Speaking with Dr. Lawrence Bass was like listening to the sound of science and business fusing into one. A graduate of Columbia’s College of Physicians and Surgeons, Dr. Bass is a nationally recognized innovator of advanced technologies in aesthetic plastic surgery and a practicing plastic surgeon in Manhattan with over 90 scientific publications in journals such as Plastic & Reconstructive Surgery, Annals of Plastic Surgery and Lasers in Surgery and Medicine. Read below to hear about how a physician can transition into business and what opportunities lie ahead for scientist/entrepreneurs. Also, we talk briefly about diamond knives.
When did you start doing research? How did you find opportunities in the medical device field?
I started doing research as an undergraduate. Having already done a year of general chemistry before college, I began taking organic chemistry as a freshman. Second semester of organic chemistry, my organic chemistry lab professor was doing x-ray crystallography research. He was a particularly engaging lecturer, and I enjoyed working with him, so I asked if I could work in his lab. For the rest of college, I did research with him. X-Ray crystallography is used to determine the 3-dimensional structure of various molecules that you might be interested in because they are possible new antibiotics, anti-tumor, or other useful medical compounds. First, you crystallize the substance and then shoot x-rays through it and observe the behavior of the rays to determine the chemical structure and the 3-D conformation. Crystallography will tell you which enantiomer (left or right conformation) the compound has; often one enantiomer is biologically active while the other is not. Once you have determined which one is active, and have worked to determine the structure, you try to find a way to synthesize it to produce a potential pharmaceutical. So you’re using physics to solve a chemistry problem to work on biological problems. It is a very productive merging of the three fields.
While I was in college, I also did research at New York Blood Center in immuno-hematology a couple of summers. Then, in my first two years of medical school, I did research with one of the cardiac surgeons at Columbia-Presbyterian Medical Center writing software for 2 and 3 dimensional ultrasonagraphy.
I was eating lunch in the physicians lounge in the Surgical Intensive Care Unit one Saturday, early in my surgical internship, with one of the general surgery professors. He was telling me about one of his new lasers he thought could be used for removing adenomatous polyps during colonscopy. The problem he was having was with the sessile polyps. One strategy was to vaporize the polyp from the top down, take a little bit, little bit, and hopefully stop before reaching the wall of the colon. However, he was having some issues with dependability. Lasers are used in medicine for coagulation, vaporization or cutting. Above the vaporization threshold, the reality is that you produce some vaporization and some coagulation; some lasers give a little bit of vaporization with a lot of coagulation, some give a little coagulation and a lot of vaporization. His new laser had a shallower depth of penetration (older ones were 3mm and this one was 285 microns) so he hoped it would avoid penetrating the colon wall during polyp removal. At the time, I was doing microsurgery research, and as I was listening to him talk, I started thinking about the possibility of using the coagulation component for welding tissues instead of using sutures because the penetration depth was just right for blood vessels. So I asked him if I could use it to weld rat arteries together. He said, sure, why not, you can fool around with it. So I ended up working in his laser lab.
We began looking at various applications for the laser, including vaporization of atherosclerotic plaques in coronary arteries. That’s how I started working in the medical device arena and medical product development, since the laser was not yet an FDA approved device; it was still experimental and a company was trying to develop it for clinical use. It was my first real exposure to FDA applications, animal experimentation, human clinical trials and some of the commercial issues associated with creating medical devices and products.
What are some of the commercial issues?
The first issue is FDA approval. The approval process varies greatly depending on what the product is, but devices generally follow one of two paths for approval. Either they follow the path of 510-K, where the device company will go to FDA and assert that their product is substantially equivalent in effect and application to an existing product that’s already approved. Otherwise the company will have to apply for a pre-market approval (PMA) application, which will require them to develop more background data on the product or device. They will need to conduct background studies on the biological effects and safety of the product, design and conduct animal studies, examine and statistically analyze results and data from any clinical use abroad, and then formulate multiple phases of clinical testing. This will usually include an initial patient safety trial with a few patients, followed by a dose safety study with a larger base of patients, and finally a phase III clinical trial that will demonstrate safety and efficacy in a sizeable cohort of patients. This final trial is called a pivotal trial because it is the deciding point for FDA approval, and it is usually a multi-center, randomized, and blinded clinical trial.
