She called Corey’s dad Ethan and discovered that even though they’d done the talk show circuit, no one was writing about their story. "And so I drove about a half hour north, into the Adirondacks, to meet them. They were charming and anxious to share their incredible story. The project soon grew to embrace the other cases I had floating around in my brain and in the pages of my textbooks."
The opening to the book sounds like fiction, but it’s true. "On a sunny September Sunday in 2008, Corey and his parents approached the gate to the Philadelphia zoo. When Corey heard other kids screaming to look up, at the giant balloon, he did, and screamed. It was the first time he’d seen the sun – just four days after gene therapy at Children’s Hospital of Philadelphia. An ophthalmologist had injected billions of viruses into Corey’s most severely affected eye. Each virus bore a copy of the gene that was abnormal in the boy.
"The zoo scene was all the more amazing because nine years earlier, an 18-year-old had had a far different reaction to gene therapy, performed in the same city – he died, derailing the biotechnology for years, yet making it safer today."
Today gene therapy is closer to the clinic than ever, with the first approval in Europe on November 2. And in the U.S., phase 3 clinical trials for gene therapies for a few diseases are soon to start. But the elephant in the room is how willing pharma is to develop a cure – compared to a treatment that a patient is tied to for life. A similar situation was the delay in accepting short-term antibiotic treatment for ulcers – a lifetime of acid-lowering drugs provided a larger market.
"No gene therapy has yet to receive FDA approval. I think that it will proceed on a disease-by-disease trajectory, because the approach makes more practical sense for some diseases than others. The first may indeed be Corey’s disease, Leber congenital amaurosis type 2 (LCA2). His physicians have already stockpiled enough of the gene-loaded viruses that are the therapy to treat the 300 or so people with the condition, and have developed educational modules to train ophthalmologists to deliver it. In contrast, gene therapy for HIV/AIDS – already possible – would likely not be as cost-effective as existing drug treatments."
The first FDA approval may come within 5 years, says Dr. Lewis. "But gene therapy will have competition – from conventional drugs, devices such as retinal implants, and new approaches such as stem cell-based therapies."
Dr. Lewis' textbook, Human Genetics:Concepts and Applications, is the go-to academic book on the subject, now in its 10th edition.
How did you get started?
Geneticist Dr. Ricki Lewis has colored days of the week.
What a long, strange trip it’s been.
I was born a scientist – loved it for as long as I can remember. I wanted to be a doctor, but organic chemistry and I did not get along. In college at Stony Brook, I took several genetics courses, did research, and decided to pursue a doctorate in that field – which I did, at Indiana University. But as I neared the end, I grew less interested in flies with legs growing out of their heads (see “The Making of a Mutant: A Fruit Fly Love Story” (http://blogs.scientificamerican.com/guest-blog/2012/04/14/the-mak...) and took a graduate science journalism course. It changed my life.
Although my interest had veered towards a writing career, I got a faculty position at Miami University in Ohio teaching genetics, but also began freelancing for several magazines. Then, acquisitions editors from five academic publishers visited, saw a nine-months-pregnant science PhD with magazine writing experience, and offered me contracts to write textbooks. I’d never even thought about who actually wrote textbooks. That was 1981, and I’ve been doing it ever since. I’m the founding author of the intro textbook “Life,” an co-author on two human anatomy and physiology textbooks, and author of the human genetics textbook. I’ve also published a short genetics book, an essay collection, and a novel.
You are a synesthete. Do you feel there are advantages to synesthesia? It's often thought of as a good mnemonic...does it enhance your creativity?
I think synesthesia is helpful in ways that we synesthetes do not even realize, because it is so automatic. Only recently have I realized that I can find things in my rather messy office because I use different colored file folders. I very often know just where to look, because I remember the color associated with a topic.
Creative people are over-represented among synesthetes. I can’t even draw a straight line, but I’ve always had a facility with words. I also like to connect topics that other people do not see as connected – I wonder too if this is a manifestation of my linked senses.
If you could study anything about the genetics of synesthesia, what would you focus on?
I suppose I would look at identical twins separated at birth (concordance) but I’m not convinced synesthesia is genetic. I think it is more likely to be developmental, a connecting of neurons in a particular way at some point during the prenatal period.
If it is inherited, it is likely to be a multifactorial trait, with contributions from many genes and the environment.
Why do you suppose synesthesia has persisted in evolution?
