When Amber Freed first told doctors her baby boy wasnt able to move his hands, they said that wasnt possible.

Freed had given birth to twins in March 2017. While her baby girl, Riley, squirmed and babbled and crawled through the first year of her life, her fraternal twin, Maxwell, was different. He didnt crawl or babble like Riley did. I would fill out their baby books each month, and Riley had met all of these milestones. Maxwell didnt reach one, she said. Most alarmingly, however, Freed noticed that he never moved his hands.

She knew the news was going to be bad when they sent her to the sad room at the hospital, a featureless conference space filled with grim-faced doctors, to hear the diagnosis.

You take your baby to the doctor and you say, He cant move his hands. And they look at you and they say, Of course he can, said Freed.

Then they look for themselves, and you can see from the look on their faces that they have never seen anything like this.

On June 14, 2018, at the Children's Hospital Colorado in Denver, Maxwell was diagnosed with a genetic disease called SLC6A1. The diagnosis explained why the infant hadnt moved his hands or learned how to speak for the first year of his life, while Riley was thriving. But it didnt explain much else: All the doctors who diagnosed Maxwell knew about the genetic disease came from a single five-page study published in 2014, the year of its discovery. It was too rare to even have a name, she was told, so the doctors just called it by the name of the affected gene: SLC6A1.

Now her 2-year-old son is at the center of a multimillion-dollar race against time, one thats come to include genetics researchers whom Freed personally recruited, paid for by $1 million that Freed and her husband, Mark, have raised themselves. At the center of their research will be specially crafted mutant mice that Freed paid scientists in China to genetically alter to have the same disease as Maxwell. The four mice are scheduled to arrive stateside next week, but Freed said shes prepared to smuggle them into the US disguised as pets if there are any problems.

In total, Amber and Mark will need to raise as much as $7 million to test a genetic treatment for their child. And unless they can find and fund a cure, SLC6A1 will condemn Maxwell to severe epileptic seizures, most likely starting before he turns 3. The seizures may trigger developmental disabilities for a lifetime, often accompanied by aggressive behavior, hand flapping, and difficulty speaking.

And the Freeds will have to do it largely alone there are only an estimated 100 other people diagnosed with SLC6A1 in the world. This is the rarest of the rare diseases, pediatric geneticist Austin Larson of the Children's Hospital Colorado told BuzzFeed News.

SLC6A1 is just one of thousands of untreatable rare diseases, and the perilous path it has set up for Freed, half science quarterback and half research fundraiser, is one that few parents can follow. My dream is to create a playbook of how I did this for those that come after me, said Freed. I never want there to be another family that has suffered like this.

You can think of SLC6A1 as a vacuum cleaner in the brain, genetic counselor Katherine Helbig of the Childrens Hospital of Philadelphia, told BuzzFeed News. Helbig will speak at the first conference on the gene at the American Epilepsy Society meeting in Baltimore on Dec. 5, an effort organized by Freed.

The protein made by the gene acts as a stop sign to message-carrying chemicals in the brain, halting them by vacuuming them up once they reach their destination brain cell, Helbig explained.

When one of the two copies of the SLC6A1 gene in every brain cell is damaged, like in Maxwells case, too little of its protein is available to perform its vacuuming duties, leading to miscommunication between cells, developmental disorders, autism-like symptoms, and, often, severe epileptic seizures.

Maxwell is about the age when epileptic seizures typically start in kids with the genetic disease, said Helbig, adding, There probably are many more children out there who have it, but they just havent had the right test to find it. At least 100 similar genetic defects cause similar kinds of epilepsy, afflicting about 1 in 2,000 kids, she said.

I was the one who presented this diagnosis to Amber, said Larson of the Children's Hospital Colorado. There was no medicine or diet or any other treatment for SLC6A1. It wasnt an easy conversation. Most of the time when we present a diagnosis for a genetic condition, there is not a specific treatment available.

At that moment, it was just vividly clear that the only option was for me to create our own miracle, said Freed. Nobody else was going to help.

Half the battle with a rare genetic disease is getting researchers interested, said Helbig.

At that moment, it was just vividly clear that the only option was for me to create our own miracle. Nobody else was going to help.

So that is what Freed set out to do. She quit her job as a financial analyst and started making phone calls to scientists, calling 300 labs in the first three months. For those who didnt respond, she sent them snacks via Uber Eats.

Her search, and a rapid-fire education on genetic diseases, led her to conclude the best hope for helping Maxwell was an experimental technique called gene therapy.

All the roads zeroed in on one scientist: Steven Gray of the University of Texas Southwestern Medical Center in Dallas. In 2018, a team headed by Gray reported the first human experiments of gene transfer by spinal injection, conducted in 5 to 10 children with mutations in a gene called GAN that causes swelling in brain cells.

The GAN gene transfer in that experiment, first tested in mice, attached a corrected version of the damaged gene to a harmless virus. Viruses reproduce by infecting cells and hijacking their DNA machinery to reproduce their own genes, making more viruses. The gene therapy virus in turn leaves behind a corrected gene in the DNA of cells they infect. Injected into the spinal cord, Grays virus can travel straight to the brain, leaving behind the corrected gene after the virus has run its course.

I gave him my 30-second equity analyst pitch. I told him why Maxwell was a good patient, that we would raise $4 million to $7 million, and quarterback every step of the research, she said. And it worked. He agreed to make it a priority if we could raise the money.

The SLC6A1 researchers with the Freeds at a science meeting. From left: Terry Jo Bichell, Frances Shaffo, Amber Freed, Katty Kang, and Mark Freed.

