Issue 6 Online Extra Autism: The Clinical View with Stan Lapidus, CEO of SynapDx Corp

Stan Lapidus
Stan Lapidus

This article is a companion piece to The New Idealist Issue Six: The Autism Issue which you can download here.

Please note: This article was originally published in The New Idealist section of The Intelligent Review site in August 2014 before being transferred to this new site in July 2015.

Stanley (Stan) Lapidus is a life-science entrepreneur and inventor who was recently inducted into the American Institute for Medical and Biological Engineering (AIMBE) College of Fellows, in recognition of Stan’s contributions in the field of biomedical engineering (Stan has previously pioneered new technology in PAP tests for cervical cancer screening and developed a non-invasive, DNA-based screening test for colorectal cancer). Stan holds academic appointments at Tufts and MIT and is now turning his attention to Autism screening as founder of the US-based SynapDx Corp, which is currently running the industry’s largest prospective, multi-site autism clinical study to evaluate its new blood test designed to help doctors identify children with autism at a younger age. The New Idealist spoke to Stan to find out more.

On moving into Autism Research

The things that I look for, both as a scientifically curious guy and as an entrepreneur, are problems in medicine that are clinically important and scientifically overlooked. At this point, the number of really smart people cracking problems in cancer makes it really hard to come up with “Aha! I see something that others don’t”. It was true for the work we work we did with the pap smear, it was true for the work we did with colon cancer, but my curiosity started ranging more broadly and I got introduced – it was actually 2009 when we started the company – got introduced to autism by, it was actually a colleague, a professional colleague who simply asked me: “Stan, have you ever looked at the diagnosis of autism?”

a professional colleague who simply asked me: “Stan, have you ever looked at the diagnosis of autism?”

I had not and, in a night’s reading, I leaned a number of things that lit me up, again, both as a curious guy and as an entrepreneur. And they were the prevalence of autism, the impact it has on families, and the benefit of early detection… This is a disorder, as prevalent as it is, that was, and still largely is, invisible in American society.

One of the most frightening things that happened to me over the years as our story has unfolded is I’ve learned that people who I have known professionally – for years, in some cases for decades – have children at home with serious developmental issues, with autism, with other developmental issues, because these are private. You write about mental health, and so you understand these, these are private family burdens in the way that, say, being a cancer patient is not. That was important learning for me.

(Editor’s Note: I think Stan is referring to an interview I conducted with Adam Rickitt on his Mental Health in the Workplace Initiative, which was published on our sister site; TheIntelligentReview around the time of the interview with Stan. This does not reference mental health as a ‘burden on families’).

And then, as I was getting the company going, it turned out that a grand-nephew of mine was diagnosed with an Autism Spectrum Disorder, and so that which was started purely [as] an intellectual exercise became personal. The little guy is doing really well now; he responded well to behavioural therapy, but it is a story that is repeated in so many families.

On the blood test for early diagnosis of autism that he is developing

So in the United States, and I think this is true for the UK as well, the median age of diagnosis is about four-and-a-half. People who have studied the benefits of early intensive intervention – we’ll talk about some of the people…but people who deal with education and early intervention strongly support the notion that starting a child on intensive behavioural therapy is most effective when you begin before the age of three.

Our goal as a company, our business goal, is to collapse the time to diagnose, so that children are diagnosed not at four-and-a-half, but at two-and-a-half.

So there’s an 18-month, a 24-month, today, delay between when the median child is actually diagnosed and when the child could be diagnosed to have an optimal outcome. Our goal as a company, our business goal, is to collapse the time to diagnose, so that children are diagnosed not at four-and-a-half, but at two-and-a-half.

We are conducting…we announced…in March of 2013 roughly…an 880 patient study. The study is underway and the enrolment phase will finish in summer. We expect to have a look at the data some time in early 2015. Not quite sure when but roughly early 2015.

We don’t know what the results are and the time to actually launch a test is unknowable. So we’re not making any statements about that. We hope to have results certainly in the first half of 2015.

On the partnership with Google Ventures

the smartass answer is ask Google, but I’ll give you my version. We asked the question after they invested of “why did you invest?” It was a question I was afraid to ask right before they’d invested.

So, in a sense, the smartass answer is ask Google, but I’ll give you my version. We asked the question after they invested of “why did you invest?” It was a question I was afraid to ask right before they’d invested.

The answer had three parts. It was a problem they have recognised as a large problem… mental health issues and autism in particular. They were fascinated, as we are, that multi-analyte markers – DNA, RNA and others, together – might break the path of a problem that’s been unbreakable; that is to say, it’s a math problem, and they’re really good at math. We like to think we are too. So it’s a big problem. It’s one that captures Google’s strengths, its own strengths, its own wisdom – you know, analysing large data sets – we do work with them on data analysis…

It’s a problem that scales, which is a word of Google parlance that means if you’re successful you can go from small to large rapidly, which is absolutely true.

