“I think the advantage we have with our technology is that it's so simple," says Aaron Blanchard, left, a PhD student in Emory's Laney Graduate School, shown using the Rolosense with his advisor, Emory chemist Khalid Salaita.
By Carol Clark
The first rolling DNA motor – the biological equivalent of the invention of the wheel for the field of DNA machines – is headed from its origins in an Emory University chemistry lab to the finals of the 2016 Collegiate Inventors Competition in Washington D.C.
Kevin Yehl and Aaron Blanchard make up one of six teams of graduate students who will be flown to the finals in early November. Yehl and Blanchard developed the DNA motor (dubbed Rolosense), and its application as a chemical sensor, in the laboratory of their advisor – Emory chemist Khalid Salaita.
The entries of the elite student teams represent the most promising inventions from U.S. universities. “Their ideas will shape the future,” wrote Michael Oister, CEO of the National Inventors Hall of Fame, in a letter announcing the finalists.
The Collegiate Inventors Competition annually gives out about $100,000 in cash prizes and is considered the foremost program in the country encouraging invention and creativity in undergraduate and graduate students. The competition also promotes entrepreneurship, by rewarding ideas that hold value for society.
The Rolosense is 1,000 times faster than any other synthetic DNA motor. Its speed means a simple iPhone microscope can capture its movement through video, giving it potential for real-world applications, such as disease diagnostics.
Kevin Yehl sets up a smart-phone microscope to get a readout for the particle motion of the rolling DNA-based motor.
"It's exciting," Yehl says. "Previous winners have gone on to start companies with their inventions and become successful scientists. It will be great to get feedback from the judges on the Rolosense."
The judges will include inductees to the National Inventors Hall of Fame, officials from the U.S. Patent and Trademark Office, and scientists from the global healthcare firm AbbVie.
Some of the best discoveries involve serendipity, and that was the case for the Rolosense. Yehl was working last year as a post-doctoral fellow in the Salaita lab, which specializes in visualizing and measuring mechanical forces at the nano-scale. He was conducting experiments using enzymatic nano-particles – micron-sized glass spheres. “We were originally just interested in understanding the properties of enzymes when they’re confined to a surface,” Yehl says.
During the experiments, however, he learned by accident that the nano-particles roll. That gave him the idea of constructing a rolling DNA-based motor using the glass spheres.
The field of synthetic DNA-based motors, also known as nano-walkers, is about 15 years old. Researchers are striving to duplicate the action of nature’s nano-walkers. Myosin, for example, are tiny biological mechanisms that “walk” on filaments to carry nutrients throughout the human body.
So far, however, mankind’s efforts have fallen far short of nature’s myosin, which speeds effortlessly about its biological errands. Some synthetic nano-walkers move on two legs. They are essentially enzymes made of DNA, powered by the fuel RNA. These nano-walkers tend to be extremely unstable, due to the high levels of Brownian motion at the nano-scale. Other versions with four, and even six, legs have proved more stable, but much slower. In fact, their pace is glacial: A four-legged DNA-based motor would need about 20 years to move one centimeter.
A cell phone app is in the works.
The Rolosense design mows over these limitations. Hundreds of DNA strands, or “legs,” are allowed to bind to the sphere. These DNA legs are placed on a glass slide coated with the reactant: RNA.
The DNA legs are drawn to the RNA, but as soon as they set foot on it they destroy it through the activity of an enzyme called RNase H. As the legs bind and then release from the substrate, they guide the sphere along, allowing more of the DNA legs to keep binding and pulling.
“The Rolosense can travel one centimeter in seven days, instead of 20 years, making it 1,000 times faster than other synthetic DNA motors,” Salaita says. “In fact, nature’s myosin motors are only 10 times faster than the Rolosense, and it took them billions of years to evolve.”
The researchers next demonstrated the Rolosense could be used to detect a single DNA mutation by measuring particle displacement. Yehl simply glued lenses from two inexpensive laser pointers to the camera of an iPhone to turn the phone’s camera into a microscope and capture videos of the particle motion.
The simple, low-tech method could come in handy for doing diagnostic sensing in the field, or anywhere with limited resources.
Nature Nanotechnology published the work on the rolling DNA motor. The researchers have filed an invention disclosure patent for the concept of using the particle motion of the Rolosense as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water.
Yehl has since left Emory for a position at MIT, but he continues to work with Salaita and Aaron Blanchard, a second year student of biomedical engineering in Emory’s Laney Graduate School, on refining the Rolosense.
Blanchard, who has a background in computer coding, is integrating the data analysis of the Rolosense into a smart phone app that will provide a readout of the results.
“I feel really fortunate as a graduate student to be working on this project,” Blanchard says. “As the molecular detection field grows, I think that Rolosense will grow with it.”
For their demonstration during the finals, Yehl and Blanchard plan to hand the judges smart phones and samples of water (including some containing lead), and let the judges use Rolosense to test the samples.
“It can be easy to dazzle with complex technologies like a robot,” Blanchard says, “but I think the advantage that we have with our technology is that it’s so simple. We can let the judges see for themselves how they can use Rolosense to quickly learn something useful, like whether a water source is contaminated with a heavy metal.”
“I think the advantage we have with our technology is that it's so simple," says Aaron Blanchard, left, a PhD student in Emory's Laney Graduate School, shown using the Rolosense with his advisor, Emory chemist Khalid Salaita.
By Carol Clark
The first rolling DNA motor – the biological equivalent of the invention of the wheel for the field of DNA machines – is headed from its origins in an Emory University chemistry lab to the finals of the 2016 Collegiate Inventors Competition in Washington D.C.
Kevin Yehl and Aaron Blanchard make up one of six teams of graduate students who will be flown to the finals in early November. Yehl and Blanchard developed the DNA motor (dubbed Rolosense), and its application as a chemical sensor, in the laboratory of their advisor – Emory chemist Khalid Salaita.
The entries of the elite student teams represent the most promising inventions from U.S. universities. “Their ideas will shape the future,” wrote Michael Oister, CEO of the National Inventors Hall of Fame, in a letter announcing the finalists.
The Collegiate Inventors Competition annually gives out about $100,000 in cash prizes and is considered the foremost program in the country encouraging invention and creativity in undergraduate and graduate students. The competition also promotes entrepreneurship, by rewarding ideas that hold value for society.
The Rolosense is 1,000 times faster than any other synthetic DNA motor. Its speed means a simple iPhone microscope can capture its movement through video, giving it potential for real-world applications, such as disease diagnostics.
Kevin Yehl sets up a smart-phone microscope to get a readout for the particle motion of the rolling DNA-based motor.
"It's exciting," Yehl says. "Previous winners have gone on to start companies with their inventions and become successful scientists. It will be great to get feedback from the judges on the Rolosense."
The judges will include inductees to the National Inventors Hall of Fame, officials from the U.S. Patent and Trademark Office, and scientists from the global healthcare firm AbbVie.
Some of the best discoveries involve serendipity, and that was the case for the Rolosense. Yehl was working last year as a post-doctoral fellow in the Salaita lab, which specializes in visualizing and measuring mechanical forces at the nano-scale. He was conducting experiments using enzymatic nano-particles – micron-sized glass spheres. “We were originally just interested in understanding the properties of enzymes when they’re confined to a surface,” Yehl says.
During the experiments, however, he learned by accident that the nano-particles roll. That gave him the idea of constructing a rolling DNA-based motor using the glass spheres.
