The science of autism is a story of real people (Books - In a Different Key by John Donvan & Caren Zucker)

Ruth had stopped doubting herself the morning she saw Joe do a jigsaw puzzle upside down.  For some time, she had been nagged by a feeling that he was not like her other children in some crucial way.  Six months earlier, Joe had stopped speaking, even though, up to that point, he had seemed to be developing normally...

And then there were these puzzles.  He was working on one just then, a map of the United States whose parts were sprawled, like him, all over the kitchen floor and through the doorway into the living room.  He was getting it done: New Hampshire met Maine, and New Mexico snapped in next to Arizona.  But he was getting it done fast, almost too fast, Ruth felt, for a two-year-old.  On a hunch, she knelt down to Joe's level and pulled the map apart, scattering the pieces. She also, deliberately, turned each piece upside down, so that only the gray-brown backing was showing.  Then she watched what Joe did with them

He seemed not even to notice.  Pausing only for a moment, Joe peered into the pile of pieces, then reached for two of them.  They were a match.  He immediately snapped them together, backside-up, between his knees on the floor.  It was his new starting point.  From there he kept going, building, in lifeless monochrome, out of fifty pieces, a picture of nothing. 

What John Donvan's and Caren Zucker's In a Different Key: The Story of Autism (Crown Publishers, 2016) is especially good at, is conveying a picture of autism historically, scientifically, and socially, by telling the stories of the people involved.  One in 68 children have a diagnosis, so it's hard to live in today's America without hearing about autism.  Understood as a lifelong neurodevelopmental disorder, it is diagnosed based on impairments in communication, especially social relatedness, and a restricted repertoire of activity and interests. The dysfunctions it results in manifest themselves in different persons as impaired eye contact, failure to develop peer relationships, an absence of or delay in developing communicative speech, an inability to conceive of other people's mental states or emotions, lack of spontaneous imaginative play, inflexible adherence to routines which are disruptive to daily functioning, and persistent preoccupation with part of objects rather than their conventional uses, symptoms which must be present prior to three years-of-age to be diagnostically relevant and which often are noticed suddenly, after a period of apparently typical development.

Two maverick souls struggle for closeness (Books - Three Weeks in December by Audrey Schulman)

Two maverick American souls travel to Africa 100 years apart.  Each faces an utterly unfamiliar culture and physical hardships that challenge them to change fundamentally or to perish.  In 1899, Jeremy an engineer, is charged with the construction of a bridge in British-held East Africa, employing a crew of Indian workers.  The work is plagued by two lions who have begun attacking humans.  Max is an ethnobotanist hired by a pharmaceutical company to track down a rare vine in Rawanda that could be the source of a valuable hypertension drug.  Her search is pressured by the advancing Congolese rebel army who threaten her with bodily harm, and the mission of her co-workers who study silverback gorillas.  The habitat of the gorillas, for whom Max develops an intense sympathy, will potentially be ravaged by commercial drug development.

"Golly Moses, natcherly we're punks" -or everything I know about neuroscience and the law I learned from West Side Story

Lotus reads and I have had an exchange in her comments and mine since I wrote on Capgras syndrome and she on alexia - my how neuroscience is in the news! She brought up the case of comedian Tony Rosato (links here and here) who defended the charges of harrassment against his ex-wife and their child with his diagnosis of Capgras. That made me think of a New York Times Sunday Magazine article from a few months back - The Brain on the Stand, in which Jeffrey Rosen discusses how neuroscience and the law are becoming more and more frequently intertwined.

Herbert Weinstein, a 65-year-old ad executive who was charged with strangling his wife, Barbara, to death and then, in an effort to make the murder look like a suicide, throwing her body out the window of their 12th-floor apartment on East 72nd street in Manhattan. Before the trial began, Weinstein's laywer suggested that his client should not be held responsible for his actions because of a mental defect - namely, an abnormal cyst nestled in his arachnoid membrane, which surrounds the brain like a spider web.

The implications of the claim were considerable, American law holds people criminally responsible unless they act under duress (with a gun pointed at the head, for example) or if they suffer from a serious defect in rationality - like not being able to tell right from wrong. But if you suffer from such a serious defect, the law generally doesn't care why - whether it's an unhappy childhood or an arachnoid cyst or both. To suggest that criminals could be excused because their brains made them do it seems to imply that anyone whose brain isn't functioning properly could be absolved of responsibility. But should judges and juries really be in the business of defining the normal or properly working brain?

