Chandra Ghose, PhD., Chief Scientific Officer of Emily’s Entourage
How can we navigate the looming threat of antimicrobial resistance (AMR) and shape the future of healthcare by 2049? Dr. Chandra Ghose, Chief Scientific Officer at Emily's Entourage, delves into the complexities of AMR, highlighting the critical need for global collaboration and innovative funding models. Drawing inspiration from the rapid response to the COVID pandemic, Dr. Ghose explores the economic challenges hindering antibiotic development and envisions a future where technology, particularly artificial intelligence, plays a pivotal role in personalized antibiotic solutions.
Chandra Ghose serves as the Chief Scientific Officer of Emily’s Entourage, a non-profit organization that funds research and drug development for individuals in the final 10% of the cystic fibrosis (CF) community that do not benefit from currently available therapies.
Before joining EE, Chandra founded Bioharmony Therapeutics, an early-stage biotech startup specializing in developing novel antimicrobials to combat drug-resistant bacterial infections. In advance of that, she worked at the Aaron Diamond AIDS Research Center, an affiliate of Rockefeller University, where she focused her research on developing life-saving vaccines. She was a postdoctoral fellow at Harvard Medical School in the Division of Infectious Diseases, Massachusetts General Hospital.
Chandra holds a PhD in microbiology from New York University School of Medicine and a bachelor’s degree from Saint Louis University in biology and theology. She is a Health Innovators Fellow at the Aspen Institute’s Global Leadership Network, and a Trustee at the Trinity School in New York. An avid volunteer and entrepreneur, Chandra is involved in a number of causes close to her heart, including Beyond Pads, a non-profit she founded that provides menstrual products to children living in shelters.
Born in Kolkata, India, Chandra now resides in New York City with her husband, daughter, and their pandemic puppy, Jaws.
Show Notes
Chandra Ghose shares her scientific background in infectious disease and developing antimicrobials. [03:40]
A healthcare vision of the future based on research from the UK government. [10:04]
A multi pronged medical solution to a bleak future prediction. [13:33]
Why don't we see more development of new antibiotics in the marketplace today? [17:42]
How can we ensure the development of new, life-saving antibiotics? [22:56]
Are there new approaches to treating infectious disease that go beyond antibiotics? [25:58]
Will we get to a point in the future where we don't have human trials for new treatments? [30:33]
What’s one change that could have the greatest positive impact in our healthcare future? [34:05]
Transcript
Chandra Ghose 00:07
We have the capacity to really rise to the occasion when we are met with these types of challenges. And we saw this with the COVID pandemic, we've never seen a vaccine trial move that fast. We've never seen different countries, companies, governments coming together to supercharge the development of the COVID vaccines. So, I think there are lots of different parts to this complex problem of Amr. It would require a multi pronged approach, it would require everyone to come together and work together to address this issue.
Jason Helgerson 01:58
Today's guests Dr. Chandra Ghosh is the Chief Scientific Officer at Emily's Entourage, a nonprofit organization that fast tracks research for new treatments and a cure for cystic fibrosis. With a PhD in microbiology from New York University School of Medicine, and extensive research experience, including Aaron Diamond's AIDS Research Center, Chandra has dedicated her career to developing life saving vaccines and treatments. Chandra's expertise has earned her recognition and awards from prestigious organizations such as the Infectious Disease Society of America. Passionate about raising awareness of antimicrobial resistance, she volunteers her time with organizations such as the C Diff Foundation and the Pew Charitable Trusts Supermoms Against Superbugs program. In addition to all her work as a scientist, Chandra is also an entrepreneur. Chandra founded Bioharmony Therapeutics, a biotech startup specializing in combating drug resistant bacterial infections. Prepared to be inspired by Dr. Ghose's journey as an entrepreneur, scientist and advocate for a healthier world. I'm Jason Helgerson, and you're listening to Health2049 and it's my pleasure to welcome Dr. Chandra Ghosh to the program. Chandra, welcome.
Chandra Ghose 03:21
Thank you, Jason. Thank you for having me on today.
