Doctoral student on the go - part four

Controlled release of drugs, microsystems, biomaterials and tissue engineering.Roey Tsezana is debating between the different tracks at the biomedicine conference in Antwerp. live report

The second day of the conference, after the festive opening in the evening. In fact, it can be said that this is the first day of the conference, because yesterday was only the opening lecture and the dinner, and today we begin the real series of lectures - starting at 8:30 in the morning and ending at XNUMX in the evening (and then the social events begin). When I went to bed the night of the opening, I set an alarm clock for seven in the morning in advance, which helped like a toast to the dead. I woke up at half past eight, like clockwork, just in time for the first lectures of the day, unshaven and unshowered. the clock? He has been humming shyly by the side of the bed for an hour and a half.
I resigned myself to the fact that I would miss the first lectures (no big deal, everyone is tired at this hour anyway) and decided to come to the conference as a human being. I shaved, showered and even got dressed from Gunder, in my newest jeans with a polo shirt and a cute knit. I remembered that the invitation to the conference specifically stated that the dress code would be informal. It turns out, by the way, that everyone has their own definitions of what is formal and what is not. All the lecturers came with a tailored button-down shirt, a quality tie and a camel or llama wool coat. Luckily, I also brought the lilac button-down shirt in my suitcase for the day of the big lecture, but I left the tie at home (after all, they said informal!). I'll probably have to go buy a tie. I wonder if a Mickey Mouse tie meets the definition of 'informal'.

The conference itself is divided into almost ten halls, each of which deals for an hour and a half with lectures on a certain topic. Some subjects do not interest me at all - for example, computerized image analysis. Others are interesting, but not in my area of ​​expertise, so the chances of me understanding something there are pretty low. And finally, there are the areas that are important for my research: controlled release of drugs, microsystems, biomaterials and tissue engineering. So I apologize to anyone interested in computerized image analysis or the mobility of the inner wall of the heart. You will need to find other reports from the conference to read about these areas.

Each of the sequences is divided into short lectures of twelve minutes, and another three minutes for questions from the audience. The lecturers, in general, are the master's and doctoral students - master's or third degree students - who worked on the research and came to report on their successes and failures. especially their successes. I came to the first series of lectures, which dealt with microsystems, towards the middle, just before the start of the lecture about a new and efficient micropump for controlling the sphincters (anus). exciting.

The truth is that it turns out that this project - Project GASS, as the German researchers call it - can be very important to a large number of people. Sphincter control problems exist in many elderly people, either after prostatectomy, or as a result of other medical problems. There is no doubt that this is a very embarrassing problem for many who have to go back to diapers. The researchers' solution in this case is to implant a particularly economical pump in the pelvis area - five times more efficient in its power consumption than the pumps that exist today - which will control the closing and opening of the valves.

The next young researcher - also with a well-tailored tie and shoes that cost as much as my monthly salary - chose to survey an innovative system of micro-needles he is working on, for a simple and time-coordinated injection of drugs. It is now known that there is a close connection between our biological clock and the administration of the drug. There are drugs that work better while sleeping than while awake, but of course it is difficult to achieve convenient self-injection during the night. For this purpose, a new system was developed that focuses on the transfer of drugs through the skin.

The system is based on plastic microneedles, which proved to be hard and strong enough to penetrate pig skin in a controlled experiment, and the drug can still be injected through it. The whole system is the size of a postage stamp, but allows drugs to be injected at a controlled rate and at controlled times. And the best - it is without a trace of electronics. It's all based on cheap liquid diffusion technology, and the 'ball' is designed for single use throughout the day/night.

So the truth is that after seeing this, I already feel that my research is really small and useless compared to this tiny 'calculator' that works on diffusion and not on electronics. But the first meeting ended after a short time, and we continue to the keynote lecture by Professor James Kirkpatrick who is already involved in my field - tissue engineering and the creation of scaffolds from smart biomaterials.

