Biomedicine Update – Healing the Heart

The expression “in a heartbeat” may not have the same meaning in the future if technology under development has a say. Conventional thinking on replacing the heart with a device that works the same way as the heart is being turned on its head by devices that don’t beat at all. These new artificial hearts are turbines that push blood through the body, not in spurts but in a steady stream. Called continuous-flow devices they have been under development for the last two decades.

The model for continuous-flow is Archimedes’ screw, the 3rd century B.C. device designed to pump water from the Nile River to the fields that lined its banks. Archimedes’ screw is still in use in Egypt today and Richard Wampler, a surgeon and engineer, first encountered them in a trip to Egypt in 1976. A decade later he patented a device based on this ancient technology but instead of moving water his was designed to move blood.

In use since the 3rd century B.C., Archimedes' screw is the technology behind new artificial hearts.

Initially the device was used to assist failing and post-surgical left ventricles (the primary pumping chamber for delivering blood through the ascending and descending aorta to the body). Before Wampler’s device left ventricle assist devices or LVADs required external compressors and pulsed like the heart. Wampler’s device didn’t. Many surgeons and cardiologists were skeptics. They were concerned that blood passing through a turbine would be damaged. But the continuous-flow turbines did no damage to blood cells when implanted in test animals.

In November 2003 a commercial version of the pump, called the HeartMate II was implanted in a young patient from Central America. He left the hospital and didn’t return. The young man’s heart prior to the surgery was weakened but still functioning. During the eight months he was away before coming back for a followup examination his heart pretty much stopped functioning. When examined he had no pulse and nothing that one would recognize as a heartbeat. But he was walking around and functioning and described himself as “feeling fine.”

The continuous-flow artificial heart consists of twin turbines designed to circulate blood throughout the body. Unlike prior artificial hearts, it doesn't try to emulate the natural heart. It doesn't beat. It doesn't create a pulse in its recipients. Source: Popular Science

Since 2008 HeartMate II has been installed in 11,000 people worldwide. This device, an enhanced LVAD, has had a wonderful side effect in many patients. It reverses heart failure confounding cardiologists who assumed that any damage to the heart was permanent.

From LVAD to a continuous-flow artificial heart implanted in humans is a matter of less than a decade according to the developers of this technology and the medical teams that are implanting them. Currently these new devices are undergoing animal clinical trials with encouraging results. It is only a matter of time, not in a heartbeat, but certainly within a decade before artificial hearts will be commercially available for humans.

Identifying the Problems of the 21st Century – A Commentary on James Martin’s 16 Challenges

When I was a younger man working in the world of information technology I was an avid reader of James Martin’s books on computers and telecommunications. Recently I came across one of his books of which a part is published online. Entitled, “The Meaning of the 21st Century,”  it outlines 16 challenges that humanity faces in the coming century. I’ve added comments of my own in Italics.

1. GLOBAL WARMING Global warming will lead to severe climate change. Unless stopped, it will upset the basic control mechanisms of planet Earth.
2. EXCESSIVE POPULATION GROWTH World population may grow to 8.9 billion people, with a growing demand for consumer goods and carbon-based energy, far exceeding what the planet can handle. Forecasts of population growth indicate human population will start to peak around mid-century, level out and then slowly decline. Peak variable projections indicate a population as little as 9 billion or as high as 12 billion.
3. WATER SHORTAGES Rivers and aquifers are drying up. Many farmers will not have the water essential for food growing. There will be wars over water. Freshwater is one of the most challenging issues we face.
4. DESTRUCTION OF LIFE IN THE OCEANS Only 10% of edible fish remain in the oceans, and this percentage is rapidly declining. Aquaculture is only a partial solution to the problem of the collapse of fish stocks. Climate change influencers like CO2 are acidifying the ocean changing impacting krill, coral and shellfish, principal food sources for most marine life.
5. MASS FAMINE IN ILL-ORGANIZED COUNTRIES Farm productivity is declining. Grain will rise in cost. This will harm the poorest countries. Agricultural production in the Developing World needs to reach the same yield levels as in the factory farms of the Developed World replacing subsistence agriculture.
6. THE SPREAD OF DESERTS Soil is being eroded. Deserts are spreading in areas that used to have good soil and grassland. Grazing and improper land use including deforestation continue to impact soils in the Developing World contributing to desertification.
7. PANDEMICS AIDS is continuing to spread. Infectious pandemics could spread at unstoppable rates, as they have in the past, but now with the capability to kill enormous numbers of people. Although pandemics will always put humans at risk we have the means today to contain outbreaks and develop rapid response to them when they occur.
8. EXTREME POVERTY 2 to 3 billion people live in conditions of extreme poverty, with lack of sanitation. The difference between rich and poor is becoming ever more extreme. This is even a problem in the Developed World as indicated by the recent Wall Street protest movement and Arab Spring.
9. GROWTH OF SHANTYCITIES Shantytowns (shantycities) with extreme violence and poverty are growing in many parts of the world. Youth there have no hope. We need a global commitment to addressing informal urban environments and the poverty and despair associated with these areas.
10. UNSTOPPABLE GLOBAL MIGRATIONS Large numbers of people are leaving the poorest countries and shantycities, wanting to find a life in countries with opportunity. Migration from rural to urban is happening today at the rate of 80,000 per day. Migration from the Developing World to the Developed is increasingly more difficult although illegal immigration continues at a steady if not increasing pace.
11. NON-STATE ACTORS WITH EXTREME WEAPONS Nuclear or biological weapons are becoming easier to build by terrorist organizations, political groups or individuals, who are not acting for a given state. The evidence of this development frames the beginning of the 21st century and may be with us for a long time to come.
12. VIOLENT RELIGIOUS EXTREMISM Religious extremism and jihad may become widespread, leading to large numbers of suicide terrorists, and religious war between Muslims and Christians. This is nothing new. Religion, nationalism, and tribalism have been a part of the human condition and will continue. The real challenge will be to overcome our baser nature.
13. RUNAWAY COMPUTER INTELLIGENCE Computers will acquire the capability to increase their own intelligence until a chain reaction happens of machines becoming more intelligent at electronic speed. Artificial intelligence and humanity will experience convergence throughout the century. The question will become can we distinguish one from the other?
14. WAR THAT COULD END CIVILIZATION A global war like World War I or II, conducted with today’s vast number of nuclear weapons and new biological weapons, could end civilization. War in the 21st century will be fought in entirely new ways. Cyberattacks, militarization of space and new weapon technology (robotics, lasers) will change war just as the first atomic bomb altered the rules of warfare in the 20th century leading to the disappearance of global conflicts only to be replaced by regional wars.
15. RISKS TO HOMO SAPIEN’S EXISTENCE We are heading in the direction of scientific experiments (described by Lord Martin Rees) that have a low probability of wiping out Homo sapiens. The combination of risks gives a relatively high probability of not surviving the century. Humanity will survive the century. This is just too pessimistic.
16. A NEW DARK AGE A global cocktail of intolerable poverty and outrageous wealth, starvation, mass terrorism with nuclear/biological weapons, world war, deliberate pandemics and religious insanity, might plunge humanity into a worldwide pattern of unending hatred and violence – a new Dark Age. We are just as likely to emerge at the end of the 21st century with entirely new purpose as we look outward bound beyond our planet while using technology to restore much of what the Industrial Age has wrought.

