that gay men are born that way, [which is] the most common mistake people make in interpreting my work.

Three decades after publishing his study, he still thinks media coverage is doing an injustice to research even if its not his. Ive seen some headlines saying, basically, that this study [i.e., that of Ganna and his associates] shows its not genetic, or that are no gay genes, or something like that; and, of course, its not what the study shows at all.

Truly gay

In recent decades, scientific research (on men and women alike) in this realm has relied on an additional field: molecular genetics. The pioneer is geneticist Dean Hamer, who in 1993 conducted the first study of its kind.

We noticed that being gay, for males, tended to pass down through the mothers side of the family, he told Haaretz. And that is characteristic in genetics of something on the X chromosome because males get their X chromosomes from their moms That led us to look in families where there were gay brothers, to see if they shared anything on the X chromosome.

And thus, recalls Hamer, he and his team discovered Xq28: a genetic marker that plays a part in determining whether a person will be heterosexual or gay. He emphasizes that this is a factor, its not the factor and actually, overall, its not even the most important factor. He adds, Whats good about genetic studies, is that you know that whatever you find is a causal factor, because of course people are born with their genes, and its not something that changes over time.

LeVay, he explains, is looking directly at the brain, and were looking at what we think is building the brain and genes. Yet, its very difficult to know whether one was born with a brain like that, or whether that brain developed that way because of your behavior the causality is rather unknown.

At the same time, Hamer adds, That doesnt mean there arent specific pathways, because there has to be some sort of a pathway in the brain that controls sexual orientation. We know, for example, that the reason you become a male or a female is very simple: If you have a certain gene on the Y chromosome, you will produce male hormones, and if you have those you make a penis and scrotum and you become male. Accordingly, Theres probably some pathway in the brain that does same thing for sexual orientation, but were not going to discover it from genetics The answer will probably emerge from some sort of very sophisticated brain and developmental studies.

For 35 years, Hamer accumulated experience as a scientist at the National Institutes of Health in Bethesda, Maryland. That period is behind him. He doffed the white coat and now lives in Hawaii, where he makes films. But even if hes no longer occupied with research, it still occupies him.

Hamer: Back in the 1990s, I, along with all the scientists involved, believed that if we did good genetic studies wed find the important genes. For example, well find a gene that is responsible for the production of testosterone, and if its functioning was low, it would be possible to say that this is the cause of homosexuality in a particular person. But it turns out that it doesnt work that way. For every mental trait that has been studied everything you can imagine in the brain, for every single trait, theres a [vast number of] genes not to mention a host of complex societal and environmental factors.

For his part, Hamer has much praise for the Broad Institute study: The new GWAS study is really important, because for the very first time they used a huge sample and they mapped every inch of the genome. And this has never been done before. All the other studies were much smaller, or used many fewer genetic markers. But he also demurs: Whats very important is to look at what they actually analyzed. They didnt analyze people who were gay or lesbian, but anyone who had one single same-sex experience, which is quite different... They were measuring something more like openness to sexual experimentation.

As Hamer sees it, If you look for those five markers, or even just the three strongest markers, they are not necessarily found in people who actually identify as gay or lesbian. If you take people who are gay, like me, and look for those markers theyre not significantly there.

Hamer thinks that the whole field is lagging behind because of insufficient research, owing to the stigmas that plague the subject. I dont think sexuality is any more complicated than many other areas of human personality and individual differences, he observes, noting, We formally established that male sexuality is something that is deeply ingrained in people, its not any sort of choice really. It starts really early in life, and it has a major biological component to it. But, how it works? What the biological component is? Were completely unaware and dont know anything, and we barely know more than we did 25 years ago, or in the 1940s, when Kinsey did his work, to be honest.

Hamer was referring to biologist Alfred Kinsey, who in 1948 stunned the American public with his book, Sexual Behavior in the Human Male, which addressed previously taboo subjects, and challenged the traditional beliefs and existing knowledge about human sexuality. Kinsey had conducted a survey of men, which found that 37 percent of his subjects said they had undergone a homosexual experience of some kind, and 10 percent said they had been exclusively gay for three years of their adult life a statistic which to this day is generally said to represent the proportion of people engaging in same-sex behavior.

At the same time, subsequent studies reveal that the percentage of people who define themselves as exclusively homosexual is far lower, though it fluctuates from one article to the next. For example, a 2011 survey of nine different studies on the subject revealed that approximately 3.5 percent of Americans identify themselves as gays, lesbians or bisexuals. A poll involving 1,000 Jewish Israelis in 2012 found that 11.3 percent of the male respondents and 15.2 percent of the female ones said they felt an attraction to members of the same sex. However, only 8.2 percent of the men categorized themselves as gay or bisexual, while 4.8 percent of the women said they were lesbian or bisexual.

For his part, Ganna, of the Broad Institute, understands some of the criticism of his research. What we studied is not related directly to the biology, but to extended environmental factors related to it. Its not about our sample size once you have a lot of individuals, you can capture very small effects. But are these directly influencing same-sex behavior, or other things related to this topic? As a medical example, think about a study that looks for associations between genetic markers and lung cancer. In that example, what we found are genetic variants regarding how much you smoke, which is related to lung cancer.

One of the lessons, and one of the most interesting points arising from the study has to do, says Ganna, with the mode of measurement that had been in use since 1948, when Kinseys scale ranked individuals as being between 0 (totally heterosexual) and 6 (totally homosexual).

Ganna: Basically, the tendency is to locate individuals on a continuum. You can supposedly be anywhere between 100 percent heterosexual to 100 percent homosexual, which implies that the more youre homosexual, the less youre heterosexual, and vice versa. We show that this assumption actually doesnt hold water: When we look at the genetic data, its not that straightforward, theres no simple continuum of sexuality.

So, actually, you are refuting the Kinsey scale?

Ganna: Thats exactly one of our conclusions. What were now doing is, rather than asking people to put themselves on a scale somewhere between being exclusively heterosexual or exclusively homosexual, we ask them how much theyre attracted to men and women. You could be attracted to either of them, very attracted to both of them or to one more than the other. And that information will be crossmatched with genetic markers.

In the final analysis, he adds, We showed that this is just another natural human variation. Sexual orientation, similar to many other behavioral traits, is complicated and is composed of different factors. The interesting thing is how genetics and environment work together. If you think about how much more prevalent same-sex behavior has become lately, people engage in it more than in the past. And thats clearly not because our genetics are changing. Its because of the environment, because society is becoming more open and laws are changing.

Further research should focus on the relationship between environmental factors and genetics, Ganna says, and on how they interact. Its somewhat misleading to think of nature and nurture as separate aspects; they both contribute. So, it would be wrong to say that you can use only DNA to predict if someone will engage in same-sex behavior, but you also cant say its simply a [matter of] choice.

In summary, he says, I think that the more people who will understand that there are genetic and environmental components to sexual behavior, the better and this is a message that goes beyond just sexuality.

Choice and lifestyle

However, the relationship between science and the environment, and particularly the people living in it, is a complicated one. The subject definitely should be studied, but the social aspect of it is problematic, says LeVay, the neurobiologist. I am gay myself, and I feel strongly that gay people should be valued and accepted into society, regardless of what caused their sexual orientation. I dont think its vital for gay liberation to prove that gay people cant help but be gay there are plenty of other reasons [for accepting them], including basic human rights.

At the same time, he adds, this issue is socially relevant, because of traditional notions that see same-sex relations as a choice, a lifestyle or sinful behavior.

In recent years, there have been many studies showing that peoples attitudes toward homosexuality are closely tied to their beliefs about what makes people gay, says LeVay, citing a survey that showed there was a high probability that people who think homosexuality is a choice will object to a gay person being their childrens teacher which in a way might make sense, he adds: If you think being gay is something infectious, socially contagious, and you didnt want your kid to be gay, then you wouldnt want their teacher to be gay ... It follows that demonstrating that biological factors are involved, helps counter those ideas. Still, Im a bit ambivalent about the use of this type of research as some sort of a political weapon in the struggle for gay rights.

The Broad Institute study contains a reminder of the problems and stigmas that still exist with regard to the LGBTQ community. One of the parameters it considers are genetic correlations between genes that are ascribed to homosexuality, and certain psychological problems.

Bailey, the psychologist: One thing that was perceived as controversial, was to look for and find a genetic overlap between homosexual sex genes and genes associated with depression. Its not the same as saying all people who engage in homosexual sex are depressed for genetic reasons, but its also not something that can be easily ignored. There are assumptions that the higher rates of depression among gay men and lesbians is due to the way they are mistreated by society, but the evidence for that is not so overwhelming. There is also the fact, for example, that you have as high a rate of depression among homosexual men in the Netherlands, which is very tolerant, as you have in some less tolerant places, like the United States.

Ganna, for his part, tries to soften that criticism: Even if we see genetic overlap, or correlation, it is not set in stone that weve found a biological mechanism that causes depression and same-sex behavior, he says. There are many explanations for why this one genetic marker is associated with both things. But finding these correlations help us study human traits in general.

