In this episode, we tell the story of how a deadly infection was successfully treated with viruses, and how this treatment could impact the future of healthcare.
The Power to Rethink Treatment
The World to Come - Episode 5: The Power to Rethink Treatment
TESS VIGELAND: When antibiotics fail to fight off an infection - the options are limited. But a treatment that relies on VIRUSES could change the future of healthcare.
STEFFANIE STRATHDEE: Literally, I signed the consent form for kidney dialysis the day that phage therapy began. He was literally within a couple hours of death. So we're just really, really fortunate and we don’t take it for granted. Every day is a gift.
TESS VIGELAND: So he was a miracle.
SAIMA ASLAM: He was a miracle. Yes. And that miracle is going to hopefully lead to other miracles.
TESS VIGELAND: Coming up… you might find this story hard to believe: a remedy that’s as old as the planet, but a feat of modern medicine in the age of antibiotic-resistant bacteria. We’ll learn about bacteriophage therapy, phage therapy for short. Scientists at the University of California San Diego -- and beyond -- think it could win the global fight against superbugs. The World Health Organization says WITHOUT solutions, drug-resistant diseases could lead to millions of deaths a year by 2050.
TESS VIGELAND: This is The World To Come, a podcast brought to you by Bank of America -- exploring life in the future, starting with the visionaries of today. Featuring clients and partners affiliated with Bank of America. I’m Tess Vigeland, and in this episode: the power to rethink medical treatment.
PATRICK WOOD: I think for the healthcare system overall it's an imperative and I think we need to be forward looking on this issue.
TESS VIGELAND: Antibiotic resistance is one of the major threats to our health in the 21st century.
Bank of America Global Research Analyst Patrick Wood studies this issue as part of his work.
PATRICK WOOD: I lead the medical technology team, and my main role is to look at the health care system and understand what it does.
TESS VIGELAND: What is the definition of antibiotic resistance? What does that mean?
PATRICK WOOD: Antibiotics are a weapon that we employ to destroy bacteria. And over time, and as living organisms that they are, they've evolved if you like a form of defense. So you can obviously have oral but also you can have intravenous antibiotics, and over time bacteria gain resistance through exposure. This is very, very problematic for a number of reasons - not in the least clinical outcomes.
TESS VIGELAND: How did we get here, to this point where antibiotics are becoming ineffective? Is it simple overuse, or is it does it go beyond that?
PATRICK WOOD: It's a plethora of causes. While it's an issue that's been flagged, we've all become quite lazy about it over the last 50 years or so. You can see this in a very acute way when people turn up to their local general practitioner and they say, you know, ‘I don't feel very well, give me antibiotics’ and even if that patient actually has a viral infection where antibiotics really won't do much other than destroy your gut flora and in many instances they still pressure their doctor to prescribe them antibiotics.
TESS VIGELAND: Is that really the main problem when you're talking about overuse, is it that people are going in and either asking for antibiotics when they don't need them... or are doctors for some reason giving them out when they aren't necessary, maybe just to placate a patient?
PATRICK WOOD: It is a non inconsiderable proportion of the issue. It’s definitely within there. But overexposure. Non-completing of your prescription over time. Use in agriculture. All of these things have contributed to the issue…
I think at the end of the day, they’re trying to make sure that we have public discourse about the issue because this is really a public health issue where you need both physicians and you also need the public to be thinking about it, and behaving appropriately to control this.
TESS VIGELAND: This discourse is already happening in earnest at the University of California San Diego. It was sparked in the wake of a near-tragedy that happened to two of its professors, who happen to be married. And their journey is changing our understanding of what’s possible in medicine.
TOM PATTERSON: Hi, I’m Tom Patterson.
STEFFANIE STRATHDEE: And I’m Steffanie Strathdee.
TESS VIGELAND: Tom and Steffaine share a single-story ranch home in La Jolla, California.
It’s got a cactus garden, and a giant picture window out to the backyard, with a spectacular view of the Pacific Ocean. And they’re not the only ones enjoying the yard… local wildlife does too.
TOM PATTERSON: All these birds... ooh the hawk is after, see this guy?
TESS VIGELAND: Yeah, oh beautiful.
TOM PATTERSON: He’s a sharpshinned. That’s this nest over there on the top of this tree.
TESS VIGELAND Oh yeah, yeah.
TESS VIGELAND: The view… the birds… all of it became utterly irrelevant a couple of years ago.
Tom is a psychiatry professor at UC San Diego School of Medicine and Steffanie is Associate Dean of Global Health Sciences -- she’s an infectious disease epidemiologist.
Their lives, and the direction of their work, changed forever after a vacation in 2015.
STEFFANIE STRATHDEE: Well, Tom and I have been to about 50 countries together, and on his list was to visit Egypt to see, you know, the wonders of the world and the pyramids. We'd been there for about a week. And it was the last night of our trip we just thought, wow tomorrow we're going to see the Valley of the Kings, and then we go home. Well, it didn't quite turn out that way. Tom got really sick. I thought he had food poisoning.
TESS VIGELAND: What had you been doing that day - I mean, when you thought back? What were you thinking back on in terms of what might have caused this?
STEFFANIE STRATHDEE: Well, I was thinking it was something he ate for dinner because we had seafood and you know we’re on the Nile. And, I was just assuming that he was going to have a garden variety stomach bug and that, you know, he would ride it out. And he didn't.
TOM PATTERSON: I just kept getting worse and worse and my back started hurting and I was getting dehydrated. And when they did call, the doctor came and he said no, we really get to get you to a clinic.
TESS VIGELAND: So you get to the clinic and what happens?
STEFFANIE STRATHDEE: They medi-vac’ed us to Frankfurt, Germany. And there, they confirmed that he had a giant abscess in his abdomen the size of a football. And that's when I started to get worried - really worried.
TESS VIGELAND: Tom, are you out of it at this point?
TOM PATTERSON: By this time I was beginning, I mean throughout the illness I was in and out of a coma and hallucinating. But by the time we got to Germany I was hallucinating a lot, just out of it.
TESS VIGELAND: So then the doctors come back and tell you what?
STEFFANIE STRATHDEE: They said, look, it's the worst news that we could have had. It's the most terrible bacterial infection on the planet and we need to see whether or not it's resistant to multiple antibiotics, because this organism tends to be a superbug. A superbug is resistant to more than two or three antibiotics. The results came back on this one and it was resistant to 15 antibiotics right off the bat.
