Human Practices Gold Criterion

The information compiled in this site originates from multiple sites on our wiki. If you wish to see them in their native context please visit them via the following links.

• Integrated practices
• Interviews with experts

Introduction

Human practice has been a cornerstone in our iGEM project right from the start. We have spent a great deal of time teaching others about our ideas and methods. We have been able to use the feedback to improve our presentation and get ideas for new future perspectives, as well as avoiding any potential pitfalls. We have also been reaching out to companies and experts in different fields to get a more qualified view on our work. The information they gave helped us to develop new goals for the future perspectives of our project and to expand our knowledge about the different sub elements. By interviewing all these experts and companies we have gained insight into today's market and we can see that there is a demand for developing solutions, which our sub elements would be to good use for.

Projects

Evaluation from KOLD College

We finished our visit at KOLD College with an evaluation in order to get a better idea of our performance and project idea. They were generally very positive about Bacto-Aid, especially because they already were aware about the problems antimicrobial resistance poses today. It was rewarding to see, that we are trying to solve an issue, that many people worry about. Some of the comments, which we have integrated in our future presentations of the project were: "There is a lot of potential in these areas". The future potential for the different parts of the project tended to cause a positive response and therefore we added a slideshow exclusively for the potentials of the sub projects. "It lacks focus on problematics”. We took this comment into consideration and decided to start the presentation with an explanation of why this area still needs a solution. The feedback we got from KOLD College helped us especially with what was important to focus on in the presentation.

Interviewing Laura Jakobsen

We interviewed a nurse, Laura Jakobsen, who is working at the plastic surgery department at the University Hospital of Odense (OUH). In Denmark, burn patients are mainly sent to OUH and Rigshospitalet (another major hospital unit in our country). This helped us getting an idea of what kind of issues the hospitals are facing when treating wounds, and what kind of requirements they would have for our Bacto-Aid. At her work, they have encountered resistant bacterial infections, which required special care and extra awareness. This confirms the problem of resistance and proving how actual the problem is.

One of the major issues there was with our product, according to Laura Jakobsen, was the suction capacity of the silk. Burn wounds have a tendency to leak a lot the first few days after the incident. This is an important aspect we should look into if our Bacto-Aid should be used for treating burns. Despite this current limitation of our product, she did see a potential for it as a bandage applied after lymph node removal surgery in the inguinal region. It is a particularly problematic healing region due to the constant pressure it is undergoing (a patient has to sit) and due to the serum accumulation. Serum tapping is an important aftercare that has to be done regularly. It consists of removing the serum produced in the limb, which lymph nodes typically would transport away, manually. It is therefore a highway to infections in this region due to the missing lymph nodes (which also is a center for the immune system), regularly breaching the skin (barrier to foreign bacteria), and it is a moist area where many types of bacteria from the normal flora of the skin are present. Bacto-Aid could create a barrier that has antimicrobial effect and help to protect the vulnerable patient to any further complication.

Interviewing Hans Jørn Kolmos

Hans Jørn Kolmos is a professor in clinical microbiology at the University of Southern Denmark. He is an expert in the history of the use of antibiotics and he is familiar with the status of the resistance problem. We had a great talk, where he told us that the media sometimes have a tendency to worsen the situation. The Danish documentary “Når penicillin ikke virker" translated to: “when Penicillin does not work anymore” shows the problem in a realistic way. We talked about how to tackle the problem and he said: “Nature is smart. Humans have only been here for a few millenniums and microorganisms have been here for billions of years. It would be foolish to believe that we could outsmart nature in 100 years”. He also said: “we could limit the distribution of antibiotics by following these three steps 1) isolate the potential bacteria 2) ask the question; is the isolated bacteria the reason to the infection or is it something else? 3) evaluate whether antibiotics can be used against the infection”. As a future plan, or a prospective for our project, he said that the bacteriocins could be used in local treatment. The ones we have looked at could probably be integrated in an ointment to the nose to potentially treat MRSA carriers.

Statement from Frank Møller Aarestrup

We received a statement from Frank Møller Aarestrup, because we were interested in hearing an expert’s opinion about the use of bacteriocins as an alternative way of treating wounds. Mr. Aarestrup is a professor at the Technical University of Denmark and is the head of a research group for genomic epidemiology. He believes that there are great future prospects in the use of bacteriocins as new antimicrobial components, because it seems that resistance is rarely developed towards them. However, Mr. Aarestrup points out that if we choose to inject the proteins into the body, we should be aware of the fact that they easily can be decomposed. Since we keep the proteins at the body’s surface, this should not be a problem for us. Mr. Aarestrup agreed with our choice of testing with S. Aureus strains and he also suggested that we tested our bacteriocins in relation to Streptococcus. If we had any time left, we would have been interested in testing Mr. Aarestrup's suggestion.