Insanity pleas have been around for a long time, in fact, 19th century French law allowed a crime passionel, a sudden jealous rage, as a valid defense for the charge of murder. But it seems we are now having courts judge not only whether someone's state of mind made them do it - which our legal system has long asked juries or judges to decide as it is an unanswerable question, as certainty resides only with the accused (and sometimes not even they could say) - but questions around science itself, i.e. could a cyst make him do it. Does a delusional syndrome, a cyst, or a truly rotten childhood make someone act? Can they truly not help it? If a cyst is responsible is the person with the cyst not responsible? Does the cyst eliminate free will altogether? Just some of it? Just at certain times?

the trouble is he's crazy, the trouble is he drinks, the trouble is he's lazy, the trouble is he stinks...

...gee Officer Krupke, it's just our bringin' up-kee...

And is a jury of our peers really qualified to say - especially in a climate in which people are poorly educated enough to legislate the teaching of "intelligent design" in a science class (I'm not discussing its legitimacy, mind you, just its place in a science class), when people believe that their thoughts can be "read" by the electrodes placed on the surface of their scalps or even worse, when they fear that we could plant thoughts into their brains by such a devise (They can't). Now don't get me wrong, I know that the branch of science I'm getting into is highly technical and difficult to understand and that our knowledge of science has been muddied by access to a lot of really cool science fiction - but that's my point. And, frankly, neuroscience is a burgeoning field- and those working in it would be the first to tell you how much we DO NOT understand, So, while I'm troubled by the fact that courts are being asked to decide upon someone's future by interpreting their will, I guess in some ways we are all equally ignorant when it comes to someone else's intent and therefore the courts have to decide, because laboratories cannot. I hope those decisions will be made with a more and more solid understanding of the science of the brain but that that will be coupled with a reasonable modesty about what we don't know.

However, I'm even more troubled when courts are being asked to decide what must be determined by scientific process - like whether childhood vaccines cause autism, see my post on Cedillo v. Department of Health and Human Services. Granted we can't even agree on what autism actually is, but the most recent scientific evidence has clearly pointed us away from that explanation with well designed studies. Scientific causality needs to be determined with double-blind studies, as a result of rigorous and repeated hypothesis testing in laboratories, so that belief about outcome (known as experimenter bias) is reduced as much as possible. Having nothing but the belief be the determining factor is a grave error, it demonstrates a sad lack of understanding about how conclusions regarding causality in science are reached. Courts cannot and should not carry out this work.

Anyway... lots to think about. And in my ramblings I discovered The Project on Law and Mind Sciences for those of you wanting to think further about culpability, cysts, and our bringing up-kee.

Home is where the books are

As a companion piece to Matt's post about those who buys books by the yard, here's a lovely story by Jim Dwyer from Saturday's New York Times about a man whose home is books - Kurt Thometz. And I didn't know this was possible, he owns a New York book store I have never heard of - Jumel Terrace Books. It's in a neighborhood full of gorgeous old homes and lovely gardens, that receives little traffic by those who visit New York - North Harlem. There's also a tie-in with one of this blog's topics as Mr. Thometz son, Adam, is said to have autism:

By the age of 5, Adam had not yet spoken an intelligible word - not Mommy, not Daddy, not milk or no. Mr. Thometz read to him every night for two and a hlaf years. With Adam in the crook of his arm, the weight of the day on him, Mr. Thometz was reading Thomas the Tank Engine for the 200th time.

"Henry the engine," he read.

"Green," Adam interrupted.

Yes: the proper name was Henry the Green engine. Mr. Thometz had dropped the word. "He supplied it,k" Mr. Thometz said. "It was the first time he had used a word on purpose." And it was the first rung on the ladder he climbed from his isolation.

This is not a story of scientific explanation - I don't know how or by whom his son was diagnosed, etc., and the reading is not discussed as formal "treatment." But it is a lovely story about a man persisting and finally reaching across the divide to his son with the power of a story.

Zeitgeist Alert - Autistic Girls are Different from Autistic Boys

This Sunday's New York Times Magazine had an excellent article on autism in girls. Boys are four times as likely to be diagnosed autistic as girls, and the ratio for Asperger's syndrome is even higher - perhaps 10:1 (boys:girls). Since girls are diagnosed so much less frequently, there are less data on them - leading to less frequent diagnosis, less research, etc...- an unfortunate catch-22.

