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  • I want to talk to you

  • about one of the biggest myths in medicine,

  • and that is the idea

  • that all we need are more medical breakthroughs

  • and then all of our problems will be solved.

  • Our society loves to romanticize

  • the idea of the single, solo inventor

  • who, working late in the lab one night,

  • makes an earthshaking discovery,

  • and voila, overnight everything's changed.

  • That's a very appealing picture,

  • however, it's just not true.

  • In fact, medicine today is a team sport.

  • And in many ways,

  • it always has been.

  • I'd like to share with you a story

  • about how I've experienced this very dramatically

  • in my own work.

  • I'm a surgeon,

  • and we surgeons have always had

  • this special relationship with light.

  • When I make an incision inside a patient's body, it's dark.

  • We need to shine light to see what we're doing.

  • And this is why, traditionally,

  • surgeries have always started so early in the morning --

  • to take advantage of daylight hours.

  • And if you look at historical pictures

  • of the early operating rooms,

  • they have been on top of buildings.

  • For example, this is the oldest operating room in the Western world,

  • in London,

  • where the operating room

  • is actually on top of a church

  • with a skylight coming in.

  • And then this is a picture

  • of one of the most famous hospitals in America.

  • This is Mass General in Boston.

  • And do you know where the operating room is?

  • Here it is

  • on the top of the building

  • with plenty of windows to let light in.

  • So nowadays in the operating room,

  • we no longer need to use sunlight.

  • And because we no longer need to use sunlight,

  • we have very specialized lights

  • that are made for the operating room.

  • We have an opportunity

  • to bring in other kinds of lights --

  • lights that can allow us to see

  • what we currently don't see.

  • And this is what I think

  • is the magic of fluorescence.

  • So let me back up a little bit.

  • When we are in medical school,

  • we learn our anatomy from illustrations such as this

  • where everything's color-coded.

  • Nerves are yellow, arteries are red,

  • veins are blue.

  • That's so easy anybody could become a surgeon, right?

  • However, when we have a real patient on the table,

  • this is the same neck dissection --

  • not so easy to tell the difference

  • between different structures.

  • We heard over the last couple days

  • what an urgent problem

  • cancer still is in our society,

  • what a pressing need it is

  • for us to not have

  • one person die every minute.

  • Well if cancer can be caught early,

  • enough such that someone can have their cancer taken out,

  • excised with surgery,

  • I don't care if it has this gene or that gene,

  • or if it has this protein or that protein,

  • it's in the jar.

  • It's done, it's out, you're cured of cancer.

  • This is how we excise cancers.

  • We do our best, based upon our training

  • and the way the cancer looks and the way it feels

  • and its relationship to other structures and all of our experience,

  • we say, you know what, the cancer's gone.

  • We've made a good job. We've taken it out.

  • That's what the surgeon is saying in the operating room

  • when the patient's on the table.

  • But then we actually don't know that it's all out.

  • We actually have to take samples from the surgical bed,

  • what's left behind in the patient,

  • and then send those bits to the pathology lab.

  • In the meanwhile, the patient's on the operating room table.

  • The nurses, anesthesiologist, the surgeon,

  • all the assistants are waiting around.

  • And we wait.

  • The pathologist takes that sample,

  • freezes it, cuts it, looks in the microscope one by one

  • and then calls back into the room.

  • And that may be 20 minutes later per piece.

  • So if you've sent three specimens,

  • it's an hour later.

  • And very often they say,

  • "You know what, points A and B are okay,

  • but point C, you still have some residual cancer there.

  • Please go cut that piece out."

  • So we go back and we do that again, and again.

  • And this whole process:

  • "Okay you're done.

  • We think the entire tumor is out."

  • But very often several days later,

  • the patient's gone home,

  • we get a phone call:

  • "I'm sorry,

  • once we looked at the final pathology,

  • once we looked at the final specimen,

  • we actually found that there's a couple other spots

  • where the margins are positive.

  • There's still cancer in your patient."

  • So now you're faced with telling your patient, first of all,

  • that they may need another surgery,

  • or that they need additional therapy

  • such as radiation or chemotherapy.

  • So wouldn't it be better

  • if we could really tell,

  • if the surgeon could really tell,

  • whether or not there's still cancer on the surgical field?

  • I mean, in many ways, the way that we're doing it,

  • we're still operating in the dark.

  • So in 2004, during my surgical residency,

  • I had the great fortune

  • to meet Dr. Roger Tsien,

  • who went on to win the Nobel Prize for chemistry

  • in 2008.

