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.

Biomedicine – Part 10: Bioengineering the End to Aging

In our last blog we introduced telomeres, the genetic information that slowly vanishes from chromosomes each time cells divide. Researchers who study aging see a correlation between those vanishing telomeres and growing older. But I am getting ahead of myself. Before we can talk about the mechanism of stopping aging we really need to understand aging processes and current theories. Scientists have differing opinions on what causes us to age. One opinion states that our bodies have a biological built-in timeline that switches genes on and off, alters hormones over time and impacts our immune system making us less capable of fighting off disease. The second opinion asserts that we are victims of our environment and the damage it does to us over time. That damage includes genetic mutation in cells, accumulated proteins that impair cell function, and general wear and tear.

Our Biological Limits

In the latter part of the 18th century the average human lived 24 years. By the end of the 19th the average lifespan had doubled. In the second decade of the 21st century we are approaching a doubling again. Is there a biological limit?

We are the sum of our genetics. How long your parents lived may indicate how long you will live. But then again it may not.  We know that altering genes can alter the lifespan of animals and plants we study in laboratories. We have doubled the lifespan of mice by splicing genetic material into their chromosomes.

This picture shows two mice from a study done at the University of Washington. By suppressing a protein in a control study, the mouse on the left lived twice as long, was much healthier and demonstrated higher cognitive functions. Source: Technology Review, MIT

In an earlier blog we described the structure of DNA, genes, base pairs and chromosomes. It may be helpful to click on the link provided as a quick refresher before reading further.

We have two DNA repositories in every cell in our body (blood cells not included). That DNA is found in the nucleus and mitochondria within the cell. The DNA organizes itself as chromosomes. When cells replicate the chromosomes divide and copy themselves. This is called mitosis.

Telomeres are repeating DNA base pair sequences that sit at the end of each chromosome. They act as buffers to ensure that DNA replication during mitosis remains accurate. A ribonucleic protein enzyme, telomerase, maintains the telomeres.  As cells divide some telomere information does not replicate, usually between 25 and 200 base pairs. The average telomere can be as long as 15,000 base pairs so what is lost is not significant until the cells divide many times. The accumulation of lost base pairs starts adding up.

Why do we lose telomeres? This may be a reflection of our natural aging process, the unwinding of our biological clock so to speak. Or telomeres may shorten because of external forces such as exposure to toxins, disease or injury. Ultimately when chromosomes no longer have a telomere buffer cells they no longer can divide and we call this cellular state senescence. The Hayflick limit, named after the scientist (see the image below) who, in 1961, first discovered this phenomenon, is the natural limit of a cell’s life after multiple replication.

Dr. Leonard Hayflick, a gerontologist, first observed that a normal population of cells has a finite limit in which cell division occurs. Source: Technology Review, MIT

Do all cells have a Hayflick limit? Apparently not as scientists have observed in studying cancer. Tumor cells do not suffer from DNA strand shortening. They can infinitely replicate because in cancer cells telomerase remains active restoring telomere length. Other cells that don’t exhibit the shortening of telomeres include sperm and egg cells. Hormones may impact telomerase activity and telomere lengths. It is believed that estrogen plays a role and may explain why women live on average longer than men.

If we were to alter the behaviour of our normal cells by stimulating telomerase could we reverse the aging process, ending senescence? This is possible. Use of telomerase in laboratory settings has shown that it can confer “immortality” on several types of human cells. That same capability makes telomerase one of the key factors in cancerous tumor cell growth and is leading to research into telomerase inhibitors that would transform cancer cells by starving them of the protein and putting them into senescence.

Telomeres alone do not extend life. If they were the sole means by which we could stop aging we have the technology to produce on mass altered cells containing high levels of telomerase and bank these for use to cure incalculable diseases. Right now scientists believe that stopping telomere shortening may add 10 to 30 years to the average life span. That would mean a child born today could expect to easily achieve an average lifespan of a  century.

Other Factors to Consider that Impact Aging

If you are over 60, which I am, your risk dying doubles every 8 years. Research shows that shortening of telomeres only accounts for 4% of the difference. Chronological age and gender account for an additional 33%. The remaining 63% can be attributed to:

1. Oxidation
2. Glycation
3. Inflammation
4. Stress
5. Immune Response

Oxidation sounds like a strange contributor to aging. After all, we need oxygen to breathe and a byproduct of this basic life function is oxidants. Oxidants result from oxygen combining with sugar to produce energy and byproducts called free radicals. Not all free radicals are internally produced. They can also come from infections, inflammation, alcohol, smoking, excessive sun exposure, radiation from x-rays and environmental toxins. Free radicals can have a negative impact on individual cells, proteins and fatty tissue.   Free radicals over time can build up in the body and are associated with aging. In a  recent study the lifespan of worms was increased by 44% by neutralizing oxidants.

Glycation involves excess glucose binding with our DNA, proteins and fats. Excess glucose begins to interfere with normal body tissue functions. The older we get the more the glucose creates health problems contributing to aging let alone body mass. Research shows that restricting calorie intake and selecting foods low in sugar leads to reduced age-related disease and extended lifespans in mice to monkeys.

Inflammation is the body’s natural response against infections and injuries. It also contributes to tissue injury and ultimately to aging. Chronic or persistent inflammation without significant infection is evidence of an immune system that no longer recognizes host body tissue as its own. As we age autoimmune conditions including chronic inflammation become more prevalent. Chronic inflammation destroys normal cells and contributes to the aging of the cardiovascular and nervous system. Inflammation contributes to age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s.

Stress  harms DNA and speeds the aging process. A study in 2004 showed that psychological stress shortens telomeres in immune cells.  Evidence shows that stress, the endocrine system response and the occurrence of disease define age more than chronological aging. Certain diseases occur when anabolic hormone levels start to decline and catabolic hormones start to increase. The latter, such as Cortisol, can contribute to the breakdown of body tissue. As proof of just how much stress contributes to aging and premature death, interviewers who spoke with centenarians found that they exhibited healthy coping strategies in dealing with illness describing their behaviours as accepting, non worrying and taking life one day at a time.

Immune Response refers to the specialized cells generated by our bodies to fight off disease. Researchers in Israel at the Technion studied the natural decline in the immune system as we age. This inability to fight off diseases when we are older is one of the reasons for the statistics about the risks to humans when they reach 60 and over. By suppressing B-lymphocyte immune cells in aging mice and using a drug commonly used to treat rheumatoid arthritis, the mice were able to manufacture healthy replacements using bone marrow. Clinical trials have begun in human populations suffering from B-cell lymphoma.

Aging contributors include telomere shortening, oxidation, glycation, inflammation, stress and immune response. Source: University of Utah

What are the prospects for human immortality?

The SENS Foundation is dedicated to re-engineering our bodies to end aging through rejuvenation biotechnology.  These biotechnologies cover major research areas including cell loss, tissue atrophy, nuclear and mitochondrial mutations, immunotherapy, and targeted ablation. The goals are:

1. Apply enzymes to lysosomes in cells to destroy the junk that accumulates in them leading to neurodegenerative diseases like Parkinson’s, Alzheimer’s and macular degeneration
2. Reduce mutations in the mitochondria of non-dividing cells such  as neurons and muscle fibres through applied gene therapy
3. Eliminate the extracellular junk that makes artery walls become rigid leading to high blood pressure, or causes amyloidoses in Alzheimer’s sufferers using repair proteins or vaccines to stimulate the immune system
4. Remove senescent cells, immunosenescent cells, (white blood cells that no longer work) and visceral fat cells (the fat around our internal abdominal organs that contributes to adult-onset diabetes) cells that accumulate in the body during aging
5. Replace lost cells in vital tissues such as brain, heart and skeletal muscles using cell therapy
6. Make cancer mutations harmless by interfering with the natural machinery for renewing telomeres
7. Develop ways to introduce new ribonucleic proteins into the body and remove those present through transplantation, cell therapy, somatic gene and protein therapy and germ line gene therapy.