Kirkpatrick works according to the maxim of the great philosopher of science from the past - Aristotle - according to which nature does nothing without a reason. In his opinion, rehabilitative (regenerative) medicine should focus on biomimetics and understanding the way the body restores itself - and find the right tool to use to give the push at the right place and at the right time that will speed up and start the full and natural restoration process. As an extreme example, if we take a salamander and cut off one of its legs, we will get a new leg within forty days. We know that gene sets are conserved among many creatures, and according to Kirkpatrick there is a good chance that if we find out how the body does it, we can mimic the process in humans as well.

"The first generation of implants started in the XNUMXs and constituted one of the first technology transitions from existing technological areas. It was very effective, but they soon discovered that the body does not like foreign substances being introduced into it," explained Professor Kirkpatrick, "therefore in the seventies and eighties they began to produce inert substances, to which the body does not react. But they found that no substance is truly inert, so in the nineties they started trying to create substances that would react with the body in the right way."

In rehabilitation medicine there are two main subfields - cellular therapy and therapy using biomaterials. In the case of biomaterials, we can reengineer tissues with the help of scaffolds and extracellular matrices, or engineer new drugs and preparations for gene transfer using nanoparticles. And of course, the two can be combined by coating a scaffold for tissue engineering with nanoparticles.

Kirkpatrick emphasizes that there is a lot more we don't know, but it doesn't bother him much. "As a pathologist, I tell my students that we are very simple people. We can take advantage of our lack of knowledge and use nature's black box.” As a good example of this, he presents studies in which seeding bone cells of a certain type (osteoblasts) together with endothelial cells led to the differentiation and organization of the endothelial cells into blood vessel structures. We don't understand how the osteoblasts got the endothelial cells to do this, but we can use it to our advantage.

Another idea (reviewed in the 'Hidan' a few weeks ago) is that of Professor Stoop from Chicago: Use a nanofibrous scaffold with laminin. Laminin induces neural differentiation in cells and Stop showed that he could inject the polymer into the area of ​​spinal cord amputation and achieve a partial restoration of motor control.

The main problems that still exist today in the field of tissue engineering are poor vascularization (formation of blood vessels). If there are no blood vessels in the new tissue, then the cells will not be able to survive in it for a long time as a result of the lack of nutrients. The second problem is that despite (and perhaps thanks to) the use of the 'black box' method, we simply do not fully understand the body's rehabilitation niche. Sometimes we work with all the best intentions, but accept that the body reaches a fundamentally pathological rehabilitation - for example, in the case of a defect in the cartilage, the body will not fill the space with healthy cartilage, but with scarred and dysfunctional tissue. Another example is the misuse of stem cells, which may cause cancer.

In the end, despite all the problems that still exist in the field, Kirkpatrick is convinced that the most likely approach to success is that of biomimetics. This, by the way, makes me very happy because this is also the approach I take in my research - but that's a story for another time.

When the lecture ends, I start to wonder: what to do now? The main debate is between a seminar on microsystems 2, and a symposium on the employment options facing biomedical engineers in academia and industry, and the fields of study in which it is worth investing in universities. In the end, I decide to expand my horizons and check out the symposium on education and employment - also because I myself should finish my third degree in a year and a half and am still not sure which direction to continue (academia, industry or homemaker) and also because I have a class of fifty children are great at the Technion, that I need to know what to tell them about their professional future when I return from the conference. (I have a suspicion that some of them are older than me, but my developed Polish sense dictates to me that as long as they give me homework and I answer them on the phone about questions from other subjects, they are still my children).

The truth is that it is very difficult to understand what some of the lecturers at the symposium want. In general, professors from different universities come and talk about the biomedical engineering programs they lead, and why they are better than those of all the others. Some claim that the field should be 'harmonized' - that certain universities will concentrate on specific subjects and others will concentrate on other fields - and then go on to explain why the program at their university is better than all the others. In short, a lot of words, less real meaning. But what do I already know? I didn't do a bachelor's degree in biomedical engineering, so I probably have no real right to speak on the subject.

The more interesting topics come from the last two lectures in the symposium. Jörg Weinken, a researcher in the biomaterials sciences and a professional collaborator with the industry for over twenty-five years, tried to explain how to get from the academy to the industry, in a lecture called "The biomedical engineer, the hottest job of the decade?"

