What is autism? An expert explains | CNN



CNN
 — 

Some individuals with autism have challenges processing senses. Others struggle to communicate. Still others might have a tough time socializing, thinking, physically moving or just going about daily living.

People with autism have their own ways of interacting with the world, because autism is a developmental disability that affects everyone who has it a little differently, according to Dr. Daniel Geschwind, the Gordon and Virginia Macdonald distinguished professor of human genetics, neurology and psychiatry at UCLA.

Geschwind has spent 25 years studying autism and what causes it. To mark Autism Awareness Month, CNN talked with him about what autism is and what causes it.

This conversation has been lightly edited and condensed for clarity.

CNN: What is autism?

Dr. Daniel Geschwind: Autism refers to a broad range of conditions characterized by challenges with social skills and social and communication and repetitive behaviors, resistance to changes in routine, or restricted interests. I prefer to call it “the Autisms,” because it’s not one thing, and no two autistic children or adults are exactly alike even though they may share basic features. People with autism may also have some sensory-motor integration issues, especially sensory hypersensitivity.

CNN: How prevalent is autism today?

Geschwind: It isn’t rare. The most recent statistics (from the US Centers for Disease Control and Prevention) came out in March, pulled data from 11 sites (in the United States) and reported 1 out of every 36 kids is autistic. The study before that estimated around 1 in 40. About 10 years ago, the autism rate was 1 in 100, or even lower.

It would be easy to look at this trend and say autism is increasing, but that’s not really what is happening. The most recent data reflects that our ability to recognize autism and diagnose it early has improved dramatically. We’re now able to diagnose people with autism who might have (previously) fallen through the cracks.

Everybody is neurodivergent to some extent. For example, if you look at a simple IQ test, a substantial portion of people will perform really badly on one specific item. That doesn’t mean they have problems — it’s just that it means we all have strengths and weaknesses.

If I were being tested on artistic ability, for example, or engineering ability, I would be far below what’s called typical. I think we have to accept that intelligence is not just one thing, that cognition isn’t one thing, that there’s not just one way to behave.

CNN: What does it mean when people describe some as being “on the spectrum”?

Geschwind: About a decade ago, the term “autism spectrum disorder” was adopted to encompass everything that we called autism into one rubric. The intent was simply to describe the variability in how people with autism act and behave biomedically. There are some autistic individuals who just need accommodations and don’t need treatment. There are other autistic individuals who need a lot of treatment. The spectrum was intended to include them all.

Over time, non-autistic people began referring to the spectrum in a linear fashion: high to low. That means some autistic individuals were categorized as “high-functioning,” while others were categorized as “low-functioning.” For many, the notion of a spectrum is now a loaded term. Many believe that instead of talking about autism in a linear fashion, we should talk about it as a wheel or pie, where each slice represents a different trait and every individual has different strengths and weaknesses.

CNN: Is there a cure for autism?

Geschwind: There is no cure. At the same time, we’ve come very far in understanding what autism is, and we’re making progress on how to treat it. When I started researching autism 25 years ago, the autism rate was 1 in 1,000 or 1 in 2,000. To put it in deeper historical perspective, I think at that time there was only about $10 million a year or less in autism research being done that was funded (by the National Institutes of Health). And so, there was a huge disconnect between the research dollars, public awareness and the real needs of patients and families.

The notion of the term “curing” autism can be controversial. From my perspective, our true goal is to establish a kind of personalized medicine, or precision health in autism and other neuropsychiatric disorders, so that each autistic person is seen as the individual they are. We envision a world where individuals who are severely impacted by autism have the opportunity to get therapy and drugs that can help them — and those for whom a therapy is not warranted or who don’t want it will have opportunities to live life the way they want to as well. Patient autonomy and societal accommodation are important aspects when considering these issues.

CNN: What causes autism?

Geschwind: Almost every medical condition has both genetic and environmental components. In autism, it seems that heritability is very high. The most recent large study suggested that heritable genetic factors — the things that you get from your parents that your parents have in their DNA — are probably somewhere around 80% or slightly higher.

That leaves 20% that’s nonheritable, and of that we know that at least 10% of autism is caused by rare mutations that are not inherited. And that sounds like a paradox, but it’s not. If you think about Down syndrome, that’s a genetic mutation that the parents don’t have in their DNA. That’s called a new, or de novo, mutation.

You can calculate a risk score for having autism based on genetics, (but) right now, the risk score for autism is not that predictive because we haven’t done enough research. For other conditions like cardiovascular or certain cancers, risk scores are very predictive because very large numbers of people have been studied.

Even so, this autism risk score is strongly correlated with high educational attainment, or a high IQ, which again speaks to the strengths associated with being autistic and highlights that we need to be more aware of the strengths that autistic individuals may have as well to optimize their opportunities to achieve their goals or contribute to society.

There also are several environmental factors that have been shown to increase the risk of autism. One of them is maternal exposure to valproate, which is an anti-epilepsy medication. There are several maternal viral infections that have been associated with autism. And two other things: the interbirth interval — how quickly after one birth a mother has another — and the age of the father. The thought on the last point is that as a man ages, their DNA repair mechanisms are maybe less active, and there are more frequent mutations in sperm.