In the meantime, there is a price to be paid for conducting research in this realm, which all those involved must be aware of. Reminders of this abound, and are almost routine. In some cases whats at stake is not even a groundbreaking study or one of tremendous scientific importance. In 2017, for example, two researchers from Stanford published an article stating that gay men are predicted to have smaller jaws and chins, slimmer eyebrows, longer noses, and larger foreheads; the opposite should be true for lesbians. In the next stage, they created a facial-recognition program with the aid of more than 14,000 images taken from a singles site of straights and LGBTQs. The program was able to distinguish between gays and lesbians and heterosexuals with an accuracy of 81 percent for men and 71 percent for women, in contrast to an average rate of successful human guesses of 61 percent and 54 percent, respectively. Even though the program achieved relatively impressive results, the study as such drew widespread criticism not unusual for researchers engaged in such studies.

The Stanford gays identification program may be an extreme example, in this respect, but its also a byproduct of the considerable surge in studies in this field, a trend that began in the early 1990s. Together with the scientific community, media interest in the subject of same-sex orientation and its causes has contributed substantially to transmitting messages and shaping public opinion.

In the United States, this can be seen in a series of polls conducted by Gallup, Inc. The first one, conducted in 1977, found that only 13 percent of the respondents believed that homosexuality is an innate tendency, while 56 percent attributed it to environmental factors. This approach remained largely constant until the period between 1989 and 1996, when the rate of those supporting the innate thesis leaped from 19 percent to 31 percent; by 2001, it stood at 40 percent. Almost a decade and a half later, the annual poll produced, for the first time, a larger proportion who agreed with the innate argument. The latest survey, from the end of last year, showed this trend continuing: More than half of the American public believes that gay people are born with their sexual orientation, whereas only 30 percent attribute it to environmental factors (10 percent said both factors play a part, 4 percent cited other factors and 6 percent said they werent sure).

Changes in the perceptions of the origins of sexual orientation are having a pronounced effect on the struggle LGBTQ individuals are waging for equal rights. The latest Gallup poll shows that an absolutely majority (88 percent) of those who believe that homosexuality is an innate trait also support legitimizing same-sex marriages. In contrast, most of those who see this orientation as being environmentally driven (61 percent) are against.

When it comes to public opinion, which is very important, the born this way idea has been really resonant and has had a very positive impact on society, Hamer maintains. Public opinion polls asked people whether they think [gays] were born this way or not, and we know that believing that homosexuality is innate correlates with having positive feelings toward gay rights. Overall, its been important in educating the public about who we are, as gay people.

Such messages are reaching Israel as well. A poll conducted by the Dialog Institute for Haaretz at the end of 2013 found that 70 percent of those questioned favored full rights for same-sex couples, while 64 percent specifically backed their right to surrogacy. However, two polls conducted in the wake of the surrogacy law protest in July 2018 presented slightly lower numbers: About 57 percent of respondents expressed support for the right of same-sex male couples to surrogacy.

These polls did not ask Israelis whether they believe the origin of same-sex orientation is innate or environmental. If you ask Bailey, though, that doesnt really matter.

Ive gone to great lengths to try to persuade people not to base equal rights for gay people on the causal hypothesis, he says. Its a terrible idea to say gay people should have equal rights because they were born that way. Its terrible in part because some criminals might be born that way, and you dont want to them to have the same rights. Being gay doesnt harm anybody, other than people who are close-minded and easily offended. Preventing people from expressing their homosexuality is quite destructive for them. Thats true whether gay people are born that way or not.

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Is sexual orientation genetic? Yes and no, an extensive study finds - Haaretz

Sexual orientation cannot be wilfully changed and is a product of genetic and environmental factors, said lawyers arguing for the repeal of Section 377A of the Penal Code.

They argued that the law, which criminalises acts of "gross indecency" between men, violates Article 9 of the Constitution guaranteeing the right to life and personal liberty, and Article 12 guaranteeing equal protection before the law.

The legal team, consisting of Mr Eugene Thuraisingam, Mr Suang Wijaya and Mr Johannes Hadi of Eugene Thuraisingam LLP, represented disc jockey Johnson Ong Ming in the High Court yesterday in the second of three cases to be brought against Section 377A this month.

The Attorney-General's Chambers (AGC) has been listed as the respondent in all of the cases.

Mr Ong's lawyers presented expert evidence from six medical professionals to back up their claims, including three called by Mr Ong and three called by the AGC.

Those called by Mr Ong were British psychiatrist Dinesh Bhugra, a professor of mental health and diversity at the Institute of Psychiatry at King's College London; Dr Jacob Rajesh, a senior consultant psychiatrist at the Promises Clinic in Novena Medical Centre; and American public health and epidemiology professor Chris Beyrer of the Johns Hopkins Bloomberg School of Public Health.

Those called by the AGC were Dr Cai Yiming, an emeritus consultant in the Department of Developmental Psychiatry at the Institute of Mental Health; retired geneticist John Tay Sin Hock, the former head of the Human Genetics division at the National University of Singapore; and Dr Derrick Heng Mok Kwee, group director of the Health Ministry's Public Health Group.

The experts on both sides largely agree that sexual orientation cannot be wilfully changed and that one's genes and non-social environmental factors such as exposure to different levels of hormones in the womb are contributors to one's sexual orientation, the lawyers argued.

There is also no credible scientific evidence that "conversion therapy" aimed at changing sexual orientation is safe or effective, they added.

But the experts differed on whether choice and social factors like culture play a role as well.

Dr Cai said there is "very little we can scientifically conclude about whether there is choice in sexual orientation". Dr Tay said that genetics may play some part in determining sexual orientation but is not the sole cause of it, suggesting that culture plays a role as well.

Mr Ong's lawyers contended that the scientific literature Dr Cai cited contradicted his conclusion. They also argued that Dr Tay did not cite any evidence to support his claim that cultural factors play such a role.

"It is absurd, irrational and discriminatory to criminalise a person on the basis of his natural, unchangeable identity and for non-harmful private acts," the team said in a statement to the media yesterday.

The lawyers noted that their case differs from a previous case brought against Section 377A in 2010 by Mr Tan Eng Hong, whose lawyer had argued that a person's sexual orientation is biologically determined. Mr Tan had provided the court with statements from medical and scientific bodies which were not formally entered as evidence, they said.

"For the first time, there is expert evidence before the courts on the nature of sexual orientation," the lawyers said in their statement.

The first of the three recent cases, brought by Mr Bryan Choong Chee Hong, 42, the former executive director of lesbian, gay, bisexual and transgender (LGBT) non-profit Oogachaga, was heard last week.

The third case, brought by LGBT activist and retired doctor Tan Seng Kee, was also heard yesterday.

Mr M. Ravi of Carson Law Chambers, who represented Dr Tan, argued that other laws make it legally obligatory for anyone to report those who violate Section 377A, including gay men themselves, their friends or family members and their medical care providers.

For example, Section 424 of the Criminal Procedure Code (CPC) states that every person aware of the commission of - or intention to commit - any arrestable offence punishable under Chapter XVI of the Penal Code, among others, shall report that commission or intention to the police. Section 377A falls under Chapter XVI of the Penal Code.

Mr Ravi argued that Parliament's stance that Section 377A will not be proactively enforced "interferes with Article 9(1) of the Constitution, as it leads to an inconsistent and arbitrary application of criminal procedure as well as being incongruous with the mandatory obligation" under Section 424 of the CPC.

The three cases were heard by Justice See Kee Oon in chambers and were not open to the public.

The AGC began its submissions yesterday, which are expected to conclude at the next hearing tomorrow.

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Sexual orientation cannot be changed at will, lawyers argue - The Straits Times

An oft-repeated claim by skeptics is that geneticists have disproved the possibility of Adam and Eve. Because existing human genetic diversity is so great, there can be no original couple from whom all people are descended.

Or, thats what were told.

Biology professor and author Dennis Venema summarizes this argument in his book, Adam and the Genome. In it, he claims that every genetic analysis estimating ancestral population sizes has agreed that we descend from a population of thousands, not a single ancestral couple.

Some Christian authors have reacted to this apparent consensus by proposing new ways of reading Genesis that make Adam and Eve either mythological or not really our first parents. The goal has been to accommodate theology and the Bible to what were told is settled science.

But what if the science on Adam and Eve isnt so settled? Thats the argument of a new paper by Discovery Institute senior fellow and developmental biologist Ann Gauger and Swedish mathematician Ola Hssjer, recently published in the journal, BIO-Complexity.

In order to test whether it really is impossible to account for modern variation in human beings by starting with just two people, these researchers did something that, incredibly, no one had tried before: They started with just two people, and ran the numbers.

Using accepted population growth and mutation rates, Gauger and Hssjer programmed a computer to start with a genetic Adam and Eve and replicate the known distribution of diversity in todays human population. Their results, to put it simply, fly in the face of the much-touted consensus.

According to their model, a couple who shared some genetic markers could generate all the diversity we see today within about 2 million yearswhich Venema and others claim is impossible.

