Chemotherapy works wonders for some people and not at all for others.  The cause of this was not known until recently when the Center for Environmental Health Sciences (CEHS) and Departments of Biological Engineering and Biology from MIT discovered a group of 48 genes.  Several of these 48 genes have been linked to cancer, but what they all have in common is that they can all show how susceptible a patient is to MNNG, which is a DNA-damaging agent present in chemotherapeutic agents.

MNNG induces unstoppable DNA damage by creating lesions in the DNA, thereby killing the cells.  Everyone’s DNA reacts to MNNG by attempting to repair itself, however some people’s DNA reacts more strongly while others’ reaction can be more passive.  Everyone’s DNA is so different that two seemingly equally healthy individuals were tested by MIT researchers and it was found that they could have completely different responses to the same chemotherapy treatment.

The MIT team continued with this research by measuring the expression of each of the 48 genes in every cell line.  They measured the sensitivity of each gene to MNNG several times and found they were 94% accutrate in their results.  They followed by measuring responses to other common chemotherapeutic toxic agents that are typically used to treat cancer patients.  They have discovered how and why different patients react differently to the same chemotherapy treatments.  This means that chemotherapy may not be the right cancer treatment for every patient, it depends on their genetic reactions to MNNG and other toxic agents.

The basic unit of light from which this entire process begins is called a photon. A photon contains energy that can be calculated via the following equation:

Energy = h · c/λ

The energy of any type of light can be calculated by just knowing its wavelength because h is Plank’s constant (4.14×10-15 eV/s), c is the speed of light (3×1010 cm/s) and λ is the wavelength in centimeters. The wavelength of light can determine its color and affects the laser’s energy. Figure 1 below shows the light spectrum and how it relates to the types of light humans use for different medical applications (Dr. Michael Berns, Beckman Laser Institute, 2007).

Figure 1: The figure above describes the different types of light and their associated wavelengths. Lasers generally exist in the infrared, visible, and ultraviolet wavelengths.

The use of lasers has revolutionized medicine because lasers are accurate, quick, and minimally invasive. Many different types of lasers exist and are FDA approved for various medical uses. There are six different types of laser-tissue interaction illustrated in figure 2. The accuracy of the laser assures that only the desired portion of a specimen is affected by the laser. The strength of the laser provides any medical treatment with adequate power to ablate the plaque, no matter how large the obstruction may be. The efficiency of the laser provides a better medical treatment because it takes less repetitions of the treatment to complete the procedure. There are many different types of lasers used in medicine today and they have diverse applications depending on their wavelength, absorption, strength, and accuracy (Dr. Michael Berns, Beckman Laser Institute, 2007).

Figure 2: Of the six types of laser-tissue interaction illustrated above, each has a different function an medical application. For example, photoablation can be used to break apart hard particles while heat can be used to grow tissue and increase cell division (Dr. Michael Berns, Beckman Laser Institute, 2004).

February 17-23, 2008 is National Engineers Week, or E-week. This is a week in which people all over the nation hold events to strengthen the community’s understanding and awareness of engineering. It is also designed to encourage students to pursue careers in engineering and related technological fields to help advance the country.

E-week is celebrated everywhere and locations can be found at the National Engineers Week website.

I would like to promote E-week in California, USA. The Henry Samueli School of Engineering at the University of California, Irvine (UCI) is holding a giant celebration for E-week. Many events and competitions will be hosted by Engineering Student Council (ESC), which is an undergraduate organization that helps spread and promote engineering throughout the local community and mainly on the UCI campus. This year’s motto is “The Future is Not Written, it is Engineered”, and that couldn’t be more true. Everyone and anyone is welcome to al the events of E-week held on UC Irvine campus:

Tuesday, February 19

Dean’s Breakfast
Time: 9:30 AM to 11:30 AM
Location: Engineering Gateway (EG) Plaza

