There are 537 million people around the world living with
diabetes, and that number is growing. The burden of diabetes is massive. It's a huge cost to our government health care system for
type one people. And I have Type one diabetes. It's a huge, huge problem. Over the last 20 years, significant advancements in stem
cell research and therapies have been one of the most promising methods of creating new insulin making cells
needed to cure Type one diabetes. It's one of the few diseases where a single cell type is
destroyed or missing. And so the idea that if you could create those cells and
replace them, you can really address the underlying causal biology of the disease directly. Vertex Pharmaceuticals, a biotech company that works on
treatments for many diseases, including cystic fibrosis, got into the diabetes space a few years ago. Its stock has been on a steady climb over the past five
years. I've had type one diabetes for 25 years, and when I heard
that Vertex Pharmaceuticals had cured a man of his type one, I had to find out more. I'm really interested to know this transition from needing
insulin to being almost off it. Can you tell me what that was like for you? Can you imagine winning $1,000,000 lottery? Like while sitting here, somebody says, Hey, here's a
ticket. Boom! Winner! That was me. Bryan Shelton is the first patient in vertex clinical trial
to be infused with new stem cell derived beta cells. The cells that make insulin Shelton's insulin needs are
almost completely gone. The amount of insulin he was taking has dropped by 92%. And I was like, this is this is what I've been dreaming
about. Everything is working fine. My numbers are great. Other companies around the world, including ViaCyte and
CRISPR, as well as Novo Nordisk, one of the biggest insulin manufacturers in the world, are also working on curing the
disease. We wanted to find out why finding a cure for diabetes is so
hard and just how close Vertex and other companies are to solving this problem. Before we look at why it's tough to cure, it's important to
understand how Type one diabetes affects the body. It's not known why, but the immune system attacks and
destroys the cells in the pancreas that make insulin known as beta cells. These cells regulate glucose levels in the blood which the
body needs for energy. Without insulin, blood sugar will continue to rise. That auto immune response has really limited the ability to
create a simple regenerative strategy to cure type one diabetes. Type one diabetes is different from the more common type
two. Type one diabetics have to take insulin for the rest of
their lives. Type two diabetics still make insulin, although their
bodies become resistant to it. It can be managed with diet, exercise, medication. But some do need to take insulin. All types cause high blood sugar, which cause kidney
disease, heart disease, blindness and other complications down the road. Neither have a cure. There have been incredible advancements in diabetes
technology, including continuous glucose monitors and smarter insulin pumps. But managing the disease is still a lot of work. People don't really necessarily realize that we're doing
regular day to day things, but also trying to keep ourselves alive at the same time. And that can be a lot. There's so many other factors that
can impact my blood sugar is if it's not hormones, it's stress, it's illness, it's food, obviously exercise,
hydration, different medications. And I can do things the same way each day and
it's always going to give a different trajectory. So even right now, I'm actually having a high blood sugar
doing this interview. People often say, well, what's the big deal? Don't eat sugar, inject insulin and like get on with it. But there's another aspect of what I would call the
psychosocial cost of the disease. So when a child gets the disease, it affects the whole
family in a way that is never ending. The most stressful part of having diabetes for me is
worrying about low blood sugars, especially while I'm sleeping. If you go too low, it can cause seizures and even
kill you. And while I do have insurance, it's still incredibly
expensive. The Diabetes Research Foundation estimates it costs about
$20,000 a year for an adult with type one in the US and more than $90 Billion a year globally. And fortunately, we're seeing research change the course of
the disease. Dr. Doug Melton started researching a cure for diabetes when
his six month old son was diagnosed in the 1990s. He received a grant from JDRF in 2000 to try to turn stem
cells into insulin making cells. And I was extremely fortunate to work at a private
university, Harvard University, which made it possible for us to use human embryonic stem cells. So the first challenge was to derive those cells and get
access to them and make use of them. And as people may know, they come from leftover material
from IVF clinics. In the early 2000, there was some controversy associated
with stem cell research, but we advocated on Capitol Hill to the president and then through funding to
researchers that this was the pathway to a potential cure for diabetes. And what was that idea? The idea is pretty simple. It's to turn a stem cell, which in theory can be any cell
in the body into functional insulin producing cells. And that's not a one step process. Cells need to be instructed as to what to become. So what we learned over a long period of time is a six step
procedure where we first tell the cells to become part of like the gut tube, then to become part of the pancreas,
then to become what's called endocrine or hormone making, and then become beta cells and then become
functional cells. It just was a lot harder than I thought it would be. Dr. Felicia Pagliuca was a post-doc student working in
Melton's lab. They knew if the cells turned blue they were producing
insulin. And one night in 2014, it finally worked. That night we were watching the plate rotate and we started
to see blue appearing in these wells. And it was one of those moments that you have so rarely, I
think, in science, where you're seeing something that no one's seen before, that no one's been able to do before. And that was a moment we knew we had cracked some really
important biology. How much did all of this cost? Maybe an important way to think about the cost is how many