The field of synthetic DNA-based motors, also known as nano-walkers, is about 15 years old. Researchers are striving to duplicate the action of nature’s nano-walkers. Myosin, for example, are tiny biological mechanisms that “walk” on filaments to carry nutrients throughout the human body.
So far, however, mankind’s efforts have fallen far short of nature’s myosin, which speeds effortlessly about its biological errands. Some synthetic nano-walkers move on two legs. They are essentially enzymes made of DNA, powered by the fuel RNA. These nano-walkers tend to be extremely unstable, due to the high levels of Brownian motion at the nano-scale. Other versions with four, and even six, legs have proved more stable, but much slower. In fact, their pace is glacial: A four-legged DNA-based motor would need about 20 years to move one centimeter.
A cell phone app is in the works.
The Rolosense design mows over these limitations. Hundreds of DNA strands, or “legs,” are allowed to bind to the sphere. These DNA legs are placed on a glass slide coated with the reactant: RNA.
The DNA legs are drawn to the RNA, but as soon as they set foot on it they destroy it through the activity of an enzyme called RNase H. As the legs bind and then release from the substrate, they guide the sphere along, allowing more of the DNA legs to keep binding and pulling.
“The Rolosense can travel one centimeter in seven days, instead of 20 years, making it 1,000 times faster than other synthetic DNA motors,” Salaita says. “In fact, nature’s myosin motors are only 10 times faster than the Rolosense, and it took them billions of years to evolve.”
The researchers next demonstrated the Rolosense could be used to detect a single DNA mutation by measuring particle displacement. Yehl simply glued lenses from two inexpensive laser pointers to the camera of an iPhone to turn the phone’s camera into a microscope and capture videos of the particle motion.
The simple, low-tech method could come in handy for doing diagnostic sensing in the field, or anywhere with limited resources.
Nature Nanotechnology published the work on the rolling DNA motor. The researchers have filed an invention disclosure patent for the concept of using the particle motion of the Rolosense as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water.
Yehl has since left Emory for a position at MIT, but he continues to work with Salaita and Aaron Blanchard, a second year student of biomedical engineering in Emory’s Laney Graduate School, on refining the Rolosense.
Blanchard, who has a background in computer coding, is integrating the data analysis of the Rolosense into a smart phone app that will provide a readout of the results.
“I feel really fortunate as a graduate student to be working on this project,” Blanchard says. “As the molecular detection field grows, I think that Rolosense will grow with it.”
For their demonstration during the finals, Yehl and Blanchard plan to hand the judges smart phones and samples of water (including some containing lead), and let the judges use Rolosense to test the samples.
“It can be easy to dazzle with complex technologies like a robot,” Blanchard says, “but I think the advantage that we have with our technology is that it’s so simple. We can let the judges see for themselves how they can use Rolosense to quickly learn something useful, like whether a water source is contaminated with a heavy metal.”
“Everyone has his dream; I would like to live till dawn, but I know I have less than three hours left. It will be night, but no matter. Dying is simple. It does not take daylight. So be it: I will die by starlight.” –Victor Hugo
Whether you’re at rest or in motion, you can be confident that — from your point of view — the laws of physics will behave exactly the same no matter how quickly you’re moving. You can move slowly, quickly or not at all, up to the limits that the Universe imposes on you: the speed of light.
Light, in a vacuum, always appears to move at the same speed — the speed of light — regardless of the observer’s velocity. Image credit: pixabay user Melmak.
But what if you’re actually a photon? What if you don’t move near the speed of light, but at the speed of light? As it turns out, the way any massless particle experiences time, distance, and the Universe in general is entirely counterintuitive, and there’s nothing in our common experience that matches up.
A relativistic journey toward the constellation of Orion. Image credit: Alexis Brandeker, via http://ift.tt/1kvZ4B9. StarStrider, a relativistic 3D planetarium program by FMJ-Software, was used to produce the Orion illustrations.
“Everyone has his dream; I would like to live till dawn, but I know I have less than three hours left. It will be night, but no matter. Dying is simple. It does not take daylight. So be it: I will die by starlight.” –Victor Hugo
Whether you’re at rest or in motion, you can be confident that — from your point of view — the laws of physics will behave exactly the same no matter how quickly you’re moving. You can move slowly, quickly or not at all, up to the limits that the Universe imposes on you: the speed of light.
Light, in a vacuum, always appears to move at the same speed — the speed of light — regardless of the observer’s velocity. Image credit: pixabay user Melmak.
But what if you’re actually a photon? What if you don’t move near the speed of light, but at the speed of light? As it turns out, the way any massless particle experiences time, distance, and the Universe in general is entirely counterintuitive, and there’s nothing in our common experience that matches up.
A relativistic journey toward the constellation of Orion. Image credit: Alexis Brandeker, via http://ift.tt/1kvZ4B9. StarStrider, a relativistic 3D planetarium program by FMJ-Software, was used to produce the Orion illustrations.
Just got the application referees’ evaluation for a job I’ve been hoping for. I’m afraid to read it. Taking a walk first.
I’m really tired of this thankless shit. Impatient for December, when I’ll know if I’ll have money to write that castles book or if I should start calling people about a steady job in contract archaeology. The one I stupidly turned down in fucking 1994.
Osteologist Rudolf Gustavsson has documented traces of flaying on cat bones that we’ve found at Stensö Castle. Reading the ribald 15th century “Marriage Song” that has just appeared in a new critical edition, I found a passage where the poet warns a father of daughters: “If he has beautiful cats, then my advice is not to invite many furriers to his feast”.
Affluent Chinese Swedes who want to throw out the Middle Eastern refugees. I can’t even.
Torbjörn Lodén writes something interesting in the latest issue of the Swedish-Chinese Association’s monthly. According to him, the Chinese Communist Party’s continued emphasis on Mao Zedong Sixiang, “Mao Zedong’s Thought” after the man’s death should be read as an implicit step away from his many disastrous actions. Apparently Mao Zedong failed to follow his own Thought.
I see flashing knobs!
These castle sites really aren’t very rich in pottery. Birgittas udde didn’t yield a single sherd. Skällvik offered only 68 g of Medieval wares and 332 g of Modern stuff.
Not-so-great usability. The interface of our front door’s inside lets you do four things. Press the handle, pull the handle, turn the lock knob one way, turn the lock knob the other way. When the door is locked, if you press the handle, the pressure of the door’s rubber insulation seal disables the lock knob. You can then only leave our house if you know that you have to pull the handle first.
Sewed the buttons back onto my crappy Lithuanian shirt and imposed Ordnung on the needlework box.
Much-needed encouragement: a journalist did a long interview with me about my new book.
It’s 100 meters high and several 100 degrees Celsius warm inside. It’s a pile of ashes from a mid-20th century shale oil plant. It’s just
outside Örebro.
Reasonable commentators unanimously declare Trump unfit for office. Sadly this makes Trump voters unfit for democracy.
I’ve never tossed a grocery basket onto a roof. Have I really lived at all?
from ScienceBlogs http://ift.tt/2df8iSO
Just got the application referees’ evaluation for a job I’ve been hoping for. I’m afraid to read it. Taking a walk first.
I’m really tired of this thankless shit. Impatient for December, when I’ll know if I’ll have money to write that castles book or if I should start calling people about a steady job in contract archaeology. The one I stupidly turned down in fucking 1994.