Jason Helgerson 03:24
Well Chandra it's great to have you here with us today, we always like to start by giving our guests the opportunity to tell our audience a bit more about their interesting background. So tell us a bit more about your journey that got you to where you are today and your career.
Chandra Ghose 03:40
Yeah. So I always start by talking about going way back. I grew up in Calcutta, India and came to the US for college. I guess the seminal moments in my life have in many ways been defined by infectious diseases that I've been exposed to. So for example, growing up in India, we were always warned not to drink tap water, make sure the water is boiled, if it's the monsoon season, don't have ice cream and so on and so forth. So whether it's cholera, typhoid, these are infections that I had, my friends had, my family, but we always recovered, thanks to really good antibiotics. So, from the get go, even when I was younger, I kind of knew the value of antibiotics, the value of vaccines, and I guess that common thread and interest kind of propelled me as I grew up, went to school, college, grad school and then as my career as an entrepreneur, starting Bioharmony Therapeutics and my current position as the Chief Scientific Officer at Emily's Entourage. One really interesting anecdote and maybe this is pretty unique to me and maybe you won't have another guest on your podcast who has actually experienced a plague outbreak. When I was in high school in the 1990s, there was a plague outbreak in India and we lived through that nothing happened, other than we had to wear knee high socks in the middle of Calcutta summers and go to school like that to prevent being bitten by fleas and ticks. So that was kind of how my formative years spent in India. When I came to the US, I did my PhD at NYU. I was exposed to something really interesting, my thesis was on H. pylori, which is, again, a really interesting bacteria, one of the few bacteria that are related to cancer. So, H. pylori is known to be one of the causative agents of gastric cancer. I did my postdoc at MGH, and that was probably the two most important years of my life. I started off by working in a lab that was developing vaccines, worked on cholera, again, very close, I have had cholera in the past. They were working with an institute called the Diarrheal Institute in Dhaka, Bangladesh and that's what I was initially working on for a month or two. And at that point, there was an outbreak of C. diff at MGH and it was really interesting to see how quickly academic labs and the MDs and the nascent biotech at Boston in 2005, kind of jumping in and springing into action to develop vaccines to treat C. diff infections and therapeutics, such as microbiome pills, for example, that just got approved by Seres Therapeutics, they were being spun out of the lab as I was there. So that kind of put a little bit of the entrepreneur's translational bug in me and I came back to New York in 2007 and I joined David Ho's lab at Rockefeller University. David Ho is really well known in the HIV world for developing therapeutics for HIV and initially, that's what I was working on, but very quickly, I started working on developing vaccines for C. diff. So in a way I continued the work I was doing at Mass General Hospital at Aaron Diamond AIDS Research Center here in New York. Following that, I started up Bioharmony Therapeutics. It was a huge leap of faith, I had never done anything like that. And the work there was to develop new antimicrobials to address this global silent pandemic, which is antimicrobial resistant, which kills hundreds of 1000s of people every year. That's what I spent the past eight years of my life doing. And I recently transitioned to my current position at Emily's Entourage, which is an organization like you said, that funds and accelerates research for the final 10% of CF patients who do not benefit from the amazing modulators that Vertex has developed over the past 20 some odd years. So at Emily's Entourage, my job is to look at really interesting, innovative research and find ways to fund it and accelerate it so that these therapeutics can make it to the patients who really need them the most. There's a lot of common things between infectious diseases as well as ultra rare diseases such as the final 10%, which is this roadblock of funding, this roadblock of return on investment and that's kind of been another reason why I joined Emily's Entourage because I feel my training in the infectious disease world where, I'm sure we'll touch on this at some point where it's funding economics is what holds back the development of novel antimicrobials that is so, so needed, and it's a similar sort of situation and for the final 10% of patients who do not benefit from the current modulators. So that's pretty much me in a nutshell.