TESS VIGELAND: Even as the doctors were treating Tom, the bacteria were becoming more and more resistant to the antibiotics, every day.
STEFFANIE STRATHDEE: There was only three antibiotics that it was partially sensitive to at the beginning but by the time we medivaced Tom back home to San Diego, it was resistant to even those. So now it's fully resistant to all antibiotics in the modern medicines arsenal.
TESS VIGELAND: What are you thinking at that point?
STEFFANIE STRATHDEE: Well now I was terrified. I was reading on my own, brushing up on microbiology. You know, I have a degree in microbiology from 35 years ago. So I was catching up on all of what I'd missed over the last couple of decades and getting more and more terrified.
TESS VIGELAND: So your doctors tell you that they've run out of options?
STEFFANIE STRATHDEE: That's right.
STEFFANIE STRATHDEE: Well they basically said, Tom is too weak for surgery. So they said look, we'll siphon out all of this infected fluid and hopefully his immune system will be able to kick in and fight it - and it's the best option we have. And so for a while the superbug was contained in this abscess. But this one particular day when he sat up in bed, one of the tubes inside of him slipped, and it jumped all of that infected fluid into his abdomen and into his bloodstream and right in front of me, a doctor and a nurse he went immediately into septic shock.
TESS VIGELAND: Oh my god.
STEFFANIE STRATHDEE: And he started sweating profusely and then he began to shake. The bed frame was hitting the wall. About 50 percent of people who develop septic shock die right from, right then and there. So they rushed him back to the ICU. They put him on a ventilator to help him breathe, which is life support. They put him into a medically induced coma. From that moment on he was dying a little bit more each day because there was nothing that they could do. Now his body was fully colonized with this superbug.
TESS VIGELAND: But despite odds that were dropping by the hour, Steffanie refused to give up hope. She asked Tom if he wanted to continue the fight.
STEFFANIE STRATHDEE: When it dawned on me that he really was dying, I had a conversation with him. Even though he was in a coma and I said: Honey I know that you're fighting really hard but I want to grow old with you. And if you want to live, please, please somehow, could you just squeeze my hand so that I'll know? And I can leave no stone unturned, I'll do whatever I can to fight this thing. But, the doctors have run out of options. So I waited. And about a minute later he squeezed my hand really hard!
And I was really excited! I fist pumped into the air, I’m like: Yes! And then I realized, like, what am I going to do now? I don’t know how to solve this thing. I’m not a medical doctor, you know? And I thought, well, I'm a scientist and you know, I can at least research some alternative treatments. And so I went to the Internet and up popped a paper which had several different options that we hadn't thought of. And one was phage therapy.
TESS VIGELAND: Phage therapy... That’s P-H-A-G-E by the way. Now, it turns out this is an idea that’s been around for a long time. Phages are these special viruses. Scientists have known about them for more than a hundred years. In fact, they were discovered around the same time as antibiotics. But... antibiotics were a lot easier to use and administer. So, they became the default treatment for bacterial illnesses like pneumonia and mono and infections of all kinds.
As she searched desperately for answers, Steffanie found that research paper taking another look at this science.
The paper said you know... maybe we should give phages another try.
I asked Patrick Wood, the Bank of America Global Research analyst, to explain for us exactly how phage therapy works.
PATRICK WOOD: In basic terms, it is the use of a viral mechanism so a virus, that when most people think of a virus, it’s something that makes you feel bad or is attacking your body and that can be the case but there are a lot of viruses out there phage therapy is the use of viruses that attack bacteria .... And so, they’re viruses that are on your side. Friendly viruses if you like.
TESS VIGELAND: [Laughter] That's something I can't even wrap my head around. A friendly virus. So how does that work? Talk us through the process of how that works within someone's body.
PATRICK WOOD: In this instance, your body doesn't recognize the incoming virus as a threat. And so it doesn't attack it, much like your body doesn't attack the natural bacteria that exists in your gut. The virus attacks the bacteria, destroys it, and so over time they attack faster and faster the bacteria that exists within you.
The real thing is that your body doesn't recognize them as a threat. That bit’s very important.
TESS VIGELAND: So again… this is a friendly virus. It only wants to kill bacteria - and it isn’t going to make you sick.
PATRICK WOOD: It's like the analogy of the lock and the key is because one will only fit uniquely to the other, they’re very specifically tailored only to fit the other one.
TESS VIGELAND: Okay, so the virus that is used in the phage therapy, is that designed specifically for what it's going after - for what it's trying attack?
PATRICK WOOD: Yes. So each virus is bespoke if you like and unique to the target that it's trying to attack. That is the advantage in that it's a sniper rifle not a bazooka.
TESS VIGELAND: Each type of phage has to match a specific type of bacteria. Going back to Steffanie... I wondered how she even began her search for a solution.
TESS VIGELAND: First of all you have stumbled upon this potential treatment that is not in wide use, and then the doctors say you need to go find the viruses. I’m pretty sure your background is not in virus hunting. So what’s your first step at that point?
STEFFANIE STRATHDEE: So I went back to the internet, and I made a list of researchers around the US that were studying these phages that attack his type of bacteria. And it was a mighty short list, a handful of researchers. And I wrote every single one of them, and so... they did find several phages.
TESS VIGELAND: You're just in a race against time?
STEFFANIE STRATHDEE: We were in a total race against time. His kidneys were just hanging on by a thread. He was still on the ventilators, he was on three different medications to keep his heart pumping. And then his kidneys started to fail.
TESS VIGELAND: The phages arrived just in time. The big question was how much of it - how many of them - to give him. No American hospital had ever used phages like this before for this purpose.
Remember, these are live viruses. Living things. Too few and it might not work. Too many and... well, nobody knew what might happen.
STEFFANIE STRATHDEE: So it was a billion phages per dose. A billion viral particles per dose and every two hours we injected these first into the catheters in his abdomen and then when he survived that we injected those in his bloodstream every two hours.
TESS VIGELAND: Are the phages in a syringe and they're just injected into the catheters? Is it that simple?
STEFFANIE STRATHDEE: It was that simple.
