Jessie Jacobsen: seeking answers for autism

Dr Jessie Jacobsen isn’t seeking to cure autism.

Instead, the neuroscientist is focused on helping Kiwi kids with neurodevelopmental conditions pinpoint a possible underlying genetic cause.

Over the past decade, Jessie and her team have provided genetic diagnoses for more than 100 people who would otherwise never know the cause of their condition.

This is set to rise with the launch of New Zealand’s first dedicated Autism Research Clinic at the Centre for Brain Research, with Jessie at its helm.

“When you have an answer, it can have a really immediate and profound impact on a family and their life course,” says Jessie. “It can range from reassurance that a condition is real to, in some cases, helping inform life-saving treatment options.”

The clinic will use the groundbreaking genome-wide sequencing capabilities at the Centre for Brain Research and build on the Minds for Minds project – a decade-long study into the DNA variations of autism and neurodevelopmental conditions, led by Jessie and a multidisciplinary team of researchers, clinicians and community members.

The clinic will initially work with children and will combine genetic testing with follow-up support and clinical management, carried out in close collaboration with hospitals and clinicians.

With an estimated two to three percent of the New Zealand population autistic, and increased awareness and diagnoses seeing cases rise, the clinic arrives at a crucial time. Using genome-wide approaches to provide precise diagnoses for autism is relatively recent and isn’t routinely funded in New Zealand’s public health system.

“The demand from families is huge,” says Jessie, who in 2007 was named the MacDiarmid Young Scientist of the Year; in 2010 the University’s Young Alumna of the Year; and in 2013 received a Rutherford Discovery Fellowship. In 2007, she was also shortlisted for New Zealander of the Year.

“Autism is incredibly complex and will often overlap with other conditions, which genetic sequencing can help us to understand,” she says.

“For some individuals, particularly those with high support needs, identifying a change in a specific gene can reveal increased risks for other co-occurring conditions. They can then go into early management and have proactive screening.

“One recent case revealed a change in a gene associated with the development of benign tumours, so now that individual has regular check-ups for it. That kind of proactive outcome is quite amazing.”

Not every family with an autistic individual wants to go down the DNA track, says Jessie.

“But for those who do, it can be really transformative. We just want to help give these kids the best possible start in life, and that might mean supporting their strengths, as well as the difficulties they might face.”

The path to discovery

Gene discovery is poised to transform how neurodevelopmental conditions are diagnosed and managed, and Jessie is perfectly placed to lead its introduction in New Zealand.

A relatively early-career researcher, Jessie made her first major contribution to genomics as a PhD student aged only in her 20s. Working alongside Professor Russell Snell and Distinguished Professor Sir Richard Faull, she was part of the team that successfully created a sheep model of the fatal brain disorder Huntington’s disease.

It was a technique that had previously only been achieved in small animals, such as rodents. However, a sheep brain is remarkably similar to the human brain, explains Jessie and, crucially, sheep live longer than rodents, so the technique has enabled researchers to discover more about the progression of the disease before symptoms appear. This has paved the way for the development of targeted treatments.

“I remember running down the hallway in my lab coat to see Richard. We both thought ‘oh my gosh, this has worked, this could really make a difference’. That moment is seared in my mind.

“We spent a long time trying to generate an accurate and useful model of Huntington’s disease. It was such a hard-fought PhD, but so worthwhile in the end. That kind of work is immensely satisfying.”

Then, like so many talented Kiwis with the potential to shape the future, she left our shores. Her relocation to Harvard Medical School and Massachusetts General Hospital eventually worked in our favour, however, when she made the decision to return home after working in a lab at the forefront of her field.

In the US, Jessie joined a centre that was at the vanguard of a revolution in genetic research and DNA sequencing in the late 2000s.

The team was conducting groundbreaking studies in medical genetics, autism, and rare genetic disorders.

“There I was at this amazing genetics centre right in the middle of it all,” recalls Jessie.

“Massive parallel sequencing took off, and costs were coming down, making a genetic diagnosis for rare and complex conditions much more accessible.”

At the beginning of the 2000s, the cost of sequencing a human genome was about $1 million; today it sits at just over $1,000.

“It was an incredibly exciting time and it gave me the confidence to come back and say, ‘we need to be offering this in New Zealand’.”

The human impact of research

Jessie’s time in the US was funded by the Neurological Foundation of New Zealand’s prestigious Philip Wrightson Fellowship. When she decided to return home, the Foundation supported her with a repatriation fellowship.

She also received a Rutherford Discovery Fellowship, helping her to build up the Minds for Minds network and, notably, identifying several causative variations in genes for neurodevelopmental conditions, including autism.

That breakthrough came as a result of a landmark study involving 201 autistic individuals, which found almost 13 percent had a clearly identified genetic variant, while an additional 16 percent had a DNA change that likely explained their autism.

The findings have attracted international attention, however Jessie quickly points out the collaborative effort behind the work (Professor Snell and Professor Klaus Lehnert have been mainstays of her research team).

The team, she says, adheres to rigorous ethical standards.

“Being given access to a person’s genetic data is a privilege. We’ve developed protocols alongside clinical geneticists trained in delivering genetic information to families.”

And while she admits making new discoveries is thrilling, Jessie says it pales in comparison to seeing the human impact of research – an ethos heavily influenced by the altruistic nature of her parents.

Both teachers, Jessie’s parents were great believers in the power of education to transform lives. Her mother taught English as a second language, and helped to resettle Vietnamese refugees. Her father worked with students with diverse learning needs at Pakuranga College (where Jessie was head girl).

“He would have worked with autistic individuals with high support needs, but at the time many were broadly characterised as having profound learning difficulties,” she says, adding that our understanding of autism is now far more nuanced.

“There’s a saying that, if you’ve met one autistic individual you’ve met one autistic individual,” says Jessie.

“It presents uniquely in every person, with support needs varying depending on an individual’s skills and interests.

“It’s about embracing that neurodiversity while providing an accurate diagnosis to support an individual to contribute to, and be a part of our community that, unfortunately, can expect everyone to conform in the same way.”

Jessie expects that in five years, with sufficient funding, the Autism Research Clinic will be able to meet the demand for genetic diagnoses for autism across New Zealand. Generous support from the Freemasons Foundation helped fund the initial stages of the clinic.

“I’d love to involve more adults in genetic testing. Many people have grown up thinking they didn’t quite fit in but now suspect they may have autism.
“The plan is to really reach further into the community to bring world class research and informed diagnosis to the people of Aotearoa.”

Danelle Clayton