HD66: Search for a cure or a killer? Page 3

  “Years,” she admitted with a roll of her eyes. “I’ve been here the whole time you know.”

  Ignoring her quip, Errol was on a roll. “First I had to develop a mouse model. Because Huntington’s is a genetic defect, I had to create a knockout mouse where I removed some of the mouse’s genome and replaced it with the human defective gene that causes Huntington’s. To create the same effect as HD in humans.”

  “The repetition on chromosome four?” She smiled at his surprised look. “I do listen, you know.”

  “Ha. Imagine being able to offer my patients a cure.” He held up his hands, helpless.

  “Yes, Errol, I can imagine,” Amy responded softly.

  “Think about their faces, their bent and twisted bodies.”

  “I think about their families.” She carried the tray back into the kitchen and began to load the dishwasher.

  Errol closed the dishwasher and pushed her up against it. “I have another idea.”

  “Oh… that.” She laughed as he led her by the hand upstairs.

  Later, in the shower, Errol pondered the steps of his journey. His positive results from the lab had propelled him to Centre-University’s technology transfer office. The university applied for patent protection for the HD66 drug and then helped Errol submit the paperwork to conduct his own investigator-initiated Phase I clinical trial in humans. The small study proved that the drug was tolerated and had no discernible side effects. He was accepted into the faculty incubator, Startups@Centre, which provided him with seed money, mentorship, and basic entrepreneurship training. He got help in recruiting a startup team. One of the best lessons drilled into him was the Jim Collins admonition to get the right people on the bus, even if you don’t know exactly where the bus is headed. I’m on the bus, Errol told the Voice, and stepped out of the shower with renewed determination.

  “What’s the name of the company?” Amy asked from the bedroom.

  “Her name is Quixotic.”

  “Funny you should name her like a boat,” she remarked as Errol loped downstairs to his home office. He peered at his lab book scratches once again. He had to hurry, knowing that he needed to stop by the university lab to talk to his students, then make his way to his clinic to see his patients. He would end the day back at the university – for Quixotic.

  “Remember, I have the day off.” Amy called down the stairs. “I have plans for the kids. Starting with Sam’s doctor appointment at 10.” She waited, her foot on the top stair. “Oh, and Ariel has a gymnastics tournament at five.” She paused, “You coming?”

  “Oh, wow,” he started.

  “Oh never mind,” Amy stopped him. “I didn’t know how big a day this was for you, but I figured you’d be busy. I promised Ariel a night out with her friends. Sam will be at Brett’s, and I have a report to write tonight. We’ll be fine. Get going, Errol. Oh, and rock ’em babe,” she said as the bathroom door closed with a click.

  He patted Luna goodbye and went out to his bike on the porch. I have it all: my research at the university, my neurology practice and now my startup – my life. He jumped on his bike and pedaled down Grafton Street, thinking about his afternoon meeting with co-founders, Matt, Jim, and, of course, Gigi. He couldn’t wait. They legally formed the company some time ago, but today they would sign the license for HD66 with the university. They would receive “exclusive, global, and in-perpetuity rights,” the document said. Why it takes 80 pages to say that, he didn’t get. As co-founders, they planned the signing as a group event, even though they had agreed that the sole signature would be his. I hope someone remembers champagne, he smiled as he turned south onto Highland Avenue.

  Errol thought about his patients. He has no good news for his HD patients – their unmendable brains, the inevitable athetosis of the fingers and toes, the uncontrollable chorea. He knew that he word came from the Greek “χορεία,” which means dance. But chorea is far from a dance. There was nothing that he could offer his patients, beyond managing the inevitable descent. No good news – yet. But soon.

  Errol swerved to avoid a car door opening. “Jerk,” he shouted and pushed his bike faster along Ellsworth Avenue, cutting back to the right as he neared the university. As he turned onto Centre Avenue, Errol recalled the thrill of discovery. He had focused on HD and other neurological diseases for his whole adult life. It’s why he became a university researcher. For years, he experimented with different drugs to counteract the CAG repeats on chromosome four – the huntingtin gene, or HTT, spelled differently from the disease, codes for the huntingtin protein. Eventually, he discovered that small interfering RNA, abbreviated as siRNA, would interfere with the expression of specific genes – in this case with HTT. siRNAs and their role in gene silencing was only found in 1999, and Errol had been experimenting since the article came out in Science. It took him almost three years to make it work.

