CRISPR / Technology

Will Advancements in Synthetic Biology Benefit Everyone?

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“The genesis machine will power humanity’s great transformation, which is already underway. Soon, life will no longer be a game of chance, but the result of design, selection and choice.”

Amy Webb, Author, The Genesis Machine – CEO, Future Today Institute
Image Credit: Shutterstock.com

Synthetic biology is a relatively new interdisciplinary field of science that combines engineering, design, and computer science with biology. Researchers design or redesign organisms on a molecular level for new purposes, making them adaptable to different environments or giving them different abilities. A recent McKinsey report anticipates applications from this bio revolution could have a direct global impact of up to $4 trillion per year over the next 10-20 years, enabling the production of 60% of physical inputs to the global economy and addressing 45% of the world’s current disease burden. However, for synthetic biology applications to reach their full potential, it’s critical to ensure that access and development of knowledge in this sector, along with the relevant research tools, are distributed in low-resource contexts. This can help to avoid the technology being centered solely in advanced, resource-rich economies and widening inequalities in the global bioeconomy.

We can now program biological systems like we program computers. In synthetic biology, DNA sequences are loaded into software tools—imagine a text editor for DNA code—making edits easy. After the DNA is written or edited to the researcher’s satisfaction, a new DNA molecule is printed from scratch using something akin to a 3D printer. The technology for DNA synthesis (transforming digital genetic code to molecular DNA) has been improving exponentially. Today’s technologies routinely print out DNA chains several thousand base pairs long that can be assembled to create new metabolic pathways for a cell or even a cell’s complete genome. Get used to the term bio-economy because these scientific innovations have fueled the rapid growth of an industry intent on making high-value applications that include biomaterials, fuels, specialty chemicals, drugs, vaccines, and even engineered cells that function as microscale robotic machines. Progress in artificial intelligence has provided a significant boost to the field, as the better AI becomes, the more biological applications can be tested and realized.

“We are going from reading our genetic code to the ability to write it. That gives us the hypothetical ability to do things never contemplated before.”

J. Craig Venter, geneticist, biochemist and biotechnology pioneer

In the next two decades, synthetic biology technologies will be harnessed to eradicate life-threatening diseases and develop personalized medicines for individual people and their specific genetic circumstances.

What are some of the current advancements in synthetic biology that will drive this growth? For this post, I’ll focus on the healthcare applications and companies working on them at a relatively high level. If you are interested in exploring the topic in more detail, I’ll provide links to curated articles at the end of the discussion.

  • Faster gene synthesis at a lower cost: Synthesis transforms digital genetic code into molecular DNA, allowing scientists to design and mass-produce genetic material. This is what Twist Bioscience does to form as many as 300 base pairs of DNA. Joining these snippets or oligos together forms genes. The price for oligos and the time to produce them are decreasing—while the length and complexity of base pairs are increasing. Twist’s innovation reduces the need for expensive reagents by a factor of 1 million while increasing the number of genes that can be synthesized by a factor of 9,600. It now costs an average of just nine cents per base pair. The DNA snippets produced by Twist can be ordered online and shipped to a lab within days; the synthetic DNA is then inserted into cells to create target molecules, which are the basis for new food products, fertilizers, industrial products, and medicine.
  • Genome sequencing at a lower cost: The first human genome cost roughly $2.7 billion and took 13 years to complete. Today, you can sequence your genome from the comfort of your home for less than the price of a cheap TV. Nebula Genomics, a spinout from a Harvard University lab run by synthetic biologist George Church, offers to provide a person’s genetic code with “medium accuracy” for $99 or, for $900 more, you could have 100% of your DNA decoded “with ultrahigh accuracy and … over 300 gigabytes of DNA data,” according to the company’s website.
  • Create on-demand molecules: Scientists now use synthetic biology to discover and produce molecules on de- mand. The Defense Advanced Research Project Agency and the MIT-Broad Institute Foundry proved that new molecules could be rapidly generated for practical use. In a research challenge, teams used artificial intelligence and synthetic biology to deliver six of the ten requested designer molecules in just 90 days.
  • CRISPR-based antibiotics: Antibiotic resistance is rising due to overuse or incorrect application. But a new approach could enable us to tackle antibiotic-resistant infections. CRISPR can be programmed to kill certain bacterial cells that contain specific DNA. Researchers at the University of Sherbrooke demonstrated that a CRISPR-edited bacterium could be used to target an antibiotic-resistant strain of E. coli. Soon, CRISPR-edited probiotic bacteria could be used to treat bladder and skin infections.
  • CRISPR-based therapies: Several trials will test emerging CRISPR therapies in 2022. In Germany, a patient with beta-thalassemia, a genetic disorder that results in low levels of hemoglobin, had the genomes of their blood stem cells edited. Post-treatment, they have not required blood transfusions. Other patients in the trial show normal to near-normal hemoglobin levels. CRISPR is being used to edit T cells, a white blood cell essential for immune system response. A treatment for urinary tract infections, CRISPR-Cas3, combined with three bacteriophages, successfully killed the strain of E. coli responsible for 95% of UTIs.
  • Programmable gene-editing proteins: Scientists at MIT’s McGovern Institute and the Broad Institute of MIT and Harvard have discovered a new class of programmable DNA modifying systems called OMEGAs (Obligate Mobile Element Guided Activity), which could move small bits of DNA throughout bacterial genomes.