TESS VIGELAND: After that… all Steffanie could do was wait. The phage treatment continued with injections every two hours for the next three days. And then... on the third day…
STEFFANIE STRATHDEE: He woke up, from a deep coma to awake and conscious and recognizing people. I leaned over him and I said: honey, it's me and he kissed me. And it was just, like, my heart melted. And it was like, oh my God. It blew us all away.
TESS VIGELAND: Tom, what do you remember if anything about that first time you
woke up?
TOM PATTERSON: I remember that it wasn’t like in the movies. I do remember being extraordinarily tired, and you know I wouldn't say that I was you know ready to write another paper for a journal. But I was, you know, certainly elated to be alive.
TESS VIGELAND: The phages fought against the antibiotic-resistant bacteria throughout Tom’s system. The infection slowly came under control, and Tom was healing.
It would take several more weeks of treatment to get all of it out of his system. He spent more months in the hospital recovering from the ordeal.
TESS VIGELAND: So there it was. An experimental treatment using live viruses, curing an infection that would have killed Tom. So here’s the big question: can his experience become the therapy of the future?
STEFFANIE STRATHDEE: Heck we saved you with a hundred year old forgotten cure that we don't want to have buried for another hundred years.
TESS VIGELAND: News of Tom’s treatment spread quickly throughout the medical community. Steffanie felt she had a new calling. She wanted others - she wanted the world - to benefit from phages. She gave a TED talk, and then she and Tom wrote a book. And, alongside doctors at UC San Diego, Steffanie helped establish a research center dedicated to bringing phage therapy to others who need it. It’s called the Center for Innovative Phage Applications and Therapeutics and she serves as co-director.
STEFFANIE STRATHDEE: We were getting so many requests from patients all over the world and their doctors and their families for phage therapy. We're fund raising and trying to move phage therapy into clinical trials, to show whether phage therapy is going to be superior or at least equal to antibiotics. And if that's the case then it will mean that the FDA can license it as options for people that are running out of antibiotics.
TESS VIGELAND: I got to visit the Center for Innovative Phage Applications and Therapeutics... IPATH for short. The FDA gave the center clearance in early 2019 for the very first clinical trial of phage therapy in the United States.
Doctor Saima Aslam is one of the primary physicians using the therapy in cases where nothing else is working. She sees and treats antibiotic resistant infections every day. We sat down between patient visits in her office.
SAIMA ASLAM: Tom's case... really I feel like it's a seminal event in a good way, in that we were able to cure an incurable infection really, and have him walk out of the hospital and do well. So I think that is a huge, huge deal and will affect health care in the U.S. and all over the world really.
TESS VIGELAND: Talk about your work with IPATH.
SAIMA ASLAM: So, my role is to be one of the main physicians associated with IPATH. We've actually treated a total of seven patients here at UCSD. I've treated five of them. They've all had come to a point where they lost hope. And I think using bacteriophage therapy gave them hope, and certainly led to successful outcomes for all of them. And we've learned from each patient. From Tom's case we learned we can actually do this, but after each after that we've learned more about dosing. We learned about how to do this as an outpatient. So all of them I think have been seminal in their own way, but certainly you know Tom's was a huge deal.
TESS VIGELAND: What are the challenges facing further usage at this point. Is it is it just simply what we don't know? Or is it a lack of resources? Is it a lack of phages?
SAIMA ASLAM: Well I think there's certainly no lack of phages, they outnumber bacteria by far. The issue is I think we need to learn more about it but we need to learn in a systematic manner and certainly in terms of FDA clearance I think we need to do clinical trials, and try to use them in patients upfront and not when they've run out of all options. And our goal is to make it more mainstream. But yeah, I mean, number one would be research and funding for that research.
TESS VIGELAND: When you look out 10 years, 20 years, 50 years... where do you think phage therapy will fit within medicine?
SAIMA ASLAM: So my hope is that for certain infections we are able to have these pre-formed combinations of maybe three or four or five phages that have good shelf life that you could stock in a pharmacy and actually use it as needed... I think that would be amazing.
TESS VIGELAND: Phages in the pharmacy, and a medication that everyone will someday know about and use. And what about the potential role of phages in the broader healthcare system? Analyst Patrick Wood says there’s a bright future for any treatment that can meet or exceed the promise of antibiotics.
PATRICK WOOD: It probably saves a considerable amount of cost, mostly by keeping patients out of hospitals or in them for a far reduced time. You have this situation in many instances where elderly patients are generally advised not to go to hospitals purely because picking up a resistant infection can be a serious, serious issue for them. With more effective treatment you don't have that same issue. At the end of the day when you have a better clinical solution, you tend to reduce costs the healthcare system, reduce the time the patients spend in hospital - and that can only be a good thing.
TESS VIGELAND: Then if you had the power to make phage therapy workable what would you need to make that happen?
PATRICK WOOD: I think the reality at the end of the day it always comes down to money. I would love the power for a little bit more clinical data and acceptance and development of either new antibiotics or phage therapies or any other solution to antimicrobial resistance that we can get our arms around. I think for the healthcare system overall it's an imperative and I think we need to be forward looking on this issue.
TESS VIGELAND: For Steffanie Strathdee and Tom Patterson, being forward-looking is a way of life. It’s clear they believe that phage therapy is the future. And, I also wanted to know what’s next in their future.
TOM PATTERSON: Travel is on the horizon lots more of it. You know, we've already been to Costa Rica, Africa. We're about to go off to Canada.
TESS VIGELAND: Tom, if you had the power to change anything in the future of medicine based upon what's happened to you, your own personal experience, can you think of what that might be?
TOM PATTERSON: I would say that the one message I like to get through is there's growing evidence - and I think I myself am evidence based hope - that this therapy really does work. And my hope is that thousands and thousands of lives will be saved as a result of my case.
TESS VIGELAND: A goal that now seems possible because of his experience.
Patrick Wood says that he sees the potential of phage therapy as part of a broader, hopeful trend in health care.
PATRICK WOOD: I think one of the most encouraging things about healthcare system now is just how good we have it relative to many prior generations. Thirty years ago if you had to have your knee replaced you'd be in the hospital for three weeks. Nowadays, you can be going home and spending time with your loved ones in one day. It's unbelievable. And so many other areas like minimally invasive surgeries and our understanding of the human body it's just extraordinary. The generations that come after us will have healthier, longer lives [and] that's really what healthcare’s about.
TESS VIGELAND: We’ve explored a century-old remedy for a modern-age medical problem. We’ve also gone this season from a factory that turns plastic bottles into fiber, to how we could harness solar power from space… and much more.
