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.

Agriculture – Part 3: Bio Engineering of Plants

Humanity has engineered plants and animals since the dawn of the Neolithic Revolution, selecting seeds from the best plants, and cross-pollination to create new plant and animal varieties. Humans used observation and experimentation to achieve improved crop yields and better livestock. Charles Darwin and Gregor Mendel provided the foundational science behind what we know of today as genetics and bioengineering. Through Darwin we discovered how the natural processes of selection are influenced by environmental factors. Through Mendel we learned how inherited characteristics are passed down through human selection. Their scientific work comprised of observation and detailed record keeping.

Charles Darwin on the left, a failed teacher, and Gregor Mendel on the right, a priest, worked largely on their own in discovering the science behind natural and human-derived selection.

In 1859 Darwin published “The Origin of the Species.” Between 1856 and 1863 Mendel studied pea plants and made two discoveries which he called the Law of Segregation and the Law of Independent Assortment, the fundamentals of how inherited traits get passed along. When Mendel was promoted to abbott in 1868 he ended his experiments. Neither man knew of each other. Interestingly in 1869 another scientist, Friedrich Miescher identified something he called the nuclein inside human white blood cells. Miescher had found DNA. But it was 84 years later that James Watson and Francis Crick discovered the unique characteristics of the DNA molecule.

DNA Allows Us to Bio Engineer Living Things

DNA is  found in every chromosome in the nucleus of almost every cell in our bodies (red blood cells have no nucleus so they are the exception) as well as in all the cells in plants and animals on this planet. Every strand of DNA contains genes and it is genes that determine  inherited traits. Sexual reproduction combines the DNA of two parents in the offspring. When egg and sperm meet each represents half of the genetic content of each parent. This means that not all characteristics of a parent get expressed in an offspring. When Mendel studied his pea plants he uncovered how traits could be transmitted from generation to generation, some traits dominant and some recessive. Mendel didn’t know about genes when he was recording his observations. But he had discovered the mechanism of genetic manipulation. Today agricultural science manipulates genes in living things, not only intraspecies but interspecies.

Why Do We Want to Modify Agricultural Products Using Genetics?

On Monsanto’s website, a company that is heavily invested in genetically engineered crops, herbicides and pesticides, it describes our human dilemma caused by population growth. Monsanto is seen by environmentalists as a pariah because its genetically modified crop solutions help bolster the sales of its own herbicide and pesticide products. But nonetheless Monsanto is not wrong in stating the facts that by 2050 the planet will have a human population exceeding nine billion. That more than nine billion represents a 30% increase over our present human population, a number equivalent to adding a today’s China and India to the planet. What that means is we simply need to produce much more through agriculture to meet food demands. In Monsanto’s words “farmers must produce more in the next few decades than they have in the past 10,000 years combined.”

Genetic Engineering in Modern Agriculture

Genetic engineering is playing a significant role in worldwide agricultural production today. What proportion of  foods today are genetically manipulated?

• 60 to 70% of processed foods in U.S. grocery stores contain oils or ingredients derived from biotech corn and soybeans
• 45% of all corn grown in the U.S. is genetically engineered
• 85%  of soybeans in the U.S. are genetically altered

For farmers the attractions are obvious.  Genetically engineered crops produce higher crop yields and cost far less to maintain.

A brief discussion on some of the most commonly grown genetically modified crops follows:

Tomatoes

In attempting to stop tomatoes from rotting the Flavr Savr  was invented in 1994. It was the first genetically engineered food crop to receive human consumption approval. A tomato enzyme polygalacturonase, PG for short, was identified as having the ability to contribute to the ripening of tomatoes. Researchers at Calgene, Inc., introduced an altered antisense gene to reduce the formation of PG. The benefit to farmers was immediate. Tomatoes with the antisense gene could be left to ripen longer in the field. Rather than being treated chemically to ripen, Flavr Savr tomatoes could naturally mature enhancing the flavour of the end product.

Extensive testing by the U.S. Food and Drug Administration determined that these altered tomatoes posed no harm to humans. But what was an agricultural success in genetic engineering turned into a commercial failure when the product was introduced and labelled as genetically engineered. Today genetically engineered products are not so blatant in their labelling.

Corn

Corn of all plants cultivated in North America seems to be most associated with genetic engineering. Corn was domesticated in North America very early in the Neolithic Revolution. It has been engineered from its ancestral form, teosinte, a grass, into modern corn varieties. Farmers cross-bred various strains of primitive corn to improve yields and cultivate desirable traits. This manipulation of corn was intraspecies.

The genetic modification being made by agribusiness research companies today are more interspecies than intraspecies. Corn is no exception.

A protein toxic to caterpillars found in a strain of bacteria called Bacillus Thuringiensis (Bt) has been bioengineered into corn plants. The gene allows the corn to express the toxin and kill the caterpillars that feed on its leaves and cobs. But it has become an arms race between genetic engineers and the insect pests. By planting  too much bioengineered product farmers are speeding up evolutionary resistance to the toxin by new generations of caterpillars and ultimately crop yields have been affected.

Companies like Monsanto have invested heavily in developing new types of corn engineered to tolerate herbicides such as Roundup(TM), a popular weed killer used on home gardens and lawns. Monsanto is the inventor of Roundup. So developing Roundup-ready crops that contain genes tolerant to glyphosate, a chemical toxic to weeds, means crops can be sprayed and only the weeds die. But some weeds over time develop resistance to herbicides and these survivors pass along inherited traits. You see, Darwin was right.

Soybeans

Corn isn’t the most genetically manipulated crop grown globally. That honour goes to soybeans. Genetically modified soybeans containing resistance to herbicides like Roundup were first planted in the United States in 1996. By 2006 genetically modified soybean plantings extended to 9 countries.