What are some of the leading research applications of synthetic biology in healthcare? Here’s a sampling of current research work:

  • mRNA vaccine development: Leveraging the work done during the pandemic to develop mRNA vaccines to protect against COVID-19, both Moderna and BioNTech were researching immunotherapies for cancer. BioNTech is running clinical trials for personalized vaccines for many cancers, including ovarian cancer, breast cancer, and melanoma. Moderna is developing similar cancer vaccines.
  • Genetic screening for pregnancy: New genetic screening techniques that test embryos before implantation are making their way into fertility centers. California-based MyOme and New Jersey-based Genomic Prediction use the genetic sequences of parents, along with cells retrieved during a biopsy, to generate an embryo’s entire genome. Next, they use algorithms to calculate the probabilities of certain ailments.
  • “Body-on-a-chip”: The Wake Forest Institute for Regenerative Medicine is leading a unique $24 million federally funded project to develop a “body on a chip,” including different combinations of organoids. Imagine a computer chip, but with a transparent circuit board that’s connected to a system pumping a blood substitute through it. With it, researchers can poison a mock respiratory system with new viruses, lethal chemicals, or other toxins to see how the body would react and then test potential treatments on living human tissue without harming humans or other animals.
  • Development of synthetic wombs: In an experiment at Northwestern University’s Feinberg School of Medicine, researchers successfully printed and implanted synthetic ovaries in mice, resulting in a successful pregnancy. Researchers at the Children’s Hospital of Philadelphia created an artificial womb called a bio bag and used it to successfully keep premature lambs alive and developing normally for 28 days. We are still years away from synthesizing and growing a full-size organic womb—but the bio bag represents an intervention that could help the thousands of premature babies born before 25 weeks each year.
  • Synthetic age reversal: As we age, the sequence might stay constant, but chemical changes do occur to our DNA. Observing those changes could lead to new techniques to halt or reverse age-related diseases. I’ve written on the topic of human longevity previously, and you can read that post here.

How do we ensure that advances in synthetic biology are available to all, not just advanced, resource-rich economies? First, we must correct the perception and narrative firmly embedded in biotechnology at all levels that “open source” means “uncommercialisable.” Unfortunately, this leads to an unwillingness to creatively explore openness as one possibility within a range of Intellectual Property (IP) strategies. Many researchers and The World Economic Forum propose an “open source” approach to sharing these developments. Open source approaches play an important role here because, beyond open licensing, they also encourage collaborative development and sharing of know-how, which is essential to overcome barriers to building capacity and innovation.

“Now that we’re two decades into #synbio, it’s a good time to revisit our founding principles — e.g. what kinds of societies do we want to build and who can participate — all while continuing to mature as an industry.”