We’ve asked visionaries all over the globe what kind of future they want to create. What would YOU like the power to do?
This is the final episode of this season of The World to Come. If you haven’t heard the others, please go back and listen. You can find out more about the series at BankofAmerica.com/WorldToCome.
I’m Tess Vigeland. Thanks for listening.
BofA Merrill Lynch Global Research is research produced by BofA Securities, Inc. “B-of-A-S” and/or one or more of its non-U.S. affiliates. B-of-A-S is a registered broker-dealer, Member S-I-P-C, and wholly owned subsidiary of Bank of America Corporation.
Any opinions or other information correspond to the date of this recording and are subject to change. This information discusses general market activity, industry or sector trends, or other broad-based economic, market or political conditions and should not be construed as research or investment advice.
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In this episode
In 2015, Tom Patterson was on vacation with his wife, Steffanie Strathdee, when he came down with a life-threatening antibiotic-resistant infection. Steffanie, the Associate Dean of Global Health Sciences at UC San Diego School of Medicine, explains “We were in a total race against time. His kidneys were just hanging on by a thread. I’m not a medical doctor, so I went to the Internet and up popped a paper which had several different options that we hadn't thought of. And one was phage therapy.” In this episode, we tell the story of how Tom’s infection was successfully treated with viruses, and how this treatment could impact the future of healthcare.
Guests
Patrick Wood
BofA Global Research Analyst
Steffanie Strathdee
Co-Director at the Center for Innovative Phage Applications and Therapeutics (IPATH); Co-Author of The Perfect Predator
Tom Patterson
Professor at UC San Diego School of Medicine; Co-Author of The Perfect Predator
Saima Aslam
Infectious Disease Specialist at UC San Diego Health; Associate Professor at UC San Diego School of Medicine
Host
Tess Vigeland
Veteran US Journalist,
NPR Host, Author
NPR Host, Author
A well-known voice for millions of American radio listeners, Tess spent 11 years as an anchor for public radio’s Marketplace. Over her career, she has received numerous national awards, including most recently a 2019 Gracie Award as Best Host/Anchor, and a 2019 National Murrow Award for Continuing Coverage.
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Bank of America N.A., Oficina de Representacion (Chile), is a representative office in Chile of Bank of America N.A., supervised by the Superintendencia de Bancos e Instituciones Financieras and authorized to promote in Chile select products and services that Bank of America N.A. provides outside of Chile. Neither Bank of America, N.A., nor its Representative Office in Chile, is authorized to carry out in Chile any activities that are reserved by Chilean law to locally licensed banks.
Bank of America Corporation does not have banking affiliates, branches or bank representative offices in any other jurisdiction in Latin America.
Securities, strategic advisory, and other investment banking activities are performed globally by investment banking affiliates of Bank of America Corporation, including, in the United States, BofA Securities, Inc., Merrill Lynch, Pierce, Fenner & Smith Incorporated and Merrill Lynch Professional Clearing Corp., which are registered broker-dealers and members of FINRA and SIPC, and in other jurisdictions, by locally registered entities.
Investment products offered by Investment Banking Affiliates:
Are Not FDIC Insured * May Lose Value * Are Not Bank Guaranteed.
©2020 Bank of America Corporation.
Disclaimer for France:
BofA Securities Europe SA (“BofASE”) with registered address at 51, rue La Boétie, 75008 Paris, registered under n° 842 602 690 RCS Paris, is governed by articles L. 531-1 and following of the monetary and financial code. BofASE is authorized as an investment firm by the Autorité de Contrôle Prudentiel et de Résolution (“ACPR”), is regulated by the ACPR and the Autorité des Marchés Financiers, and is not a credit institution. BofASE’s share capital is 5,276,300,000 €.
©2020 Bank of America Corporation.
Disclaimer for Hong Kong:
“Bank of America Merrill Lynch" is the marketing name for the global banking and global markets businesses of Bank of America Corporation. Lending, derivatives, and other commercial banking activities are performed globally by banking affiliates of Bank of America Corporation, including Bank of America, N.A., Member FDIC. Securities, strategic advisory, and other investment banking activities are performed globally by investment banking affiliates of Bank of America Corporation ("Investment Banking Affiliates"), including, in the United States, BofA Securities, Inc., Merrill Lynch, Pierce, Fenner & Smith Incorporated, and Merrill Lynch Professional Clearing Corp., all of which are registered broker-dealers and Members of SIPC, and, in other jurisdictions, by locally registered entities. BofA Securities, Inc., Merrill Lynch, Pierce, Fenner & Smith Incorporated and Merrill Lynch Professional Clearing Corp. are registered as futures commission merchants with the CFTC and are members of the NFA.
Bank of America, National Association, Hong Kong Branch, is a branch of a national banking association organized and existing with limited liability under the laws of the United States of America.
Disclaimer for Canada:
"Bank of America Merrill Lynch" is the marketing name for the global banking and global markets business of Bank of America Corporation. Lending, derivatives and other commercial banking activities are performed globally by banking affiliates of Bank of America Corporation including Bank of America, National Association, Canada Branch (BANA CB ) which is a foreign bank branch regulated by the Office of the Superintendent of Financial Institutions. Deposits with BANA CB are not insured with the Canada Deposit Insurance Corporation. BANA CB shall not impose undue pressure on, or coerce, a person to obtain a product or service from a particular person, including bank and any of its affiliates, as a condition for obtaining another product or service from BANA CB.
Securities, strategic advisory and other investment banking activities are performed globally by investment banking affiliates of Bank of America Corporation including in Canada by Merrill Lynch Canada Inc. which is a registered broker-dealer regulated by the Investment Industry Regulatory Organization of Canada (IIROC) and a member of the Canadian Investor Protection Fund (CIPF).
Terms and Conditions
These Terms and Conditions ("Terms and Conditions") are for the Bank of America Corporation ("Bank of America") website and those websites of its affiliates (collectively the "Sites") including Bank of America, N.A., Merrill Lynch, Pierce, Fenner & Smith Incorporated, BofA Securities, Inc., Bank of America Capital Management and certain other affiliates enumerated herein (collectively "Affiliates") that are available through the Bank of America Sites and apply to all services, programs, information and products (collectively "Service") that you ("Client") may use or otherwise access from time to time through the Sites ("Agreement").