Osteologist Rudolf Gustavsson has documented traces of flaying on cat bones that we’ve found at Stensö Castle. Reading the ribald 15th century “Marriage Song” that has just appeared in a new critical edition, I found a passage where the poet warns a father of daughters: “If he has beautiful cats, then my advice is not to invite many furriers to his feast”.
Affluent Chinese Swedes who want to throw out the Middle Eastern refugees. I can’t even.
Torbjörn Lodén writes something interesting in the latest issue of the Swedish-Chinese Association’s monthly. According to him, the Chinese Communist Party’s continued emphasis on Mao Zedong Sixiang, “Mao Zedong’s Thought” after the man’s death should be read as an implicit step away from his many disastrous actions. Apparently Mao Zedong failed to follow his own Thought.
I see flashing knobs!
These castle sites really aren’t very rich in pottery. Birgittas udde didn’t yield a single sherd. Skällvik offered only 68 g of Medieval wares and 332 g of Modern stuff.
Not-so-great usability. The interface of our front door’s inside lets you do four things. Press the handle, pull the handle, turn the lock knob one way, turn the lock knob the other way. When the door is locked, if you press the handle, the pressure of the door’s rubber insulation seal disables the lock knob. You can then only leave our house if you know that you have to pull the handle first.
Sewed the buttons back onto my crappy Lithuanian shirt and imposed Ordnung on the needlework box.
Much-needed encouragement: a journalist did a long interview with me about my new book.
It’s 100 meters high and several 100 degrees Celsius warm inside. It’s a pile of ashes from a mid-20th century shale oil plant. It’s just
outside Örebro.
Reasonable commentators unanimously declare Trump unfit for office. Sadly this makes Trump voters unfit for democracy.
I’ve never tossed a grocery basket onto a roof. Have I really lived at all?
Autumn 2016 in the Colorado Rocky Mountains. Photo via Jessi Leigh Photography. Thanks Jessi!
The vivid yellow and orange colors have actually been there throughout the spring and summer, but we haven’t been able to see them. The deep green color of chlorophyll, which helps plants absorb life-giving sunlight, hides the other colors. In the fall, trees break down the green pigments and nutrients stored in the leaves. The nutrients are shuttled into the roots for reuse in the spring
As leaves lose their chlorophyll, other pigments become visible to the human eye, according to Bryan A. Hanson, professor of chemistry and biochemistry at DePauw University who studies plant pigments. Some tree leaves turn mostly brown, indicating that all pigments are gone.
Autumn leaves at Hurricane Mountain in the Adirondacks, New York, September, 2015. Photo by John Holmes. Thank you John!
Autumn leaf in about mid-September from our friend Colin Chatfield in Saskatoon, Saskatchewan.
Burgundy and red colors are a different story. Dana A. Dudle is a DePauw professor of biology who researches red pigment in plant flowers, stems and leaves. Dudle said:
The red color is actively made in leaves by bright light and cold. The crisp, cold nights in the fall combine with bright, sunny days to spur production of red in leaves – especially in sugar maple and red maple trees. Burgundy leaves often result from a combination of red pigment and chlorophyll. Autumn seasons with a lot of sunny days and cold nights will have the brightest colors.
In some cases, about half of a tree’s leaves are red/orange and the other half green. Dudle says that results from micro-environmental factors – such as only half the tree being exposed to sunlight or cold.
Hardwoods in the Midwest and on the East Coast are famous for good color selections. Some of the more reliably colorful trees, Hanson notes, are liquid amber trees (also called sweet gum) that turn a variety of colors on the same tree, and sometimes the same leaf. Ash tree leaves often turn a deep burgundy color. Ginkgo trees, although not native to North America, will feature an intense yellow, almost golden, color.
A lone red tree against bare branches. Photo via Daniel de Leeuw Photog.
“Autumn picture from Sweden…” from our friend Jörgen Norrland
The colors are doing something for the plant, or they wouldn’t be there, said Hansen. But what is the colors’ purpose?
Scientists think that with some trees, pigments serve as a kind of sunscreen to filter out sunlight. Hanson said:
It’s an underappreciated fact that plants cannot take an infinite amount of sun. Some leaves, if they get too much sun, will get something equivalent of a sunburn. They get stressed out and die.
Image via Tosca Yemoh Zanon in London.
Another theory is that the color of a plant’s leaves is often related to the ability to warn away pests or attract insect pollinators. Hanson said:
In some cases, a plant and insect might have co-evolved. One of the more intriguing scientific theories is that the beautiful leaf colors we see today are indicative of a relationship between a plant and insects that developed millions of years ago. However, as the Earth’s climate changed over the years, the insects might have gone extinct, but the plant was able to survive for whatever reason.
Because plants evolve very slowly, we still see the colors. So leaf color is a fossil memory, something that existed for a reason millions of years ago but that serves no purpose now.
Autumn 2016 in the Colorado Rocky Mountains. Photo via Jessi Leigh Photography. Thanks Jessi!
The vivid yellow and orange colors have actually been there throughout the spring and summer, but we haven’t been able to see them. The deep green color of chlorophyll, which helps plants absorb life-giving sunlight, hides the other colors. In the fall, trees break down the green pigments and nutrients stored in the leaves. The nutrients are shuttled into the roots for reuse in the spring
As leaves lose their chlorophyll, other pigments become visible to the human eye, according to Bryan A. Hanson, professor of chemistry and biochemistry at DePauw University who studies plant pigments. Some tree leaves turn mostly brown, indicating that all pigments are gone.
Autumn leaves at Hurricane Mountain in the Adirondacks, New York, September, 2015. Photo by John Holmes. Thank you John!
Autumn leaf in about mid-September from our friend Colin Chatfield in Saskatoon, Saskatchewan.
Burgundy and red colors are a different story. Dana A. Dudle is a DePauw professor of biology who researches red pigment in plant flowers, stems and leaves. Dudle said:
The red color is actively made in leaves by bright light and cold. The crisp, cold nights in the fall combine with bright, sunny days to spur production of red in leaves – especially in sugar maple and red maple trees. Burgundy leaves often result from a combination of red pigment and chlorophyll. Autumn seasons with a lot of sunny days and cold nights will have the brightest colors.
In some cases, about half of a tree’s leaves are red/orange and the other half green. Dudle says that results from micro-environmental factors – such as only half the tree being exposed to sunlight or cold.
Hardwoods in the Midwest and on the East Coast are famous for good color selections. Some of the more reliably colorful trees, Hanson notes, are liquid amber trees (also called sweet gum) that turn a variety of colors on the same tree, and sometimes the same leaf. Ash tree leaves often turn a deep burgundy color. Ginkgo trees, although not native to North America, will feature an intense yellow, almost golden, color.
A lone red tree against bare branches. Photo via Daniel de Leeuw Photog.
“Autumn picture from Sweden…” from our friend Jörgen Norrland
The colors are doing something for the plant, or they wouldn’t be there, said Hansen. But what is the colors’ purpose?
Scientists think that with some trees, pigments serve as a kind of sunscreen to filter out sunlight. Hanson said:
It’s an underappreciated fact that plants cannot take an infinite amount of sun. Some leaves, if they get too much sun, will get something equivalent of a sunburn. They get stressed out and die.
Image via Tosca Yemoh Zanon in London.
