"COVID 19 and Long Covid: Rapidly Developing Therapies For a New Disease" - An Interview With Art Wallace M.D. Ph.D. of the VA Medical Center San Francisco and UCSF

by Samantha Dvorin, Archie Williams High School 

Art Wallace is a cardiac anesthesiologist and biomedical engineer who works as a professor emeritus of anesthesiology and perioperative care at UCSF and the Chief of Anesthesia at VAMC SF. He researches drug and device development to reduce perioperative risk. He has a B.S. in engineering and applied science from Yale. He also has an M.D. and Ph.D. from Johns Hopkins Medical School in Biomedical Engineering. On Wednesday, November 30, 2022, Dr. Wallace presented "COVID 19 and Long Covid: Rapidly Developing Therapies For a New Disease" at the Marin Science Seminar. We asked him some questions about his work.

1. How has the world of drug development and research changed since the emergence of COVID-19?

Science has had to speed up dramatically. Normal drug development takes one to two decades. In COVID we had to do it in 1-2 years. Prior to COVID, the fastest any vaccine had ever been developed was 4 years. With COVID, it was done in 1 year! AIDS has been around 40 years and we still don't have a vaccine.

2.  Who is most at risk for Long COVID and is it preventable?

Older people, people with co-existing disease, and unvaccinated people. But, young, healthy, vaccinated people, who didn't get very ill with covid can still get Long COVID. Prevention is very simple, don't get COVID and get vaccinated and boosted.

3. What are some common misconceptions people have about COVID, especially Long COVID?

There are several diseases such as myofascial syndrome and chronic fatigue syndrome which we don't understand. We don't know the cause or have any treatment or know if they are really diseases. When a disease is of unclear origin with no therapy there is a tendency to say it is psychosomatic (in your head) or is just depression. When Long COVID came along some people thought it was just depression. Some thought it was psychosomatic. The NIH invested more than 1 billion dollars with the sole question of “is this a real disease?” and gave the grantees four years to figure it out. These grants were not allowed to search for cures for long covid, just ask, does it exist. A month after the request for proposals, an epidemiologist in the VA Al-Aly did epidemiology to show exactly what the symptoms were, how many people got them, and how long they last, essentially making the NIH studies, which hadn't yet even started, useless. 

4. Why does every patient experience Long COVID differently and does it have anything to do with previous health issues or the severity of their initial COVID diagnosis?

Long COVID seems to be a multitude of problems. Microvascular damage, autonomic damage, neuroinflammatory processes, cardiac and renal damage, and psychiatric problems. People who get severe COVID have more problems with long covid, but people who get mild COVID can still develop long covid. The exact cause is unclear. It is likely multiple factors including immune response, the severity of illness, microvascular damage with small thrombi causing stroke, neuroinflammation, and maybe some residual virus. The causes are unknown.

5. Does having the COVID vaccine and the subsequent boosters have any effect on the likelihood of getting Long COVID or on the severity of the disease? 

Yes. Vaccination reduces the risk of long covid by about 15%.

6.  What does a typical day as a cardiac anesthesiologist and biomedical engineer look like?

Get up at 5 am to go to work. Three days a week I work in the OR providing anesthesia care to patients. Two days a week I do administrative work (hire people, get them paid, etc, etc, etc). I then use the rest of the time to do science (figure out how to pay for it, fill out paperwork to get it approved, write grants, develop software, publish papers). Then go home around 7 pm. Oh, then I am on call at night and on weekends when people have a disaster.

Dr. Wallace in the operating room

7.  What advice would you give a young person interested in medicine or medical research? 

Study hard, take science, math, etc classes. Do well in class. Apply to the best college you can get into. Get perfect grades. Then take a year of English, a year of calculus or higher math, a year of chemistry with a lab, a year of organic chemistry with a lab, a year of physics with a lab, biochemistry, psychology, statistics, and then major in something. I was an electrical engineer. Volunteer in hospitals so you can decide if and why you want to be a doctor. Volunteer in a lab doing research to learn how to do research. Then apply to medical school and or an MD/Ph.D.