However, given two people who share no genetic markersin other words, two people who werent born but were created with four unique sets of chromosomesthat time frame drops to a few hundred thousand, not millions, of years.

Writing at Evolution News, Gauger points out that further tweaks in the rates of population growth, structure, mortality, birth, and mutation could place that theoretical first couple even more recently in history.

In any case, the authors are careful to note that the point of their paper was not to date Adam and Eve, or even to prove from a genetic standpoint that they existed. Rather, they just wanted to demonstratecontrary to the oft-repeated claimthat it is possible for all human beings to have descended from an original pair.

Of course, much more work remains to be done, but the paper has served to clarify two things.

First, scientists assumptions about the past can change their results. Gauger explains that once hurdles in computing power were overcome, this experiment was an obvious way to test existing dogma on human origins. But in her words, no one bothered because They believed that starting from two was useless.

In fact, many researchers failed to use standard methods for modeling population genetics because of their baked-in evolutionary assumptions. For instance, one popular tool relies on comparisons between human and chimpanzee DNA to track mutationssomething Gauger points out is useless if we dont share a common ancestor with chimps.

Second, and more importantly, this paper hints at how tentative so-called settled science can be. Christians who rush to revise their understanding of characters like Adam and Eve to make way for the latest consensus should think more about the theological consensus theyre tinkering with, like the fall, the image of God, original sin, and creation.

They should also consider all the un-tinkering they may have to do one day when that scientific consensus changes.

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BreakPointis a program of the Colson Center for Christian Worldview. BreakPoint commentaries offer incisive content people can't find anywhere else; content that cuts through the fog of relativism and the news cycle with truth and compassion. Founded by Chuck Colson (1931 2012) in 1991 as a daily radio broadcast, BreakPoint provides a Christian perspective on today's news and trends. Today, you can get it in written and a variety of audio formats: on the web, the radio, or your favorite podcast app on the go.

John Stonestreetis President of the Colson Center for Christian Worldview, and radio host ofBreakPoint,a daily national radio program providing thought-provoking commentaries on current events and life issues from a biblical worldview. John holds degrees from Trinity Evangelical Divinity School (IL) and Bryan College (TN),and is the co-author ofMaking Sense of Your World: A Biblical Worldview.

Publication date:November 18, 2019

Photo courtesy:Getty Images/Digital Imagination

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Adam and Eve Are Possible: A Second Bite at the Genetic Apple - Christianheadlines.com

REDWOOD CITY, Calif.--(BUSINESS WIRE)--

InterVenn Biosciences, a company in the life sciences and technology sector, is pleased to announce that the interim results of its prospective clinical trial for its Ovarian Cancer Clinical Decision Tool have successfully exceeded its milestones and expectations.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20191118005886/en/

The clinical validation trial is currently ongoing in the United States, Malaysia, and the Philippines with women from five different ethnic groups Caucasian, Indian, Chinese, Malay, and Filipino taking part. The full clinical trial is expected to be completed in April 2021.

The trial, called InterVenn Ovarian Cancer Liquid Biopsy (V.O.C.A.L.), is aimed at confirming that a novel blood test based on mass spectrometry data processed by a proprietary, artificial intelligence- and machine learning-driven algorithm exceeds the accuracy of currently available approaches to distinguish between malignant and benign pelvic tumors, with a primary focus on early recognition of ovarian cancer, the deadliest of gynecological malignancies.

The interim results confirmed that the InterVenn test performance significantly exceeds that of the current state-of-the-art ovarian cancer test, CA 125, with both markedly better specificity and sensitivity. The V.O.C.A.L. test analyzes glycoproteomic signatures as highly accurate biomarkers for disease states, as well as for advanced drug target discovery. By combining AI and mass spectrometry, InterVenns technology provides unprecedented power to leveraging the heretofore largely inaccessible, vast information content of the glycoproteome for the improvement of health care.

These interim results clearly demonstrate the power and performance of our AI and mass spectrometry platform. We were consistently able to differentiate malignant from benign tumors with unparalleled specificity and sensitivity using only a blood test - weve set a newer, much higher, standard for performance, said InterVenn CEO, Aldo Carrascoso.

This performance means that we were able to detect not only the more common epithelial ovarian cancer but also rare ovarian cancer subtypes aside from non-ovarian primary cancers such as lung, colorectal and others. These findings are of major clinical importance, since 20% of all women will develop an ambiguous pelvic mass during their lifetime, and among those, 12%-18% are typically malignant. Being able, based on our blood test, to distinguish malignant pelvic masses from benign ones without having to undergo surgery will have a major impact on patient outcomes, unnecessary suffering, and health care expenditures.

Ovarian cancer ranks fifth in cancer deaths among women, according to the American Cancer Society, which reported that 22,250 were diagnosed with ovarian cancer in 2019, and that 13,980 died from the disease. InterVenn Biosciences V.O.C.A.L. test is more than just a new weapon bringing patients hope against a deadly disease; it is also a key example of how health AI and machine learning can be used in the health care space to address life-threatening diseases with a more proactive approach.

InterVenn Biosciences also announced the latest addition to its team, Klaus Lindpaintner, MD, MPH, FACP, FACMG, as Chief Scientific Officer and Chief Medical Officer, a role in which he will be the head all of InterVenns global scientific operations and clinical affairs.

Klauss previous roles include an assignment at Pfizer as VP and Global Head of Human Genetics and Computational Biomedicine, four years as CSO at Thermo Fisher Scientific, and many years as Sr. VP and Head of the Roche Center for Medical Genomics, where he was intimately involved in Roches transition to becoming the first major personalized health care company. Previous to that, Klaus served as a faculty member at Harvard Medical School and the Harvard School of Public Health.

We finally have the quintessential scientific leader in Klaus. He will be working closely with my two other co-founders, Carlito Lebrilla, Ph.D. Distinguished Professor of Chemistry, Biochemistry and Molecular Medicine at UC Davis, and Carolyn Bertozzi, Ph.D., Anne T. and Robert M. Bass Professor of Chemistry and Professor of Chemical & Systems Biology and Radiology at Stanford University to propel their foundational work, since InterVenns core science and approach is their legacy, added Carrascoso.

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Coupling Klaus strategic and translational experience with Carlitos high throughput mass spectrometry expertise and Carolyns glycobiology leadership makes for an unbeatable team. We are very fortunate to have Klaus on board; his deep expertise in medicine, genomics, and translational research will be a critical addition to the team.

To find out more about InterVenn Biosciences and how the company is leveraging artificial intelligence and mass spectrometry to transform medical technology, visit https://intervenn.bio. For all general and media inquiries about InterVenn Biosciences, please contact Andrea Vuturo by telephone at (877) 772-2205 or email press@venn.bio.

About InterVenn Biosciences

InterVenn Biosciences utilizes a proprietary glycoproteomic biomarker interrogation platform using AI and mass spectrometry for next-gen precision medicine. The companys applications include diagnostics/prognostics for ovarian, pancreatic, liver, breast, and kidney cancer, together with applications from the Vista suite of solutions for treatment and monitoring, immune profiling, patient stratification, and disease progression. For more information about InterVenn Biosciences, please visit the companys website.

Website: https://intervenn.bio/ LinkedIn: https://www.linkedin.com/company/intervenn/ LinkedIn (2): https://www.linkedin.com/in/klaus-lindpaintner-b327551b/ Clinical Trials: https://clinicaltrials.gov/ct2/show/NCT03837327?term=NCT03837327&rank=1 Mayo Clinic: https://www.mayoclinic.org/tests-procedures/ca-125-test/about/pac-20393295 American Cancer Society: https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html Forbes: https://www.forbes.com/sites/tomtaulli/2019/10/12/ai-artificial-intelligence--whats-the-next-frontier-for-healthcare/ Science Daily: https://www.sciencedaily.com/releases/2019/02/190215082340.htm

InterVenn BioSciences 800 Chesapeake Drive Redwood City, CA 94063 United States of America

View source version on businesswire.com: https://www.businesswire.com/news/home/20191118005886/en/

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InterVenn Biosciences Announces Positive Interim Clinical Trial Results and Appoints Biotech Veteran Klaus Lindpaintner, M.D. as Chief Scientific and...

The current study was initiated when a patient presented with a small brain size at birth and severe abnormalities in brain structures at the Baylor Hopkins Center for Mendelian Genomics (CMG), a center directed by Dr. Jim Lupski, professor of pediatrics, molecular and human genetics at Baylor College of Medicine and attending physician at Texas Childrens Hospital, said Dr. Hugo J. Bellen, professor at Baylor, investigator at the Howard Hughes Medical Institute and Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital.

This patient and others in a cohort at CMG had not been infected by Zika virus in utero. They had a genetic defect that caused microcephaly. CMG scientists determined that the ANKLE2 gene was associated with the condition. Interestingly, a few years back the Bellen lab had discovered in the fruit fly model that ANKLE2 gene was associated with neurodevelopmental disorders. Knowing that Zika virus infection in utero can cause microcephaly in newborns, the team explored the possibility that Zika virus was mediating its effects in the brain via ANKLE2.