  Every scientist lives for that moment, that “Eureka-I-found-it” moment of discovery. Many never get there. It’s just too elusive. He was lucky. But the Voice would not call it luck. “The fish do not come to you; you have to find them,” the Voice had reprimanded him.

  “I got the big fish,” he whispered.

  A few hours later, he was smiling as he walked into Centre-Pitt’s tech transfer office, on the 40th floor of University Tower. As he stepped off the high-speed elevator, Jim and Matt greeted him with broad smiles. Gigi reached up to hug him. He spotted a bottle of champagne bulging out of her designer purse. She giggled as they strode into the conference room.

  “Let’s rock!” Errol shouted. Quixotic was born.

  Chapter 4

  June 1, five years before the incident

  Shala was the first one to arrive this morning. She unlocked the laboratory door and stepped inside. It was her first day back. It was also the first day that she entered the lab, not as a PhD student, but as a post-doctoral researcher. She was proud and happy. Sure that she was alone, she sang a song from her childhood. As she sang, she twirled around the room, enjoying being completely free.

  Thinking that she heard something she stopped mid-twirl. She stepped over to the lab bench to appear busy. But it was only someone outside. She could hear them talking even though the windows were closed. She began to hurry as she knew the others would be here soon.

  Pushing aside papers from the lab bench, she turned on the computer. It was brand new. Dr. Errol had bought it for her. She’d never had a computer of her own. As a PhD student she had access to a computer, but she had to share it with other students. She would have been able to have a laptop like the other graduate students if she hadn’t sent money back home.

  The computer screen lit up. She entered her username and password. She had only a few minutes before Dr. Errol and the others arrived. She hoped that the new students would not come in until Dr. Errol was here. She wasn’t sure what to do with them if he was not there. She was afraid they would laugh at her if she said she was the boss now. She wished that they were not all men. She looked at the clock on the wall and started to type.

  Dear Pliya,

  My dear sister, you cannot imagine the joy with which I write and am now sharing with you. I am so glad to have seen you. It was a long flight back to the United States, and then I slept for a whole day from the jet lag, you know? But I awoke to very good news.

  I have been chosen for my post-doctoral work at Centre with Dr. Errol in his lab! This is very important university near other important universities. Also it is nearby the hospitals. Important because we are working in the health studies. During the defense of my thesis Dr. Errol and others they asked me very difficult questions. It made me so nervous. But Dr. Errol told me yesterday that it will be an honor to have me stay on in his lab. An honor for him! Think of what an honor this is for our family. I am a real scientist now with letters after my name and a job in the United States!

  I told you that I am very happy here. Pittsburgh is a nice place with many things to see and favorite places that I go. Because I have been
offered a post-doctoral position, I am hoping that this will be my home forever. Here, women have much freedom. I am trying very hard to be like an American girl here. I am just doing as others do. Ha ha!

  I hope that you like that I am writing you in English. It is good practice. Not only for me, but for you! One day, you will thank me because your English will be so good.

  I am nervous on this first day of my new job. As I told you, we are making important discoveries in the lab. We are finding cures to bad diseases. Dr. Errol says that we will help people everywhere. Not everywhere, I think, but I do not tell him. He does not know, Pliya. I will not tell him.

  Dr. Errol is such a jokester. I used to be afraid of this. But now I am determined to join in the fun, and I will try to play little jokester games to make Dr. Errol smile and laugh. It is so freeing to not have to watch what I say, what I do, where I go. I remember. I am still sad for you. My heart reaches out to you with my love. This morning I read in the newspaper that there have been more rapes. I read that police not arresting any people. I am sad to read these terrible stories.