USE OF SITES
Client agrees that any trade confirmation, account statement or other document delivered through the Sites by "clicking" on the designated spaces in or relating to such document shall be deemed to be "in writing" and to have been "signed" and delivered for all purposes by Client. Any record of such transaction or confirmation (including, without limitation, electronic records) shall be deemed to be "in writing." Client further agrees that it shall not contest the legally binding nature, validity or enforceability of any transaction, document or confirmation based on the fact that it has been executed by "clicking" on the designated spaces and expressly waives any and all rights it may have to assert such claim.
Bank of America hereby grants to Client a worldwide, non-exclusive, non-sublicensable, non-transferable, non-assignable, personal right and license to access and use the Sites solely for Client's internal use in accordance with the terms of this Agreement. Client accepts the right and license granted herein to access and use the Sites solely in accordance with this Agreement and any rules or restrictions or procedures published by Bank of America on the Sites from time to time. Client acknowledges and agrees that the Sites, and all intellectual property and proprietary rights therein and thereto, anywhere worldwide, including such rights in copyrights, trademarks, service marks, trade dress, patents, patent applications and trade secrets and other proprietary and/or confidential information (collectively, "IP"), are the valuable property of Bank of America and/or its affiliates and licensors. Other than the license granted hereunder, Client obtains no rights to the Sites. Client may not access or use the Sites in any way that may infringe any IP right of Bank of America or its Affiliates or licensors. Client promptly shall notify Bank of America of any actual or threatened infringement or misappropriation of IP, or any portion thereof, of which it becomes aware. Client acknowledges and agrees that it will not use, or allow the use of the Sites in contravention of, and will comply with, any applicable laws, rules, regulations or interpretations (collectively, "Applicable Law").
Client agrees that it will not, and will not authorize or permit any person ("Authorized Person") under its control, under any circumstance to:
- sell, lease, transfer, recirculate, republish, redistribute, make available or otherwise provide access to the Sites, or any portion thereof or data thereon, to any person other than its Authorized Persons, including through oral, written, or electronic means whether as a demonstration or otherwise;
- photocopy, download or otherwise reproduce in any medium any portion of the Sites, except that Client may download into Client's internal computer system, or print a hard copy of, content on the Sites, in whole or in part, provided that, in each case, all copyright and other proprietary notices are retained and complied with; or
- alter, decompile or reverse engineer any software component of the Sites.
All cost and expense of equipment, operating platforms, and software necessary to access and use the Sites, and the maintenance thereof shall be the sole responsibility of Client.
No provision of these Terms and Conditions shall restrict Client from taking any action required by any Applicable Law, any self-regulatory organization or any governmental entity to which it is subject. Prior to taking any such action, Client shall, to the extent reasonably practicable given the then-current circumstances, notify Bank of America in writing thereof and consult with Bank of America regarding the steps to be taken to ensure compliance with Applicable Law.
CLIENT ACKNOWLEDGES AND AGREES THAT IT WILL BE RESPONSIBLE TO ENSURE THAT ANY ACTIVITY UNDERTAKEN BY CLIENT OR ITS AUTHORIZED PERSONS IN ANY JURISDICTION AND WITH ANY PERSON IN WHOLE OR IN PART ON OR THROUGH THE SITES IS IN COMPLIANCE WITH APPLICABLE LAW.
Client agrees to provide Bank of America with all information, cooperation and assistance, documents and data as shall reasonably be requested by Bank of America in order to enable Bank of America to comply with any and all Applicable Law. Client understands and agrees that Bank of America may report such information to regulatory authorities to the extent necessary, in its reasonable discretion, to comply with Applicable Law.
SECURITY
Bank of America shall assign to each Authorized Person a unique User ID ("User ID") and a corresponding password and/or other access codes (each, an "Access Code") to enable Authorized Persons to access and use such functions within the Sites as Client shall authorize. Client shall (i) maintain, (ii) take appropriate steps to ensure that its officers and employees maintain, and (iii) inform all Authorized Persons of Client's obligation to maintain, the confidentiality of User IDs and Access Codes and the security of the Sites. Client shall not permit any person other than an Authorized Person to access or use the Sites on its behalf or to use any User ID or Access Code and shall educate and familiarize those Authorized Persons who access and/or use the Sites with Client's obligations under this Agreement. Client acknowledges and agrees that Client and/or its Authorized Persons may access the Sites through the World Wide Web or other Internet service which is not necessarily secure, and Bank of America does not warrant that such system is secure. Client agrees to be bound by all communications (and the consequences thereof) placed on, executed through or facilitated by the Sites that are accompanied by a valid User ID and a valid Access Code assigned to Client or an Authorized Person. Upon becoming aware of, or if Client suspects, a technical failure or any improper access to or use of the Sites or Access Codes by any Authorized Person or other person, Client shall promptly notify Bank of America of such occurrence, and shall, as promptly as practicable, to the extent any improper access or use is by an Authorized Person, take immediate actions to terminate such Authorized Person's access to and use of the Sites. Bank of America reserves the right to limit or terminate Client’s or any Authorized Person’s access to and use of the Sites immediately and without notice.
NO OFFERS
Unless specifically identified as an offer to sell or a solicitation of any offer to buy, under no circumstances should any information on the Sites be used as or considered to be an offer to sell or a solicitation of any offer to buy the securities or any other instruments of Bank of America or any other issuer. Offers can only be made where lawful under applicable law. Any information, services, or securities offered via the Sites are intended to be available only to residents of Argentina, Brazil, Canada, France, Germany, Hong Kong, Ireland, Japan, Italy, Korea, the Netherlands, Singapore, the United States and the United Kingdom. The viewing or distribution of the Sites may be restricted by law in certain jurisdictions. Persons using the Sites are required to inform themselves about and observe any legal restrictions on the use of the Sites and any restrictions set forth in the Sites. The Sites do not constitute an offer of, or a solicitation to purchase any securities in any jurisdiction in which such offer or invitation would be unlawful. If you wish to obtain further details about any information contained through the Sites, there are several areas on the Sites that will provide you with contact information.