According to Weinken, getting into the industry is particularly difficult because a large amount of money needs to be invested before returns start to come back into the pocket, if at all. 25% of the funding goes to the development and production of the device, 50% goes to development and marketing and the remaining 25% goes to sales and marketing. Even before developing the initial device, it is necessary to develop a prototype that will show that your idea even works - and this requires between three and seven million euros. And if you want to take it further, there is a need for clinical tests that will cost several tens of millions of euros.

If all this is not enough, it turns out that the successful development of medical devices these days requires cooperation from all possible fields - both technological and scientific. A global approach is needed to obtain approvals from all major health authorities such as the American FDA, the European EMEA and the Japanese MHW. If you want to really succeed, then you must invest a huge fortune in the miniaturization of the device, to provide the cutting edge of technology. And of course, you have to decide what the target audience will be (which requires investing in an audience survey) and adapt the device for it, or the audience for the device. And after all these, you should also make money.

So how will you still profit from your academic achievements? Well, you can take your idea and sell it to industry – or start your own company. If you open a start-up, this has great advantages: you are your own boss, you can change direction immediately, all the success is yours, you are going to be rich (soon), you don't have to write applications for grants or research projects, etc. . But there are also problems. First of all, you are the boss and that means all problems come directly to your doorstep. Your shareholders must approve any change of direction. It takes much longer than you think to get rich. You need to write grant applications for open projects and technical reports. You must listen to the market and obey it all the time and so on. When you think about it from this point of view, it's a bit surprising that there are people in academia at all who are willing to make the big leap into the world of industry and startups in particular.

But even if all this good advice doesn't interest you, dear readers, Weinken emphasizes one thing, the most important of all: always register a patent.

After Weinken, Mr. Wilson d. (whose first name did not come up for discussion), who tried to answer the question of whether it is even worth transferring from the Academy of Industry. He himself can be proud of a doctorate in biomedical engineering and experience in academic research, but in the end he chose to move to a large biomedical company called Smith & Nephew, where he supervises projects, raises his own small doctoral students, obtains research and development grants of millions of dollars and has already managed to publish eight International patents.
So what is still better? Academia or industry?
"In industry you focus on problems of real importance to society," Wilson explained. ” In academia, on the other hand, you can work on whatever you want. In industry you do what needs to be done, but in academia you do what you want to do. In industry there is the pressure of trading - you must do what the markets require, while in academia there is the pleasure of learning. In industry there are higher salaries and various bonuses, but in academia there is the pleasure of teaching students and supervising them."
Where should you start the transition to industry? As usual, it all depends. Small companies, with less than a hundred employees, provide a great opportunity to advance your career and experience. You should take into account that the working hours are indeed long, but any progress can lead to a big jump in salary. On the other hand, such companies are always at risk of collapse. In large companies (of a billion dollars or more) there is a smaller risk that the company will collapse, the career paths are more structured, there are more budgets and there are many flights. If you like flying, it turns out, you should work for a big company.
The challenges in today's industry are different from the past. The successful biomedical engineer needs to specialize in engineering, biology and medical sciences - all together and each separately. You have to contribute to the development, design, manufacture and testing of the devices. You need to bridge the gap between clinical medicine and medical technology. In addition to all these, you should be innovative, creative, able to work in groups with people from all fields and still pay attention and listen to your customers. In short, Superman.
So how to ensure success? Wilson outlined a number of basic rules that all apply to academia as well, except for the last one:
1. Set realistic short-term goals, and break the research into these small pieces.
2. Identify your mentor and learn from them.
3. Find your personal style. You may want to work on just one project, or juggle several projects.
4. Develop disciplined work habits.
5. Work closely with customers, the sales and marketing department. They are the ones who will eventually have to sell your device.
Last but not least, emphasizes Wilson, the beginning industrialist must understand that his products will greatly affect the market and the hospitals and it is necessary to prepare accordingly.