Wednesday, February 20

EngiTECH Career Fair
Time: 10:00 AM to 3:00 PM
Location: Engineering Tower / Computer Science Plaza

Pub Night
Time: 8:00 PM to 10:00 PM
Location: AntHill Pub

Thursday, February 21

High School Shadow Day
Time: 9:00 AM to 2:00 PM

E-Week BBQ
Time: 11:00 AM to 3:00 PM
Location: Engineering Gateway (EG) Plaza

Friday, February 22

E-Week Awards Banquet
Time: 6:30 PM to 9:30 PM
Location: University Club

Broomball!
Time: 12:00 AM - 2:00 AM (Friday night / early Saturday morning)
Location: Westminister Ice Arena

There are many more competitions that have prizes! If you enter and win, you can get up to $500!!

To find your way around the UCI campus, here is a Campus Map.

There will be hundreds of people at the e-week events include UCI faculty, undergraduates, and graduate students as well as many company representatives and hiring managers from over 50 different technical companies both local and international. Please come out and enjoy the events, free food, and networking opportunities!

The figure above shows a green molecule bis-intercalated to DNA.  This demonstrates how the nucleotides can adjust their bonding in reaction to a chemical reagent.

The researchers are continuing to perform in vitro studies on this anti-brain cancer drug with a partnership through PhytoMedical Technologies, Inc. (located in Princeton, NJ).

For more detailed information, please see PhytoMedical’s press release.

-Amy Shah

Figure 1: Although the government provides some barriers for personalized medicine, the Department of Defense has allocated increasing amounts of funds ($ in millions) towards The Human Genome Project. However, the majority of funding for the Human Genome Project research came from from NIH grants.

The majority of physicians prefer to stick to traditional trial-and-error medicine. Perhaps this is because of the great risk involved in trying new therapies when existing protocols are usually successful. Physicians who practice personalized medicine must create a unique treatment plan that takes into account the patient’s exceptional physiology, metabolism, and genome. Personalized medicine faces several boundaries, for example traditional physician practice, the pharmaceutical industry, the medical payment system and regulatory procedures. After personalized medicine can overcome these obstacles, much benefit prevails with this methodology such as saving more lives, reducing treatment costs, and improving patient recovery time through the accuracy, efficiency, safety, and speed that personalized medicine has to offer.

Obstacles of Personalized Medicine

Since personalized medicine is a new diagnostic approach that requires a good amount of training and studying to prevail in, there are many obstacles blocking its path to success. The most prominent barrier present is traditional trial-and-error medicine because it is extremely difficult to replace something that has been used for hundreds of years. Trial-and-error medicine has become a standard treatment process for doctors all over the world. It works in the sense that a patient presents typical symptoms, the physician provides a typical diagnosis, and then follows up with a typical treatment plan. When the treatment plan does not provide relief for the patient, the physician will go through this loop again and again until a diagnosis and treatment bring the patient back to being healthy. The problem with this type of protocol is that several treatments cost the patient more money and occupy an increasing amount of the patient’s time. The down-fall of this methodology is that the wrong treatment (although not occurring the majority of the time) can also lead to the patient becoming sicker, or even dying. One big reason for why physicians are not switching to personalized medicine is because many medical schools do not cover genomics and genetics completely in their curriculum, therefore graduating doctors may not understand the relevance and promise of incorporating their patient’s genome into their diagnosis. Personalized Medicine is very complicated and incorporates many specialties (figure 2) in order to serve the patient well, without a thorough education, physicians cannot be expected to take up this new protocol right away.

Figure 2: Personalized Medicine is a complicated health care practice which utilizes many fields and specialties.