Jason Helgerson 09:31
All right. Well, thank you so much for that. And I'm really excited to ask you this next question, because on Health2049, we really have not had that many scientists, people who are on the frontlines of developing new innovative treatments to complex conditions and diseases. And so I think I'm dying to hear how you're going to answer this question, which is a standard question we ask all our guests, which is what does health and healthcare look like in the year 2049?
Chandra Ghose 10:04
This is actually a really easy question for me. So about seven or eight years ago, the UK government spent quite a bit of time and resources to ask this question. It wasn't 2049. But the question was, what does antimicrobial resistance look like in 2050? So I'll read out some numbers to you, which, frankly, are so frightening that as we're on somewhat of the other side of the global COVID pandemic, it is even more scary. So the number that the World Health Organization published, thanks to this O'Neill Report was that by 2050, up to 10 million deaths could occur annually, affecting economies and shifting more people into poverty. That's just one aspect of antimicrobial resistance. So today, as we speak, more than 700,000 deaths per year is attributed to antimicrobial resistance. And by the year 2050, that number is going to be 10 million unless we do something about this today. And this number, again, it sounds crazy and huge, but I can't imagine 10 million deaths per year, especially affecting those who are the most vulnerable. This would affect low and middle income countries, mostly, they are the ones again, who bear the brunt of a lot of these health inequities. EMR could also significantly affect agricultural production, again, affecting economic and food security, again, for those in the low and lower middle income countries. So I think whether you call it 2049, or 2050, what keeps me up at night is I've envisioned this scenario from where I would be in 2050. So in 2050, I'm in my 70s, hopefully, I won't need it, but let's say I have routine surgery. Nowadays you have routine surgery and if you get an infection, you just reach over, call your doctor, and you can get a prescription for pretty widespread antibiotics, but in 2050, that may not be the case, you may be going to the gym and getting Mrsa. You may be shaving your face every day and you can make it and get an infection and die from that. Common procedures, for example, childbirth, a knee replacement, heart valve replacement, I mean, forget, cancer care, or even transplants. So imagine those routine day to day activities or even routine day to day medical interventions, they could become a life or death decision at that point, because we would be at a post antibiotic age. So that is where I see Health2049 being unless we do something about antimicrobial resistance today.
Jason Helgerson 13:10
All right, so tell us what should we do about it today or in the near future in order to prevent, and I'm quite scared about the future state that you just described, if we don't do something, so what do we need to do to ensure that we have the the treatments necessary to prevent those 10 million deaths.
Chandra Ghose 13:33
So even though I painted a pretty bleak future, what gives me a lot of hope is that we have the capacity to really rise to the occasion when we are met with these types of challenges. And we saw this with the COVID pandemic, like we've never seen a vaccine trial move that fast. We've never seen different countries, companies, the government coming together to supercharge the development of the COVID vaccines where we ended up getting two vaccines with upwards of 96-97% efficacy and while everyone was excited about that, the thought that was running through my head was, do we really need this AMR pandemic to be that severe before we do something about it? So I think there are lots of things that are already in place. There's tons of exciting research happening. We do have a little bit more vaccine hesitancy now post COVID and you can see those in the numbers of small percentages, but it's still there, where the normal childhood vaccinations are decreasing. So at this point, I would say we should think of ways to fund basic science research. We should think of ways to pump up public health. We should put in resources in the CDC so that when the time comes, they can communicate with people and assure people that they do have our backs, they do know what they're doing. So I think there are lots of different parts to this complex problem of AMR and it would require something called a One Health Approach. So it's not just we focus on human health, but there's a whole aspect of the environment playing a major role in development of antimicrobial resistance. So, I think different sectors have to come together to address this issue. The government can play a huge role, and they are trying to do like, at least the US government is trying to do its part, and also to improve the appropriate use of antibiotics, because we've used antibiotics so easily and so much that it's leading to this development of antimicrobials. And also, we have to make sure that we have a stockpile of antibiotics for the cases where the bacteria is so resistant, that you need one or two or even three different combinations of antibiotics to address it. So not just a stockpile for things like anthrax, but stockpile for Mrsa infection, stockpile common bacterial infections, diarrheal infections, and so on. So, it would require a multi pronged approach. It would require everyone to come together and work together to address this issue. So it's complex.