8. What is your team working on now to advance the drug development process for Covid and Long COVID? 

We are looking at publishing continuously a daily update on vaccine efficacy and boosters. We are trying to get funding for the long covid drug development project. Paying for research is the hardest part.

Learn More:

• https://marinscienceseminar.com/covid-19-and-long-covid-rapidly-developing-therapies-for-a-new-disease/ 

• https://www.commonwealthfund.org/blog/2022/two-years-covid-vaccines-prevented-millions-deaths-hospitalizations 

• https://www.nytimes.com/2022/12/14/health/long-covid-deaths.html 

More than a Surgeon's Sidekick: The Anesthesiologist

An anesthesiologist at work.

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      Dr. Art Wallace is a professor of anesthesiology and perioperative care at UCSF, and an attending anesthesiologist at the San Francisco Veterans Affairs Hospital. He is a man of sharp wit, wry humor, and countless analogies to explain the complexities of anesthesia. He was also kind enough to answer a couple of questions for me over the phone.

What exactly is anesthesiology?

      An anesthesiologist makes patients become compatible with surgery. They put patients in a state in which they can undergo painful operations and surgeries. Anesthesia requires the use of several powerful, lethal drugs and is extremely dangerous. Its cultivation over the last 150 years has been geared toward making it more effective, more efficient, and thus more safe.

      Anesthesiology has helped reduce the risk of surgical care tremendously. Around the 1950s, the ratio of fatal to nonfatal procedures was 1:200 to 1:1500. The present day ratio of 1:100000 to 1:1000000 looks multitudes more reassuring.

      In particular, Dr. Wallace has researched ways to reduce stress during surgery.

What’s the difference between stress and pain?

      Pain is a sensory experience and can cause stress, such as increased heart rate or blood pressure. Stress is the physical effects of the strain, which can ramp up to heart attacks and strokes. While a person can be unconscious and not experience pain, stress can still occur.

What can anesthesiologists do?

      Anesthesiologists can manipulate what a patient experiences under surgery. Consciousness, feelings of pain, autonomic responses, movement, and even memory can all be suppressed by an anesthesiologist during surgery. A patient could not remember the operation at all, or, during the operation, “feel pain but not care.”

      The range of parts an anesthesiologist can turn off allows more people access to safe surgery. People terrified of surgery can choose to be unconscious or not remember any of it at all. Mortality rates of women in childbirth have lessened from a ratio of one death in ten survivals to one death in ten thousand, or even one death in one hundred thousand. As Dr. Wallace put it, anesthesiology serves a “nice, noble cause.”

 A venn diagram on some uses of anesthetics.

(source)

How do you decide what to give a patient?

      There are typically two main components to deciding what to dose a patient. The first are the patients themselves. Are they terrified? Are they at risk of heart attack or stroke? Do they have a cardiovascular or lung disease that drugs could possibly irritate? Depending on the attitude and the physical condition of the patient undergoing surgery, different doses with different effects might be prudent. 

      The second component is the type of operation. Depending on the severity of the injury and the operation needed to fix it, more or less anesthetics are required. “What I’m going to give for a broken finger, versus a heart transplant, will be a lot different,” Dr. Wallace explained.

What sorts of fields come into play in anesthesiology?

      The general knowledge of medicine that comes from med school, residencies and internships are all pre-requisites for any practicing doctor. Anesthesiologists need an understanding of physiology and cardiology, as well as the ability to interact with surgeons. Fixing the monitors that check on the patient’s condition—in other words, some engineering—is also needed.

What are monitors and how do they help anesthesiologists?

      Monitors are the screens connected to machines that watch a patient’s physical condition, including things like blood pressure, cardiac output, isofluorine concentration, EKG, etcetera. The ability of a computer to constantly monitor a patient’s condition when the patient is unconscious and unable to give indications of discomfort is incredibly useful and critical to the safety of patients undergoing surgery.