  • Roger and his team

  • were working on a way to detect cancer,

  • and they had a very clever molecule

  • that they had come up with.

  • The molecule they had developed

  • had three parts.

  • The main part of it is the blue part, polycation,

  • and it's basically very sticky

  • to every tissue in your body.

  • So imagine that you make a solution

  • full of this sticky material

  • and inject it into the veins of someone who has cancer,

  • everything's going to get lit up.

  • Nothing will be specific.

  • There's no specificity there.

  • So they added two additional components.

  • The first one is a polyanionic segment,

  • which basically acts as a non-stick backing

  • like the back of a sticker.

  • So when those two are together, the molecule is neutral

  • and nothing gets stuck down.

  • And the two pieces are then linked

  • by something that can only be cut

  • if you have the right molecular scissors --

  • for example, the kind of protease enzymes

  • that tumors make.

  • So here in this situation,

  • if you make a solution full of this three-part molecule

  • along with the dye, which is shown in green,

  • and you inject it into the vein

  • of someone who has cancer,

  • normal tissue can't cut it.

  • The molecule passes through and gets excreted.

  • However, in the presence of the tumor,

  • now there are molecular scissors

  • that can break this molecule apart

  • right there at the cleavable site.

  • And now, boom,

  • the tumor labels itself

  • and it gets fluorescent.

  • So here's an example of a nerve

  • that has tumor surrounding it.

  • Can you tell where the tumor is?

  • I couldn't when I was working on this.

  • But here it is. It's fluorescent.

  • Now it's green.

  • See, so every single one in the audience

  • now can tell where the cancer is.

  • We can tell in the operating room, in the field,

  • at a molecular level,

  • where is the cancer and what the surgeon needs to do

  • and how much more work they need to do

  • to cut that out.

  • And the cool thing about fluorescence

  • is that it's not only bright,

  • it actually can shine through tissue.

  • The light that the fluorescence emits

  • can go through tissue.

  • So even if the tumor is not right on the surface,

  • you'll still be able to see it.

  • In this movie, you can see

  • that the tumor is green.

  • There's actually normal muscle on top of it. See that?

  • And I'm peeling that muscle away.

  • But even before I peel that muscle away,

  • you saw that there was a tumor underneath.

  • So that's the beauty of having a tumor

  • that's labeled with fluorescent molecules.

  • That you can, not only see the margins

  • right there on a molecular level,

  • but you can see it even if it's not right on the top --

  • even if it's beyond your field of view.

  • And this works for metastatic lymph nodes also.

  • Sentinel lymph node dissection

  • has really changed the way that we manage breast cancer, melanoma.

  • Women used to get

  • really debilitating surgeries

  • to excise all of the axillary lymph nodes.

  • But when sentinel lymph node

  • came into our treatment protocol,

  • the surgeon basically looks for the single node

  • that is the first draining lymph node of the cancer.

  • And then if that node has cancer,

  • the woman would go on to get

  • the axillary lymph node dissection.

  • So what that means

  • is if the lymph node did not have cancer,

  • the woman would be saved

  • from having unnecessary surgery.

  • But sentinel lymph node, the way that we do it today,

  • is kind of like having a road map

  • just to know where to go.

  • So if you're driving on the freeway

  • and you want to know where's the next gas station,

  • you have a map to tell you that that gas station is down the road.

  • It doesn't tell you whether or not

  • the gas station has gas.

  • You have to cut it out, bring it back home,

  • cut it up, look inside

  • and say, "Oh yes, it does have gas."

  • So that takes more time.

  • Patients are still on the operating room table.

  • Anesthesiologists, surgeons are waiting around.

  • That takes time.

  • So with our technology, we can tell right away.

  • You see a lot of little, roundish bumps there.

  • Some of these are swollen lymph nodes

  • that look a little larger than others.

  • Who amongst us hasn't had swollen lymph nodes with a cold?

  • That doesn't mean that there's cancer inside.

  • Well with our technology,

  • the surgeon is able to tell immediately

  • which nodes have cancer.

  • I won't go into this very much,

  • but our technology, besides being able

  • to tag tumor and metastatic lymph nodes with fluorescence,

  • we can also use the same smart three-part molecule

  • to tag gadolinium onto the system

  • so you can do this noninvasively.

  • The patient has cancer,

  • you want to know if the lymph nodes have cancer

  • even before you go in.

  • Well you can see this on an MRI.