In my blog I don’t just point out the problems but show how our human inventiveness is finding solutions. Nonetheless, James Martin has pointed out challenges we must face and overcome for humanity and the other travellers on our planet.

Biomedicine – Part 11: Curing in the 21st Century – Influenza and the Common Cold

In this blog we look at potential 21st century cures for two diseases that have plagued humanity each creating an unwarranted burden on society – one more economic than deadly, the other more frightening in its potential to take human life. Both derive from viral infections. The former disease is the common cold. The latter is influenza or flu.

The Common Cold

The common cold is associated with 200 virus types. These include rhinovirus of which there are 110 types, coronavirus, 30 types, and a smattering of others such as adenovirus (pictured below),  coxsackievirus, echovirus, coxsackievirus, respiratory syncytial virus and enterovirus. Among cold viruses are some that cause even more serious illnesses. These include orthomyxovirus with strains associated with influenza, and paramyxovirus with its parainfluenza virus strains.

With so many cold viruses, developing a cure becomes a challenge. But recently researchers in Cambridge in the United Kingdom have made a discovery that could lead to a way to defeat cold viruses even after they have invaded cells.

Adenovirus, mentioned in an earlier blog, is one of over 200 viruses responsible for the common cold. Source: Protein Data Bank

To appreciate this discovery it is important to understand how viruses propagate and cause cold symptoms.  Viruses cannot replicate by themselves. They need the machinery of the cells they invade to generate copies of themselves. Initially a cold virus is introduced to the body by penetrating through the mucus membranes in the nose and throat. The virus is small enough to slip through the mucus defence barrier. It binds with a surface receptor on cells lining the nose and throat and by doing so gets access to the protein-making machinery within the cell. Using the cell proteins the viruses replicate and rapidly invade nearby cells.

Virus-infected cells emit chemical signatures that attract the body’s immune system to them to fight off the invaders. It is the white cells in the immune system that cause an immune system response which includes the symptoms we associate with a cold: stuffy nose, mucus and phlegm, and the cough response to the irritation and inflammation of the nasal and respiratory membrane.

Colds normally don’t last very long, a few days and a few days going. After a week they are usually gone. But sometimes cold viruses leave the body susceptible to other infectious agents of a far more serious nature. So besides finding a way to defeat the cold for its own sake, there are other good reasons to come up with a cure.

Can We Cure It?

Detection and disruption represent the key strategies for curing the common cold. If our immune system could disrupt the virus before it harnesses the machinery of infected cells, the virus would be unable to replicate and would die. At the Laboratory of Molecular Biology, at Cambridge in the United Kingdom, researchers have discovered that anti-viral antibodies have the ability to ride piggyback on an invading virus as it enters the cell and to kill the virus before it replicates. Previously this had never been observed. Scientists thought antibodies only worked outside cells.

In making this discovery, researchers may be able to harness proteins within the cell to fight the virus. The principal antibody recognition cellular protein is tripartite motif-containing 21 or TRIM21. In a normal cold it takes several days before TRIM21 builds up in cells to fight off the viral invasion. But if a vaccine could boost the TRIM21 response by enhancing its fighting power it could neutralize the virus earlier, disrupting it within a few hours and before the infection leads to immune response symptoms.

The findings were recently published in the Journal Proceedings of the National Academy of Sciences. Before human clinical testing scientists will begin lab animal studies. It is expected that a human vaccine will be available before 2020.

This approach could lead to cures for many other disease caused by viruses including rotavirus and enterovirus, a group of viruses that infect millions of children annually resulting in hundreds of thousands of deaths.

Influenza

In 1918 with the World War coming to an end, a flu epidemic later called the Spanish Flu killed more people than the war it followed. Spanish Flu infected 20% of the world’s population over its two-year run and killed between 20 and 40 million. Those most susceptible were young adults between the ages 20 and 40.

Every year when flu season comes around we are encouraged to get a flu shot. Flu can be deadly and influenza viruses can jump species from animal to human hosts such as H1N1 known as Swine Flu. Where the animal may have acquired immunity over time, the human may not. Hence Swine Flu killed many young people who had no immunity to it, Bird Flu in Asia killed handlers of domestic fowl for the same reason, and SARS, a virus that originated in China and spread by airplane around the world, caused many deaths before isolation controls ended the pandemic.

Flu is very different from the common cold. Its onset is faster and the symptoms are more profound. It infects the respiratory tract from the nose to the lungs. It can in any single flu season, associated with late fall and winter months, infect as much as 20% of the population and kill thousands.

It is caused by three types of influenza viruses labelled A and B and C. C is the mildest and not associated with epidemics or pandemics. Type A influenza includes H1N1 or swine flu and along with Type B are associated with these large-scale outbreaks.

There are three types of Influenza virus, A, B, and C. A and B are responsible for pandemics. C causes mild outbreaks. The cutaway shows the RNA and proteins that disrupts the chemistry of infected cells.

The influenza virus constantly evolves making it very difficult for biomedical researchers to develop infection controls to deal with the changes. Flu vaccines are formulated for the most part to fight last year’s influenza virus variant. Scientists in the Northern Hemisphere get a sneak peek at the next influenza virus when outbreaks occur in the Southern Hemisphere, a 6-month window to develop a vaccine that combines last year’s and the current influenza happening at the opposite side of the planet. The most recent flu pandemic occurred in 2009 with the H1N1 outbreak in Australasia before arriving in North America and Europe. H1N1 resulted in 57 million cases in the United States and 11,690 deaths.

Can We Do Better than the Annual Flu Shot?

The answer is yes and researchers at MIT’s Lincoln Laboratory may have found the answer. They call it DRACO for short. It stands for Double-stranded RNA Activated Caspase Oligomerizer, an antiviral therapy designed to find and kill virus-infected cells, leaving uninfected cells unharmed.

Rather than specifically targeting a single virus DRACO takes a broad-spectrum approach, targeting a type of RNA produced by virus-infected cells. DRACO as a therapeutic cure is not limited to treating influenza. It has the potential to deal with outbreaks of almost any virus.

Through animal studies, MIT researchers identified a form of RNA that only appeared in virus infected cells. Dubbed dsRNA, or double-stranded RNA, the cells natural defence systems attach a protein to the strand in an attempt to block it with the virus countering the cell’s defence every step of the way.

The researchers decided  to combine one of these dsRNA-binding proteins with a more lethal protein, one that causes cellular death, known as apoptosis. Apoptosis occurs in cells naturally after many replications when telomeres shorten to the point that the protein initiates the cell’s demise. It also can initiate when a cell begins to exhibit cancerous behaviours.