A key point is that all these known environmental factors act prenatally, so in most cases the tendency towards being on the spectrum is something that individuals are born with.

CNN: To what extent has research debunked the controversial notion that vaccines can cause autism?

Geschwind: The notion that vaccines cause autism has been entirely (disproved). There have been dozens of studies, using very different methodologies. There is absolutely no evidence that vaccines cause autism, and there’s been much more harm than good done by purveyors of that fiction.

CNN: How do you treat autism?

Geschwind: It is imperative to have an early diagnosis, because we know that early identification and early intervention with behavioral therapies can be effective in up to 50% of kids. Some kids will respond so well that it’s very hard to make a diagnosis of autism when they’re 9 years old if the therapy is started early enough.

The problem is that for many autistic individuals, current therapies are not that effective. There’s a lot of work being done developing more effective cognitive behavioral therapies, figuring out which therapy is the best for which child. There’s also work being done to develop medications that can be helpful to treat certain symptoms such as injurious behavior, repetitive behavior or difficulty with changes in routines.

My colleagues and I want to use treatment to augment and improve people’s symptoms, not change who they are fundamentally. We believe strongly in every individual’s autonomy. We also believe in personalized medicine so that it’s not one-size-fits-all. There will be some patients in whom we’re trying to correct a severe genetic mutation that has profound consequences, and there’ll be others that need only a handful of accommodations, just like we provide for folks who need wheelchairs.

CNN: What will your research focus on next?

Geschwind: There are two basic frontiers in my research. One recognizes that most of the work in neuropsychiatric disorders and autism has been done in primarily White European populations and focuses on a pressing need to be studying diverse populations. About seven or eight years ago, I started working with African American communities because certain aspects of genetics are population-specific, and we as researchers really need to understand that.

The frontier that is crosscutting across all of this is we need to be able to move from genetics in a population to genetics in an individual, so that by looking at somebody’s genetic makeup, we can understand the mechanism of their autism. This is precision medicine.

My work is trying to understand how specific genetic variants, how specific mutations, impact brain development to eventually lead to the symptoms of autism. If my colleagues and I can understand that mechanism, just like we can understand the genetic mechanism in cancer, we can find a drug to target that and improve those symptoms over time.

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Colorectal cancer is rising among younger adults and scientists are racing to uncover why | CNN



CNN
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Nikki Lawson received the shock of her life at age 35.

A couple of years ago, she noticed that her stomach often felt irritable, and she would get sudden urges to use the restroom, sometimes with blood in her stool. She even went to the hospital one day when her symptoms were severe, she said, and she was told it might be a stomach ulcer before being sent home.

“That was around the time when Chadwick Boseman, the actor, passed away. I remember watching him on the news and having the same symptoms,” Lawson said of the “Black Panther” star who died of colon cancer at age 43 in August 2020.

“But at that time, I was not thinking ‘this is something that I’m going through,’ ” she said.

Instead, Lawson thought changing her diet would help. She stopped eating certain red meats and ate more fruits and vegetables. She began losing a lot of weight, which she thought was the result of her new diet.

“But then I went for a physical,” Lawson said.

Her primary care physician recommended that she see a gastroenterologist immediately because she had low iron levels.

“When I went and I saw my gastro, she said, ‘I’m sorry, I have bad news. We see something. We sent it off to get testing. It looks like it is cancer.’ My whole world just kind of blanked out,” Lawson said. “I was 35, healthy, going about my day, raising my daughter, and to get a diagnosis like this, I was just so shocked.”

Lawson, who was diagnosed with stage III rectal cancer, is among a growing group of colon and rectal cancer patients in the United States who are diagnosed at a young age.

The share of colorectal cancer diagnoses among adults younger than 55 in the US has been rising since the 1990s, and no one knows why.

Researchers at Dana-Farber Cancer Institute are calling for more work to be done to understand, prevent and treat colorectal cancer at younger ages.

In a paper published last week in the journal Science, the researchers, Dr. Marios Giannakis and Dr. Kimmie Ng, outlined a way for scientists to accelerate their investigations into the puzzling rise of colorectal cancer among younger ages, calling for more specialized research centers to focus on younger patients with the disease and for diverse populations to be included in studies on early-onset colorectal cancer.

Their hope is that this work will help improve outcomes for young colorectal cancer patients like Lawson.

Among younger adults, ages 20 to 49, colorectal cancer is estimated to become the leading cause of cancer-related deaths in the United States by 2030.

Lawson, now 36 and living in Palm Bay, Florida, with her 5-year-old daughter, is in remission and cancer-free.

The former middle school teacher had several surgeries and received radiation therapy and chemotherapy to treat her cancer. She is now being monitored closely by her doctors.

For other young people with colorectal cancer, “my words of hope would be to just stay strong. Just find that courage within yourself to say, ‘You know what, I’m going to fight this.’ And I just looked within myself,” Lawson said.

“I also have a very supportive family system, so they were definitely there for me. But it was very emotional,” she said of her cancer treatments.

“I remember crying through chemotherapy sessions and the medicine making you so weak, and my daughter was 4, and having to be strong for her,” she said. “My advice to any young person: If you see symptoms or you see something’s not right and you’re losing a lot of weight and not really trying to, go to see a doctor.”