The article talks about the fact that boys with autism and Asperger's often manifest their social deficits by isolating themselves from other people, whereas girls seem to wish to connect socially but lack the tools, which often leads to severe anxiety and depression. Depression is co-morbid with autism in girls at a rate much higher than that of boys.

Boys with Asperger's, while exhibiting social deficits generally are seen to excel in subjects like math and engineering, but girls exhibit their strong abilities in more in realms such as writing and reading.

One of the conundrums in researching autism is the many ways symptoms can be manifest are not consistent. It is not the same as studying polio, where the presence or absence of a single biological market, i.e. the virus, determines a diagnosis. Leading researchers agree that one single cause for what we now call autism is very unlikely. That complicates an already complicated puzzle because the target is moving. Are girls not diagnosed as often because not as many of them have autism or because girls manifest the condition with different symptoms? If not as many cases are seen in girls should autism be redefined or is that because fewer girls have it? Since we haven't completely figured out what "it" is, that's not a question we can answer right now.

Autism - a mystery wrapped inside an enigma

As I've mentioned before, I work in a lab that is studying both normally developing brain's and those of kids affected by autism and other disorders. I'm reading lots of articles right now (that somehow never made it to the Summer Reading Challenge) about other scientists' work in the area. The dialogue among members of the scientific community is vital to the process of discovery as each new experiment is built upon the findings (whether successful or not) of those that preceded it.

Autism has become an industry these days, as the above picture suggests. The topic has entered public awareness, but well tested experimental results are indiscriminately mixed with old theories that should have given up the ghosts given more recent work, and the crackpot notions that arise because people with good hearts want answers. As I'm digesting these articles I thought I'd summarize some of the ones I find more interesting for those of you who care. Some of them are more global theories about what might lie behind the syndrome, others look at highly specific symptoms, or characteristics. I'll do one of each today. I'll define any terms that seem potentially difficult or are usually referred to in the media too generally (as in the term 'autism' itself), and I'll try to use layman's language. If I can find free sources with greater detail I'll link to them, otherwise I'll just reference them.

Autism is a developmental disorder that is characterized by a certain number of impairments in social and emotional behaviors, delays in language development leading to impairments in verbal and non-verbal communication, and a restricted repertoire of interests and activities present from early childhood. The range of autistic disorders spans intelligence and language abilities from high functioning to severely impaired.

Asperger's syndrome is on the same spectrum of syndromes as autism but it is distinguished from it based largely on a lack of language delay, if one only considers literal language skills. Yet people with AS have difficulty in what M. D. Rutherford and Simon Baron-Cohen term "reading the mind in the voice," understanding more hidden and subtle meanings that most of us learn to perceive automatically from a fairly early age. It has been thought that those with AS lack that ability, because they have problems in producing and perceiving prosody . Prosody can be thought of as the music of speech. It comprises the rhythm, intonation and pitch that colors words and phrases to convey intent, mood and function. (For those interested in detailed background on this see McCann & Peppe, 2003 and Rutherford et. al. 2002).

These effects were primarily based on reports of patients with AS - which is not insignificant, but it is difficult to measure individual accounts, when the brains and ears that are perceiving the speech each have their own individual differences producing unique subjective experiences. The study I read (Neurophysiological evidence for cortical discrimination impairment of prosody in Asperger syndrome - Kujala et al, 2005) compared the responses of "normally developing" women to women with AS in their neural responses to spoken sounds with varying emotional content. Their results confirm the prosody processing abnormality through an objective measure - an EEG recording (which measures electrical activity of the brain from the scalp) and delineates specific differences in how the women with AS process prosody:

1. The subjects notice fewer differences in prosody

2. The differences they do notice produce less noticeable effects in the brain but for a longer duration (in relatively small units - milliseconds)

3. The wave demonstrating the effect reveals that the impairment occurs at a point early in auditory processing (a low-level or fundamental deficit may be the root of the problem).