DISCLOSURE OF INTEREST
Affiliates of Bank of America may make a market or deal as principal in the securities mentioned in these Sites or in options based thereon. In addition, Bank of America or its Affiliates, their shareholders, directors, officers and/or employees, may from time to time have long or short positions in such securities or in options, futures or other derivative instruments based thereon. One or more directors, officers and/or employees of Bank of America or its Affiliates may be a director of the issuer of the securities mentioned at these Sites. Bank of America or its Affiliates may have managed or co-managed a public offering of, or acted as initial purchaser or placement agent for a private placement of, any of the securities of any issuer mentioned on the Sites, or may from time to time perform consulting, advisory, lease, loan solicitation, investment banking or other services for, or solicit investment banking or other business from, mentioned companies.
ACCOUNT INFORMATION
Certain information from Client’s account(s) at Bank of America or its Affiliates is accessible on the Sites and can be downloaded by Client ("Account Information"). While Bank of America and its Affiliates believe that this Account Information will be accurate at the time of access and/or downloading by Client, this information may have certain technical flaws, typographical errors or other inaccuracies. Additionally, the Account Information is subject to immediate change resulting from market conditions, price fluctuations and other related factors. Bank of America and its Affiliates expressly disclaim any responsibility or liability for the accuracy or use of such Account Information upon its being downloaded by Client and will not be liable for any difficulty, damage or inaccessibility of such information due to hardware or software incompatibility.
PRICING AND MARKET INFORMATION
Actual prices can be obtained only on a real-time, expressly agreed-upon basis. Any indicative valuations on the Sites are provided for information only. They are not an offer to enter into, transfer and assign or terminate any transaction, or a commitment by Bank of America or its Affiliates to make such an offer. An indicative valuation may differ substantially from an actual value. Such estimates do not necessarily reflect Bank of America’s or its Affiliates’ internal bookkeeping or theoretical model-based valuations. Certain factors, which may not have been assessed for purposes of these valuations, including, for example, notional amounts, credit spreads, underlying volatility, costs of carry or use of capital and profit, may substantially affect a stated valuation. Indicative valuations may vary significantly from indicative valuations available from other sources. While Bank of America and its Affiliates have obtained the information on which these evaluations are based from sources they believe are reliable, Bank of America and its Affiliates make no representations or warranties with respect to any indicative valuations. Prior to the execution of a Transaction based upon the Content of these Sites, Client is advised to consult with its broker or other financial representative to verify pricing information.
HYPOTHETICAL OR PAST PERFORMANCE
Hypothetical or simulated performance results have inherent limitations. Unlike an actual performance record, simulated results do not represent actual trading. Also, since the trades have not actually been executed, the results may have under or over-compensated for the impact, if any, of certain market factors, such as lack of liquidity. Simulated trading programs in general are designed with the benefit of hindsight. Past performance is not indicative of future results; no representation is being made that any account will or is likely to achieve profits or losses similar to those shown.
MATERIAL IN ITS ENTIRETY
All materials at these Sites are meant to be reviewed in their entirety, including any footnotes, legal disclaimers, restrictions or disclosures, or any copyright or proprietary notices. Any disclaimers, restrictions, disclosure or hedge clauses apply to any partial document or material in the same manner as they do to the whole, and will be deemed incorporated in the portion of any material or document that you consult or download.
LINKED SITES
Certain hyperlinks on the Sites may link websites maintained by the Affiliates, which are not to be considered a part of the Sites. Certain other links on the Sites to non-affiliated third-party sites may contain information over which we have no control. We take no responsibility for the content, accuracy, content, completeness, timeliness, current value or any aspect of the information on these sites and disclaim any liability to Client for it or for any consequence of your decision to use the links provided or your use of such information. Links to non-Bank of America sites do not imply any endorsement of or responsibility for the opinions, ideas, products, information or services offered at such sites, or any representation regarding the content at such sites. We also disclaim all liability and make no representations or warranties for any products or services sold or provided to Bank of America or its Affiliates by any third party. Your purchase of products or services through one of those other sites is subject to agreements and/or the terms and conditions in effect between Client and the providers of products and services at those other sites. Client agrees that it shall not bring a suit or claim against Bank of America or its Affiliates arising from or based on your purchase or use of products or services through those other sites. Links do not imply that Bank of America, its Affiliates or the Sites sponsors, endorses, is affiliated or associated with, or is legally authorized to use any trademark, trade name, logo or copyright symbol displayed in or accessible through the links, or that any linked sites is authorized to use any trademark, trade name, logo or copyright symbol of Bank of America or its Affiliates.
CONTENT AND SERVICE AVAILABILITY
Bank of America or its Affiliates may make changes to the Sites and reserves the right to do so without prior notice to you. Client acknowledges that not all products and services listed or discussed in the Sites are available in all geographic areas. Your eligibility for particular products and services is subject to final determination and acceptance by Bank of America or its Affiliates.
CONSENT TO ELECTRONIC DELIVERY
You agree to receive certain documents and information provided by Bank of America and its Affiliates through the Sites and/or through email provided to you via the Sites. This delivery will generally consist of certain Content on the Sites, and certain other documents relating to Bank of America and its Affiliate’s business. This electronic provision and delivery will be regarded by you as appropriate delivery pursuant to any delivery requirements under the various statutes and rules, where applicable, of the Securities and Exchange Commission, the National Association of Securities Dealers and any state or other jurisdiction. You acknowledge that you have the appropriate technological equipment to use the Sites and to receive email via the Internet and understand that your use of the Internet may incur certain operational costs such as monthly fees for a service provider. You agree to notify Bank of America or the applicable Affiliate in the event that you no longer desire to receive content through this delivery procedure and will allow a reasonable amount of time to permit proper delivery to you through other means.
NO WARRANTY
Client acknowledges that any information provided through the Sites is not intended to be a recommendation, offer or solicitation of any particular products or services. In addition, all research, analysis and similar market information from non-affiliated third parties provided represent the views and opinions solely of the author or the indicated source. Bank of America and its Affiliates do not independently verify the accuracy or completeness of such information, nor does Bank of America and its Affiliates endorse any particular views expressed therein. Except for offering memoranda, Bank of America and its Affiliates disclaim any liability to Client for this information or for any consequence of your decision to use it. Client agrees that it shall independently confirm any such information presented through the Sites before relying on such information. Bank of America, its Affiliates and their respective employees, contractors, agents and various contributors to the Sites have no duty to correct or update any inaccurate or out-of-date information on the Sites.