people were involved. So I would say over that period of several decades, it's 50
to 100 students and postdocs who dedicated themselves to join on this quest. And as many people have said, good science is hardly ever
done by one person. It's a team activity. But I think you're asking about how many pennies, how many
dollars did it cost? I don't have an exact number. A reasonable estimate would be $50 Million. That's a lot of money. But compared to the cost of treating diabetes or the amount
of money spent on injecting insulin, I daresay it's a near trivial amount of money. After this breakthrough, Milton created a company called
Semma Therapeutics, named after his two children. After his second child was also diagnosed with Type one. The company focused on reproducing more cells and turning
it into an actual treatment. In 2019, it caught the interest of Vertex, who bought the
company for $950 million. Then in 2021, Vertex received FDA approval for a clinical
trial. The first trial that we've started is a trial of a of a
therapy called VX-880. Patients in this trial will receive a one time infusion of
the cells, and then they will take standard immunosuppression drugs to protect those cells
from being destroyed. Brian Shelton has been a Type one diabetic for 44 years. He's the first patient in Vertex's clinical trial and only
one of two people who have been dosed so far. Within a few days, the amount of insulin he typically would
inject dropped by 91%, and his pancreas, with a new infusion of beta cells, started producing insulin again. The first human using this method to do so. Now my body does it all along its own. Took a couple of days for me to realize that things are
different now. You know that I can actually live like a regular person and
I'm doing it and I'm doing it pretty well. As a matter of fact, everything is working fine. My numbers are great. Before he entered the clinical trial, Shelton suffered many
hypoglycemic episodes, losing consciousness more times than he could count. When we talked to Brian, it had been seven
months since his infusion of new cells. His insulin needs were still down by 92%. His average blood sugar was 146, down from 200 before the
clinical trial began. This is within good range for someone who has type one, but
still a bit higher than someone who doesn't have diabetes. Regardless, the worry and stress of keeping his blood sugar
under control is, according to him, almost completely gone. Last night I had an ice cream. And when was the last time you bought an ice cream? Just. Just to eat it? Not for any special reason, you know? But I did, and it was delicious. But, you know, you stop eating all these things, and I'm
like, why should I have to give up living to live? You know, and and it's working. The news of this great result spread quickly and was
especially surprising because as the first person in the trial, Shelton only received half of the anticipated dose
to ensure it was safe. What was your reaction when you heard about the first
patient's results? Well, I guess I'm one of the lucky people in the world that
thought about doing an experiment for 20 some years, and then the first results in were even better than I had
hoped. I can't imagine a better first patient result. Vertex's clinical trial plans to infuse 17 participants over
the next few years.There is now a second patient in the trial and the company expects to release additional data
later this year. It's demonstrated that one can make fully functional insulin
producing cells from stem cells. That moves us to the problem of why are they killed off or
rejected. Saying that Shelton is cured is complicated. His body is making its own insulin again. But there is one major caveat he has to take
immunosuppressants in order to stop his immune system from destroying these new cells. We need to be precise in what we talk about when we when we
use the term cure. A cure, in most scientists view in this field, is a
treatment or set of treatments that ultimately renders the individual completely free of
diabetes, able to live with the control of blood glucose being expected and long lasting without any other
therapeutic intervention that needs to be given to them on any kind of regular basis for that control to happen. One of the things that you'll see in the type one community
is a skepticism to a degree of will there be cures for type one? And there are a variety of reasons that happens. Many of us were promised cures a long time ago. This is a major advancement. A major, major advancement. The ability to have an unlimited cell supply and to prove
that these cells can restore blood sugar levels in people, to me says this is
doable. I would caution as a scientist that we need more data, we
need more people in these trials. We need competition, multiple companies working on this
because there are still obstacles. For some diabetics, trading in their insulin for
immunosuppressants would not be worth the risk. I absolutely probably wouldn't. And I know that sounds wild for a lot of people because
it's like, well, that's basically a cure, but it's when you look at it underneath the surface, it's it's not right. It's another another fix and be it a great fix for some
people. For me, I think that it's just treating one thing for
another. It can be the case that an individual will take an
immunosuppressive cocktail and have very few problems over over decades in response to it. But that's not necessarily predictable because each
immunosuppressive agent has its own risks. It's not just vulnerability to infection. Some forms of immunosuppression can actually impact body
weight can actually impact insulin sensitivity and resistance and the risk for a different
type of diabetes, which we call type two diabetes. Shelton, who is no longer having severe swings in his blood
sugars, says it's worth it. What's it like being on immunosuppressants now? I'm loving it. It was like life started on that day, the day that I came home from the hospital when my body was
doing what it should have been doing 30 years ago. If that product comes to the market with the requirement for
immunosuppression, for example, people who have severe risk due to hypoglycemia, that's the the recruitment criteria
