Today I want to talk about a book that will change the way you look at genetic research. Too often we forget that science is made of people: not just scientists, not just physicians, but first and foremost the patients and their families. I often come home frustrated because of clashing egos, reviewers that don't get it, projects that don't get funded. It's too easy to forget why we are doing this. Reading The Forever Fix: Gene Therapy and the Boy Who Saved It helped me put things back into perspective.
Dr. Ricki Lewis is a geneticist, a counsellor, a writer, an educator, and the creator of the PLoS blog DNA Science Blog. Her book, The Forever Fix: Gene Therapy and the Boy Who Saved It, is a journey that retraces the failures and successes of gene therapy, told from the point of view of families who had no other choice than entrust their loved ones into the hands of an experimental therapy. All this topped by Dr Lewis's beautiful writing that seamlessly folds the science and the history of science into the narrative.
As you know, some diseases come from "mistakes" in one or more genes. The only way to fix them is to fix the gene. Gene therapy is a medical procedure that in principle is simple -- send the "good" genes to replace the defective ones -- but that in practice is really hard to actuate and can lead to devastating complications. Yet for some, often young children, it's the only hope to live. Ricki has met these families, and she tells their stories both in her book and in her blog. I'm really excited to have Ricki here on CHIMERAS today!
EEG: What prompted you to study genetics and, later on, to write about it?
RL: I suppose I imprinted on genetics. I had wanted to be a physician since early childhood. Once at college, the first course for biology majors was genetics – not intro bio – and that was it for me. I had taken several genetics courses and done research in genetics by the time I graduated, and my grades were not good enough for medical school. When I discovered that grad school pays the student rather than the other way around, that seemed a logical route.
But I always loved writing. I won essay contests as a child. I wrote for fun. And it never occurred to me, through high school and college, to actually BE a writer – I was always so driven towards science.
The writing came together for me in grad school. I was just months away from earning my PhD, but was tired of the intense focus on one problem (flies with legs growing out of their heads). I took a graduate science journalism course, and instantly loved it. What freedom, to be able to switch topics every few weeks, and nowadays, days or hours! And so I interviewed with the Cincinnati Enquirer as well as applied for an assistant professor position in zoology at Miami University, to teach and do research in genetics, and got both. We moved to Ohio and I began my first academic position while freelancing for the newspaper’s Sunday magazine. This was the era of Legionnaire’s disease and toxic shock syndrome – two of my first articles. It was at Miami University that the textbook acquisition editors came around, and five of them, after seeing my magazine articles, tried to sign me up. So that’s how my career as a textbook author began, beginning with the intro bio textbook Life. I’ve since become co-author of two human anatomy and physiology textbooks, and of course my beloved human genetics textbook. I’ve also taught on and off, and have been a genetic counselor since 1984. Nowadays I teach an online course in “Genethics” for PhD students at Albany Medical College.
EEG: I totally get the need to change topics! That's why I write too, except then the science keeps coming back, even though in fictional form.
Genetics is a fast-changing field. I still remember when I started as a graduate student in 2004: my institution had just acquired an Illumina machine and they had no clue on how to read and organize the output. In ten years the focus has shifted from single genes, to whole genomes, and then again to ENCODE, RNAs and proteomes. The amount of data is overwhelming. How does one keep up to date with such a fast-changing field? In particular, do you have any recommendations for clinicians who might come across rare diseases? How can they be prepared?
RL: I agree, the pace is crazy! I blog for the Public Library of Science and I’m always backed up with posts, about 4 weeks out. The stories come faster than I can write them.
I can’t really answer the first question about keeping up for a normal person, because, as my husband always points out, I’ve never had a “real” job. All I do is write, and read. So I keep up to date that way. And as a journalist, I get “news” before it is published or announced – press releases every day. This is why I seem so obnoxious to people who send me articles from the New York Times or similar publications – to me it is old news. Writing for Medscape a few times a week, which I’ve been doing for about 18 months now, has really helped keep me up to date too. And I go to meetings – that is really how to stay on top of things. The American Society of Gene and Cell Therapy meeting is coming up next month. Can’t wait!
A clinician can’t really be prepared to recognize a rare disease simply because it is so rare. But I attended a talk at last year’s American Society of Human Genetics meeting – I forget the company – and they combined sequencing with database analysis and were able to diagnose a rare disease in minutes. It was one of the diseases in my book The Forever Fix that usually takes years to diagnose, simply because physicians are looking for horses and then zebras, unaware of the unicorns.
EEG: I loved reading your book for many reasons -- I'm fascinated by gene therapy, I loved your writing and narrative style, and I love genetics and the complexity of the human genome. But, the one thing I loved the most is that you "humanized" science. You gave a face and a voice to the scientists, the researchers, and the families who struggle with rare diseases by portraying their ordeal. Your book paints the reality of the many failures we face for every tiny step forward we make. I know you are a parent, too, so what was it like to meet and talk to the parents of the "gene therapy children"?
RL: I had been writing about families with genetic disease in my textbook, Human Genetics: Concepts and Applications, since 1993. The Forever Fix was actually more a side project, because textbooks must be revised every 2-3 years, and I have 3 of them. The genetics textbook has always had a feature called “In Their Own Words” in which parents and sometimes the children describe their daily lives, or their experiences with the health care system. The book has featured one boy (Max from Forever Fix) since he was 3, and he’s now 15! So I basically had all the stories buried in my textbook. I’d always intended someday to write a trade book on gene therapy, and when I learned about Corey, I knew it was the perfect story. Blindness is terrible, but it isn’t as terrible as many of the other single-gene diseases.