Signs and symptoms of colorectal cancer include changes in bowel habits, rectal bleeding or blood in the stool, cramping or abdominal pain, weakness and fatigue, and weight loss.

A report released this month by the American Cancer Society shows that the proportion of colorectal cancer cases among adults younger than 55 increased from 11% in 1995 to 20% in 2019. Yet the factors driving that rise remain a mystery.

There’s probably more than just one cause, said Lawson’s surgeon, Dr. Steven Lee-Kong, chief of colorectal surgery at Hackensack University Medical Center in New Jersey.

He has noticed an increase in colorectal cancer patients in their 40s and 30s within his own practice. His youngest patient was 21 when she was diagnosed with rectal cancer.

“There is a phenomenon of decreasing overall colorectal cancer rates in the population in general, we think because of the increase in screening for particularly for older adults,” Lee-Kong said. “But that doesn’t really account for the overall increase in the number of patients younger than, say, 50 and 45 that are developing cancer.”

Some of the factors known to raise anyone’s risk of colorectal cancer are having a family history of the disease, having a certain genetic mutation, drinking too much alcohol, smoking cigarettes or being obese.

“They were established as risk factors in older cohorts of patients, but they do seem to be also associated with early-onset disease, and those are things like excess body weight, lack of physical activity, high consumption of processed meat and red meat, very high alcohol consumption,” said Rebecca Siegel, a cancer epidemiologist and senior scientific director of surveillance research at the American Cancer Society, who was lead author of this month’s report.

“But the data don’t support these specific factors as solely driving the trend,” she said. “So if you have excess body weight, you are at a higher risk of colorectal cancer in your 40s than someone who is average weight. That is true. But the excess risk is pretty small. So again, that is probably not what’s driving this increase, and it’s another reason to think that there’s something else going on.”

Many people who are being diagnosed at a younger age were not obese, including some high-profile cases, such as Broadway actor Quentin Oliver Lee, who died last year at 34 after being diagnosed with stage IV colon cancer.

“Anecdotally, in conferences that I’ve attended, that is the word on the street: that most of these patients are very healthy. They’re not obese; they’re very active,” Siegel said, which adds to the mystery.

“We know that excess weight increases your risk, and we know that we’ve had a big increase in body weight in this country,” she said. “And that is contributing to more cancer for a lot of cancers and also for colorectal cancer. But does it explain this trend that we’re seeing, this steep increase? No, it doesn’t.”

Yet scientists remain divided when it comes to just how much of a role those known risk factors – especially obesity – play in the rise of colorectal cancer among adults younger than 55.

Even though the cause of the rise of colorectal cancer in younger adults is “still not very well understood,” Dr. Subhankar Chakraborty argues that dietary and lifestyle factors could be playing larger roles than some would think.

“We know that smoking, alcohol, lack of physical activity, being overweight or obese, increased consumption of red meat – so basically, dietary factors and environmental and lifestyle factors – are likely playing a big role,” said Chakraborty, a gastroenterologist with The Ohio State University Comprehensive Cancer Center.

“There are also some other factors, such as the growing incidence of inflammatory bowel disease, that may also be playing a role, and I think the biggest factors is most likely the diet, the lifestyle and the environmental factors,” he said.

It has been difficult to pinpoint causes of the rise of cases in younger ages because, if someone has a polyp in their colon for example, it can take 10 to 15 years to develop into cancer, he says.

“During that, all the way from a polyp to the cancer stage, the person is exposed to a variety of things in their life. And to really pinpoint what is going on, we would need to follow specific individuals over time to really understand their dietary patterns, medications and weight changes,” Chakraborty said. “So that makes it really hard, because of the time that cancer actually takes to develop.”

Some researchers have been investigating ways in which the rise in colorectal cancer among younger adults may be connected to increases in childhood obesity in the US.

“The rise in young-onset colorectal cancer correlates with a doubling of the prevalence of childhood obesity over the last 30 years, now affecting 20% of those under age 20,” Dr. William Karnes, a gastroenterologist and director of high-risk colorectal cancer services at the UCI Health Digestive Health Institute in California, said in an email.

“However, other factors may exist,” he said, adding that he has noticed “an increasing frequency of being shocked” by discoveries of colorectal cancer in his younger patients.

There could be correlations between obesity in younger adults, the foods they eat and the increase in colorectal cancers for the young adult population, said Dr. Shane Dormady, a medical oncologist from El Camino Health in California who treats colorectal cancer patients.

“I think younger people are on average consuming less healthy food – fast food, processed snacks, processed sugars – and I think that those foods also contain higher concentrations of carcinogens and mutagens, in addition to the fact that they are very fattening,” Dormady said.

“It’s well-publicized that child, adolescent, young adult obesity is rampant, if not epidemic, in our country,” he said. “And whenever a person is at an unhealthy weight, especially at a young age, which is when the cells are most susceptible to DNA damage, it really starts the ball rolling in the wrong direction.”

Yet at the Center for Young Onset Colorectal and Gastrointestinal Cancers at Memorial Sloan Kettering Cancer Center, researchers and physicians are not seeing a definite correlation between the rise in colorectal cancer among their younger adult patients and a rise in obesity, according to Dr. Robin Mendelsohn, gastroenterologist and co-director of the center, where scientists and doctors continue to work around the clock to solve this mystery.