4. The waves recorded at the time the speech was heard seem to originate from a different place in the brain than those of the normal subjects to whom the women were compared. This does not necessarily imply a "cause," of autism, it could be an effect. I'll explain: given the fact that autistic spectrum brains are different from others and given the fact that autistic people exist in the same world as we do and attempt to accomplish many (but not all) of the same things, they sometimes end up compensating by employing different combinations of brain structures - i.e. they wire things a little differently - than others do.

The second article looks at another popular neuroscience phenomenon - mirror neurons - and discusses a theory connecting autism spectrum disorders with a dysfunction in the "mirror neuron system."

Mirror neurons are a type of nerve cell that fire both when someone performs a given action and when they observe that same action being performed by someone else. They are thought to match observed behavior of another with executed behavior by oneself. Many think this mechanism helps us automatically give meaning to others' intentions and actions. It is a fairly recent theory that a dysfunction of this system could result in the range of impairments seen across the autistic spectrum which include problems in imitation, social interaction, and theory of mind (the ability to attribute mental states, desires and intents to others that can be different from our own). A further development of this theory suggests a connections between the mirror neuron system and the limbic system (a brain area associated with emotion) via the insula which allows us to interpret the meaning of observed emotions in others. Here's one good recent article Iacoboni & Dapretto, 2006 on the theory from Nature Neuroscience.

The article I read - Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders - Dapretto et al, 2006 summarizes this theory, and performs a study of their own comparing "normally developing" and autistic children observing and imitating emotional expressions from photographs adding two additional pieces of information. They measure their ability to measure and imitate as well as scanning the brain with fMRI, which creates a picture of relative activity of brain areas at the time of a specific event. They saw the following:

1. Both autistic children and controls were capable of observing and imitating emotional expressions, but children with autism did not show increased activation of the brain area normally associated with mirror neuron activity whereas the controls did

2. The less activity observed in the mirror neuron system brain area, the more severe the social impairments of the subjects - which they conclude could indicate that a dysfunctional mirror neuron system might cause the social deficits seen in autism.

It's an excellent and short article but it's too soon to judge, however, if one is compelled by the concept of mirror neurons and the described link to emotional understanding, it's a short leap to connecting their dysfunction to a syndrome so characterized by social deficits. There are many other good articles on this subject. There's this one for the general reader by the omnipresent Vilayanur Ramachandran from Scientific American. And here are two more technical ones from various scientific journals:
Oberman & Ramachandran, 2007
Oberman, et al, 2005

Knowledge and myth, hard science and caring art - the confusions of autism

The Neurology of Autism edited by Mary Coleman, Emeritus Clinical Professor of Pediatric Neurology at Georgetown University, is a collection of chapters on the latest information in such topics as the difference between syndromic and non-syndromic autism, chromosomes which might be implicated, brain regions affected, whether autism can be reversible, therapies - both traditional and alternative, and the epidemiology of autism. Each of the chapters is written by an expert in that area and provides a comprehensive review of the work. They are explicit about the limits chosen for that review, and give a broad view - not just concentrating on the most mainstream material. While the book jacket advertises the book as suitable for everyone - clinicians, students, researchers, and parents - I would say that is only true for some parts. The chapters focusing on chromosomal disorders and neurotransmitters are complicated and the writing is dry. Discussions of the many disorders that can feature autistic symptoms and on the brain regions affected by it are byzantine and pretty technical - if words like dentatothalamocortical and vermian freak you out, these chapters would be difficult for you. However, the discussions on therapies and the chapter on epidemiology are particularly thorough and accessibly written.

I'll summarize some key points from the book that might be of general interest:

More than 90% of children with autism appear to have a genetic component to their disease.

It seems to be agreed that the autistic syndromes begin impairing the brain before birth, even though the the markers clinicians routinely used to make a diagnosis tend not to be apparent until the child is between 18 and 24 months old.

There is likely not one single anatomical location in the brain whose abnormality underlies autism in all patients.

Autism likely involves the development of abnormal connections between regions of the brain - some models involve too many connections, others involve too few, yet others involve the rewiring of connections for purposes other than those which they are usually used as a compensatory strategy.

The two major diagnostic handbooks used by the mental health professions define the chief criteria for autism as possessing a certain number of abnormalities of social interaction, impairments in verbal and non-verbal communication, and a restricted repertoire of interests and activities present from early childhood.

There is a range of autistic disorders which spans intelligence and language abilities from high functioning to severely impaired.