  I have a surprise for you. You will be receiving a wheelchair very soon. My gift to you! Guess what? It have buttons to help you do things! Someday I hope to push you on an American street. I would like for you to see what I see here in this different and freedom land.

  I will write you again and I hope that you will find a way write to me. I miss you so very much. I am thinking of you, my dear sister.

  All my love, from your doctor PHD sister with letters after her name,

  Shala

  Chapter 5

  March 8

  We’re a mess since Errol’s death. It’s been only a few days since we found out. Almost two weeks since NGX stopped the trial. Everything is a blur. I have lost all sense of time. We come into the office; I’m not sure that we are working. I know that I’m physically present, but I’m really not – present or working. Glancing at my phone, I see that it’s 11 p.m. The office lights are still on. I don’t know who’s here, who’s not. I don’t care. I don’t want to go home. I can’t face it.

  Buzz. It’s Errol! No, it can’t be. It’s Neal. I tell him that I have a few more things to do, to wrap up. He’s understanding. We haven’t talked about it much – about Errol, about what happened.

  To top it off, I sprained my ankle walking up the path from the falls that day. It’s not a bad sprain, but I’ve been obeying RICE: rest, ice, compression, exercise. I’m elevating my injury by keeping my ankle on top of my desk, but that makes it difficult to work. Which doesn’t matter because there’s no work to be done. No one tells me what to do. Not even Gigi. We’re lost.

  As I re-wrap the ace bandage around my ankle, dutifully applying compression, I can’t stop thinking about the timing of NeuroGenex cancelling our deal and Errol’s death. I know what the others think: something big like that could have caused a heart attack. They’re right. To know that his cure would never make it to market – that could kill anyone. But so could something else or someone else.

  I stare through my glass door at the DNA sculpture that hangs in our hallway. Errol made the 20-foot aluminum wire sculpture in his basement. In his spare time, I muse, thinking about Errol the scientist, Errol the doctor, Errol the university professor, and Errol the artist. The sculpture is visible from the outside too, and at night, like now, it’s beautifully lit. I was so impressed by it when I first saw the office. I remember that first time like it was yesterday.

  …….

  Three and a half years earlier

  Although I interned at the company the summer before, while getting my MBA, Gigi insisted on a full orientation on my first day. Which was kind of a joke, since Quixotic was still a startup, and they didn’t have any processes or procedures in place. I began by reading the business plan that the team wrote in 2007 when they founded the company.

  I realized before I joined Quixotic that we had something unique – our drug. It’s a great story. It’s why I took the job. I get to help tell the story about treating a previously untreatable disease. Ha! F you, fellow MBA students working on Wall Street. What the heck difference can you make in your job? Me, I get to CURE PEOPLE!

  I was so glad to get this job. In my masters’ program, everyone knew EXACTLY what they wanted to do post-graduation. Me, I had no clue. I wanted to do something real, something that would “make meaning,” as Guy Kawasaki would put it. I loved my internship at Quixotic. But I never thought that they would offer me a job. They were so experienced. I was so – not.

  But I wanted to stay in Pittsburgh. I’d met Neal. Cute, square-jawed Neal Raja, whose white teeth against his dark skin made me swoon when he smiled. At Quixotic, I am geographically proximate to him. His office is also in East Liberty, although in a different building than ours. We’re in an old warehouse; he’s in a remodeled factory where they used to make aluminum parts. He has a driveway INSIDE the building! How cool is that?

  “Join us, Brie,” Jim had said after the lunch that was an interview. I felt drunk. I was wanted. Working for a startup is exciting and dynamic. But it’s also scary. They’re not kidding when they say it’s like a roller coaster. I hoped that I was up to the challenge.

  I barely made it through that first day. I remember Gigi interrupted my business plan reading because she wanted me to create an investor presentation. I didn’t know that she would do this over and over since then – no sooner am I in the middle of some project, than she demands something else, something impossibly difficult.