If we eliminate all of these physical processes inherent in aging and develop appropriate delivery systems for restoration and repair some scientists project that we can live 1,000 years. Will someone born in the 21st century be the first millenarian?

Biomedicine – Part 9: Cloning

“Hello Dolly,” not the musical but the sheep. Seen below, Dolly was the first adult mammal cloning success using sheep.

Born in July 1996, Dolly was the first mammal known to be cloned from an adult of the same species. Source: Farmers Guardian

Her journey from the petri dish to birth began as a cell taken from a mammary gland of a 6-year old female donor. The technique included putting the cell into a suspended state to extract its DNA. A host egg cell came from another female donor. With the egg cell nucleus removed the DNA from the mammary cell was inserted. Then an electric current was applied to simulate the energy accompanying fertilization and embryonic development. After 148 days, Dolly was born.

It wasn’t all that simple a task. The researchers tried this with 277 fused eggs. Only 29 embryos survived and of these 13 were successfully implanted, but only one, Dolly, was born.

Cloning is not new to nature, just new to humanity. Many creatures practice asexual reproduction, or parthenogenesis, producing exact copies of themselves. Many plants reproduce themselves by sending out roots laterally and sprouting exact DNA copies of themselves. Researchers studying Aspen trees in British Columbia, however, report that this form of cloning leads to an increasing likelihood of creating some bad genetic material. We call altered genes mutations. The scientists studying Aspens counted the accumulated mutations of 20 different male Aspen trees and noted that cloned trees were less hardy than their parents. The same can be said about Dolly. She aged prematurely and passed away after 6 years.

Dolly wasn’t the first vertebrate to be cloned. That honour belongs to a carp, cloned in 1963.

The first cloned mouse, named Cumulina, was created in 1997 and died in 1999.

Mira the goat, born in 1998, was actually 3 goats, all identical. Their DNA was modified so that their milk produced recombinant human antithrombin (rhAT), a protein that prevents blood from clotting.

Cow clones, made in Japan, appeared in 1998. Recently, a newspaper in the United Kingdom described some of the challenges related to cloned farm cows with reports of pain, ill-health, organ defects and gigantism.

The first cloned guar (an Indian bison) named Noah was born in 2000 and died 48 hours after birth.

Pig clones have popped up in the United States, the United Kingdom, Japan and other locations, the first appearing in 2000. In 2001 scientists produced the first pig clones genetically modified to grow organs suitable for human transplantation. This feat was accomplished by knocking out a pig gene that produces the coating on organs containing sugar molecules that trigger acute rejection when transplanted.

Talk about copycat, scientists in Texas successfully cloned a cat born in December 2001.

Joining all the above we have cloned dogs, rats, mules, horses, water buffalo, camel and a Pyrenean Ibex, a species of antelope that was declared extinct in 2000. Unfortunately in the case of the latter, it died shortly after birth and remains extinct.

Why Do We Want to Clone? – 10 Reasons. theWhy and the Why Not

Cloning has great biomedical potential to help humanity tackle and cure diseases. In cloning animals we may yield enormous medical and agricultural benefits. But cloning also presents ethical challenges. The following lists the most commonly expressed reasons for cloning:

1. For medical research to create transgenic animals bred with genetic mutations that cause specific human diseases to study and find cures.

In 2009 a team at Seoul National University created the world’s first transgenic dog to model human diseases. The researchers cloned a red flourescent gene produced by sea anemones and inserted it into the dog genome producing Ruppy, a beagle pup who glowed red in ultraviolet light. A virus was used as the gene transport mechanism to introduce it into a cell nucleus. That nucleus was then removed and then inserted as a replacement nucleus in a dog egg cell. A few hours later the egg divided to become an embryo which was then implanted into a surrogate mother. The red flourescent gene serves no medical purpose other than a validation that this technology works. But currently the failure rate is better than 98% in taking altered egg cells and successfully producing cloned offspring that survive through pregnancy and birth.

2. For creating human stem cells, a perfect match from donors, banked and withdrawn when needed to insert into and repair damaged or diseased organs and tissue.

In October 2011, scientists at the New York Stem Cell Foundation Laboratory announced the first successful cloning of human stem cells to treat conditions such as diabetes and spinal cord injury. Researchers used a method similar to the one that created Dolly. The adult somatic cell source used came from skin. This field of study shows great promise.

3. Therapeutic generation of matched tissues and organs for transplant back into the donor.

Therapeutic cloning remains in the laboratory using animal studies with early successes treating neurodegenerative diseases like Parkinson’s, generating blood vessels and skin to deal with severe burns, producing endocrine cells to generate glucagon and insulin within a pancreas to cure diabetes, corticospinal axon regeneration to repair severed spinal cords, and photoreceptor regeneration to treat blindness.

4. For genetically engineering animals to generate life-saving drugs or proteins for use in humans.

In this area of research we are already seeing significant results. See my earlier comments about Mira the goat.

5. To create domestic animals with superior genetics by copying livestock with desirable traits.

Regarding genetically superior domestic breeding using clones, we have yet to prove we have mastery in this field. Today the success rate in cloning of less than 2% is very low. Cloned animals that make it to term tend to be larger than average. Called Large Offspring Syndrome or LOS, cloned animals with this condition have abnormal organs. Many have breathing and blood flow problems. Even normal-sized clones may experience kidney, brain and immune system health issues. Our early experience with adult cell nuclear transfer may be the reason why clones on average don’t live as long as normally bred animals because the nuclear material being used comes from an older donor cell. Our research shows that when normal human cells continually divide, the DNA sequences at the end of each chromosome shorten. The older the animal, the shorter the chromosome. We call these chromosome ends telomeres. Are the shorter telomeres affecting the lifespan of clones? Researchers continue to study the phenomenon because we have yet to see consistent outcomes in the DNA of cloned animals.

6.  To recreate extinct or copy endangered animals to restore biodiversity.

We may be closer to resurrecting an extinct species after some of the pioneering work done in the last decade. In 2008, researchers cloned a mouse from one that had been frozen for 16 years. Although the cloned Pyrenean Ibex died from defective lungs, the Spanish scientists who carried out this resurrection attempt showed us the potential for bringing back an animal from extinction.

From this pile of Woolly Mammoth hair and from marrow extracted from bones, scientists have reconstructed the DNA of this extinct Ice Age creature.

In Russia, scientists at the Siberian Mammoth Museum, in association with Japan’s Kinki University, have extracted marrow cells from a woolly mammoth and are planning to use an elephant egg cell as a host for cloning an animal that disappeared well over 10,000 years ago. Considering the failure rate in successful clone births the opportunity to recreate the mammoth will require a large enough sample to produce a successful baby and that is without consideration for other conditions such as the size of the animal in utero and the potential for birth complications for the surrogate mother elephant.

7. To duplicate a favourite pet.

If I told you TLC, the cable television channel, launched a reality TV program called “I Cloned My Pet,” would you believe me? It’s true. Just launched on January 11, 2012, each episode features a pet owner reminiscing about their animal friend who has passed on. The pet owner has saved locks of hair, or harvested cells and has sent them to a Korean laboratory offering pet cloning services. Scientists in South Korea have cloned dogs since 2005, not just for bereaved pet owners, but also to recreate highly prized working dogs. View the link to read about cloned airport security and drug detection dogs. This is big business in Korea.

8. To duplicate a dead child.

Although a positively Frankensteinian idea, in an article published in 2009, a fertility doctor claimed he had created 11 cloned human embryos made from adult skin cells and placed them in the wombs of four of his patients. In the same article the doctor claimed he created clone embryos of dead people, one of them a 10-year old girl. The attempt to reproduce the girl involved a sample of her blood. The doctor at the time claimed it was not his intention to actually bring the dead girl back to life.

Attempts at the United Nations in 2005 to create a worldwide ban on human cloning of this kind failed. Instead a resolution passed which stated “all forms of human cloning inasmuch as they are incompatible with human dignity and the protection of human life” should be condemned.