Another barrier in the way of personalized medicine is the pharmaceutical industry. This is a helpful industry that has lead medicine along its way throughout history, however the pharmaceutical field has created a habit often referred to as the “blockbuster drug” model. A “blockbuster drug” is a product that is capable of achieving sales over $1 billion annually. In order to achieve these results, the product must be in wide enough use to earn this much revenue (i.e. a large number of patients should be using the product). Many patients, although they are the minority, suffer from adverse effects of largely prescribed medication and this can often lead to death. If the number of dying patients is statistically insignificant when compared to the amount of patients with no complaints, the pharmaceutical industry considers the drug of product economically favorable and continues production and distribution. This explains the fact that pharmaceutical companies are most profitable when they treat large populations of people with a given disease because the most profits come to industry when there are more consumers. Personalized medicine clashes with the “blockbuster drug” model because it incorporates each and every patient’s needs into a particular treatment plan, hence a small group of patients with similar treatment needs may not be supported by the pharmaceutical industry. As for drugs that are linked to diagnostics, pharmaceutical companies run in the other direction in fright that this may complicate the market to physicians and slow the identification and treatment of patients.

The reimbursment system that exists today is also working against personalized medicine. Medicare, Medicaid, and health insurance companies cover the majority of medical costs. These reimbursement institutions provide financial support for each procedure conducted. Therefore, rather than spending time to correctly diagnose a patient, physicians are often pressed for time to squeeze as many procedures into their schedule as possible for the most economic gain. If companies develop new and improved diagnostic testing methods to help physicians more accurately diagnose their patients, perhaps physicians would be more likely to provide their patients with the proper treatment plan.

The most popularly despised barrier of personalized medicine is the world of regulatory affairs, referred to as the FDA (Food and Drug Administration) in the United States. The current regulatory system is not economically feasible with the way that personalized medicine works, however the FDA is not in opposition to personalized medicine. Since clinical trials of drug-development costs are high, it takes much time to pass the safety and efficiency of new drugs. If a certain drug pertains to a small percentage of patients (as in personalized medicine), a clinical trial may not be cost effective enough to put that drug through the FDA process. In the FDA’s support of personalized medicine, Dr. Andrew Von Eschenbach, Director of the FDA, gave a briefing to the Personalized Medicine Coalition at the National Press Club. He announced that the FDA is working on ways to bring new testing and treatment methods to the molecularly-based market. On the other side of regulatory affairs lies the U.S. government. Despite what many citizens may think, the government is quite involved with this scientific advancement. Since very few genomics-based tests and treatments are available to consumers, government officials have been taking a stand to support personalized medicine. For example, Senator Barak Obama introduced the Genomics and Personalized Medicine Act to overcome scientific barriers by promoting medical advancements to regulatory obstacles. Mike Leavitt, United States Secretary of Health and Human Services, has created a committee called the Secretary’s Advisory Committee on Genetics Health and Society. A specific committee dedicated to updating government officials on genetic health and advancements is a big step in the direction of personalized medicine. Although regulatory obstacles do exist, there are also steps being taken to help medical advancement towards personalized medicine.
Advantages of Personalized Medicine

Patients with acute or fairly progressed diseases do not have the comfort of time that it takes for traditional trial-and-error medicine. If the first diagnosis and treatment plan doesn’t work, it may be too late to save the patient. As you can see in figure 3 below, symptoms progress and diseases worsen quickly and many patients don’t have the luxury of time that it takes for traditional medicine to treat them. By utilizing the patient’s unique genome and identifying which treatments are sure not to work, personalized medicine can save this patient much sooner than traditional medicine. If the patient is treated sooner, their bed and room in the hospital may open up in time to save another patient’s life. Saving time is crucial to the patient, the hospital, and physicians alike.

Figure 3: Shows the relationship and correlation between time, disease management of traditional trial-and-error medicine, and disease progression.

With that said, less treatment therapies used means less money spent. Personalized medicine has the potential to save each patient thousands of dollars. The FDA estimates that if diagnostic tests based on genomics were used on just the patients needing warfarin, the United States health care system could save as much as $1.1 billion dollars every year. These types of tests are currently available and can be used hand-in-hand with personalized medicine to refine each patient’s treatment plan; unfortunately these tests are underused. If each physician were to routinely utilize these diagnostic methods, they could save billions of dollars by just avoiding adverse patient reaction to the inaccurate treatment.