And the third [reason] is that they were very intrigued by the people with whom we surrounded ourselves. In the company we have an outstanding team of accomplished individuals, and our… clinical science guys and advisors are all among the top scientists and clinicians in the field.

That was what they were looking for. It was, again: large market, problem that scales and a team that’s likely to succeed.

That was what they were looking for. It was, again: large market, problem that scales and a team that’s likely to succeed.

Stan’s view of the link between autism and mental health issues

We speculate that the ultimate findings that we’ll take out of this study regarding autism will have important ramifications for other areas of mental health. The markers that we have discovered in people, and hopefully will continue to discover as the study draws to its final phase, will prove to be markers that are specific to autism and others that are specific to impairment, perhaps to other disorders that may develop later in life.

It’s useful to recall that when autism was first described as a unique disorder it was thought of as a sub-set or a kind of infantile schizophrenia… Today… [with] schizophrenia usually the earliest twinges usually come with adolescence and, in the United States at least, the median age is in the late teens/early twenties. So, we hope to find common denominators and if we’re successful – there are a lot of “ifs” here – if this, if this, then we’ll be able to develop other tests for other disorders in the realm of mental health. But that’s highly speculative.

So anxiety is a prevalent feature of autism but is not part of autism per se.

Many people, adults and children, with autism have other mental health issues, including anxiety disorder [which] is not a core of autism. Autism is characterised by speech and language impairment, by impairments of social interaction and repetitive behaviours – repetitive and inappropriately focused behaviours. So anxiety is a prevalent feature of autism but is not part of autism per se.

Lowered IQ is a feature of autism. In the U.S. between the high thirties and the low forties, in terms of the percentage of people who have a diagnosis on the spectrum, have IQs of 70 or under, but low IQ is not a requirement for a diagnosis of autism; it is a feature that about a third have. You may know that about a quarter of children diagnosed with something called Rett disorder, Rett syndrome, have autism. One percent of all autism cases are children with Rett’s. So, there is a clear link…

(Editor’s Note: Stan’s own figures say that two-thirds of autistic people do not have low IQ; low IQ is not a key feature of autism).

A fraction of kids with autism, a disproportionate fraction, have seizure disorders. So, again, to be on the autism spectrum you don’t have to have a seizure disorder; it’s a disproportionately prevalent co-factor. So a range of disorders. And as you may know people with seizure disorders have a lot of anxiety about having seizures – the way that that influences their ability to conduct daily life. So people who have seizure disorders controlled with meds, that’s one thing, but about fifteen percent or so have intractable seizure disorders.

So, autism is one facet into a complex picture of early onset, that is to say in childhood and in adolescence, disorders and we hope that our work will be a further window into understanding broadly… these disorders.

On Simon Baron-Cohen’s comment that a prenatal test for autism could be available in five years’ time

That’s his speculation. I have no comment on pre-natal testing.

I’ll explain why. In order to develop a pre-natal test, first you have to know what the marker is you’re looking for, then you have to identify a population of children – mothers are high risk during pregnancy – then follow those children until they develop a diagnosis. He is, of course, an accomplished scientist and has got his own opinions. My sense is that these things take longer and cost more.

We don’t know yet what precise markers to look for prenatally.

We don’t know yet what precise markers to look for prenatally. So my view is that first you identify the markers and establish their clinical validity, and if you’ve done that – and by the way that literally costs tens of millions of dollars, not to have a research paper that’s speculative but to have solid evidence across multiple sites, that’s tens of millions of dollars – only after you do that can you start to ask the question of “now can I detect autism? Do these markers appear, reliably, in children before the symptoms occur and, in fact, do the markers appear in utero? Can you measure it in… Mom’s urine, or some sample that you can get at?

It’s really expensive, very expensive. That’s a hundred million dollar problem

So there’s too many “ifs” there for a start-up company to grapple with that problem at this time. It’s really expensive, very expensive. That’s a hundred million dollar problem. And again the difference between a scientific paper and validated data across multiple sites is most of that hundred million.

On ethics and corporate-social responsibility  

I think that’s a very important point that companies like ours will play a role in explaining, not just in diagnosing but in explaining. We use the medical term “to suffer”, where in fact what we have here are children who are different. They’re not less valuable; they are simply different, and we have a role in being a voice in that discourse.

We use the medical term “to suffer”, where in fact what we have here are children who are different. They’re not less valuable; they are simply different, and we have a role in being a voice in that discourse.

On Stan’s previous comment about autism as a ‘disease’ which may imply it needs a ‘cure’ 

Nope. No, I think that our goal is one in which, for those families that believe that behavioural therapy can be important to the family and to the child, what is clear is that starting behavioural therapy sooner leads to better outcomes; most notably measured by integration into mainstream classrooms. That’s the metric that some people use. We hope to be part of that.