But if we can bring back an extinct animal then what is to stop someone, somewhere, from cloning a lost loved one?

9. To create a child for infertile couples and not use adoption or a surrogate.

If we can clone other animals then theoretically we can clone humans. In 2001, at the Human Therapeutic Cloning Conference in Rome, a consortium of doctors proclaimed they were in agreement on the question of human cloning as a medical treatment for infertile couples.  The agreement recognized that sterile men could pass along their genetic attributes to offspring only this way and should be given the opportunity. The scientists at this conference recognized that “the genie had already been let out of the bottle,” and better that they were the ones to do this then some “quack.”

10. To create a duplicate of an individual as an alternative to a surrogate for those who are not married but want an heir who is an exact match.

I recently visited a website called Clonaid. At first I thought this has to be a hoax. But Clonaid is real and claims its first human clone baby, named Eve, was born on December 26th, 2002. The juxtaposition of the date so close to Christmas made me even more skeptical.

Since 2002, Clonaid has made unverified claims that include four other clones including a second birth to a Dutch woman, and a third to a Japanese family who had their lost son cloned. Clonaid may be perpetrating a fraud but they are not alone in pursuing human clones. China’s Xiangya Medical College, in Changsha, is one of three research centres studying human cloning. In one Clonaid case the company described the desire of a homosexual couple who wanted to have sons, duplicates of themselves and that Clonaid was capable of fulfilling their wishes.

Indeed it seems that with Dolly the genie has been let out of the bottle and we are, at this point in the 21st century, wrestling with the demons that may follow.

Biomedicine – Part 8: Robotic Exoskeletons

Animals come in many shapes and forms. Insects and other arthropods share a common physical attribute. They wear their skeletons on the outside. We call them invertebrates. Humans and other mammals, birds, reptiles, amphibians and fish, called vertebrates, have an internal or endoskeleton. In this blog we explore the fusing of internal skeleton-based biology with external robot-based outer skeletons or exoskeletons to give mobility and strength to humans suffering from catastrophic injuries and diseases that impair mobility.

The Necessity and History of Human Exoskeleton Technology

Our earliest forays into exoskeleton technology had nothing to do with restoring movement to a human suffering from an injury or disease. We began with the goal of protecting warriors in battle as we found ourselves often in conflict with neighbours. An escalating arms race included not just weapons but also defences. We invented shields, breastplates, chain mail, and full body armor to counter increasingly sophisticated weapons.

Medieval warriors wore an armor exoskeleton to protect them from a variety of weapons.

The medieval iron-plated suit, seen above, protected warriors but also encumbered them. When suited and on horseback a warrior was mobile and capable of using lance, mace and broad sword to attack enemies. When out of the saddle a warrior became almost helpless, with walking a chore, let alone fighting.

We have yet to end warfare and our fascination for finding new methods of putting armor on soldiers continues. Today’s army wears synthetic-fibers such as Kevlar, stronger than steel, lighter, and malleable to conform to a body. Soldiers encased in these materials encounter heat stress when worn over a long period because the materials do not breathe. To counter the heat buildup of modern body armor researchers are experimenting with personal cooling systems using phase change materials or PCMs, acting as heat sinks to cool  the wearer.

A more recent phase in research is studying how wearable robots can enhance the strength and capability of soldiers. Scientists studying the attributes of arthropod exoskeletons have always been fascinated by the strength exhibited in these animals. For example an ant can carry objects 10 to 50 times its own weight. Could a soldier outfitted with an exoskeleton exhibit similar capability?

Exoskeletons and Military Research

Hardiman, designed by General Electric in 1966, proved to be a balky first attempt at building a powered exoskeleton capable of giving its human operator superhuman strength. Wearing Hardiman (seen below) its operator could lift weights of up to 680 kg. (1,500 lbs).

Hardiman weighed 680 kg and allowed its human operator to lift objects equivalent to its own weight.

But Hardiman suffered from lots of technical problems. It was heavy, its hydraulics and electro-mechanical systems frequently failed, and it used heavy inefficient batteries.

At about the same time Project PITMAN, out of the Los Alamos Laboratories, began long-term development of an exoskeleton prototype suitable for military field deployment. What the army sought was a powered, armored external apparatus easily worn by a soldier in the field. The suit would feature invulnerability to gunfire and its wearer would be able to easily lift heavy equipment and weapons, and carry wounded soldiers from the field of battle. The suit would give its operator the ability to jump easily and move at a faster than normal human pace.

Research in the last twenty years continues to focus on prototype designs for wearable exoskeletons. One company, Sarcos, recently acquired by Raytheon, has made considerable progress with its XOS robotic suits. The current model, XOS 2 gives its wearer the strength and endurance of two or three soldiers. Consisting of sensors, actuators and controllers, and powered by high-pressure hydraulics, XOS 2 is operator friendly. A wearer can step into it and immediately augment his or her ability to lift 90 kg (200 lbs) repeatedly, and run at a speed of 16 kilometers per hour (10 mph) without tiring. At the same time the wearer climbs ramps and stairs with agility, kicks a soccer ball, handles and passes a basketball, or punches a boxing bag  repeatedly without fatigue. The wearer of a XOS 2  can step out at anytime as it waits or operates autonomously on an assigned task.

XOS 2 is a robot exoskeleton that enhances the ability and strength of its wearer. Source: Raytheon Company

Lockheed Martin is developing HULC(tm), the Human Universal Load Carrier, a lower torso exoskeleton designed to allow soldiers in the field to carry loads of up to 90 kg (200 lbs) for extended periods of time across all types of terrain without feeling fatigue. Click on the link above to see HULC in action. HULC uses a titanium exoskeleton, a computer controller with hydraulics and servomotors, and allows the field operator to snap in modular components such as a lifting frame for hands-free assistance. The wearer can travel at speeds up to 16 kilometers per hour (10 mph). It is easy to put on and take off in battlefield conditions. Currently the lithium-ion battery gives it limited field range. The company is working with Protonex to develop a fuel-cell power source to give it 72 hours of continuous power.

The Biomedical Payoff

Military research in the United States has always led to civilian applications. It is no different when discussing exoskeleton technology. Immediate benefits include enabling people with spinal injuries or neuromuscular diseases to leave their wheelchairs, stand and walk without help.

Ekso Bionics Engineering, a company located in California, is pursuing that goal. Its product, Ekso, offers an escape for wheelchair users through its lower torso exoskeleton. Ekso contains 40 electromechanical servo-motors, operating through intelligent networked software and giving its operator a natural walking gait. An Ekso wearer can sit, stand and walk. At $100,000 the device represents an expensive solution but the company expects the price to decline by half in the near future while it adds many more functions and features. The goal for Ekso is a wearable device that the operator puts on in the morning and uses all day to function in a normal way including going up and down stairs in a home or driving the car to work, or going to a baseball game or a movie at night.

Ekso uses 4 electric motors, an onboard computer and 15 sensors to drive it. Source: Ekso Bionics

Other companies are pursuing a similar goal. One of them is Cyberdyne, a company headquartered in Tsukuba, Japan, and the creator of the HAL 5 Hybrid Assistive Limb. HAL 5 features a wearable exoskeleton, battery-operated and usable for over 2 hours between recharges. Unlike Ekso, this exoskeleton provides robotic assistance for upper and lower body. HAL 5 takes it cues from nerve signals transmitted from the brain. The wearer controls it by thinking about an action. Sensors attached to the skin pick up the nerve impulses and translate them into movement commands such as standing and walking. The robot’s voluntary control system combines with its autonomous control system to create a full range of movement capability powering both upper and lower limbs.

HAL 5 gives us some insight into exoskeleton design in the near future. Neuroprosthetics that capture electrical signals from the brain will make it possible for seamless integration of exoskeletons with their wearers. As we improve the human-robotic interface we will largely eliminate motor disabilities.

