Tag Archives: disease

Café Scientifique Vancouver (Canada) talk on August 28th 2018: Getting the message: What is gene expression and why does it matter?

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Here’s more about the latest Café Scientifique talk from an August  22, 2018 announcement received via email,

Our next café will happen on TUESDAY, AUGUST 28TH at 7:30PM in the back
room at YAGGER'S DOWNTOWN (433 W Pender [St., Vancouver]). Our speaker for the
evening will be DR. KATIE MARSHALL from the Department of Zoology at
UBC [University of British Columbia]. Her topic will be:

GETTING THE MESSAGE: WHAT IS GENE EXPRESSION AND WHY DOES IT MATTER?

Many of us think that DNA is like a light switch; you have a particular
sequence of base pairs or a particular chromosome, and these directly
cause a large change in biological functioning. But the truth is that
any given gene can be up or downregulated through a dizzying array of
biochemical “dimmer switches” that finely control how much that
particular gene is expressed. Understanding how this works is key to
answering questions like “How does a sequence of base pairs in DNA
become a whole organism?” and “Why is it that every cell has the
same DNA sequence but different function?”. We’ll chat about the
advances in computing needed to answer these questions, the importance
of gene expression in disease, and how this science can help us
understand social issues better too.

I wasn’t able to find out too much more about Dr. Katie but there is this profile page on the UBC Zoology Department website,

The long-term goal of my research is to understand how abiotic stress filters through physiology to shape species abundance and distribution. While abiotic stressors such as temperature have been used very successfully to predict population growth, distribution, and diversity of insect species, integration of the mechanisms of how these stressors are experienced by individuals from alteration of physiology through to fitness impacts has lagged. Inclusion of these mechanisms is crucial for accurate modelling predictions of individual (and therefore population-level) responses. My research to date has focused on how the impact of frequency of stress (rather than the duration or intensity of stress) is a superior predictor of both survival and reproductive success , and used insect cold tolerance as a model system.

At UBC I’ll be focusing on the cold tolerance and cryobiology of invertebrates in the intertidal. These organisms face freezing stress through the winter, yet remarkably little is known about how they do so. I’ll also be investigating plasticity in cold tolerance by looking for interactive effects of ocean acidification and community composition on thermal tolerance.

Enjoy!

Could CRISPR (clustered regularly interspaced short palindromic repeats) be weaponized?

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On the occasion of an American team’s recent publication of research where they edited the germline (embryos), I produced a three-part series about CRISPR (clustered regularly interspaced short palindromic repeats), sometimes referred to as CRISPR/Cas9, (links offered at end of this post).

Somewhere in my series, there’s a quote about how CRISPR could be used as a ‘weapon of mass destruction’ and it seems this has been a hot topic for the last year or so as James Revill, research fellow at the University of Sussex, references in his August 31, 2017 essay on theconversation.com (h/t phys.org August 31, 2017 news item), Note: Links have been removed,

The gene editing technique CRISPR has been in the limelight after scientists reported they had used it to safely remove disease in human embryos for the first time. This follows a “CRISPR craze” over the last couple of years, with the number of academic publications on the topic growing steadily.

There are good reasons for the widespread attention to CRISPR. The technique allows scientists to “cut and paste” DNA more easily than in the past. It is being applied to a number of different peaceful areas, ranging from cancer therapies to the control of disease carrying insects.

Some of these applications – such as the engineering of mosquitoes to resist the parasite that causes malaria – effectively involve tinkering with ecosystems. CRISPR has therefore generated a number of ethical and safety concerns. Some also worry that applications being explored by defence organisations that involve “responsible innovation in gene editing” may send worrying signals to other states.

Concerns are also mounting that gene editing could be used in the development of biological weapons. In 2016, Bill Gates remarked that “the next epidemic could originate on the computer screen of a terrorist intent on using genetic engineering to create a synthetic version of the smallpox virus”. More recently, in July 2017, John Sotos, of Intel Health & Life Sciences, stated that gene editing research could “open up the potential for bioweapons of unimaginable destructive potential”.

An annual worldwide threat assessment report of the US intelligence community in February 2016 argued that the broad availability and low cost of the basic ingredients of technologies like CRISPR makes it particularly concerning.

A Feb. 11, 2016 news item on sciencemagazine.org offers a précis of some of the reactions while a February 9, 2016 article by Antonio Regalado for the Massachusetts Institute of Technology’s MIT Technology Review delves into the matter more deeply,

Genome editing is a weapon of mass destruction.