Jason Helgerson 16:45
So I would like to maybe double click into a little bit about this need for a multi prong strategy. I'm just wondering, of those prongs, I hear that the need to begin to really prescribe antibiotics, the ones that exist today, to prescribe differently to not over prescribe. I hear the need for the development of new antibiotics. I also hear the need to stockpile antibiotics that exist, so that they are easily available if there are outbreaks. And so I'm wondering, are any of those strategies more important than others? I mean, I'm particularly interested in this idea around the development of new antibiotics. And obviously, you started a company to do such work. I'm just wondering why we don't see more development of new antibiotics in the marketplace today.
Chandra Ghose 17:42
The short answer is economics. You can always follow the money and the reason behind it is, back in the 1990s - 1980s, which was kind of known as the golden era of antibiotics, every single pharmaceutical company at that point, was developing some sort of antibiotic. What happened very quickly after that some of the more traditional antibiotics became generic, and some of the more specialized antibiotics were being held for the most serious cases. So from a pharmaceutical company's point of view, and we need pharmaceutical companies to develop these large scale to do the clinical trials that need 10s of 1000s of people to do these trials when you bring a drug to market, if you're telling the pharmaceutical company, thanks so much, you spend a billion dollars to develop this drug but now we won't use it, these will only be used in very rare conditions when those patients really need it. So there is a huge disconnect between how essential these drugs are and then how these drugs are paid for. I'll give you a very easy example, let's say you go to a hospital and you get heart valve surgery, and you get infected with Mrsa in the valves, it's a really horrible infection to get. The first drugs they'll try at the more generic types. If those drugs fail, more and more of those narrow spectrum drugs will be used to treat these infections. And what happens in the meantime, is that patients are getting sicker and sicker. One of the issues Jason, you know better than anyone, is the whole idea of a DRG. You will pay, I'm going to make this up, let's say $5,000 for a heart valve infection and whether you get an infection or not, that is covered within that $5,000. So a pharmacy, the formulary in the hospital sometimes may not even carry those very expensive and by very expensive I mean $20,000 at most, antibiotics that could make the difference between life and death in these patients. So there's a huge economic issue when it comes to incentivizing startups to develop antibiotics. For example, at Bioharmony Therapeutics, we were developing a non-traditional anti microbial, which is a phage license for the treatment of pneumonia for patients who have Acinetobacter, and Acinetobacter is the superbug of superbugs, if you will. It's number one on CDCs list of priority pathogens because there's very few drugs that can treat a multi drug resistant Acinetobacter infection. But what we faced very early on was this issue with funding. VCs were not interested because they'd been burned in the past. Pretty much every well known VC had invested in an antimicrobial company, many of them were able to get those drugs approved, they ended up on WHOs list of essential medicines, but then went bankrupt because they couldn't sell the drugs. So there's a whole group of antimicrobial companies that have gone through that. So VCs are not interested in funding antimicrobials because they know in the end, there is no acquisition by pharmaceutical companies to acquire these startups. Even if you have a company that's publicly traded, let's say they acquire the assets of a smaller startup that are developing antimicrobials, you can see their shares, prices actually fall on the day those announcements are made. So because of this economic issue, more and more antibiotics are not being developed, because it costs the same amount of money, whether developing a cancer drug or an antimicrobial. So that's where we are. And the Pasteur Act that we just touched upon is trying to address that where you're trying to delink economic incentives from the development of these drugs.
Jason Helgerson 22:11
So it sounds like there's a pretty clear market failure, that the traditional market for pharmaceuticals, we need highly specialized drugs to meet the unique needs of individual patients and there doesn't appear to be enough market opportunity there for manufacturers to be willing to invest in the development of these new drugs. And so it sort of screams out for government intervention, screams out for government investment, which it sounds like we've seen legislation introduced to help in that regard, are you optimistic that the government's going to step in here in the not too distant future to help address this market failure and hopefully lead to the development of more life saving drugs in this area?