Stan’s role in the Personal Genome Project (In 2008 Stan volunteered to be one of the first 10 people to have his DNA publicly sequenced)

I’ve not stayed close to it, and I’ll tell you why. George Church is a brilliant scientist… It was very important for him to assess the impact of what happens to individuals whose genomes are simply publically available. When one learns about one’s genome and… that information is public, is that important? And the short version of my answer is no. [There] is no repercussion at all of my genome being available for all to look at.

So I stopped being a believer in genetic privacy

So I stopped being a believer in genetic privacy, if for no other reason than it can’t be enforced anyway, and made my statement by making my genome public, but it was a non-event – which I guess is a good answer, but it was a non-event in the case of me and my family.

…George has got a programme of publishing, I think it’s ten thousand, ten thousand genomes and it’s as much about the ethical questions of making genome information public as not. So at the time all of us signed up for the study, a law called the Genetic Information Nondiscrimination Act (GINA) had not yet been passed. So there was some question of would we be uninsurable if our genomes were public and if there were deleterious.

But in the interim, during the time of the programme…, the law did pass. The law could be used by life insurers to reject claims, but to my knowledge there are no instances of that. To make someone uninsurable, there are no instances of that. And even before the passage of GINA to only, I think there was only one, recorded case of genetic discrimination and oddly it was from a branch of government. I think it was the state government of California but I’m a little not clear on the details. But private corporations don’t… life insurance companies can, but so far don’t. That was some of the social questions that George wanted to explore: did having our genomes public change our lives?

That was some of the social questions that George wanted to explore: did having our genomes public change our lives?

The group of folks who volunteered were all above average in education because you had to know George. So you had to hang out in one way or another on the fringes of or on the mainline of genetics and/or Harvard medical school. By and large we were probably, if not the top one percent in incomes, the top ten percent. The kind of folks that if they got rejected for life insurance or healthcare insurance would not be wiped out. In the event none of us did.

By and large, given that we were older, an older group of folks, probably all of us were in our forties, probably most of us in our fifties, maybe some a little older at the time, most, if not all, genetic diseases, at least based on our current understanding, are earlier onset than that. So, we weren’t likely  to learn, for example– well, I was, based on some of my findings – at an increased risk of multiple sclerosis – well, a small increase in risk – I think it was between one and twofold since the risk of multiple sclerosis is low to being with. Devastating of it happens but a low risk. My elevated risk was not essentially concerning, given that I was already past the age that most people who ever get it get it, it was less concerning.

So I think that George’s population, given the level of income, education and age probably weren’t an ideal test case, but were certainly a very good starting case for asking the question of what happens if your genome becomes public.

On his hopes for the future of The Genome Project

You know, it’s an interesting question. The greatest benefit of having public genomes, and of course people have to consent to have their genomes public, is the aggregation of the kind of data that’s only possible when the number of subjects is [in the] tens of millions, as opposed to the tens, or the hundreds or even the thousands. And that is getting at the root of our most elusive disorders that are heritable, which means in laymen’s terms “in families”, for which genes have been elusive. Knowing that helps identify the targets, they’re called targets, for drugs, so that disorders like Type 2 diabetes can be really effectively treated.

Today we’re treating symptoms… we’re controlling glucose metabolism we’re not curing the disorder. The goal is to aggregate data sets that are sufficiently large that disorders that are caused by multiple genes interacting in peculiar ways can be characterised so that we can develop therapies.

It’s certainly the challenge of medicine in the 21st century. We’re just in the second decade of the 21st century. This has a long way to play yet.

Stan on his future goals for the bioscience sector

An excellent question. Well, I certainly think that disorders of the complex interaction between metabolism, genetics, environmental factors is the great challenge of 21st century medicine. So, the main medical outcome of the 20th century was the doubling of [the] lifespan of people in western countries and industrially advanced nations. In 1900 life expectancy at birth, which is always based on past data, in the U.S. was about forty; in the U.S. now it’s 78. It’s roughly doubled.

certainly one wants to not be frail in one’s last years. One wants not to suffer dementia, one wants not to be a congested heart failure patient, one doesn’t want to undergo what amounts to the slow death of Type 2 diabetes that’s not controlled.

I don’t know that it’s in our species to double again and one doesn’t know if one wants to, but certainly one wants to not be frail in one’s last years. One wants not to suffer dementia, one wants not to be a congested heart failure patient, one doesn’t want to undergo what amounts to the slow death of Type 2 diabetes that’s not controlled.

These disorders, the code will be broken by looking at large data sets from large numbers of people. How to organise that ethically, how to organise that being mindful of privacy, how to organise that in a way that’s scientifically efficient… the answers are unfolding in front of our eyes. Sometimes you can’t see them because they’re in front of your eyes. This is the challenge of 21st century medicine. Yeah that’s it.

You can find out more about Stan’s research at www.synapdx.com

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