In a subsequent fruit fly study, the researchers demonstrated that overexpression of Zika protein NS4A causes microcephaly in the flies by inhibiting the function of ANKLE2, a cell cycle regulator that acts by suppressing the activity of VRK1 protein.

Since very little is known about the role of ANKLE2 or VRK1 in brain development, Bellen and his colleagues applied a multidisciplinary approach to tease apart the exact mechanism underlying ANKLE2-associated microcephaly.

The team found that fruit fly larvae with mutations in ANKLE2 gene had small brains with dramatically fewer neuroblasts brain cell precursors and could not survive into adulthood. Experimental expression of the normal human version of ANKLE2 gene in mutant larvae restored all the defects, establishing the loss of Ankle2 function as the underlying cause.

To understand why ANKLE2 mutants have fewer neuroblasts and significantly smaller brains, we probed deeper into asymmetric cell divisions, a fundamental process that produces and maintains neuroblasts, also called neural stem cells, in the developing brains of flies and humans, said first author Dr. Nichole Link, postdoctoral associate in the Bellen lab.

Asymmetric cell division is an exquisitely regulated process by which neuroblasts produce two different cell types. One is a copy of the neuroblast and the other is a cell programmed to become a different type of cell, such as a neuron or glia.

Proper asymmetric distribution and division of these cells is crucial to normal brain development, as they need to generate a correct number of neurons, produce diverse neuronal lineages and replenish the pool of neuroblasts for further rounds of division.

When flies had reduced levels of Ankle2, key proteins, such as Par complex proteins and Miranda, were misplaced in the neuroblasts of Ankle2 larvae. Moreover, live imaging analysis of these neuroblasts showed many obvious signs of defective or incomplete cell divisions. These observations indicated that Ankle2 is a critical regulator of asymmetric cell divisions, said Link.

Further analyses revealed more details about how Ankle2 regulates asymmetric neuroblast division. They found that Ankle2 protein interacts with VRK1 kinases, and that Ankle2 mutants alter this interaction in ways that disrupt asymmetric cell division.

Linking our findings to Zika virusassociated microcephaly, we found that expressing Zika virus protein NS4A in flies caused microcephaly by hijacking the Ankle2/VRK1 regulation of asymmetric neuroblast divisions. This offers an explanation to why the severe microcephaly observed in patients with defects in the ANKLE2 and VRK1 genes is strikingly similar to that of infants with in utero Zika virus infection, Link said.

For decades, researchers have been unsuccessful in finding experimental evidence between defects in asymmetric cell divisions and microcephaly in vertebrate models. The current work makes a giant leap in that direction and provides strong evidence that links a single evolutionarily conserved Ankle2/VRK1 pathway as a regulator of asymmetric division of neuroblasts and microcephaly, Bellen said. Moreover, it shows that irrespective of the nature of the initial triggering event, whether it is a Zika virus infection or congenital mutations, the microcephaly converges on the disruption of Ankle2 and VRK1, making them promising drug targets.

Another important takeaway from this work is that studying a rare disorder (which refers to those resulting from rare disease-causing variations in ANKLE2 or VRK1 genes) originally observed in a single patient can lead to valuable mechanistic insights and open up exciting therapeutic possibilities to solve common human genetic disorders and viral infections.

Others who contributed in this study are Hyunglok Chung, Angad Jolly, Marjorie Withers, Burak Tepe, Benjamin R. Arenkiel, Priya S. Shah, Nevan J. Krogan, Hatip Aydin, Bilgen B. Geckinli, Tulay Tos, Sedat Isikay, Beyhan Tuysuz, Ganesh H. Mochida, Ajay X. Thomas, Robin D. Clark and Ghayda M. Mirzaa. They are affiliated to one or more of the institutions: Baylor College of Medicine, Texas Childrens Hospital and the Jan and Dan Duncan Neurological Research Institute in Houston, TX; University of California at Davis and San Francisco; Zeynep Kamil Maternity and Children's Training and Research Hospital, Istanbul, Turkey; Marmara University School of Medicine, Istanbul, Turkey; Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases, Ankara, Turkey; Boston Childrens Hospital; Harvard Medical School, Boston, MA; Massachusetts General Hospital, Boston, MA; Loma Linda University Medical Center, Loma Linda, CA; University of Washington, Seattle, WA; and Seattle Children's Research Institute, Seattle, WA.

The study was funded by the National Institutes of Healths F32NS092270, NIH/NINDS R35NS105078, NIH U54NS093793, NIH R24OD022005, NIH/NINDS K08NS092898, Howard Hughes Medical Institute (HHMI), Medical Research Fellowship, Jordans Guardian Angels, a jointly funded NHGRI and NHLBI grant to the Baylor-Hopkins Center for Mendelian Genomics (UM1 HG006542) and the Huffington Foundation.

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How maternal Zika infection results in newborn microcephaly - Baylor College of Medicine News

Turns out Dicerna wasnt done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH is also purchasing $50 million worth of Dicernas equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

Dicerna CEO Doug Fambrough describes the deal as a capstone for its partnering efforts in the liver space and a further sign that the biotech has entered a more mature phase of partnering with increased scope and value.

In a call with analysts and investors following the announcement, he adopted a real estate analogy:

If you think of the liver as an island, there are individual properties on the island that we have partnered complement with Alexion, a couple of particular targets in NASH with BI, et cetera. The collaboration with Novo has as its purview the rest of the land on the island that is not partnered in any of the four existing collaborations and we will not be selling any additional real estates, so to speak, that Novo could choose to develop. This allows new insights that come from human genetics or frankly any source to inspire Novo to include a target in the collaboration.

Dicerna is tasked with discovery and preclinical candidate selection on a number of liver cell targets for disorders spanning chronic liver disease, NASH, type 2 diabetes, obesity, and rare diseases. Novo Nordisk has committed to $25 million per year during the first three years. While the duo hasnt disclosed how many years they expect the collaboration to run, the plan is to explore around 30 throughout the period.

But Dicernas ambitions here go beyond starting programs for bigger companies to take over. It has negotiated an option to opt into two drugs for more prevalent ailments after viewing clinical data generated by Novo allowing their clinical team to buy into successes without bearing the cost, Fambrough highlighted. Under the deal, it can also initiate the development of two orphan drugs that the bigger partner can opt in to.

The really broad collaboration is designed to focus less on individual genes than the potential of different combination approaches in a number of liver diseases, COO Jim Weissman said.

Internally, Dicerna has been applying its platform routinely to examine a list of genes associated with different cardiometabolic diseases, according to CSO Bob Brown.

We just routinely knock them out and then use the GalXC molecules we identified there to interrogate the gene function in the relevant disease models that we run routinely in house, he said on the call. Theres no direct alignment of lists yet, but weve interrogated approximately 40 genes this way in different models of cardiometabolic disease.

Novo has yet to identify the genes that they would like to start with, but Fambrough noted that the targets they have expressed interest in are still very much available.

Adding to previous deals with Boehringer Ingelheim, Alexion, Eli Lilly and Roche, the influx of capital from Novo should keep Dicerna fully funded for at least a year after the envisioned commercial launch of their lead program in primary hyperoxaluria, the management said.

Social image: AP Images

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Dicerna scores broad, 'rest of liver' deal with Novo Nordisk, bagging $225M in cash to hit some 30 targets with RNAi platform - Endpoints News

SINGAPORE - Sexual orientation cannot be wilfully changed and is a product of genetic and environmental factors, said lawyers arguing for the repeal of Section 377A of the Penal Code.

They argued that the law, which criminalises acts of "gross indecency" between men, violates Article 9 of the Constitution guaranteeing the right to life and personal liberty, and Article 12guaranteeing equal protection before the law.

The legal team, consisting of Mr Eugene Thuraisingam, Mr Suang Wijaya and Mr Johannes Hadi of Eugene Thuraisingam LLP, represented disc jockey Johnson Ong Ming in the High Court on Monday (Nov 18) in the second of three cases to be brought against Section 377A this month.

The Attorney-General's Chambers (AGC) has been listed as the respondent in all of the cases.

Mr Ong's lawyers presented expert evidence from six medical professionals to back up their claims, including three called by Mr Ong and three called by the AGC.

Those called by Mr Ong were British psychiatrist Dinesh Bhugra, a professor of mental health and diversity at the Institute of Psychiatry at King's College London; Dr Jacob Rajesh, a senior consultant psychiatrist at the Promises Clinic in Novena Medical Centre; and American public health and epidemiology professor Chris Beyrer of the Johns Hopkins Bloomberg School of Public Health.

Those called by the AGC were Dr Cai Yiming, an emeritus consultant in the Department of Developmental Psychiatry at the Institute of Mental Health; retired geneticist John Tay Sin Hock, who was the former Head of Division of Human Genetics at the National University of Singapore; and Dr Derrick Heng Mok Kwee, group director of the Public Health Group in the Ministry of Health.

The experts on both sides largely agree that sexual orientation cannot be wilfully changed and that biological factors such as one's genes and non-social environmental factors such as exposure to different levels of hormones in the womb are contributors to one's sexual orientation, the lawyers argued.

