On October 16, 1846, the first successful public demonstration of the use of ether for surgical anesthesia was performed at Massachusetts General Hospital, making pain-free surgery possible. Since then, the field has established a rich history, marked with countless advancements in patient care.

The impact of the anesthesia provider—whether a clinician, nurse anesthetist, technician, etc.—extends well beyond their patient’s bedside. Advancement in the field is often facilitated through dedicated research, innovation and development.

In celebration of the 175th anniversary of the birth of anesthesiology, William “Pepper” Denman, MD, Julian M. Goldman, MD, and Douglas Raines, MDMass General Department of Anesthesia, Critical Care and Pain Medicine pioneers in anesthesia business and research—share how they got where they are today, why clinical representation is critical in innovation and the lessons they have learned today.

Q. Did you always know that you would want to expand to areas outside of clinical care?

Denman: I always knew I wanted to help health care adopt new and better processes. In my clinical practice, I would get frustrated when it was difficult to get new devices and processes implemented into practice. The biggest driver for me was always, how do I change that? I had to answer that question.

Goldman: Early in my career, I saw many opportunities to leverage technology to improve a patient’s outcome and satisfaction and enhance a caregiver’s vigilance. I was frustrated that technologies that were easily deployable outside of health care, such as artificial intelligence, could not be translated to anesthesia to improve patient care. These early career experiences drove me to realize my interest in enabling health care interoperability as a key enabler of health care transformation (whereby different medical and information technology systems are able to communicate and exchange usable data).

Raines: I became interested in anesthetic mechanisms and molecular pharmacology as an undergraduate. The way that we thought about the function of anesthetics back then was very different. I purposefully came to Mass General because it is the world's center for anesthetic mechanisms research, but I did not anticipate one day commercializing the technology that I helped to research.

Q. How did you get started?

Denman: You can look back at your journey and make it seem like you knew what you were doing. My career shifted when I met someone from a major medical device company, and he asked if I would consult for them part-time on malfunctions and complaints. When I started, I realized this organization didn’t have a clinical affairs team nor a health care economics team. This was my gateway, and I decided to try to build one.

Goldman: When I was a resident, I developed a point-of-care tool using a new hand-held touch-screen computer to pre-calculate doses for pediatric cardiac anesthesia to reduce dosing errors (this was way before the iPhone!). That led to my development of AI-based patient monitoring systems. These projects solidified my interest in translating technologies to anesthesia to enable smarter, safer ways to deliver care. My vision for the transformative role of technology was a bit ahead of the adoption curve, since medical technology, device standards and FDA regulation were still directed at the past, rather than focused on enabling a pathway for the future. But Mass General is a place where it's okay to be ahead of the curve and has provided us with the platform to drive change.

Raines: I was a chemistry major in college, and I started working with a researcher who was studying membrane biophysics and lipid bilayers. Since this is where we thought the anesthetics were working, it was a natural shift to anesthesia research. This led to a lot of positive experiences in medical school. When looking at residencies, I knew that I wanted research to be integral in my future career.

Q. How does your work in research and industry influence your approach to patient care?

Denman: I am so much more appreciative and aware of all the things Mass General does to allow me to practice medicine. The business side of my work has benefited me as a clinician and helped me think several steps ahead. I am more attuned to managing the clinical process and workflow; I make sure that everyone understands the goal and the thought process behind it. When people feel like part of the solution, they feel empowered.

Goldman: Few things have given me more joy than taking a patient through a difficult time in their life. Working in technology and innovation, we have the ability to impact patients on a much larger scale than through individual doctor-patient interactions. But it is the patient interactions that have motivated me to identify barriers and develop solutions to improve care.

Raines: It’s helped make me a better teacher for both trainees and patients because I understand the pharmacology of the drugs that we use and how drugs interact with one another.

Q. What do you consider to be the major successes in your career?

Dr. Raines, Dr. Denman and Dr. Goldman pictured with the Ether Dome's glass ceiling overhead
(left to right) William “Pepper” Denman, MD, Julian Goldman, MD, and Douglas Raines, MD, in the Mass General Ether Dome.

Denman: I am very grateful for my 20 years of work in Vietnam. It started as medical missions and grew to working with the health ministry to build residency programs in Ho Chi Minh City. Today, our residents get to travel overseas to serve in underserved areas with an attending as an approved part of their training.

Goldman: I was a member of the Mass General team that opened the “operating room of the future,” a dedicated OR “testbed” for providers to evaluate clinical and operational technologies. The idea to stand up a clinical test bed for intra-operative workflow and technology was an audacious undertaking. Our goal was to safely and efficiently increase the number of procedures while enhancing patient and provider satisfaction. One of its key capabilities was dedicated induction and emergence rooms to reduce the downtime between procedures and create a more comforting environment for the patient. There were many challenges with implementing this—funding, data collection, finding a team comfortable with new technology and constant change—but the project succeeded and has informed OR development worldwide. Notably, the technology barriers identified in the OR of the Future led directly to the founding of the MD PnP program to develop solutions such as interoperability and software-as-a-medical device.

Raines: You don’t always get to do innovation in research, and I am grateful that I have had the good fortune to translate ideas into something that can improve human health. What was thought to be impossible when I started 30 years ago is now considered possible. Ideating an anesthetic, synthesizing it, developing the drug and bringing it to trial—it’s been amazing. In some ways, it feels like we're following in the footsteps of Dr. William Morton.