  That first day she burst into my office: “Brie! I know that it’s your first day, but I need a PowerPoint presentation and I need it now!” She explained that they had been wooing a regional angel investment group for some time. The managing partner of the group, GreenBush Angels, had just called, saying that they had a screening committee meeting the next morning. “If we want to present to them, now’s the time!”

  “OK.” I felt incredibly dumb. “I got it.”

  “Take all the time you need. As long as it’s less than two hours,” she said, pointing her red nail at her diamond watch. As she whooshed out of my office she tossed an aside over her shoulder,” You’ve got to be better at PowerPoint than we are!”

  What exactly is she asking me to do? I don’t know what goes into an investor presentation. I panicked. I was about to screw up and get fired before I had even finished the first day.

  My parents were so proud of me when I got this job. I told them that the startup was commercializing a drug for a neurodegenerative disease. I didn’t tell them which disease; that was irrelevant. What was relevant was that it was an important disease; that I had a position in the real world, outside of my cloistered upbringing in the Coho that we called home.

  “Most scientists never get the chance to see their work in patients,” Matt told me the morning of my orientation. “You can spend your whole fucking life at the bench working to solve a dreaded disease, but, at the end of the day, you are just one more drug program, and the chance that you will get to see the light at the end of the tunnel is almost nil. I saw my chance and jumped at it.”

  “We knew that it would take everything that we could muster and then some to build Quixotic,” Jim had told me during his part of the orientation. “As we went through due diligence on the drug, HD66, we recognized that it had some exceptional properties. It was safe, and its properties were really promising. That is the pearl of great value. When you find something like that, you pursue it with everything you have.”

  Errol told me that he didn’t need much convincing to start a company based on his technology. Peering down at me over his glasses, he told me, “One of science’s dirty little secrets is that it tells you the puzzle, but it doesn’t tell you the answer. You have to discover those pieces and how they fit together. When you do, it’s beautiful. When you might save someone’s life, it doesn’t get any better.”

  Yep, startups are sexy. Few know how hard it really is, however. A lot has happened since
my first day. It’s after midnight. I have to go home. Errol’s memorial service is tomorrow. Errol trusted me. I don’t know why he picked me. But he did. He told me that I was the only one who would understand. Not his wife, not his students, not his Quixotic colleagues, not his university peers. Me. What did you leave for me? Where is it?

  …….

  There would be no funeral for Errol, Amy had informed us two days after he was gone. She would hold a memorial service in University Chapel on Centre’s campus. She wanted his colleagues to say goodbye to him as well as chance to celebrate his life. “The service will be about his living and his accomplishments,” she told us by email.

  I choose a simple dark blue dress and put on my grandmother’s pearls. I don’t wear these often enough, I think as I gaze into the mirror, admiring their sheen.

  By the time I walk through the arched, wooden doors facing the campus green, the back two thirds of the chapel is full of people standing in the aisles. I don’t recognize most of those attending. I see Errol’s colleague, Maya, standing with a group of other professor-looking folks in the right aisle. She looks like she is crying. On the other side, I see a lot of younger folk, Errol’s students probably. Near them is a small group that I recognize: Shala, Yahya, and Patrick, Errol’s lab students. I go over to them. Shala is crying, and the others looked exhausted. Like us, they are in shock. I hug Shala lightly and am surprised when she hugs me hard back.

  “Oh, Brie, I am so deeply sad. I cannot bear Dr. Errol to not be here. It is unimaginable.” Her lovely brown face is streaked with tears.

  Yes it is. I shake hands with Yahya and Patrick. Both are stiff and awkward in what look like new, ill-fitting suits.

  The organ starts playing a mournful tune and those of us still standing move to find seats on the dark oak benches. I move away from the students to take a seat in the middle, next to people I don’t know. Jim beckons me up front, and I slide into place beside him. The whole second row is taken up with my Quixotic colleagues. In front of us is Amy, the Pyrovolakis kids, and others who I assume are university leadership. The service begins. It’s a typical non-denominational service. There is much music. I can hear sniffles from all around. The minister officiates, and people speak, extolling the virtues of he-who-is-gone. I can’t bear to listen.