There are some strategies you can employ to help you structure your plan for FDA approval. For example, if you are coming up with a new antacid, you can look at how the last antacid released on the market did their clinical studies. Then you have to make sure the FDA has not changed or raised their standards in some way. If you decide to do something innovative that no one has done before, you will have more difficulty validating your data with the FDA. You have to define a whole new set of criteria, both objective and subjective, that you will use to evaluate your study. It’s a much harder process for the commercial entity and the clinicians, as well as the government regulators. Obviously the FDA doesn’t want to block something that may be tremendously useful, like a new anti-cancer drug, but they also can’t let everything out on good wishes. You really need to have solid data and it often requires a lot of time and effort to figure out the best way to quantify, measure, and collect this data in the best and most informative way possible.
Sometimes your best option is to meet directly with the FDA, just to sit and put your heads together and decide how to do the assay or how to get the most meaningful results or data by structuring the clinical trial in the most effective way possible. The worst thing to do is to move through an entire clinical trial that costs tens of millions of dollars and have a bunch of useless data as your end point. Everybody is trying earnestly. It’s not really a fight between the sponsor and the FDA; it’s more a matter of effective communication.
There’s another interesting point here and it takes me back to the professor that I first started working with on laser research. We were involved in some start-up activities through product and company development. We said, “We’re doctors, we work really hard, we’re as smart as anybody, we can really do everything. We can be the business manager, the fundraiser, the marketer, the engineer, the medical researcher, we can do it all.”
Theoretically we probably were smart enough to learn each job, but in reality, it takes a lot of time and effort to learn each component of the start-up business. You don’t have the expertise, prima facie, to do all of it. You’re much better off getting people who are experts in those respective areas and slicing up the pie and sharing the company. It took us a while to learn that.
However, there’s always a risk in hiring others, because if you bring the wrong people you can tank a project. I’ve seen a number of products, that were great medical devices or treatments, die, not because they didn’t work, but because of how the company development played out.
What do you do in terms of your corporate work?
I do a lot of different things. I do a small amount of laboratory research which is usually at NYU, although sometimes in outside corporate venues. I’m currently on the clinical faculty at NYU. I also do clinical academic research – I write and teach to report clinical experiences or advances in techniques and outcomes. Because I do a fair amount of lecturing and teaching about new techniques and new devices in plastic surgery, some device companies seek me out to help them in developing educational programs for doctors and also to help them in various different ways in developing new products and getting them approved.
In the current structure of FDA clearance, if the FDA feels a new device or treatment is novel enough that it will require provider education to be used effectively, the FDA can compel a company to provide some kind of education in the form of a webinar, online course, or a nation-wide lecture tour with a standardized slide deck. Companies will pull together 50 experts from around the country to develop the educational materials to teach doctors about the new technique.
Earlier in product development, I often help pick clinical applications or focus areas where they will be most useful. For example, say you have a new device for cutting and sealing – will it be most useful in endoscopic surgery or neurosurgery or vein harvest for coronary artery bypass?
So it’s not just plastic surgery.
Right. Plastic surgeons are basically biomaterials specialists. We borrow almost every body tissue to rebuild some damaged function elsewhere in the body. We understand about tendon, bone, muscle, nerve, fascia, fat; all of these tissues are routinely used or handled by the plastic surgeon.
I work with a company to help improve the function or point out the deficiencies or limitations of an existing device that they will need to overcome. Sometimes they will have me use the device in an animal lab, or if it’s ready, in the clinical setting, just by brainstorming and trouble shooting. Sometimes it’s me inventing a new device or they’ll come with a problem “we want a way to do this” and we’ll think through a number of options. Sometimes it’s looking at intellectual property and figuring out a way for a new company to provide a product or device in an existing area without infringing on another company’s patent. Sometimes I’m hired to look at a patent held by one device company, and determine if their patent is being infringed by another company or device. If yes, then I’ll serve as an expert witness in their patent litigation case.
I have also gone on behalf of companies to speak with the FDA during their approval process or while trying to formulate the structure of a particular study. Most medical device and pharmaceutical companies have a regulatory department whose personnel understand how to work with the FDA, so they need clinical expertise and input from someone who also understands the regulatory side – how FDA regulations work and how they make decisions and what conditions they are bound by because they have to follow specific rules. You need to propose something that is workable for FDA. The same holds true with patent infringement. You need to understand enough about patents and enough about patent law to give useful advice and information. You’re mostly there for clinical knowledge but you need to know how to best interface with the legal and corporate parties involved.