There is also no credible scientific evidence that "therapy" aimed at changing sexual orientation, such as reparative or conversion therapy, is safe or effective, they added.

But the experts differed on whether choice and social environmental factors like culture play a role in determining sexual orientation.

Dr Cai said there is "very little we can scientifically conclude about whether there is choice in sexual orientation".

Dr Tay said that genetics may play some part in determining sexual orientation but are not the sole cause of it, suggesting that culture plays a role as well.

Mr Ong's lawyers contended that the scientific literature cited by Dr Cai contradicted his conclusion.

They also argued that Dr Tay did not cite any evidence to support his conclusion that cultural factors play such a role.

"It is absurd, irrational and discriminatory to criminalise a person on the basis of his natural, unchangeable identity and for non-harmful private acts," the team said in a statement to the media summarising their arguments.

The lawyers noted that their case differs from a previous case brought against Section 377A in 2010 by Mr Tan Eng Hong, whose lawyer had argued that there was overwhelming evidence that a person's sexual orientation is biologically determined.

Mr Tan had provided the court with statements from medical and scientific bodies which were not formally entered as evidence, they said.

"For the first time, there is expert evidence before the courts on the nature of sexual orientation. In the previous cases, the court was only asked to take judicial notice of scientific facts which required a different legal test," the lawyers said in their statement.

The first of the three recent cases, brought by Mr Bryan Choong Chee Hong, 42, the former executive director of lesbian, gay, bisexual and transgender (LGBT) non-profit Oogachaga, was heard last week.

The third case, brought by LGBT activist and retired general practitioner Tan Seng Kee, was also heard on Monday.

Mr M. Ravi of Carson Law Chambers, who represented Dr Tan, argued that other laws make it legally obligatory for anyone to report those who violate Section 377A, including gay men themselves, their friends or family members, and their medical care providers.

For example, Section 424 of the Criminal Procedure Code (CPC) states that every person aware of the commission of - or the intention of any other person to commit - any arrestable offence punishable under Chapter XVI of the Penal Code, among others, shall report that commission or intention to the police. Section 377A falls under Chapter XVI of the Penal Code.

Mr Ravi argued that Parliament's stance that Section 377A will not be proactively enforced "interferes with Article 9(1) of the Constitution, as it leads to an inconsistent and arbitrary application of criminal procedure as well as being incongruous with the mandatory obligation" under Section 424 of the CPC.

The three cases were heard by Justice See Kee Oon in chambers and were not open to the public.

The AGC began its submissions on Monday and will conclude by the end of the day or at the next hearing on Wednesday.

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Sexual orientation cannot be wilfully changed, say lawyers fighting to repeal Section 377A - The Straits Times

News

Researcher Tom Cappola tells us about the latest clinical trials and medical breakthroughs to be announced during Scientific Sessions.

Chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania, Tom Cappola.

For the first time in its near 100-year history, the American Heart Association (AHA)will host its annual meeting in Philadelphia. AHAs Scientific Sessions is the largest cardiovascular meeting in the United States. On November 16-18, the meeting will attract nearly 18,000 attendees from more than 100 countries to the Pennsylvania Convention Center, and an additional two million medical professionals who will participate virtually in lectures and discussions about basic, translational, clinical and population science innovations aimed at reducing disability and deaths caused by cardiovascular disease and stroke.

The American Heart Association is excited to be in Philadelphia, said Michelle Kirkwood, director of National Science Media Relations for AHA. It has been on our wish list for some time, especially since the renovations at the Pennsylvania Convention Center and the citys landmark, robust nonsmoking laws that align directly with the American Heart Associations health and wellness goals. We are excited for our thousands of attendees to visit Philadelphia.

More than 610,000 people die of heart disease in the United States every year, according to the CDC. While heart disease is a leading cause of death for both men and women, it claims the lives of over 400,000 American women each year, or one death every 80 seconds. During the three-day meeting, more than 12,000 leading physicians, scientists, cardiologists and healthcare professionals in the global cardiovascular health community will host 850 educational sessions and more than 4,100 original research presentations to unveil the late-breaking science, clinical trials, and novel therapeutics and pathways that are shaping the future of cardiovascular care.

Its very fitting for Scientific Sessions to be here, chief of the cardiovascular medicine division in the Perelman School of Medicine at the University of Pennsylvania Tom Cappola said. We have the first medical school in the country and the first teaching hospital in the country. It makes sense that these new innovations would be presented in a place where theres already been so much innovation.

Cappola will be one of several Penn researchers leading the Cardiovascular Expert Theater, Innovations in Cardiovascular Therapies session during the meeting. Here are just a few big trends in heart care that Cappola says we can expect to learn more about during this weekends meeting:

Using artificial intelligence to monitor heart health

Artificial intelligence (AI) is having a big impact on cardiovascular care. Results from two preliminary studies to be presented this weekend will show AI can be used to accurately examine electrocardiogram (ECG) test results to possibly predict irregular heartbeat and risk of death. There will also be a presentation on the Apple Heart Study, which found that the Apple Watch and other wearable remote monitoring devices may be capable of detecting atrial fibrillation (aFib), an irregular and often rapid heartbeat that can lead to blood clots, stroke, heart failure and other complications.

Identifying new risk factors for aFib and stroke

George Mason University researchers will present results from two studies that found young people who smoke marijuana regularly have an increased risk of stroke. According to the study findings, young adults between the ages 18 and 44 who reported frequent use of marijuana, cigarettes and e-cigarettes were three times more likely to suffer stroke than young adults who did not smoke marijuana at all. The study also found that African-American males between the ages of 15 and 24 faced the highest risk of being hospitalized for arrhythmia.

In one Penn study to be presented this weekend, researchers found women who are diagnosed with peripartum cardiomyopathy (PPCM) during late pregnancy or within a month following delivery are more likely to experience restored cardiac function and improved outcomes compared to those who are diagnosed later in the postpartum period. The findings underscore the need for increased awareness and monitoring of heart failure symptoms, particularly among black women, who, on average, are diagnosed significantly later than white patients, according to study results.

Making advances in genetics and genomics

Another big trend at this years meeting will be the continued advancement in genetics and genomics, and how thats impacting cardiovascular care.

I think that genomic medicine has arrived and its arriving in waves, but it will ultimately affect all aspects of cardiovascular care, Cappola said. We have lots of people getting their 23andMe for sort of recreational purposes and they dont know what to do with it. But were starting to figure out what to do with that genetic information to improve care.

Another Penn Medicine study to be presented during the meeting will show why taller people may have an increased risk of developing atrial aFib. The research found a strong link between the genetic variants associated with height and ones risk for AFib, for the first time demonstrating that height may be a causal not correlated risk factor for the condition. Researchers hope insight from human genetics in large studies like this one will help them better understand causal risk factors for common disease.

It takes expertise to find links like this. Thats why researchers go to the American Heart Association meetings. You get all the experts together, they share their knowledge and this helps us to actually figure out what to do with this genetic information, Cappola said. Thats true across the board, but its particularly important for genomic medicine as it continues to advance.

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The American Heart Association's Annual Conference Comes to Philly This Weekend - Philadelphia magazine

Researchers have found that taller people have an increased risk of developing atrial fibrillation (AFib), an irregular and often rapid heartbeat that can lead to stroke, heart failure and other complications.

The research, which reveals a strong link between the genetic variants associated with height and one's risk for AFib, is the among the first to demonstrate that height may be a causal--not correlated--risk factor for AFib.

Researchers found that the risk for AFib climbed as one's height increased, with every one-inch increase in height translating to about a three percent increase in risk of Afib--independent of other clinical factors--as compared to those at average height (5 feet and 7 inches).

"Our findings suggest it may be beneficial to incorporate height into risk-prediction tools for AFib," said the study's lead author Michael Levin from University of Pennsylvania.

"While current guidelines advise against widespread screening for AFib, our findings show that a certain group of patients--specifically, very tall patients--may benefit from screening," Levin added.

AFib, which affects more than 33 million people worldwide, is a common, abnormal heart rhythm.

There are a number of clinical risk factors for developing AFib, including high blood pressure, heart disease, diabetes, and obesity.

Observational studies, examining population-level data, have found that taller individuals appear to have a higher risk of developing AFib.

To further examine the association between height and Afib, the research team leveraged data from the Genetic Investigation of Anthropometric Trials (GIANT) consortium, which studied more than 700,000 individuals to identify genetic variants associated with height.

They also examined data from the Atrial Fibrillation Genetics (AFGen) consortium, which studied more than 500,000 individuals to identify genetic variants associated with AFib.

The authors employed a statistical method which uses genetics to precisely estimate the relationship between two traits.

Their analysis revealed that genetic variants associated with height were also strongly associated with Afib, suggesting that increased height may be a cause of atrial fibrillation.

This relationship remained strong even after adjusting for traditional AFib risk factors, like heart disease, high blood pressure, and diabetes, among others.

From there, researchers used a similar statistical method to conduct an individual-level analysis of nearly 7,000 individuals enrolled in the Penn Medicine Biobank.

