Jérôme Lejeune Foundation: Why did you get involved in this very specific and not very well known field of research? Back then, you were a memory specialist, there were other possible fields of research, why choose genetic mental intellectual disability ?
Lynn Nadel: Back then, in the mid-80s, the domain of knowledge I had was essentially focussed on memory and, more precisely, the role of the hippocampus. It is within this framework that I started reading the emerging literature about the possible links between the hippocampus and the cognitive deficiency which is observed in patients with Down Syndrome. One has to understand that the mechanisms of the memory and cognitive abilities are multiple and extremely complex. In Down Syndrome and other pathologies, characteristic disabilities could already be observed, such as a defined set of more or less important disorders. I then went to a scientific congress on Down Syndrome which increased my will to enlighten what I was reading with my own understanding and, as a way of speaking, intuition, all this based on the knowledge I have of memory.
JLF: In short, these congresses are fertile exchange platforms between the various researchers which can lead to new ideas in a particular field thanks to common reflection, each researcher speaking of his own field of expertise?
Lynn Nadel: Exactly, these meetings are essential in order to stimulate one another’s creativity, particularly in fields of research that are less well known or very specific and which can greatly benefit from the expertise of others. In my case, memory. They can also provide new knowledge to more central fields of research. I am thinking, amongst other fields, about research on Down Syndrome helping with Alzheimer disease. This is called cross-fertilization and is fundamental to keep moving forward.
It is precisely because public funding for Down Syndrome is very little, or even not at all, financially supported that it must rely on these exchanges. It seems to me the situation is more or less the same in France as it is in the United States. The amount given, per inhabitant, to this pathology is extremely low compared with other pathologies, including certain rare diseases. Research is supported mainly by private parts, as is the Jérôme Lejeune Foundation in the United States for example. However, as mentioned about Alzheimer disease, all advances in one field can provide knowledge and enlighten research in other fields.
JLF: Let’s go even deeper into the subject: you have been working on evaluation for over 15 years. In English, it has a very large meaning, so what exactly does it refer to when speaking of genetic mental intellectual disability ?
Lynn Nadel : Let me start with a very precise case: let’s say that a surgeon or a general practitioner wants to carry out an operation or a study, whatever it may be: environmental, surgical, behavioural. The only way to know whether it has a positive impact or not is to set up a very precise protocol in order to take measures before and after the action so as to be aware of its effect. The test battery I put in place for the evaluation studies are based on exactly the same principle, applied to the cognitive capacities of patients with Down Syndrome. It is all about giving a study a solid and reliable scientific basis.
JLF : In what way are the stakes particularly important but also a challenge when it comes to Down Syndrome, amongst other diseases?
Lynn Nadel: The main difficulty comes from the fact the initial deficiencies need to be taken into account so as to have at least one reliable methodology. For Down Syndrome, in particular, it is essential to know the specific characteristics of these patients such as difficulties with languages or the rapid loss of motivation. Consequently, proximity with the patients, families, their environment, their life is determining in order for the tools that are used to remain unbiased. Of course, specific tests need to be carried out for each hypothesis or drug that is to be tested but there is a convergence in terms of methodology to insure the “robustness” of an evaluation which is the result of years and years of work.
JLF : What recent applications have you been able to make of the test batteries you have set up?
Lynn Nadel: I can mention two examples. The first is sleep apnea. We have been closely looking into the impact of this phenomenon in people with genetic intellectual disabilities. We were to evaluate whether this sleep disorder had or not the effect of increasing the disabilities of these patients compared to the general population. We were able to prove that, indeed, sleep apnea has an aggravating effect on these patients.
On the contrary, we have been able to show that children who grow up in bilingual families don’t have any additional difficulties compared to other children living in a similar situation. Of course, they are faced with difficulties in expressing themselves and in learning languages related to their intellectual disability, and, of course, any child must make an extra effort to speak two languages rather than just one but the fact that parents speak Spanish and English at home, for example, does not add an extra difficulty for children with intellectual disability more that it does for other children. These results were very important for the so called Latin- American families, who have a child with this kind of pathology: they stopped feeling guilty about talking to each other in two different languages at home and felt more relaxed which, in generally, is felt by the child.
JLF: You speak of precise cases, taken from close field observation. Do you also sometimes work with researchers who work on a purely fundamental basis? How do you interact with these various areas of research?
Lynn Nadel: Yes, a lot and in two different senses. Evaluation plays both a role of scout and broom wagon. Let me explain: in the 80s and 90s, my work based on evaluation got me interested very specifically in the hippocampus as a potential source of disorder in certain nervous systems. It is then by working with the best techniques of imagery and with researchers specialized in studies on mice models that I was able to explore these initial leads and, in this case, validate them. Studies with animals are marvellous in the sense that they enable researchers to carry out a great number of tests to evaluate the cognitive capacities of these mice while having a total control over the environment and other factors of influence in general. It is evidently less so with patients and that is a good thing! In parallel, the evaluation test enables researchers to validate or negate the tests carried out on the animal. This double entry bridge is fascinating for evaluation.
JLF: It all makes sense when coming back to what you said at the beginning on the limited research funds. It is very important to target one side and control the other rather than explore things as they come, is that what you meant ?
Lynn Nadel: It is clear that evaluation enables us to target pertinent adequate research leads and bring up results that are convincing and which interact with all research actors. It is the perpetual come and go that enables one to not lose oneself and to go forward in both a reasonable and ambitious way.
JLF: What are your ambitions for times to come ?
Lynn Nadel: At the moment, the test batteries with which I work enable me to be precise and reliable for patients from 10 to 25 years old. The double challenge for me is to extend the expertise to younger patients in order to put in place solutions at a very early age and also at an older age in order to, first, check that what goes on in childhood and adolescence is still true in old age and, secondly, to ameliorate the quality of life until the end, and, in particular, because you know it, the life expectancy of people with genetic intellectual disabilities has increased thanks to past advances. What comes next is yet to be build and nothing is ever finished!