Less than a month after meeting Gray, Freed contacted a lab at Tongji University in Shanghai that was also researching SLC6A1. The lab agreed to develop a mouse with Maxwells specific mutation for less than $50,000, using a gene modification technology called CRISPR that has revolutionized genetic engineering in the lab. CRISPR mice are much more expensive in the US, and this lab had experience with the gene, said Freed.

By July of this year, an experiment with a gene therapy virus that corrects SLC6A1 was tested on normal lab mice, which showed no sign of a toxic response, an encouraging sign. And by September, a line of CRISPR mice with Maxwells exact genetic mutation had been created at Tongji University.

It is the literal mouse version of him, said Freed. Testing a therapy in this mouse is as close as science can get to testing in my son directly.

To pay for all this, Maxwells family started fundraising last November and organized the first medical symposium on SLC6A1 in New Orleans that same month. They opened a GoFundMe account, which has raised $600,000, and held 35 fundraisers, which raised an additional $400,000 by October. In one charity competition, Larson from the Colorado Childrens Hospital, who diagnosed Maxwell, personally helped her raise $75,000.

It is the literal mouse version of him. Testing a therapy in this mouse is as close as science can get to testing in my son directly.

That money is helping to pay for the next step getting the CRISPR mice to Grays lab to test the SLC6A1-correcting virus on them. But its not as simple as putting the mice in a box and shipping them by mail. The mice will be transferred through a lab at Vanderbilt University headed by Katty Kang, an expert on the neurotransmitter disrupted by Maxwells mutation.

Amber is helping us to advance science, and everyone is making this a priority because of the young lives at stake not just Maxwell, but other children this could help, Kang told BuzzFeed News.

Once the four mice arrive, they will spend several weeks in quarantine, be tested to make sure they have Maxwells specific point mutation in the SLC6A1 gene, and breed with normal lab mice to produce generations of mixed-inheritance mice to serve as controls in future experiments. The mutant mice will be closely monitored before they head to UT Southwestern to make sure that they demonstrate the same problems and genetics as human patients with SLC6A1 and can therefore be used in any future clinical trials of gene therapy.

Right now at UT Southwestern, results from a safety test of the gene therapy virus conducted by Grays lab on young, normal lab mice is awaiting publication. If that works out, once the Chinese mice are sent over, they will also receive the gene-correcting virus. His team will see if their symptoms improve and to what extent their brain cells accept the corrected gene.

Maxwell's brain cells seen through a microscope (left), and a sample of his cells in a petri dish.

And then, Freed just needs another $5.5 million. Half a million dollars will go to test the virus in a second SLC6A1 animal model, likely a rat, as another safety step. Two million dollars will go toward creating more of the gene-correcting virus for a human safety study if that proves to be safe. And finally, if all that works out, $3 million will be needed to conduct the experiment on Maxwell and other children next year, following the path of the GAN clinical trial led by Gray.

Its a really horrible realization that the only thing standing in the way of a cure for your 2-year-old is money, said Freed.

Freed acknowledges that she has only been able to pursue a cure for Maxwell because her family has the resources to do so which she would never have had growing up in small towns in Texas, Montana, and Colorado in a poor family affected by alcoholism. I grew up visiting my parents in rehab and knew what to say to put a family member on a 72-hour psychiatric hold by age 12, she said. She dug herself out to build a career in finance, and hoped her kids would never have to experience the struggles she did growing up.

Even so, the fight hasnt been easy on them or on Maxwells sister, Riley.

Freed worries her daughter is growing up in doctors' waiting rooms, waiting on treatments for her brother to end. Maxwells disease has progressed, causing him to constantly clench his fingers, and sometimes pull his sisters hair. His 3-year-old sister will gently remind him, Soft hands, Maxie.

Families like the Freeds are at the forefront of efforts to turn diagnoses of rare genetic ailments, which often used to be the stopping point for medicine, into treatments. A similar case saw the family of a 3-year-old girl, Mila Makovec, raise $3 million for gene therapy to cure her Batten disease, a deadly genetic brain disease that affects 2 to 4 of every 100,000 children born in the US.

In a New England Journal of Medicine editorial on that case published in October, FDA officials questioned how high the agency should set the safety bar for such treatments, meant for severe diseases affecting so few people. In these cases, parents are often collaborators in developing treatments, and might not want to stop efforts that come with high risks. Even in rapidly progressing, fatal illnesses, precipitating severe complications or death is not acceptable, so what is the minimum assurance of safety that is needed? wrote senior FDA officials Janet Woodcock and Peter Marks.

This is way beyond what anyone expects of families.

Finally, Woodcock and Marks wrote, finding sustainable funding for such interventions may prove challenging, because the cost of production can be quite substantial, particularly for gene therapies.

In our era of financial inequality, the specter of wealthy parents buying custom genetic treatments for their childrens ailments while other parents desperately resort to GoFundMe accounts, or else do nothing looms as a possibility.

This is way beyond what anyone expects of families, said Larson. The pathway has been opened up by the brave new world of improved genetic diagnoses, and the coming of age of rapid genetic engineering tools like CRISPR.

But only 20 years ago, an experimental gene therapy that relied on a harmless virus killed an 18-year-old volunteer, Jesse Gelsinger, in a research misconduct case that brought gene therapy to a standstill. Now more than 2,500 gene therapy clinical trials have been conducted, and more than 370 are underway. The human genome was not sequenced until 2000; today, mapping an entire human gene map costs around $700. In this new era, customized treatments for rare genetic diseases like Maxwells are suddenly possible.

What I hope is that we are paving the way for other parents to help their children, said Freed.

Families of children with rare genetic diseases are also working together to make treatments like the one Freed is spearheading possible, said Larson.

They support each other and work together, he said. The best example might be the families of children with cystic fibrosis, who through the Cystic Fibrosis Foundation and the discovery of the gene responsible for the disease in 1989 have pushed for the discovery of new drug treatments. In October, the FDA approved a breakthrough pharmaceutical that could treat 90% of cases.

