Month: July 2017

In the early nineties, more than 14,000 pregnant women enrolled into ALSPAC, the Avon Longitudinal Study of Parents and Children – known to its friends as ‘Children of the 90s’. Every year for over two decades, these parents and children have provided all kinds of information to researchers to create a dataset unique in the world. Combining hundreds of different elements, including biological samples, environmental measures, clinical assessments, and key life events, it’s an astoundingly detailed picture of human development which continues to yield surprises. Professor Jean Golding OBE, who founded the study, says of her unprecedented project:

“When we started ALSPAC, they asked why we collected so many participants. Later, they asked why we collected so few!”

Professor Golding had to convince funders, scientists, and other epidemiologists of the benefits of a broad approach with open-ended questions, rather than the focused approach favoured at the time. When asked how she was able to push through these concepts in the face of critics, she says lightly: “Oh, they thought I was mad for at least 20 years – it made me more determined!” She mentions notable support from the vice-chancellor of the University of Bristol at the time, who was a mathematician and statistician, and “really got it”.

The study participants, on the other hand, she says, ‘understood it all, and really bought into it’. Jean explained to the cohort their aims – “We were going to look with fresh eyes, on the basis that we actually didn’t know what were the appropriate ways to make children healthy” – and asked for their contribution to this joint effort.

This is an activity that of course requires trust, and imposes a duty on the researchers towards the participants. Jean says: “I think you have to be extremely careful. As long as the study parents and participants trust you – that is a burden, you have got to get it right. If they don’t trust you, you have to get it right too, but it’s not so damaging. If they lose trust in you, they lose trust in the future. That would be really disastrous.”

Some of her understanding of the participants’ concerns come from her own experience. Her own grandson, born, conveniently, two years before the start of the study, was used as a ‘guinea pig’ for some of the assessments which ALSPAC families would complete.

In a novel approach, ALSPAC carers and babies were asked to report their lives and habits, such as smoking, and also to undergo assessments, such as language ability, and to give biological samples. The last two elements were made at the suggestion of Professor Golding’s long-term collaborator, Professor Marcus Pembrey (also of the University of Bristol), who Golding says made sure the right data was collected at the right times. This has enabled geneticists to use the dataset to look at how the genetic code changes in response to environmental conditions – showing the prescience of the study, since the samples were stored long before the technology to examine this information efficiently existed. Jean describes this modestly as another example of her “picking up people’s ideas and putting them into practice.”

Data collected on the ‘Children of the Nineties’ includes such categories as (chosen at random as an illustration): physical activity levels of children, blood samples from everyone, IQ scores, dietary reports, 3D face scans, ball skills, the number of days pubescent girls experienced menstrual cramps, measure of air pollution exposure in year-old babies, short term memory in four year olds, waist circumference, the smoking habits of the ALSPAC mothers’ mothers, and amount of screen-time for the grandchildren of the original pregnant participants (the children of children of the 90s, or COCO90s). It’s a dizzying amount of data.

The ALSPAC findings have yielded over 1,500 publications so far, on topics ranging  from the increased risk of obesity in children whose grandparents smoked, the relationship between lead levels in blood and SAT results, to the non-correlation of cat ownership with psychosis[could substitute if wanted]. However, many relationships remain to be explored.

Jean is currently particularly interested in early pregnancy and how that affects the child and its development into early adulthood. She describes with engagement an illustrative issue; the benefits of seafood for the developing brain weighed against concerns around the accumulation of heavy metals. With access to information about trace metals in the blood, the diet of a pregnant mother and her child, and the child’s developmental progress, the epidemiological team at ALSPAC have the pieces to make a recommendation. Jean’s analyses, with colleagues, suggest that there are no harmful effects from mercury if the mother eats fish, while if she doesn’t eat fish, there is some indication that there is harm to the child.

However, translating these findings into policy proves difficult, and current advice on this one issue lags behind the latest work. I ask if she has any ideas for improving uptake of such research outputs, and she replies cheerfully: “All we can do is batter away!” Cod (or a non-endangered alternative) and chips all round, then.

Current work for Professor Golding includes ongoing work with the geneticist, Professor Pembrey, looking at transgenerational effects – not just in the genome, the sum of the DNA information in an individual, but the epigenome, the DNA and the chemical changes modifying how it interacts. Their work so far shows that the habits, such as smoking, in the mothers of the cohort pregnant in ‘91 affect the adolescence of their babies – that is, the habits of the grandmothers are visited upon their grandchildren. In this case, the team have identified various effects including associations with obesity and cognition.

In the future, Professor Golding is excited about looking into the effects of stress on development through the generations, perhaps from historical tragedies such as famine or personal ones such as bereavement. Another interesting possibility is to extend the study a generation further, since some of the children from the original cohort are having children. But given that not all the cohort are taking that step, another option is linking through older records to consider the life histories of great-grandparents of the contributors. Could it be possible to see traces of a childhood in the 1930s workhouse in their 21st century great-grandchild?

