Monday, June 13, 2016

Sunday Globe Special: China's Dr. Frankenstein

More frightening than fiction:

"Doctor’s plan for full-body transplants raises doubts even in daring China" by Didi Kirsten Tatlow New York Times  June 11, 2016

HARBIN, China — The idea for a body transplant is the kind of thinking that has experts around the world alarmed at how far China is pushing the ethical and practical limits of science. Such a transplant is impossible, at least for now, according to leading doctors and experts, including some in China, who point to the difficulty of connecting nerves in the spinal cord. Failure would mean the death of the patient.

The orthopedic surgeon proposing the operation, Dr. Ren Xiaoping of Harbin Medical University, who assisted in the first hand transplant in the United States in 1999, said he would not be deterred. In an interview, Ren said that he was building a team, that research was underway and that the operation would take place “when we are ready.”

His plan: Remove two heads from two bodies, connect the blood vessels of the body of the deceased donor and the recipient head, insert a metal plate to stabilize the new neck, bathe the spinal cord nerve endings in a gluelike substance to aid regrowth, and, finally, sew up the skin.

Sounds like the plot of a movie, doesn't it?

Critics attribute such medical experimentation in China to national ambition, generous state funding, a utilitarian worldview that prioritizes results, and a lack of accountability to the outside world.

Last year, researchers at Sun Yat-sen University, in the southern city of Guangzhou, altered a gene in the human embryo that causes thalassemia, a rare blood disease, using a technique developed in the United States.

They just held a global summit on the matter.

The experiment crossed an ethical line, some scientists in China and abroad said, because the changes would be inheritable if conducted on viable embryos. (The experiment used unviable embryos.) That could pave the way for permanent gene modification for qualities such as looks or intelligence.

I was told “genetic medicine is a substantial opportunity” if you partner up with the right people.

I hope that gave you some insight into where this is all headed (never you mind the flawed tests).

Despite the concerns, in April another team in Guangzhou altered embryos to make them HIV resistant. Internationally, some scientists criticized the experiment, citing a lack of consensus on the ethics of such work.

The team, from Guangzhou Medical University, said that “significant technical issues remain to be addressed.” It added that on ethical grounds it would not advocate genome editing on viable lines “until after a rigorous and thorough evaluation and discussion are undertaken by the global research and ethics communities.”

Ren has experimented with head transplants on mice, but they have lived only for a day. He said he had also begun practicing on human cadavers, but declined to give details.

The doctor and his supporters say the operation could help people with potentially fatal diseases affecting body function, such as spinal muscular atrophy, as well as those with paralysis like Wang....


Of course, when work such as gene-editing and other things are part of a growing indu$try in the state and AmeriKa it is a different story:

Targeting the ‘gene next door’ to fight hard-to-treat tumors

"Foundation Medicine Inc. received a boost as the country’s largest health insurer began covering its genetic test for a type of lung cancer. Still, it is unclear how much of an impact this new contract will have on Foundation Medicine’s bottom line because the company already does business with UnitedHealth as an out-of-network provider, said Zarak Khurshid, an analyst with Wedbush Securities, a Los Angeles-based investment firm. "

Khursid rats.

"Synlogic Inc., a Cambridge startup that is synthetically engineering microbes into disease-fighting drugs, said Wednesday it raised $40 million to help bring a pair of its custom-made treatments for rare metabolic disorders into clinical trials next year."

Excuse me.

"A pair of venture capital firms Monday formally launched Homology Medicines Inc., a Lexington-based genetic medicines startup, with a $43.5 million funding round. Homology, which has been working for months in stealth mode, will be developing therapies in the fields of gene therapy and gene editing. While a trio of other Cambridge gene editing startups are using a tool called Crispr-Cas9, Homology will be taking a different approach involving “in vivo” editing of DNA within cells, rather than removing and repairing DNA. The company, launched by lead funders 5AM Ventures of Menlo Park, Calif., and Arch Venture Partners of Chicago, said it has hired industry veterans Arthur Tzianabos as chief executive, Sam Rasty as chief operating officer, and Albert Seymour as chief scientific officer."

Time to te$t the market:

Cambridge startup Editas plans to test IPO market for biotech

"Editas Medicine has boosted its fundraising target in an forthcoming initial public offering to as much as $122.1 million, stating in a regulatory filing Monday that it plans to sell 6.78 million shares of stock at a range of $16 to $18 a share. The Cambridge biotech, a leader in the emerging gene-editing approach known as CRISPR-Cas9, initially disclosed its plans to go public in a Jan. 4 filing with the Securities and Exchange Commission that said it would offer up to $100 million in stock, a placeholder sum. Editas is expected to price its shares next week, according to the IPO calendar published by Greenwich, Conn., research firm Renaissance Capital. Three other biotech firms are also set to price shares next week -- PLx Pharma Inc. of Houston, BeiGene of China, and Mapi-Pharma of Israel -- testing the strength of the biotech IPO market for the first time in 2016."