If synesthesia is a fortunate accident of neural plasticity, then it wouldn’t be subject to natural selection and its persistence would reflect recurrence, because neural connections are not passed to the next generation. But if synesthesia has a high heritability (meaning most of the variability is due to genetics), then it must offer some advantage that makes people with it more likely to leave fertile offspring than others – written like a true textbook author! But the advantage may not be obvious. That is, synesthesia could be a marker of sorts for some other advantage.
One can imagine all sorts of scenarios. Perhaps linking senses enabled early peoples to better memorize their surroundings, which might have been helpful in finding food, escaping predation, or seeking shelter.
If you could design a gene therapy in which one can have a certain form of synesthesia, which one would you want?
Colored numbers would have been wonderful in math classes! Also colored functional groups in organic chemistry – I think I have a touch of this. And I’m fascinated by the connections involving food. I think I have this too. Don’t laugh. Certain tastes make me think of a vacuum cleaner – hummus, for example. My kids are used to me saying that things taste like a vacuum cleaner.
My synesthesia manifests as colored days of the week. But months have colors too, although I have to concentrate to describe them – it isn’t as automatic as the days of the week. Traveling across the international date line makes all the days turn brown until I get back home.
Are you musical? Do you sing (perfect pitch?) Do you paint or draw?
I played guitar until arthritis prevented me from doing so. I can sing on key, but certainly not perfect pitch.
What is your favorite part of The Forever Fix?
That’s easy. The scene was the American Society of Gene and Cell Therapy Annual meeting in Washington DC, May 2010. At the final symposium, 3,000+ geneticists who never thought they’d witness a gene therapy success filled the room. Corey and his parents took the stage, and answered questions from Dr. Jean Bennett, the head of the gene therapy trial. Seeing scientists moved to tears was astonishing, but what stopped me cold was watching a woman named Lori Sames. I was rooming with her. Her little girl Hannah is one of 52 people in the world with giant axonal neuropathy. It’s like ALS in a child, and she will likely not survive early adulthood – without the gene therapy that she will have very soon. Lori is a chatterbox who is always on the go, as she must be to raise the funds for the gene therapy trial. But when she saw Corey, she stood absolutely still, and silent, as the tears flowed, for in Corey, she saw Hannah. She has no recollection of this.
You’ve said that The Forever Fix is more than just the story of a biotechnology reborn. What else is the book about?
Themes emerged as I was writing that I never expected. Several incredible women contributed to the return of gene therapy. It’s hard to pick a favorite. Kristina Narfström is the veterinary ophthalmologist who discovered Corey’s disease in dogs, which led to the gene therapy. But her student blabbed the finding at a scientific meeting, and competitors repeated the work and published it first. That’s why I call Chapter 16 Kristina’s Dogs. Jean Bennett and Lori Sames are heroines of gene therapy, as are Paola Leone who works with Canavan disease and the amazing Salzman sisters, who spearheaded development of gene therapy for adrenoleukodystrophy, the “Lorenzo’s Oil” (a 1993 film) disease.
Another powerful theme is the value of animal research. The dogs who have the gene therapy for their natural blindness get to go home with the kids who have had their vision restored.
Perhaps the most overriding theme is that of activist parents who take on the world to find treatments for the rare diseases that affect their children. I’ve become a rare disease advocate since writing the book.
Where did the book title come from?
Lori and I were at a fundraiser for Hannah’s Hope Fund. People were taking turns carrying Hannah around, dancing to the music, and Lori looked at me, tears shining, and said about the gene therapy, “Ricki, if it works, it’ll be a forever fix.” When neuroscientist Paola Leone said much the same thing, I knew I had the title.
What advice do you give students about careers?
Take a hint from synesthesia, and combine skills. I got a PhD in genetics, but I’m 99% a writer. If you can do two or three things, combining them in creative ways, you can stand out. Another bit of advice is to follow your heart, because it’s difficult, if not impossible, to predict future career trends – or the careers themselves.
What else do you do besides write?
I lecture, provide genetic counseling, and teach an online course in “Genethics” for the Alden March Bioethics Institute, a doctoral degree program at Albany Medical College. I volunteer for an adult education program, and am a hospice volunteer. I enjoy exercise, reading, and cooking, and doing things with my family. My husband Larry is a chemist, and we have three grown daughters, one of whom also has colored days of the week. I also write news for Medscape and have a blog, DNA Science, at Public Library of Science (http://blogs.plos.org/dnascience/).
Dr. Lewis' colored days of the week follow:
Sunday -- shimmery pink
Monday -- emerald green
Tuesday - white
Wednesday - medium brown
Thursday - dark brown
Friday -- sparkly orange
Saturday -- off-white
"Each day is an upright rectangle, and the day starts at the bottom and works its way up. Hard to explain. But all of it is."