Interviewing plastic companies

We sent out question forms and made phone calls to 14 different plastic companies, in order to evaluate the sustainability and future perspectives of our biodegradable plastic. Their opinions are very important to us, because they could be the future consumer of our plastic. The companies were very positive toward using plastic that have been produced from bacteria. However, there were some concerns if the plastic was going to be used to food. Likewise, the plastic should be approved by UL and FDA, before they will use it.

The use of bacteria for the production of plastic, would also open the doors for a product, which would be capable of competing in price with the current forms of plastic. The companies were very interested in using biodegradable plastic, but not with today’s prices. Several companies have already investigated some biodegradable plastics, but due to its much higher cost they did not end up using it. If we can offer them a cheaper alternative, then they would be very interested. This will make them able to offer more options for their customers and provide them with a more environmental friendly solution. We will therefore keep on trying to optimize the production of our plastic from bacteria, so that we one day can end up with a competitive product.

The plastic companies will only be able to use our plastic if it fulfills the customer's requirement for sustainability. Since our plastic is biodegradable, there will also be limitations to its application forms. The final choice of material will be made by the customer. It is therefore the customers, which will make the decision of whether they want to the use biodegradable plastic or not. Therefore, it could be them we need to persuade and not the plastic companies. Some of these companies are dependent on people like us to buy their products, which means that we can end up influencing whether companies are using biodegradable plastic or not.

Interviewing Morten Østergaard Andersen

In relation to the possible functions our biodegradable plastic can fulfill in medicine, we consulted Morten Østergaard Andersen. Morten is an Associate Professor at the Southern University of Denmark, researching in different biomaterials. Morten introduced us to several experiments, which we could conduct for our plastic Nygaard, J. V., et al. (2008). "Investigation of Particle-Functionalized Tissue Engineering Scaffolds Using X-Ray Tomographic Microscopy" Biotechnology and Bioengineering 100(4): 820-829. Andersen, M. Ø.., et al. (2010). "Surface functionalisation of PLGA nanoparticles for gene silencing." Biomaterials 31: 5671-5677.. One of them was how we could use our plastic for coating of different proteins. The plastic could for instance be used for coating of antimicrobial peptides onto implants. The PHB will decompose slowly, which also means that the antimicrobial peptides will be released continuously from the implant and thereby reducing possible infections and biofilm. The PHB could also be used as the implant itself in cases where e.g. the bone needs a scaffold until it has healed. However, here we should be aware of the side effects of using PHB as bone implants, if the patient is also ingesting bone stimulating drugs. These drugs can lead to the formation of bones other places in the body than intended to. Mr. Andersen made us also aware of the side effect with the use of PHB inside the body.

Mr. Andersen introduced us to how we could 3D print our plastic. He also provided us with materials about plastic polymers, which we could use for background knowledge and for inspiration of possible opportunities. Furthermore, Mr. Andersen gave us the contact to two of his master students; Martin and Casper. They had the knowledge and the equipment to make the 3D printing possible. This corporation also provided them with a new experience, since it was the first time they had the opportunity to print with this type of plastic material and see how it responded to the 3D printing.

Interviewing Ming Ding

We had a great talk with Ming Ding, professor in orthopaedic surgery at the Southern University of Denmark, about how we can use our plastic as coating for implants and how the material can be used for slow release of antimicrobial peptides. Mr. Ding’s team is currently working on some experiments with release of E-vitamin from implants in animals. This method could also be tested with combining our plastic and antimicrobial peptides. Especially since our plastic is biodegradable, which is a requirement for this type of coating. Mr. Ding also pointed out that it would be an advantage if the material would be able to stimulate blood vessel formation and thereby increase the speed of wound healing. This is some of the qualifications that our spider silk contains, so the silk could also be worth considering when working with implants. The interview gave us information about the possibilities in our project and reassurance of the great potential there is in developing new biomaterials for implants.

Interviewing Coloplast

We presented our project to Coloplast with the intention of getting their point of view on our project as a whole and in relation to our three sub elements. They believe that our spider silk and bacteriocins are the most interesting and relevant elements in relation to a commercial product perspective of our Bacto-Aid. The reason why PHB is not the most relevant, is that the use of plastic materials in wound care dressings are low compared to other uses of plastics. Instead, the topic of biodegradable polymers is more relevant in other areas and applications. Coloplast are already aware of the great qualities of recombinant spider silk and bacteriocins, however the idea of combining the two elements are completely new to them. They see a big opportunity in this idea and encourage us to continue the work on this project. Their feedback really helped us finding our focus in relation to future development of our product and in relation to how we could improve our project.

