In mythology, a chimera is a hybrid creature made up of multiple improbable parts – think of a lion with a goat’s head jutting out of its back and the tail of a dragon. But chimeras exist in real life, too. In genetics, it’s an organism or tissue consisting of at least two sets of DNA. And in the biotech world, the closest thing to a chimera may be James Sabry.
James grew up in Canada, the son of academics who were scientists and professors. As the eldest child, everyone assumed he would follow in their footsteps. And he did.
“In other words, it had no practical application, but I would investigate how the world works at the level of chemistry, physics or biology,” he says. “So that's what I went to university to study.”
But something happened on the way to basic science. Midway through his studies in chemistry and physics, James got interested in medicine. It was totally random, he says. Before he knew it he’d been accepted to Queens University Medical School in Kingston, Ontario. By his second year of medical school he saw his first patient.
“I remember thinking, ‘wow, this is really incredible!’” James says. “And for some reason that I don't know, that first patient encounter got me really excited about the ethical relationship between the physician and a patient. How does this call for me to behave in a different way than I would have, not having this experience? And that’s been my North Star ever since.”
So his scientist’s brain made room for the healing heart of a Harvard-trained doctor. He went on to earn his Ph.D. in biochemistry from the University of California San Francisco, and a post doctorate at Stanford University. He was offered a faculty and physician position at Harvard’s Brigham and Women’s hospital, with his own lab to study neurobiology.
But this wouldn’t be a chimera story without a dragon’s tail.
James turned down the academic offer to launch his own San Francisco biotech company, Cytokinetics. He led it until 2007, and then led another after that. The three parts of James were finally complete: science, medicine and business aligned in one career. In 2010 he joined Genentech, a member of the Roche Group, to lead its pharma partnering team.
Today, he is Global Head, Roche Pharma Partnering, leading business development for Roche and Genentech worldwide. We talked with him about what drives his passion and the strategy that he and Roche use to pursue, propel and shape the future of medicine.
“The more you dive into the science behind human disease, the more you realise that every disease is curable. It is impossible for us to go faster than the speed of light. It is impossible for us to create matter out of nothing. But it is not impossible for us to cure all human disease. It's just difficult. And once you get past realising it's just difficult, then all it takes is time, money and work to actually eliminate human suffering from disease. Once you really understand that, then going to work becomes even more interesting, because you know you can make a difference.
To take that down one level, the kinds of diseases that are the most difficult to treat are those that react to the treatment and become resistant to the treatment as the disease progresses. The main way that biological systems do this is through evolution. Just like we've evolved from bacteria, if we give a drug to a cancer patient, the cancer evolves so quickly in the patient that it becomes resistant to the drug we give it. And that's because the cancer genome, the actual DNA and the cancer cell, is mutating and changing very quickly. And this allows it to take advantage of the same mechanism that biology used to create humans. The cancer in its own bunch of cells is using that same mechanism to live in the presence of the drug we just gave it.
Now, that is not true in Alzheimer's disease. It's not true in rheumatoid arthritis. It's not true in cardiovascular disease or renal disease. It's only true in those diseases where the genome is changing quickly. In other words, it's what we call hyper-mutable or hyper-evolutionary. And there are only two disease types that have that: cancer and infectious diseases.
So those become the toughest ones to treat, because they will always be one step ahead of us. We create a medicine, and it creates ways of getting around that medicine. So we have to create a different medicine,and on and on forever, because it's using the same fundamental biological mechanism that we're using.”
“Now for things like Alzheimer's disease – which looks so daunting to treat right now, not because of mutation-driven resistance to drugs, but because we know so little about the molecular and cellular mechanism of the disease – this will change over time, and we will eventually be able to cure this disease. So my guess is that we can cure most of human disease in the next 100 or 200 years, with the exception of viruses like the one we're just going through now, and bacteria and cancer. Those will be the ones we will have to continue to dance with for the rest of our existence.
But we should be able to get rid of everything else; schizophrenia, Alzheimer's disease, rheumatoid arthritis, cardiovascular disease, renal disease. What will happen eventually is that we as a species will live long enough to get either cancer, or viral infections or bacterial infections, and we'll die from that. And the healthcare industry, 400 years from now, will constantly be developing new treatments for just those.
The pace at which we're building new medicines is changing very quickly. If you look at the most important medicines in the world 10 years ago, they were all small molecules, orally available, chemically synthesized tablets you would take like hypertension drugs, lipid drugs, things like that.