It is easier working with FDA on this kind of approach rather than starting from scratch, Gray told BuzzFeed News by email. After all, he said, its easier to follow a path that youve already walked down.

Similarly, Freed hopes the SLC6A1 Connect advocacy group she started can lead to similar treatments for other children with genetic epilepsies caused by the gene.

I dont think any parent should be expected to single-handedly cure his or her childs rare disease, said Helbig. Amber is a very tenacious and persistent person, and she will fight tooth and nail for her kids. But a lot of people dont have the resources and they shouldnt have to.

Helbig says that cautious optimism is appropriate on the chances of research yielding a genetic therapy for children like Maxwell. For SLC6A1, its really too early to say whether this is going to work.

But if it works, it might lead many more parents to get genetic tests for children that will reveal undiagnosed problems, she said. Many doctors discourage extensive genetic tests, thinking they wont find anything helpful. In the absence of known treatments, insurers are also reluctant to pay for such tests, discouraging all but the most fortunate and resourceful parents. Even for them, there are no guarantees.

The other tough reality is the possibility this treatment wont be completed in time to help Maxwell, said Freed. I love him with every ounce of my being, and I want him to know that I did everything humanly possible to change his outcome.

Originally posted here:
This Mom Is Buying Mutant Mice From China To Find A Cure For Her Sons Rare Genetic Disease - BuzzFeed News

Monday on NBC3 at 11: The genetics of autism and the growing number of parents diagnosed  CNYcentral.com

Original post:
Monday on NBC3 at 11: The genetics of autism and the growing number of parents diagnosed - CNYcentral.com

Asthmahas long been associated with lower quality of life as a result of reducedactivity and increased psychological stress.1 Indeed, any identifiedlinks between asthma and mental health have primarily been unidirectional, withasthma leading to mental illness. However, recent studies have revealed geneticlinks between asthma and mental health.

Research suggests that people with asthma are more likely to develop mental health problems compared with the general population. In a study conducted with school children, the prevalence of diagnosed mental health conditions among those with asthma was 8.2%, which was nearly double the prevalence among those without asthma (4.8%).2 Another study comprising adults showed that mood disorders were strongly associated with allergic asthma, late-onset asthma, and infection-based asthma.3 In addition, researchers discovered that mental health care services were more likely to be used by people after a diagnosis of asthma.4

Morestudies are underway to investigate the bidirectional connection between asthmaand mental health. One study has linked asthma severity to lifetime and currentanxiety, with asthma preceding anxiety in 48% of the patients and anxietypreceding asthma in 52% of the patients.5

Thereis growing evidence for the involvement of genetics in this asthma-mentalhealth connection. A Swedish study that identified self-report associationsbetween asthma and major depressive disorder (MDD), anxiety, and neuroticismalso found genetic correlations between asthma and MDD, but not between asthmaand anxiety or neuroticism.6

Anotherstudy, a large-scale genome-wide cross trait analysis, has shown a strongassociation between asthma and 3 mental disorders: attention-deficit/hyperactivitydisorder (ADHD), anxiety disorder, and MDD.7 A total of 7 loci werefound to be jointly associated with asthma and ADHD; 1 loci with asthma andanxiety disorder; and 10 loci with asthma and MDD.

Accordingto Dr Zhaozhong Zhu, a lead researcher, Mendelianrandomization a method of using measured variation in genes of known function was used to inferputative causal relationshipsbetween asthma and mental health disorders in both directions, with our resultssuggesting that ADHD and MDD might increase the risk for asthma. Dr Zhu makesit clear that the mechanismof the association is unknown. Thecausal relationship found in the study is only based on genetic variables, heexplains. The epidemiologic association includes 2 key components: genetics(ie, genes and biological mechanisms) and environment (ie, social factors,exposure to certain conditions [asthma], and medication use).

The study findings indicate geneticcausality in the direction of mental illness causing asthma. However, theenvironmental causality is in the reverse direction and outweighs the geneticcausality; thus, the overall epidemiologic causality is in the direction ofasthma causing mental health disorders.

Compared with other mentaldisorders, depression appears to have the strongest link to asthma. In additionto the 10 loci found by Dr Zhu and his team, a single-nucleotide polymorphism(SNP) known as rs4672619, located on the Erb-B2 receptor tyrosine kinase 4gene, has been implicated in the comorbidity of depression and asthma.8The researchers who discovered the SNP evaluated the relationship between thedepressive status of the individuals and the rs4672619 genotypes on asthmasymptom severity. In childhood asthmatics, severe depression was related toless severe asthma symptoms, while in those with heterozygous and homozygousvariant alleles, severe depression was related to more severe asthma symptoms.

In elderly patients with asthma, thereverse was true. Those with the homozygous reference allele had a positivecorrelation between depression and asthma symptom severity, while a negativecorrelation was seen in those with heterozygous and homozygous variant alleles.Further studies on the relationship between the conditions could lead to thedevelopment of personalized therapies for the simultaneous treatment of bothconditions.

Few studies have established thegenetic link between asthma and anxiety. A Chinese investigation demonstratedthe effect of interactions between serotonin transporter (5-HTT), brain-derivedneurotrophic factor (BDNF), and the neuropeptide S receptor 1 gene, NPSR1-AS1 polymorphisms on anxiety and depression.9Interactions between 5-HTT (LL alleles) and BDNF (A+ allele) led to anincreased anxiety score, while interactions between BDNF (A+, GG) and NPSR1(AA, T+) increased the depression score.