Through DRACO therapy the naturally occurring apoptosis protein bound to the dsRNA protein can cross the cell membrane of any cells in the body. If no dsRNA is present DRACO leaves the cell unharmed. If dsRNA is present, DRACO initiates cell suicide. Mice treated with DRACO were completely free of viral infections with no toxic side effects. Clinical human trials are not too far in the future.

Biomedicine – Part 11: Curing Technologies in the 21st Century – Overcoming Addiction

Is drug addiction a disease? It may start with a voluntary sampling of a cigarette, an amphetamine, a stimulant, a depressant….but what eventually happens is in fact a dependency driven by our brains. We continue to use the drug for its effect even though it adversely affects our lives. Addictive substances impact the brain’s frontal cortex. That’s the area of our brain that governs decision-making and judgment.  Addiction acts like a runaway train by interrupting the normal brain circuitry making the craving for whatever the substance is overwhelming.

Is everyone susceptible to addiction? It’s a good question because environment may be a strong determining factor.

What motivates someone to try an addictive substance? Often it’s curiosity. Other times it’s stress brought about by circumstances. Sometimes it’s peer pressure, a wish to be a part of a social group, sharing something in common. So circumstances play a role in susceptibility.

What makes an addictive drug work?

Why does our body accept this type of foreign substance?

The chemical structure of most addictive drugs mimics brain chemistry fooling our neurons and in particular neural receptors.

Let’s look at marijuana as an example.

Is the natural brain chemical Anandamide really similar to THC, the active chemical in marijuana? Source: NIDA

The active chemical in marijuana is THC (tetrahydrocannibol). As you can see from the illustration above THC (on right) is a fairly complex molecule. It is fat-soluble allowing it to slip through the barrier that isolates the brain from the rest of our body systems. THC binds with a neural receptor that is the same one used by a naturally occurring molecule, Anandamide (the molecule on the left).

First identified in 1992, Anandamide was discovered by Dr. William Devane at University of Wisconsin, and Dr. Raphael Mechoulam, at Hebrew University of Jerusalem. Synthesized in an area of the brain that governs memory, higher thought processes and body movement, the two researchers named it after the Sanskrit word that means bliss. Why? Because in finding Anandamide these researchers were identifying the natural human-generated equivalent to THC, a chemical that regulates pain, appetite, mood and short-term memory in the brain.

How do Addictive Drugs Interact with Our Brains?

Neural receptors are the key to nerve cell communication. Chemicals that mimic those naturally produced need a way to take part in that communication. In the example we have looked at THC versus Anandamide, the former binds with receptors on the surface of nerve cells in the same way as the latter.

Anandamide is a “key” molecule because it unlocks a cell by binding with receptors on the cell surface. It does this because its shape fits the receptor like a key entering a lock. When it interacts a door opens through the cell membrane causing a flood of chemicals to enter the nerve cell affecting its positive or negative charge.

THC does exactly the same thing because its shape can also bind with the neuron receptor. The difference in the body response to THC versus Anandamide is one of duration. Where Anandamide is fragile and very short-lived, THC is far more robust. So the bliss effect of Anandamide is short-lived, where the bliss effect of THC can go on for a long time producing the perpetual “high” associated with smoking marijuana.

Most of the drugs we use for pain management work in a similar way. Morphine locks into an opiate receptor in nerve cells. Its natural molecular equivalent is enkephalin. Morphine is addictive because when it binds with a nerve cell receptor it locks even tighter than enkephalin and remains attached. Pharmaceutical companies recognized the addictive nature of morphine and developed less potent substitutes like codeine and demerol.

Addictive drugs elevate another brain-synthesized molecular chemical, dopamine. Dopamine acts like adrenaline affecting the brain processes that govern emotional response, pleasure, pain and body movement. Excessive dopamine creates brain euphoria. Drugs that induce strong dopamine responses are called dopamine agonists. Cocaine is one of these. It binds with the dopamine receptor on the surface of a neuron inducing an excessive dopamine response.

Dopamine is a synthesized molecule that stimulates the pleasure centres in the brain. Cocaine and amphetamines are dopamine agonists increasing the response. Source: Squidoo

Over time neurons exposed to drugs like cocaine and amphetamines become desensitized or tolerant to dopamine. In these cases each exposure produces less of drug response. The neurons, in anticipation of the drug, stay in a state of stimulation requiring more to create the same effect. How cocaine does this is by binding and hanging on to the proteins that transport dopamine and remaining longer elevating the dopamine response. Amphetamines work similarly leading to over stimulation of the neurons.

Is There an Addiction Vaccine in the Near Future?

Traditional treatments for addiction have involved finding a less addictive drug such as methadone to help reduce heroin dependency, or using a nicotine patch to help stop smoking. Another drug, Vivitrol, has been used to treat alcoholism and opium addiction. There are even anti-smoking pills that don’t act as drug mimics but instead inhibit the neural receptors.

A vaccine approach pursued since the 1970s, has only recently been able to see dramatic progress in creating cocaine immunity. Dr. Ronald Crystal, at Weill Cornell Medical College, has led a team that has produced a  vaccine to treat cocaine addiction.

The vaccine was created from a modified version of the adenovirus, the virus for the common cold, discarding the content that causes colds and using the remainder as a carrier medium. A molecule constructed to resemble cocaine is injected into the adenovirus and when a human is vaccinated results in an immune system response. The reason for using the adenovirus is simple. Most addictive drugs are too small for detection by the immune system which allows them to get by the body’s defences. By combining the synthesized drug molecules with a carrier already recognized as pathogen, the immune system learns to attack the smaller drug molecules as pathogens as well so they never reach the neural receptors of the brain. In laboratory tests the vaccine’s effect lasted more than 13 weeks causing an immune response anytime mice “snorted” cocaine.

A similar medical project has used a modified cholera bacteria as a transport mechanism with cocaine creating an immune system response to produce antibodies. In 2009 Baylor College of Medicine in Houston ran clinical trials using this cholera-based anti-addiction cocaine vaccine with 115 human subjects. The results showed a strong antibody response in 38% of patients who received the vaccine, and 45% of remained cocaine free in follow-up examinations up to 4 months after. The vaccine is currently in national clinical trials in the United States. Eventually vaccines of this type could be delivered regularly much the way some people take allergy shots, continually boosting the immune response and eliminating the negative body responses to cocaine ingestion.

Recent researchers at The Scripps Research Institute have had successful results developing a similar vaccine for heroin addiction and have tested it in animal models.

Research into vaccines focused on treating smokers for nicotine addiction is on the way. But alcoholism, the most prevalent addiction, remains untreatable through vaccination.

Considering the cost society bears to deal with addiction, policing the illegal drug trade. and the cost of incarceration for repeat drug dealers and offenders, anti-addiction vaccinations represent a better future.

Biomedicine – Part 11: Curing Technologies in the 21st Century – Ending Obesity

Our image of wellness and health has changed in the last two centuries. In the late 19th and early 20th century the healthy and wealthy looked like the men who appear in the picture below. By today’s standards we would consider these men fat or even obese.