That’s according to James Clapper, [former] U.S. director of national intelligence, who on Tuesday, in the annual worldwide threat assessment report of the U.S. intelligence community, added gene editing to a list of threats posed by “weapons of mass destruction and proliferation.”

Gene editing refers to several novel ways to alter the DNA inside living cells. The most popular method, CRISPR, has been revolutionizing scientific research, leading to novel animals and crops, and is likely to power a new generation of gene treatments for serious diseases (see “Everything You Need to Know About CRISPR’s Monster Year”).

It is gene editing’s relative ease of use that worries the U.S. intelligence community, according to the assessment. “Given the broad distribution, low cost, and accelerated pace of development of this dual-use technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications,” the report said.

The choice by the U.S. spy chief to call out gene editing as a potential weapon of mass destruction, or WMD, surprised some experts. It was the only biotechnology appearing in a tally of six more conventional threats, like North Korea’s suspected nuclear detonation on January 6 [2016], Syria’s undeclared chemical weapons, and new Russian cruise missiles that might violate an international treaty.

The report is an unclassified version of the “collective insights” of the Central Intelligence Agency, the National Security Agency, and half a dozen other U.S. spy and fact-gathering operations.

Although the report doesn’t mention CRISPR by name, Clapper clearly had the newest and the most versatile of the gene-editing systems in mind. The CRISPR technique’s low cost and relative ease of use—the basic ingredients can be bought online for $60—seems to have spooked intelligence agencies.

….

However, one has to be careful with the hype surrounding new technologies and, at present, the security implications of CRISPR are probably modest. There are easier, cruder methods of creating terror. CRISPR would only get aspiring biological terrorists so far. Other steps, such as growing and disseminating biological weapons agents, would typically be required for it to become an effective weapon. This would require additional skills and places CRISPR-based biological weapons beyond the reach of most terrorist groups. At least for the time being.

…

A July 5, 2016 opinion piece by Malcolm Dando for Nature argues for greater safeguards,

In Geneva next month [August 2016], officials will discuss updates to the global treaty that outlaws the use of biological weapons. The 1972 Biological Weapons Convention (BWC) was the first agreement to ban an entire class of weapons, and it remains a crucial instrument to stop scientific research on viruses, bacteria and toxins from being diverted into military programmes.

The BWC is the best route to ensure that nations take the biological-weapons threat seriously. Most countries have struggled to develop and introduce strong and effective national programmes — witness the difficulty the United States had in agreeing what oversight system should be applied to gain-of-function experiments that created more- dangerous lab-grown versions of common pathogens.

As scientific work advances — the CRISPR gene-editing system has been flagged as the latest example of possible dual-use technology — this treaty needs to be regularly updated. This is especially important because it has no formal verification system. Proposals for declarations, monitoring visits and inspections were vetoed by the United States in 2001, on the grounds that such verification threatened national security and confidential business information.

…

Even so, issues such as the possible dual-use threat from gene-editing systems will not be easily resolved. But we have to try. Without the involvement of the BWC, codes of conduct and oversight systems set up at national level are unlikely to be effective. The stakes are high, and after years of fumbling, we need strong international action to monitor and assess the threats from the new age of biological techniques.

Revill notes the latest BWC agreement and suggests future directions,

This convention is imperfect and lacks a way to ensure that states are compliant. Moreover, it has not been adequately “tended to” by its member states recently, with the last major meeting unable to agree a further programme of work. Yet it remains the cornerstone of an international regime against the hostile use of biology. All 178 state parties declared in December of 2016 their continued determination “to exclude completely the possibility of the use of (biological) weapons, and their conviction that such use would be repugnant to the conscience of humankind”.

These states therefore need to address the hostile potential of CRISPR. Moreover, they need to do so collectively. Unilateral national measures, such as reasonable biological security procedures, are important. However, preventing the hostile exploitation of CRISPR is not something that can be achieved by any single state acting alone.

As such, when states party to the convention meet later this year, it will be important to agree to a more systematic and regular review of science and technology. Such reviews can help with identifying and managing the security risks of technologies such as CRISPR, as well as allowing an international exchange of information on some of the potential benefits of such technologies.

Most states supported the principle of enhanced reviews of science and technology under the convention at the last major meeting. But they now need to seize the opportunity and agree on the practicalities of such reviews in order to prevent the convention being left behind by developments in science and technology.