Biomedicine – Part 8: Robots to the Rescue – Emergency Robots

In a controlled setting like a hospital doctors and other medical staff work with all the tools needed to save a patient. That is not necessarily the case in the field at a rescue site where victims found may require immediate intervention. Think about scenarios where surgical intervention is impossible because the victim is inaccessible, trapped under rubble, suffering from internal injuries, unconscious, or unresponsive. With no physical contact possible or with the space in which the victim lies so confined to permit much in the way of any physical interaction, rescue and emergency robots have a significant role to play.

If you think of the most recent disasters that made headlines in 2010 and 11 you can begin to envision how robots can play a part in prolonging life in emergencies. From the earthquakes in Haiti and South Island, New Zealand, to trapped miners in Chile, the tsunami in Japan, and most recently the  foundering of  the cruise ship, Costa Concordia, engineers get inspired to come up with new ways of supplementing human intervention and rescue efforts using robotic systems. In some of these recent tragedies robotic devices were deployed. But that is not the only use for robots in emergency medicine.

The Robot Will See You Now

Robots are used in emergency medicine in many ways. One is as patient screening tools, marrying robotics with computing science. Hospital emergency rooms represent bottlenecks with patients spending long hours waiting for a doctor or nurse. Shortening the wait times using a triage robot has inspired engineers at Vanderbilt University to develop TriageBot,

TriageBot monitors patients and notifies medical staff on site about an emergency. Source: ManAlive Magazine

A smart kiosk, TriageBot takes a medical history, measures vital signs and detects problems. The robot prioritizes patients based on severity of symptoms and history and can connect to on site staff even outside the emergency department should they be needed. The form of TriageBot is still under development. It could look like the fanciful and friendly robot displayed above or resemble an airport check-in terminal, or it could be built into a hospital waiting room chair. Designed to continuously monitor the patient before being seen by a member of the medical team, TriageBot represents an innovative use of robots in hospital settings.

But not all emergencies happen in the waiting room of hospitals. TriageBot systems when hooked up to a telecommunications network can provide both screening as well as monitoring of patients in remote areas. As the software evolves this type of emergency medical robot should prove invaluable.

The Japanese have a way with robotic systems and not to be outdone, Kyushu University has been experimenting with a robot prototype mobile monitoring system. (Click on the hyperlink in the last sentence to watch the movie. Although the narrative is in Japanese, you quickly get an understanding of how this apparatus works.)

Built for AICHI Expo 2005 this mobile chair features remote control driving done by emergency medical staff off site, vital signs monitoring, emergency first aid and even a defibrillator. The remote operator can talk and see the patient, communicate with bystanders and give them information on how they can help a person having a seizure, fainting or heart attack.

The Robot Will Find You Now

CRASAR is the Center for Robot-Assisted Search and Rescue at Texas A&M University. On its website it lists participation in using rescue robots going back to the collapse of the World Trade Center buildings in 2001. One area of development focuses on using robots as human proxies to provide communication with a trapped person that cannot be reached immediately after a disaster.

Survivor Buddy can work with medical staff to interact with a survivor during the period when help is not yet able to extricate the person. The robot includes a monitor that displays non-verbal human attributes by rotating and moving in a human-like way.

Sandia National Laboratories have been working on robots that can deliver food, water, oxygen and medical supplies to trapped miners underground while encountering environments that could prove lethal to human rescue workers. Designed to withstand flooded areas and explosions from pockets of methane gas the Gemini-Scout Mine Rescue Robot comes equipped with a range of sensors as well as pan-and-tilt, and thermal cameras that elevate to see over obstacles. It travels on flexible treads that climb over obstacles. Using a game controller, Gemini-Scout is designed to work with first responders and can be outfitted for earthquakes, fire and other disaster scenarios.

Sandia National Laboratories are creators of the Gemini-Scout, a search and rescue robot. Source: photo by Randy Montoya

The Snakebot employs biomimicry to do search and rescue for trapped victims of disaster. An active scope camera that slithers, this robot was used to find trapped people under the wreckage of the 2011 earthquake and tsunami that struck Japan.

But snakebots can even go beyond search and rescue. Carnegie Mellon University roboticist, Howie Choset, has designed a snakelike camera device that with 102 joints is capable of imaging and mapping internal organs such as the heart muscle. Although not a search and rescue application, these types of robot designs demonstrate flexibility with capability to serve multiple biomedical applications.

Nowhere have emergency medical robots been studied more than in the military where they are seen as extraction and evacuation tools that reduce collateral casualties. The United States military increasingly uses robots in all of its field operations including drone aircraft as surveillance and strategic strike weapons, as well as robotic land vehicles. With the goal of having 1/3 of its land vehicle fleet unmanned by 2015, robotic medical evacuation will become a common feature. The American army is testing both robotic evacuation and extraction vehicle technology to move patients from fire zones to hospitals. This includes using humanoid robot designs like the one pictured below.

The United States military is actively researching the development of medical evacuation robots. Source: Photo by Lori DeBernardis

Using robots capable of picking up an injured soldier on a battlefield represents a way of reducing deaths associated with casualty recovery operations.

The military is also testing unmanned aerial systems that can land and working with casualty extraction robots, remove wounded soldiers from environments where radiation or toxic gas would make it impossible for human intervention. Unmanned aircraft are also being tested to provide surveillance and medical response. To provide the human touch, robot extraction systems include telepresence so that a soldier remains connected to a medical support person even though they are not physically on site.

In our next blog we look at the emerging field of robot exoskeleton technology and its biomedical uses.

Biomedicine – Part 8: Robots to the Rescue – Robots that work on the inside

In our last blog we introduced HeartLander, a device that when inserted into the chest cavity can deliver medication, ablation therapy and provide assistance in lead placement for pacing the heart muscle. HeartLander’s developers hope to shrink it to 3 millimetres from its current size, 8.5 mm. Devices of this type represent the start of a new use of robotic devices built to operate autonomously within a human body. We’ll look at where the technology is today and what we can expect in the near future.

In the world of internal medical robots HeartLander is a giant. Researchers have much smaller in mind when they conjure up micro-robot designs. These researchers develop robots on a nanoscale. We have broached this subject before in a blog and stated at the time of writing that there were no existing biomedical nanobots. That remains true but researchers at ETH Zürich have been building what they call micro-robots that are bacterial-scaled measuring lengths of between 5 and 15 nanometers.  Called Artificial Bacterial Flagella or ABF for short, these devices swim like bacteria with corkscrew tails.

ETH Zürich are building micro-robots as small as bacteria, observable only under a microscope. Source: Institute of Robotics and Intelligent Systems/ETH Zürich

Made by depositing vaporized indium, gallium, arsenic and chromium onto a surface substrate a few atoms thick, the ABFs are patterned using lithography and etching. When thin sliced they naturally form the curled ribbon corkscrew you see in the picture above. The ABF head seen on the right contains a tri-layer film of chromium, nickel and gold. Nickel’s magnetic properties make it possible to use an external magnetic field to provide locomotion. The ABF uses helical propulsion (the same method of locomotion used by many bacterium) to swim through liquid at speeds of up to 20 nanometers at present with plans to increase it to 100 nanometers. Compare that to E. coli which swims at 30 nanometers per second.

To give ABFs autonomous power researchers are looking at thin-film rechargeable batteries. Currently these batteries can be manufactured and shaped with thicknesses of less than 50 nanometers. Chemical fuel sources may prove to be even more promising. An ABF running on energy it harvests from the blood would be capable of running indefinitely within a body harvesting glucose and oxygen to provide motive and computing power. Some researchers are looking at using bacteria as an ABF, modifying a living cell by attaching nanoparticles to it so that it can be mobilized for biomedical purposes.

What can ABFs do that current biomedical technology cannot?