Chandra Ghose 22:56
The Pasteur Act that we talked about was initially introduced first in, I believe 2020, and then it didn't move, and then it got reintroduced this year. I think more and more, maybe not in the US, but we're seeing a lot of the European governments coming together, coming up with innovative ways of delinking income from development of these antibiotics, coming up with different ways of paying for these antibiotics. So it would be almost the most interesting thing I've heard being proposed is this subscription model. So it's almost like a Netflix model, you pay a certain amount of money per month or per year for a drug, whether you use it or not. So whether you're watching 20 shows a day or one show in a month, you pay a certain amount. And that kind of gives cover to a lot of these companies when it comes to economics so that the linking of economics with the amount of drugs being used would be way forward. And I think there's this perception that, at least initially, at least in 2020, that if the Pasteur Act is passed, it wouldn't be seen as a handout to pharmaceutical companies. I think this is changing a little bit post COVID because we've seen Pfizer kind of jump in with a smaller biotech company to move their COVID vaccine forward. So I am hopeful but then that's just me in general, but I think in the next few years we will have to see something move, some sort of a national action plan that would include bipartisan legislation that addresses these issues.
Jason Helgerson 24:46
Gotcha. So one question I have is, and this may be a very naive as a non scientist question, but it feels to me like antibiotics is an old technology in the sense that we've been using antibiotics to treat illness for decades, and it sounds like for a variety of reasons, we're getting to a point where some of these drugs that have served the global health well, their effectiveness is in serious threat. But are there at all down the line in the future, new approaches to treating infectious disease? Going beyond antibiotics? Is there a new technology, a new approach that people can be optimistic about? Or is it, we're going to be in for a hard, long slog of developing drugs in similar ways to address these very specific superbugs that sit out there in threat. And so I'm just interested to see as you look forward towards 2049, is there any sort of potential for new ideas to come to the fore between now and then?
Chandra Ghose 25:58
One thing that has come out of all of this is this one Health Action Plan, where addressing human health is not going to be enough, we've seen these amazing antibiotics that have been around for 100 years, since Alexander Fleming and his experiment with the discovery of penicillin and this One Health Approach touches on many different aspects. So if you take the human health aspect we have, the traditional small molecule antibiotics, any kind of antibiotic that you've taken till now is a small molecule, but we are now looking at non-traditional approaches. For example, phage license, bacteriophage therapy, these non traditional therapies are also coming to the forefront. It's almost like an all hands on deck approach. You use small molecules, you use antibacterial products from viruses, which are at the tippy top of the food chain and that's the human health part. The other aspect is animal health. So much of the antibiotics that the world uses today is, 80% almost, used in animal health. We are seeing a movement against that, as well. A lot of different countries, for example, India is promising to kind of move away from using that much. I don't know what would happen in the end, because you have to balance the need for food with the judicious use of antimicrobials in animals. But that is an interesting approach as well. So if we can use all these approaches to decrease the speed or the progress of AMR, I think that would give companies and scientists time to come up with even more innovative approaches to address antimicrobial resistance. So, again, if I could reiterate, we need to create robust national level governance, planning, regulatory legal frameworks to allow for these types of approaches to come to the forefront. It's almost like a G 7 or G 20 approach and these things do get discussed at these G 20 kind of meetings to address AMR. So anything to slow the progress of AMR before 2049 would include environmental approaches, animal health approaches, human health approaches, economics and economic incentives, and so on and so forth. So it's not just the science, but it's also kind of understanding the nuances of where antimicrobial resistance does pop up.