Experts (military, intelligence, medical, etc.) are not the only ones concerned about CRISPR according to a February 11, 2016 article by Sharon Begley for statnews.com (Note: A link has been removed),

Most Americans oppose using powerful new technology to alter the genes of unborn babies, according to a new poll — even to prevent serious inherited diseases.

They expressed the strongest disapproval for editing genes to create “designer babies” with enhanced intelligence or looks.

But the poll, conducted by STAT and Harvard T.H. Chan School of Public Health, found that people have mixed, and apparently not firm, views on emerging genetic techniques. US adults are almost evenly split on whether the federal government should fund research on editing genes before birth to keep children from developing diseases such as cystic fibrosis or Huntington’s disease.

“They’re not against scientists trying to improve [genome-editing] technologies,” said Robert Blendon, professor of health policy and political analysis at Harvard’s Chan School, perhaps because they recognize that one day there might be a compelling reason to use such technologies. An unexpected event, such as scientists “eliminating a terrible disease” that a child would have otherwise inherited, “could change people’s views in the years ahead,” Blendon said.

But for now, he added, “people are concerned about editing the genes of those who are yet unborn.”

A majority, however, wants government regulators to approve gene therapy to treat diseases in children and adults.

…

The STAT-Harvard poll comes as scientists and policy makers confront the ethical, social, and legal implications of these revolutionary tools for changing DNA. Thanks to a technique called CRISPR-Cas9, scientists can easily, and with increasing precision, modify genes through the genetic analog of a computer’s “find and replace” function.

…

I find it surprising that there’s resistance to removing diseases found in the germline (embryos). When they were doing public consultations on nanotechnology, the one area where people tended to be quite open to research was health and medicine. Where food was concerned however, people had far more concerns.

If you’re interested in the STAT-Harvard poll, you can find it here. As for James Revill, he has written a more substantive version of this essay as a paper, which is available here.

On a semi-related note, I found STAT (statnews.com) to be a quite interesting and accessibly written online health science journal. Here’s more from the About Us page (Note: A link has been removed),

…

What’s STAT all about?
STAT is a national publication focused on finding and telling compelling stories about health, medicine, and scientific discovery. We produce daily news, investigative articles, and narrative projects in addition to multimedia features. We tell our stories from the places that matter to our readers — research labs, hospitals, executive suites, and political campaigns.

Why did you call it STAT?
In medical parlance, “stat” means important and urgent, and that’s what we’re all about — quickly and smartly delivering good stories. Read more about the origins of our name here.

Who’s behind the new publication?
STAT is produced by Boston Globe Media. Our headquarters is located in Boston but we have bureaus in Washington, New York, Cleveland, Atlanta, San Francisco, and Los Angeles. It was started by John Henry, the owner of Boston Globe Media and the principal owner of the Boston Red Sox. Rick Berke is executive editor.

So is STAT part of The Boston Globe?
They’re distinct properties but the two share content and complement one another.

Is it free?
Much of STAT is free. We also offer STAT Plus, a premium subscription plan that includes exclusive reporting about the pharmaceutical and biotech industries as well as other benefits. Learn more about it here.

Who’s working for STAT?
Some of the best-sourced science, health, and biotech journalists in the country, as well as motion graphics artists and data visualization specialists. Our team includes talented writers, editors, and producers capable of the kind of explanatory journalism that complicated science issues sometimes demand.

Who’s your audience?
You. Even if you don’t work in science, have never stepped foot in a hospital, or hated high school biology, we’ve got something for you. And for the lab scientists, health professionals, business leaders, and policy makers, we think you’ll find coverage here that interests you, too. The world of health, science, and medicine is booming and yielding fascinating stories. We explore how they affect us all.

….

As promised, here are the links to my three-part series on CRISPR,

Part 1 opens the series with a basic description of CRISPR and the germline research that occasioned the series along with some of the other (non-weapon) ethical issues and patent disputes that are arising from this new technology. CRISPR and editing the germline in the US (part 1 of 3): In the beginning

Part 2 covers three critical responses to the reporting and between them describe the technology in more detail and the possibility of ‘designer babies’.  CRISPR and editing the germline in the US (part 2 of 3): ‘designer babies’?