• Targeted delivery of drugs to a specific area in the body reducing the total risk to the body of side effects. This kind of therapy can even be sub-cellular, delivering medicine to alter genes within a chromosome.
• Placement of radioactive seeds near tumor cells. Called brachytherapy, targeted radiation therapy delivers a killing dose only to selected cells, leaving healthy cells alone.
• Delivering heat therapy called thermoablation to selected cells to destroy them without damaging healthy surrounding tissue. The ABF’s magnetic properties would prove useful for this type of therapy.
• Implanting of stem cells using the ABF as the carrier. Stem cells could then be delivered to an area of the body to regenerate hearing, site, organs and bones.
• Collecting tissue samples for biopsy. The ABF would excise a small sample and when excreted or removed from the body allow for quick on-the-spot analysis to determine if cancer is present.
• ABFs could be used as scaffolding material similar to the way stents are used today. But the ABF scaffolding would be on a nanoscale to act as cellular building blocks for regrowing blood vessels, nerves and organs. As small as today’s stents are, an ADF could act as a stent in the smallest of blood vessels, or a group of them could be combined to form a larger scaffold.
• ABFs could be used to block or occlude blood vessels feeding a tumor causing the tumor to starve and die.
• ABFs with specialized implanted electrodes could be used to restore severed nerves in a spinal column or provide neural connections to reverse brain damage.
• Remote sensing represents one of the most promising uses of ABFs. An ABF could be packed with instrumentation to measure blood-oxygen levels, arterial flow, blood pressure and other vital signs instantly transmitting the results to external monitors.
• ABFs introduced into a patient suffering from multiple injuries could hover at sites where organ damage or  internal bleeding has been identified and constantly provide status updates to physicians dealing with the emergency.
• Fetal surgery represents a promising field for the use of ABFs, providing doctors with the means to correct congenital heart defects in utero, or performing ablation therapy to deal with congenital malformations, or clearing obstructions in blood vessels and the urinary tract, or replacing needles to collect samples for amniocentesis and other fetal tests

Currently ABFs are confined to the research laboratory. But soon we will microscopically see these devices applied to all kinds of medical procedures reducing the need for surgical procedures, minimizing the side affects of cancer chemotherapy, and giving biomedical professionals a new set of tools for tackling conditions for which current medical practice has few solutions.

For those developing this technology it’s a question of tinkering with the power source to come up with the best way to deploy micro-robots.

Biomedicine – Part 8: Robots to the Rescue – Advances in Imaging and Irradiation Technology in the 21st Century

Image-guided therapy has revolutionized medicine in the latter part of the 20th century and into these first two decades of the 21st. The operating room, once the exclusive domain of surgeons, is today a very different world. Radiologists, oncologists, cardiologists, nephrologists, lung specialists, gastroenterologists and other medical specialists have invaded the operating room space using sophisticated imaging and interventional technology that replaces surgical procedures.

These disciplines just like surgeons, are more and more using robotics because robots can be far more precise in delivering therapy to a specific location in a patient’s body, and because robots can use technology with no ill effect to the machine, but if undertaken by a physician could unduly expose them to excessive radiation.

In this blog we will look at interventional radiology, cardiology and other medical disciplines to describe where we are using robotics today and where we are headed in the near future.

Today it is hard to tell where the surgical suite ends and radiology begins. Radiology labs like the one illustrated below look as sophisticated as operating rooms.

Interventional Radiology technology supports both diagnosis and treatment. Source: Indiana University, School of Medicine

A Short History of Radiology Before Interventional

Radiology began with a late 19th century discovery by Wilhelm Roentgen, a German scientist. In 1901 he won the first Nobel Prize ever awarded in physics. Roentgen’s first application of the technology involved x-raying his wife’s hand including the wedding ring she was wearing. X-ray technology became a standard in the first half of the 20th century as a diagnostic tool for everything from skeletal injuries to welded metal plate seams.

In the 1950s contrast agents made it possible to use X-ray technology to see soft tissue and body organs. Development of X-ray movies made it possible to view internal organs at work expanding the capability of this technology as a diagnostic tool.

The 1960s saw the development of sonar imaging using ultrasound, sound wave frequencies of 20,000 or more vibrations per second. The marriage of ultrasound and computer software  further perfected this new imaging technology leading to today’s 3D and 4D ultrasounds used in looking at heart, kidney, uteri and abdominal organ studies. Today expectant mothers and fathers throughout much of the world can get a first look at their future child through fetal ultrasounds. Some even post these images on Facebook.

The 1970s saw the emergence of computed tomography or CT, the digital mapping of the human body producing detailed images of anatomy and physiology.

In the 1980s magnetic resonance imaging or MRI was added to the arsenal of diagnostic tools, creating images in fine slices that could be assembled to provide detail never seen before.

Interventional Radiology

Moving X-rays made it possible for radiologists to become more than diagnosticians. I first encountered the power of X-ray in this format as a new father when my daughter underwent a cardiac catheterization study involving the insertion of a catheter into a vein in her leg that was threaded into her major blood vessels and heart. A cardiologist injected contrast dye into the catheter to measure my daughter’s pulmonary arteries, heart chambers, lungs and study her blood flow patterns. The results confirmed a diagnosis of complex heart and lung disease, first imaged through ultrasound, and now studied in greater detail using X-rays. Although purely diagnostic in nature these initial catheterization my daughter experienced were forerunners of what is today a significant medical breakthrough, the implanting of medical devices to repair the body using catheters.

Today radiologists, cardiologists and other specialists routinely do procedures called angioplasty, using catheters with balloon tips that are inflated to open blocked arteries, or to insert stents and heart valves into patients (see pictures below).

The picture on the left shows two stents. The top one has been inflated after insertion using a balloon-tipped catheter. The picture on the right shows a catheter with an implantable heart valve in stages of insertion and deployment.

Catheters give radiologists other means to deliver treatment. A catheter can be outfitted with a heatable tip containing a platinum electrode with a temperature sensor. Using radio-frequency (microwave) energy, the catheter can literally nuke tissue in the body to kill it. Called radio-frequency ablation or RFA, catheterizations of this type cure arrhythmias (abnormal heart rhythms), and reduce cancerous tumors in the liver and esophagus. A catheter containing an optical fiber can use lasers to treat cancers. Called laser-induced interstitial thermotherapy or LITT, the laser can deliver heat to destroy or shrink a tumor. Another laser treatment called photodynamic therapy, or PDT, activates photosensitized agent chemicals that specifically target cancer cells.

Catheters can deliver chemicals and drugs to a body site to attack a tumor or destroy abnormal tissue. A procedure developed in 1994, called alcohol septal ablation (ASA) is commonly used today to treat a deadly heart condition called hypertrophic cardiomyopathy, where abnormal muscle thickening reduces the heart’s ability to pump leading eventually to blockage of the aorta, the main artery in the body. In the case of the latter the alcohol is injected directly at the point of the muscular blockage site to kill the excessive tissue restoring normal blood outflow.

Catheters can deliver freezing fluids to perform cryoablation or cryotherapy, used to treat prostate, liver and some forms of bone cancer.

Enter the Robots

As interventional treatments have become more the norm than the exception in dealing with many complex health and disease problems, the need for precision and accuracy has led to the development of robotics devices. Some of these devices provide real-time magnified imaging in 3D. Others are used in conjunction with surgical applications to assist in minimally invasive procedures. Most are designed to reduce exposure of both patient and physicians to X-ray irradiation with the latter able to operate these devices remotely.

Siemens has been a pioneer in robotics in manufacturing and other industries and is now applying this expertise to the medical field by building a number of  systems and devices. One of these is Treago, an image-guided robotic treatment table designed to position patients for radiation therapy treatments. Other Siemens devices include Artis Zeego, an radiology system capable of rotating 360 degrees in 6 seconds producing detailed images of entire tumors including blood vessel feeds. Because Artis Zeego is so fast it minimizes patient exposure to X-rays and radioactive contrast.

