100. ADVANCES IN HEALTH RESEARCH

This entry marks the hundredth blog I have written over the past 30 months.

Looking at the genuine advances being made on so many fronts, including computer technology, environmental improvements, and space exploration, I believe the most favorable projection for our future rests on the genetic revolution that promises positive improvements in our lives in the 21st century. Advances in biotech have already made it possible to feed the world in new ways. The crop yields of wheat, rice, corn and other cereals have increased dramatically. We enjoy the result of breakthroughs which have increased our life spans, reduced diseases like malaria and improved technology in hospitals to correct a wide range of disorders.

Since the mid-19th century most countries have had continuing improvements in the health of their inhabitants. In 1850 four in ten English babies died before their first birthday, today less than five out of every thousand infants in Britain die before the age of one. As a consequence, we have come to expect continuing advances in medicine and health care. Sir William Castell, the retired chairman of the Welcome Trust thinks “We are on the cusp of spectacular change, as genomics, imaging, diagnostics, data analysis and other technologies come together to make real precision medicine possible for the first time.”1 Precision has become a key word in the practice of 21st century medicine. Precision demands that patients be diagnosed for the exact cause of the their ailments and only after examining their genetic make-up, prescribed the best treatment.

Now the laboratory development of CRISPR* will be making the editing of the genomes of all living species much more rapid, cheaper and more accurate. Each of our cells contain all of our 22,000 human genes. These are not all simultaneously active all of the time, but are controlled by complex networks of programs and circuits in our body’s systems. The CRISPR breakthrough now makes it possible to modify the DNA without altering the gene sequencing itself. Earlier this month, the US National Academy of Sciences published a paper on altering the genetic composition of mosquitoes which can render the female offspring sterile and potentially open to extermination. The technique now employed assures that certain genetic changes are passed on to the offspring. CRISPR could also be employed on pig embryos injected with human cells to create new kidneys, pancreases, and livers, which could then be transplanted into humans without the risk of rejection by the immune system.

Microbiologists continue to make startling advances in understanding the complex microbiome, that is all the bacteria, microbes, viruses, fungi and eukaryotes that inhabit our guts. Massive groupings of competing and co-operative microbes have evolved in our species. Microbes in our guts are essential for survival and the loss of microbiotic diversity in our digestive system (due to the overkill by antibiotics as well as the use of radiation in food preservation and agricultural pesticides) is detrimental to our well-being. Even our nervous systems are dependent on gut bacteria. These produce hundreds of neurotransmitters which regulate mood, memory and learning. They also produce much of the body’s supply of serotonin which is recognized as one of the keys to our sense of well-being.

Methods are being explored which might enable doctors to tell immediately whether an infection is bacterial or viral. If doctors were then able to tell which antibiotics could eradicate an infection, they would not prescribe some drugs, as they often risk doing now, which offer only partial resistance and advance the progress of resistant strains.2 Competing microbes in the gut, trying to keep others in check, secrete antibiotics. In the search for these microbes pharmaceutical groups are extracting antibiotics from bacteria living in dirt. This has led to testing new drugs like Teixobactin.

With the spectacular advance of antibiotics over the past century the rise of drug resistant organisms, such as Staphylococcus aureus, has increased the risk of hospital infections. Some three quarters of a million people die each year from drug resistant infections. Immunotherapy is being used increasingly to fight many illnesses which do not respond to penicillin and other antibiotics. Reserving some of the new breakthrough drugs for emergencies keeps sales low and prices high. This in turn discourages some of the big pharmaceutical companies from costly research, development and testing. Cheaper diagnostic techniques may partially correct this imbalance.

Medical technology, such as stem cell therapy, has moved swiftly from the drawing board two decades ago into human trials and now into transplant operations as in patients suffering macular degeneration of their eye cells. Other technological advances are focused on ways to radically alter our biological composition.3 Tissue engineering is creating functional matter that avoids rejection by patients having transplants. Their porous structure is such that it induces the body’s cells to integrate with the artificial tissues to ultimately transform into normal tissues. Progress is being made in creating biomaterials and artificial polymers (that is, chains of molecules) which will interact with networks of stem cells.4

Because of the lack of donors, thousand of patients around the globe are desperately awaiting organ transplants. Organoids are another of the dramatic new breakthroughs in which laboratory grown body parts are used to test patients about to receive transplants for kidneys, liver, intestines and other organs. Such organoids are grown from stem cells similar to those found in embryos. However, some organoids are actually created by treating skin cells with chemicals which transform them into stem cells. These organoids are then placed in the lab into glass vessels where they respond to drugs being tested for toxicity exactly in the same way as would a corresponding transplanted organ of the afflicted patient. Most people who currently have transplant surgery must take immune system suppressing drugs for life.

Cerebral organoids are 3D tissues generated from stem cells that allow modeling of human brain development in glass vessels which are turned into supportive microenvironments. Such “neural precursor tissue can spontaneously self-organize to form the stereotypic organization of the early human embryonic brain,” explains Madeline Lancaster of Cambridge University.5 Her current interests focus on neurodevelopmental disorders like autism and intellectual disability by introducing mutations seen in these disorders and examining their roles in pathogenesis in the context or organoid development. The researchers in the Medical Research Council’s labs are studying mechanisms underlying the progression of neurological diseases and the potential therapeutic advances.

Researchers also are moving towards the creation of implantable pacemakers for the brain which could be used to treat problems like Parkinson’s, drug addiction, dementia and depression much as we have developed cardiac pacemakers for heart problems. Intense research is also focusing on testing strategies which could treat or even prevent Alzheimer’s where sticky plaques of a protein called amyloid build up in the brain forming deposits that suffocate nerve cells. The advances in brain imaging enable scientists to spot small amyloid clusters before they cause damaging symptoms. Vaccines are being tried (so far unsuccessfully) to develop vaccines which could eliminate amyloid plaques.

