Questioning authority: A conversation with Martine Rothblatt

The more you listen to Martine Rothblatt, the more the fact that she’s transgendered becomes one of the less interesting things about her. Instead, you get caught up and inspired by her journey—from satellites to organ farms, from founding a pharmaceutical company to BINA 48, a “mindclone” robot that embodies her wife Bina’s beliefs, attitudes, memories and feelings.

Rothblatt, currently chief of United Therapeutics, is among the world’s highest paid female CEOs. Her motto is, “Do the right thing and the money will take care of itself.”

This is a lightly edited excerpt of her interview with Jane Clayson, guest host of NPR’s On Point.

In the early 1990s, you founded Sirius XM — satellite radio.

I was very active in the satellite communications field and I kept asking — one of my big motivations is to question authority — why do satellite dishes have to be so large? I learned that the signal is so weak, it needs a large collecting area. So I got very deep into satellite communications technology to see what could make signal powerful enough that it could be received by something small enough to embed in an automobile.

Everyone thought it wouldn’t be possible. Today, there are 30 million subscribers to Sirius XM in the U.S.

Then, your fourth child got sick.

Yes, Genesis. We were on a family ski trip at a pretty high altitude. She got really sick and never got better. She was out of breath and became dyspneic with very little exercise. She saw the pediatrician over and over.

Close to half of people with pulmonary arterial hypertension die without it ever being accurately diagnosed. It progresses very rapidly. It was a grim situation. We spent all our time at Children’s National Medical Center. Finally, when spending night after night at the hospital, I just began to go to the library and read everything I could find on pulmonary hypertension, and all the references for those articles.

I found one tiny article out of 100 — about a tiny molecule that selectively dilated the pulmonary vasculature. A light bulb went off in my head — maybe, just maybe, I could get the company to develop this medicine.

The company was Glaxo Wellcome, and they weren’t interested. They said, “You can’t give us enough money to develop this.” They wanted a blockbuster that would have billions in sales, and the last time they checked there were only 3,000 patients with pulmonary hypertension.

I had learned by being rejected so many times in satellite communications to ask “why?” I’m a little bit like a 7-year-old. I asked, “Could you license it to me?” They said no, it would be abnormal to license a molecule to a satellite communications expert. I said, what if I had a team of expert drug developers? They said, “Come back when that’s the case.”

For me, it was a challenge, and I do like challenges. I did find the experts in this field of drug development, including Nobel Laureate Sir John Vane. I flew to the UK to meet him, and I told him my story. He was fascinated that one of my satellite communications companies tracked elephant locations. He loved that and said, “OK Martine, I’ll do whatever can to help you.”

So you wrote a check to Glaxo for $25,000 for the right to develop the drug.

We had the exclusive rights to develop the molecule, a little tiny bit of powder that would not have been safe enough to give to people. That’s all we had. By that time, our daughter was about half the time in the intensive care ward.

Rothblatt and Clayson-Cohen-croppedUltimately we found a manufacturer for the medicine, which requires a 23-step chemical synthesis, and developed a clinical trial. We found the medication has a half-life of only two hours. But you can’t take a pill every two hours, so we developed a new delivery method.

In 2002, the drug was approved by FDA. Today, there are almost 40,000 people with pulmonary hypertension. That’s good, because all those people would have been dead.

Can you explain how you put this drug, Remodulin, on the market?

Glaxo Wellcome was correct that they could not make $1 billion out of 3,000 people. So there’s a lot of justifiable room for cynicism. But I envisioned that there’d be tens of thousands of people taking the medicine for longer and longer periods of time.

I calculated how much I would have to charge to repay the development costs.

It came to be $100,000 per patient per year – that was a shock. There were no drugs that expensive at the time. So I said, OK, will anybody pay for this? I pulled out my Blue Cross insurance policy – they said they’d pay for any medication that’s medically necessary. It didn’t say anything about a price gap.

So we decided to announce it at $100,000 per year, but anyone who didn’t have the money for it would still get it. It would avoid a lung transplantation. We’ve never turned away anyone for inability to pay, including undocumented people.