The CyberKnife, a product of Accuray, a California-based company, features a robotic arm capable of moving around a patient to deliver precise radiation to tumors with sub-millimetre accuracy. The system can sense movement in the patient such as the rise and fall of the chest during breathing and adjust the radiation beam to compensate. How does the CyberKnife know where the tumor is located? The technology communicates with CT scanners and uploads data from these sources to create an accurate location map for the targeted tumor and for healthy surrounding tissue. The medical team creates a treatment plan for the CyberKnife along with desired radiation dosage. CyberKnife’s precision allows for larger doses of radiation focused on the cancer, not healthy cells. Where typically a patient would undergo 20-30 visits using conventional radiation therapy, a CyberKnife treatment plan requires from one to 5 sessions. Because of this precision CyberKnife can treat complex, dispersed and inoperable tumors in the prostate, lung, brain, spine, liver, pancreas and kidney.

As the 21st century continues to unfold we will see more robotic-assisted technology in radiology designed to be less invasive and more precise in treating cancers and other diseases.

Cath Lab Robotics

The same can be said about the use of robots in cath labs where computer-guided catheters combined with navigation systems are allowing cardiologists to do procedures that were once far more invasive and done exclusively by surgeons.

The first use of a robotic system in cardiology dates to 1997. The robot was named Aesop (see our previous blog). Today, catheter-based therapies increasingly rely on robot-assist devices for both diagnostic and interventional procedures. These labs include catheter manipulation by robots directed by computer-aided imaging, and therapeutic robotic devices.

Corindus Vascular Robotics, in Massachusetts, is the developer of the CorPath 200, a robotic system for doing percutaneous coronary intervention procedures, called PCIs. Remember when I mentioned my daughter in this article. Less than 3 years ago she had a PCI done to implant a pulmonary valve and stent. But in her case it was done without robotic assistance and involved a full cardiac team of doctors and nurses. CorPath 200 provides an articulated robotic-arm combined with a remote cockpit containing a workstation with multiple screens and joystick controllers. The cardiologist, from the comfort of the cockpit, does a procedure using the robot arm to accurately place stents and other implanted devices using balloon catheters.

Corindus' CorPath 200 System represents where cardiac cath labs will be in the very near future. Note the similarities betwwen the interventional radiology lab setup and cath labs. Source: Philips Healthcare

Even more interesting are robotic devices that can get inserted into the chest cavity and placed on the surface of a beating heart. One of these is HeartLander, a miniature mobile robot designed to facilitate minimally invasive therapy. Designed to adhere to the outer surface of the heart (the epicardium), this devices moves like an inchworm to position itself on the heart muscle for administering a variety of therapies.

HeartLander is an insertable robotic device that navigates autonomously across the surface of the heart muscle to deliver therapy. Source: Carnegie Mellon University

It navigates autonomously using suction to adhere to the surface and an internal drive wire to create push and pull. The cardiologist can control HeartLander using a joystick and view its progress through a graphical computer interface. The current device is 8.5 mm in diameter with plans to shrink it further to 3 mm.

HeartLander in trials has been used for ablation treatment of arrhythmias, to place leads on the heart muscle for pacing and for delivering medication and chemicals to targeted areas of the heart muscle.

Currently still in the laboratory and being used in animal studies, HeartLander represents the next stage in the evolution of robotic systems for use in biomedicine.

Biomedicine – Part 8: Robots to the Rescue – Surgical and Diagnostic Robotic Systems

In earlier blogs we have looked at the evolution of robots and artificial intelligence. In this blog we’ll tackle the subject from the perspective of advances in biomedicine. Why are we humans developing robots for biomedical use? Because robots when properly designed are masters of precision and process, seldom making errors. That is why robots dominate assembly line manufacturing today. But can you compare surgical procedures on people to manufacturing automobiles? Or can you replace the heart with an electro-mechanical device that delivers the same reliability as a healthy muscle? Apparently yes to the former and maybe to the latter.

So where are robots and robotic devices making an impact on biomedicine in the second decade of the 21st century? And where are we going with this type of technology as the century unfolds?

We have already described implantable sensors and devices as well as intelligent prosthetics in a previous blog. In this discussion divided into 5 sections we will look at the following:

1. Surgical and Diagnostic Robotic Systems
2. Imaging and Irradiation Systems
3. Insertion Systems
4. Robot Delivery and Rescue Systems
5. Exoskeletons

Surgical and Diagnostic Robotic Systems

In the last 20 years we have seen the evolution of remote presence technology giving doctors the ability to provide medical help to patients in remote areas of the world. These technologies have proven useful for creating virtual presence for interviewing, patient screening and diagnosis, and medical consultation. One such device is called RP-7, a robot that looks like it came right out of a sci-fi. RP stands for remote presence and gives physicians the ability to see and speak with patients and  hospital staff. Through its interface the RP-7 gives a doctor the ability to use electronic stethoscopes, otoscopes and ultrasound and receive transmission of all medical data.

RP-7 has a sci-fi appearance to it but today can provide sophisticated medical telepresence to remote areas. Source: Intouch Health

But diagnostic robotic tools like RP-7 are just the beginning. A number of robotic designers have built or are building surgical robots with dexterity that is equal to if not better than the best surgeon. These systems feature 3 or 4 arms, stereoscopic 3D imaging and dexterity that no human surgeon can match. Why is there such a growing interest in these types of devices? Because robotic surgeons increase accuracy, decrease operating times, lead to shorter hospital stays, and produce fewer complications.

Here is a quick history of some of these devices beginning in the 1990s and ending in 2012.

Aesop

Computer Motion, out of Santa Barbara, California, was the creator of Aesop a surgical-assist robot built in the 1990s. The acronym Aesop does not have Greek-authored roots but rather stands for Automated Endoscopic System for Optimal Positioning. Developed to assist surgeons for endoscopies, NASA hoped to use Aesop in space where its better than human dexterity made  it highly useful for doing repairs. Aesop was voice-command controlled, much preferred over eye or head-tracking motion control for operating room procedures.

Zeus

This robotic device was a second generation successor to Aesop and was first demonstrated in laboratory studies in 1995. It allowed surgeons to do minimally invasive complex procedures through incisions smaller than the diameter of a pencil. The company that created Zeus eventually merged with the creator of the next system featured in this blog.

da Vinci

Intuitive Systems of Sunnyvale, California, after its merger with Computer Motion, developed a robotic-assisted minimally invasive surgical system called da Vinci(R). Pictured below this robot first received FDA approval in 2000. It features a surgical console with 3D high-resolution magnified viewing connected to 4 interactive highly flexible robotic arms that can be manipulated to perform operations.

da Vinci Surgical System uses 4 precision robotic arms in tandem controlled by a single surgeon seated at a computer console. Source: Intuitive Surgical

Each robotic arm features EndoWrist instruments with a range of motion far greater than a human hand. For many surgeons hand tremors can be a career ending problem but with da Vinci tremors are dramatically lessened with the robotic arms providing enhanced dexterity.

Amadeus

Titan Medical, out of  Toronto, Canada, is in the process of developing Amadeus(R), a robotic surgical system designed for remote access surgical procedures. Amadeus gives surgeons the ability to do procedures from anywhere, whether in the operating room or on the other side of the globe. Amadeus lets the surgeon feel the patient through touch feedback technology. Several models are under development with one specifically designed to perform surgery in confined spaces where a surgeon would find it impossible to access the patient.

The Near Future for Surgical Robots

Surgeons have two hands. When more are needed two or more surgeons get involved in an operation. Medical robots are not so limited and more arms means more tools can be brought to bear during a procedure with fewer surgeons needed to operate them. Robotic arms can feature touch feedback systems that provide tactile and pressure sensation to the surgical operator. Robotic arms can be generalists or specialists. One can control a 3D camera that can maneuver in the surgical site providing better than human vision while others can use multiple attached instruments to help a surgeon complete a procedure faster minimizing trauma to the patient. Robotic arms and fingers can be smaller than any human’s arms and fingers. Robotic surgeons can be autonomous entering a body, guided remotely to a surgical site, doing the repair and then exiting.