“When we looked at our patients, the majority were more likely to be overweight and obese, but when we compare them to a national cohort without cancer, they’re actually less likely to be overweight and obese,” she said. “And anecdotally, a lot of the patients that we see are young and fit and don’t really fit the obesity profile.”

That leaves many oncologists scratching their heads.

Some scientists are also exploring whether genetic mutations that can raise someone’s risk for colorectal cancer have played a role in the rise of cases among younger adults – but the majority of these patients do not have them.

Karnes, of UCI Health, said “it is unlikely” that there has been an increase in the genetic mutations that raise the risk of colorectal cancer, “although, as expected, the percentage of colorectal cancers caused by such mutations, e.g., Lynch syndrome, is more common in people with young-onset colorectal cancer.”

Lynch syndrome is the most common cause of hereditary colorectal cancer, causing about 4,200 cases in the US per year. People with Lynch syndrome are more likely to get cancers at a younger age, before 50.

“In my practice and in the medical community, the oncologic community, I don’t think there’s any proof that genetic syndromes and gene mutations that patients are born with are becoming more frequent,” El Camino Health’s Dormady said. “I don’t think the inherent frequency of those mutations is going up.”

The tumors of younger colorectal cancer patients are very similar to those of older ones, said Mendelsohn at Memorial Sloan Kettering Cancer Center.

“So then, the question is, if they’re biologically the same, why are we seeing this increasingly in younger people?” she said. “About 20% may have a genetic mutation, so the majority of patients do not have a family history or genetic predisposition.”

Therefore, Mendelsohn added, “it’s likely some kind of exposure, whether it be diet, medication, changing microbiome,” that is driving the rise in colorectal cancers in younger adults.

That rise “has been something that’s been on our radar, and it has been increasing since the 1990s,” Mendelsohn said. “And even though it is increasing, the numbers are still small. So it’s still a small population.”

Dormady, at El Camino Health, said he now sees more colorectal cancer patients in their early to mid-50s than he did 20 years ago, and he wonders whether it might be a result of colorectal cancer screening being easier to access and better at detecting cancers.

“The first thing to consider is that some of our diagnostic modalities are becoming better,” he said, especially because there are now many at-home colorectal cancer testing kits. Also, in 2021, the US Preventive Services Task Force lowered the recommended age to start screening for colon and rectal cancers from 50 to 45.

“I think you have a subset of patients who are being screened earlier with colonoscopies; you have advancing technology where we can potentially detect tumor cell DNA in the stool sample, which is leading to earlier diagnosis. And sometimes that effect will skew statistics and make it look like the incidence is really on the rise, but deeper analysis shows you that part of that is due to earlier detection and more screening,” he said. “So that could be one facet of the equation.”

Overall, pinpointing what could be driving this surge in colorectal cancer diagnoses among younger ages will not only help scientists better understand cancer as a disease, it will help doctors develop personalized risk assessments for their younger patients, Ohio State University’s Chakraborty said.

“Because most of the people who go on to develop colorectal cancer really have no family history – no known family history of colon cancer – so they would really not be aware of their risk until they begin to develop symptoms,” he said.

“Having a personalized risk assessment tool that will take into account their lifestyle, their environmental factors, genetic factors – I think if we have that, then it would allow us hopefully, in the future, to provide some personalized recommendations on when a person should be screened for colorectal cancer and what should be the modality of screening based on their risk,” he said. “Younger adults tend to develop colon cancer mostly in the left side, whereas, as we get older, colon cancer tends to develop more on the right side. So there’s a little difference in how we could screen younger adults versus older adults.”

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How human gene editing is moving on after the CRISPR baby scandal | CNN

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CNN
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For most of her life, Victoria Gray, a 37-year-old mother of four from Mississippi, had experienced excruciating bouts of pain.

Born with the blood disorder sickle cell disease, lengthy hospital stays and debilitating fatigue disrupted her childhood, forcing her to quit pursuing a college nursing degree and take potent and addictive painkillers.

“The pain I would feel in my body was like being struck by lightning and hit by a freight train all at once,” she said this week at the Third International Summit on Human Genome Editing in London.

In 2019, she received an experimental treatment for the inherited disease that used the gene-editing technique CRISPR-Cas9, which allowed doctors to make very precise changes to her DNA. While the procedure itself was grueling and took seven to eight months to fully recover from, she said it has transformed her life.

“The feeling is amazing. I really feel that I’m cured now,” Gray said. “Because I no longer have to face the battles that I faced on a day-to-day (basis). I came from having to have an in-home caregiver to help me take baths, clean my house and care for my children. Now I do all those things on my own.”

She’s now able to enjoy a life she once felt was passing her by. She holds down a full-time job as a Walmart cashier, and she’s able to attend her children’s football games and cheerleading events and enjoy family outings. “The life I felt I was just existing in I’m now thriving in,” she said.

Gray shared her experience with doctors, scientists, patient advocates and bioethicists who gathered in London for the human genome editing summit, at which participants reported on advances made in the field and debated the thorny ethical issues posed by the cutting-edge technology.

“I’m here really to be a light because there’s mixed feelings about gene editing. And I think people can see the positive result of it. You know that a person who was once suffering in life, was miserable, now is able to be a part of life and enjoy it,” Gray told CNN.