Now, the market is $1.5 billion per year. Glaxo said it was the best investment they ever made.

Genesis is doing well, a remarkable young lady.

What was the most surprising thing?

That the FDA approved it. The FDA has to have a ‘p’ value of less than .05, meaning that the odds that a medicine is working by chance — that it’s essentially a placebo — are less than 5 out of 100.

So what if you have a p value of .06? Almost always, this means your drug will not be approved by the FDA. But does this mean it isn’t a good drug? Not at all.

In satellite communications, I didn’t feel the need to bow down before a p value.

If you ask most people, a 7 out of a 100 chance of being given a placebo is not a problem.

The FDA staff recommended that it not be approved. I hope you can empathize with the tremendous sense of dread and exhaustion I felt. But we had a tremendous friend in Bob Temple [of the Center for Drug Evaluation and Research] at FDA, and in patients telling their stories — how the drug had allowed them to see milestones like weddings. Remember, this is all about the patients.

Bob Temple said, “We should not be slaves to p values.” I thought that was astonishing given that Bob is a biostatistician and that the FDA is devoted to biostatistics.

Remodulin has been given to thousands of patients who have gone on to be mayors of cities, to deliver babies. And but for a difference between 0.05 and 0.06, it would all have gone down the drain.

Let’s talk about your latest projects. You teamed up with Craig Venter to genetically modify the pig genome to create an unlimited supply of human organs.

Here I was inspired by my grandmother who had required a heart valve replacement. She received a porcine heart valve. She was a very observant Jewish Russian immigrant who kept kosher. Here she had a pig inside her, but she was very pragmatic, and all religions are very pragmatic when it comes to saving a human life.

Pigs’ organs are the closest size match to human organs and are able to be reproduced in quantity. The pig valves are stripped of all living tissue – it’s just the form of the valve that people receive, which causes no immunogenic reaction.

I began to think, now that we’ve decoded the human genome and have gene editing, why not transplant an entire human organ and just strip off the antigenic molecules that react with the human immune system? Craig Venter was very receptive.

We [Synthetic Genomics] have created the largest herd of cloned pigs, with knockouts of the genes that would otherwise interfere with human immunology. Maybe 10 genes at most would need to be suppressed to make a tolerant organ. Hopefully all immunosuppressants given with a xenotransplant could wind down within six months. This way we could provide a supply of transplantable organs for everybody.

Tell us about Bina 48.

We are storing unprecedented parts of our minds in big data — for e-commerce, in social media. All of this is being digitized outside our bodies and stored in one or another cloud. Bina48, as she is known, is a pre-alpha-test version of this mind clone concept.

Efforts to create mindware are going to increase rapidly, [as evidenced by] the fact that apps such as Siri are so popular. Different companies are all trying to out-Siri Siri. Lots of maker companies are trying to make digital doppelgangers, working on elements of human cognition and human personality with open source software.

Then you’ll have something that will act like Jane, talk like Jane, recognize the people Jane recognizes. Whether that clone is a part of Jane will be a topic for philosophers, psychologists and ultimately lawyers.

What Bina likes best is all the young people getting interested in software coding. Bina 48 is the biggest hit with the FIRST Robotics Competition—where hundreds of thousands of students compete across the country to create robots.

Through the FDA voucher program, United Therapeutics recently got approval for the first neuroblastoma drug in the United States. Tell us about that.

Yes — Unituxin. True to our roots, for the two years it was under review by FDA we gave it free to all physicians. The FDA gave us a [priority review] voucher — the result of a tremendous effort by pediatric rare disease and cancer advocates. They lobbied Congress to require the FDA to give vouchers that would cut the drug review time in half for the first few companies that developed a new medicine for pediatric oncology. Because Big Pharma was ignoring these.

When we got the voucher, finally, companies were banging on our door saying, “we’ll buy the voucher from you.” We put it up for bid — at $350M AbbVie was the highest bidder.

Ultimately, it’s proof of the adage, if you do the right thing, the money will take care of itself. I didn’t make a medicine for money, but it has produced a lot of money.

Watch video highlights of the 2015 Global Pediatric Innovation Summit + Awards.