Preparing for this TEDMED talk gave me a wonderful occasion to pause and reflect. With the release of the talk I have the space to give more color to experiences and ideas I shared there.
When my husband Pat and I were faced with the pseudoxanthoma elasticum (PXE) diagnosis of our children, we were shocked. The linear, idyllic, progression of life that we expected was derailed. Instead, a surreal unfolding ensued. Day by day we realized that we couldn't go backwards to BEFORE. We also realized that we would have to go ahead into a space we never knew existed. This foray into biomedical research was beyond groping in the dark for a light switch to illuminate our world; it was like having to find the source of electricity to power us through.
Pat and I had no reference points, no landmarks, no understanding of genes, multi-systemic disease, or the fact that many conditions simply do not have treatments. We were attempting to plot solutions using tools we had never seen nor heard of before. As Pat said, "We didn't know a gene from a hubcap".
Because we were neophytes, we had beginner's mind and heart. For us, there was immense space around each of the problems we encountered and many opportunities for considering novel solutions.
It was that spaciousness that led us to build a registry and BioBank as our first endeavor. We could see something incredibly obvious, but seemingly unimportant to the research community. We could see that the intense competition between labs to build biospecimen and clinical data collections was thwarting discovery or at least decreasing its speed.
In the talk, I remark that for us the solution to the problem of herding cats - getting scientists to work together – was to move the food. If we aggregated and managed the blood, tissue, and clinical data, the cats would follow. This turned out to be quite true. Building these resources in 1995, opened the field. There was greater opportunity for everyone to work with more clues and to accelerate the quest to understand this premature aging disease.
"Can we wash your test tubes?", we asked post docs at Harvard. We did not know that washing test tubes wasn't really needed, but we did learn to extract DNA from blood, run and score gels, and enter data into excel spreadsheets in the search for the gene. We were very lucky that our neighbor Martha volunteered to watch the kids several nights a week. We would tuck them in, make sure Martha had what she needed, and drive 30 minutes from the suburb of Sharon, MA to Boston. There, from 8 PM to 2 AM, we would perform the rather monotonous activities required to discover the gene. Some of the most creative aspects were trying to pinpoint exactly which Staedtler marker wrote on the film the best, and which kind of light box made the blurry dark and faint lines on the gel more obvious. The most magical part was when Pat put the data into the spreadsheet and saw the locus emerge. His dyslexia allowed him to see patterns the rest of us needed analysis to see.
I remember very well convening our consortium of researchers and discussing the locus - the place likely to harbor the gene responsible for PXE. There were five genes in the locus, which one was it? The young researchers wanted to work on elucidating the genes that no one knew about, rather than the already known ones. We were once again faced with an important opportunity to refocus our researchers. We asked the team if they could put finding the responsible gene above characterizing the unknown genes. The answer, for the most part, was yes and off we went through each of the genes until the magic of the DNA on one family definitively identified ABCC6 as the culprit. That was a happy day. To simplify the filing, Pat and I decided that for the gene patent application, I would be a co-inventor of the gene, along with our colleagues in Hawaii. He could have also been listed, but we thought we were pushing the envelope enough listing one lay inventor.
Filing the gene patent and having it awarded was another point of consternation in the research arena. There were many ethicists who thought it was immoral to patent a gene. For us, it was supremely important that we have a mechanism for ensuring the gene would be freely available for research. To do that we had to be the gene’s stewards. I assigned my rights to the foundation and we could keep our institutional partner from charging high fees for licensing its use. We charged very minimal fees, bringing in only about $100 in licensing fees overall. It's a good thing that the wonderful pro bono lawyers from K&L Gates did the filings.
As the millennium was flirting with Y2K, we loved ABCC6 more than any other alpha-numeric combo. Our neighbors in Sharon, MA rallied to our cause: served on our board, helped us run wine and beer tastings, did a walkathon and more. We walked into the PXE research world with a naïveté that gave us space to transform the landscape around us, but in that few short years, a great deal had transpired.
From the start, we believed, and never questioned, that the lived experience of people affected by PXE, and their loved ones, was the only reference point. We saw the individual as expert in PXE, not those who by their training or credentials claimed to be experts. A lawyer ethicist slammed us in a journal editorial declaring that “the Terrys will thwart research because of their conflict of interest”; stating that the Terrys’ love for their children will get in the way of letting the 'real experts' do their thing. We were stunned that someone would put forward such a hypothesis without evidence and dismiss those who live with the condition day to day as true authorities. It was then that we began to eschew the medical model and work to scale and expand our tools for the largest body of experts: people who have a direct experience of the disease.
I believe that over these years our propensity to follow what emerges, as it emerges, has served our quest well. We work now to retain our beginner's mind, even as we continue to be shocked by the inability of researchers and institutions to see beyond their own interests, which often are linked to securing funding, getting published, and promoted. We continue to seek ways to show the research community the value of true partnership with individuals, families, and communities. It would be unconscionable in any other industry to leave out the parties who will be the biggest customer of the product. We continue to look for ways to find that tipping point where it will make sense to include the true experts. We welcome all in our quest.