Gray’s uplifting story, which received a standing ovation from the audience, stood in contrast to a presentation made the last time the conference was held, in Hong Kong in 2018, when Chinese doctor He Jiankui stunned his peers and the world with the revelation that he had created the world’s first gene-edited babies.

The two girls grew from embryos He had modified using CRISPR-Cas9, which he said would make them resistant to HIV. His work was widely condemned by the scientific community, which decried the experiment as medically unnecessary and ethically irresponsible. He received a three-year jail sentence in 2019.

Questions about the baby scandal still linger more than four years later, and after being recently released from prison, He is reportedly seeking to continue his work. China has tightened its regulation of experimental biomedical research since 2018, but it hasn’t gone far enough, said Joy Zhang, a medical sociologist at the University of Kent in the United Kingdom.

“Ethical governance in practice is still confined to traditional medical, scientific, as well as educational, establishments. The new measures fail to directly address how privately funded research and other … ventures will be monitored,” Zhang said at the conference.

Ethically questionable experimental research isn’t an issue confined to China, said Robin Lovell-Badge, head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute in London, who chaired the 2018 Hong Kong conference session in which He attempted to defend his work.

“(He Jiankui) is not the only concern in this area. One of our big concerns I always have is the possibility that there will be rogue companies, rogue scientists setting up to do genome editing in an inappropriate way,” Lovell-Badge said on Monday at the conference.

Gray shared her story at Monday's conference.

While the CRISPR baby scandal tarnished the technology’s reputation, CRISPR-Cas9 and related techniques have made a major impact on biomedical research, and two scientists behind the tool — Emmanuelle Charpentier and Jennifer A. Doudna — won a Nobel prize for their work in 2020.

“Clinical trial results demonstrate that CRISPR is safe, and it’s effective for treating and curing human disease — an extraordinary advance given the technology is only 10 years old,” Doudna said at the conference in a video address. “It’s important with a powerful technology like this to grapple with the challenges of responsible use.”

In addition to the sickle cell trial that includes Gray, clinical trials are also underway to test the safety of gene editing in treating several other conditions, including a related blood disorder called beta thalassemia; leber congenital amaurosis, which is a form of inherited childhood blindness; blood cancers such as leukemia and lymphoma; type 1 diabetes; and HIV/AIDS.

DNA acts as a instruction manual for life on our planet, and CRISPR-Cas9 can target sites in plant and animal cells using guide RNA to get the Cas-9 enzyme to a more precise spot on a strand of DNA. This allows scientists to change DNA by knocking out a particular gene or inserting new genetic material at a predetermined site in the strand.

People with sickle cell disease have abnormal hemoglobin in red blood cells that can cause them to get hard and sticky, clogging blood flow in small vessels.

In the trial that Gray was part of, doctors increased the production of a different kind of hemoglobin, known as fetal hemoglobin, which makes it harder for cells to sickle and stick together. The process is invasive and involves removing premature cells from the bone marrow and modifying them — by using CRISPR-Cas9 in the lab — to eventually produce fetal hemoglobin. The patient has to undergo a round of chemotherapy before receiving the gene-edited cells to ensure the body doesn’t reject them.

The conference also shed light on new, more sophisticated gene-editing techniques, such as prime editing and base editing, which recently was used to modify immune cells and successfully treat a teen with treatment-resistant leukemia.

These next generation techniques will allow humans “to have some say in the sequence of our genomes so we are no longer so beholden to the misspellings in our DNA,” said David Liu, the Richard Merkin professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad Institute of MIT and Harvard University.

The gene therapy trials currently underway involve treating people who were born with a certain disease or condition by altering non-reproductive cells in what’s known as somatic gene editing.

The next frontier — many would say red line — is heritable gene editing: altering the genetic material in human sperm, eggs or embryos so that it can be safely passed onto the next generation. The goal would be to prevent babies from inheriting genetic diseases.

A researcher handles a petri dish while observing a CRISPR/Cas9 process through a stereomicroscope at the Max-Delbrueck-Centre for Molecular Medicine in 2018.

“It’s a very different set of ethical trade-offs when you’re not a treating disease in an existing individual but you’re in fact preventing an individual yet to be born from suffering from a disease. That’s a very different set of considerations,” said George Daley, Caroline Shields Walker Professor of Medicine and dean of the faculty of medicine at Harvard Medical School.

In a statement released at the end of the conference, the organizers said “heritable human genome editing remains unacceptable at this time.”

They added that public discussion and policy debates should continue and were important for resolving whether this technology should be used.

The hope offered by gene therapy is creating fresh ethical storms — primarily over who gets access to such treatments. The therapy Gray received, which is expected to soon receive regulatory approval, is likely to cost more than $2 million per person, putting it out of reach for many who need it in the United States and in low-income countries.

“If we want to be serious about equitable access to these kinds of therapies, we have to start talking early on about ways to develop them and make them available and make them cost effective and sustainable,” said Alta Charo, the Warren P. Knowles Professor Emerita of Law and Bioethics at the University of Wisconsin at Madison.

Researchers want to develop CRISPR therapies that can be delivered though an injection rather than the chemotherapy and invasive bone marrow transplant Gray went through.