From left to right, J.P. Morgan, Edward VII and Andrew Carnegie represented what was considered a healthy figure at the end of the 19th century.

Back in their time these men were society’s elite, an example of success in life. Of the three only Edward VII died from the kinds of complications we associate with bad health decisions and obesity, indulging in 20 cigarettes and 12 cigars per day, gluttonous eating habits and dying from a succession of multiple heart attacks. The other two managed to survive their obesity.

Today we have a different human paradigm as seen in the image below. Obesity doesn’t fit with this picture. Yet today obesity is reaching epidemic proportions, and not just in North America, but worldwide.

Our image of what healthy looks like has changed over time. Source: Modern Athlete

Why? Because our obesity grows:

• As more of us move from rural to urban areas
• As we move from physical work to knowledge work
• As we add more labour-saving technology to our homes
• As we bring new entertainment technologies to our living rooms and dens
• As we rely more and more on drugs that have side-effects contributing to obesity

We eat saturated fats and sugar. We are less active physically than any previous generation. In 2012 according to a recent Australian study 1.5 billion of us are overweight. Of these 400 million are obese.

Our genetics contributes to this condition in part but our growing bulkiness stems from the combination of all of the issues described above. Since 1980 these behaviours and lifestyle changes have led to obesity growth rates of 300% in North America, parts of Europe, the Middle East, the Pacific Islands, Australasia and China. And there doesn’t appear to be an end in sight.

There are consequences. Obesity and being overweight comes with increased risk including (in alphabetical order):

• Cancer of the breast, colon, endometrium, kidney, gall bladder and prostate
• Cardiovascular disease
• Chronic musculoskeletal problems effecting joints such as knees and hips
• High blood pressure
• High blood cholesterol
• Hypertension
• Infertility
• Osteoarthritis
• Skin problems
• Stroke
• Type-2 Diabetes

Obesity in adults is accompanied by obesity in children. In a recent United Nations report it was estimated that 22 million children under five years of age worldwide were overweight.

Even more alarming is a correlation between obesity and Type-2 Diabetes and exposure to air pollutants. Recent studies reported by the American Diabetes Association indicate that exposure to particulate matter in the air leads to increased obesity and diabetes. The study concludes that exposure to particulate matter in the air results in inflammation in fatty (adiopose) tissue as well as insulin resistance and that this is contributing to the doubling of reported cases of diabetes over the last 15 years in the United States to almost 24 million.

There is a correlation between obesity and pharmaceuticals. So many medical conditions we treat with drugs that have an unwanted side affect — obesity. Drugs that treat depression, psychoses, and epilepsy are known to stimulate appetite. So do anti-viral and anti-HIV drugs. Steroids, progesterone and estrogen to treat autoimmune and hormonal imbalances also contribute to weight gain. We are, infact, medicating ourselves to obesity.

Effective Lifestyle and Eating Remedies for Obesity

It is in our nature to ignore a condition until it leads to more serious outcomes and that is the way most of us treat obesity and being overweight. As a result we treat the complications, medicating for all the diseases described above, rather than coming up with strategies to deal with the initial problem.

The easiest way to deal with obesity is through managing diet and changing lifestyle. To do this we need to:

1. Change the type of foods we eat as well as the quantity. This involves increasing the amount low-fat and high-fibre foods we eat. It means more fruit and vegetables, more whole grains and nuts in our diet, less saturated animal-based fats, more unsaturated vegetable-oil fats, and less sugary foods. And it means eating less.
2. Develop an active lifestyle involving daily exercise to burn the food we eat. This doesn’t mean becoming a marathoner. It does mean developing active hobbies, walking instead of driving, and cycling instead of using a car.

As a writer I am very aware of how my work environment can contribute to weight gain. I have watched my weight go up and down over the years. Today I am once more shedding pounds to reach my ideal weight, around 80 kilograms (176 pounds).  I am about 7 kilograms away right now. How I’m doing it is by combining portion control in my eating with increased activity. I make a point of walking one hour every day to offset the long deskbound hours when I am doing research and writing. I conscientously take frequent breaks from my desk to walk from my office upstairs to our main floor or our basement. By doing this I hope to lessen the impact of sedentary work.

But even with diet and exercise overweight problems and obesity don’t necessarily go away. And if you are on a drug treatment program to deal with other maladies, you may find it very difficult to keep weight off.

In the University of Melbourne study in Australia that we talked about earlier in this blog, researchers tracked 50 overweight men and women with an average weight of 95 kilograms (209 pounds). The group was put on a 10-week low-calorie diet and on average lost 13 kilograms (29 pounds). At the end of the weight-loss period,  body hormone levels changed leading to an average weight regain of almost 5 kilograms (11 pounds). So even when humans lose weight many regain a portion of it quickly. And it appears this has something to do with our body chemistry, the proteins that are part of us that determine when we are hungry and when we are not.

Can Science and Technology Save Us from being Overweight?

Two gastric endocrine hormones play a significant role in dealing with enhancing and suppressing our appetite.  One is leptin. The other is ghrelin. Researchers study the interrelationship between these two in trying to understand why some people are more prone to obesity or eating disorders.

The hormones are truly a balancing act. Leptin regulates energy levels in the body by suppressing the desire to eat. It is an anorexigenic (as in anorexia) hormone. Ghrelin acts as a counterweight to leptin. If energy levels are low it encourages us to to eat. The term to describe the ghrelin hormone characteric is orexigenic.

Obese patients are orexigenic. They are leptin-resistant because they either do not produce enough leptin protein in their systems to stop them from wanting to eat or they produce too much ghrelin within their bodies which stimulates the appetite.

In studying the leptin-ghrelin cycle researchers at the Scripps Research Institute in La Jolla, California have identified a way to suppress grhelin using an antibody. Under the leadership of Dr. Eric Zorrilla, a neuroscientist who specializes in eating disorders, the Scripps research team has developed an antibody-based therapy that combine an anti-ghrelin with a carrier protein harvested from a mollusc, the Keyhole Limpet.

The Keyhole Limpet manufactures Hemocyanin, a protein that binds with anti-ghrelin to provide a vaccine for obesity. Image Source: Popular Science

The protein, Keyhole Limpet Hemocyanin or KLH, is currently being studied as a carrier protein for cancer treatment vaccines to treat non-Hodgkins lymphoma, cutaneous melanoma, breast and bladder cancers. But what it can do for cancer also works when it is coupled with ghrelin antibodies. Currently being tested in animal studies, Scripps plans a human vaccine trial in the near future.

Is the future of obesity tied to a vaccine rather than dieting and lifestyle changes? For most of us who can control obesity and being overweight by changing diet and behaviour the obesity vaccine will probably never be something we need. But like so much of the progress we make in technology we may just choose the easy way out and get a shot to deal with being overweight.