So much for the concern regarding China (that Frankenstein story meant to demonize) and look who else is getting in on gene editing. Has to be some supreme irony there.

Meet one of the world’s most groundbreaking scientists. He’s 34.

And Chinese!

Advances in gene editing, and hype, underlie Editas move to go public

Editas Medicine raises $94.4 million in year’s first IPO

There sure is a lot of money out there when it comes to pushing the agenda.

Editas’s surge brightens IPO outlook

They needed a gene or two edited.

Biotech stocks are underwater in uncertain IPO market

When unsettled markets force companies to delay IPOs, or when newly public shares sink underwater, it can leave executives embarrassed and investors chastened. Industry insiders constantly gauge the health of the IPO market to see whether economic or political trends, from energy price declines to a backlash against the rising cost of specialty medicines, are spooking investors. “Biotech and the overall equity markets have been under siege the past few months from macro forces, like oil and the economy, as well as sector-specific concerns like drug pricing.”

Weakening IPO market could slow momentum of biotech sector

Then they better find another source of revenue, 'eh?

Local tech firms eschew IPOs in favor of venture capital

Yeah, take it out of those college endowments and pension funds and place your bets.

Bayer bets $335M on CRISPR Therapeutics and the future of gene editing 

It's a Fierce competition for investors!

"When billionaire philanthropist and entrepreneur Paul Allen, a co-founder of Microsoft, went looking for scientists to spend big on, he had one main rule: No sheep need apply. “We wanted to find people who might not be where the herd is going,” said Tom Skalak, executive director of the new Paul G. Allen Frontiers Group, a $100 million initiative to back risky, cutting-edge science that more conventional funders might avoid."

What a tacky move.

"Top scientists hold closed meeting to discuss building a human genome from scratch" by Ike Swetlitz, May 13, 2016

Over 130 scientists, lawyers, entrepreneurs, and government officials from five continents gathered at Harvard this week for an “exploratory” meeting to discuss the topic of creating genomes from scratch — including, but not limited to, those of humans, said George Church, Harvard geneticist and co-organizer of the meeting.

They used to call that playing God.

The meeting was closed to the press, which drew the ire of prominent academics, but a different narrative appeared during the week on social media. Endy posted a tweet that included a screenshot appearing to be a message from the meeting organizers. It said, in part, “We intentionally did not invite the media, because we want everyone to speak freely and candidly without concerns about being misquoted or misinterpreted as the discussions evolve.”

Marcy Darnovsky, executive director of the Center for Genetics and Society, based in Berkeley, Calif., said that the “semi-secret” nature of the meeting runs counter to the principles established in December at the International Summit on Human Genome Editing....

Then I'm told this is “purely a thought experiment, [and] it may not be as big news as it sounds.”


The "project" had to be kept secret because it is so audacious.

"‘Gene drive’ organisms should be tested in field trials, not widely released, experts say" by Ike Swetlitz, June 8, 2016

Research on a genetic engineering technique that, for the first time, could enable scientists to quickly modify entire populations of organisms in the wild should continue in the laboratory — and potentially under restrictive conditions in the field — an expert panel said Wednesday.

This “gene drive” technology, in its current form, is only two years old, but some are already calling for its use against mosquitoes that carry Zika virus or malaria. The National Academies of Sciences, Engineering, and Medicine panel reins in this enthusiasm.

“There is insufficient evidence available at this time to support the release of gene-drive modified organisms into the environment,” it writes. However, it adds, “highly-controlled field trials” should proceed.

The thing is, they have already done that with the mosquitos -- or so the limited hangout goes. Zika actually caused by vaccines, but the solution to Zika has become -- you guessed it -- another vaccine!

Gene drives enable genetic modifications to a single organism to spread rapidly through the entire population by ensuring that targeted genes are passed on to nearly all offspring. Scientists could release swarms of mosquitoes that produce sterile offspring, reducing the number of bugs that can transmit malaria or Zika virus. Or, they could engineer mice not to transmit Lyme disease to ticks – an idea aired at a community meeting Monday on Nantucket.

Or it could run the other way, right? Pathogens could be introduced in such ways, and that opens up a scary new realm looking back and forward -- especially considering the source I'm reading. 