Another theory is that the color of a plant’s leaves is often related to the ability to warn away pests or attract insect pollinators. Hanson said:
In some cases, a plant and insect might have co-evolved. One of the more intriguing scientific theories is that the beautiful leaf colors we see today are indicative of a relationship between a plant and insects that developed millions of years ago. However, as the Earth’s climate changed over the years, the insects might have gone extinct, but the plant was able to survive for whatever reason.
Because plants evolve very slowly, we still see the colors. So leaf color is a fossil memory, something that existed for a reason millions of years ago but that serves no purpose now.
In a corner of our head office, sits a team of six people. And since 2010, they’ve been quietly, but resolutely helping to develop new treatment options for cancer patients.
This is the team behind the Combinations Alliance, one of several projects run through the Experimental Cancer Medicine Centre network (ECMC).
The Alliance brings together UK researchers and drug companies from around the world to explore new combinations of cancer drugs. By combining multiple drugs in a single clinical trial, they can test whether or not the combination is better at treating cancer than the standard treatment available.
It’s a unique scheme that’s increasing treatment options for patients, and tackling drug resistance – arguably one of the biggest problems in cancer treatment.
The Combinations Alliance works very much like a match-making agency for researchers and drug companies. The goal of developing these relationships is to hopefully launch clinical trials that test promising new combinations of drugs to treat different types of cancer.
The Combinations Alliance focuses on therapies that wouldn’t progress without our support
– Dr Ian Walker, director of clinical research and strategic partnerships at Cancer Research UK
So why exactly was the Combinations Alliance set up? Surely companies have thought of collaborating in this way before? Well, this can be tricky. Each company has a different way of working.
So it’s often much simpler for many drug companies to go it alone. But they’re beginning to see how limiting this approach is. Despite huge resources, it’s simply impossible for any company to test every combination of drugs.
But our Combinations Alliance offers a structured way for drug companies – alongside researchers – to work together. And, ultimately, get better treatments to patients, sooner.
How the initiative works
Our team begins by meeting a drug company that’s developing promising cancer drugs. Researchers within our ECMC network then consider which drugs could work together in a clinical trial.
So far twelve partners have signed onto the scheme, with many more set to join in the next few years.
Alternatively, the team receives an idea from a researcher to combine two or more drugs, which aren’t necessarily owned by an existing Alliance partner.
The team then approaches the company who owns that drug for permission to use it in a clinical trial.
Most trials to date have tested a single company’s experimental new drug in combination with a drug that’s already available as standard treatment for patients – or with radiotherapy. There have also been a few trials involving two new experimental drugs owned by the same company.
But for the first time today, the Alliance has brought together two drug companies to test an exciting combination of two drugs: one an immunotherapy drug, the other a so-called ‘targeted’ cancer treatment.
And it’s thanks to the inspirational idea of two researchers – Dr Stefan Symeonides, at the University of Edinburgh, and Professor Dean Fennell, at the University of Leicester.
The bright idea
Together, Symeonides and Fennell designed the combination clinical trial that will be managed at Cancer Research UK’s Clinical Trials Unit in Glasgow. It’s an idea that’s based on work from another of our researchers, Professor Margaret Frame, at the University of Edinburgh.
But designing the trial was only one part of the story. To run it, Symeonides and Fennell needed approval to use the drugs, which are owned and made by two different drug companies.
Let’s step back a couple of years to see how the team made this happen.
Back in 2014, a small drug company based just north of New Jersey in Massachusetts in the US, called Verastem, got in touch with the team.
They’re an existing Alliance partner, introduced by Fennell, and have been working on a drug called VS-6063, which switches off a molecule called FAK that’s found inside cells.
But once the barrier is down, how can the body attack the tumour itself?
Symeonides and Fennell believe that Verastem’s drug could work better with another drug that boosts the immune system and the army of cells it unleashes. And they had a good idea of what could work.
The final piece of the jigsaw
Fast-forward to 2015 and the answer to this problem could be found back in New Jersey at a different drug company, MSD, which is one of the largest drug companies in the world.
Although not an Alliance partner at the time, they were in talks with the team, and agreed to let Symeonides and Fennell use an immunotherapy drug called pembrolizumab (Keytruda) for the trial. Pembrolizumab is designed to target an antenna-like molecule that sticks out on the surface of certain forms of immune cell.
Normally, this ‘antenna’ – called the programmed cell death 1 (PD-1) receptor – picks up signals, preventing the immune system from inappropriately reacting to certain triggers. But in people with some types of cancer, the same antenna receives signals stopping the body’s immune system from recognising the cancer cells, allowing the tumour to remain undetected.
Pembrolizumab blocks these signals, jumpstarting the immune system into recognising, targeting and destroying tumours.
Symeonides and Fennell thought that once the barrier surrounding the cancer cells has been taken down by Verastem’s drug, MSD’s pembrolizumab could then activate cancer-killing immune cells to attack the tumour.
Pembrolizumab on its own has shown promise in treating bladder, melanoma, kidney and non-small cell lung cancer, but it’s had little effect in people with other types of cancer. So this would be a chance to see if the drug could treat more types than originally thought.
Fast-forward to today, and both Verastem and MSD have agreed to the use of their drugs in combination for the first time in a clinical trial. The trial will look at whether the two drugs can be used safely together, and test whether the combination is better for treating people with mesothelioma, non-small cell lung and pancreatic cancers – all of which have very low survival.
What’s next?
By working with UK researchers, and drug companies around the world, there are still many more trial ideas to be explored. These aren’t limited to those involving drug combinations, but using radiotherapy and surgery too. It’s just about getting the right people with the right drugs to start working together.
What the Combinations Alliance team have achieved to date is no small feat. They’re responsible for pulling in some of the best science and making sure that these trials are run in the UK (MSD and Verastem are both American companies and logistically, it’d be a lot easier for them to run the trial in the US), so that patients here can benefit first.
It’s early days, the trial isn’t recruiting patients yet – but it should be up and running later this year.
So far 356 people have taken part in a Combinations Alliance trial and have been given another shot at tackling cancer that’s come back.
One trial in particular was so promising that it’s now progressed to the next step, a larger clinical to see how well it actually works in a larger number of people.
The Combinations Alliance team might be sitting quietly in the corner in our office, but make no mistake, they’re causing quite the stir outside it.
Amille
from Cancer Research UK – Science blog http://ift.tt/2cQegZI
In a corner of our head office, sits a team of six people. And since 2010, they’ve been quietly, but resolutely helping to develop new treatment options for cancer patients.
This is the team behind the Combinations Alliance, one of several projects run through the Experimental Cancer Medicine Centre network (ECMC).
The Alliance brings together UK researchers and drug companies from around the world to explore new combinations of cancer drugs. By combining multiple drugs in a single clinical trial, they can test whether or not the combination is better at treating cancer than the standard treatment available.
It’s a unique scheme that’s increasing treatment options for patients, and tackling drug resistance – arguably one of the biggest problems in cancer treatment.
The Combinations Alliance works very much like a match-making agency for researchers and drug companies. The goal of developing these relationships is to hopefully launch clinical trials that test promising new combinations of drugs to treat different types of cancer.
The Combinations Alliance focuses on therapies that wouldn’t progress without our support
– Dr Ian Walker, director of clinical research and strategic partnerships at Cancer Research UK
So why exactly was the Combinations Alliance set up? Surely companies have thought of collaborating in this way before? Well, this can be tricky. Each company has a different way of working.
So it’s often much simpler for many drug companies to go it alone. But they’re beginning to see how limiting this approach is. Despite huge resources, it’s simply impossible for any company to test every combination of drugs.