Upcoming meeting with LEGO^®

We have been in contact with LEGO^® in the weeks up to our wiki deadline, and they were very interested in our sub project with producing PHB. Due to a Danish holiday it was not possible to meet up before the deadline, but we have already set a meeting with LEGO^®'s director of materials for when we come home from Boston. LEGO^® has a large division with research and development of materials from whom we can learn a lot. LEGO^® could also end up being a future consumer of our plastic.

Interviews with Experts and Companies

Interviewing Laura Jakobsen

Do you see our product usable for patients with burns?

“With a bit of change, the product could become useful.”

What kind of wishes have you had earlier for a useful product to burn patients?

“A better handling of the liquid production of the wound, that is often a major problem in the first week after the accident (includes first and second degree burns).”

According to you, is it a type of product that should be focused more on, even though the number of burn patients is decreasing?

“Yes, there is always a need to develop a better, cheaper and more patient friendly bandage.”

Could you imagine our product being used for a different condition or type of wound?

“It could be used as a bandage after surgery in the inguinal region. It is often a quite problematic healing region due to the serum that can create pressure and tighten the region. Serum tapping is a passage for infection every time tapping is made. It is a region of contamination due to tight bandage, patients can not avoid to create pressure on the wound (when they sit), often very moist region (due to sweat) and many more challenges are encountered with diabetics, smoking and overweight patients.”

Should there be added anything to our product so it could be more effective or making the burn treatment easier?

“ A better fluid handling.”

Have you ever encountered resistant bacteria in your working department of the hospital? What measurements have been taken into account to treat these patients?

“Yes, and many different kinds of them. Isolation, protection, hand hygiene and antibiotic treatment after current guidelines for every kind of bacteria, are being followed.”

Can you see a potential in covering the silk in lidocain* to reduce the amount of pain burn patients have to go through? Are there any cons in giving this (today patients who come in to get their bandage removed and gets fibrin** scratched off are not receiving any kind of pain killer)? Can anything be done to get the bandage easier off when it has to be changed after the first couple of days (this type of wound is typically very wet the first couple of days after the injury)?

“Typically, the caregivers recommend the patient to take pain killers (paracetamol and ibumetin, and sometimes morphine preparates) approximately an hour before changing the bandage to reduce any kind of discomfort if the bandage should grab or got stucked in some skin. It could be a possibility to cover the silk with, for example, Ibumetin (NSAID-preparate), so you could kill the pain locally and avoid the side effects which Ibumetin can have (such as increased stomach acid production, blood thinner effect and much more), or could expand the movement and not prevent limitation of movement under rehabilitation of, for example, fingers. If the patient is hospitalized, the bandage will be washed off with lukewarm water mixed with NaCl (commonly known as salt). This can not be done in the ambulance or elsewhere due to the time and the space that is needed for this kind of treatment. When the wound is kept moist it increases the movement and the flexibility of the surrounding skin/new skin. The pain is minimized because the skin is not as tight and the bandage will not grab skin.”

Footnote

*Lidocain:is a local analgesic widely used in ambulatory surgeries in Denmark.

**Fibrin: is created in the body under the healing process of a wound. Fibrin and granulation has to be present for an effective healing of the wound. If there is only fibrin when healing, the healing process stops. It is therefore important to ensure that the excess of fibrin is scratched off (often made by a nurse or a doctor).

Interviewing Hans Jørn Kolmos

From your point of view, how big is the resistance problem?

He believes that it is an increasing problem, but it should not be the cause of any panic yet. New strategies should be devolved in the use of antibiotics so the increase in antibiotic resistance becomes limited. Antibiotics should not be used to treat infections that we do not know the cause of. Instead a more careful approach in the distribution should be taken. He suggested a simple approach to this issue: three simple steps should undertaken before giving an antibiotic treatment to an infection. First step is to isolate the bacteria. This can be done by evaluating the microorganisms species, its concentration and the origin of isolation. The second step is to conclude whether the isolated microorganism is the cause of infection. This can be done in association with e.g. a prosthesis where an infection has occurred. The third step is to evaluate whether antibiotics can be used against the infection. If the infection occurred in a prosthesis, the bacteria would most likely develop a biofilm. If treated with antibiotics, the infectious bacteria will only be exposed to small concentrations of antibiotics and this will provide time to develop resistance. Under these circumstances, the prosthesis should be removed before given any form of treatment. We should be more retained with the use of antibiotics.

“Nature is smart. Humans have only been here for a few millenniums and microorganisms have been here for billions of years. It would be foolish to believe that we could outsmart nature in only 100 years.” - Hans Jørn Kolmos

Does the media highlight antibiotic resistance as a bigger problem than it actually is?

A documentary in danish television called: “When Penicillin doesn’t work anymore.” says that the resistance problem is huge. The documentary shows families experiencing MRSA, and how health care deal with the problem. We asked Mr. Kolmos if the media makes a bigger problem out of it, that it is? He replied that: No, the documentary gave a realistic perspective of the problem.