In the first version of the outline I pitched to agents, all those other kids and families were squished into one chapter. The book was to tell only the full story of Corey, the blind boy who no longer is. But unlike your experience with agents telling you different things, a dozen of them told me the same thing – give each family/disease a separate chapter. And that’s how the book was born.
I was extraordinarily lucky in writing the book. I had known about the gene therapy for Leber congenital amaurosis type 2 (Corey’s disease), but had no idea the little boy lived a half hour from me. And Hannah Sames, the little girl with giant axonal neuropathy who is the subject of my two favorite chapters, also lives nearby. And I learned about both of them through my local newspaper!
I knew the story of Jesse Gelsinger, as everybody does, and I knew the back story from the early 1990s of the first gene therapy trial. It was Corey’s doctor who put me in touch with French Anderson, who founded the field and is now in prison. He edited my chapters in pencil from prison. Of course I included his story but the publisher yanked it.
I also knew Lorenzo’s story from the 1992 film, and was lucky enough to interview his father. And so the pieces of the story all fell into place.
My training helped with doing interviews. I’m a genetic counselor, a hospice volunteer, and a mother. The hospice training was particularly helpful – if you’re used to talking with people who are facing the end of life, you can talk to the parent of a child with a genetic disease, although genetics introduces the guilt factor. The most moving encounter was listening to the mother of a boy who’d died of adrenoleukodystrophy practice her talk for reporters on me, at the gene therapy meetings in 2010. She went well beyond what she would say the next day, and really opened up to me. It was heartbreaking. She said I was the only one who asked her about Oliver other than what his illness was like, rather than avoiding talking about him.
Some of the interviews I’d do on the phone late at night, in the summer of 2010. The parents and siblings would be crying on the phone, their stories pouring out. It gave me a new appreciation for being healthy.
I had experience interviewing from my years as a science writer. Once upon a time, writers had something called work. We’d write for magazines, and they’d all pay us at least $1 a word. At one time in the early 1990s, I’d typically have up to 8 assignments at a time. I wrote hundreds of articles for The Scientist, thousands in total. Nowadays, writers either have no work, or are expected to work for free or a pittance – with the exception of a few class acts like Scientific American that still pay. So the magazine writing and that course way back in grad school prepared me to be a good listener and to gently ask the right questions to pull a story out. My PhD in genetics enabled me to speak the same language as the researchers and physicians. And journalistic sleuthing skills came into play too. Corey’s first doctor, who put him on the road to gene therapy, wouldn’t speak to me, so I reconstructed that part from medical records. I told Jesse’s tragic story through newspaper reports from the time and also through interviews with his father and the researcher blamed for the death.
Unfortunately there are too many “faces of genetics” out there. In fact, I’ve been giving a lecture called just that at the undergrad workshop of the American Society of Human Genetics the past few years. Sadly I present different families each year. There are so many of them. I’m facebook friends with several and feature their children – some are able to see for the first time thanks to gene therapy – in my blogs and lectures.
EEG: I've noticed that most gene therapy trials are funded not by the NIH, which would be the usual course of a clinical trial, but through fundraisers initiated by the parents of the sick children. You've told me that's because some cases are so urgent that there isn't enough time to go through all the NIH loops and caveats. How does a single family embark on such an arduous task?
RL: For every case that gets a great deal of attention there are many more that are less known. I can think of half a dozen families off the top of my head who are working 24/7 to raise funds to support gene therapy clinical trials.
Rather than showcasing one family, I like to connect the families so that they can share resources. This is an idea that is the brainchild of Lori Sames, whose little girl Hannah is awaiting her gene therapy but might not ever have it unless her immune system can be suppressed (she is a double nonsense mutation). That story is more tragic than Eliza's case, the 4-yr old affected by Sanfilippo Syndrome-Type A whose parents are collecting funds for a two-million dollar gene therapy experiment. Lori and her husband Matt have worked 24/7 since 2008 to get this trial up and running, and now, on the brink, their little girl can’t receive it. Yet. She is losing the ability to walk, talk, and see. Lori is the one who said to me, “If the gene therapy works, it’ll be a forever fix.” She named my book. And of course I hope it works.
Another example is Taylor King, who at age 7 was diagnosed with infantile Batten disease. Both Taylor's and Hannah's families are raising funds for gene therapy trials through the Hannah’s Hope Fund for Giant Axonal Neuropathy, and the Taylor's Tale fund.
When parents contact me because their children have just been diagnosed with disease X and they don’t know what to do, I put them in touch with Lori. And she helps. These families can share friendship, resources such as access to doctors and researchers and funding agencies, and hope. Lori is the nexus in gene therapy. The families she’s helped insist she knows more than any doctor – and she does.
This is the most powerful lesson I learned from writing The Forever Fix. Parents can take the finding of a treatment – I hate the word cure – into their own hands. They can raise enough funds to save time compared to going the NIH grant route, or supplement government funds, although of course the regulatory hurdles are still there. With social media helping immeasurably, families are confronting genetic disease head on now on a regular basis.
EEG: Wow. You have a vocation. I applaud you for the courage and the great support you give to all these families. Thank you for being with us today and for giving us a glimpse into what it is like to go through these ordeals.
Here's a summary of the relevant links where you can find out more about Dr. Lewis's work, her book, and the families raising money for gene therapy trials:
- Dr. Lewis's website.
- Dr. Lewis's PLoS blog.
- The Forever Fix on Amazon.
- Hannah’s Hope Fund for Giant Axonal Neuropathy.
- Taylor's Tale fund.
- The Saving Eliza GoFundMe campaign.
- Past posts on gene therapy.