Definitely an instructive lecture and right after it I approached Wilson with a private question of my own. I have an unusually talented friend who is currently doing a master's degree and is debating whether to continue in academia or industry. I explained the details of the case to Wilson, and he answered without hesitation, "If she's talented, let her go to industry. In the academy she won't be able to really create anything. She can earn much more in the industry and achieve much more."
I can deal with this advice (even though I myself try to constantly push it in the academic direction), but what it turns out is that only the untalented remain in the academy! When I presented the problem to Wilson, he hesitated for a moment and then gently explained that it depended on the areas of research she wanted to pursue. If she prefers to concentrate on theory, then the academy is the place for her. But if she is ready to turn the theory into reality - she should move to industry. So now everything is fine. She just needs to decide what she is going to research for the rest of her life, and based on that determine what is more suitable for her - industry or academia.

And here, two seminars are over and it's time for lunch on behalf of the conference. After paying a 380 Euro conference registration fee (not including hotel or flight. Basically it doesn't include anything except attending the conference and lunch every day), I dared to hope that the conference organizers would provide a lunch that was worth the price. I have already promised that I will concentrate mainly on the scientific program, so I will not whet the appetite of the readers by describing the wonderful meals I experienced during my first two days in Antwerp. I won't tell you about the restaurant La Place, where I chose my tender and ruddy piece of entrecote myself, watched and controlled the degree of doneness and seasoning with direct instructions to the cook and received it at the table with a heaping portion of thick, golden chips (twelve euros). The result - lust for the palate and stomach.
No, I won't go into detail about the Leonardo De-Vinci restaurant either, where I ordered the Mixed Grill dish - meat of all kinds and experienced my second culinary thrill in two days. I'm actually a picky eater, but this meat was so good, the seasoning subtle yet tickling all the right places on the palate, that I couldn't help but compliment the waiter, chef and cashier on the masterpiece embodied in the plate on my table (18 euros, worth every penny) .
Which brings us to the conference lunch. There is a phrase that says, "It's not even wrong", referring to ideas that don't even try to check their level of correctness. The lunch reminded me very much of this sentence. The food didn't even try to pretend to be delicious. I will not detail the dimensions of the horror, but I will only mention that in my last reserve at BHD 10 I ate better food. And really, but really that says it all.
In the name of fairness, I will note that all the other guests walked around with plates full of the same semi-liquid ecological-culinary disaster, and it seemed that some of them even managed to adjust their minds to the idea that it was edible.

And on to the next sequence of lectures, which dealt with inventions and nanotechnology. The first lecturer was Phil Troik, who spoke about the holy grail of modern medicine: restoring light to the blind. It turns out that every seven minutes, another American goes blind. As of today, ten million Americans are blind or suffer from particularly severe visual impairment. Beyond the humane problem, there is also a financial issue involved here because seventy percent of the blind are unemployed, and some of them are also depressed and cut off from the environment.
The intra-optical approach uses camera glasses that send electrical messages directly to the wearer's brain. The final idea is to take advantage of the photon mapping capability of the grunt to obtain a clear image. The electrodes that connect to the brain are incredibly delicate, with a final diameter of less than the size of a neuron. The electrode turns the current of electrons into a current of ions in the tissue, and is able to stimulate specific areas of the brain at different levels.
Although in ancient times they used to transfer the electrical information to the electrodes using thin cables, it is clear that this is not the way to continue the development of the electrodes. Even a low-quality image would require thousands of electrodes in one brain, and the cables would take up too much space. Therefore, the researchers chose in this case not to use cables and switch to external activation of the electrodes using an external magnetic field. Each electronic chip in the brain will contain an electric coil, and the changes in the field will convey the messages to it - as well as the energy for activation. The coil and the entire chip will be contained in a protective polymer sheath, apart from the current-conducting needles, which will connect to the appropriate point in the brain. And the best - all this hardware is not only possible, but is already in the most advanced stages of development.
According to Troik, most of the technical problems have long since been solved, but the problem of high complexity still remains. "We can create hardware that is smaller than the neurons it is supposed to stimulate, but we still have problems: placing the electrodes in exactly the right place, and the fact that a few thousand electrodes will not, of course, provide perfect evidence even if they are placed in exactly the right places and receive the right information."
Still, it's nice to see how advanced this scientific-engineering field is. It is amusing to note that the person in charge of the event, during the lecture, was very interested in updating his Facebook profile and browsing the profiles of half-dressed girls. Still, it's good we have eyes.