Researchers are currently trying to trace metabolic pathways, genetic variants, and treatment resistance in the human genome. Once each of the three are linked together, they will develop diagnostic tools for each situation. The advantages of personalized medicine are enormous, however there are many difficult road blocks to overcome before personalized medicine can hit the mainstream. The people fighting for personalized medicine, like the Personalized Medicine Coalition (PMC), need to work harder and faster to get it over the hurdles, but most of all they need more support. Personalized medicine is for YOU and you only, so do a little work for it.

For further information on Personalized Medicine: FUSE, Realizing the Promise of Personalized Medicine, MayoClinic, and Pharmacogenomics.

Atherosclerosis is caused by many factors, some of which can be controlled by the patient. Hypertension, obesity, smoking, diabetes, high cholesterol, and congenital heart disease can all be individual or combined causes of atherosclerosis in a patient. Depending on where in the body plaque builds up, symptoms may include angina, heart attack, severe pain, stroke, and/or dizziness.

Significance of Atherosclerosis
Atherosclerosis progresses slowly and is cumulative over time, beginning with macrophage infiltration into the artery. A fatty streak results and a lesion advances to eventually create an atheroma, as shown in the figure below. This continues to advances to create a larger, more complicated lesion. Over time, if the lesion is not treated, the plaque will suddenly rupture and form a thrombus that severely slows down, or even stops blood flow. This can lead to an infarction, which is death of the tissues feeding off of the artery within five minutes if it is not tended to immediately.

In the United States alone, atherosclerosis leads to the death of almost 15,000 people every year. It is also the cause of hospitalization for 20,000 patients per year and over 730,000 physician office visits per year.

Current Treatments
Current treatments include improvements in diet, cholesterol reduction medication, anticoagulate medication, blood pressure medication, surgical procedures and sometimes even gene therapy. Our medical device plans to make improvements upon the current surgical procedures, which are endarterectomy, angioplasty, bypass surgery, and thrombolytic therapy.

Above is an image of an embryonic stem cell in an extracellular matrix.

Where do the Human Embryos come from?

Assisted Reproductive Technology (ART) was created over 20 years ago to overcome fertility problems. ART utilizes In Vitro Fertilization (IVF), which is fertilization of an egg by a sperm outside the body (for example, in a petri dish). Many ART procedures result in an excess amount of embryos and the people involved in creating those embryos have the option of cryopreserving them to be stored for future attempts to enable pregnancy. Over 400,000 of these cryopreserved embryos are stored in the United States alone. Therefore, once the “owners” of the embryo choose to terminate treatment, they have a number of options for their excess embryos. One of those options is to donate them for research purposes. The only way to get these embryos (which are in the form of blastocysts) into labs for research is to get consent from all of the gamete donors for the blastocyst to be used in research.

Above is am image of an eight cell embryo obtained from an In Vitro Fertilization Program (IVF).

How are Embryos Stored?

Storage, maintenance, and distribution of cell lines must also adhere to certain national standards. There exist national stem cell banks** (and international stem cell banks as well) that store stem cells according to legal requirements. They are established for various functions to ensure legitimate protocol. On the privacy plane, stem cell banks ensure that the rights of the gamete donors have not been abused and make sure that proper consent forms by all gamete donors are completed and accurate. These banks also limit the number of embryos that any one institution can receive, which is vital in regulating abuse of stem cell research. Further regulation of storing and obtaining tissues lies in the requirement that any identifiable tissue is required to pass an Institutional Review Board (IRB) review at the collection site.