They found that height, and genetic variants associated with height, are strongly associated with an increased risk of AFib, independent from traditional clinical and echocardiographic risk factors.

"These analyses show how we can use human genetics to help us better understand causal risk factors for common disease," said the study's senior author Scott Damrauer.

The study is scheduled to be presented at American Heart Association 2019 Scientific Sessions in Pennsylvania, US.

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Taller People have Increased Risk of Irregular Heartbeat - News18

"It has a whole bunch of other things surrounding it, but it creates depressive symptoms."

According to SANE Australia, up to 4 per cent of Australians will develop BPD at some point in their life, with the symptoms usually manifesting in late adolescence.

Sufferers have trouble managing their emotions and impulses, and can also struggle to maintain a stable self-image.

The causes of BPD are not well understood, although they are believed to be a combination of biological and lifestyle factors.

Ms Collett said despite her diagnosis being relatively simple compared to other mental health issues, it was "frustrating" that there still wasnt a clear diagnosis and treatment for many sufferers.

Its hoped that new research from QIMR Berghofer Medical Research Institute could help change that, with scientists there identifying key areas on the human genome with direct links to depressive symptoms.

Senior study investigator Professor Eske Derks said the research uncovered seven distinct regions on the human genome with links to symptoms.

"We identified, for the first time, three genetic regions related to sleep problems, two for anhedonia [a loss of interest or pleasure in life], one related to changes in appetite, and one for depressed mood," Professor Derks said.

Overall, about one in 11 people, or 9 per cent of Australians, reported having depression or depressed feelings in 2014-15, according to figures from the Australian Bureau of Statistics.

The QIMR findings provide insight into why the symptoms of depression can vary hugely between patients, and they point the way to more targeted therapies.

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"In some patients, depression will manifest as a reduced appetite, while for others, there will be increased appetite," Professor Derks said.

"So normally if youre looking for the genetic risk factors for depression, you tend to collapse all of these symptoms together, even though they can be quite different from patient to patient."

Professor Derks said being able to accurately assess exactly what genes were in play for individual patients meant they would be able to get tailored treatment instead of the current method of "trial and error", where patients are prescribed the most common medication and then put on other drugs if that fails.

Ms Collett said it would be a comfort going forward to have a more certain diagnosis.

"Im naturally curious about my own health situation, so it would be really good to know the underlying reason why I have it. Was it genetics? Was it something that happened when I was a kid? Who knows?" she said.

The study, which examined genetic data and self-reported symptoms from 150,000 people from the UK Biobank, has been published in the journal Psychological Medicine.

Stuart Layt covers health, science and technology for the Brisbane Times. He was formerly the Queensland political reporter for AAP.

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Clear link between genetics and depressive symptoms uncovered - The Age

By Stephanie Miceli | Nov. 13, 2019

When Sara Altschule took a 23andMe ancestry test, the results confirmed what she already suspected: She is 77 percent Ashkenazi Jewish. However, months later, after opting into add-on health tests, she received life-changing news: She had a BRCA2 gene mutation, which is particularly prevalent among Ashkenazi Jewish women. Altschules BRCA2 mutation meant her lifetime risk of developing breast cancer is about 69 percent; for ovarian cancer, it is about 17 percent.

As at-home genetic tests grow in popularity, some individuals have expressed concern about the complexities of the results. Speaking about her experience with at-home genetic testing at a recent workshop of the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine, Altschule told attendees, The results not only probably saved my life, but may have also saved the lives of people in my family who now know they are also BRCA2 positive. While empowering for her, she also wishes she had received the results from a genetic counselor not via email.

Traditionally, there have been two main types of genetic testing: traditional tests initiated by a doctor, and direct-to-consumer (at-home) tests. Most people do a combination of both, said keynote speaker Robert Nussbaum, chief medical officer of Invitae. About one-third of people who take an at-home test share the results with a provider, who can make appropriate referrals based on the results, he said.

Knowledge Is Power

After seeing a genetic counselor and getting a more comprehensive blood test, Altschule decided to undergo a preventive double mastectomy at the age of 31. I felt powerless during this process, and I wanted to take my power back. This was the easiest and toughest decision of my life, said Altschule.

Panelist Dorothy Pomerantz, who also received news of her BRCA status via 23andMe, said online test results are not a replacement for a one-to-one conversation with a trusted provider. Pomerantz considers herself lucky to have received actionable information, though she still has complicated feelings about how that information was delivered.

This information is complicated and nuanced. We need someone to walk us through the dark, said Pomerantz. When my genetic counselor confirmed my results, she asked me what I needed in that moment. Did I need to vent? Did I want information? Did I need to be alone or cry?

Affordability Is Part of Accessibility

Aside from having access to genetic testing in the first place, Altschule and Pomerantz acknowledged they had the resources to get immediate follow-up testing and surgery.

What about those who cant get their doctors on the phone? What about those who dont have doctors at all? asked Pomerantz.

Without insurance, someone with a risk of cancer may not have those options, said Sadie Hutson, director of the Cancer Genetics Program at Pikeville Medical Center in Kentucky. In the Appalachian communities where she works, coal mining, the dominant industry, has been linked to high incidences of lung cancer. However, many people have to live with the knowledge of that risk and the inability to act on it.

Affordability of genetic testing is a very real problem, said Hutson.

There is also a dire shortage of genetic counselors in the region, she added. Hutson has partnered with mobile clinics and faith-based organizations that provide genetic testing and counseling free of charge, particularly to the regions Medicaid population. Hutson also noted the importance of offering free follow-up testing to family members.

Panelists discussed the accessibility of direct-to-consumer genetic tests for underserved and rural populations and ways to increase engagement, literacy, and reduce disparities.

Steps Toward Including All of Us

We have a skewed evidence base in human genomics research, said Malia Fullerton, professor of bioethics and humanities at the University of Washington School of Medicine. Because certain populations are underrepresented in research, when they do receive genetic testing, there is a lack of data that they can act on. Joyce Tung, 23andMes vice president of research, acknowledged most of the companys customers are white people of European descent and it wants to change that.

We cant provide information that we dont have, she said. A lack of data can halt progress and new discoveries in diseases that primarily affect diverse communities such as sickle cell disease, which is prevalent in people of African descent. Tung highlighted several initiatives at 23andMe that aim to improve diversity, including the African American Sequencing Project, Global Genetics Project, and the Latino Sequencing Project.

In addition, underrepresented populations are more likely to receive uncertain test results, often because their genetic variants have not been well-studied. As a result, they may experience unnecessary testing or lifestyle changes, or false reassurance, and the psychological burden that comes with it, Fullerton said.

To address the lack of diversity in genetic databases, last year, the National Institutes of Health launched its All of Us research initiative. It aims to collect data from 1 million Americans from various population groups.

The vast majority of 23andMe consumers 80 percent agree to share their data in the hopes of contributing to science and new insights about health and disease. However, the current lack of diversity in genetic databases risks hindering the science.

There is a critical opportunity for multiple sectors to come together to ensure proper inclusion of all individuals in genetic and genomic testing, said Hutson.

Integrating Consumer Genomics into Health Care

Speakers throughout the day acknowledged the challenges around integrating consumer genomics data into clinical care. Consumers often want information fast, but health systems may not be able to quickly provide the confirmation genetic testing following a positive DTC result.

This continuum of care has a lot of access points and a lot of people trying to find pathways, but really it is reflective of the overall health system, said Siobhan Dolan, a professor and vice chair for research at Albert Einstein College of Medicine. Maybe genetics has given people an opportunity to find alternative routes and maybe we could continue to learn from that try to put something together that is continuous.

Visit http://nationalacademies.org/hmd/Activities/Research/GenomicBasedResearch/2019-OCT-29.aspx to view speaker presentations and other information about the Workshop on Exploring the Current Landscape of Consumer Genomics.

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At-Home DNA Tests Still Need the 'Human Touch,' Say Panelists at Genomics Roundtable Workshop - National Academies of Sciences, Engineering, and...

A new study led by researchers at Baylor College of Medicine revealed how in utero Zika virus infection can lead to microcephaly in newborns. The team discovered that the Zika virus protein NS4A disrupts brain growth by hijacking a pathway that regulates the generation of new neurons. The findings point at the possibility of developing therapeutic strategies to prevent microcephaly linked to Zika virus infection. The study appeared Thursday in the journal Developmental Cell.

Patients with rare genetic mutations shed light on how Zika virus causes microcephaly

The current study was initiated when a patient presented with a small brain size at birth and severe abnormalities in brain structures at the Baylor Hopkins Center for Mendelian Genomics (CMG), a center directed by Dr. Jim Lupski, professor of pediatrics, molecular and human genetics at Baylor College of Medicine and attending physician at Texas Childrens Hospital, said Dr. Hugo J. Bellen, professor at Baylor, investigator at the Howard Hughes Medical Institute and Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital.