While the genetic link betweenasthma and ADHD was strongly revealed in Dr Zhus study, most other studieshave been anecdotal. A large Swedish study found a significant associationbetween asthma and ADHD, even after removing possible confounding variables.10It has been hypothesized that because asthma and ADHD both have large geneticcomponents, people who are genetically susceptible to one condition may besusceptible to the other.11

Studying genetic variants raises thequestion of whether any genetic links have cross-cultural implications. Whilethe participants in Dr Zhus research were mainly European, Dr Zhu expectsthat, Asthma and mental health disorders should be genetically similar, butnot the same across major populations, such as African American, Hispanic, orAsian. He points out that one of the shared genetic loci between asthma andMDD, the human leukocyte antigen region on chromosome 6, has a pervasivegenetic effect in many diverse populations.

Currently, corticosteroids areconsidered the most effective long-term treatment for asthma. However, chroniccorticosteroid use has been associated with psychosis, depression, anxiety, andmania in people with asthma.12,13 Psychological treatments are being exploredas alternative interventions for asthma and while no psychotherapy has beenscientifically proven to improve asthma and comorbid mental illness, there hasbeen an increased interest in the use of cognitive behavioral therapy.14,15

Understanding the geneticassociation between asthma and mental health creates an opportunity for thedevelopment of more effective drugs and therapeutic approaches that could treatasthma and associated mental health disorders together. In Dr Zhus study, functionalanalysis revealed that the identified variants regulated gene expression intissues of various body systems, including the respiratory and immune system.Thus, further understanding of these variants may lead to treatments thataddress the respiratory and immune system problems often seen in people asthma.

According to Dr Zhu, In the short term,we aim to inform the general population that mental health disorders can haveshared genetic factors with asthma. Therefore, controlling environmentalfactors, such as eating healthy, enjoying a happy life, and being careful withthe potential adverse effects of medication, will help to prevent asthma andmental health disorders. In the long term, with more mechanistic studies, wehope to provide direction in the development of drugs for preventing andtreating both conditions at the same time.

References

1. American Academy of Allergy Asthma & Immunology. Increased mental health care use in adults after asthma diagnosis. http://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/mental-health. April 7,2017. Accessed November 5, 2019.

2. Lawson J, Rennie D, Dyck R, Cockcroft D, Afanasieva A. The relationship between childhood asthma and mental health conditions.Eur Respir J. 2017;50(suppl 61):PA595.

3. Labor M, Labor S, Juri I, Fijako V, Grle S, Plavec D. Mood disorders in adult asthma phenotypes.J Asthma. 2017;55(1):57-65.

4. To T, Ryckman K, Zhu J, et al. Mental Health Services Claims and Adult Onset Asthma in Ontario, Canada.J Allergy Clin Immunol Pract. 2017;5(5):1388-1393.e3.

5. Del Giacco S, Cappai A, Gambula L, et al. The asthma-anxiety connection.Respir Med. 2016;120:44-53.

6. Lehto K, Pedersen N, Almqvist C, Lu Y, Brew B. Asthma and affective traits in adults: a genetically informative study.Eur Respir J. 2019;53(5):1802142.

7. Zhu Z, Zhu X, Liu C et al. Shared genetics of asthma and mental health disorders: a large-scale genome-wide cross-trait analysis [published online October 17, 2019].Eur Respir J. doi:10.1183.13993003.01507-2019

8. Park H, Song W, Cho S, et al. Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics. Exp Mol Med. 2018;50(7):77.

9. Yang Y, Zhao M, Zhang Y, Shen X, Yuan Y. Correlation of 5-HTT, BDNF and NPSR1 gene polymorphisms with anxiety and depression in asthmatic patients. Int J Mol Med. 2016;38(1):65-74.

10. Cortese S, Sun S, Zhang J, et al. Association between attention deficit hyperactivity disorder and asthma: a systematic review and meta-analysis and a Swedish population-based study. Lancet Psychiatry. 2018;5(9):717-726.

11. Rapaport L. Links seen between asthma and ADHD. Reuters website. http://www.reuters.com/article/us-health-adhd-asthma/links-seen-between-asthma-and-adhd-idUSKBN1L12FZ. August 15, 2018. Accessed November 14, 2019.

12. Kewalramani A, Bollinger M, Postolache T. Asthma and mood disorders.Int J Child Health Hum Dev. 2008;1(2):115-123.

13. University of Newcastle Australia. Severe Asthma Toolkit. Asthma and Mental Health. https://toolkit.severeasthma.org.au/living-severe-asthma/mental-emotional-health/. Updated February 12, 2019. Accessed November 5, 2019.

14. Kew K, Nashed M, Dulay V, Yorke J. Cognitive behavioural therapy (CBT) for adults and adolescents with asthma.Cochrane Database Syst Rev. 2016;9:CD011818.2

15. Pateraki E, Morris P. Effectiveness of cognitive behavioural therapy in reducing anxiety in adults and children with asthma: a systematic review.J Asthma. 2018;55(5):532-554.

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The Genetic Link Between Asthma and Mental Health - Pulmonology Advisor

After reading Christina Adamss new book Camel Crazy: A Quest for Miracles in the Mysterious World of Camels(New World Library), I may have a new favorite animal (sorry, cats and hippos).

Most of us know camels as curiosities at zoos. As beasts of burden highly adapted to hot and dry climates, theyve served the trade routes that helped build civilizations, and may indeed flourish in our increasingly hot and dry world. We value their hide, meat, and especially their milk.

Camels are unusual, biologically speaking. And that may be why their milk can alleviate some aspects of autism.

Camel milk sounds weird to American ears, but camels are a domestic fact of life elsewhere. Although the US classifies them as exotic animals, they actually have early origins here; fossils have been found in Los Angeles. But the true reservoir of knowledge on camels is found in rural cultures and universities in the Middle East, Asia, and Africa, Christina told me.

Got Camel Milk?