But our Combinations Alliance offers a structured way for drug companies – alongside researchers – to work together. And, ultimately, get better treatments to patients, sooner.
How the initiative works
Our team begins by meeting a drug company that’s developing promising cancer drugs. Researchers within our ECMC network then consider which drugs could work together in a clinical trial.
So far twelve partners have signed onto the scheme, with many more set to join in the next few years.
Alternatively, the team receives an idea from a researcher to combine two or more drugs, which aren’t necessarily owned by an existing Alliance partner.
The team then approaches the company who owns that drug for permission to use it in a clinical trial.
Most trials to date have tested a single company’s experimental new drug in combination with a drug that’s already available as standard treatment for patients – or with radiotherapy. There have also been a few trials involving two new experimental drugs owned by the same company.
But for the first time today, the Alliance has brought together two drug companies to test an exciting combination of two drugs: one an immunotherapy drug, the other a so-called ‘targeted’ cancer treatment.
And it’s thanks to the inspirational idea of two researchers – Dr Stefan Symeonides, at the University of Edinburgh, and Professor Dean Fennell, at the University of Leicester.
The bright idea
Together, Symeonides and Fennell designed the combination clinical trial that will be managed at Cancer Research UK’s Clinical Trials Unit in Glasgow. It’s an idea that’s based on work from another of our researchers, Professor Margaret Frame, at the University of Edinburgh.
But designing the trial was only one part of the story. To run it, Symeonides and Fennell needed approval to use the drugs, which are owned and made by two different drug companies.
Let’s step back a couple of years to see how the team made this happen.
Back in 2014, a small drug company based just north of New Jersey in Massachusetts in the US, called Verastem, got in touch with the team.
They’re an existing Alliance partner, introduced by Fennell, and have been working on a drug called VS-6063, which switches off a molecule called FAK that’s found inside cells.
But once the barrier is down, how can the body attack the tumour itself?
Symeonides and Fennell believe that Verastem’s drug could work better with another drug that boosts the immune system and the army of cells it unleashes. And they had a good idea of what could work.
The final piece of the jigsaw
Fast-forward to 2015 and the answer to this problem could be found back in New Jersey at a different drug company, MSD, which is one of the largest drug companies in the world.
Although not an Alliance partner at the time, they were in talks with the team, and agreed to let Symeonides and Fennell use an immunotherapy drug called pembrolizumab (Keytruda) for the trial. Pembrolizumab is designed to target an antenna-like molecule that sticks out on the surface of certain forms of immune cell.
Normally, this ‘antenna’ – called the programmed cell death 1 (PD-1) receptor – picks up signals, preventing the immune system from inappropriately reacting to certain triggers. But in people with some types of cancer, the same antenna receives signals stopping the body’s immune system from recognising the cancer cells, allowing the tumour to remain undetected.
Pembrolizumab blocks these signals, jumpstarting the immune system into recognising, targeting and destroying tumours.
Symeonides and Fennell thought that once the barrier surrounding the cancer cells has been taken down by Verastem’s drug, MSD’s pembrolizumab could then activate cancer-killing immune cells to attack the tumour.
Pembrolizumab on its own has shown promise in treating bladder, melanoma, kidney and non-small cell lung cancer, but it’s had little effect in people with other types of cancer. So this would be a chance to see if the drug could treat more types than originally thought.
Fast-forward to today, and both Verastem and MSD have agreed to the use of their drugs in combination for the first time in a clinical trial. The trial will look at whether the two drugs can be used safely together, and test whether the combination is better for treating people with mesothelioma, non-small cell lung and pancreatic cancers – all of which have very low survival.
What’s next?
By working with UK researchers, and drug companies around the world, there are still many more trial ideas to be explored. These aren’t limited to those involving drug combinations, but using radiotherapy and surgery too. It’s just about getting the right people with the right drugs to start working together.
What the Combinations Alliance team have achieved to date is no small feat. They’re responsible for pulling in some of the best science and making sure that these trials are run in the UK (MSD and Verastem are both American companies and logistically, it’d be a lot easier for them to run the trial in the US), so that patients here can benefit first.
It’s early days, the trial isn’t recruiting patients yet – but it should be up and running later this year.
So far 356 people have taken part in a Combinations Alliance trial and have been given another shot at tackling cancer that’s come back.
One trial in particular was so promising that it’s now progressed to the next step, a larger clinical to see how well it actually works in a larger number of people.
The Combinations Alliance team might be sitting quietly in the corner in our office, but make no mistake, they’re causing quite the stir outside it.
Amille
from Cancer Research UK – Science blog http://ift.tt/2cQegZI
I’ve referred to so-called “right to try” laws as a cruel sham.on more than one occasion. Since 2014, these laws, all based on a template provided by the libertarian Goldwater Institute, have been proliferating at the state level with the help of lobbying by the aforementioned Goldwater Institute and a concept that makes it pitifully easy to caricature opposition to these laws as wanting to heartlessly snatch away from terminally ill patients the last chance at life while laughing and twirling one’s mustache like Snidely Whiplash. Not surprisingly, state legislatures all over the country have found such laws irresistible, leading to their passage in over 30 states in just two and a half years. Over the last week, right-to-try has had a major victory in that, contrary to what he did last year and contrary to the hope of science advocates, California Governor Jerry Brown signed the right-to-try bill (AB-1668) that was passed earlier this month. However, it has also suffered a major defeat in that a couple of days ago the federal right-to-try bill was blocked in the Senate.
The basic premise behind right-to-try laws is that people are dying in droves because the FDA is too slow and too hidebound to allow dying patients access to experimental drugs that are still undergoing clinical trials to be approved by the FDA. No, really, that’s the argument libertarians make, that the FDA is literally (yes, I mean literally—just ask Nick Gillespie and Ronald Bailey) “killing” people. Enter right-to-try, laws that purport to allow terminally ill patients (or, in some cases, patients with life-threatening but not necessarily terminal illnesses) to access experimental therapeutics in a desperate bid to save their lives. Sounds reasonable on the surface, right? What is assiduously not mentioned are other libertarian-based aspects of these laws. For instance, there is no mechanism in most right-to-try laws to help patients seeking to access experimental therapeutics financially. Indeed, pointedly, such bills go out of their way to state that health insurance companies do not have to pay for suc treatments and can be interpreted to state that they don’t have to pay for treating complications arising from the use of right-to-try drugs or devices. Given that such bills also allow pharmaceutical companies to charge for experimental therapeutics and such expenses can be very high, this effectively means that only the rich or those skilled (or whose families are skilled) at using social media to raise a lot of money fast could potentially access right-to-try.
These laws also explicitly remove patient protections in that most of them state that doctors recommending right-to-try can’t be sued for malpractice or disciplined by their state medical boards, seemingly no matter how inappropriate or incompetently executed such a request might be. Nor can drug manufacturers be sued. Basically, these laws tell terminally ill patients: Good luck. You’re on your own. And don’t sue if things go bad, no matter what. Given that right-to-try laws also only require that experimental therapeutics have passed phase I trials and still be in clinical trials to be eligible, there’s a high probability of adverse events and harm. Indeed, I not uncommonly laugh derisively and contemptuously whenever I hear a Goldwater Institute flack claim with a straight face that right-to-try only allows drugs that have been shown to be safe to be used, because phase I trials generally only have a few dozen patients followed briefly. Let’s just put it this way: No one who knows what he’s talking about views drugs that have passed phase I trials as having been shown to be safe. At best, such drugs have been shown not to have high levels of life-threatening toxicity.