Fast forward to today; the most important medicines are biologics. They're proteins. And this is what Roche is extremely well known for through its Genentech acquisition. But if you fast forward 10 years from now, what will it look like? It's changed so quickly in the last 10 years.”
“We don't know what medicines 10 years from now are going to look like, but I will guarantee you they will not be biologics or small molecules. It would be something else, simply because it's changing. What could they be? Gene therapy, cell therapies, bacterial therapies, RNA-based therapies, these things that are just on the cusp of understanding right now will be the most important medicines 10 or 20 years from now. And that's what we are gradually building capabilities for at Roche.
And because business development has this long timeframe of being able to look 20, 30 years into the future – combined with the fact that Roche is fundamentally a family owned business – makes the job that we have in business development so interesting. Because we can do deals like the one with Spark Therapeutics last year, knowing that gene therapy may be the most important type of therapy for every sort of disease in 20 or 30 years.”
“In the end, all our therapies are doing is trying to reestablish normal regulation of genes that we all have in these diseases. How you do that can be all sorts of different ways: small molecules, large molecules, or gene therapy where you go in and specifically replace the gene. If you have a cancer gene that's dysregulated, for instance, there's a famous one called KRAS: if one of the letters in the genetic code for KRAS is mutated, that KRAS molecule just keeps on pumping. As a result, the cell just keeps on dividing. So imagine you go in there and just replace the bad KRAS gene with the normal one. That would be the end of that cancer. That's a form of genetic engineering or gene therapy that we could do. Now, we can't do that right now. So we have drugs that are being developed, both at Roche and other companies, that simply inhibit the hyperactive KRAS protein. But that's kind of a clumsy way of doing it. Wouldn't you rather just go right to the source and change the code of the cell, so that the normal one is there?”
“These therapies can change as we get more information. I believe that genetic therapy, or what I call genetic surgery – where you go in and remove the bad gene and put in the normal one – will be possible.
Again, it doesn't require you to go faster than the speed of light, or to make matter from nothing. It is physically possible to do this. We just don't know how to do it right now. But that doesn't mean that 40 years from now we won't. And then the question is: what should Roche do today to build the capabilities so that we are the ones who are leading that 20, 30 or 40 years from now?”
“Partnerships represent a major way in which Roche gets pioneering medicines into its portfolio. Our vision is to support hospitals and patients throughout their journey, so we don't just say, ‘here's a pill, take the pill.’ That was the way it was done 10 years ago.
As we go forward, we will say, ‘here's a solution to the medical problem you have. Here's a diagnostic that will help you understand if you have a disease, and here's a pioneering medicine that will treat the disease. Here's another diagnostic that will help follow you if the disease develops resistance, or if the disease evolves. And here's a database that will allow us to treat you with the best possible sequence of medicines given our current knowledge – just like Google maps helps you get around without getting into a traffic jam. Because it takes into consideration where all the cars are between you and your destination.”
“So imagine if we had something like Google maps, but for human disease, that takes into consideration that you have this kind of cancer, and these are the insights we're getting from every other patient in the world who has your kind of cancer at this moment, and who is either responding or not responding to disease. That's what insights can get us.
While we have very strong internal innovation, many of the molecules we actually market have come from outside of Roche; they weren't initially discovered at Roche, but we worked with the originator company to further their discovery and to develop them. It's this wonderful collaboration that happens between us and other businesses that say ‘can you help us develop and commercialise this drug?’ And it gave rise to many of our life-changing medicines today.
“You hear people talking about ‘big pharma’ and ‘evil biotech.’ But when you go to work at Roche, no one talks about that stuff. I don't go to work thinking about how we can gouge the healthcare system. I mean, no one does, right?
The time I've spent in this industry, my whole career actually, and definitely the last 10 years at Roche and Genentech, have been all about ‘how we can create pioneering medicines and really help patients?’
People say I get fired up about this, and I do. The reason I'm so excited about the future of medicine is because this is ethically the way we ought to behave. Because patients are out there with the vision that everyone at Roche is working 24 hours a day, seven days a week to find the best medicine for their disease. That’s a bit of an exaggeration, of course. But what they believe is that we're using everything in our brain, our heart and our business to alleviate human suffering through disease. And in the end, that's what I believe, too.”
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