In 2005, Christina met a camel at a childrens book fair in Orange County CA. Rather than hauling kids around, the animal was standing near a display of lotions and soaps made with camel milk. When the owner started to tell Christina how the milk is hypoallergenic and helps premature babies in the Middle East, she glanced over at 7-year-old Jonah. Hed already had four years of costly treatments for autism.

Might it help reboot my sons immune system and help his autism symptoms? she recalls thinking, aware of a link to immune dysfunction. Cow milk and cheese made him hand-flap and walk in circles, which he described as feeling like having dirt in my brain. Vegan substitutes like rice, nut, or soy increased his allergic response.

Camel Crazy details Christinas two-year journey to find the milk. Once she started giving it to Jonah, four ounces at a time, mixed in with food like cereal, his behavior changed quickly.

He became calm. Inquisitive. Caring. His language became more emotional and focused. He held his head straight instead of rolling it. Eating became neat, not a mess fest. He dressed himself and began making eye contact. He even got his shoes and backpack on and was calmer in the car going to school.

By the third dose, Jonah was sleeping through the night. He became more fluid, social, and attuned. Within days he could cross the street without me holding on to him. Within weeks his skin grew smoother. The milk also reversed his skin irritation, agitation, mental distraction, hyperactivity, and stomach pain, Christina recalled.

So she did research and spread the word, first in an article Got Camel Milk? that went viral, then in a peer-reviewed case report, Autism Spectrum Disorder Treated With Camel Milk, published in Global Advances in Health and Medicine. After describing Jonahs early difficulties, she wrote on October 10, 2007, two weeks before my sons tenth birthday, he drank his first half cup (4 oz) of thawed raw unheated camel milk. The case report documents Jonahs sustained symptom improvements associated with drinking half a cup a day from 2007 to 2013.

Christina then began traveling the world, giving presentations on camel milk and autism, and consulting with scientists and vets. Camel Crazy details her immersion into the world of camels and cameleers, from Tuareg, Amish and Somali people in America to herders in India, Dubai and Abu Dhabi. She serves on the editorial board of the new International Journal of Camel Science.

I was a beta reader for Camel Crazyand loved it. Being a nerd I searched for the science, and wasnt disappointed. The milk indeed has some startling differences from other milks, yet tastes, Christina says, like cows milk.

Camels drink a lot, pee a little, exhale minimal vapor, have insulating coats, and their red blood cells balloon and shrink as the water content in the bloodstream shifts. Natural selection has favored persistence of these traits that provide adaptation to heat, aridity, and exposure to intense ultraviolet radiation and choking dust. Body temperature ranges from 93.2-104F (3440C).

Being specifically a genetics nerd, I delved deeper into the DNA that encodes the unusual versions of proteins that might explain the magic of camel milk, as well as other details of the physiology. Much of the info below comes from the article Desert to Medicine: A Review of Camel Genomics and Therapeutic Products, from three researchers at United Arab Emirates University.

Fighting an Opioid Released from Casein Breakdown

The first technical paper Christina found was The etiology of autism and camel milk as therapy, from Ben Gurion University researchers Reuven Yagil and Yosef Shabo. Parent reports inspired their work.

They zeroed in on an opiate-like effect. Casein, the most abundant milk protein, breaks down into peptide pieces. And one of them, beta-casomorphin-7, is an opioid. It can slip through the leaky gut of a person with autism and enter the brain. Could an opiate bathing the brain affect social interactions and lack of interest in surroundings?

Other breakdown peptides of casein (-casein and no -lactoglobulin), which are more abundant in cows milk, may spike milk allergies.

Upping Anti-Oxidants

Camel milk delivers potent anti-oxidants that might temper autism symptoms, wrote King Saud University researchers Laila Al-Ayadhi and Nadra Elyass Elamin in a2013 report. People with autism are more sensitive to oxidative stress, which is damage from unstable forms of oxygen called oxygen free radicals.

The researchers measured levels of three anti-oxidants in the blood of 60 kids with autism: superoxide dismutase, myeloperoxidase, and an enzyme needed to make glutathione. Over a two-week period, 24 children drank raw camel milk, 25 drank boiled camel milk, and 11 drank cows milk. The trial was double-blinded and randomized, but it wasnt a crossover, in which each child would have had all three milk experiences. Nevertheless, raw camel milk was superior in anti-oxidant levels and a behavioral rating scale.

Special Tiny Antibodies

Camels share with only their camelid brethren (llamas, alpacas, vicunas, and guanacos) tiny antibodies in milk, called nanobodies. Most antibodies have one or more Y-shaped subunits; a nanobody is one arm of one Y, the variable region that distinguishes species. A student discoveredcamel nanobodies in a lab course at the University of Brussels in 1993, analyzing a dromedarys blood serum. Camels make large antibodies too.

Nanobodies can squeeze into places more bulbous antibodies cannot, vanquishing a wider swath of viruses and bacteria. They look strikingly like monoclonal antibodies, and so have become darlings of pharma, particularly in cancer drug discovery.

A camels streamlined nanobodies arose from a mutation that removed the hinges that connect the Y-shaped arms of more conventional antibodies. Sometimes a mutation is a good thing!

Further infection protection comes from the milk protein lactoferrin, which fights hepatitis C.

Tolerating High Blood Sugar

A camel-herding people in India, the Raika, drink camel milk and dont get diabetes. Thats because camels tolerate high blood glucose levels, and some of that ability seeps into their milk.

P. Agrawal, at the SP Medical College, Bikaner, India and colleagues have conducted clinical trialsthat show that camel milk decreases blood glucose and hemoglobin A1c (a three-month-measure of blood glucose), and, in people with type 1 diabetes, reduces the insulin requirement by up to 30 percent .