The same thing is true with product development. It is a classic refrain from doctors: “Well this would be a great product and it would really help us if we had this.” And they don’t understand why it’s not being made. But it’s not being made because it’s not commercially viable. It would never be approvable from an FDA regulatory standpoint, or it would never be profitable enough to pay back the development costs so the company making it would eventually end up going bankrupt. And that’s not productive because if the company’s bankrupt the product’s not going to be there for the patients. It must be done in a way that allows the company to pay back venture capitalist investments or, if it’s a bigger company, research and development costs. If not, the company won’t be around long enough to develop more wonderful new things. So you have to develop and pick specific application areas such that the product has the potential to be fiscally viable and allow the company making it to survive. Not every product is going to be a billion dollar a year market – not every product is a Botox.
What additional value does the medical degree have that might not be immediately obvious?
There are a lot of people who have studied on the PhD level and maybe even worked for many years in a research lab. They have studied the biological basic science that we studied in medical school. In fact, they have a much more in depth exposure than we have in our survey medical school courses. However, that is basic science. Doctors are basically applied scientists, just like engineers. There’s physics and then there’s engineering physics, which is an applied science. Medicine is applied science in the biological arena. That’s very important because the big buzzword right now is translational research. Translational research is moving from the lab into the clinic, getting it out there. The basic idea is making it useful and integrated into clinical care. It’s very hard for a basic scientist to do that. It is hard for a basic scientist to understand what clinical needs are, and how clinical practice is performed. And doctors have the ability to understand that.
If you’re selling a product your customer doesn’t need, then you’re not going to have a lot of sales. If you’re selling a product there is a tremendous need for, he’s probably going to buy a lot and pay a high price. And it’s very important to identify that, particularly considering the tremendous expense of developing new devices and new products, especially pharmaceuticals and biologicals. Just in round numbers, device approvals can run tens of millions of dollars in development costs and drug approvals can run a couple of hundred million to half a billion dollars. You need to be pretty clear that there is a need for what you are creating, and that it fits in with the current evolution of the specialty it is intended for, as well as look at multiple specialties it could be applied to in a multidisciplinary way. Sometimes that is something that can be challenge for a doctor since everyone is so clinically specialized these days. You have to be able to figure out if it will good in general surgery or in ob/gyn surgery. Everybody’s got his own set of problems so having a broad understanding and a good generalist medical education is tremendously valuable.
However, the trend is currently going away from that. It is towards this very specialized training, which makes it extraordinarily hard to cultivate a broad range of general medical knowledge. But there is a need for generalists in the sense of bridging all specialty divides and being able to advise a company: your first application should be urology, not gynecology, etc. That is the kind of knowledge that doctors can provide, which is very hard for anyone else to be able to do.
What are the other aspects of your career that you’ve been involved with as a result of having the M.D.?
Because of the medical product development work I’ve done, I’ve been introduced to a number of venture capitalists, entrepreneurs who work with start-up companies, engineers. In some cases, it’s allowed me to play more of a business role or a medical advisory role than a medical doctor role.
How does one go about finding these opportunities?
It’s hard to innovate on schedule. But all you can do is keep your eyes open, be a curious person, be creative and inventive and analytical. And when you least expect it, you will run into something. You will run into people like the professor I met in the lunch room who first introduced me to laser research. If you want to be involved in something, you just have to keep your eyes and ears open.
Any last words?
To a large extent, doctors have, understandably, not been highly business savvy. I think the only way we’re going to defend ourselves is being smarter on the business side and being engaged in the process of how healthcare is administered. We have no business training, we have no time, and we’re trained to heal the patient. But the problem is, if the system collapses financially, we’re not going to be healing a whole lot of patients. We can’t kill the goose that lays the golden egg. We need to have a healthy healthcare system so we can continue to help our patients.
“One of the very few silver linings about me getting sick is that Reed’s [his son] gotten to spend a lot of time studying with some very good doctors… I think the biggest innovations of the twenty-first century will be the intersection of biology and technology. A new era is beginning, just like the digital one when I was his age.” –Steve Jobs (from his biography, Steve Jobs)