In countries like Argentina almost 100% of the soybean crop is genetically modified. The United States is a close second. Today 58.6% of worldwide soybean production comes from genetically modified crops.

We ingest food additives laced with genetically modified soybeans. Our domestic farm-bred animals are raised on soybean-derived feeds.

When Monsanto developed Roundup-Ready(TM) soybeans the goal was to create plants that could be dosed with a less toxic herbicide than atrazine. Atrazine was a commonly used herbicide before Roundup. Atrazine had long-term environmental consequences where Roundup was perceived to have a shorter impact in the environment. But glyphosate, the active chemical in Roundup has proven to be highly toxic to many plants, and to aquatic life when it enters lakes and streams through agricultural runoff.

In some areas where Roundup-Ready soybeans are grown, nearby plants have begun to exhibit glyphosate resistance. When these plants are weeds the benefit of the herbicide is diminished impacting crop yields. As more weeds become Roundup resistant, new genetically modified soybean variants will need to be developed to counter this escalating arms race. New herbicide treatment plans will potentially introduce more herbicide residue into the larger environment.

New methods of tillage, crop rotation, growing of cover crops, and other biointensive techniques including weed tolerance may prove to be far more effective tools for maintaining quality and crop yield.

Rice

Rice provides basic nutrition to much of South and East Asia. Golden Rice, developed in 1999, contains two turned-off and two inserted genes that cause beta-carotene to accumulate in the rice grains. The golden colour indicates the concentration of Vitamin A to meet the recommended daily dosage in 100 to 200 grams of rice. Golden Rice is contributing  to reductions in diseases related to Vitamin A deficiency. Vitamin A Deficiency (VAD) causes blindness in 250,000 to 500,000 children annually. The blindness is an indicator of a more serious problem that leads to half of these  children dying within a year of becoming blind. That’s because VAD impacts a child’s immune system putting them at increased risk to common infections.

Cabbage, Broccoli, Sprouts and Cauliflower

Even members of the cabbage family have been targets for genetic modification. The insertion of a Bacillus Thuringiensis (Bt) genes in cabbage, broccoli and cauliflower was introduced as a toxin to kill Cabbage Butterfly larvae. Increasing resistance on the part of the butterfly population eventually led to a decline in Bt-cabbage. More recently a gene responsible for the poison in scorpion tails has been inserted into cabbage plants. The poison expressing genes are modified to not harm humans.

Using Genetic Engineering to Turn Plants into Medicine

Hepatitis B and cholera are among a number of diseases that may be treated by making humans eat fruit or vegetables that are genetically modified to produce vaccines.  Researchers are engineering bananas, potatoes, lettuce, carrots and even tobacco to produce a way to vaccinate people without a needle.

Bananas are particularly useful. An altered form of  the disease virus is injected into banana saplings. The altered virus genetic information is reproduced in the plant and fruit. When consumed by humans the bananas help build immunity to fight these diseases.

Agriculture – Part 1: Setting Our Future Food Table in the 21st Century

When we think of technology we often overlook agriculture because it has been part of humanity since the Neolithic Revolution, a span of more than 10,000 years. Yet agriculture is intensively technological in nature and in the 21st century we are going to see dramatic changes in the way we farm and in our agricultural distribution strategies. What is driving agricultural technological advances in the 21st century?

1. The cost of energy and the transportation of agricultural products

The rising cost of fuel and energy impacts agriculture many ways.  Industrial farms in North America and Europe need to find ways to reduce hydrocarbon energy dependency. The grow local movement is reinventing the very definition of what is a farm.

2. Our changing view on chemicals, fertilizers, herbicides and pesticides.

We have created both a revolution in agriculture and a potential monster in making our crop yields so chemical dependent. In saturating the soil with herbicides and pesticides we have created new varieties of resistant weeds and insects. This ongoing accelerating arms race between our technical fixes and the evolution of pests is one that we could inevitably lose with catastrophic consequences.

3. Bioengineering of crops and livestock

Bioengineering is changing the very nature of what we grow and eat. We have always been in the business of bioengineering ever since humans first changed food sourcing from being hunter-gatherers to farmers. The difference today is our bioengineering is in the laboratory and not through selective fertilization in the fields. We are now inserting genes into the DNA of plants and animals to fundamentally alter the end products. We are growing meat in the laboratory rather than on hoof. We are farming bioengineered fish rather than catching wild varieties in the open seas largely because we have overfished and exhausted natural population regeneration.

4. Climate change

Our fossil fuel dependency is altering the climate raising temperatures, causing prolonged droughts and more severe weather events. The impact on agriculture from environmental change cannot be underestimated.

5. Fresh water availability

Whether we draw water from lakes and rivers or aquifers, cities compete with agriculture for what is becoming a very precious resource. What can we do when we start reaching the limits of fresh water accessibility?

6. Human population growth

Can we continue to grow enough to feed a burgeoning human population let alone our livestock? At 7 billion today and with predictions of 9 billion by mid-century, will agricultural intensification meet our  food needs. Considering today that over 1 billion people on this planet are underfed or malnourished, what will that number be at the end of the 21st century?

7. Implication of biofuels on growing food

Do we grow crops to feed our engines or are stomachs? This is a basic dilemma in countries like the United States and Brazil where corn in the former and sugar cane in the latter are both food and fuel crops. Part of the challenge lies with the practicality of moving food from where it’s grown to where it’s needed. The United States has had huge corn surpluses for years. Farmers have been paid to not grow it. A food industry has grown up built around corn byproducts just to suck up the surplus yield. Now the surplus is being used for biofuel rather than being shipped to where it can feed the hungry.

If I have missed any issue please feel free to comment. The subsequent blogs on agriculture will explore each of these topics in greater detail.