How can camels have high blood sugar yet low HbA1C? In most animals, the beta chains of hemoglobin bind glucose at several points, upping HbA1C. This doesnt happen in camels. If glucose binding to hemoglobin in us is like Velcro, then in camels, its like contact between a boot and slippery ice.

Conserving Water

Milk requires water, and camels are masters at conserving it. A self-contained cooling system, as Christina describes it, cycles body water from a camels nostrils to its mouth. The multi-layered eyelids and double row of eyelashes keep out blowing sand. Their unique oval blood cells compress as camels safely dehydrate, then swell up again as they refill with water, keeping their blood flowing in extreme conditions.

Camels dont dry out in the desert, as we would, thanks to variants of the genes that encode the cytochrome P450 (CYP) enzymes. They enable camels to resorb lots of water while tolerating high salt conditions, without their blood pressure spiking. Their kidneys are keenly attuned to taking back water.

Camel milk is also high in the calming neurotransmitter GABA, low in lactose, and has more vitamin C than cows milk.

Beyond Milk

The astonishing adaptations of the camel arent restricted to its milk. Here are a few more that have their roots in the animals genes.

Variations on the Camel Theme

About 94% of the worlds 35 million camels are the domesticated, one-humped dromedaries (Camelus dromedaries) of northern and eastern Africa, the Arabian Peninsula, and southwest Asia. A feral branch lives in Australia. Wild dromedaries are extinct and are in a separate genus, Camelops hesternus. They dwelled in western North America.

About 2 million two-humped domesticated Bactrian (Camelus bactrianus) camels live on the steppes of central Asia, and each weighs about 1,000 pounds. Fewer than 100 wild Bactrian camels remain; they split from a shared ancestor about 700,000 years ago. Today they live in Mongolia and in northwest Chinas Xinjiang Province, in an area that was a nuclear testing site for 45 years. In 2008 the wild Bactrians were designated a distinct species, Camelus ferus.

When bactrian and dromedary camels interbreed, most offspring have one hump, some with a dip in the middle.

Camel Genomics

Camel genomes are remarkably diverse with many mutations, perhaps because people havent controlled their breeding. Doing so is challenging.

The jelly-like consistency of camel semen complicates both freezing and using artificial insemination. Still, researchers from Oman and France recently published a report about possible genetic improvements: selecting for traits that ease of using milking machines, provide resistance to infections, improve racing ability, and enhance beauty. Camels are, after all, gorgeous creatures.

The first camel genome sequence, published in 2012, revealed 20,821 genes splayed out among 37 chromosome pairs. Some 2,730 genes have evolved faster in camels than in their cattle relatives, many involved in carbohydrate and lipid metabolism. Perhaps the unusual variants contribute to the camels ability to conserve water.

Researchers from Kuwait University report in PLOS Onethat they analyzed DNA from the blood, spit, and hair of nine camels, concluding that tail hair follicle DNA is the best tissue source to create a biobank.The International Camel Consortium for Genetic Improvement and Conservation promotes camel genetic conservation.

Bring on the Camel Fro-Yo!

The milk isnt cheap. Camel Milk Cooplists $36.99 for a weeks supply. And as Christinas book explains, theres little to no incentive to conduct a clinical trial or to attempt to replicate natures magical mix of milk ingredients. Camel Crazy includes a users guide and directory of global sources.

The milk is available in liquid, frozen, and powdered form. Camel-milk-containing products include skin cream, cheeses, ice cream pops, chocolate milk, and a delectable-looking sweet called barfi, which means snow in Persian (not vomit).

When will camel milk come to Starbucks?

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Camel Milk and Autism: Connecting the Genetic Dots | DNA Science Blog - PLoS Blogs

Living implies change. This is what happens to the cells of our bodies as we grow older: they accumulate genetic alterations, most of which are harmless. However, in some specific cases, these mutations can affect certain genes and can lead to the development of cancer. The source of these alterations can be exogenous (e.g., solar radiation, tobacco smoke or some toxic substance) or endogenous (e.g., errors in DNA processing).

Scientists led by ICREA researcher Nria Lpez-Bigas, head of the Biomedical Genomics Laboratory at the Institute for Research in Biomedicine (IRB Barcelona) and Assistant Professor at the Pompeu Fabra University, have characterized for the first time the genetic alterations caused by six therapies widely used for the treatment of cancer (five based on drugs used as chemotherapies, and radiotherapy).

Chemotherapies have revolutionized the treatment of cancer, allowing the survival of large numbers of patients. Some of these therapies kill cancer cells by damaging their DNA. However, these drugs can also harm the healthy cells of the patient, thereby explaining their side effects.

It is important to remember that chemotherapies are highly efficient for the treatment of cancer, says Oriol Pich, first author of the study. But long-term side effects have also been reported in some patients. Studying the DNA mutations that occur in cells as a result of chemotherapies is the first step towards understanding the relationship between these mutations and the long-term side effects of these treatments.

To carry out the study, the Hartwig Medical Foundation in the Netherlands provided the scientists with the sequences of the metastatic tumors of around 3,500 patients and information about the treatments that they received. Using bioinformatics techniques, Lpez-Bigas group has been able to identify a specific pattern of mutations in the metastatic tumors of the patients for each of the most widely used therapiestheir mutational footprint.

Once this footprint has been identified, we can quantify the DNA mutations that have been caused by each kind of chemotherapy, as well as those caused by treatment combinations, explains Lpez-Bigas. We have compared these numbers with the genetic alterations caused by natural endogenous processes. We have calculated that, during treatment, some of these chemotherapies cause DNA mutations at a rate that is between 100 and 1000 times faster than what normally occurs in a cell.