Client acknowledges that it is acting for its own account, and it has made its own independent decisions to enter into a Transaction and as to whether a Transaction is appropriate or proper for it based upon its own judgment and upon advice from such advisors as it has deemed necessary. Client is not relying on any communication (written or oral) of Bank of America or its Affiliates as investment advice or as a recommendation to enter into a Transaction; it being understood that information and explanations related to the terms and conditions of a Transaction shall not be considered investment advice or a recommendation to enter into that Transaction. Further, Client has not received from Bank of America or its Affiliates any assurance or guarantee as to the expected results of a Transaction.
COMPLIANCE WITH LAWS AND INDEMNITY
The Sites may be used only for lawful purposes. Client’s conduct may be subject to local, state, national and international laws. Client agrees that it and any of its Authorized Persons shall comply with this Agreement, applicable laws, rules, regulations, ordinances and other similar national and international requirements of the country, state and province in which you are accessing and using the Sites.
Client agrees to abide by applicable export control laws and not to transfer, by electronic transmission or otherwise, any content on the Sites subject to restrictions under such laws to a national destination prohibited under such laws, without first obtaining, and then complying with, any requisites government authorization. Client further agrees not to upload to the Sites any data or software that cannot be exported without prior written government authorization, including, but not limited to, certain encryption software. This assurance and commitment shall survive termination of these Terms and Conditions. Offices, residents and operations of your organization in Cuba, Iran, Iraq, Libya, North Korea, Sudan, Syria and any other countries that are the subject of sanctions by the United States Office of Foreign Asset Control or other general U.S. embargo restrictions are not permitted to access and use the Sites, and any such access and use is a violation of these Terms and Conditions.
Upon request by Bank of America or its Affiliates, you agree to defend, indemnify and hold harmless Bank of America, its Affiliates, their officers, directors, employees, agents, contractors or other suppliers from all liabilities, claims and expenses, including attorneys fees, that arise from a breach of these Terms and Conditions for which you are responsible, or from third-party claims arising from your use of the Sites. Bank of America and its Affiliates reserve the right to assume the exclusive defense and control of any matter otherwise subject to indemnification by you. Notwithstanding the foregoing, you are not required to indemnify Bank of America or its Affiliates for its own violations of applicable laws.
FOR RESIDENTS OF BRAZIL:
The information contained here does not constitute a public offering or distribution of securities in Brazil and no registration or filing with respect to any securities or financial products available on the Sites has been made with Commisao de Valores Mobiliarios.
FOR RESIDENTS OF CANADA:
The information contained here does not constitute a public offering or distribution of securities in Canada or any of its provinces. No registration or filing with respect to any securities or financial products available on the Sites has been made with any regulatory agency thereof.
FOR RESIDENTS OF FRANCE:
The Sites do not constitute a solicitation to enter into a transaction involving financial instruments, is not being distributed in the context of a public offer in France within the meaning of Article L. 411–1 of the Monetary and Financial Code, and has thus not been submitted to the COB for prior approval and clearance procedure. Any offers, sales or distribution of financial instruments through the Sites shall only be made in France to qualified investors (investisseurs qualifi?s) as defined in and in accordance with Article L. 411-2 of the Monetary and Financial Code and d?cret no. 98–880 dated 1st October, 1998. The contents of the Sites may not be redistributed or reproduced (in whole or in part) by any User. The Sites are made available with the understanding that Users will make investment decisions for their own account with the conditions set out in d?cret no. 98–880 dated 1st October, 1998. By using the Sites, Users undertake not to transfer, directly or indirectly, any financial instrument acquired through the Sites to the public in France, other than in compliance with applicable laws and regulation. Services hereunder may be provided by Banc of America Securities, Limited, as agent or otherwise.
FOR RESIDENTS OF GERMANY:
The Sites are made available only to professional investors as such term is defined in the Securities Sales Prospectus Act.
FOR RESIDENTS OF HONG KONG:
Access to the Sites is by invitation only to institutional investors. No information or material contained in the Sites is or should be construed as amounting to an offer to enter into any transaction or investment whatsoever. The information on these Sites is provided by the Hong Kong branch of Bank of America, N.A., and is compiled from information prepared by subsidiaries and affiliates of Bank of America Corporation. Your agreement for the use of this Site is with the Hong Kong branch of Bank of America, N.A.
FOR RESIDENTS OF IRELAND:
Access to the Sites is by invitation only to professional investors.
FOR RESIDENTS OF ITALY:
Access to the Sites is by invitation only to professional investors as defined in article 31 of CONSOB regulation no. 11522 of July 1, 1998.
FOR RESIDENTS OF JAPAN:
Access to the Sites is by invitation only to financial institutions as defined under the Law Concerning Foreign Securities Firms.
FOR RESIDENTS OF KOREA:
Access to the Sites is by invitation only to professional investors with a valid password. The information contained here does not constitute a public offering or distribution of securities in Korea.
FOR RESIDENTS OF NETHERLANDS:
Access to the Sites is by invitation only to professional market parties as defined in the Dutch Securities Transactions Supervision Act 1995. Securities or other instruments on these Sites are only offered to professional market parties.
FOR RESIDENTS OF SINGAPORE:
Access to the Sites is by invitation only to institutional investors. The information contained here does not constitute a public offering or distribution of securities in Singapore. The information in these Sites is provided by Bank of America Singapore Limited and is compiled from information prepared by subsidiaries and affiliates of Bank of America Corporation. Your agreement for the use of these Sites is with Bank of America Singapore Limited.