Worldwide, more than 300,000 children are born with sickle cell disease every year, over 75% of whom live in sub-Saharan Africa, where screening programs and treatment options are limited.

Even relatively affordable drugs to treat sickle cell disease, such as hydroxyurea, don’t reach everyone who needs them in India, said Gautam Dongre, the secretary of the National Alliance of Sickle Cell Organizations in India and father of two children with sickle cell disease.

“After 40 years if these drugs aren’t reachable for the common people, then what about gene therapy?” Dongre asked at the conference.

Julie Makani, an associate professor in the department of haematology and blood transfusion at Muhimbili University of Health and Allied Sciences in Tanzania, said more genomic research should take place in Africa.

“The ultimate thing for me, particularly as a physician scientist, is not just discovery, but also seeing the application of knowledge…into (an) improvement in health,” Makani said.

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Millions have the same ‘bendy body’ disease as my daughter. Why isn’t the medical profession paying more attention? | CNN



CNN
 — 

One day in July 2021, my then 15-year-old daughter Poppy stumbled and fell while walking down some stairs, grazing her knee. It wasn’t a serious wound, but over the weeks it didn’t heal.

Around the same time, her wrists and knees became sore; her ankles started rolling when she walked; her hands began shaking; her headaches and stomach aches became more frequent and intensely painful. She was always exhausted.

Before her health declined, Poppy had enjoyed horse riding and gymnastics, she’d competed in cross country races and been a fearless goalkeeper for the school hockey team.

But within a couple of months, as walking became increasingly difficult, she asked me for a walking stick. We found one that folds up and fits neatly in her school bag.

I took Poppy to doctors who conducted tests, but they couldn’t find out what was wrong with her. Then, in October, a breakthrough.

A podiatrist who was measuring Poppy for insoles to support her aching feet asked if Poppy could bend her thumb to reach her forearm. She could. Could she pull her little finger back to form a 90-degree angle with the back of her hand? She could do that, too.

“Have you heard of Ehlers-Danlos syndrome?” the podiatrist asked me. I hadn’t – so as soon as I got home, I went looking on the internet.

There are 13 types of Ehlers-Danlos syndrome (EDS), according to research and advocacy organization The Ehlers-Danlos Society. Most types are very rare, and can be diagnosed using genetic tests. However, the genes that cause hypermobile EDS (hEDS) – the most common form, accounting for about 90% of cases – are unknown, so diagnosis is based on a checklist of symptoms. The list includes a hypermobility rating, known as the Beighton Score.

Poppy had enough symptoms to qualify for hEDS, and the diagnosis was confirmed by a doctor one year ago, on Christmas Eve. He told us that although we can do our best to alleviate some symptoms, there is no cure.

Poppy reacted to the news better than I did. She had known for some time that something was fundamentally wrong. The diagnosis was upsetting but identifying her illness also gave her a sense of relief. I felt shocked and overwhelmed, and I cried for weeks.

Reading about EDS was like a dreadful slow reveal.

I learned that it’s a genetic disorder that causes the body to make faulty connective tissue, and connective tissue is everywhere – in the tendons, ligaments, skin, heart, digestive system, eyes and gums.

Weak connective tissue leads to hypermobility, which may sound like a good thing, but some people with bendy bodies suffer a mind-boggling array of symptoms, including joint dislocations and subluxations (like a mini dislocation, when the joint partially slips out of place), soft stretchy skin, abnormal scarring, poor wound healing, gastrointestinal disorders, chronic pain and fatigue.

The severity of symptoms varies wildly. Patients with milder cases can lead relatively normal lives, while others become housebound, and some can’t digest food and must be fed through tubes.

What’s more, people with hEDS are prone to other conditions, including POTS (postural orthostatic tachycardia syndrome, which makes you dizzy when you stand up) and MCAS (mast cell activation syndrome, which gives you allergy-type symptoms).

I learned a lot of new acronyms and they all spelled bad news.

I initially thought hEDS was rare, because all forms of EDS are commonly referred to as rare. But within a few weeks, I felt like I was seeing references to hEDS everywhere. Actor, writer and director Lena Dunham; actor and presenter Jameela Jamil; and drag queen Yvie Oddly live with it. I deep dived into EDS Twitter and EDS Instagram, while Poppy found it comforting to watch TikTok videos made by teenagers with the condition.

I discovered multiple patient groups on Facebook, each with tens of thousands of members, which turned out to be great sources of support. I asked questions (what kind of shoes are best for weak ankles? Which knee braces are easiest to pull on and off?) and kind strangers sent helpful advice. At the same time, scrolling through countless personal stories of pain, despair and shattered dreams made me feel terrified about what might lie ahead.

I noticed common themes. Many EDS patients had spent years seeking the correct diagnosis; others felt they’d been neglected and gaslit by doctors.

There was also a lot of talk of zebras.

Linda Bluestein, a Colorado-based physician who specializes in EDS and other hypermobility conditions, and has hEDS herself, explains why.

“I was told in medical school, ‘when you hear hoofbeats think horses, not zebras,’” she says. Many trainee doctors receive the same advice – when a patient presents with symptoms, “look for the common thing.” That’s why EDS patients commonly refer to themselves as zebras – and also use the fabulous collective noun “dazzle.” The name represents rarity and evokes the stripy stretch marks that are a common feature on EDS skin.