What sorts of problems are being worked on by anesthesiologists today?

      Drugs still need to be developed to better prevent heart attacks and strokes for patients. In general, anesthesiology is constantly working towards safety. Safer drugs, more efficient methods, and less room for error means less risk in surgery.

How would you go about becoming an anesthesiologist?

      The usual track is four years in college with any major. Afterwards is medical school, where the pool of majors narrow down to the general field of medical science. Then there’s clerkships, where students rotate through a multitude of different medical professions, usually a month or two in each. Afterwards is an internship, where young doctors hone the glorious ability to write prescriptions. Throughout all of these stages, the medical student is narrowing down their field of study, until they can go through their residency, where real hands-on experience and learning begins, and specific fields are explored. Afterwards, the newly minted doctor has enough experience to begin practicing.

How do robots come into the whole thing?

      The robots that are going to be the topic of this Wednesday’s seminar are new technological developments used for training young doctors. Originally, beginning doctors spent ridiculous hours—maybe even 110 hours out of 160 in a week—writing prescriptions and deducing problems. The sheer amount of work tired the doctors and caused them to make errors on very real prescriptions, for very real patients. Instead, robotic patients are being developed for doctors to practice on. Like a simulation, the robot patients can simulate everyday illnesses to rare diseases, or specific instances that seldom arise. All of these situations prepare doctors for as many different occurrences in their career. “You wouldn’t want a pilot to crash on the job,” Dr. Wallace explained, “and you don’t want a doctor to mess up on a real patient.”

How did you become interested in anesthesiology?

      Already interested in becoming a doctor since his mother’s death in middle school, Dr. Wallace pursued the sciences straight into college (though he preferred the challenges of physics over the memorization of biology in middle school). He majored in electrical engineering but, after a summer job doing surgery, he became interested in medical school. Initially a surgeon, Dr. Wallace became an anesthesiologist later in his career. 

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      Then we got talking about some wacky things. Take Michael Jackson, for instance. His doctor had prescribed him drugs more under the jurisdiction of an anesthesiologist. According to Dr. Wallace, had Michael Jackson hired a trained anesthesiologist instead, he might still be alive.

      Exactly how lethal are those anesthetics, anyways? Narcotics more than a hundred times more potent than heroin, barbiturates that send patients to sleep, drugs that stop the heart, invoke paralysis, stop nerve transmission, and stop brain function, are all used by anesthesiologists. “All of them can be  fatal,” confirmed Dr. Wallace.

      Any jokes about rising to evil overlord-ship dissolve in the face of Dr. Wallace’s actual occupation. Not only does anesthesiology help terrified patients undergo necessary surgeries, but Dr. Wallace works as an anesthesiologist at the Veterans Affairs Hospital in San Francisco. At the VA, surgery is free. Veterans can access the procedures and the treatment they need, easily. They do well under the care of surgeons, doctors, and anesthesiologists like Dr. Wallace. Nothing could be farther from nefarious deeds.

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Come see Drs. Art Wallace and Hirsch present “Computers, Robots, and Medical Education, Oh My!” on Wed., December 5th, at the Marin Science Seminar. The Marin Science Seminar takes place on Wednesdays in room 207, from 7:30 to 8:30 p.m. 

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Sandra Ning

Invention in Medicine: How Medical Devices get Invented and Go to Market

with Art Wallace M.D. Ph.D.
December 10, 2008, Room 207

Dr. Wallace started out in experimental surgery and radiology studying imaging of the heart using CT scanners. He has worked on a number of devices that originally were built for experimental studies that evolved into clinically useful devices including a cardiac output monitor, the off pump CABG, off pump aneurysm surgery, electronic sedation, and a selective coronary vasodialtor. Dr. Wallace will explain his experiences with the inventive process using examples from both device design and drug development. There will be a brief discussion of the importance of intellectual property, patents, venture capital, FDA approval, and business development in completing the invention process.