Yes, this is all for the good, and the new$paper would tell us were it otherwise.

Some scientists urge caution even in conducting controlled experiments, noting how powerful even a single organism might be.

“There is a nontrivial chance that [the genes] will spread from a single organism released into a wild population into most or all members of the local population — and very possibly into every population of the target species around the globe,” said Kevin Esvelt, an MIT Media Lab professor who has studied gene drives in yeast. “This makes field trials of [current gene] drives unwise.”

Look what happened to the lobsters!

The technology itself is spreading so quickly through the scientific community that the government is struggling to catch up — it’s unclear who, if anyone, would have the authority to regulate this technology or prevent scientists from releasing modified organisms.

Heck, the plants and animals are already that way and the government scientists approve.

“There is nothing in our regulatory system that could possibly take on this challenge given the glacial pace of regulating chemicals and of the voluntary regulations in certain areas of food biotechnology,” said Sheldon Krimsky, a Tufts University professor of urban and environmental policy and planning.

The report notes that gene drives could have unintended consequences — mosquitoes modified not to transmit the dengue virus might become better at transmitting a different virus, for example, while sterilization and removal of mosquitoes may upset the balance of the ecosystem. So, the report calls for intense consideration of environmental, social, and economic issues.

It recommends “phased testing” — starting in a lab, moving up to field-based research, and eventually releasing organisms into the wild.

To prevent the genes from migrating to unintended organisms, these experiments must be carefully isolated from the surrounding environment. The report recommends that field trials could take place in geographically-isolated areas, such as islands, or occur far away from environments into which the gene drive might spread.

Currently, lab work with gene drives is done with extensive security precautions — one experiment was conducted behind five locked doors, and the engineered flies were kept inside three nested containers.

Researchers lauded the report as a good start to the conversation about a territory lacking clear regulation, but some say that the panel should have explicitly instructed researchers to engage members of the public before doing their research.

This is critical because gene drives, in their current form, are all about unilaterally and rapidly changing environments shared by many people, Esvelt said.

“We should at the very least have the courtesy to inform people what is being planned — and let them voice their opinions — before we begin,” he said.

The question of where eventual field research might occur also comes up in the report. The authors note that such research “is most likely to occur” in “low- and middle-income countries,” and thus it is especially important to build long-term relationships with scientists in those countries. 

Like where they dumped the toxic waste (what a real humanitarian, huh?)

So what is next for union leader Larry Summers? Posing as a global health advocate or political consultant!?

“Starting the work in low-income countries is especially problematic,” said Jaydee Hanson, a policy director at the International Center for Technology Assessment. He pointed out that the United States did not ratify international environmental treaties, such as the Convention on Biological Diversity, and other countries may be skeptical of US researchers conducting field trials in their backyards.

Ya' think?

Yeah, just be AmeriKan guniea pigs for who knows what? 

It's not like it's never been done before.


And they wonder why we fear giving a drop of blood?

"Inside the sci-fi world of growing human tissue and organs in the lab" by Meghana Keshavan, June 8, 2016

Inside a North Carolina lab, row upon row of plastic bioreactor bags pulsate gently to the beat of an artificial heart. Within each bag, a lab-forged blood vessel slowly expands, feeding off a primordial cocktail of vitamins and proteins.

The blood vessels start as individual cells, placed inside a sinewy scaffold. Weeks later, they’ve grown into full-fledged arteries and veins that surgeons can use for transplants.

Welcome to the age of tissue engineering.

For decades, scientists and doctors have been seeking a way to manufacture human tissue — including entire organs — in a lab, hoping to make grafts and transplants easier and safer than they are now. The goal has proved elusive, because it’s hard to replicate the complexity of human tissue outside the body. But those in the trenches say the industry could be on the verge of a breakthrough.

The work is still fraught with risks, both scientific and commercial.

One cautionary tale: the San Diego startup Advanced BioHealing, which created a promising lab-grown replacement for human skin, to be used in wound care. Anticipating a billion-dollar market, the Irish drug giant Shire bought out Advanced BioHealing in 2011 for $750 million. But insurers such as Medicare were reluctant to cover the skin replacement. Three years later, Shire shed that unit at a loss.

See: Carl Icahn says he’s taken position in Allergan

So much for the fountain of youth.

“Tissue engineering has to mature a bit as a market,” said Keith Murphy, the CEO of Organovo. Pharma companies haven’t been rushing to invest in the field, in part because of flops like the skin replacement technology. But Murphy is optimistic....


Time to put this post in the CRISPR until I can get my head back on straight.

UPDATE: Stem cell factory opens door for trials of personalized diabetes treatment