Quality Assurance of Embryos

Safety, security, and risk assessments are performed on the management side of this issue in order to ensure appropriate handling and storage of the embryos. This is vital to maintain high quality stem cells for research and clinical studies. Validating submitted tissues, culturing and expanding cell lines, process control, packaging for distribution and documentation are all processes that are monitored and constantly checked by the quality management team of the stem cell banking facility. Detailed reports of every aspect for every tissue that enters a banking facility are required in order to assure accuracy and enable tracking. It is increasingly vital for research institutions to obtain high quality cell lines as they approach their in vivo testing. Poor stem cell quality could create adverse effects on the test subject’s body and put the subject’s life in danger.

All information obtained from Guidelines for Human Embryonic Stem Cell Research.

-Amy

In the figure above, visual A shows the patient’s EKG results and differing QRS complexes can be viewed by at the arrows D (donor heart) and N (native heart). Visual B shows a front view of the patient in which a cardiac defibrillator is treating the native heart. Visual C shows the top view and demonstrates the close proximity of the two hearts and the amount of space they occupy in the chest cavity.

Information obtained from the American Heart Association and the New England Journal of Medicine.

-Amy

Infection due to VADs can be caused by the biomaterial used, poor sterile technique, device failure, and percutaneous line design. Shear forces caused by excessive bleeding upon implantation of the device can also cause infection, and infection leads to tissue necrosis.

Thrombosis and thromboembolism are problems that all devices face when coming into contact with blood. To avoid this issue, surgeons use drugs like Heparin or Coumadin to avoid coagulation when devices come into direct contact with the blood.

Many scientists believe that nothing can be solved unless it can be quantified. Infection and thrombosis (believe it or not) can be crudely measured through microembolic signals (MES). Dr. Wagner suggested that scientists should get more out of animal models by analyzing MES, explants, and gross neurological health more thoroughly to minimize plately aggregation and avoid thrombosis. An example of a thoroughly tested device that has been underway for 30 years is the Heartmate II, which is implanted in the chest to aid the heart in pumping (shown in the figure above). This device can be used as a treatment method for patients with severe heart failure, or as a bridge until a transplant is available. When tested in calves, this device showed a spike in platelet aggregation (which is expected and normal) and then a steady decrease in aggregation due o microaggregates leaving the implant site. In previous VADs, the platelet aggregation spiked and then didn’t decline at a steady enough rate for thrombosis to cease. Another research project underway by EvaHeart to improve the downfalls of VADs is to replace bovine (cow) with ovine (sheep) products due to this superior configuration of ovine tissue (methacryloyloxyethyl phosphorylcholine).

-Amy

Treatment of HF depends on the stage of the disease’s progression and is rated on a scale from case I to case IV. The five year survival rate of patients in stage IV is only 20%, therefore this is considered severe heart failure. There are several minimally invasive devices used in HF treatment. The most common treatment device is an artificial pacemaker (shown below), which successfully prevents about 50% of all heart failures from re-occurring. Another treatment option for HF that is extreme is a heart transplant. This is called the “Gold Standard” treatment because it is the best to use, however the availability of donors is slowly declining while the number of patients who need a transplant is steadily rising. Only about 2200 heart transplants are preformed every year.

The ideal solution would be an artificial heart…In 1985, at the University of Pittsburgh Medical Center (UPMC), the first artificial heart was implanted. Five years later, UPMC was the first medical institution to release a patient with a ventricular-assist device (VAD) (shown below). Today, VADs called positive displacement pumps are the leading treatment therapy for HF patients. Dr. Marc Simon presented the idea of positive displacement pumps at the BMES Conference and spoke of future improvement for these devices. He announced that second and third generation prototypes are currently underway in many institutions and will be ready for release soon. Dr. Simon discussed that there is an ideal period during HF in which it is ideal to implant there devices into the patient in order to maximize recovery success. There is a certain point in HF in which an acute, catastrophic event leads to sudden progression of the disease, eventually leading the patient to death. The closer researchers are able to pinpoint the time immediately prior to this turn of events to implant the device, the greater the patient’s chances are for survival.

-Amy