Part 3 is all about public discussion or, rather, the lack of and need for according to a couple of social scientists. Informally, there is some discussion via pop culture and Joelle Renstrom notes although she is focused on the larger issues touched on by the television series, Orphan Black and as I touch on in my final comments. CRISPR and editing the germline in the US (part 3 of 3): public discussions and pop culture

Finally, I hope to stumble across studies from other countries about how they are responding to the possibilities presented by CRISPR/Cas9 so that I can offer a more global perspective than this largely US perspective. At the very least, it would be interesting to find it if there differences.

Overpromising and underdelivering: genome, stem cells, gene therapy and nano food

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When people talk about overpromising (aka hype/hyperbole) and science, they’re usually referring to overexcited marketing collateral and/or a public relations initiative and/or news media coverage.  Scientists themselves don’t tend to be identified as one of the sources for hype even when that’s clearly the case. That’s right, scientists are people too and sometimes they get carried away by their enthusiasms as Emily Yoffe notes in her excellent Slate essay, The Medical Revolution; Where are the cures promised by stem cells, gene therapy, and the human genome? From Yoffe’s essay,

Dr. J. William Langston has been researching Parkinson’s disease for 25 years. At one time, it seemed likely he’d have to find another disease to study, because a cure for Parkinson’s looked imminent. In the late 1980s, the field of regenerative medicine seemed poised to make it possible for doctors to put healthy tissue in a damaged brain, reversing the destruction caused by the disease.

Langston was one of many optimists. In 1999, the then-head of the National Institute of Neurological Disorders and Stroke, Dr. Gerald Fischbach, testified before the Senate that with “skill and luck,” Parkinson’s could be cured in five to 10 years. Now Langston, who is 67, doesn’t think he’ll see a Parkinson’s cure in his professional lifetime. He no longer uses “the C word” and acknowledges he and others were naive. [emphasis mine] He understands the anger of patients who, he says, “are getting quite bitter” that they remain ill, long past the time when they thought they would have been restored to health.

The disappointments are so acute in part because the promises have been so big. Over the past two decades, we’ve been told that a new age of molecular medicine—using gene therapy, stem cells, and the knowledge gleaned from unlocking the human genome—would bring us medical miracles. [emphasis mine] Just as antibiotics conquered infectious diseases and vaccines eliminated the scourges of polio and smallpox, the ability to manipulate our cells and genes is supposed to vanquish everything from terrible inherited disorders, such as Huntington’s and cystic fibrosis, to widespread conditions like cancer, diabetes, and heart disease.

Yoffe goes on to outline the problems that researchers encounter when trying to ‘fix’ what’s gone wrong.

Parkinson’s disease was long held out as the model for new knowledge and technologies eradicating illnesses. Instead, it has become the model for its unforeseen consequences. [emphasis mine]

Langston, head of the Parkinson’s Institute and Clinical Center, explains that scientists believed the damage to patients took place in a discrete part of the brain, the substantia nigra. “It was a small target. All we’d have to do was replace the missing cells, do it once, and that would cure the disease,” Langston says. “We were wrong about that. This disease hits many other areas of the brain. You can’t just put transplants here and there. The brain is not a pincushion.”

Disease of all kinds have proven to be infinitely more complex than first realized. Disease is not ’cause and effect’ driven so much as it is a process with an infinite number of potential inputs and any number of potential outcomes. Take for example gene therapy (Note: the human genome project was supposed to yield gene therapies),

In some ways, gene therapy for boys with a deadly immune disorder, X-linked severe combined immune deficiency, also known as “bubble boy” disease, is the miracle made manifest. Inserting good genes into these children has allowed some to live normal lives. Unfortunately, within a few years of treatment, a significant minority have developed leukemia. The gene therapy, it turns out, activated existing cancer-causing genes in these children. This results in what the co-discoverer of the structure of DNA, James Watson, calls “the depressing calculus” of curing an invariably fatal disease—and hoping it doesn’t cause a sometimes-fatal one.

For me, it seems that that the human genome project was akin to taking a clock apart. Looking at the constituent parts and replacing broken ones does not guarantee that you will be able assemble a more efficient working version unless you know how the clock worked in the first place. We still don’t understand the basic parts, the genes,  interact with each other, within their environment, or with external inputs.

The state of our ignorance is illustrated by the recent sequencing of the genome of Bishop Desmond Tutu and four Bushmen. Three of the Bushmen had a gene mutation associated with a liver disease that kills people while young. But the Bushmen are all over 80—which means either the variation doesn’t actually cause the disease, or there are other factors protecting the Bushmen.