Jason Helgerson 28:50
Gotcha. So it seems like part of the problem here is just, and you know this as well as anyone, the time and cost that it takes to develop a new drug or therapy, that with the need for obviously, the initial research leading to the clinical trials, and eventually to bring a drug are new treatment to the market, that process takes years. I mean, you mentioned what happened during the pandemic for the vaccines, being like a lightspeed compared to what had happened in the past. I hear a lot about the role that technology can play in speeding up the drug development timeline and reducing significantly the costs and whether that technology is artificial intelligence or quantum computing or already what we've achieved is the ability to map the human genome and gather genetic information on large numbers of people. Eventually getting to a point where we don't even have to do human trials for new treatments and this timeline between now and 2049, how optimistic are you that we'll be able to make some scientific breakthroughs that will basically speed up the drug development so that perhaps it'll reduce the cost of some of this and just make it easier for companies to develop these drugs and bring them to market much more quickly than historically has been the case?
Chandra Ghose 30:33
Yeah. So what I'm really excited about artificial intelligence, and where that could take us, and machine learning and so on, we've already seen in the anti microbial development where in the science, at least, or in the research space, AI playing a big role in identifying new small molecules that could address a bacteria with X type of resistant mechanism. We've seen companies that are using AI to look at different bacterial cell wall structures to identify which antibiotics could work against those infections. So, in a way by 2049, is it so unrealistic to imagine a personalized approach to antibiotic development? What if you could make, on a desktop, a small PCR machine, or some sort of machine that could make a small molecule that has different nucleotides thrown on that could address the infection you have right at that point. So you're basically getting rid of every single clinical trial at that point and you're developing personalized antimicrobials to treat each and every person who needs it. And because each small molecule would be different, there hopefully wouldn't be an issue with having wide scale resistance to these small molecules. So I'm quite excited to see where this would go, there's already so much happening in this space. But it's still a very early stage. There's a company that spun out from Princeton called Ara Path that's looking at imaging of various different bacteria to develop antimicrobials that could address or that could get through the cell wall of these bacteria by just doing optical imaging at a grand scale. So, I think we'll get to that point where we may not even need traditional clinical trials because one of the roadblocks for these ultra rare infections, these are still rare in the US, but an Acinetobacter multidrug resistant, Acinetobacter pneumonia is still pretty rare in the US, so to expect a clinical trial of, I don't know, 10,000 people is going to take the company 10 to 15 years and that company wouldn't survive. So I think, from the regulatory perspective, we also need the FDA to open up and acknowledge where these clinical trials are. We've seen a lot of personalized clinical trials in the cancer oncology world and in the rare disease world, like N-of-1 trials. Imagine these as N-of-1 trials, but at the grander scale happening every day in every hospital in every ward.
Jason Helgerson 33:28
Gotcha. Well, a final question for you Chandra and very eager to hear your answer to this, which is, if you could wave a magic wand today and change one thing and with that change would have the greatest positive impact in terms of us reaching the year 2049. Or use the UK of 2050, in a world in which AMR is not only not worse than today, but maybe even the threat is much diminished, by that point, what change would you make?
Chandra Ghose 34:05
So if you asked me to pick one, I would wave a magic wand and come up with some sort of technology that could help us go back 100 years to Alexander Fleming and look at the way he developed penicillin. So a lot of the traditional antibiotics are made by bacteria to kill off other bacteria. I wish we could go back and really dig deep and see whether there was some other technology that could really mind the virus of the human body and see if you look at the top of the food chain, can viruses give us a hint of how to kill bacteria without having resistant pop up at all. So I would go back and be like, Hey, Dr. Fleming, let's look at viruses a little bit more and see what they have to offer because nowadays, if you look at viruses, like CRISPR, gene editing, all of this is coming from pretty simple organism, such as a virus. So if I could go back and look at ways antibiotics were first discovered and made, I would like to come up with an idea that could address this issue without resistance, because 100 years ago, that was the first time we had antibiotics. In Fleming's own words, he basically predicted that within 10 or 20 years his penicillin would become obsolete. And that's literally what happened.
Jason Helgerson 35:42
Well, thank you very much, and we'll have to leave it there but it's been a very exciting episode here on Health2049. And that was Dr. Chandra Ghose's vision for health and healthcare in the year 2049. As always, thank you for listening to Health2049. If you enjoyed what you just heard, please subscribe to us on Apple Music and Spotify and share this podcast with a friend. Thank you and see you next time.