Of course, the biggest flaw in these laws is that it is federal law, not state law, that controls drug approval. Right-to-try laws can say that terminally ill patients have the “right” to access experimental therapeutics, but it is the FDA that determines whether they, in fact, do. Companies are understandably reluctant to grant access to experimental therapeutics without the FDA’s prior approval because (1) the FDA will not look kindly upon it and they want FDA approval and (2) if there are any adverse events it could harm their chances of winning approval for their drugs. Also, the FDA does have what it calls its Expanded Access Program (sometimes referred to as Compassionate Use) already to allow terminally ill patients to access experimental therapeutics, and it does it without removing patient protections under Institutional Review Board (IRB) supervision. Moreover, the FDA already grants the overwhelming majority of Expanded Access requests. Indeed, as I pointed out, thus far, after two and a half years of existence, right-to-try has been a miserable failure. The Goldwater Institute can’t identify a single patient who has received an experimental drug under a state right-to-try law, although it claims to know of 40-60. Meanwhile a quack like Stanislaw Burzynski has abused right-to-try. Meanwhile, the only patient I’ve been able to find who actually used right-to-try died.
Terminally ill patients in California will be able to try potentially life-saving medication before it passes FDA final review thanks to a new piece of legislation inspired by the movie “Dallas Buyers Club.”
The bill, dubbed the “Right to Try” law, makes California the 32nd state to allow patients with terminal illnesses to try drugs that have passed the FDA’s Phase 1, but haven’t been fully approved.
Phase 1 is the first stage of drug testing in human patients. Drugmakers earn approval to conduct clinical trials on people after presenting the results of successful trials on animals, according to the FDA. After presenting the data — and a plan for human trials — the FDA determines whether drug companies can go forward with additional testing.
Patients can try experimental treatments only after exhausting all other options, according to the libertarian think tank Goldwater Institute, and the patients’ treatments with Phase 1 drugs cannot be included as data in ongoing clinical trials.
Of course, as I pointed out before when I discussed the California bill, this description is utter bollocks. In a way, the California bill (now law) is worse than the average state right-to-try law. It doesn’t actually require that the patient be terminally ill, only that he has an “immediately life-threatening disease or condition.” As I put it at the time, that’s incredibly broad. A severe case of pneumonia could be “immediately life-threatening.” A heart attack is definitely “immediately life-threatening.” A stroke is “immediately life-threatening.” “Immediately life-threatening” is not the same thing as “terminal.” Yet AB-1668 tries to have it both ways, as it defines “immediately life-threatening disease or condition” as “a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months.” That implies something less acute, but “within a matter of months” encompasses more immediately life-threatening diseases as well.
You could ask, quite reasonably: Why does this matter? One reason is that it’s California, the most populous state in the country. Any law passed in California matters. California is always the biggest prize, and right-to-try advocates were bitterly disappointed when Gov. Brown vetoed a previous right-to-try bill last year.
Unfortunately, the Goldwater Institute has been very effective in co-opting terminally ill patients to use the considerable justified sympathy voters and legislators feel for them to lobby for right-to-try:
In a guest column for the Washington Post, 32-year-old Matthew Bellina says Right to Try laws are an improvement on the FDA’s Expanded Access program because they stipulate that the FDA won’t shut down or delay clinical trials if an experimental treatment goes wrong.
Because derailing clinical trials can deal a significant blow to drug companies that have poured millions of dollars into research and development, drug companies are less likely to sponsor terminally ill patients without guarantees that the FDA won’t retaliate for failed treatment.
Bellina, a military veteran and father who has terminal ALS — amyotrophic lateral sclerosis, also called Lou Gehrig’s disease — testified before the Senate on a federal version of Right to Try.
Turning down someone dying of Lou Gehrig’s disease is pretty much close to impossible for a politician, even if the legislation being proposed is profoundly anti-patient, as right-to-try is. Also, this is one of the most pernicious aspects of right-to-try, as you will see. So let’s segue to the federal right-to-try bill. Gov. Brown might have buckled and signed what I like to refer to as “placebo legislation,” which makes legislators feel good and believe that they’ve done something when in reality they’ve done nothing, but the federal bill is where the action is because that’s the real goal of the Goldwater Institute, to weaken and then ultimately neuter the FDA. The Goldwater Institute is politically savvy enough not to come right out and explicitly say this, but other libertarians are not.
A week ago, hearings were held on a federal right-to-try bill, S.2912, known as The Trickett Wendler Right to Try Act of 2016. This is a bill being pushed by Republican U.S. Sen. Ron Johnson. Interestingly, as the bill has been US Senate Committee on Health, Education, Labor, and Pensions, Johnson used his position as committee chair of the US Senate Committee on Homeland Security and Government Affairs to hold hearings on the bill, even though it has nothing to do with his committee’s purview. Sen. Johnson’s opening statement is basically a rehash of Goldwater Institute talking points, complete with the usual anecdotes about patients with terminal illnesses who might have been saved:
Despite the legal uncertainty there are doctors willing to jeopardize their practice to give patients needed, but unfortunately unapproved, treatments. One of them is Houston oncologist Dr. Ebrahim Delpassand. Even though the FDA has told him no, he bravely continues to treat patients under his state’s law. Now nearly 80 patients, whose chance of survival would be, as he puts it, “close to none,” are alive thanks to his treatment.
This caught my attention, as this is a potentially verifiable claim. There is a video of Dr. Delpassand giving a statement included in the testimony:
Whoa. He’s with Excel Diagnostics, the very same company that I discussed when I looked into the one patient in Texas whom I could find who had accessed right-to-try and who had not been saved. Contrary to Sen. Johnson’s claims, he is not an oncologist; he is a radiologist. Of course, nothing Dr. Delpassand claims in his video statement shows that 80 patients who would have died have been saved, thanks to his being a brave maverick doctor willing to buck the FDA. One notes a highly one-sided account designed to make Dr. Delpassand look as good as possible. In any case, the therapy discussed by Dr. Delpassand does have potential, as I mentioned before. However, one thing that stood out to me was how the Goldwater Institute reached out to Dr. Delpassand. So basically, right-to-try allowed Dr. Delpassand to charge for the use of his treatment, even though it is not FDA-approved. Not surprisingly, the Goldwater Institute is painting this example as the nefarious FDA preventing patients from saving their lives, even though this treatment is not curative, as I described. He’s also a flack for the Goldwater Institute, having participated in a promotional video touting right-to-try:
So his evidence is that “many of these patients were given three or six months to live” and are alive a year later? Seriously? Stanislaw Burzynski uses the same argument about the patients he treats.
In any case, as I pointed out three weeks ago, the federal right-to-try bill is even worse than state right-to-try bills because (1) it would actually do something and (2) what it would do would be very, very bad for patients indeed. For example, it would forbid the FDA from considering adverse events suffered by patients utilizing experimental drugs under right-to-try when considering a drug for approval. Seriously, it says that. A patient could die, clearly as a result of an experimental drug, and the FDA would be explicitly barred from considering that information when deciding whether to approve the drug or not.