Biomedicine – Part 11: Curing Technologies in the 21st Century Continued – Ending Heartache

Of all the topics I have written about to-date, this one strikes closest to home. My daughter was born with congenital heart disease 27 years ago. At the time the odds in favour of her survival to adulthood were low but she made it. Today, children born with her form of congenital heart disease are far more likely to live a full life because of medical discoveries, development of new devices, better medical protocols, and a better understanding of the science of human physiology.

A Quick Primer on Heart Disease

Humans get two types of heart disease: congenital (that is born with) and acquired (disease that develops over time). Congenital tends to be structural. It can express itself in abnormal anatomy or physiology. Acquired begins with normal anatomy but physiology changes as the heart becomes diseased. Both can lead to heart failure which you can live with for a very long time or heart attacks which can lead to death.

Tetralogy of Fallot is one of many congenital heart defects, structural diseases that happen during fetal development. Source: New England Journal of Medicine

Structural defects to the heart and blood vessels in congenital heart disease can be repaired surgically, missing valves implanted and blood flow restructured using human grafts and artificial materials. Drugs can help regulate heart rhythm or improve the pumping efficiency. Pacemakers can help overcome structural problems that impact the electrical system that regulates heart rhythm.

Acquired, which represents the bulk of what we normally think of as heart disease, can also benefit from surgical intervention, drugs, pacemakers and other devices.

Atherosclerosis is an acquired heart disease that leads to partial to full blockages in the coronary arteries. Source: Medline

What causes heart disease? Lifestyle and inherited genes are the principal cause with 30 to 60% of the risk associated with the latter when it comes to acquired, rather than the former. Recent international studies identified 17 new genetic variants linked to increased heart disease risk.  Five of these were associated with genetic regions that govern lipid metabolism processes, genetic controllers that impact the build up of fatty deposits in arteries. Ten others were in genes involved with other diseases and traits such as autoimmune diseases like Celiac and Type 1 Diabetes, cerebral and abdominal aneurysms, and lung cancer. What this means is there is no single genetic “smoking gun” that defines whether a person is likely to get heart disease in his or her lifetime. Instead we have a complex of genetic markers.

New Therapies for Repairing Bum Hearts and Blood Vessels

Stem Cells

In past blogs we have talked about stem cell therapy. Because stem cells have the potential to develop into a range of tissue types we can use them to regenerate and replace diseased tissue.

Cellular Dynamics International (CDI), is an American company located in Madison, Wisconsin, that is experimenting with the reprogramming of adult somatic cells to make them revert to a pluripotent state so that they can grow into any cell type needed for doing repairs to the body. These are induced pluripotent stem cells or iPS. Since 2008 CDI has used iPS cells to manufacture cardiomyocytes (heart muscle cells), freezing and sending them to pharmaceutical companies doing research on new drugs to treat heart disease.

Induced Pluripotent Stem (iPS) cells are generated from adult donors to grow organs and body tissue. Source: http://stemcells-research.net

But iPS cells have a brighter future if we can work out some of the bugs. Those bugs include faint traces of chemical residue from the parent cells used to create the reverted cells. Those residues can lead to mutations and as we have already written in previous blogs, mutations can lead to runaway cancer cell proliferation.

You can create iPS cells from almost any human tissue source. If a patient with a damaged heart provides a tissue sample, the cells from the sample can be induced to revert to iPS cells. They then can be transplanted back into the patient at the location requiring treatment. iPS cells from the donor are not rejected because they are from the donor who is also the recipient. The iPS cells in their reverted state can take on the characteristics of those cells that are in proximity to them and start to divide. iPS cells in the heart can generate heart muscle. iPS cells in the spine can generate nerve cells. CDI charges pharmaceutical companies $1,500 for 1.5 million iPS cells. That’s not cheap but the potential for iPS as an alternative therapy to transplants makes this a desirable area of ongoing research.

In research being conducted in Bristol, England and Glasgow, Scotland, Doctor Costanza Emanueli, along with a team of scientists are studying a variety of approaches to treating heart attack victims including using embryonic stem cells to create blood vessel cells to inject into patients. The method of delivery is a skin patch.

Gene Therapy

Researchers are looking at ways to tweak DNA to repair injured hearts. This involves manipulating a variety of genes that impact muscle and blood vessel growth.

Dr. Emanueli’s team, mentioned in the previous section, is studying boosting levels of nerve growth factor (NGF) to improve heart attack survival rates. In studies with mice the death rate from heart attacks was reduced by half using NGF. The gene responsible for NGF was attached to a specially engineered virus and delivered into the hearts of mice. Mice that received the NGF gene showed much improved circulation and heart function. In previous studies NGF was known to regrow nerves but in this case it encouraged new blood vessels to grow inside the injured heart muscle.

In another study conducted at Harvard’s Beth Israel Deaconess Medical Center, the gene C/EPB-beta spurred the growth of cardiomyocytes. This study showed that a genetic trigger responding to physical exercise turned on a molecular pathway to get cells to start dividing. For a very long time cardiologists could not find evidence of cell division in adult heart cells. Hearts under stress or subject to exercise would swell but cell proliferation in these enlarged hearts was poorly understood.

Heart muscle enlargement, called hypertrophy, can be associated with disease or with what is referred to as “athlete’s heart.” In the study cardiomyocyte growth was attributed to molecular events rather than factors such as high blood pressure.

Reprogramming Heart Cells After a Heart Attack

Heart attacks in the past have caused irreparable damage to heart muscles. What causes them? The usual suspects are accumulations of deposits on the walls of arteries that supply the heart with blood. When an artery is partly to fully blocked oxygen and nutrients are cut off to the area next to the blockage. This kills the muscle near the blockage affecting the heart’s ability to beat. But what if the section of damaged heart muscle can regrow?

Professor Paul Riley, of Oxford University’s Department of Physiology, Anatomy and Genetics, and his team of researchers are looking at a layer of cells known as the epicardium. The epicardium is the inner wall of the sac of tissue known as the pericardium that surrounds the heart. The embryonic epicardium contains many types of cells used by the heart and circulatory system including blood vessels and heart muscle. But after birth the epicardium gets quiet and stops generating these tissues. Dr. Riley and his team looked at ways to switch the epicardium cell generation back on. In mice studies they achieved just that by administering doses of Thymosin Beta 4, a natural occurring protein, to stimulate the embryonic genes in the epicardium to create cardiomyocytes. The researchers found that administering Thymosin Beta 4 before a heart attack proved to stimulate faster regrowth of heart muscle tissue.

The team continues to hunt for other naturally occurring molecules that can stimulate heart muscle and blood vessel growth. Along with drug and interventional therapies to clear arterial blockages, administering these proteins pre-emptively could create a bank of healthy new heart muscle to speed recovery should an attack occur.

Dr. Anastasis Stephanou, University College Hospital, London, is part of a team looking at creating patches to repair damaged hearts. Sheets of protein impregnated with biological material including three types of heart cells form a scaffolding to grow cardiac tissue. So far they have been able to create small pieces of cardiac tissue with an aim to create larger sheets that could be used to patch a damaged heart.