This knowledge will allow the optimization of cancer treatments. The aim is to maximize the beneficial effects of chemotherapies by destroying tumor cells while minimizing the number of mutations caused in the healthy cells of the patients. This would be achieved through a careful combination of dose and treatment duration, says Lpez-Bigas.

Reference

Pich et al. (2019) The mutational footprints of cancer therapies. Nature Genetics. DOI: https://doi.org/10.1038/s41588-019-0525-5

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Genetic Alterations Caused by Cancer Therapies Are Identified - Technology Networks

A rare genetic disorder caused three siblings' blood to flood with fat and turn "milky" white, according to a new report of the unusual case.

The three siblings consisted of one set of fraternal twins (a daughter and son) and an older son, all born to a first-cousin couple in a Pennsylvania Dutch family. In their teens and early 20s, all three siblings experienced mysterious symptoms, including bouts of abdominal pain. They had all been diagnosed with hypertriglyceridemia, a fairly common disorder that causes fatty molecules called triglycerides to build up in the blood.

Now in their 50s, the siblings recently underwent genetic testing and learned that they have a condition that's much more rare, affecting only 1 in every million people, according to the case report, published today (Nov. 18) in the journal Annals of Internal Medicine.

Those with the ultrarare disorder, known as familial chylomicronemia syndrome (FCS), may accumulate more than 1,000 milligrams of triglycerides per deciliter (mg/dL) of blood. For comparison, normal blood levels of the fat should fall below 150 mg/dL, and 500 mg/dL would be considered "very high" in a healthy person, according to the National Institutes of Health.

Indeed, in people with FCS, blood fat levels are so high that the normally crimson fluid turns the color of milk. (FCS is not the only condition that can cause milk-colored blood; the symptom may also appear in people with severe hypertriglyceridemia.)

Related: The Color of Blood: Here Are Nature's Reddest Reds (Photos)

The three siblings had long struggled to keep their triglyceride levels under control and suffered frequent inflammation of the pancreas, also known as pancreatitis a serious condition that can cause abdominal pain, fever and vomiting. At the hospital, the male twin's triglyceride levels reached as high as 5,000 mg/dL, while the other brother's levels peaked at around 6,000 mg/dL. The female twin's triglyceride levels soared highest of all, reaching 7,200 mg/dL at maximum.

The siblings hoped their doctors could help subdue those aggressive symptoms.

To confirm the sibling's rare diagnosis, the doctors looked to their patients' genes. Triglycerides typically build up in the blood due to multiple malfunctioning genes and other related health conditions, such as diabetes or high-blood pressure, according to the Journal of the American Board of Family Medicine. But when doctors probed the siblings' genetic code, the researchers spotted only one mutated gene that was key for breaking down triglycerides in the body.

In healthy people, the gene contains instructions to build a protein called lipoprotein lipase (LPL), which typically coats the blood vessels that run through muscles and fatty tissues in the body, according to the Genetics Home Reference. LPL breaks down fats carried in the blood; without an adequate supply, the siblings' blood plasma ran thick with excess triglycerides.

Related: How to Speak Genetics: A Glossary

Each sibling carried two copies of the mutated LPL gene, meaning both their parents passed down the mutated genetic code to the children, the case report noted. What's more, the particular genetic mutation in the siblings had never been seen before, the authors said. The doctors placed the siblings on a fat-restricted diet, which successfully stabilized their triglyceride levels and quelled their bouts of pancreatitis. Sometimes, when triglyceride levels spike, doctors must manually replace the fat-filled blood of their patients with healthy blood from donors, Live Science previously reported. Thankfully, the siblings' condition could be curtained with diet alone.

Originally published on Live Science.

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A Rare Genetic Disorder Turned These Siblings' Blood 'Milky' White - Livescience.com

A devastating fungal disease, the cause of ash dieback, is on course to decimate Europes ash trees, with 70 million in the UK currently expected to perish over the coming years, costing the economy an estimated 15bn.

But in some pockets of woodland, resistance to the sickness has been detected, offering a glimmer of hope that ash trees will not be permanently erased from the landscape.

Scientists sequenced whole genomic DNA from 1,250 ash trees in 31 different areas in order to identify the inherited genes associated with ash dieback resistance.

Sharing the full story, not just the headlines

The study, published in the journal Nature Ecology & Evolution, shows resistance is controlled by several genes, offering hope survivors could be used to restore diseased woodlands, either by natural regeneration or selective breeding.

Professor Richard Nichols, author of the study from Queen Mary University of London, said: We found that the genetics behind ash dieback resistance resembled other characteristics like human height, where the trait is controlled by many different genes working together, rather than one specific gene.

Overall winner of the competition

Csaba Daroczi/NPOTY 2019

Winner in the Underwater category

Alexey Zozulya/NPOTY 2019

Finalist in the Mammals category

Jose Juan Hernandez/NPOTY 2019

Finalist in the Man and Nature category

Tom Svensson/NPOTY 2019

Finalist in the Mammals category

Marcio Cabral/NPOTY 2019

Winner of the Youth category

Giacomo Redaelli/NPOTY 2019

Finalist in the Man and Nature category

Britta Jaschinski/NPOTY 2019

Finalist in the Other Animals category

Wei Fu/NPOTY 2019

Finalist in the Landscapes category

Brandon Yoshizawa/NPOTY 2019

Finalist in the Man and Nature category

Pedro Narra/NPOTY 2019

Overall winner of the competition

Csaba Daroczi/NPOTY 2019

Winner in the Underwater category

Alexey Zozulya/NPOTY 2019

Finalist in the Mammals category

Jose Juan Hernandez/NPOTY 2019

Finalist in the Man and Nature category

Tom Svensson/NPOTY 2019

Finalist in the Mammals category

Marcio Cabral/NPOTY 2019

Winner of the Youth category

Giacomo Redaelli/NPOTY 2019

Finalist in the Man and Nature category

Britta Jaschinski/NPOTY 2019

Finalist in the Other Animals category

Wei Fu/NPOTY 2019

Finalist in the Landscapes category

Brandon Yoshizawa/NPOTY 2019

Finalist in the Man and Nature category

Pedro Narra/NPOTY 2019

Now we have established which genes are important for resistance we can predict which trees will survive ash dieback. This will help identify susceptible trees that need to be removed from woodlands, and provide the foundations for breeding more resistant trees in future.