After Troik, Weiringa (whose first name I don't have) took the stage, who spoke with great interest about aluminum foil systems - opening new perspectives in medical technology.
The company where Weiringa works has developed a technology that makes it possible to print flexible organic electronic circuits on aluminum foil. This technology is capable of enabling the creation of many applications, such as smart bandages and smart packaging for medicines.
In many wounds, and especially in burns, it is mandatory to remove the bandage once a day and check how the wound heals. If everything is fine, then it's a real shame that you took off the bandage - you can reopen the wound that way, or simply expose it to infections in the air in the room. The technology of printing the flexible circuits can be used to embed wireless detectors in the bandage, which can scan the wound at different wavelengths and produce analysis at different levels. Such an electronic bandage would be able to monitor the wound continuously so that there would be no need to remove it - unless there is a real reason.
Another place where the flexible circuits can help is in the administration of medication. According to statistics, about 120,000 people die every year in the United States as a result of improper use of drugs. Circuits printed on the aluminum packages of the pills can remind us to take the pills on time through a link to other systems (for example, the alarm clock, the personal computer or the cell phone). They will also be able to directly inform our doctor whether we have taken the pill or not.
Although the idea is not new, the researchers are interested in marketing it at a particularly attractive price - five cents per pack. At this price it will be possible to integrate the system into every medicine box and every bandage. The drugs in the future will be able to remind us to take them, contain a clock that will notify us when the validity expires and even monitor the temperature around them and tell us when it has crossed the permissible threshold.
The next lecturer is Mr. Syryujkina from Ukraine. The chairman of the seminar calls his name. Silence in the crowd. He again calls Mr. Syryujkina to stand up and present his research. The Ukrainian disappeared as if swallowed by the earth, and without prior notice. Apparently he is also stuck with the Minister of Traffic on the way to the conference. It is strange, very unusual and unacceptable, but there is nothing left to do but hope that he is well.

After a few more short lectures we disperse for a short coffee break. In Israel, the coffee breaks are actually croissant breaks, and as a big fan of croissants, I was eagerly anticipating the coffee breaks at the conference. big disappointment. We get a narrow square of lesson cake and biscuit cookies in the shape of letters (I created the name of the conference from them and took a photo). I repeat again - 380 euros registration for the conference.

At 18:30 the lectures end and we go on the promised trip to Antwerp, on foot.
cold.
rainy.
snow.
You read that right: we are going for a walk. An hour and a half during which every survival instinct in my body calls me to find a warm cave, find flints and start slamming them together hoping for every spark of warmth. From the faces of most of the group members it seems that they also share the same feeling. The toilet papers in the bags quickly run out, and morale plummets to a new low. But, don't worry, the guide is blonde and happy, walking around without a hat and stocking in a skirt, while we're all wrapped up like woolly mammoths. She drags us through the length and breadth of the city, ignoring the coughs, sneezes, loud nose-desserts and curses about the day we were born. She explains to us with a broad smile about the welcoming nature of the city - the Romans conquered it, Napoleon bought a house there, the Germans took it over - and they all disappeared in the end. Not surprising, actually. Winter must have come.
What did I learn about Antwerp? The whole plot can be summed up in three recursive sentences:
1. Four hundred years ago, a famous painter named Rubens lived there. This is his house.
2. Robbins had a mother. This is her house. He also had a grandmother. Here is her house.
3. The Germans dropped bombs and leveled many buildings, so rebuilt everything. Go back to number 1.
The sharp-eyed among you must have already realized that this loop can go on forever. It is not impossible to assume that as early as the year 3000, robots of the suicidal variety will visit Antwerp, go on a tour of the city, and hear that this house is a reconstruction of the house destroyed in World War V, which was a reconstruction of the house destroyed in World War III, which was a reconstruction of the house where Rubens' niece lived And here is her mummy. Restored, of course.
I returned to the hotel, finished writing my stories, sent them to my father and now I'm starting to work on my lecture. Still, two more days to Maniac!

Stay tuned for tomorrow's next episode of... "Doctoral Student on the Road!"