Are we there yet? Are we near the time when robots will do procedures autonomously without the presence of a surgeon? Not yet but ultimately that is where the technology is headed in the 21st century.

Biomedicine – Part 7: Life Mapping, Genomics and Unnatural Selection in the 21st Century

In the original Star Trek television episode, entitled Space Seed we are introduced to Khan Noonien Singh, a product of eugenic breeding programs on Earth. Khan and his crew are discovered  by the crew of the Enterprise in deep space on a ship named the SS Botany Bay. Rescuing Khan has consequences as he and his exiled crew attempt to commandeer Enterprise to continue their original quest in building an empire led by genetically altered super beings, products of late 20th century selective breeding.

Star Trek introduced us to Khan, a product of eugenics from the late 20th century.

We did not fight a eugenics war in the 1990s as described in Space Seed. But we laid the foundation for creating Khans and people like him in this century. Far fetched you say? Not so much when you consider two major scientific and technological breakthroughs, products of the latter part of the 20th and the first decade of this century – the mapping of the human genome and in vitro fertilization (IVF).

IVF is responsible for 1% of babies born today in Canada, approximately 3,800 in total.

In 1978, Louise Joy Brown came into the world. Louise was no ordinary child. She was conceived in a test tube using IVF, combining a donor sperm and egg together to create an embryo and ultimately a baby. Her creators, other than the parent donors were British scientists, Dr. Patrick Steptoe, a surgeon, and Robert Edwards, a physiologist. By the time Louise turned 11 we had learned how to look inside embryos and examine gene sequences. A mere 14 years later we had a detailed map of our entire genetic makeup.

Today we have the ability to screen sperm and egg DNA and ensure that what gets combined to produce an embryo is free of inheritable traits that could cause disease in a child. The social implications of this technological capability are enormous. Parents now, if given the opportunity, have choices. They can alter the end results of natural selection using unnatural selection.

Will we in the 21st century breed Khans, a new generation of super-humans? Will we limit our ability to manipulate genes to free us of hereditary illnesses like cystic fibrosis, Tay-Sachs, sickle-cell anemia, muscular dystrophy, diabetes, blindness, deafness and heart disease? Or will we take it one step further and give parents the ability to choose eye, hair and skin colour, height and weight, sex, athletic ability and other traits having nothing to do with inherited disease?

The revolution that is unnatural selection comes with its own terminology. In this blog we will introduce you to some of it so that you can better understand what lies ahead on the road to our genetic future.

Genomics

In part 2 of this biomedicine blog I described the basic components of DNA and human genome sequencing so I would suggest you go back and read that blog before you read this next section.

We are multicellular creatures. Our cells contain nuclei (with the exception of blood cells) and each nucleus consists of paired chromosomes. We have 24 pairs in all cells except sperm and egg. Each chromosome contains linearly arranged genes. Each gene contains thousands of chemical units called base pairs, the nucleotides that combine and chain together to form DNA strands. The human genome contains 30,000 genes and 3 billion base pairs. That means on average each gene can contain 100,000 base pairs. Today we have the capability of looking at 800 base pairs at a time. So when we want to see an entire gene sequence we have to take snapshots of 800 base pair segments, overlap them and stitch the entire image together to make sure we haven’t made an error.

When we talk about an entire gene sequence we are referring to the order of the chemical unit base pairs (adenine, thymine, cytosine and guanine) in a strand of DNA. Sequencing involves breaking up a DNA strand into fragments by exposing it to free-floating nucleotides that have been assigned flourescent tags. The base pairs reassemble incorporating the flourescent tagged base units which can then be read by a computer.

In sequencing the 3 billion base pairs that make up our genetic map and comparing these maps to the sequences of people with diseases we can discover where the DNA strands have flaws. In some cases a flaw may be a base pair substitution. In other cases it could a deleted or additional base pair. In many diseases it can be a deletion of thousands of base pairs.

In developing a comprehensive database of human genome sequences from healthy and unhealthy people we have the means to create DNA screening and diagnostic testing tools.

Pre-implantation Genetic Diagnosis (PGD)

Today parents undergoing IVF can select a child’s sex and other desirable physical traits by having a doctor do PGD testing to pinpoint abnormalities in embryos, and implanting only those that are deemed healthy. PGD was first developed by Dr. Yury Verlinksy, an American, to detect potential birth defects. Today it is the standard for early prenatal diagnosis of abnormalities.

For older couples planning a pregnancy PGD testing can identify Down Syndrome, Turner Syndrome, Trisomy 18, Trisomy 13, conditions that normally do not run in a family’s medical history. PGD testing reveals specific genetic conditions like Tay Sachs, muscular dystrophy and cystic fibrosis, diseases that do run in families. In some cases an embryo can be matched to a transplant recipient such as a brother or sister suffering from leukemia by using donor stem cells and cord blood from the newborn child’s umbilicus.

Today PGD can be used to test a single gene. If you can test to eliminate any undesirable disease traits, you can also test for desired cosmetic or intellect traits and ensure that the embryos that get implanted through IVF contain the “right” genes. The implications for unnatural selection are enormous.

Preconception Screening

Why stop at just screening embryos for IVF when you can map the human genome of parents before conception? That is what preconception screening and genetic carrier screening is all about. Genetic disorders have a 25% chance of being passed to a future child when both parents carry deleted, additional or other base pair flaws in their genomes.

What is the value of preconception screening? Let’s look at one disease, cystic fibrosis. In the United States this disease affects 30,000 children and adults annually. But there are more than 8 million Americans who are asymptomatic carriers of the genes that lead to this disease. Screening could eliminate a great deal of the pain and cost associated with this inherited condition.

That’s why companies like Existence Genetics and Ambry Genetics offer genetic testing. In the case of the former, parents can take a saliva-based genetic test that screens for 1,217 rare diseases, conditions and traits. Ambry’s approach includes testing for a range of childhood diseases including a 76 disease panel test as well as individual panel tests for cystic fibrosis, Marfan Syndrome, Pancreatitis, Paranganglioma, and intellectual disabilities.

Human Germline Genetic Modification (HGGM)

This is exactly what it sounds like, changing genes in the human genome to pass along new characteristics to offspring or to correct a defect in a living person. Currently most HGGM studies are confined to laboratory mice.

HGGM is seen as a tool to be used in conjunction with IVF. An embryo can be repaired before implant, fixing a genetic mutation that could lead to disease. HGGM can also not jut fix but enhance an embryo to add athletic skills or intelligence traits. It is this enhancement capability that represents an ethical issue for many medical practitioners.

Where HGGM has application is in the treatment of defective-gene-caused diseases in living humans. The mechanism for altering the associated gene responsible for a disease involves creating a healthy gene and transferring it to the affected cells. Copies of the healthy gene are placed in a transfer agent such as a virus. The virus is inserted into affected cells where it combines with the existing DNA. The revised genome upon cell replication then is copied over and over replacing defective cells and eradicating the disease.

Of course if you extend the full capability of HGGM you can see an entire adult human genome from a somatic cell being transferred from a living person to an embryo resulting in a clone. But we’ll look at that in a separate blog.

Expect to see HGGM for IVF and disease treatment coming to a hospital or medical clinic near you in the very near future.

Pharmacogenomics

Pharmacogenomics is the study of genes and drug interactions. It looks at inherited traits in the genome and drug metabolism and response. The field combines pharmacology, biochemistry and genomics.

Drug companies are focused on developing tailor-made pharmaceuticals targeted to a specific individual’s genome. They see this as an important step in reducing adverse drug reactions in patients responsible for an estimated 100,000 deaths and 2 million hospitalizations annually in the United States alone.

Today some chemotherapy drugs such as thiopurines are not used on patients that test for an inability to produce a metabolic protein. Similar kinds of screening helps identify patients who are unable to use 3o different classes of drugs because their livers lack metabolic enzymes to breakdown the medications.