Speaking of Stanislaw Burzynski, I couldn’t help but note the testimony of Peter Lurie, MD, MPH. He repeated the same points about how the FDA’s Expanded Access Program rarely rejects requests and then notes:
However, even patients with serious or life-threatening diseases and conditions require protection from unnecessary risks, particularly as, in general, the products they are seeking through expanded access are unapproved – and may never be approved. Moreover, FDA is concerned about the ability of unscrupulous individuals to exploit such desperate patients. Thus, with every request, FDA must determine that the potential patient benefit from the investigational drug justifies the potential risks and that the potential risks are not unreasonable in the context of the disease or condition to be treated.
“Unscrupulous individuals”? That would well describe Stanislaw Burzynski. It could also describe pharmaceutical companies willing to profit off of drugs that made it through phase I studies but are not approved yet.
Fortunately, for now at least, the federal right-to-try bill has been blocked:
Republican U.S. Sen. Ron Johnson’s push for a right-to-try bill ran up against the reality of hardball politics Wednesday.
Johnson’s measure to allow terminally ill patients to receive experimental drugs not approved by the Food and Drug Administration was blocked by Senate Minority Leader Harry Reid (D-Nev.).
Johnson sought to move the bill through unanimous consent, meaning one senator could halt its progress. And that’s what Reid did, blunting a Johnson initiative for the second time in recent months. In July, Reid blocked Johnson’s bill to protect federal whistleblowers from retaliation.
Johnson faces a tough re-election fight against Democrat Russ Feingold, so any move to get legislation through by a parliamentary maneuver was always going to be difficult.
And it’s even harder since Democrats are still upset that Republicans have blocked President Barack Obama’s nominee to the U.S. Supreme Court, Merrick Garland.
Reid said he understood the “seriousness” of the Johnson proposal and acknowledged “the urgency that patients and their families feel when they’re desperate for new treatments.”
In objecting to the measure, Reid said Johnson’s bill didn’t have bipartisan support — there were 40 Republican co-sponsors and two Democrats. He said the bill didn’t go through the hearing process where all the major players on the issue have voice. The Johnson-chaired Homeland Security & Governmental Affairs panel held two hearings on the subject.
“I think we should have had a hearing on Merrick Garland,” Reid said on the Senate floor.
This is what I would call doing the right thing for the wrong reason. Unfortunately, that’s what happens in politics a lot. I’ll take it, though. If state right-to-try bills are basically symbolic rants against the FDA, the passage of a federal right-to-try bill would be a disaster for patients and the clinical trial process.
from ScienceBlogs http://ift.tt/2dwd1gJ
I’ve referred to so-called “right to try” laws as a cruel sham.on more than one occasion. Since 2014, these laws, all based on a template provided by the libertarian Goldwater Institute, have been proliferating at the state level with the help of lobbying by the aforementioned Goldwater Institute and a concept that makes it pitifully easy to caricature opposition to these laws as wanting to heartlessly snatch away from terminally ill patients the last chance at life while laughing and twirling one’s mustache like Snidely Whiplash. Not surprisingly, state legislatures all over the country have found such laws irresistible, leading to their passage in over 30 states in just two and a half years. Over the last week, right-to-try has had a major victory in that, contrary to what he did last year and contrary to the hope of science advocates, California Governor Jerry Brown signed the right-to-try bill (AB-1668) that was passed earlier this month. However, it has also suffered a major defeat in that a couple of days ago the federal right-to-try bill was blocked in the Senate.
The basic premise behind right-to-try laws is that people are dying in droves because the FDA is too slow and too hidebound to allow dying patients access to experimental drugs that are still undergoing clinical trials to be approved by the FDA. No, really, that’s the argument libertarians make, that the FDA is literally (yes, I mean literally—just ask Nick Gillespie and Ronald Bailey) “killing” people. Enter right-to-try, laws that purport to allow terminally ill patients (or, in some cases, patients with life-threatening but not necessarily terminal illnesses) to access experimental therapeutics in a desperate bid to save their lives. Sounds reasonable on the surface, right? What is assiduously not mentioned are other libertarian-based aspects of these laws. For instance, there is no mechanism in most right-to-try laws to help patients seeking to access experimental therapeutics financially. Indeed, pointedly, such bills go out of their way to state that health insurance companies do not have to pay for suc treatments and can be interpreted to state that they don’t have to pay for treating complications arising from the use of right-to-try drugs or devices. Given that such bills also allow pharmaceutical companies to charge for experimental therapeutics and such expenses can be very high, this effectively means that only the rich or those skilled (or whose families are skilled) at using social media to raise a lot of money fast could potentially access right-to-try.
These laws also explicitly remove patient protections in that most of them state that doctors recommending right-to-try can’t be sued for malpractice or disciplined by their state medical boards, seemingly no matter how inappropriate or incompetently executed such a request might be. Nor can drug manufacturers be sued. Basically, these laws tell terminally ill patients: Good luck. You’re on your own. And don’t sue if things go bad, no matter what. Given that right-to-try laws also only require that experimental therapeutics have passed phase I trials and still be in clinical trials to be eligible, there’s a high probability of adverse events and harm. Indeed, I not uncommonly laugh derisively and contemptuously whenever I hear a Goldwater Institute flack claim with a straight face that right-to-try only allows drugs that have been shown to be safe to be used, because phase I trials generally only have a few dozen patients followed briefly. Let’s just put it this way: No one who knows what he’s talking about views drugs that have passed phase I trials as having been shown to be safe. At best, such drugs have been shown not to have high levels of life-threatening toxicity.
Of course, the biggest flaw in these laws is that it is federal law, not state law, that controls drug approval. Right-to-try laws can say that terminally ill patients have the “right” to access experimental therapeutics, but it is the FDA that determines whether they, in fact, do. Companies are understandably reluctant to grant access to experimental therapeutics without the FDA’s prior approval because (1) the FDA will not look kindly upon it and they want FDA approval and (2) if there are any adverse events it could harm their chances of winning approval for their drugs. Also, the FDA does have what it calls its Expanded Access Program (sometimes referred to as Compassionate Use) already to allow terminally ill patients to access experimental therapeutics, and it does it without removing patient protections under Institutional Review Board (IRB) supervision. Moreover, the FDA already grants the overwhelming majority of Expanded Access requests. Indeed, as I pointed out, thus far, after two and a half years of existence, right-to-try has been a miserable failure. The Goldwater Institute can’t identify a single patient who has received an experimental drug under a state right-to-try law, although it claims to know of 40-60. Meanwhile a quack like Stanislaw Burzynski has abused right-to-try. Meanwhile, the only patient I’ve been able to find who actually used right-to-try died.
Terminally ill patients in California will be able to try potentially life-saving medication before it passes FDA final review thanks to a new piece of legislation inspired by the movie “Dallas Buyers Club.”
The bill, dubbed the “Right to Try” law, makes California the 32nd state to allow patients with terminal illnesses to try drugs that have passed the FDA’s Phase 1, but haven’t been fully approved.
Phase 1 is the first stage of drug testing in human patients. Drugmakers earn approval to conduct clinical trials on people after presenting the results of successful trials on animals, according to the FDA. After presenting the data — and a plan for human trials — the FDA determines whether drug companies can go forward with additional testing.
Patients can try experimental treatments only after exhausting all other options, according to the libertarian think tank Goldwater Institute, and the patients’ treatments with Phase 1 drugs cannot be included as data in ongoing clinical trials.