LIMITATION OF LIABILITY
THE FOLLOWING LIMITATIONS OF LIABILITY IN THIS SECTION SHALL NOT APPLY TO VIOLATIONS OF LAWS RELATING TO THE OFFER AND SALE OF SECURITIES. YOU ACKNOWLEDGE THAT NEITHER Bank of America, ITS AFFILIATES NOR THEIR OFFICERS, DIRECTORS, EMPLOYEES, AGENTS, CONTRACTORS OR OTHER SUPPLIERS MAKES ANY WARRANTIES OR GUARANTEES WITH RESPECT TO THE SITES, INCLUDING WITHOUT LIMITATION, WARRANTIES REGARDING THE ACCURACY OR COMPLETENESS OF ANY CONTENT, OR WARRANTIES OF MERCHANTABILITY, NON-INFRINGEMENT OF INTELLECTUAL PROPERTY, TITLE OR FITNESS FOR A PARTICULAR PURPOSE. Bank of America, ITS AFFILIATES AND SUCH PERSONS SHALL NOT BE LIABLE TO YOU FOR ANY LOSS, COST, DAMAGE OR OTHER INJURY, WHETHER IN CONTRACT, TORT, NEGLIGENCE OR OTHERWISE, ARISING OUT OF OR CAUSED IN WHOLE OR IN PART BY (I) CLIENT'S USE OF OR RELIANCE ON THE SITES, OR (II) Bank of America’s PERFORMANCE OF ITS OBLIGATIONS UNDER OR IN CONNECTION WITH THESE TERMS AND CONDITIONS. Bank of America DOES NOT REPRESENT, WARRANT OR GUARANTEE THAT THE SITES WILL BE FREE FROM ERRORS OR WILL BE AVAILABLE. FURTHERMORE, Bank of America WILL NOT BE LIABLE FOR ANY DELAY, DIFFICULTY IN USE, INACCURACY OF INFORMATION, COMPUTER VIRUSES, MALICIOUS CODE OR OTHER DEFECT IN THE SITES, OR FOR THE INCOMPATIBILITY BETWEEN THE SITES AND FILES AND THE USER'S BROWSER OR OTHER SITES ACCESSING PROGRAM. NOR WILL Bank of America BE LIABLE FOR ANY OTHER PROBLEMS EXPERIENCED BY THE USER DUE TO CAUSES BEYOND THE Bank of America’s CONTROL. IN NO EVENT WILL Bank of America, ITS OFFICERS, DIRECTORS, EMPLOYEES, AGENTS, CONTRACTORS OR OTHER SUPPLIERS BE LIABLE TO YOU OR ANY THIRD PARTY FOR ANY PUNITIVE, INCIDENTAL, CONSEQUENTIAL, SPECIAL OR SIMILAR DAMAGES, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
Because some states or jurisdictions do not allow the exclusion or limitation of liability for certain damages, in such states or jurisdictions, the liability of the Bank of America, its officers, directors, employees, agents, contractors or other suppliers shall be limited in accordance with this agreement to the extent permitted by law.
Neither Bank of America, its Affiliates nor any of their officers, directors, employees, agents, contractors or other suppliers shall be liable in any way, and you agree to indemnify and hold harmless Bank of America, its Affiliates and such persons for (1) any inaccuracy, error, or delay in, or omission of (a) any information on the Sites, or (b) the transmission or delivery of any information on the Sites; (2) any loss or damage arising from or occasioned by (a) any such inaccuracy, error, delay, or omission, (b) non-performance, (c) interruption of use of the Sites due either to any negligent act or omission by Bank of America, its Affiliates, their officers, directors, employees, agents, contractors or other suppliers or to any "force majeure" (i.e., flood, extraordinary weather conditions, earthquake, or other act of God, fire, war, insurrection, riot, labor dispute, accident, action of government, communications, power failure, or equipment or software malfunction) or any other cause beyond the control of the Bank of America, its Affiliates, their officers, directors, employees, agents, contractors or other suppliers. You understand that Bank of America accepts no responsibility for security of information on the Internet.
UK CONDITIONS
Banc of America Securities Limited has approved the Sites for the purpose of Section 57 of the Financial Services Act of 1986. Banc of America Securities Limited is regulated for the conduct of investment business in the United Kingdom by the Securities and Futures Authority Limited. No access to the Sites shall be given in the United Kingdom to Private Customers, as that term is defined under the rules of The Securities and Futures Authority Limited; and any investments will not be made by us to any Private Customer.
CHANGES TO AGREEMENT
Bank of America may make changes to this Agreement at any time, without prior notice to you. Your continued use of the Sites indicates your continued agreement to be bound by this Agreement, as changed from time to time. You should view these Terms and Conditions often to stay informed of changes that may affect you.
GOVERNING LAW
This Agreement shall be governed by and construed under the law of the State of New York and the Federal law of the United States. You hereby consent and submit to jurisdiction in the Federal or state courts of the State of New York, U.S.A. You hereby irrevocably waive your rights to a jury trial.
THIRD-PARTY LICENSORS
The Sites may, from time to time, provide Client with various licensed programs ("Licensed Programs") from third-party vendors ("Vendors") which have been licensed by Bank of America for Client use and/or which require Client to sign a third-party license agreement ("License Agreement"). In using the Licensed Programs, Client agrees that it will
- protect any confidential information of Bank of America, its Affiliates or Vendors contained in the Licensed Programs;
- restrict the use of the Licensed Programs by Client solely to conditions agreed upon in the Agreement and the License Agreement;
- restrict the copying of Licensed Programs to that number reasonably required for Client use and backup purposes
- include Bank of America and Vendor copyright and all other proprietary notices in the use of all Licensed Programs;
- prohibit the sale, relicensing, leasing, rental, lending and transferring of Licensed Programs;
- prohibit, and take reasonable measures to prevent, the decompiling, disassembly, reverse engineering or modification of Licensed Programs;
- comply with all export laws in respect of Licensed programs;
- disclaim any liability on the part of Vendors for damages, liabilities, costs or expenses incurred by Client in the use of License Programs; and
- make all vendors a third-party beneficiary of all Client waivers, disclaimers, limitation of liabilities, confidentiality and IP provisions contained in the Agreement.
BOFA SECURITIES, INC. – FURTHER INFORMATION
"Bank of America Merrill Lynch" is the marketing name for the global banking and global markets businesses of Bank of America Corporation. Lending, derivatives and other commercial banking activities are performed globally by banking affiliates of Bank of America Corporation, including Bank of America, N.A., member FDIC. Securities, strategic advisory, and other investment banking activities are performed globally by investment banking affiliates of Bank of America Corporation ("Investment Banking Affiliates"), including, in the United States, Merrill Lynch, Pierce, Fenner & Smith Incorporated, BofA Securities, Inc. and Merrill Lynch Professional Clearing Corp., all of which are registered as broker-dealers and members of FINRA and SIPC, and, in other jurisdictions, by locally registered entities. BofA Securities, Inc. and Merrill Lynch Professional Clearing Corp are registered as futures commission merchants with the CFTC and are members of the NFA. Investment products offered by Investment Banking Affiliates: Are Not FDIC Insured • May Lose Value • Are Not Bank Guaranteed.
© 2019 Bank of America Corporation.
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