This patient and others in a cohort at CMG had not been infected by Zika virus in utero. They had a genetic defect that caused microcephaly. CMG scientists determined that the ANKLE2 gene was associated with the condition. Interestingly, a few years back the Bellen lab had discovered in the fruit fly model that ANKLE2 gene was associated with neurodevelopmental disorders. Knowing that Zika virus infection in utero can cause microcephaly in newborns, the team explored the possibility that Zika virus was mediating its effects in the brain via ANKLE2.

In a subsequent fruit fly study, the researchers demonstrated that overexpression of Zika protein NS4A causes microcephaly in the flies by inhibiting the function of ANKLE2, a cell cycle regulator that acts by suppressing the activity of VRK1 protein.

Since very little is known about the role of ANKLE2 or VRK1 in brain development, Bellen and his colleagues applied a multidisciplinary approach to tease apart the exact mechanism underlying ANKLE2-associated microcephaly.

The fruit fly helps clarify the mystery

The team found that fruit fly larvae with mutations in ANKLE2 gene had small brains with dramatically fewer neuroblasts brain cell precursors and could not survive into adulthood. Experimental expression of the normal human version of ANKLE2 gene in mutant larvae restored all the defects, establishing the loss of Ankle2 function as the underlying cause.

To understand why ANKLE2 mutants have fewer neuroblasts and significantly smaller brains, we probed deeper into asymmetric cell divisions, a fundamental process that produces and maintains neuroblasts, also called neural stem cells, in the developing brains of flies and humans, said first author Dr. Nichole Link, postdoctoral associate in the Bellen lab.

Asymmetric cell division is an exquisitely regulated process by which neuroblasts produce two different cell types. One is a copy of the neuroblast and the other is a cell programmed to become a different type of cell, such as a neuron or glia.

Proper asymmetric distribution and division of these cells is crucial to normal brain development, as they need to generate a correct number of neurons, produce diverse neuronal lineages and replenish the pool of neuroblasts for further rounds of division.

When flies had reduced levels of Ankle2, key proteins, such as Par complex proteins and Miranda, were misplaced in the neuroblasts of Ankle2 larvae. Moreover, live imaging analysis of these neuroblasts showed many obvious signs of defective or incomplete cell divisions. These observations indicated that Ankle2 is a critical regulator of asymmetric cell divisions, said Link.

Further analyses revealed more details about how Ankle2 regulates asymmetric neuroblast division. They found that Ankle2 protein interacts with VRK1 kinases, and that Ankle2 mutants alter this interaction in ways that disrupt asymmetric cell division.

The Zika connection

Linking our findings to Zika virus-associated microcephaly, we found that expressing Zika virus protein NS4A in flies caused microcephaly by hijacking the Ankle2/VRK1 regulation of asymmetric neuroblast divisions. This offers an explanation to why the severe microcephaly observed in patients with defects in the ANKLE2 and VRK1 genes is strikingly similar to that of infants with in utero Zika virus infection, Link said.

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For decades, researchers have been unsuccessful in finding experimental evidence between defects in asymmetric cell divisions and microcephaly in vertebrate models. The current work makes a giant leap in that direction and provides strong evidence that links a single evolutionarily conserved Ankle2/VRK1 pathway as a regulator of asymmetric division of neuroblasts and microcephaly, Bellen said.

Moreover, it shows that irrespective of the nature of the initial triggering event, whether it is a Zika virus infection or congenital mutations, the microcephaly converges on the disruption of Ankle2 and VRK1, making them promising drug targets.

Another important takeaway from this work is that studying a rare disorder (which refers to those resulting from rare disease-causing variations in ANKLE2 or VRK1 genes) originally observed in a single patient can lead to valuable mechanistic insights and open up exciting therapeutic possibilities to solve common human genetic disorders and viral infections.

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How in utero Zika virus infection can lead to microcephaly in newborns: Baylor research - Outbreak News Today

In a surprising finding using the standard animal model of Down syndrome (DS), scientists were able to correct the learning and memory deficits associated with the condition the leading genetic cause of cognitive disability and the most frequently diagnosed chromosomal disorder in the U.S. with drugs that target the bodys response to cellular stresses.

In a study published Nov. 14, 2019, in the journal Science, a team led by researchers at UC San Francisco and Baylor College of Medicine show that some of the intellectual impairments associated with DS may be traced to altered protein production in a region of the brain called the hippocampus, which is central to learning and long-term memory formation.

But in the so-called Ts65Dn mouse, engineered to capture genetic, behavioral and cognitive features of human Down syndrome, these changes can be undone. When the researchers administered drugs that target one of the cells key stress response pathways, they were able to bring protein levels back to normal, which caused the cognitive deficits typical of the Ts65Dn mouse to vanish.

Although the cognitive features of DS have generally been thought of as irreversible, the researchers say, these findings indicate that it may be possible to improve cognitive function in human DS using similar compounds.

Because DS is caused by an extra copy of chromosome 21, scientists have generally studied the disease through the lens of genetics, focusing primarily on ways in which the superfluous chromosome disrupts normal gene activity. But in the new study, rather than restricting their efforts to genes and chromosomes, the scientists trained their sights on the largely unexplored role of proteostasis a technical term for the cells protein manufacturing and quality control machinery in DS.

Peter Walter, Ph.D., co-senior author of the study, spearheaded the research to uncover a link between proteostasis defects and DS.

The vast majority of the field has been focusing on individual genes on chromosome 21 to figure out which ones are causally related to Down syndrome and its pathologies. Our approach was different. We were trying to uncover a link between proteostasis defects and DS, said Peter Walter, Ph.D., professor of Biochemistry and Biophysics at UCSF and co-senior author of the new study.

Walter spearheaded the new study with collaborator Mauro Costa-Mattioli, Ph.D., a professor of neuroscience at Baylor College of Medicine who is currently a visiting professor in Walters lab thanks to a UCSF Presidential Chair Award.

To identify proteostasis problems that might contribute to DS, the researchers turned to a common mouse model that captures most of the chromosomal, developmental and cognitive abnormalities that define the human version of the syndrome.

Using polysome profiling, a technique that allows scientists to take a detailed snapshot of the cells protein factories in action, the researchers found that up to 39 percent less protein was being produced in the hippocampus of DS mice, prompting them to ask why extra copies of genes could lead to a decline in protein production.

The researchers discovered that hippocampal cells in DS mice had activated whats known as the integrated stress response (ISR), a biological circuit that detects when somethings awry the presence of an extra chromosome, for example, in the case of DS and engages a protective response that activates machinery to tamp down protein production.

The cell is constantly monitoring its own health. When something goes wrong, the cell responds by making less protein, which is usually a sound response to cellular stress. But you need protein synthesis for higher cognitive functions, so when protein synthesis is reduced, you get a pathology of memory formation, said Walter.

Backing up these results, the scientists also found that the ISR was also activated in postmortem samples of brain tissue from people with DS. And by a stroke of pure luck, the researchers were able to obtain a tissue sample from a person with DS in whom some cells carried the expected third copy of chromosome 21, while others were genetically normal the ISR, however, was only active in the cells with the extra chromosome.

Taken together, these findings strongly suggest that the ISR is involved in, and perhaps even responsible for, certain DS symptoms.

Though the ISR can be activated by four different enzymes, the scientists found that only one of them, named PKR, was involved in activating the ISR in hippocampal cells in DS. By blocking the activity of PKR they were able to prevent ISR activation and reverse the declines in protein production that had been observed in the brains of DS mice. But even more impressive, the researchers found that blocking the ISR significantly improved cognitive function in these mice as well.

The researchers used three different approaches to dial down ISR activity deleting the PKR gene, using a drug that suppresses PKR activity, and finally, using a safe, well-studied drug called ISRIB that activates protein-manufacturing machinery that competes directly with the ISRs efforts to shut off protein production. All three approaches yielded a marked improvement in cognition, as demonstrated by two different memory and learning tests.

We started with a situation that looked hopeless, nobody thought anything could be done. But we may have struck gold.Peter Walter, Ph.D.

Importantly, these changes were physiological as well as behavioral. DS mice that were given ISR inhibitors showed improved function at synapses, sites between nerve cells where changes associated with learning take place. In fact, after ISR activity was blocked, the brains of DS mice were transmitting fewer of the inhibitory signals that can make it harder for the brain to learn and form new long-term memories.

Though the results of the study were extremely promising, Walter cautions that much more in this area remains to be studied. Still, the findings are an important first step toward finding therapies that could improve the lives and overall health of people living with DS, a condition that has generally been considered untreatable.

We started with a situation that looked hopeless, Walter said. Nobody thought anything could be done. But we may have struck gold.

Authors: Additional authors include Ping Jun Zhu, Sanjeev Khatiwada, Ya Cui, Lucas C. Reineke, Sean W. Dooling, Jean J. Kim, and Wei Li of the Baylor College of Medicine. Peter Walter is also a Howard Hughes Medical Institute investigator.

Funding: This study was funded by NIH grants R01NS076708, R01HG007538, R01CA193466 and R01 CA228140, Sammons Enterprises and the Howard Hughes Medical Institute.