But if people with hEDS are medical zebras, why am I encountering so many of them?

Bluestein says that for many years it was thought that one in 5,000 people had Ehlers-Danlos syndrome. But she says the limited research that’s been carried out into the prevalence of hEDS suggests the true number of cases is “much, much higher” than that.

Dr. Linda Bluestein has treated hEDS patients  who have been searching for a diagnosis for decades.

Bluestein points me to a 2019 study carried out in Wales – a country of 3.1 million people. An examination of primary care and hospital records from 1990 to 2017 found that one in 500 people there has either hEDS or joint hypermobility syndrome (a similar condition with a slightly different set of symptoms). She says it’s “a good study” but believes it’s still an underestimate. The Ehlers-Danlos Society says more population studies need to be done to give a more accurate view of its incidence elsewhere.

But despite this possible prevalence, and how debilitating hypermobility disorders can be, the average time to diagnosis from the onset of symptoms is 10 to 12 years, according to The Ehlers-Danlos Society.

Bluestein has firsthand experience of this. Growing up, she wanted to become a ballet dancer and trained six days a week. When puberty hit, she started experiencing joint pain and migraines, and at 16 had her first orthopedic surgery. She realized she wouldn’t succeed in the ballet world and instead pursued her “back-up plan,” to become a doctor. But despite her career choice, Bluestein only received her hEDS diagnosis when she was 47 – more than 30 years later.

“I told my doctor on numerous occasions, ‘there is something wrong with me, I don’t heal well, I get injured more easily than other people’,” she says. “And he just never, never listened.”

Why, for so many patients, does it take so long to get diagnosed?

In 2014 a leading EDS expert, Professor Rodney Grahame, remarked at a conference that “no other disease in the history of modern medicine has been neglected in such a way as Ehlers-Danlos syndrome.”

Far more women than men are diagnosed with EDS, which could help to explain the neglect, because the medical profession has a long history of overlooking health complaints made by women.

A 2009 study, conducted by the European Organisation for Rare Diseases, surveyed 414 families of EDS patients from five countries and found that the average delay to an EDS diagnosis was four years for men – but 16 years for women.

The report states that women with EDS tend to be “diagnosed later because their pain and hypotonia (poor muscle tone) aren’t considered as physical symptoms but rather as psychological symptoms or common complaints.”

“We tend to get dismissed a lot more easily,” says Bluestein. “People jump to the conclusion that we’re histrionic females.”

Anxiety is very common in patients with hypermobility issues, says Bluestein, which can cloud the picture. “When people with anxiety present to a physician, it can suck all the air out of the room, so that the physician almost can’t see anything else.”

This can ramp up the patient’s anxiety further “because people aren’t validating our symptoms, and then we start to doubt ourselves,” she says.

What’s more, medicine is divided into silos which creates the “worst possible model” for EDS patients, says Bluestein.

VIDEO THUMBNAIL Ehlers-Danlos Syndrome 1

‘We’re born with this and will never be free:’ Hear stories from people with Ehlers-Danlos syndrome

She explains that undiagnosed patients might consult a neurologist for their migraines, a rheumatologist for joint pain, a cardiologist for palpitations, a gastroenterologist for digestive issues and a urologist for bladder symptoms. Each doctor focuses on the symptoms that fall within their specialty but doesn’t consider the other ailments. “Nowhere along the way does somebody realize that there are certain conditions that could tie all of these things together and explain everything,” says Bluestein.

The 2009 rare diseases study found that during the quest for a diagnosis, 58% of EDS patients consulted more than five doctors, and 20% consulted more than 20.

The consequences of not getting diagnosed for years can be devastating.

Melissa Dickinson, a psychotherapist in Atlanta, Georgia, says she experienced symptoms of a “mystery illness” since childhood. Then in 2013, she “went on honeymoon to Mexico, relatively healthy, and came back disabled and with a dislocated neck.”

While on vacation, Dickinson says she got food poisoning and was prescribed ciprofloxacin, an antibiotic that can pose a serious risk of aortic aneurysm to people with EDS. Instead, she says it triggered significant nerve damage, digestive issues that almost made her go blind because her body wasn’t absorbing nutrients, and put her in a wheelchair.

Dickinson, who finally received her hEDS diagnosis in 2014, says taking the wrong medication “wrecked me from head to toe.” Now that she’s receiving treatment, “I can walk with mobility aids, but most of my body has to have constant support to function.”

Lara Bloom, president and CEO of The Ehlers-Danlos Society, who herself has hEDS, says many patients have “medicalized PTSD.”

“They have had to stop their careers, they’ve had to drop out of school, their relationships have broken down.” The delay inevitably results in worsening symptoms and a declining quality of life, she says. In worst-case scenarios, patients “are dying by suicide, they’re self-harming.”

Sometimes, the failure to diagnose EDS has led to children being taken away from their parents.

In 2010, Americans Rana Tyson and her husband Chad were falsely accused of harming their 4-week-old twin daughters, who had unexplained fractures in their legs.