Of course, as I pointed out before when I discussed the California bill, this description is utter bollocks. In a way, the California bill (now law) is worse than the average state right-to-try law. It doesn’t actually require that the patient be terminally ill, only that he has an “immediately life-threatening disease or condition.” As I put it at the time, that’s incredibly broad. A severe case of pneumonia could be “immediately life-threatening.” A heart attack is definitely “immediately life-threatening.” A stroke is “immediately life-threatening.” “Immediately life-threatening” is not the same thing as “terminal.” Yet AB-1668 tries to have it both ways, as it defines “immediately life-threatening disease or condition” as “a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months.” That implies something less acute, but “within a matter of months” encompasses more immediately life-threatening diseases as well.
You could ask, quite reasonably: Why does this matter? One reason is that it’s California, the most populous state in the country. Any law passed in California matters. California is always the biggest prize, and right-to-try advocates were bitterly disappointed when Gov. Brown vetoed a previous right-to-try bill last year.
Unfortunately, the Goldwater Institute has been very effective in co-opting terminally ill patients to use the considerable justified sympathy voters and legislators feel for them to lobby for right-to-try:
In a guest column for the Washington Post, 32-year-old Matthew Bellina says Right to Try laws are an improvement on the FDA’s Expanded Access program because they stipulate that the FDA won’t shut down or delay clinical trials if an experimental treatment goes wrong.
Because derailing clinical trials can deal a significant blow to drug companies that have poured millions of dollars into research and development, drug companies are less likely to sponsor terminally ill patients without guarantees that the FDA won’t retaliate for failed treatment.
Bellina, a military veteran and father who has terminal ALS — amyotrophic lateral sclerosis, also called Lou Gehrig’s disease — testified before the Senate on a federal version of Right to Try.
Turning down someone dying of Lou Gehrig’s disease is pretty much close to impossible for a politician, even if the legislation being proposed is profoundly anti-patient, as right-to-try is. Also, this is one of the most pernicious aspects of right-to-try, as you will see. So let’s segue to the federal right-to-try bill. Gov. Brown might have buckled and signed what I like to refer to as “placebo legislation,” which makes legislators feel good and believe that they’ve done something when in reality they’ve done nothing, but the federal bill is where the action is because that’s the real goal of the Goldwater Institute, to weaken and then ultimately neuter the FDA. The Goldwater Institute is politically savvy enough not to come right out and explicitly say this, but other libertarians are not.
A week ago, hearings were held on a federal right-to-try bill, S.2912, known as The Trickett Wendler Right to Try Act of 2016. This is a bill being pushed by Republican U.S. Sen. Ron Johnson. Interestingly, as the bill has been US Senate Committee on Health, Education, Labor, and Pensions, Johnson used his position as committee chair of the US Senate Committee on Homeland Security and Government Affairs to hold hearings on the bill, even though it has nothing to do with his committee’s purview. Sen. Johnson’s opening statement is basically a rehash of Goldwater Institute talking points, complete with the usual anecdotes about patients with terminal illnesses who might have been saved:
Despite the legal uncertainty there are doctors willing to jeopardize their practice to give patients needed, but unfortunately unapproved, treatments. One of them is Houston oncologist Dr. Ebrahim Delpassand. Even though the FDA has told him no, he bravely continues to treat patients under his state’s law. Now nearly 80 patients, whose chance of survival would be, as he puts it, “close to none,” are alive thanks to his treatment.
This caught my attention, as this is a potentially verifiable claim. There is a video of Dr. Delpassand giving a statement included in the testimony:
Whoa. He’s with Excel Diagnostics, the very same company that I discussed when I looked into the one patient in Texas whom I could find who had accessed right-to-try and who had not been saved. Contrary to Sen. Johnson’s claims, he is not an oncologist; he is a radiologist. Of course, nothing Dr. Delpassand claims in his video statement shows that 80 patients who would have died have been saved, thanks to his being a brave maverick doctor willing to buck the FDA. One notes a highly one-sided account designed to make Dr. Delpassand look as good as possible. In any case, the therapy discussed by Dr. Delpassand does have potential, as I mentioned before. However, one thing that stood out to me was how the Goldwater Institute reached out to Dr. Delpassand. So basically, right-to-try allowed Dr. Delpassand to charge for the use of his treatment, even though it is not FDA-approved. Not surprisingly, the Goldwater Institute is painting this example as the nefarious FDA preventing patients from saving their lives, even though this treatment is not curative, as I described. He’s also a flack for the Goldwater Institute, having participated in a promotional video touting right-to-try:
So his evidence is that “many of these patients were given three or six months to live” and are alive a year later? Seriously? Stanislaw Burzynski uses the same argument about the patients he treats.
In any case, as I pointed out three weeks ago, the federal right-to-try bill is even worse than state right-to-try bills because (1) it would actually do something and (2) what it would do would be very, very bad for patients indeed. For example, it would forbid the FDA from considering adverse events suffered by patients utilizing experimental drugs under right-to-try when considering a drug for approval. Seriously, it says that. A patient could die, clearly as a result of an experimental drug, and the FDA would be explicitly barred from considering that information when deciding whether to approve the drug or not.
Speaking of Stanislaw Burzynski, I couldn’t help but note the testimony of Peter Lurie, MD, MPH. He repeated the same points about how the FDA’s Expanded Access Program rarely rejects requests and then notes:
However, even patients with serious or life-threatening diseases and conditions require protection from unnecessary risks, particularly as, in general, the products they are seeking through expanded access are unapproved – and may never be approved. Moreover, FDA is concerned about the ability of unscrupulous individuals to exploit such desperate patients. Thus, with every request, FDA must determine that the potential patient benefit from the investigational drug justifies the potential risks and that the potential risks are not unreasonable in the context of the disease or condition to be treated.
“Unscrupulous individuals”? That would well describe Stanislaw Burzynski. It could also describe pharmaceutical companies willing to profit off of drugs that made it through phase I studies but are not approved yet.
Fortunately, for now at least, the federal right-to-try bill has been blocked:
Republican U.S. Sen. Ron Johnson’s push for a right-to-try bill ran up against the reality of hardball politics Wednesday.
Johnson’s measure to allow terminally ill patients to receive experimental drugs not approved by the Food and Drug Administration was blocked by Senate Minority Leader Harry Reid (D-Nev.).
Johnson sought to move the bill through unanimous consent, meaning one senator could halt its progress. And that’s what Reid did, blunting a Johnson initiative for the second time in recent months. In July, Reid blocked Johnson’s bill to protect federal whistleblowers from retaliation.
Johnson faces a tough re-election fight against Democrat Russ Feingold, so any move to get legislation through by a parliamentary maneuver was always going to be difficult.
And it’s even harder since Democrats are still upset that Republicans have blocked President Barack Obama’s nominee to the U.S. Supreme Court, Merrick Garland.
Reid said he understood the “seriousness” of the Johnson proposal and acknowledged “the urgency that patients and their families feel when they’re desperate for new treatments.”
In objecting to the measure, Reid said Johnson’s bill didn’t have bipartisan support — there were 40 Republican co-sponsors and two Democrats. He said the bill didn’t go through the hearing process where all the major players on the issue have voice. The Johnson-chaired Homeland Security & Governmental Affairs panel held two hearings on the subject.
“I think we should have had a hearing on Merrick Garland,” Reid said on the Senate floor.
This is what I would call doing the right thing for the wrong reason. Unfortunately, that’s what happens in politics a lot. I’ll take it, though. If state right-to-try bills are basically symbolic rants against the FDA, the passage of a federal right-to-try bill would be a disaster for patients and the clinical trial process.