Disclosures: Peter Walter is an inventor on U.S. Patent 9708247 held by the Regents of the University of California that describes ISRIB and its analogs. Rights to the invention have been licensed by UCSF to Calico LLC. Wei Li is a consultant for the Chosen Med. The authors declare no other competing interests.

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In Down syndrome mouse model, scientists reverse intellectual deficits with drugs - University of California

SOUTH SAN FRANCISCO, Calif., Nov. 12, 2019 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical stage biotechnology company pioneering immuno-neurology, today announced Company highlights and financial results for the third quarter of 2019.

We continue to integrate insight from human genetics, immunology, and neuroscience to advance our portfolio of novel therapeutics. AL001 has advanced to a Phase 2 trial in two genetically defined patient populations suffering from frontotemporal dementia. In addition, AL002 and AL003 are currently being evaluated in Phase 1b clinical trials in Alzheimers disease patients, said Arnon Rosenthal, Ph.D., Alectors chief executive officer. We are looking forward to our first presentation of data from the AL002 program taking place at the CTAD annual meeting and an update on our clinical and development pipelines at our R&D Day in December.

Recent Business Highlights

Third Quarter 2019 Financial Results

Revenue. Collaboration revenue for the third quarter of 2019 was $2.7 million compared to $6.5 million for the same period in 2018. Alector recognizes revenue from the upfront payments under the AbbVie Agreement over time as the services are provided. Revenues are recognized as the program costs are incurred by measuring actual costs incurred to date compared to the overall total expected costs to satisfy the performance obligation. Changes in estimates for revenue recognized over time are recognized on a cumulative basis.

R&D Expenses. Total research and development expenses for the third quarter of 2019 were $28.5 million compared to $20.4 million for the same period in 2018. The increase was driven by higher personnel-related expenses as headcount grew to support the advancement of the clinical and preclinical programs, increased expenditures related to the clinical trials, increased laboratory expenses for the development of our pipeline, and increased facilities and other unallocated research and development expenses to support the growth of the business.

G&A Expenses. Total general and administrative expenses for the third quarter of 2019 were $8.3 million compared to $2.9 million for the same period in 2018. This increase was primarily due to higher personnel-related expenses, increased facilities and general overhead expenses, and increased expenses related to information technology, accounting, legal, human resources, and other administrative functions to support the growth of the business.

Net Loss. For the third quarter of 2019, Alector reported a net loss of $31.7 million, compared to a net loss of $15.3 million for the same period in 2018.

Cash Position. Cash, cash equivalents, and marketable securities were $381.4 million as of September 30, 2019.

About AlectorAlector is a clinical stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases. Immuno-neurology targets immune dysfunction as a root cause of multiple pathologies that are drivers of degenerative brain disorders. Alector is developing a broad portfolio of programs designed to functionally repair genetic mutations that cause dysfunction of the brains immune system and enable the rejuvenated immune cells to counteract emerging brain pathologies. The Companys product candidates are supported by biomarkers and target genetically defined patient populations in frontotemporal dementia and Alzheimers disease. Alector is headquartered in South San Francisco, California. For additional information, please visit http://www.alector.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on our beliefs and assumptions and on information currently available to us on the date of this press release. Forward-looking statements may involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. These statements include but are not limited to statements regarding the Companys financial condition and results of operations, and plans for the Companys product candidates, clinical studies and anticipated regulatory and development milestones. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Important factors that could cause our actual results to differ materially are detailed from time to time in the reports Alector files with the Securities and Exchange Commission, including in our quarterly report on Form 10-Q that is being filed with the Securities and Exchange Commission (SEC). Copies of reports filed with the SEC are posted on Alectors website and are available from Alector without charge.

Selected Consolidated Balance Sheet Data (in thousands)(unaudited)

(1) Upon the closing of our IPO in February 2019, all of the outstanding shares of our convertible preferred stock converted into 45,374,836 shares of common stock.

Consolidated Statement of Operations Data(in thousands, except share and per share data)(unaudited)

Source: Alector, Inc.

Contacts

Media:1ABDan Budwick, 973-271-6085dan@1abmedia.com

orInvestors:Alector, Inc.ir@alector.com

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Alector Reports Recent Business Highlights and Third Quarter 2019 Financial Results - GlobeNewswire

As the legendary science fiction author Arthur C Clarke once suggested, JBS Haldane was perhaps the most brilliant science popularizer of his generation. #LostTales

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JBS Haldane ranks among the greatest scientists of the 20th century, particularly for his invaluable contribution to our understanding of genetics. More fascinatingly, however, this remarkable polymath left his home country of the United Kingdom in 1957 and moved to India permanently. He took up residence and Indian citizenship with his wife Helen Spurway, a gifted biologist in her own right.

Never before in the 20th century had a scientist of his standing chosen to take his scientific research to India from the Westnot to mention becoming a citizen.

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Born on 5 November 1892, in Oxford, England, JBS grew up in privilege with his father John Scotee Haldane, an Oxford University physiologist. JBS was a child prodigy, learning how to read and acquiring a certain degree of familiarity with scientific terminology by the tender age of three. The influence of John Scott loomed large on his son with the duo acting as their own guinea pigs in various experiments, including ascertaining the physiological effects of poison gases.

But the turning point for JBS came when his father took him to a lecture by A D Darbishire, a British zoologist and geneticist, about legendary scientist Gregor Mendels laws of inheritance, dominance and segregation. The lecture facilitated his fascination with genetics.

JBS studied at Eton, an elite boys school, and subsequently at Oxford University, where he pursued the Classics and Mathematics, graduating with honours in 1914. However, his academic pursuits were brought to a halt by World War I. Commissioned to the British Army, he served in France and Iraq, where he was wounded.

Following the War, he came back to Oxford to pursue his research in genetics.

His most important genetical contributions were a series of mathematical papers on the effect of natural selection, which were summarized in his book, The Causes of Evolution. This work became the foundation for population genetics along with the works of R.A. Fisher and Sewall Wright. Haldane [also] introduced the important idea that immunity to infectious diseases played an important part in human evolutionHe emphasized the importance of ethical considerations in evaluating eugenic programs and the impact of in vitro fertilization, writes Krishna R Dronamraju, a colleague of JBS, for the Indian Journal of Human Genetics.

In many ways, JBS played a critical role in laying the foundation of classical human genetics.

He derived the law of steady-state kinetics in enzyme chemistry, besides ascertaining the physiological effects of carbon dioxide and carbon monoxide by testing them out on his own body, a method he learnt from his father.

After a four-year stint as a Professor of Genetics at the University College in London, he spent the next twenty as the Professor of Biometry. As a professed socialist and humanist, JBS was also deeply engaged in popularising the science to the masses beyond the laboratory.

As the legendary author Arthur C Clarke once suggested, JBS Haldane was perhaps the most brilliant science popularizer of his generation.

However, towards the fag end of his time in England, he grew increasingly disenchanted by British politics and society. The breaking point was his governments role in the Suez Crisis of 1956, which he saw as violations of international law, while admiring the Indian Independence Movement. Moreover, the warmer climate of India and Prime Minister Nehrus experiments with socialism also offered JBS and wife Helen with the necessary rationale for shifting base.

It was the legendary statistician P C Mahalanobis, who offered JBS a teaching position in the Indian Statistical Institute, Kolkata. At this time, he also began immersing himself in Indian philosophy and logic systems, applying indigenous knowledge systems to scientific research.

He continued his work in the study of genetics in India, ranging from studies about inbreeding in Andhra Pradesh, and colour blindness in Andhra and Odisha, apart from other such studies.

Never before in modern times had a Western scientist of Haldanes calibre chosen to move to India not to speak of becoming a citizen. He was critical of Indian science and scientists but saw hopes in young people. During his stay here, he did much for research in animal and human genetics and in support of science education, writes Dr Veena Rao, a faculty member at the National Institute of Advanced Sciences. Science, he believed, must help common citizens understand what goes on inside the research laboratories, for some of which he pays, writes Dr Veena Rao, Adjunct Faculty at the National Institute of Advanced Studies, for The Hindu.

He also criticised the bureaucratic roadblocks that stifled true research in India. There was even a dust-up between him and the management at the ISI, which led to his resignation and the eventual shift to Bhubaneswar, Odisha, on the invitation of Biju Patnaik.

Haldane was appointed [the] head of an entirely independent research establishment, where he worked with his young colleagues from Calcutta, including S D Jayakar, with whom he published papers on population genetics that are as enduring as the best of Haldanes early work, says this Down to Earth profile.

Whats particularly remarkable about his life is how quickly people forgot him. More than anything else, however, he passed on to his students and peers a passion for the sciences.

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Just before passing away on 1 December 1964 of rectal carcinoma, he issued strict instructions that he wanted to dedicate his body to scientific researchthe mark of a true scientist.

Our only hope of understanding the universe is to look at it from as many different points of view as possibleNow, my own suspicion is that the universe is not only queerer than we suppose, but queerer than we can suppose, he wrote.

(Edited by Shruti Singhal)

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One of the World's Greatest Geneticists, He Gave Up British Citizenship for India - The Better India