Researchers in all these areas are getting closer to moving from the laboratory to clinical trials. We are probably less than a decade away from achieving new breakthroughs in repairing hearts.

Biomedicine – Part 11: Curing Technologies in the 21st Century Continued – Finding Cures to Stop the Body Attacking Itself

Not too many people realize that many forms of diabetes are caused by our immune system going haywire. Normally, the immune system is our first line of defence against invasive bacterium. But what happens when our system cannot tell friend from foe? In this blog we identify some of the leading autoimmune diseases and the current state of our research, and a potential cure using nanotechnology as the transport mechanism.

What is an Autoimmune Disease?

Autoimmune diseases are inflammatory response diseases caused by our immune system attacking us. They are non-discriminating and can be found in almost every organ and system in the human body. They tend to be chronic conditions continuing throughout the lifetime of the individual. There can be periods of remission followed by reappearance of symptoms. They tend to strike women more than men. Hormones may play a role. But there are some autoimmune disorders that are more prevalent in men such as Type 1 Diabetes.

How significant is the problem? It is estimated that 24 million Americans and 5 percent of the population in Western countries suffer from autoimmune diseases. Compare that to cancer at 12 million Americans and you begin to see the enormity of the problem.

There appears to be a correlation between our genetic inheritance and autoimmune diseases with children tending to develop diseases that appear in parents, and close relatives exhibiting common autoimmune diseases within extended family groups. Multiple sclerosis represents one of the most common autoimmune diseases that tends to run in families.

What confounds the medical field today about autoimmune diseases is finding the smoking gun or guns, the direct causal link that triggers the immune system response. Lots of circumstantial evidence points to viruses, chemical exposure, foods and environmental toxins but doctors and researchers continue to investigate what triggers these diseases. Having a family member who continues to experience an autoimmune disease has made studying this subject very personal to me.

Autoimmune diseases attack every part of the body. The American National Institute of Health identifies at least 80 different autoimmune diseases that include many familiar conditions you probably never thought were caused by our immune system. See how many you know from this partial list.

• Actinic Prurigo – an autoimmune response to the sun
• Addison’s disease – the autoimmune destruction of the Adrenal Gland – a disease that President John Fitzgerald Kennedy suffered from
• Ankylosing Spondylitis – an arthritic condition that attacks the pelvis and spine
• Autoimmune Myocarditis – a condition that effects the heart muscle
• Behcet’s Disease – a disease that causes oral and genital ulcers, and skin and ocular lesions, and can affect arteries and veins throughout the body
• Birdshot Chorioretinopathy – a disease of the retina in the eye that causes flashing lights and night blindness
• Chronic Urticaria and Angioedema – a condition that causes persistent eruptions of hives traced to drug, food reactions, pressure, infection or toxin response
• Celiac Disease – a disorder of the small intestine
• Crohn’s Disease – a disease that effects the entire digestive tract in the body
• Drug Hypersensitivity – a response to drugs leading to fever, skin rash, and internal organ reactions such as hepatitis, pancreatitis, myocarditis, nephritis, intestinal lung disease and muscle inflammation
• Graves’ Disease – a disease of the Thyroid Gland that leads to hyperthyroidism and goiters
• Guillain-Barre Syndrome – a response to infection that results in nerve inflammation, muscle weakness and potential paralysis
• Hemochromatosis – an adult onset disease resulting in progressive iron overload in the body with complications such as cirrhosis of the liver, diabetes, cardiomyopathy, arthritis, and testicular failure
• Hashimoto’s Thyroiditis – a disease of the Thryoid Gland that leads to hypothyroidism
• Hemolytic Anemia – a disease that attacks red blood cells destroying them prematurely
• Juvenile and Type 1 Diabetes – a disease caused by destruction of insulin-producing Pancreatic Islet cells
• Lupus or SLE (Systemic Lupus Erythematosus) – a disease that predominantly strikes women and causes skin, joint, haematologic, neurologic, renal and other organ problems and leads to seizures, psychiatric symptoms, peripheral neuropathies or stroke.
• Multiple Sclerosis – a neurodegenerative disease more common in women that attacks the myelin sheath surrounding nerves affecting coordination, balance and vision as well as many organs in the body
• Myasthenia Gravis – a neuromuscular disease that causes muscle weakness and fatigue.
• Polyarthralgia – a disease that causes inflammation in the joints and is associated with osteoarthritis
• Psoriasis – a chronic inflammatory skin disease
• Raynaud’s Disease – a response associated with other autoimmune disorders that causes blood vessels in the  hands and feet to overreact to cold temperatures
• Rheumatic Fever – a disease that may occur after a Streptococcal or other infection causing lesions in connective tissue, particularly the heart
• Rheumatoid Arthritis – a chronic inflammatory arthritis that causes deformation of joints
• Scleroderma – a disease that affects tissue fibre, particularly the skin, lungs, gastrointestinal tract, heart, small blood vessels and capillaries
• Sjogrens – a disease that attacks the salivary and tear glands
• Thrombocytopenia – a disease that effects blood platelet production leading to abnormal bleeding
• Ulcerative Colitis – a disease that causes inflammation and ulcers in the large intestine
• Uveitis – an eye disease that leads to blindness

Today’s Autoimmune Controls Create Their Own Problems

Currently autoimmune disease treatment is all about reducing or reversing symptoms. In the case of diabetes we treat sufferers with insulin rather than restore pancreatic cell function. In the case of many of the inflammatory responses from autoimmune diseases we treat patients with a cocktail of drugs that include prednisone and other corticosteroids, anti-inflammatories like aspirin, acid blockers, antihistamines and immune suppression drugs (the kind used to stop rejection in organ transplants). In many cases the side affects of these drug cocktails proves to be worse than the diseases.

HLA, T and B, Autoimmune Diseases and a Potential Cure

When scientists and researchers talk about the immune system the letters in the above title become part of the conversation.

What is HLA?

What does T refer to?

What is the B all about?

HLA stands for Human Leukocyte Antigen, the genes that reside on the 6th chromosome in our cells and that govern immune response. The proteins associated with these genes are called antigens.

The T and B refer to different types of leukocytes, the white blood cells that reside in our circulatory systems and marshal our response to infections. The T and the B refer to T-cells, and B-cells. In addition there are sub-categories to leukocyte groups. One is the T-regulatory cell  or T-reg and researchers study it because these cells play a role in regulating the level of immune response by other leukocytes.

If we could develop a technology to stop specific unhelpful autoimmune reactions while allowing our normal immune response to deal with unwanted bacterium and viruses then we would be making a big leap forward in our ability to deal with autoimmune diseases. That’s exactly what researchers at the University of Calgary in Alberta, Canada, have been working on using nanotechnology as the delivery mechanism for a vaccine that cures Type 1 Diabetes and has implications for other autoimmune disorders.

Dr. Pere Santamaria works at the Julia McFarlane Diabetes ResearcherCentre in the University’s Faculty of Medicine.