Along with their older sister, the baby girls were taken by state authorities in Texas and sent to live with relatives. “It was the worst day of my life,” Tyson tells me in a phone call.

Five months later, a geneticist identified the twins as having a connective tissue disorder, and they were subsequently diagnosed with EDS and a vitamin D deficiency. The family was reunited but “12 years later, it still hurts,” says Tyson.

Bloom says some other parents of children with EDS have been wrongly accused of “fabricated or induced illness (FII)” – a rare form of abuse, formerly known as Munchausen’s syndrome by proxy, in which a parent or care giver deliberately causes symptoms or tries to convince doctors that a healthy child is ill.

Ellie Pattison, who has hEDS, has been repeatedly misdiagnosed as having an eating disorder.

Ellie Pattison, a 19-year-old student who lives in County Durham, England, suffers from severe digestive issues linked to hEDS.

Throughout her childhood, Ellie was repeatedly misdiagnosed as having an eating disorder, she says, while her mother Caroline was accused of FII on three separate occasions. Caroline successfully fought to keep her daughter at home, says Ellie, but the ordeal has left the whole family with “an unimaginable amount of trauma.” Ellie says she suffered from PTSD and endured years of horrific nightmares, triggered by living with the fear from a young age that she could be forcibly separated from her family.

This underlines why prompt diagnosis is so important, says Bloom. “Our hope and dream is for people to get diagnosed when their symptoms begin.”

In the case of hEDS, a crucial first step is to find out what causes it.

Cortney Gensemer, a biomedical scientist in the Norris Lab at the Medical University of South Carolina’s department of Regenerative Medicine and Cell Biology, is trying to solve this mystery. She and research mentor Russell Norris, head of the lab, have been studying a gene mutation they believe causes hEDS (the results of the study are currently under peer review).

Like Poppy, Gensemer was diagnosed with hEDS as a teenager. She says the disease affects every aspect of her work. Looking down a microscope is particularly painful at times – her neck is unstable because of her hEDS, and she’s had metal screws put into some of her neck vertebrae to fuse them.

Cortney Gensemer working in the Norris Lab and recovering from neck surgery earlier this year.

Norris kitted the lab out with special equipment, including motion sensor doors (standard lab doors are very heavy), adjustable chairs and ergonomic pipettes that are gentle on the hands. “If I didn’t have all that stuff, I don’t think I’d be able to do it,” says Gensemer.

To find a hEDS-causing gene, Gensemer says she and Norris sampled DNA from a large family with cases spanning four generations and looked for a mutation that appears only in relatives who have the disease. They identified a “strong candidate gene” and inserted it into mice using gene editing tools.

Gensemer and Norris found that the hEDS mice had significantly more lax tissues, and floppier tails than regular rodents. “You can tie a loose knot into the mutant mouse tail. With a normal mouse tail, you can (only) bend it into a circle,” Gensemer says.

The gene that Gensemer and Norris found won’t account for all hEDS cases, she says. They believe that eventually multiple genes will be identified, and hEDS may be split into different subtypes. This would help to explain why different patients have different symptoms. Crucially, if genetic information sheds light on how the connective tissue is “messed up,” it could lead to effective treatments, says Gensemer.

The Ehlers-Danlos Society is also looking for genes as well as blood markers, working with a team of experts to sequence and analyze the DNA of 1,000 hEDS patients from around the world. And at the UK’s University of Warwick, Ph.D. candidate Sabeeha Malek, another scientist with hEDS, has proposed that EDS might be caused by a fault in the way that collagen binds to cell membranes in connective tissue. If she’s right, she hopes her work will lead to a skin biopsy test that could identify all forms of the disease.

Sabeeha Malek is working to identify biomarkers that could make EDS diagnosis easier.

Progress is being made but on a very small scale. “If you look at any major academic institution, there are multiple labs studying cancer, multiple labs studying heart disease. When you look at a disease that affects one in 500 people, and probably more than that, there should be a lab studying it at every single academic institution,” says Gensemer.

Gensemer hopes that as more discoveries are made and data is accumulated it will “change the way the medical community looks at the disease” – and that it will be taken more seriously.

A year has passed since Poppy’s diagnosis. The initial shock has subsided, and while I’m still grieving the loss of her health, we’ve both learned to accept our new reality and have adjusted to living with EDS.

I’ve assembled a team of supportive doctors and therapists and acquired an arsenal of paraphernalia to fight pain and manage symptoms, including braces and kinesiology tape to hold her joints in place; ice packs, heat pads, tiger balm and arnica gel for sore muscles; and a cupboard full of medications and supplements.

With Poppy often stuck at home, I also got her a giant kitten that she calls Bagel, and he provides the best therapy.

Poppy with Bagel.

Writing this article has taught me a lot more about EDS: It’s been upsetting to report on the terrible experiences some have suffered, but I’ve been awestruck by the dedication of people, many with the condition themselves, who are working to find solutions.

I don’t know what the future holds for Poppy. Some patients’ symptoms improve with age; others experience an increase in pain and a loss of mobility. I’ve learned there’s a limit to what we can control but there’s a lot we can do, to tackle symptoms and make life easier. And I believe that change is coming.

With a better understanding of the condition and diagnostic tools on the horizon, my biggest hope is that there will be a cure one day – and that it will come in time for Poppy.

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