Samples were collected from ash trees in a Forest Research mass screening trial, which comprises 150,000 trees across 14 sites in southeast England.

The researchers screened for resistance genes using a rapid approach where the DNA of diseased and unaffected trees was separated.

Many of the genes found to be associated with ash dieback resistance were similar to those previously shown to be involved in disease or pathogen responses in other species.

Ash dieback is a major threat to the UK landscape. According to the Woodland Trust, the effects will be staggering.

It will change the landscape forever and threaten many species which rely on ash, the trust has warned.

The fungus Hymenoscyphus fraxineusaffects ash trees of any age and in the UK between 70 and 95 per cent of ash trees are expected to succumb.

The 15bn economic impact is expected to be greater than that of the 2001 foot-and-mouth disease outbreak which led to more than 6 million cattle and sheep being exterminated, according to an assessment this year by a team from Oxford University.

The predicted costs include clearing up dead and dying trees, but also lost benefits provided by the trees, including water and air purification and carbon sequestration.

The loss of these services is expected to be the biggest cost to society, while millions of ash trees also line Britains roads and urban areas, and clearing up dangerous trees will cost billions of pounds.

The disease has spread throughout Europes ash populations, and was first recorded in the UK in 2012.

Professor Richard Buggs, senior research leader in plant health at the Royal Botanic Gardens, Kew and lead author of the paper, said: There is no cure for ash dieback and it threatens to kill over half of the 90 million ash trees in the UK. This will have huge impacts on the British landscape.

Our new findings of the genetic basis of natural resistance found in a small minority of British ash trees help us to predict how ash populations will evolve under ash dieback. While many ash trees will die, our findings are encouraging from a long-term perspective and reassure us that ash woodlands will one day flourish again.

Original post:
Ash dieback: Genetic resistance offers new hope over unstoppable disease expected to kill 70 per cent of species - The Independent

For most patients,sudden cardiac death iscompletely unexpected, according toDr. Amit Khera, a cardiologist at Massachusetts General Hospital.

Its always particularly devastating because many dont have prior symptoms. Their first symptom is actually dropping dead, Khera said. The question is can we find these people before something really bad happens?

Many scientists, including Khera, theorizedthat one way to find people who might suffer these sudden cardiac deaths fatal events related to an abrupt cardiovascular failure could betheir genetics.

We always had a hunch that maybe there was something in their DNA that predisposed them to this tragedy, he said.

Now, he and his colleagues believe theyve found 14 different gene variants, spread across seven genes that may put their carriers at greater risk for sudden heart death.

The researchers made this discovery by sequencingthe genes of 600 people who died from sudden cardiac death and600 people of the same age whowere healthy. Khera said they focused on 49 genesalreadyknown to be important for cardiovascular disease.

These genes contribute to any of the four major causes [for sudden cardiac death], he said. Sometimes its a weak heart and the pumping function is not quite right. The second is a heart attack. The third is a problem with the hearts rhythm. The last is a tear in a major blood vessel.

After a geneticist on the team analyzed the genetic data, Khera said 14 different versions of 7 genes stood out.

These 14 variants were found in 15 people. Whats really striking is that all 15 people were sudden cardiac death cases and zero were [healthy], he explained.

The team reported their findings Saturday in the Journal of the American College of Cardiology.

After identifying the specific gene variants, theresearchers looked ata larger database of 4,000 individuals. They found that about 1% of the population without a history of heart disease carries similar mutations in one of the 49 genes scientists believe are critical to heart health.

Its a really small percent of people, but an important percent," said Khera. "These people are predisposed to sudden cardiac death, and if we can find them then we have tools to prevent disease onset.

Carrying one of those mutations doesnt mean a person is certain to suffer from sudden cardiac death, Khera says. But his analysis suggests they do make the event three times more likely over a period of 15 years.

In most cases, doctors saysudden cardiac death arises from preventable causes.

Most of the gene variations underlying [sudden cardiac death] are related to the electrical rhythm of the heart going chaotic or haywire," said Dr. Eric Topol, vice president of Scripps Research and a cardiologist who did not work on the study.

"There are many ways you can prevent this occurrence if you know a person has a high risk mutation, Topol said. Medications or a device like a defibrillator or pacemaker can fix the underlying problem.

There are likely many more mutations that increase the risk for sudden cardiac death.

The more we find of these, the more confident we are that they are the real deal, the better we will, in the future, be at preventing these catastrophes, Topol said. So, I think this is really important work.

And not every sudden cardiac death strikes healthy individuals with no previous history of heart disease, Khera added.

Of course, important lifestyle factors play a role, like smoking over the course of a lifetime or not well controlled blood pressure, he said.

But often, families and friends of those who die from sudden cardiac death dont get a reason for why it happened.

The DNA can provide an explanation as to why this happened, Khera said. And even more importantly, this persons family members may also have the gene variant, and if they know about it then they can take preventative measures.

Editor's note: There are many mutations in the 49 genes researchers looked at in this study that may increase the risk of sudden cardiac death. Those "disease-causing" mutations occur in roughly 1% of the population, according to the research. The study focused on 14 of them.

The rest is here:
Finding Mutations On These 49 Genes May Help Prevent Sudden Cardiac Death - WBUR

"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

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