Dr. Pere Santamaria has led a team developing a diabetes vaccine that uses nanoparticles to stop immune response cells from destroying insulin-producing cells in the pancreas.                                           Source: University of Calgary

Working with mice with Type 1 Diabetes, Dr. Santamaria and his team looked at stopping the autoimmune response that damages the pancreas leading to the condition. They studied the behaviour of specific T-cells responsible for the disease and the T-reg cells whose role is to inhibit the former from attacking healthy host tissue.  Their goal was to strengthen the T-reg cells to stop the destructive autoimmune response. Using synthetic iron oxide nanoparticles and a cocktail of antigens from insulin producing cells, the team created a vaccine that could be directed at the autoimmune attack, strengthening the T-reg cells. The treatment not only restored normal blood sugar and insulin levels in the mice, it also prevented the onset of the disease. At the same time the vaccine treatment did not compromise the rest of the immune system.

The implication of using nanovaccines such as the one Dr. Santamaria’s team developed to treat other chronic autoimmune diseases is enormous. For those who suffer from one or more of that long list of autoimmune diseases described above, this is technology with great promise.

Biomedicine – Part 11: Curing Technologies in the 21st Century Continued – Curing Cancer

Some Basic Facts About Cancer

When the genes in normal (somatic) cells mutate cell behaviour may change over time leading to cancer. Mutations are a normal part of the life of a cell. That’s because when cells divide they replicate their DNA but imperfectly.

In a previous blog we talked about telomeres, the ends of the DNA strands in our chromosomes and how the telomeres shorten over time with each cell division eventually leading to cellular death. But it is not just telomeres that change during cell division. Other parts of the DNA can get scrambled or lost. We call these changes mutations. Since mutations happen all the time why do some become cancerous while others remain benign?

Medical researchers suspect that specific mutations in sections of our DNA that regulate the cell life cycle, when accumulated over time, cause cancer. Mutations that govern other cellular functions appear to have no malignant implications.

Here are some additional facts about cancer.

1. Less than 5% of cancers are familial, that is, inherited. So when you are told breast cancer runs in your family this is representative of a very small percentage of all the cancers that doctors see.
2. Most cancers happen in older people and are not inherited. They result from accumulated DNA mutations in cells over a lifetime.
3. Some cancers result from epigenetic changes, that is external factors such as environment, food and nutrition and lifestyle that create DNA mutations.

As researchers study cancer they are discovering new ways to treat it and reviewing some old ideas that showed promising results in the past. Let’s look at where we were with cancer, where we are today, and where we will be in the near future in the 21st century.

Seeking a Vaccine that Cures Cancer

Does the name William Coley ring a bell? For most of you, probably not. Born in 1862, Dr. Coley, an American surgeon who decided to devote himself to finding a cure for cancer, was the first to note that exposure to an infection could arouse a person’s immune system to shrink tumors.

William Coley pioneered cancer treatment with patients by injecting them with Coley's toxin, a mixture of heat-treated bacteria. Source: MBVax Bioscience Inc.

Dr. Coley studied sarcoma (bone cancer) at his New York hospital and identified a prior case of a German immigrant who had been operated on several times to excise a tumor in his left cheek. Each time the tumor regrew and after the final operation the remaining wound became infected. Surgeons were convinced that the man’s case was terminal but 4-1/2 months after he was discharged the tumor had vanished. When Dr. Coley studied the case he discovered that Streptococcus Pyogenes, a common bacterium that causes strep throat, was the source of the wound infection. The history of the case showed that the man had several outbreaks of fever and these outbreaks coincided with dramatic changes to the tumor. Dr. Coley concluded that the infection had saved the man’s life by stimulating his immune system to eradicate not only the bacterium but also the cancer.

Dr. Coley tested his theory on late-stage sarcoma patients first injecting them with live Streptococcus Pyogenes bacterium. The injections caused the tumors to shrink but in two cases the strep infections killed the patients. Dr. Coley then experimented with heat-treated bacterium injections. His first patient was a 16-year old boy suffering from a massive abdominal tumor. Known as Coley Fluid and later Coley’s Toxin, when injected into the tumor mass, produced the symptoms of an infectious disease (fever and chills) but not the full-blown illness itself. Repeat injections caused the tumor to shrink and eventually disappear. With no further cancer treatment the patient was discharged and survived another 26 years. Death was from a heart attack and not cancer.

Today the work of Dr. Coley continues at the Cancer Research Institute in New York. Founded by Dr. Coley’s daughter, the Institute studies how our immune system responds to cancer. In the 1970s doctors at the institute discovered that Bacille Calmette-Guerin or BCG could be used to treat early onset cancer of the bladder. The Institute has also studied cell proteins, called cytokines, and their immunotherapeutic effect on tumors.

Far from being Coley’s Toxin, seen by many in the medical establishment as quackery, current research is proving that Dr. Coley’s approach may lead to multiple cancer vaccines similar to the HPV cancer vaccine used to prime the immune system to kill human papillomavirus, a cause of cervical cancer.

Provenge is a vaccine developed by Dendreon, a company in Seattle. Designed to initially treat late-stage prostate cancer, Provenge is patient-specific. Cells from a patient are collected and then exposed to a chemical bath that contains cytokines that activate the immune system to attack the cancer. The cells are reinjected into the patient over the period of a month. Clinical trials on 512 advanced prostate cancer patients have been encouraging with 1/3 of the vaccinated patients remaining alive after 3 years. Plans are to introduce Provenge into earlier stage prostate cancer clinical trials.

We now know through the legacy of Dr. Coley that immunotherapy works. But what is the actual mechanism within our cells that leads to cancer? Research using baker’s yeast is yielding some exciting results.

Why Yeast Holds Clues to Curing Cancer

Saccharomyces cerevisiae is baker’s yeast, the yeast we humans have been using for milennia to make bread and fermented beverages. When a biologist, Leland Hartwell, decided to study cancer he chose yeast to help him model and understand the cell cycle.

Leland Hartwell, 2001 Nobel Prize winner, studied baker's yeast to better understand cancer cell behaviours. Source: Fred Hutchinson Cancer Research Institute

Hartwell was able to identify more than 100 genes directly involved in yeast cells that impacted life cycle. He called these Cell Division Cycle genes or CDCs. Hartwell identifed specific yeast genes responsible for different parts of the cell cycle and found similar characteristics in human cells. Since CDC genes either stimulate or inhibit cell division at very specific times in the cell lifecycle, Hartwell was able to identify the genes that didn’t operate in a normal manner. These included:

1. Oncogenes – genes that act as if they were operating in hyperdrive
2. Tumor Suppressor Genes – genes that inhibit runaway cell division
3. Checkpoint and Repair Genes – genes that detect damage to the DNA and attempt repairs

Any mutation to these genes could lead to what he described as driving with a stuck-accelerator and broken-brakes with no awareness that something has gone wrong resulting in out-of-control cell replication and the development of cancerous tumors.