Through pharmacogenomics standard trial-and-error methods of matching patients with the right drugs will be eliminated. A physician will analyze a patient’s genome and prescribe the right drug, speeding recovery and eliminating adverse reactions.

Physicians will be able to review a patient’s genome and advise them about susceptibility to a genetic disease and include careful monitoring, diet, and lifestyle advice to lessen the impact before the disease expresses itself. Doctors will be able to provide preventive treatments to head off a genetic disease before it happens using HGGM, and vaccines designed specifically to activate the patient’s immune system.

Biomedicine – Part 6: The Promise of Nanotechnology

What is nanotechnology? What is nanomedicine? In this blog we will look at where nano and medicine meet in the second decade of the 21st century and where we expect to see it go by 2030.

Nanotechnology

I briefly described nanoscale manufacturing in a earlier blog, the building of devices at an atomic or molecular scale. To understand just how tiny this is you need to know what we are measuring when we talk about nanoscale. A nanometer, the standard measure, is one billionth of a meter. That’s the length of 3 to 6 atoms, or a DNA strand. Compare this measure to the width of a human hair – between 50,000 and 100,000 nanometers. So we are really talking small.

The world of nanotechnology has made it possible to build new materials through the manipulation of matter at a molecular level. Our industrial past started out building big things. In electronics we went from vacuum tubes to transistors to integrated circuits, each substantially smaller than the technology it replaced. When we manufactured big things like steel plate we blended iron with nickel but we did this without getting down to the level of molecules and atoms. If we were to examine at a molecular level the end products of this type of manufacturing we would be able to see just how imprecise our processes were.

That is not the case with nanotechnology were we can assemble devices by building them an atom at a time. Today we hear about nanotubes made from carbon. We see articles in the paper describing molecular motors and nanowires that operate drawing their power from the weakest of forces, the interaction involving attraction repulsion between molecules first described by Johannes Diderik van der Waals in the latter part of the 19th century. Van der Waals went on to win the Nobel Prize for Physics in 1910.

Johannes Diderik van der Waals first described the forces of attraction and repulsion at the molecular level leading ultimately to the birth of nanotechnology.

In Isaac Asimov’s science fiction novel, Fantastic Voyage, he relates a tale involving a science that shrinks atoms temporarily to a scale so small that a submersible along with its crew can be injected into the bloodstream of a scientist who has suffered a blood clot in the brain. Asimov’s tale, like much of science fiction, has provided inspiration to researchers who see in it the potential promise of nanobots that can sail the inner seas of our blood and lymphatic systems repairing cells, defeating cancer and extending our lives. Of course Asimov’s story, an adaptation of a movie script, used a matter transformer to shrink atoms and molecules, not nanotechnology.

Some scientists argue that nanotechnology has a dark side. In Michael Crichton’s novel, Prey, nanobots escape from a research laboratory, replicate, evolve and form intelligent swarms becoming a threat to humanity and life on Earth.

Nanomedicine

The nanobots in our future are far more benign and helpful than those proposed in Crichton’s novel. Let’s look at how we will exploit them and other nanotechnologies for good in the field of biomedicine. Researchers identify a number of exciting uses including:

1. Nanoparticle drug delivery
2. Nanorobotics
3. Nanoelectronics
4. Nanovaccinology

Nanoparticle Drug Delivery

MIT engineers in association with Brigham and Women’s Hospital in Boston have created synthetic nanoparticles that pass through the outer membrane of prostate cancer cells to deliver cisplatin and docetaxel, to target tumor cells. The initial challenge involved developing a nanoparticle that would pass through a cell membrane without rupturing it. Normally a cell membrane eats or encases and ejects foreign objects such as nanoparticles. But by creating synthetic materials that closely resemble the cell membrane the researchers have tricked the cells into accepting the nanoparticle intrusion.

Nanoparticles created by researchers at MIT and Brigham and Women's Hospital researchers deliver a cocktail of drugs and using tags bind to molecules found on the surface of targeted cells. Images: MIT/Brigham and Women's Hospital

The next challenge involved giving the nanoparticle the capability of recognizing the special characteristics of specific tumor cells. This required the development of tags that specifically bind to molecules found on the surface of these cells. Developing nanoparticles that can be so specific means healthy cells don’t experience the drug interactions, minimizing side effects. For chemotherapy treatment nanoparticles represent, therefore, a breakthrough in cancer treatment. The research team at MIT are working on adapting nanoparticles to treat other cancers.

Nanorobotics

Nanorobots for medicine are in our very near future. None exists today. What defines a nanorobot? This is a molecularly-manufactured machine constructed from atoms and molecules with dimension ranging from 1 to 100 nanometers. Currently carbon, nitrogen and oxygen are the elements of choice because they have a higher acceptance rate within the body with less likelihood of a rejection response brought on by the immune system. Powered by using glucose and oxygen for energy sources, or by an external power source, nanorobots would roam through the body serving general maintenance of our bodies or specific tasks focused on killing pathogens or repairing damaged organs and body tissue. A nanorobot would feature an onboard computer, sensors, signal processors and communications technology.

Nanorobots may be used in groups relying on group intelligence. Several may serve as navigation beacons to help others of their kind to navigate through the body, and to accurately relay position location to external monitors. Like their nanoparticle brethren, nanorobots will include tagged information to distinguish health cells from those being targeted.

Nanorobots can be designed to be very task specific so that once the job is done they can be retrieved or excreted, or degrade to be removed by the immune system. Others can be designed to permanently police the body to compliment the immune system in dealing with diseases or required repairs. Others may just act as biosensors constantly relaying health information periodically to external monitors.

Nanorobots could serve as arterial cleaners constantly scouring the walls of blood vessels to eliminate potential blockages. They could be used to permanently eliminate gum disease by removing plaque and tartar and policing the mouth to ensure good dental health. They could be applied in a lotion to deal with basic chronic skin problems like acne. They could target specific pathogens and destroy them working in harmony with the body’s immune system.

Nanoelectronics

For diseases such as Alzheimer’s and Parkinson’s there are no known cures. There are challenges in trying to treat brain injuries. Our bodies have a blood-brain barrier that acts as a selective filter isolating brain tissue from the rest of the body. This makes it difficult to deliver treatment through the normal body transport systems.

But nanotechnology may prove to be a means by which the process of brain degeneration is stopped and potentially reversed. This means creating nanotechnology that can cross the blood-brain barrier and be released in the brain to deliver therapy. Described as Trojan Horses, such nanotechnology would consist of an encapsulated molecule that is not seen as a threat by the body’s immune system. The molecule would be designed to degrade and release its hidden inner nano components or drugs specifically targeted to the area of the brain affected by the disease. In the case of Alzheimer’s, current investigations are looking at delivering Rivastigmine and Acetylcholine using biodegradable polymeric nanoparticles.

What if the same molecule could deliver a device and not a drug? That device could contain nanoelectronics that could replace degenerated neurons and provide new neural pathways within the brain. Curved carbon presents opportunities to develop devices on a nano scale that may lead to brain implants to enhance cognition and memory or restore motor function control. The next decade should see significant progress in nanoelectronics focused on brain-related diseases and spinal cord injuries.

Nanovaccinology

Current vaccines use adjuvant, chemicals designed to enhance the immune response to whatever is being targeted. For some people adjuvant can cause negative antibody responses leading to complications. Replacing adjuvant with nanoparticles combined with the vaccine could eliminate these types of bad reactions.

Better yet, nanotechnology can be used to eliminate the needle in vaccine delivery. Researchers at the University of Queensland, Australia, have developed a Nanopatch, a needle-free method of delivering vaccines. The Nanopatch is smaller than a postage stamp. Each contains thousands of tiny projections that when placed on skin delivers sera biomolecularly. The Nanopatch activates when placed on skin becomes moist and dissolves within minutes. Used for influenza vaccine delivery, the Nanopatch is being considered as an effective tool for delivering vaccines against West Nile and Chukunga virus.