As for the pressures acting on the scientists themselves,

There are forces, both external and internal, on scientists that almost require them to oversell. Without money, there’s no science. Researchers must constantly convince administrators who control tax dollars, investors, and individual donors that the work they are doing will make a difference. Nancy Wexler says that in order to get funding, “You have to promise cures, that you’ll meet certain milestones within a certain time frame.”

The infomercial-level hype for both gene therapy and stem cells is not just because scientists are trying to convince funders, but because they want to believe. [emphases mine]

Scientific advances as one of Yoffe’s interview subjects points out involve a process dogged with failure and setbacks requiring an attitude of humility laced with patience and practiced over decades before an ‘overnight success’ occurs, if it ever does.

I was reminded of Yoffe’s article after reading a nano food article recently written by Kate Kelland for Reuters,

In a taste of things to come, food scientists say they have cooked up a way of using nanotechnology to make low-fat or fat-free foods just as appetizing and satisfying as their full-fat fellows.

The implications could be significant in combating the spread of health problems such as obesity, diabetes and heart disease.

There are two promising areas of research. First, they are looking at ways to slow digestion,

One thing they might look into is work by scientists at Britain’s Institute of Food Research (IFR), who said last month they had found an unexpected synergy that helped break down fat and might lead to new ways of slowing digestion, and ultimately to creating foods that made consumers feel fuller.

“Much of the fat in processed foods is eaten in the form of emulsions such as soups, yoghurt, ice cream and mayonnaise,” said the IFR’s Peter Wilde. “We are unpicking the mechanisms of digestion used to break them down so we can design fats in a rational way that are digested more slowly.”

The idea is that if digestion is slower, the final section of the intestine called the ileum will be put on its “ileal brake,” sending a signal to the consumer that means they feel full even though they have eaten less fat

This sounds harmless and it’s even possible it’s a good idea but then replacing diseased tissue with healthy tissue, as they tried with Parkinson’s Disease gene therapies, seemed like a good idea too. Just how well is the digestive process understood?

As for the second promising area of research,

Experts see promise in another nano technique which involves encapsulating nutrients in bubble-like structures known as vesicles that can be engineered to break down and release their contents at specific stages in the digestive system.

According to Vic Morris, a nano expert at the IFR, this technique in a larger form, micro-encapsulation, was well established in the food industry. The major difference with nano-encapsulation was that the smaller size might be able to take nutrients further or deliver them to more appropriate places. [emphasis mine]

They’ve been talking about trying to encapsulate and target medicines to more appropriate places and, as far as I’m aware, to no avail. I sense a little overenthusiasm on the experts’ part. Kelland does try to counterbalance this by discussing other issues with nanofood such as secretiveness about the food companies’ research, experts’ concerns over nanoparticles, and public concerns over genetically modified food. Still the allure of ‘all you can eat with no consequences’ is likely to overshadow any journalist’s attempt at balanced reporting with resulting disappointment when somebody realizes it’s all much more complicated than we thought.

Dexter Johnson’s Sept. 22, 2010 posting ( Protein-based Nanotubes Pass Electrical Signals Between Cells) on his Nanoclast blog offers more proof that we still have a lot to learn about basic biological processes,

A few years back, scientists led by Hans-Hermann Gerdes at the University of Bergen noticed that there were nanoscale tubes connecting cells sometimes over significant distances. This discovery launched a field known somewhat by the term in the biological community as the “nanotube field.”

Microbiologists remained somewhat skeptical on what this phenomenon was and weren’t entirely pleased with some explanations offered because they seemed to fall outside “existing biological concepts.”

So let’s start summing up.  The team notices nanotubes that connect cells over distances which microbiologists have difficulty accepting as “they [seem] to fall outside existing biological concepts. [emphasis mine] Now the team has published a paper which suggests that electrical signals pass through the nanotubes and that a ‘gap junction’ enables transmission to nonadjacent cells.  (Dexter’s description provides  more technical detail in an accessible writing style.)

As Dexter notes,

Another key biological question it helps address–or complicate, as the case may be–is the complexity of the human brain. This research makes the brain drastically more complex than originally thought, according to Gerdes. [emphasis mine]

Getting back to where I started, scientists are people too. They have their enthusiasms as well as pressure to get grants and produce results for governments and other investors, not to mention their own egos.  And while I’ve focused on the biological and medical sciences in this article, I think that all the sciences yield more questions than answers and that everything is far more complicated and  interconnected than we have yet to realize.