What are the implications of this research in our search for cures for cancer in humans? Knowing that mutations in genes that control the lifecycle of our cells causes cancer should allow us to develop targeted therapeutic drugs specifically aimed at stopping runaway tumor growth. The tailor-making of drugs, called pharmacogenomics, should result in patient-specific cancer chemotherapy treatment without the side effects we normally associate with today’s treatments.

Having discovered the genetic mechanism that fuels cancer, the challenge is to find a way of delivering the cure and scientists may have discovered that answer. Read on.

RNA, Nanotechnology and Cures for Cancer

We’ve talked about Ribonucleic Acid or RNA in previous blogs. RNA interference or RNAi is a recent discovery and has enormous implications in delivering a cure for cancer. Why? Because RNAi can be used to silence the activity of specific genes within a cell. It does this by destroying messenger RNA or mRNA, the molecular messenger that carries coded information in genes to the protein factories needed to manage the cell’s lifecyle.

The challenge scientists faced was finding a way to dleiver RNAi  to a target without it degrading. When RNA is normally injected into the bloodstream it quickly degrades. That’s where nanoparticles come in. American researchers have developed a vaccine that contains a nanoparticle drug that can deliver RNAi to cancer cells. Using a polymer that self-assembles to create the nanoparticle, and coated with a chemical that provides each particle with protection from binding to any cells it encounters within the bloodstream, the nanoparticles target surface receptors on cancer cells, penetrate and destroy them and cause minimal side effects to surrounding healthy cells.

It has taken 15 years to develop nanotechnology delivery systems. RNAi was discovered in 1998. What will we witness in the next 15 years? We are getting much closer to one of the Holy Grails of modern medicine, a cancer cure.

Biomedicine – Part 11: Curing Technologies in the 21st Century

In this last series of  blogs we look at curing what ails humanity using 21st century technology. We’ll tackle this in several articles.

Many of our 21st century technology solutions may prove effective in treating a range of disease types. What diseases are on our immediate radar?

1. HIV and AIDS
2. Mosquito-spread Diseases – Malaria, Dengue Fever
3. Cancer
4. Diabetes
5. Allergies and Autoimmunity
6. Heart Disease
7. Obesity
8. Addiction
9. Influenza
10. The Common Cold

How close are we to finding cures? For some very close.

In this first blog will look at HIV and AIDS and diseases spread by mosquitoes.

Ending AIDS

Bioengineering a cure for AIDS means ending a global pandemic that infects 7,000 humans daily. Over 35 million humans today are infected with HIV, the virus responsible for AIDS. HIV attacks our immune system’s primary defences, the T cells. Specifically it attacks CD4+ T cells, cells that initiate the body’s response to an infection. HIV is classified as a retrovirus. Retroviruses use host cells to replicate themselves and CD4+ is HIV’s host. Once HIV has “occupied” a CD4+ cell it damages it until it dies leaving us with fewer to fight off other infections. Normal humans have 600 to 1,200 CD4+ cells per cubic millimeter of blood. Numbers below 500 require intervention in terms of treatment with retroviral drugs today. When counts drop below 200 a HIV infection turns into AIDS.

HIV takes over a lymph cell and uses its nuclear information to replicate itself. In this picture HIV is erupting from a lymphocyte.

Today HIV-infected humans can live decades with the virus before AIDS because combinations of medications can be used to fight the virus. This medical breakthrough started in the mid 1990s and in the latter part of the first decade of the 21st century we have seen very hopeful signs in combatting the infection using gene therapy.

Today HIV is a chronic disease and not necessarily a death sentence. Retroviral drugs do not eliminate the infection, just keep it at bay. This presents an economic and supply challenge. The drugs have to be taken every day. They are expensive and as a result unaffordable to people in many of the Developing World countries.

Two approaches to managing HIV include creating a vaccine, or finding an outright cure. Currently it appears that we are closer to a cure and gene therapy is the technology involved.

The case of Timothy Brown represents what may prove to be the sought for breakthrough. Mr. Brown, an American, was diagnosed with HIV and leukemia. In 2007 and 2008 he received two bone-marrow transplants to treat the leukemia. The marrow donor lacked a protein that resides on 99% of all CD4+ T cells. Called CCR5, it is the protein that HIV uses as a way to enter a CD4+ cell.

Timothy Brown, an HIV and leukemia sufferer, in receiving a bone marrow transplant for leukemia has been HIV free.

As in all bone marrow transplant cases, Mr. Brown’s own immune system had to be destroyed for him to accept the donor. The replacement immune system produced a remarkable result. Mr. Brown, who now lives in San Francisco, has been HIV free since the transplant.

Bone marrow transplants represent an impractical way of killing HIV. But this startling success has scientists experimenting using gene therapy as a method to modify a patient’s immune cells by eliminating CCR5. Recently, Sangamo BioSciences successfully demonstrated a CCR5 gene disruption technology with promising initial clinical results. Sangamo is not alone in developing CCR5 inhibitors. Researchers at City of Hope, University of Southern California, and Calimmune at UCLA are developing CCR5 disabling technology in blood stem cells. Using these types of stem cells for transplants could lead to permanent immunity to HIV.

In 2012, we are much closer to an AIDS cure than ever.

Ending the Mosquito as a Disease Spreader

Mosquitoes have been called flying hypodermic needles. They infect 700 million people annually with a variety of diseases. Dengue fever, a tropical illness, infects 50 to 100 million people per year and has been spreading northward in North America as global warming changes climate patterns. Dengue hemorrhagic fever (DHF) represents a more serious disease with a fatality rate of about 5%. Up to 1 million people die from malaria each year. The El Nino weather effect may relate to the cycle of both malaria and dengue outbreaks. Mosquitoes transmit other diseases including encephalitis, Rift Valley Fever, Yellow Fever, West Nile Virus and Canine Heartworm. If we can stop the biting we can seriously limit the spread of these diseases.

Mosquitoes are responsible for infecting 700 million people worldwide each year. Source: National Pesticide Information Center

A company in California has been studying how blood-feeding insects use olfactory neurons to detect CO2 gas plumes produced when humans and animals breathe out. Called OlFactor Laboratories, the company is creating technology that can be used as a repellent, inhibiting the detection of CO2 or,  a lure, trapping insects using a CO2 emitter. This radical new approach delivers new, easier to deploy and more cost-effective tools in the fight against the transmission of infectious disease by blood-feeding insects.

Mosquitoes detect CO2 to locate prey. OlFactor Laboratories is considering several solutions with this understanding. One would generate a chemical that mimics CO2 acting as an odour trap. Another would involve creating an odour cloud to make CO2 emitters undetectable. OlFactor is looking at a chemical, butanone as well as derivatives such as butanal and butanedione. When CO2 detecting insects sniff these chemicals their CO2 sensors don’t work.

If OlFactor succeeds we will do a lot less of applying DEET and other chemicals to our skin and will witness a dramatic decrease in disease and death from mosquito bites. OlFactor expects to have this technology readily available before 2020.

In our next blog will look at curing technologies with cancer and diabetes as the target.