The diagnostic criteria for Asperger syndrome specifies that there has been no delay in language and cognitive development - although there are some language peculiarities and motor issues often seen in Asperger, so there is some disagreement on what should constitute an Asperger's diagnosis or whether either a diagnosis of high-functioning autism on the one hand or merely describing the child as socially unusual on the other is more appropriate.

Family background, genetic factors, developmental milestones, motor coordination, and the savant skills (outstanding skill in a specific area, such as mathematics or music that are seen in around 10% of the autistic population) are all taken into account, but they are not defining criteria for diagnosis because there is not enough agreement given the current research.

Autistic symptoms are seen in connection with a wide variety of underlying diseases, each of which is probably due to a somewhat different neurological cause - Rett Syndrome, tuberous sclerosis complex, de Lange syndrom and Neurofibromatosis are a few of the diseases that fall under a larger umbrella term MCA/MR syndrom (multiple congenital anomalies and mental retardation). Furthermore, it is not know whether these syndromes can be said to manifest autistic symptoms or whether it would be more accurate to say that the individual has both the syndrome and autism.

It is likely that what is referred to as autism is actually different disease entities which will each be found to have their own pathology and resulting subset of symptoms

We see frequent mention in the popular press about whether the increased number of diagnosed cases of autism constitute an increase in the incidents of disease itself or just the awareness of it. The chapter on epidemiology by Christopher Gillberg reviews studies published in English from the 1960s through 2003 - examining them decade by decade. This intelligent analysis concludes that the prevalence of autistic spectrum disorders (autism, Asperger syndrome, and atypical autism or pervasive development disorder) are somewhere between .6% and 1.1%. That is 20 - 100 times high than the rates recorded 40 years earlier however, the definition of autism has changed in that time and now comprises a much broader group of conditions, which is what accounts for much of that difference. Clinician Lorna Wing rediagnosed her own cases from a study she conducted in the 1970s using updated criteria - it trebled that rate of diagnosis. Gillberg lists other influencing factors as well, but he is careful to point out that, given current diagnostic criteria, girls are currently probably underdiagnosed.

Another chapter on alternative therapies by Lorenzo Pavone and Martino Ruggieri reviews the literature on everything from vitamins, low-phenylalanine diets, gluten and casein free diets, and ketogenic diets to detoxification of heavy metals, auditory integration therapy, holding therapy, and dolphin assisted therapy. The reviews are balanced and respectful - never dismissive - but they are appropriately frank about whether evidence is anedoctally or research based, what type of study was conducted (i.e. whether it was controlled or double-blind), their efficacy, and the potential risks of the therapy, if any.

The final chapter by Michele Zappella is a thoughtful review of how professionals providing diagnoses, interventions, or other services can (and should) consider their patient in the context of their entire family. Everything from how to provide information given the incomplete state of our knowledge to dealing with the depression and anxiety of a parent is considered. There are useful case examples as well.

Medical professionals should be aware that their power in these moments [diagnosis] is great; they can foster hope or despair, can favor union and solidarity within the family or its opposite. Different results can occur based on how we physicians behave and speak, and from what we do... It has been said that psychic pain can be an occasion to become more flexible and sensible.

All in all, this is not a layperson's volume, but the three chapters I focused on would be accessible to any reader. As a student in the field and a potential researcher and/or clinician dealing with this disease and the people affected by it, I found its earlier chapters provided such an unconnected list of information it only made me despair that the pieces will ever come together, but the later chapters were both informative, and useful. It is more and more apparent to me that part of delivering good care is not just mastering an overwhelming body of knowledge but also learning the limits of our understanding. It's a hard lesson to swallow.

Zeitgeist Alert: Autism & Vaccines

Page one of today's NY Times has an excellent article about the rift within the family that founded the charity Autism Speaks, regarding the cause of autism. It speaks well to how beliefs and strong feelings drive this issue and relates well to my post last week. This single family's feud mirrors the debate in the autism community at-large. The large and generous charity has made an effort to be "agnostic" with regard to what it funds, according to one of its board members, but the daughter of the founders, Katie Wright, has an autistic child and believes that environmental causes are to blame. Other organizations concentrate on funding less conventional theories.