Meghan Palmer, Built with Biology Conference, 04/13/2022

Open toolkits like the Research in Diagnostics DNA Collection, designed by many collaborators and distributed through the Free Genes project at Stanford, provide a “ready to go” solution that, with the correct manufacturing practices, quality management systems, and regulatory approvals, could also be used for diagnostics kits. Another excellent example of an open project that has already directly impacted scientific progress is the Structural Genomics Consortium. This public-private partnership has openly released data, materials, and research tools for drug discovery against medically relevant human protein structures to academia and industry for around 20 years, resulting in thousands of collaborations and scientific papers and over 1500 protein structures entering the public domain. The leaders of the consortium continue to push the model further, for example, launching pharma companies that aim to apply an open approach to drug discovery for rare childhood cancers.

“My advice to global leaders and policymakers is to ensure that all countries get a seat at the table and focus on building out more than local or regional policies but also systems for international governance that can adapt to the extraordinary pace of technical and social change in the bioeconomy.”

Dr. Jenny Molloy, Senior Research Associate at the Department of Chemical Engineering and Biotechnology, University of Cambridge

My takeaways from reviewing the synthetic biology book and other resources in the recommended reading/viewing list below:

  • Synthetic biology has the potential to solve pressing issues in healthcare, climate, agriculture, global food supply, etc.
  • The U.S. has no national strategy on synthetic biology. The lack of a comprehensive national plan will put us behind other nations like China and Russia. They have committed considerable resources to develop synthetic biology as a competitive advantage.
  • The regulatory framework in the U.S. is a complicated mess with no clear delineation of who is responsible for what. Competing priorities in the FDA, Department of Agriculture, Department of Energy, Department of Interior, and others will slow the development and implementation of potential solutions to critical needs. And this isn’t unique to the U.S. The European Union, along with the United Kingdom, China, Singapore, and many other nations, approach the governance of synthetic biology in similar ways, using existing biotechnology frameworks. Who’s going to regulate mail order DYI CRISPR kits, for example? (btw, they’re already being marketed online)
  • If you thought the CRISPR patent battle between the Broad Institute and UC Berkeley was contentious, wait until you see the upcoming intellectual property and patent battles around synthetic biology. As Amy Webb discovered in the research for her book, the US government had no plan to manage the coming onslaught of intellectual property battles looming on the horizon.
  • The COVID-19 pandemic resurfaced the inequities in our health system. How do we ensure the advances in synthetic biology are available to all nations – rich and poor alike? Will the “open source” approach proposed by the World Economic Forum take hold? Or will this widen the gap between rich and developing nations further?
  • Ethical issues need to be addressed. Global ethicists have come out against germ-line editing, where changes are passed down to future offspring. But enforcement will be a problematic issue. What about gene editing to increase I.Q.? Or creating “super-soldiers” for future wars? I reported earlier about this website meant to imitate a gene-editing company that specializes in babies. It lets you try what it could be like to order a baby with technology likely to be available soon.
  • Misinformation and disinformation will polarize and politicize the conversation and create barriers to adopting synthetic biology advances. Consider what we’ve already experienced with mRNA vaccine pushback or the blowback to GMO (genetically modified organisms) in the food supply.

There are still many questions about the developments in synthetic biology. For example, what constitutes genetic privacy? And do individuals have the right to keep their genetic data private and secure from third parties? As Amy Webb states in her book: “Within the next decade, we will need to make important decisions: whether to program novel viruses to fight diseases, who will “own” living organisms, how companies should earn revenue from engineered cells, and how to contain a synthetic organism in a lab. What choices would you make if you could reprogram your body? Would you agonize over whether—or how—to edit your future children?” How can we democratize the deployment of synthetic biology to all people instead of just the affluent countries? Now is the time to advance the discussion to the level of public conversation. If we wait to have those conversations, the future of synthetic biology could be determined by fights over intellectual property and national security and by protracted lawsuits and trade wars – thus benefiting no one instead of society as a whole.

Want to learn more about synthetic biology? Here are some links to books and articles that I’ve found invaluable in my research on the topic:

YouTube Video Credit: TWiT Tech Podcast Network, 2/19/2022

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