Last year the Hinxton group of bioethicists, stem cell researchers and genome experts agreed that human genome editing is necessary if we are to gain further understanding of the human embryos — even if this is not applied to cultivating gene-edited embryos. Ultimately the hope is that genes could be edited to avoid certain inherited cancers.

Research has been going on for more than 75 years to avoid the surgery, radiation treatment or chemotherapy in breast and other cancers. The search is now becoming far more precise due to our ability to pinpoint specific cells responsible for cancer formation. For example, genetic researchers have found that a mutation in the gene named BRCA1 which affects less than 1 percent of women is responsible. Specific new drugs, such as Denosumab, will now be tested in clinical trials to ascertain and study the possible side-effects. The hope is that in the not so distant future, it will be possible to avoid mastectomies and debilitating radiation treatments for this cancer as well as for so many others.

As the power of computers has steadily advanced in assisting researchers and testers, so have the cures for human diseases. I am filled with optimism when contemplating where we are headed in tackling Alzheimer’s, autism, cancers and other genetic defects. I am less confident that these advances will eradicate the health problems of billions of people whose governments have neither the means nor the ability to raise the resources necessary to tackle the massive national inequalities in health care.


* CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR involves taking a strand of RNA, a chemical messenger, to target a section of our DNA and using an enzyme (a nuclease) that can cut unwanted genes and paste in the edited RNA. This sequence borrows from a process in nature that scientists have harnessed to snip and splice sections of DNA. To make this possible researchers found a specific slicer enzyme called Cas9. This technological advance is key to the synthetic biology and gene editing revolution and represents an amazing improvement over existing techniques.

1Clive Cookson, “The (very precise) future of medicine”, The FT Magazine, October 3, 2015.

2“When the drugs don’t work,” The Economist, May 21, 2016, p.9

3Linda Geddes, “The gene revolution,” The Observer, June 12, 2016.

4Oran Maguire, “Engineering the rise of cell therapies,” Bluesci, Easter 2016, p.12

5mlancast@ mrc-lmb.cam.ac.uk

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99. OUT NOT IN

I rarely change my mind on important issues, but I surprised myself when I shifted out of the British camp which wants to stay in the European Union and found myself recognizing that change is necessary and can only come if the UK votes OUT. Having been born in Holland and partially educated in France, the US, and the UK, I have always thought of myself as being pro-European. I strongly admired the leaders who created the Common Market after WWII as well as those who followed with the realization of the European Union in an effort to end centuries of hostility.

Until about a year ago, I took it for granted that I would support the UK remaining in the EU. My first serious doubts were aroused by the narrow and inept ways the European community dealt with the Greek financial crisis. The scandalous way the Europeans then dealt with the immigration crisis horrified me. I began to see the sprawling bureaucracy in Brussels as incompetent, reactionary and unaccountable. A serious desire for change altered my perspective.

I began to see the vitriolic exchanges coming from both the protracted electoral campaign in the United States and the four months of raging debates in the United Kingdom between the “ins” and the “outs” as a reflection of popular concerns which exist on multiple fronts: An obvious demand for change in “Big Government,” global inequality, environmental control, runaway technology, banking instability, migration and immigration, and despair over the ineffectuality of the United Nations and the European Union. Add the challenges of capitalist corruption, and the lack of genuine leadership in all of these areas and the message became clear that we cannot go on as we have in the 21st Century. The rise of populist figures like Donald Trump, Marine Le Pen and others of both the left and the right is an indication of the general disaffection.

That is why I am NOW advocating Britain’s exit from the European Union. If the “Remain” camp wins, nothing in Europe will be changed. Should the Brexit camp win, the floodgates for change could be opened, starting with the resignation of the Prime Minister and followed by unknown consequences in the European Community, the eventual break-away of Scotland, and the beginning of a major shake-up of the world banking system with unknown consequences for the global economy. My hope is that such major challenges would renew democratic initiatives and fire the spirit of people around the world with hope. A “Leave” vote could also mark a change for such huge bureaucratic organizations as the European Union in Brussels and the United Nations in New York. It could possibly lead us to smaller, cooperative groupings in which the voices of the electorate become heard. People are fed up with ever more remote bureaucratic centralization for the sake of cost-cutting and “efficiency.” The public is beginning to recognize that “efficiency” comes at the expense of both accountability and human contact.

The prospects for the European Union look increasingly bleak as the “social” part of the European social market is being sacrificed to focus on the need for greater economic stability. The politicians in Brussels still believe they can push through a fiscal union even as unity is crumbling. Acting in the interests of the big corporations which, through their army of lobbyists and inside dealers, have corrupted the administrations in London, Washington and Brussels. Moreover, the unaccountable elite in the EU, who originally embraced the lofty ideals of the “Democratic Process,” are also failing to act effectively on the increasingly undemocratic tendencies of the governments in Eastern Europe. These bureaucrats in Brussels have never been exposed to the will of the people and don’t want this to be recognized. Unless they are shocked out of their routines, the EU and the UN will continue to be more bureaucratic and more centralized. Is this not the time for change if we can affect this by voting for the Exit?

Such an exit by Britain could be the death rattle for the increasingly remote 21st Century leadership and herald in a new and hopefully sympathetic era as Steve Hilton, an ex-strategy advisor to David Cameron, has been promoting in his book More Human. The real choice for Britain is not between economic security and economic risk. It is about the birth of the kind of sustainable democratic governance which will best guide us through an increasingly challenging and unpredictable technological era.