There seems to be no end to the data that can be collected about a human life, or the questions that can be asked about it. Interviews with participants reveal that, on the whole, they were happy to contribute all sorts of personal information, and contribute their time, as long as the data is used. From the moment I meet her, Jean is clear that her job is to make sure that the efforts of the participants of the ALSPAC study, their children, and now grandchildren, are used to fulfil her promise to them two decades ago: to find out how to make people more healthy.

Find out more about Professor Jean Golding’s career, and her tips for a successful collaboration and data investigation, in the first blogpost in this series.

Written by Kate Oliver, PhD student at the University of Bristol and freelance science writer. With thanks to Professor Jean Golding for a fascinating conversation!

Get to know your data

Now past the age when many retire, Professor Jean Golding OBE still works full-time to draw conclusions from the massive data sets she has shepherded into being. The epidemiologist, for whom the new University of Bristol data science institute is named, is best known for founding the uniquely rich study ‘Children of the 90s’, or ALSPAC, which collected a wealth of biological, behavioural and social data from babies born in Bristol and their families.

At the start of Professor Golding’s career, punchcards were the height of technology. Now, having worked on three large-scale birth cohort studies and with an illustrious career, she reflects on the changes, and constants, in answering questions with data, cross-disciplinary collaboration, and the University of Bristol.

After reading Mathematics at St Anne’s College, Oxford, Professor Golding took a variety of jobs to support her family before happening upon her first role analysing medical research data. She answered an advert for a statistician, and began by calculating simple percentages for a writeup of a large epidemiological study. While this work was simple mathematically, she learnt from other group members about the medical background of the study and relevant biology, and discovered her own love of finding stories in data. Here, her career in epidemiological research began. She remembers:

That was hands on – not using computers at all. The information that I was interested in was abstracted from questionnaires, written on cards with holes around the edges and could be sorted with a ‘knitting needle’. You got to know the data very well, so you got to know that certain things were associated with one another, which if you had not been looking you might not have noticed.

Physical computing methods such as punchcards certainly let practitioners get to know their information, but became unwieldy when thousands of entries were compared, and impossible when into the  hundreds of thousands. However, as data sets have expanded and modern computational methods have come online, Professor Golding feels the fundamentals have not changed.

It’s still important to get to know the data, but you do it in a different way – through doing a variety of different cross-tabulations (a method of comparing how often different characteristics occur together).  I think it’s very important, in looking at the data, to see what is missing from your variables – what’s not there will tell you something important. Keep looking at the data, is my message!

Following on from this experience, Jean was involved in three large scale UK birth cohort studies: in 1958 and 1970, and the 1990s study she founded: ALSPAC. (Read more about ALSPAC in the second part of this interview). While the amount of variables collected in ALSPAC is far greater than the others, Jean is neutral about the possibility of further expansion in future studies; she points out that the cost of gathering so much data from each participant is the limiting factor. Asked about the current trend for talking about ‘data science’ and ‘big data’, Jean expresses no particular affinity for the terms; for her, it is all about the data, call it what you may, whether one is a data scientist in 2017 or a statistician in 1958.

As someone performing statistical analyses in an epidemiological context, I asked what discipline she identifies with. “I’ve never called myself a mathematician”,  she says, “Just an epidemiologist, although nobody ever told me I could.”

She observes that epidemiologists tend to drift in from various backgrounds, not having considered the field originally.  For instance, it’s not that different from zoology, apparently; “you observe groups of ants or bison, and deduce a lot to do with behaviour and mortality and migration. All of that is relevant – a few other come in from psychology, and now through genetics. It doesn’t set out to be cross-disciplinary, but what one studies is necessarily cross-disciplinary.”

She highlights that it’s only recently that cross-disciplinarity has been seen as a benefit by funders – that thirty years ago it was very hard to get a grant that crossed boundaries. But, she believes, it is an inherently beneficial approach, and this seems to be borne out by her success. I asked how she made such collaborations successful, and she replies modestly that it can sometimes be hard. Of a close relationship with a distinguished psychologist in America, she says: “He doesn’t understand what I’m doing, and I don’t understand what he’s saying, but somehow we get published!” The key to making it work, apparently, is that “he has ideas, I have ideas, and we’re both tolerant.” Sounds like an approach that would work in many situations.

For more than 30 years Professor Golding has made her academic home at the University of Bristol, although she maintains strong links to other institutions such as UCL, home of her long-time collaborator Professor Pembrey. She cites her collaborations and colleagues as one of the highlights of the institution for her

I think the university is really vibrant and has been changing so much for the better recently. Of course I think the Institutes are an amazingly beneficial way of getting cross-disciplinary research going. It has certainly worked well with the Elizabeth Blackwell Institute, and I’m sure it’s going to with the JGI.

Still research-active, although writing papers instead of crunching data, Jean still has many questions that she wishes to answer.  “Now I’m retired, I can work on what I’m interested in”, Jean explains, and it is clear that her interests lie where they always have; in getting to know the data, taking good ideas from everyone, and using them to find out what is going on – aims that are  reflected in the institute that now bears her name.

Read more about the ALSPAC study, what makes it unique and the findings Professor Golding has extracted from it in the follow-up blogpost.

Written by Kate Oliver, PhD student at the University of Bristol and freelance science writer. With thanks to Professor Jean Golding for a fascinating conversation!