for this trial will benefit tremendously from those cells, people who are already on immunosuppressants. Unfortunately, Type one diabetes damages people's kidneys
and sometimes they require kidney transplants. They will benefit. But our goal at JDRF is to see everyone with type one
benefit. And to do that we need to protect these cells from the
immune system. The next challenge is to stop the immune system from
destroying these cells. Several companies are working on different approaches. I actually, to be honest, think that making the
encapsulation device is just as hard or harder than developing the cells that goes into the device. Basically, it's a little bit like a tea bag. You put the cells into the tea bag and transplant them onto
the skin, and then the cells will be protected from the immune system and you avoid needing
immunosuppression. Many of the people we are going to treat with this are
going to be kids and that is basically no room for side effects. Novo Nordisk made over $8 billion from insulin sales in
2021. The company has been heavily criticized for high prices of
insulin. I asked Petersen if the company was concerned about losing
revenue, if they were to find a cure. To be honest and I know I get that question a lot. It has not for a second been on our mind. Our focus has been on developing a curative treatment or
preventing the disease and also developing new insulins. Because before we have the cure, we need to
ensure that the patients we are serving will get the best possible treatments. After working in the diabetes space for over 20 years. Petersen's daughter was diagnosed with type one. I saw I kind of knew everything about the disease, about the
patients, about the doctors. But I thought we have really good insulins. We have good glucose monitors, you know, how bad is it? But sitting there with a four year old with type one
diabetes, it changed my life in a heartbeat. What we need to figure out is that can we do it in a safe
way? And I think that that will be a matter of time. The cells need the nutrients. We need to keep them, I call it keep them happy in the
body. And that that's a challenge. What we've seen in clinical trials from a company via site
reported out is they are seeing insulin production in these macro encapsulated
cells, not enough to restore normal blood sugar levels or cure diabetes, but certainly cells living and
making insulin. Again, if some cells can live, we can start to then work
towards what are the approaches to make more cells and how to keep all of the cells happy. Very, very important. ViaCyte is already in clinical trials with an encapsulation
device. Novo Nordisk says it's a few years out and Vertex says it
has its own device in the pipeline. And we plan to bring that program to what's called an IND
filing investigational new drug application to the FDA this year. And we hope we'll be able to work with them to get a green
light to start that clinical trial. We also have a research pipeline that we have been
developing using all of the latest technologies, including things like gene editing, where we can actually
edit the cells themselves to remove things that stimulate the immune system or to add things
that reduce the immune reaction. Editing the genes could be another way to potentially
protect these cells. I call this the Harry Potter cloak of invisibility. You know, if you can put a cloak over these cells and you
can't see them, we may be able to then just inject the cells into the body with minimal burden to the type one
individual. This is also what Dr. Melton is now focusing on in his lab at Harvard. I like to think of ways of trying to make the cells kind of
opaque. And don't ask me how we do that, because I don't know yet. But that's why I like science. It involves discovery. You know, once you've had diabetes for this long and even
there's people who've had it for longer. Hearing these these echoes of a cure and not necessarily
seeing it come into fruition, you always take it with a grain of salt. I think it's great. All the work that they've done is fantastic. It's a good step in the right direction. Despite there still not being a cure. Technology has been rapidly advancing in the diabetes
space. There are several closed loop insulin pump systems on the
market. Cgms are getting smaller and more accurate. There are faster insulins and some you can even inhale. Been doing pumping for a while now. Again, it's a good tool. It does help, but it's by no means perfect. The high cost of insulin is still an issue for many people. Insulin is a life sustaining drug. If I didn't have insulin, I would die. Likely within a week or so. And that is a very, very fine line. You have to be healthy when cures arrive. I'm super optimistic about where we're headed, but I want
every person with diabetes to benefit. And you can't benefit if you can't have the very drug that
sustains your life. And while it's not known how much a stem cell derived beta
cell treatment would cost if it were ever to come to market, CGMs, closed loop systems and other technology may be more
appealing and possibly cheaper. I'm fairly certain that that, coupled with ongoing efforts
to to use nanotechnology to miniaturize all of the hardware necessary to do this, that
you're going to have something that is really Cadillac by the time the next 3 to 5 years rolls around. And then people will just be comparing whether that seems
more appealing to them versus being a part of studies and trials aimed at a more biological, fundamental biological
solution, which will also be quite compelling to some people. For diabetics who want a cure that requires no additional
treatment, it may no longer be a question of if, but a matter of when. So when do you think a cure is going to be? I think even from diagnosis and for a lot of people, that's
one of the first questions that they ask. And the joke is always that it's five years away. And that's what I'm hearing from a lot of these scientists
and a lot of these companies. So do you think we might finally be on the verge of this
happening? I am fully convinced that I will walk away from my insulin
pump and continuous glucose monitor in my lifetime, and I would be disappointed if it wasn't in this
decade.