Is there any possibility that we could face a dead end in functional antibiotics if we keep the distribution to this level?

Mr. Kolmos stated there is a potential risk for a multiresistant bacteria. If we kept using antibiotics like we do today, we could potentially get a resistant bacteria, that we could not kill with any of our antibiotic resources.

Are there any cases with patients that could not be treated because of an infection caused by multiresistant bacteria?

Mr. Kolmos told us that under the civil war in Libya, the country did not have the resources to treat all the wounded soldiers. Therefore some of them were sent to Denmark. As we treated them, we observed very odd sorts of infections that are not common in Denmark. There were bacterias with other types of resistance than the ones the doctors knew about. The worst were the Gram-negative, ESBL (Extented-Epectrum Beta-lactamase).

He also estimated 30 % of the population are carrier of S.aureus, of these 1-2 % are MRSA. The resistance problem is not just a problem on the hospitals. It is also a part of political debates.

Is there any precautions, the ordinary family can contribute with?

He told us that people could get checked if they were carrier of MRSA. S.aureus is often found in human nostrils, but if the patient got in contact with the MRSA bacteria, it could outperform the normal flora. The patient would now be a carrier. The MRSA bacteria can be killed by use of antibiotics, but an ordinary family should also take precautions. “Wash your hands, do not sneeze on people, and just be clever about bacteria and how it spreads” - quote Hans Jørn Kolmos.

What is the biggest cause to MRSA?

It is hard to isolate a single source that contributes to the development of MRSA, but we know it is a combination of the farming industry and antibiotic distribution.

The media has a tendency to blame the pigs for MRSA. It is actually estimated that only 40% of all pigs are carriers.

What antibiotics are used to treat MRSA:CC398, MRSA:USA300 and VISA(Vancomycin-intermediate-S. Aureus)?

Tough question, but Vancomycin can treat both the MRSA:CC398 and MRSA:USA300.

Can you see any potential in our project?

It could be a part of a treatment, but it could also be nice to test the bacteriocins on gram-negative bacteria. Bacteriocins could also be used for oral treatment, eg. in the nose, were MRSA is normally found on carriers.

Interviewing plastic companies

14 plastic companies responded to our questions. Each company was asked the following:

• Do you have any specific attitudes towards sustainability?
• Would you want to work with plastic which have been produced by bacteria?
• Do you know the plastic PHA, or poly-beta-hydroxybutyrate (PHB)?
• If the price of biodegradable plastic was considerably lower than it is as its present), would you then as a company have any interest in this? (it cost 4 times as much to produce at the moment
• Would you be able to incorporate such a product in your business?

Here we have listed some of the answers, which we received:

• Agstrup Plast ApS:

  “It would be a great advantage for us if we could offer production with a bio-material as well. This will give more options for our customers and a more environmental friendly image. However, it will still be the customer's’ decision and the choice will also depend on requirements such as sustainability.”

• AMU SYD:

  “Plastic produced from bacteria will be an option for us. We also see a great future in biodegradable plastic.”

• Fast Plast A/S:

  “There could be an issue with using plastic produced from bacteria, since we primarily are producing plastic for food.”

• Bogense Plast A/S:

  “At this point, our customers’ products will not be able to be produced by biodegradable plastic.”

• DAMVIG Develop A/S:

  “We believe that there are a great potential in such material in the production sector, especially for packaging which people throw away.”

• HN Group A/S:

  “We would not mind using plastic produced from bacteria. However, it will be our customers, who will be deciding this.“

• Letbæk Plast A/S:

  “The prices of biodegradable plastic is the main reason why we do not use it more in our production. If PHB can be used as a coating, we would be able to apply.”

• Malte Haaning Plastic A/S:

  “We currently do not know if we will be able to incorporate biodegradable plastic into our production.”

• Martin Høft A/S:

  “There are only a few cases where biodegradable plastic will be a good option for the products we are making.”

• MiM Plast A/S:

  “We will be able to use plastic produced from bacteria as long as it have been approved by UL and FDA. We are currently already using biodegradable plastic in our production.”

• Ossi Connectors A/S:

  “We are restricted in our choice of material due to the requirements from the customers.”

• RPC Superfos A/S:

  “We would be interested in using plastic produced from bacteria. We have already done some tests with biodegradable plastic, and would therefore also be ready to incorporate it in our company, but only if the price is right and if there is a demand for this from the customers”

• Schoeller-Plast-Enterprise A/S:

  “The durability and applicability are some of the important factors we consider when choosing the right material for the customer, but in the end it will be the customer’s decision.”

• SP Medical A/S:

  “We do not have much influence on which plastic material we are using, since this has already been determined by the customer”