Q. How does industry and research benefit when clinicians are involved?

Denman: Unmet clinical needs are resolved through innovation, research and development, product production and commercialization. Clinicians need to be part of every one of those steps to drive safer, more cost-effective care because they are the ones delivering the care and feel it when it falls short.

Goldman: Identifying unmet clinical needs and conveying those needs to industry stakeholders to develop solutions is still a challenge for the field of medical innovation. Clinicians with research, industry, standards and regulatory experience are important members of innovation teams and often serve as translators of the concepts and jargon used by diverse project stakeholders.

Raines: The anesthetics we use today are full of undesirable side effects—they depress breathing, lower blood pressure, etc. Clinical practice gives you certain insights into what the anesthesiologist really needs. In drug development, it’s helpful to know firsthand everything missing with current drugs. You get that knowledge most readily and can make medically meaningful change when you’re the one administering those drugs and seeing the effects.

Q. What is most difficult about the work that you do?

Denman: Changing hearts, minds and behaviors. There is an inherent risk in everything. When it comes to driving change, you can’t just tell people that it’s going to be better for them. You have to prove to people why it's better, show them how you're going to get there and attest to how their jobs and lives will improve.

Goldman: Breaking down misconceptions. A common one is that if we increase interoperability to facilitate innovation, we will also increase the risks from cyber security. However, in reality, when medical devices, connectivity and integration are all standardized, it is much easier to ensure that everything is protected from malware. Just as with our corporate computer systems, interoperability capabilities allow for our equipment to be checked and managed. Another challenge is the desire to see new “shiny objects” instead of investing in infrastructure. New, safe, medical apps are the shiny objects that require secure interoperable medical systems (the infrastructure) to be deployed.

Raines: Getting the financial support to bring an idea to fruition is not easy, especially in anesthesia. What we do facilitates patient care, but it’s not in and of itself a cure for a disease. When I first went to the Partners Innovation Fund (now Mass General Brigham Innovation Fund) with the idea for a newly designed anesthetic, it was more concept than data. The prompt was to build more data to support its worth. I disappeared for a year, generated more data and presented the compound to them before we could move forward with it.

Q. What unmet clinical needs are you most curious about today?

Denman: Improving the ability to treat patients at home through remote monitoring. We've been working on this for 30 years, but it’s all coming together and will be a game changer.

Goldman: During the pandemic, we renewed our focus on remote control of medical devices. Remote control has enabled clinicians to adjust ventilator settings without entering a patient’s room, thereby enabling faster clinical response and reducing caregiver exposure to SARS-CoV-2. Remote control is an element of our new programmatic focus on Smart and Autonomous Medical Systems (SaAMS). My team is working hard to construct an environment that will support this vision in partnership with the FDA, industry and the U.S. Army.

Raines: In addition to designing better anesthetics, I’m interested in developing anesthetic reversal agents, or drugs that can competitively antagonize the effects of general anesthetics at the receptor sites of action.

Q. What advice do you have for someone with similar career aspirations?

Denman: Mentors are an absolute necessity. I always had, at every point of my career, mentors who trained me, enabled my research, fostered my love of design and commercialization, kept me from getting fired, you name it!

Goldman: If you have a passion for research, build a career that allows time for it. At times, I have chosen to reduce my salary in order to ensure protected research time, because that was important to me. You may have to make a choice like that. And if you're not willing to, that's perfectly okay. But understand that you will have trade-offs if you want to pursue your passion.

Raines: Don’t get discouraged. Everybody gets rejected, everything will take twice as long as you think it will. It’s all part of the journey.

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About William “Pepper” Denman, MD
William “Pepper” Denman, MD, joined Mass General in 1990 as a pediatric anesthesiology fellow and stayed on as an attending following his training. In 2003, he became the chief medical officer of Tyco Healthcare and, four years later, the vice president for medical affairs, which had spun out as Covidien. Since then, Dr. Denman has split his time between his clinical practice at Mass General and other ventures at organizations that focus on medical device development, including GE Healthcare and Sirtex. In 2009, he established his own consulting firm, Denman Associates, where he supports start-up and early stage ventures in the medical device, diagnostics and pharmaceutical space.
About Julian M. Goldman, MD
Julian M. Goldman, MD, joined Mass General in 2002 as an attending anesthesiologist after an academic career at the University of Colorado and serving as vice president of medical affairs at Masimo Corporation. Today, he is also the medical director of biomedical engineering at Mass General Brigham and the director of the Medical Device “Plug and Play" Interoperability and Cybersecurity Research Program (MD PnP)—a program he founded in 2004 to empower a global community to improve patient care by enabling clinical innovation through advanced safe, secure and interoperable medical devices and digital health technologies.
About Douglas Raines, MD

Douglas Raines, MD, Mass General physician-scientist and Edward Mallinckrodt Jr. Professor of Anaesthesia in pharmacology and innovation at Harvard Medical School, arrived at Mass General in 1988 as an anesthesia resident. In 1991, he remained as an attending and pursued a research fellowship in molecular pharmacology under the guidance of Keith W. Miller, MA, D Phil, AM. His lab strives to uncover how general anesthetics work at the molecular level in order to design the next generation of anesthetic drugs. In 2009, he founded Annovation Biopharma, a biotech startup company that was acquired by The Medicines Company in 2015. In 2021, he founded HypnoTx to develop technologies invented in his laboratory.