Strong beliefs and debates are not going to determine the causes of autism, research will. An ill-informed or biased hypothesis is never going to lead to good research but, if one can ask a question about causes (environmental or organic) that is truly unknown, and design responsible research (whether the theories are well-trodden or unconventional), that research should be useful. Discoveries in science rarely follow a path straight from the money to the cure. Unraveling the mystery of the cure of autism needs the tools of science the minds of creative mavericks, and the support of people who care to know the truth - whatever it is. If one looks at current research, autism is still the story of the blind men and the elephant. Lots of people are describing a small piece of the puzzle, but no one description has yet to satisfyingly encompass everything we know. Sometimes backing up or looking at the problem sideways permits a creative breakthrough. The vaccine theory was superficially convincing for a time but the science against it now is stronger, but as long as these organizations have informed scientists reviewing their funding, a conventional or a conservative funding strategy is not going to decide this debate - they don't have that much control over the truth. Evidence will accumulate over time and at some point the truth will become weighty enough to tip the balance.

In the long run, research may well lead us to redefine this single word - autism - comprising a spectrum of related disorders, into more homogeneous subgroups, allowing us to look at the problem afresh. Many current researchers are already forming their questions this way. Asking good questions is a creative act. Good creators know they must continually shake up their perspective to stay active in pursuit of a solution. Loud contrary voices may have cause hurt in this family and in these organizations which I hope they can heal, but they most likely keep the research vital and honest.

Zeitgeist alert: Public opinion and the autism debate (Books: Autism: Mind and Brain)

The NY Times has an informative op-ed piece today addressing the widespread public insistence that autism is on the rise:

The claims for or against an autism epidemic simply cannot be proved given the evidence available...

The article gives a good overview of the statistics and the difficulties of classifying children who fall somewhere in the autistic spectrum, given the shifting definitions of the disease.

The article also mentions the beginning of Cedillo v. Secretary of Health and Human Services, one of many cases in the US courts claiming that childhood vaccinations lead to autism. I have yet to see any direct support for causal claims in the scientific literature, although I have seen serious direct evidence against it. There are some indirect connections made regarding emerging symptoms and time of vaccinations, but those behavioral symptoms coincide with the time in life when those behaviors develop in children - rendering them visible - and that makes it impossible to draw any conclusions. Recent work has identified some behavioral markers of the disease that might be visible earlier in development, and if these become more reliably established, that could put this debate entirely to rest. I am not politically motivated to see either argument be true and I am open to being wrong, but I have yet to see the connection between autism and vaccinations compellingly made.

Many people want this to be true because they so fervently wish for an explanation, and I can hardly blame them. If the theory about the involvement of vaccinations is true it will be conclusively borne out by evidence over time that establishes high probabilities of connection. Conclusions of this sort cannot be drawn based on anecdotes, on indirect connections however compelling, or even on the evidence of a single good experiment. Knowledge is gained in the sciences from posing hypotheses and testing them and then having that test made again by someone else, and then having another lab ask a slight variation on the question and testing it again, and then altering the group of people slightly and testing it again. One experiment does not establish cause, the evidence accumulates. And autism makes it particularly difficult because the ever shifting nature of the disease gives us a moving target. It's interesting to see this debate move out of the lab and into the court. DSM- IV and ICD-10 (diagnostic manuals) provide their diagnostic criteria, but the symptomatology of autism is heterogeneous (manifests itself differently in different people) and its underlying neurobiological mechanisms (some marker that says you have this disease in the way that the presence of the polio virus in your blood positively establishes your diagnosis of polio) are not understood. Autism is not just a disease, it's a cause celebre - diagnoses are a part of our culture now. I'm not sure how fighting the cause of one explanation for autism in court (it is fairly widely accepted that there is not only 1 cause), is possible given the fact that we still don't know exactly what autism is. It's like having witnesses testify regarding a murder they didn't actually see. I don't know if judges decide or juries rule in this type of court, but will they have uncovered the truth at the conclusion of this case in a way that has eluded leading scientists researching autism for the last decade?

In this context, a brief mention of Uta Frith and Elisabeth Hill's excellent book Autism: Mind and Brain which gives a very good summary of current work of many of the leading scientists building an understanding of autism. I'll discuss some of the more compelling work in a later post, but its chapters are written by the scientists who are conducting this work and it is well written, and careful not to draw any massive conclusions. I'd say the book is for an audience who can read scientific articles of a moderate but not highly technical nature, it's not a layman's volume.